ScienceWeek

SCIENCE-WEEK

A Weekly Email Digest of the News of Science

A journal devoted to the improvement of communication
between the scientific disciplines, and between scientists,
science educators, and science policy-makers.

December 1, 2000 -- Vol. 4 Number 48

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A man ceases to be a beginner in any given science
and becomes a master in that science when he has
learned that he is going to be a beginner all his life.
-- R.G. Collingwood (1889-1943)

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Section 1
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Contents of this Issue (Full reports in Section 2):

1. SCIENCE POLICY:
FACULTY-INDUSTRY FINANCIAL RELATIONSHIPS IN BIOMEDICINE
In the US, approximately $1.5 billion from industry flows into
academic institutions annually, and 28 percent of surveyed life
sciences faculty members report funding from private sponsors.
There is now growing concern in both government agencies and
academic institutions that industry sponsorship may influence the
outcomes of research and undermine traditionally held academic
values of intellectual freedom, open exchange of ideas, and
research in the interest of the public good. A new report
presents a study of the relations of faculty researchers at the
University of California San Francisco and the private industry
sponsors of their research.
(J. Amer. Med. Assoc. 1 Nov 00 284:2209)

2. NEUROBIOLOGY:
NEUROGENESIS AND CLINICAL DEPRESSION
The waxing and waning of neurogenesis in the hippocampus, induced
by changes in glucocorticoids, might trigger the precipitation of
and recovery from episodes of clinical depression. But other
changes may also be important in the etiology and recovery from
depression. For example, besides suppressing neurogenesis,
increased glucocorticoids might mediate additional direct
neuronal effects in various brain structures. Similarly, changes
in serotonin neurotransmission might also exert direct effects in
various brain structures. All of these changes, acting in
concert, may give rise to the complex syndrome of depression.
(American Scientist Jul/Aug 2000 88:340)

3. MEDICAL BIOLOGY:
THE PLASMA MEMBRANE AND HIV 
Recent progress in the analysis of the HIV, which is probably the
most extensively characterized of all human pathogens, provides a
good illustration of the central role played by the plasma
membrane in HIV-host cell interactions. Just as the composition
of the plasma membrane influences viral infectivity, the virus in
turn uses components of the plasma membrane that are to its
advantage and modifies other components to suit its purposes. The
interplay between HIV and the plasma membrane has much to offer
for the understanding of viral tropisms, pathogenicity, and
normal cellular functions, and for the development of new
antiviral approaches. (Genes & Development 1 Nov 00 14:2677)

4. ASTROPHYSICS: ON STARDUST
The exact composition of interstellar dust is uncertain, but
infrared absorption measurements indicate that a significant
fraction of the material is organic. As astronomers make new
discoveries about the chemical composition of both comets and
interstellar dust, they are becoming convinced that comets
originally formed as clumps of dust grains. In addition, comet
dust may have played a role in seeding life on Earth. Each loose
cluster of comet dust not only contains organic materials, but
also has a structure that is ideal for chemical evolution once it
is immersed in water. (Scientific American December 2000)

5. CONDENSED MATTER PHYSICS:
ON DIFFUSION IN SEMICONDUCTORS
Experiments on self-diffusion of gallium and antimony in gallium
antimonide demonstrate that near the melting temperature, gallium
diffuses more rapidly than antimony by over 3 orders of
magnitude. This surprisingly large difference in atomic mobility
requires a physical explanation that goes beyond standard
diffusion models, and the finding is another in a long line of
unexpected differences and similarities encountered in the
history of understanding diffusion in semiconductors. The
unusually slow antimony diffusion in gallium antimonide may be a
consequence of reactions between defects on the gallium and
antimony sublattices, these reactions suppressing the defects
that are required for antimony diffusion.
(Nature 2 Nov 00 408:69)

6. APPLIED PHYSICS:
A LIGHT-EMITTING FIELD EFFECT TRANSISTOR
Data are presented on the structure and operating characteristics
of an ambipolar light-emitting field-effect transistor based on
single crystals of the organic semiconductor alpha-sexithiophene.
In this device, electrons and holes are injected from the source
and drain electrodes, respectively, and the concentrations of
electrons and holes are controlled by the applied gate and drain-
source voltages. Excitons are generated, leading to radiative
electron-hole recombination. Moreover, above a remarkably low
threshold current, coherent light is spontaneously emitted
(amplified spontaneous emission). This three-terminal device may
be the basis of a very promising architecture for electrically
driven laser action in organic semiconductors.
(Science 3 Nov 00 290:963)

7. IN FOCUS: ON THE MEANING OF QUANTUM THEORY

8. FROM THE SCIENCEWEEK ARCHIVE: ON FRAUD IN SCIENCE

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Section 2
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1. SCIENCE POLICY:
FACULTY-INDUSTRY FINANCIAL RELATIONSHIPS IN BIOMEDICINE
During the past several decades, many people in and out of
science have become concerned about the growing incidence of
close financial ties between academic researchers and private
industry. This concern is not simply the result of some
idealistic desire for a "pristine" scientific enterprise, but a
concern based on the threat (and reality) of a corruption that
causes biased interpretations of data, withholding of data, and
in some cases fabrication of data. In 1840, Alexis de Tocqueville
(1805-1859) wrote of the impact of American democracy on American
science: "As soon as the multitude begins to take an interest in
the labors of the mind, it finds out that to excel in some of
them is a powerful method of acquiring fame, power, or wealth."
The current concern is not that scientists are financially
rewarded for their efforts, but that the quest for such rewards
must not corrupt the scientific enterprise.
... ... E.A. Boyd and L.A. Bero (2 installations, US) present a
study of the relations of faculty researchers and the private
industry sponsors of their research, the study made at the
University of California San Francisco, and including disclosure
forms and official documents dated in the period 1980 to 1999.
The authors make the following points:
     1) In the US, approximately $1.5 billion from industry flows
into academic institutions annually, and one study has shown that
28 percent of surveyed life sciences faculty members report
funding from private sponsors. There is now growing concern in
both government agencies and academic institutions that industry
sponsorship may influence the outcomes of research and undermine
traditionally held academic values of intellectual freedom, open
exchange of ideas, and research in the interest of the public
good.
     2) Several studies have shown an association between single-
source sponsorship of clinical research and publication of
results favoring the sponsor's product. Another study has shown
that unfavorable results of economic analyses of cancer drugs are
less likely to be reported when the study is funded by a
pharmaceutical company. Faculty researchers receiving research
support from industry are also more likely to restrict their
communication with colleagues than faculty not receiving industry
support, and many faculty who receive gifts from corporate
sponsors are subject to prepublication review or data use
restrictions.
     3) In addition to the effects that corporate sponsorship
might have on design, outcome, or publication of results, concern
exists that a growing number of faculty researchers also have
personal financial relationships with the companies sponsoring
their research. In 1996, Krimsky et al reported that 15 percent
of Massachusetts-based senior authors of journal articles had
personal financial interests in the company sponsoring the
research project. Although there is speculation that these
additional financial ties result in an increased potential for
conflicts of interest because the researchers stand to benefit
personally from the outcome of the study, the extent and nature
of these ties remain unknown. Furthermore, although universities
are now required by the federal government and many states to
assess and manage disclosed conflicts of interest, little is
known about how universities implement guidelines and evaluate or
manage cases of disclosed financial conflicts.
     4) At the University of California San Francisco, the
authors found as follows: By 1999, almost 7.6 percent of faculty
investigators reported personal financial ties with sponsors of
their research. Throughout the study period, 34 percent of
disclosed relationships involved paid speaking engagements (range
$250 to $20,000 per year); 33 percent involved consulting
agreements between researcher and sponsor (range less than $1000
to $120,000 per year); 32 percent involved the investigator
holding a position on a corporate scientific advisory board or a
corporate board of directors; 14 percent involved equity
ownership; 12 percent involved multiple relationships.
     5) The authors conclude: "Faculty researchers are
increasingly involved in financial relationships with their
research sponsors. Guidelines for what constitutes a conflict and
how the conflict should be managed are needed if researchers are
to have consistent standards of behavior among institutions."
[*Note #1]
-----------
E.A. Boyd and L.A. Bero: Assessing faculty financial
relationships with industry.
(J. Amer. Med. Assoc. 1 Nov 00 284:2209)
QY: Lisa A. Bero: bero@medicine.ucsf.edu
-----------
Text Notes:
... ... *Note #1: The same issue of the _Journal of the American
Medical Association_ contains several other articles (including
an editorial) on industry-biomedical research involvements. Also,
the 30 November 00 issue of the _New England Journal of Medicine_
contains 2 major articles, an editorial, and a major commentary
on conflicts of interest in biomedical research (New England J.
Med. 2000 343:1616,1621,1643,1646).
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Summary & Notes by SCIENCE-WEEK http://scienceweek.com 1Dec00
For more information: http://scienceweek.com/swfr.htm
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Related Background:
CORPORATE PAYMENTS TO SCIENTISTS FOR LETTERS TO JOURNALS
A blatant instance of corporate pressure in science was recently
revealed when a newspaper, the *St. Paul Pioneer Press* of St.
Paul, Minnesota (US), reported that more than a dozen scientists
received US$156,000 from the tobacco industry to write letters to
scientific journals disputing the carcinogenic effects of second-
hand smoke. The report was based on confidential industry
documents produced in a current litigation. Among the scientific
journals involved were the *Journal of the National Cancer
Institute*, *Journal of the American Medical Association*, *The
Lancet*, and *Pediatrics*. The authors were paid US$2250 to
US$10,000 per letter by the Tobacco Institute, and apparently two
law firms representing the industry revised some letters before
submission to the journals. According to the examined documents,
the strategy of the Tobacco Institute focused on recruiting
scientists "at or near retirement with no dependence on grant-
dispensing bureaucracies." Some of the journal editors involved
are apparently unconcerned, stating that what is important is
whether the content of a letter is solid. However, Richard
Horton, editor of *The Lancet*, says his reaction is one of
"disgust", and that the writing of such letters is "at best
unethical and at worst an example of research misconduct." 
Cardiologist Stanton Glantz (University of California San
Francisco, US) says of the tobacco industry letters: "They are
basically building up a record they could use for political and
legal purposes." One now wonders what corporate groups aside from
the tobacco industry have been promoting by generous financial
inducements the writing of letters by scientists to scientific
journals on other scientific topics of legal, political, or
commercial significance.
(Nature 13 Aug 98 394:609) (Science 14 Aug 98 281:895)
(ScienceWeek 4 Sep 98)
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Related Background:
NEW STUDY FINDS CORPORATE GIFTS IMPLY CORPORATE CONTROL
Blumenthal et al (2 installations, US) report an anonymous survey
of 2167 scientists working at 50 research-intensive universities
in the US. More than half of the university scientists who
received gifts of research material from pharmaceutical companies
or biotechnology companies report that the donors expect to exert
influence over their work, including review of academic papers
before publication, and retention of patent rights for commercial
discoveries. This is apparently the first study to examine
relations between commercial interests that give gifts of
research materials and the scientists who receive them. Unlike
research grants and contracts, gifts to US scientists are largely
unregulated by universities and are usually dismissed as
insignificant. Christopher Scott, director of research
development for the Stanford University Medical Center, says:
"There has been, in essence, a gray market of research based on
gifts for many, many years."
QY: Christopher Scott, Stanford University 415-723-2300.
(J. Amer. Med. Assoc. 1 Apr 98) (New York Times 1 Apr 98)
(ScienceWeek 10 Apr 98)
-------------------
Related Background:
INTIMIDATION OF RESEARCHERS BY SPECIAL INTEREST GROUPS
A recent issue of the highly respected New England Journal of
Medicine includes a 5 page exchange of letters on the subject of
intimidation of researchers by special interest groups. The
letters concern three different special interest-clinical science
entanglements: 1) a research study of multiple chemical
sensitivity; 2) the public health hazard of a marketed chemical
(tryptophan) product; 3) a clinical investigation of the outbreak
of interstitial lung disease among workers in a nylon flocking
plant. The first situation involves an accusation of attacks
against a researcher by special interests opposed to the
researcher's published results; the second situation involves an
accusation of peer review corruption by a large corporate entity
confronted with a billion-dollar damage suit; the third situation
involves an accusation of censorship and harassment of a medical
specialist by a manufacturing plant, a medical school
administration, and a hospital. These are all complicated
entanglements, and one cannot do full justice to them in a few
hundred words. But all parties on both sides of the issues
present their views, and these 5 pages of letters provide a
textbook illustration of the problems existing at the societal
interfaces of science. The letters are in response to an article
on the subject by Richard A. Deyo et al that appeared in NEJM on
April 14, 1997 (336:1176).
QY: R. A. Deyo, Univ. Washington Seattle (206) 543-7212
(New England J. Med. 30 Oct 97) (ScienceWeek 7 Nov 97)
-------------------
Related Background:
ACADEMIC JOURNAL REVISITS CORPORATE CORRUPTION OF SCIENCE
*Lingua Franca*, a highly respected general academic journal, has
published a review of some recent history in the arena of
corporate corruption of science and scientific research. The
fundamental problem is simply stated: Some corporations fund
scientific research with expectations, often contractual, of
control of publication and the final wording of conclusions in
the resultant papers. Several prestigious journals still do not
require scientists who report research results to reveal any
connections to interests that might profit from their
conclusions. But most of the scientific community is determined
to put an end to any corruption. The story is still to be played
out. (Lingua Franca June/July 1997) (ScienceWeek 29 May 97)
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For more information: http://scienceweek.com/swfr.htm

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2. NEUROBIOLOGY:
NEUROGENESIS AND CLINICAL DEPRESSION
     The term "depression" as used in clinical psychiatry is a
large basket filled with diagnostic ambiguities, historical
semantic baggage, and shifting therapeutic fashions.
Nevertheless, the clinical syndrome, no matter how foggy its
outlines, is real at its core, affects real people, is a major
cause of psychological dysfunction, and a major cause of suicide.
In the US alone, approximately 200,000 suicide attempts are made
each year; 75 people commit suicide every day; suicide accounts
for 30 percent of the deaths among university students and is the
second leading cause of death among adolescents. What is known is
that clinical depression is involved in over half of all
attempted suicides, a relation that defines the urgency of
research in this area. From the standpoint of clinical
neurobiology, the research problem is clear: clinical depression,
whatever it may be, is a dysfunctional alteration of behavior,
and the task of the clinical neurobiologist is to determine what,
if any, dysfunctional alterations of the brain and/or brain
dynamics are responsible for the clinical syndrome.
     The term "neurogenesis" refers to the generation of new
nerve cells. Until a few years ago, neurogenesis was considered
to be totally absent in the adult mammalian brain, but
neurogenesis has now been identified in certain regions of the
brains of several mammalian species, and there is currently much
research devoted to relating brain neurogenesis to various brain
pathologies.
... ... B.L. Jacobs et al (3 authors at 2 installations, US)
present a review of recent research relating clinical depression
and brain neurogenesis, the authors making the following points:
     1) The authors point out that many researchers believe that
*stress is the most significant causal agent (with the possible
exception of genetic predisposition) in the etiology of
depression. In addition, nerve cells in the *hippocampal region
of the brain are among the most sensitive to the deleterious
effects of stress. Consequently, a stress-induced decrease in
neurogenesis in the hippocampus may be an important factor in
precipitating episodes of depression. As a corollary, increasing
*serotinin-related neurotransmission is apparently the most
effective treatment for depression, and such treatment also
augments (in animal models) hippocampal neurogenesis. Thus,
serotonin-induced increases in neurogenesis might promote
recovery from depression. Considering all this, the authors
propose that the waxing and waning of neurogenesis in the
hippocampus might trigger the precipitation of and recovery from
episodes of clinical depression.
     2) The relation between stress and hippocampal neurogenesis
has been examined in several species. Removing the *adrenal
glands of a rat increases neurogenesis in the *dentate gyrus, and
this effect can be reversed with the *glucocorticoid hormone
corticosterone, which normally is secreted by the adrenal glands.
The circulating level of glucocorticoids apparently suppresses
the birth of neurons in the dentate gyrus under normal
conditions. It has also been demonstrated that systemic
administration of corticosterone to normal animals suppresses
dentate gyrus neurogenesis. In summary, stress apparently
suppresses the rate of dentate-gyrus cell proliferation in adults
of a number of species, and it probably does so through increases
in brain glucocorticoids.
     3) The authors point out that they do not exclude other
changes as being important in the etiology and recovery from
depression. For example, besides suppressing neurogenesis,
increased glucocorticoids might mediate additional direct
neuronal effects in various brain structures. Similarly, changes
in serotonin neurotransmission might also exert direct effects in
various brain structures. The authors suggest that all of these
changes, acting in concert, give rise to the complex syndrome of
depression.
-----------
B.L. Jacobs et al: Depression and the birth and death of brain
cells.
(American Scientist Jul/Aug 2000 88:340)
QY: Barry L. Jacobs: barryj@princeton.edu
-----------
Text Notes:
... ... *stress: See background material below.
... ... *hippocampal region: See background material below.
... ... *serotinin-related neurotransmission: The term
"neurotransmission" refers, in general, to the interactions
between nerve cells. Serotonin is one of a variety of
neurotransmitter substances, i.e., substances involved in the
mechanisms of neurotransmission.
... ... *adrenal glands: Organs that sit on the tops of the
kidneys (one on each kidney). Each adrenal gland has two parts,
adrenal cortex and adrenal medulla. The adrenal cortex secretes
corticosteroid and androgen hormones; the adrenal medulla makes
the hormones epinephrine (adrenalin) and norepinephrine.
... ... *dentate gyrus: The term "dentate gyrus" refers to one of
the two interlocking gyri (folds) composing the hippocampus.
... ... *glucocorticoid hormone corticosterone: See background
material below.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 1Dec00
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
NEUROBIOLOGY: NEUROLOGICAL CORRELATES OF LEARNING DEFICITS
PRODUCED BY PRENATAL STRESS
     The concept of "stress" has a long and rich history in
psychobiology. Hans Selye (1907-1982) pioneered the idea of a
discrete paradigm describing the linkage between psychological
stress, physiological response (usually involving hormone
secretions), and histopathological consequences. In the medical
community, during the past 50 years, the degree to which any such
paradigm linking psychological events to specific tissue
pathology has been accepted has varied widely from one individual
physician to another. In general, current neurobiological and
psychobiological researchers take the paradigm for granted;
medical practitioners accept or avoid the paradigm, depending on
their training in psychiatry. But what is not disputed by anyone
is that psychological events, particularly psychological "stress"
(in the general sense of the term) can produce physiological
changes that may include changes in the secretions of hormones,
and that such changes, in turn, may affect the behavior of
various parts of the nervous system. (As elementary examples of
physiological changes produced by psychological stress, consider
the change in heart rate produced by a frightening psychological
event, or the alteration of the capillary beds in the skin of the
face (blushing) produced by an embarrassment.)
     The central question remains of profound importance: To what
extent can environmental psychological stresses perceived by the
sensory systems produce long-lasting pathological changes in
tissues both neural and non-neural?
     But if the question is important (and rather easily stated),
attempts to obtain an answer are confronted with enormous
difficulties because of the limitations of research with human
subjects. Animal models are of prime importance in this field,
and although the extrapolation from an animal model to human
biology in this domain is often uncertain, each piece of
information is a potential nugget in a field where research is
not easy.
     The term "corticosterone" refers to a glucocorticoid,
specifically to an important corticosteroid of the normal human
adrenal cortex. Among other things, corticosterone induces
deposition of glycogen in the liver, sodium conservation, and
potassium secretion. It is the principal glucocorticoid in the
rat. (In general, a "glucocorticoid" [glycocorticoid] is any
steroid-like compound capable of significantly influencing
intermediary metabolism.
     The term "hippocampus" refers to a region of the cerebral
cortex in the medial part of the temporal lobe. In humans, among
other functions, the hippocampus is apparently involved in
short-term memory, and analysis of the neurological correlates of
learning behavior in animals indicates that the hippocampus is
also involved in memory in other species.
     The term "dentate gyrus" refers to one of the two
interlocking gyri (folds) composing the hippocampus.
... ... V. Lemaire et al (4 authors at University of Bordeaux,
FR) present a study of the effects of prenatal stress in rats on
neurological development, the authors making the following
points:
     1) There is much evidence from animal studies that during
the period immediately before, during, and immediately after
birth (perinatal period), the development of an organism is
subjected to complex environmental influences. For example,
deleterious life events during pregnancy may induce
neurobiological and behavioral defects in offspring, with some of
these effects involving the hippocampus. Indeed, there is
evidence that prenatal stress results in an enhanced production
of stress hormones by the mother during critical periods of fetal
brain development, and that prenatal stress provokes a longer
corticosterone response to stress in the offspring associated
with a reduction in the number of hippocampal corticosteroid
receptors. Behaviorally, such progeny, from adulthood to
senescence, exhibit memory deficits in a hippocampal dependent
task.
     2) The authors report that prenatal stress in rats induced
lifespan reduction of neurogenesis in the dentate gyrus and
produced impairment in hippocampal-related spatial tasks.
Prenatal stress blocked the increase of learning-induced
neurogenesis. The authors suggest their data strengthen
pathophysiological hypotheses that propose an early
neurodevelopmental origin for psychopathological vulnerabilities
in aging.
     3) In this study, stress was performed each day of the last
week of pregnancy from day 15 until delivery. Pregnant females
were individually restrained for 45 minutes 3 times a day during
the light phase in plastic transparent cylinders (7 centimeters
diameter, 19 centimeters long) exposed to bright light. Control
pregnant females were left undisturbed in their home cages.
     4) The authors conclude: "The major impact of our data lies
in the demonstration that deleterious environmental conditions
occurring early in life have profound effects on neurogenesis in
the dentate gyrus, an index of hippocampal *plasticity, and that
these alterations are associated with impaired performances in a
spatial memory task. Neurogenesis, cell number, and cognitive
capabilities are altered from adulthood to senescence in
prenatally stressed rats... Our results reinforce the hypothesis
that many psychopathological affections have their origin in
early developmental influences. More generally, they show the
heuristic value of accurate animal models to better understand
the mechanisms by which early stress and *epigenetic risk factors
promote learning disabilities in children and in age-related
disorders such as Alzheimer's disease."
-----------
V. Lemaire et al: Prenatal stress produces learning deficits
associated with an inhibition of neurogenesis in the hippocampus.
(Proc. Natl. Acad. Sci. US 26 Sep 00 97:11032)
QY: D.N. Abrous: Nora.Abrous@bordeaux.inserm.fr
-----------
Text Notes:
... ... *plasticity: In neurobiology, the term "plasticity" is
the name given to the capacity of neural tissue to adjust to
change. One variant of this concerns the dependence of the
"wiring" of the nervous system on its input. Another variant
concerns the degree to which one region can under certain
conditions assume the function of another region. Plasticity does
not occur everywhere in the nervous system, but it is often
evident in the cerebral cortex of the brain, the cortex being the
thin layer of cells apparently responsible for higher analysis of
sensory input, language, ideation, and other so-called higher
functions lumped together in the category "cognitive processes".
... ... *epigenetic risk factors: In this context, risk factors
associated with fetal and postnatal development. 
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 20Oct00
For more information: http://scienceweek.com/swfr.htm

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3. MEDICAL BIOLOGY:
THE PLASMA MEMBRANE AND HIV 
     The "plasma membrane" (cell membrane) of biological cells is
a lipid-protein bilayer barrier between the cell and its
environment, and any interaction of the cell with that
environment must necessarily involve traffic of some sort through
the cell membrane. This membrane is not passive at all, but quite
actively involved in one way or another with all the chemical
traffic and energy traffic that ordinarily moves through it, and
it is also involved with certain special events of extreme
medical importance, such as the action of hormones and
pharmacological agents, all the nutritive processes of cancer
cells, and the attacks on cells by pathogenic viruses and
bacteria.
     Human immunodeficiency virus (HIV) is the primary
etiological agent of acquired immunodeficiency syndrome (AIDS).
The illness AIDS was first described in 1981, and the virus was
isolated by the end of 1983. Since then, AIDS has become a
worldwide epidemic, expanding in scope and magnitude as HIV
infections have become prevalent in different populations and
geographic regions. The current estimate is that approximately 35
million people are infected worldwide. Once infected, individuals
remain infected for life. Within a decade, if left untreated, the
vast majority of HIV-infected individuals develop fatal
opportunistic infections as a result of HIV-induced deficiencies
in the immune system. HIV-1 is the subtype of HIV that causes
most cases of AIDS in the Western Hemisphere, Europe, and
Central, South, and East Africa.
     HIV is a spherical virus, 80 to 100 nanometers in diameter,
and with a cylindrical core containing its genome. The virus has
an "envelope", i.e., it is bounded by a lipid-protein bilayer
membrane similar to the plasma membrane of host cells. The virus
is a retrovirus (subclass lentivirus), and retroviruses are
single-stranded RNA viruses that have an enzyme called reverse
transcriptase. With this enzyme the viral RNA is used as a
template to produce viral DNA from cellular material. This DNA is
then incorporated into the host cell's genome, where it codes for
the synthesis of viral components. As noted above, HIV should be
distinguished from AIDS. Acquired immunodeficiency syndrome
(AIDS) is a secondary immunodeficiency syndrome resulting from
HIV infection and characterized by opportunistic infections,
malignancies, neurologic dysfunction, and a variety of other
syndromes.
     In order to infect cells, HIV (like other viruses) must
penetrate cells, and this requires a specific contact of the
virus with the plasma membrane of such cells. HIV uses as a cell
membrane receptor the cell surface protein CD4, which is
expressed on the surface of certain *macrophages and *T
lymphocytes of the immune system (when HIV infects neurons,
another surface receptor may be used). In general, the
interaction of HIV with host-cell plasma membrane is the first
critical step in cellular HIV infection.
... ... R.W. Doms and D. Trono (2 installations, US CH) present a
review of current research on HIV-plasma membrane interactions,
the authors making the following points:
     1) The authors point out that the plasma membrane is the
site where intracellular pathogens first clash with their target
and the place from which the immune system is subsequently called
to the rescue. Recent progress in the analysis of the HIV, which
is probably the most extensively characterized of all human
pathogens, provides a good illustration of the central role
played by the plasma membrane in HIV-host cell interactions. Just
as the composition of the plasma membrane influences viral
infectivity, the virus in turn uses components of the plasma
membrane that are to its advantage and modifies other components
to suit its purposes. The authors suggest the interplay between
HIV and the plasma membrane has much to offer for the
understanding of viral tropisms (see below), pathogenicity, and
normal cellular functions, and for the development of new
antiviral approaches.
     2) To infect a cell, a membrane-enveloped virus such as HIV
must transfer its genome across both the viral and host surface
membranes -- not a trivial task given the inherent stability of
biological membranes. Enveloped viruses accomplish this feat by
encoding and expressing on their surface integral membrane
proteins that under the right conditions undergo conformational
changes that cause the viral and host surface membranes to fuse
with one another, thus providing a portal of entry for the virus.
This entry process can be divided into 3 phases: a) attachment of
the virus to the host cell surface, involving recognition and
binding to specific host cell surface receptors; b) a triggering
event that causes a viral protein that promotes membrane fusion
to undergo conformational changes; and c) the membrane fusion
reaction itself. The presence or absence, on the host cell
surface, of specific molecules necessary for attachment and
triggering greatly influences the ability of a given virus to
infect only specific cell types ("viral tropism").
     3) The HIV-1 envelope protein (Env) is a type 1 integral
membrane protein that mediates viral attachment and membrane
fusion, and it is also the target for antiviral neutralizing
*antibodies. The primary host cell surface receptor for HIV-1 is
the protein cluster CD4, which explains the propensity of HIV-1
to infect CD4-bearing immune system macrophages and T cells (T
lymphocytes), ultimately leading to immune dysfunction. Although
CD4 binding is a prerequisite for HIV-1 entry, attachment of
virus per se may be mediated by a number of different molecules
that can serve to concentrate virus on the cell surface and thus
increase the frequency of Env-receptor interactions.
     4) Once delivered into the host cell, the HIV genome is
reverse transcribed and transported to the cell nucleus, where it
integrates in the host-cell chromosome as a "provirus". Viral
gene expression then proceeds in two stages, the first stage
yielding viral regulatory proteins, and the second stage
producing a number of gene products involved in some aspect of
*virion formation. Through several of these viral genome
products, the virus influences the *homeostasis of the host
plasma membrane, affecting in particular the surface expression
of specific receptors, including CD4. Our understanding of these
phenomena is still unclear and insignificant when compared to our
understanding of the mechanisms of viral entry into the host
cell.
     5) Just as virus infection requires an assemblage of
specific proteins at the point of entry, so does viral "budding",
the process in which new virions emerge from the plasma membrane
wrapped in a lipid bilayer and loaded with surface proteins that
include Env. Virus assembly may be the key to important insights
into viral pathogenesis. For example, in mouse cells HIV fails to
assemble and bud correctly, suggesting that mouse host cells
either lack a cellular factor needed for budding or contain a
factor that inhibits this process.
     6) The authors conclude: "Clearly, a greater appreciation of
the molecular events that describe HIV interactions with the
plasma membrane will further our understanding of viral tropism
and provide new therapeutic approaches. Furthermore, it will
continue to yield important information concerning the
complicated set of interactions and biochemical processes that
allow the plasma membrane to mastermind many aspects of biology
of a cell."
-----------
R.W. Doms and D. Trono: The plasma membrane as a combat zone in
the HIV battlefield.
(Genes & Development 1 Nov 00 14:2677)
QY: Didier Trono: didier.trono@medicine.unige.ch
-----------
Text Notes:
... ... *macrophages: Amoeba-like white blood cells (leukocytes)
that are able to surround and digest foreign entities such as
bacteria and protozoa.
... ... *T lymphocytes: (T-cells) Lymphocytes (lymph cells,
lympho-leukocytes) are a type of leukocyte (white blood cell)
involved in the immune response. There are two classes of such
lymphocytes: 1) the B-cells, which after a cascade of immune
system events involving a specific *antigen change into
proliferating specific antibody producing plasma cells; 2) the
T-cells, one subclass of which (cytotoxic T-cells) interacts
directly with foreign invaders such as bacteria and viruses,
while the other subclass of T-cells (helper T-cells) is involved
in the proliferation of *antibody-specific B-cells.
... ... *antigen: In general, an antigen is any substance or
moiety that produces an immune response.
... ... *antibodies: In general, an antibody is a protein
molecule produced by the immune system of vertebrate organisms,
the molecule designed to specifically interact with a particular
invading foreign antigen.
... ... *virion: In general, a "virion" is a virus particle that
appears structurally complete when viewed in the electron
microscope, i.e., core plus protein coat plus lipid-protein
bilayer membrane (if any) -- the complete infectious particle.
... ... *homeostasis: The term "homeostasis" refers to a
physiological equilibrium necessary in general for the viability
of an organism, and in particular for the operation of many
cellular functions. Homeostatic mechanisms in biological systems
usually involve an element of negative feedback signaling. In
vertebrates, for example, when blood temperature is too high,
temperature receptors provoke a sequence of events involving many
pathways that ultimately results in a lowering of body
temperature. Similar homeostatic mechanisms operate at cellular
levels.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 1Dec00
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
MEDICAL BIOLOGY: HIV AS THE CAUSE OF AIDS
An international plague as devastating as AIDS is bound to
produce various political and social reactions, including denials
of evidence. In South Africa, there is now a controversy about
whether AIDS is caused by the human immunodeficiency virus (HIV),
and in response to such views in South Africa and elsewhere, an
international group of more than 5000 scientists and medical
professionals released in July what is called "The Durban
Declaration". This document primarily addresses the question of
the cause of AIDS, and it makes the following points:
     1) The latest data reveal that an estimated 34.3 million
people worldwide are living with HIV or AIDS, 24.5 million of
them in sub-Saharan Africa. Last year alone, 2.8 million people
died of AIDS, the highest rate since the start of the epidemic.
If current trends continue, southern and southeast Asia, South
America, and regions of the former Soviet Union will also bear a
heavy burden in the next two decades.
     2) AIDS spreads by infection, like many other diseases
(e.g., tuberculosis and malaria) that cause illness and death
particularly in underprivileged and impoverished communities.
HIV-1, which is responsible for the AIDS pandemic, is a
*retrovirus closely related to simian immunodeficiency virus
(SIV) that infects chimpanzees. HIV-2, which is prevalent in West
Africa and has spread to Europe and India, is almost
indistinguishable from an SIV that infects sooty mangabey
monkeys. Although HIV-1 and HIV-2 first arose as infections
transmitted from animals to humans (zoonoses), both now spread
among humans via a) sexual contact; b) from mother to infant; and
c) via contaminated blood.
     3) An animal source for an infection is not unique to HIV.
The bubonic plague came rodents, and influenza came from birds.
The new Nipah virus in Southeast Asia reached humans via pigs.
Variant Creutzfeldt-Jakob disease in the UK is identical to "mad
cow disease". Once HIV became established in humans, it soon
followed human habits and movements. Like many other viruses, HIV
recognizes no social, political, or geographical boundaries.
     4) The evidence that AIDS is caused by HIV-1 or HIV-2 is
clear-cut, exhaustive, and unambiguous, meeting the highest
standards of science. The data fulfill exactly the same criteria
as for other viral diseases, such as polio, measles, and
smallpox. The major evidence that HIV causes AIDS is as follows:
... ... a) Patients with acquired immune deficiency syndrome
(AIDS), regardless of where they live, are infected with HIV.
... ... b) If not treated, most people with HIV infection show
signs of AIDS within 5 to 10 years. HIV infection is identified
in blood by detecting antibodies, viral gene sequences, or actual
viral isolation. These tests are as reliable as any used for
detecting other virus infections.
... ... c) People who receive HIV-contaminated blood or HIV-
contaminated blood products develop AIDS, whereas people who
receive untainted or screened blood do not develop AIDS.
... ... d) Most children who develop AIDS are born to HIV-
infected mothers. The higher the viral load in the mother, the
greater the risk of the child becoming infected.
... ... e) In the laboratory, HIV infects the exact type of white
blood cell (*CD4 lymphocytes) that becomes depleted in people
with AIDS.
... ... f) Drugs that block HIV replication in the test tube also
reduce virus load in people and delay progression to AIDS. Where
available, treatment has reduced AIDS mortality by more than 80
percent.
... ... g) Monkeys inoculated with cloned SIV DNA become infected
and develop AIDS.
     5) The Declaration states: "Further compelling data are
available. HIV causes AIDS. It is unfortunate that a few vocal
people continue to deny the evidence. This position will cost
countless lives."
-----------
The Durban Declaration
(Nature 6 Jul 00 406:15)
-----------
Text Notes:
... ... *retrovirus: See main report.
... ... *CD4 lymphocytes: ... The severe immunodeficiency disease
we know as AIDS is a result of depletion of immune system helper
T-cells, which are the T-lymphocytes that initiate the vertebrate
immune response. The human immunodeficiency retrovirus contains
an envelope protein (gp120) that specifically binds to a surface
glycoprotein (CD4) carried by helper T cells. The result of this
binding is the merging of the viral lipid bilayer membrane with
the T-cell membrane and entry of the virus particle into the
T-cell, where the RNA genome of the virus is uncovered, viral DNA
produced using a viral reverse transcriptase, and the viral DNA
then incorporated into the DNA of the host T-cell. Following
this, the DNA of the host T-cell begins to produce the components
for hundreds of new virus particles. These components undergo an
assembly process into virus particles. The new virus particles
diffuse to the T-cell membrane, wrap themselves with pieces of
that membrane, and then are extruded by a budding process into
the extracellular solution. Once released, the new virus
particles can proceed to infect other T-cells. The scenario
quickly wears out the T-cells and kills them. The HIV virus is
remarkably simple, its genome coding for only 4 enzymes, but it
is a virus which attacks cells critical to the immune system, the
helper T cells, which makes a natural defense against the virus
extremely difficult. Because it is a retrovirus (a virus that
uses reverse transcriptase), HIV is also a rapidly mutating
entity, which makes any natural defenses even more difficult.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 8Sep00
For more information: http://scienceweek.com/swfr.htm

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4. ASTROPHYSICS: ON STARDUST
In astrophysics, the term "dust" refers to various entities: a)
interplanetary and cometary dust are found in the Solar System;
b) circumstellar dust is found around stars; c) interstellar dust
is found between stars. Individual dust particles are usually
called "dust grains" and range in size from approximately 10
nanometers up to the micron range (with an average size about the
size of particles in cigarette smoke). Interstellar dust
extinguishes and reddens starlight, can be detected by its
absorption and emission of infrared radiation, and can be
detected by its polarizing effect on starlight. The exact
composition of interstellar dust is uncertain, but infrared
absorption measurements indicate that a significant fraction of
the material is organic. In general, interstellar dust is
believed to be carbon, iron, and silicates mixed with or coated
with frozen water.
... ... J. Mayo Greenberg (University of Leiden, NL) presents a
review of recent research on interstellar dust and cometary dust,
the author making the following points:
     1) The extinction curve for interstellar dust, which
indicates the reduction of light intensity at each wavelength,
indicates there must be 3 types of dust grains: a) The particles
that block light in the visible spectrum are elongated grains
nearly 0.2 microns in diameter and approximately 0.4 microns in
length. These particles account for approximately 80 percent of
interstellar dust, with each grain containing a rocky core
surrounded by a mantle of organic materials and ice. b) A hump in
the ultraviolet part of the extinction curve suggests the
presence of smaller particles of approximately 5 nanometers
diameter, which comprise approximately 10 percent of the total
dust mass. These grains are most likely amorphous carbonaceous
solids that probably contain some hydrogen but little or no
nitrogen or oxygen. c) Finally, an even smaller type of particle,
approximately 2 nanometers in diameter, is apparently responsible
for blocking light in the far ultraviolet region. These smallest
particles, which constitute the remaining 10 percent of the dust
mass, are believed to be large molecules similar to the
polycyclic aromatic hydrocarbons emitted in automobile exhaust.
     2) The author postulates a 100-million-year "dust cycle",
which dust grains undergo approximately 50 times before their
destruction:
... ... a) In diffuse dust clouds, where gas is sparse, the dust
is a mixture of core-mantle grains, carbonaceous particles, and
polycyclic aromatic hydrocarbon-like (PAH-like) molecules.
... ... b) When the dust enters a dense gas cloud, atoms and
molecules of gas adhere to the core-mantle grains and form an
outer mantle of ice. The carbonaceous particles and PAH-like
molecules also accrete on the core-mantle grains.
... ... c) Ultraviolet radiation affects the material in the ice
mantle, creating a layer of complex organic compounds of
yellowish color.
... ... d) As the cloud of dust and gas contracts to form a star,
some of the core-mantle dust grains clump together and become
comet nuclei. But the vast majority of the dust is dispersed.
... ... e) Returning to a diffuse cloud, the core-mantle grain is
exposed to harsher radiation that evaporates the ice mantle and
further processes the organic material. The complex of organic
compounds turns from yellowish to brown.
... ... f) Supernova shock fronts accelerate the dust grains,
causing violent collisions that shatter the organic mantles. The
debris becomes the carbonaceous particles and PAH-like molecules.
     3) The author points out that as astronomers make new
discoveries about the chemical composition of both comets and
interstellar dust, they are becoming convinced that comets
originally formed as clumps of dust grains. In addition, comet
dust may have played a role in seeding life on Earth. Each loose
cluster of comet dust not only contains organic materials, but
also has a structure that is ideal for chemical evolution once it
is immersed in water. Experiments have indicated that small
molecules could easily penetrate such clumps from the outside,
while large molecules would remain sequestered in the interior.
The author states: "Such a structure could stimulate the
production of ever larger and more complex molecules, possibly
serving as a tiny incubator for the first primitive life forms. A
single comet could have deposited up to 10^(25) of these 'seeds'
on the young Earth."
-----------
J. Mayo Greenberg: The secrets of stardust.
(Scientific American December 2000)
QY: J. Mayo Greenberg, University of Leiden, NL
-------------------
Summary by SCIENCE-WEEK http://scienceweek.com 1Dec00
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
ON CARBON IN THE UNIVERSE
Carbon is a major factor in the evolutionary scheme of the
Universe because of its abundance and its ability to form complex
chemical entities. It is apparently also a key element in the
evolution of prebiotic molecules. The different forms of cosmic
carbon range from carbon atoms and carbon-bearing molecules to
complex solid-state carbonaceous structures, and evidence
gathered during the past decade has considerably enhanced our
understanding of the physical and chemical properties of carbon
materials in space. ... ...  Th. Henning and F. Salama (2
installations, DE US) present a detailed review of the subject,
the authors making the following points: 1) More than 75 percent
of the 118 *interstellar and circumstellar molecules identified
to date are carbon-bearing molecules, and one component of
interstellar dust is evidently carbonaceous. The cosmic evolution
of carbon from the interstellar medium into *protoplanetary disks
and *planetesimals, and finally into habitable bodies, is
intrinsic to the study of the origin of life. 2) Carbon plays an
important role in the physical evolution of the interstellar
medium because it is the main supplier of free electrons in
diffuse interstellar clouds, thus contributing to the heating of
interstellar gas. 3) The observation of unidentified ubiquitous
molecular and solid-state features in astronomical spectra, and
the realization that these features are linked to carbonaceous
materials, have resulted in major scientific progress in the past
decade. Laboratory and theoretical studies stimulated by these
astronomical observations have led to a better understanding of
the various forms of cosmic carbon such as polycyclic aromatic
hydrocarbons, carbon-chain molecules, carbon clusters, and
carbonaceous solids. These investigations have also led to the
detection of novel forms of carbon and laid the foundations for
the chemistry of *fullerenes. 4) The authors present the
following categorization of carbon in space:
... a) Carbon-rich circumstellar envelopes around *red giant and
*asymptotic giant branch (AGB) stars: CO, C(sub2)H(sub2), complex
hydrocarbons, gas-phase polycyclic aromatic hydrocarbons.
... b) Diffuse interstellar medium: C+, simple diatomic
molecules, gas-phase polycyclic aromatic hydrocarbons and carbon
chains.
... c) Dense interstellar medium: CO, complex hydrocarbons.
... d) Interstellar material in primitive meteorites: polycyclic
aromatic hydrocarbons.
5) The authors suggest that the widespread distribution of
complex organics in the interstellar medium has profound
implications for our understanding of a) the chemical complexity
of the interstellar medium, b) the evolution of prebiotic
molecules, c) the impact of this evolution on the origin and
evolution of life on early Earth through the exogenous delivery
(by cometary encounters and meteoritic bombardments) of prebiotic
organics.
-----------
Th. Henning and F. Salama: Carbon in the Universe.
(Science 18 Dec 98 282:2204)
QY: Th. Henning, Astrophysikalisches Institut und Universitats-
Sternwarte, Schillergabchen 2-3, D-07745, Jena DE.
-----------
Text Notes:
... ... *interstellar and circumstellar molecules: In this
context, an interstellar molecule is any molecule that occurs
naturally in clouds of gas and dust in space. In general, a
circumstellar molecule is any molecule that occurs in gas and
dust surrounding a star.
... ... *protoplanetary disks: These are dust disks surrounding
young stars; it is from these disks that planets presumably form.
... ... *planetesimals: Planetesimals are bodies with dimensions
of 10^(-3) to 10^(3) meters that are believed to form planets by
a process of accretion. The term "accretion" refers to an
aggregation, an increase in the mass of a body by the addition of
smaller bodies that collide and adhere to it, provided the
relative velocities are low enough for coalescence. As the mass
of the agglomerate increases, so does the rate of accretion, and
this accretion process is believed to generally occur in the form
of a disk. A stellar accretion disk is a swarm of dust grains
that evolve into planetesimals and then planets.
... ... *fullerenes: Fullerenes are large molecules composed
entirely of carbon, with the chemical formula C(sub n), where n
is any even number from 32 to over 100. They apparently have the
structure of a hollow spheroidal cage with a surface network of
carbon atoms connected in hexagonal and pentagonal rings.
... ... *red giant: A red giant star is a star in a late
stage of evolution. Having exhausted the hydrogen fuel in its
core, the star is burning elements heavier than hydrogen. It has
a surface temperature of less than 4700 degrees Kelvin and a
diameter 10 to 100 times that of the Sun.
... ... *asymptotic giant branch (AGB) stars: These are stars
that occupy a strip in the *Hertzsprung-Russell diagram that is
almost parallel to and just above what is called the "giant
branch" off the *Main Sequence. Stars evolve from the horizontal
H-R branch to the asymptotic giant branch when they have
exhausted the helium in their cores and are instead burning
helium in a shell.
... ... *Hertzsprung-Russell diagram: The Hertzsprung-Russell
diagram is a plot of stellar absolute magnitude against spectral
type, and is perhaps the most useful diagrammatic aid in
astrophysics. It allows the portrayal of the evolution of a star
as occurring along various paths in the diagram.
... ... *Main Sequence: The Main Sequence is a region on the
Hertzsprung-Russell diagram where most stars lie, including our
own Sun. The evolution of a star can be diagrammed as a movement
along the Main Sequence and an eventual branching off the Main
Sequence to regions associated with various types of old stars.
-------------------
Summary & Notes by SCIENCE-WEEK http://scienceweek.com 26Feb99
For more information: http://scienceweek.com/swfr.htm

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5. CONDENSED MATTER PHYSICS:
ON DIFFUSION IN SEMICONDUCTORS
     The term "self-diffusion" refers to the diffusion of an atom
or molecule in a space occupied by a uniform distribution of
entities of the same kind (i.e., no chemical potential
gradients). In practice, experimental methods for determining
self-diffusion coefficients usually involve the diffusion of a
radioactive isotope of an entity through an ordinary non-
radioactive population of that entity. Some textbooks define the
term "self-diffusion" only in relation to the movement of atoms
or molecules in crystals, but the restriction is not justified:
self-diffusion may be measured in solids, liquids, and gases,
although mechanisms of diffusion may differ in each case.
     With reference to crystals, the term "lattice" refers (in
the case of a 3-dimensional solid) to a regular periodic repeated
3-dimensional array of points that specify the positions of
atoms, molecules, or ions in the crystal, and the term
"sublattice" refers to any determinable subset of that lattice.
     In 1896, W.C. Roberts-Austen (1843-1902) demonstrated that
gold diffused faster in lead at 300 degrees centigrade than
sodium chloride diffused in water at 15 degrees centigrade, i.e.,
solid-state diffusion could be faster than liquid-state
diffusion. This was a puzzle, since because the energy
requirements were too high, it was difficult to believe that
atoms moved in solids simply by changing places with one another.
     Mechanisms for solid-state diffusion were eventually
suggested by J. Frenkel in 1926 and by W. Schottky in 1930,
Frenkel and Schottky proposing the first exact models for what
are now called "point defects" in crystals. The general idea is
that self-diffusion in crystals must involve defects in the
crystal lattice, since only then do energetic constraints make
translocation of atoms possible. The term "point defect" refers
to defects involving a single atom or molecule: either a simple
"vacancy" at a lattice point (Schottky defect), or a vacancy plus
the presence of the atom of ion between two lattice points
(Frenkel defect). The errant atom or ion between two lattice
points is called an "interstitial". The Frenkel defect consists
of both the vacancy and the interstitial. In an ionic crystal, a
Schottky defect consists of at least two lattice vacancies, since
electroneutrality requires that the absence of one ion also
involves the absence of compensating ions of opposite sign.
     Until the 1950s, the study of diffusion in solids was a
relatively peaceful branch of condensed-matter physics, but with
the invention of transistors, and the importance of diffusion in
semiconductors, the field immediately flowered and has been the
focus of intensive research ever since. [See Report #6 in this
issue for more discussion of semiconductors.]
     Gallium antimonide is used to make infrared lasers and
photodetectors, night-vision devices, solar cells, and some
special transistors.
... ... H. Bracht et al (6 authors at 2 installations, US ES)
present a study of self-diffusion of gallium and antimony in
gallium antimonide, the authors making the following points:
     1) The authors point out that compared to conventional self-
diffusion experiments, which use radioactive probe atoms of the
matrix introduced from the surface, diffusion studies with highly
enriched stable isotopes are neither limited by the half-life of
the radiotracer nor affected by near-surface degradation. Such
diffusion experiments can therefore by extended to much longer
times and conducted over a wider temperature range. In
combination, these advantages lead to more accurate measurements
of self-diffusion parameters.
     2) The authors report self-diffusion studies with an
isotopically controlled multilayer structure of crystalline
gallium antimonide. Two stable isotopes exist for both gallium
and antimony, allowing the simultaneous study of diffusion on
both sublattices. The authors report their experiments
demonstrate that near the melting temperature, gallium diffuses
more rapidly than antimony by over 3 orders of magnitude. The
authors suggest this surprisingly large difference in atomic
mobility requires a physical explanation that goes beyond
standard diffusion models. Combining their data for gallium and
antimony diffusion with related results for foreign-atom
diffusion in gallium antimonide, the authors conclude that the
unusually slow antimony diffusion in gallium antimonide is a
consequence of reactions between defects on the gallium and
antimony sublattices, these reactions suppressing the defects
that are required for antimony diffusion.
... ... In a commentary on this work, Ulrich Goesele (Max Planck
Institute of Microstructure Physics, DE) states: "This result
contradicts earlier measurements, and was not expected from the
diffusion behavior of other semiconductor compounds... The
significance of Bracht and colleagues' result does not stem from
the technological importance of gallium antimonide. Rather, it is
because the finding is another in a long line of unexpected
differences and similarities encountered in the history of
understanding diffusion in semiconductors."
-----------
H. Bracht et al: Large disparity between gallium and antimony
self-diffusion in gallium antimonide.
(Nature 2 Nov 00 408:69)
QY: H. Bracht: bracht@uni-muenster.de
-----------
Ulrich Goesele: Surprising movements in solids.
(Nature 2 Nov 00 408:38)
QY: Ulrich Goesele: goesele@mpi-halle.de
-------------------
Summary by SCIENCE-WEEK http://scienceweek.com 1Dec00
For more information: http://scienceweek.com/swfr.htm

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6. APPLIED PHYSICS:
A LIGHT-EMITTING FIELD EFFECT TRANSISTOR
     In general, a "semiconductor" is a crystalline solid, such
as silicon or germanium, with an electrical conductivity
intermediate between that of a conductor and an insulator. In
general, an "orbital" is a space region in which an electron may
be found in an atom or molecule, the space region essentially a
probability distribution for the electron described by the
equations of quantum mechanics. Since the atoms in a crystalline
solid are in close proximity, the orbitals of their electrons
overlap and the possible electron energy levels are effectively
spread into energy "bands". Electric conduction occurs in
semiconductors as the result of a net movement under the
influence of an applied electric field, a movement of electrons
in the "conduction band" and a movement of empty states (called
"holes") in the "valence band". A hole effectively behaves as an
electron with a positive charge, and electrons and holes are
known as the "charge carriers" in a semiconductor. If a
particular semiconductor or region of a semiconductor has
electrons as the majority carriers of electric current (by
definition, more than 50 percent; the other carriers are called
"minority" carriers), the region is called an "n" region (for
negative carriers); where holes are the majority carriers, the
region is called a "p" region (for positive carriers). A "p-n"
junction is therefore a transition region between a p-region and
an n-region.
     In this context, the term "injection" refers to the process
of introducing electrons or holes into a semiconductor so that
their total number exceeds the number present at thermal
equilibrium.
     A transistor is essentially a semiconductor device in which
it is possible to control voltage or current in such a way as to
achieve gain or switching action. In general, the current flowing
between two specified electrodes is controlled or modulated by a
voltage applied at a third (control) electrode. The term
"transistor" was originally derived from the phrase "transfer
resistor", as the resistance of the output electrodes was
controlled by the input circuit (transferred). There are two
major classes of transistor: the so-called "bipolar junction
transistor" and the "field-effect transistor".
     The bipolar junction transistor was invented in 1947 by John
Bardeen (1908-1991), Walter H. Brattain (1902-1997), and William
B. Shockley 1910-1989). This type of transistor consists of two
p-n junctions placed back-to-back in close proximity: in general,
there are 3 layers of semiconductor material in a bipolar
junction transistor, the center layer having current carriers
complementary to that of the two outer layers. The central layer
is very thin and is known as the "base", the other two layers
being the "emitter" and "collector". There are two basic types of
bipolar junction transistor, p-n-p and n-p-n. Such a device
utilizes the flow of both electrons and holes across the
junctions for its electrical behavior. The current flow through
the emitter and collector electrodes is controlled by the voltage
across the base-emitter p-n junction.
     The "field effect transistor" (FET) is a transistor
consisting essentially of a channel of semiconductor material,
the resistance of which can be controlled by the voltage applied
to one or more input terminals (gates). It is a 3-terminal device
in which current flow through one pair of terminals, the "source"
and the "drain", is controlled or modulated by an electric field
that penetrates the semiconductor, with this field introduced by
the voltage applied at the third terminal, the "gate". The
controlling field applied to the gate must be isolated somehow
from the current flow in the channel, and there are two general
methods of accomplishing this isolation: a) in the "junction
field-effect transistor" (JFET), invented by Shockley, the
isolation is provided by a special junction barrier across which
current flow from gate to channel is very small; in the
"insulated gate field-effect transistor" (IGFET), first proposed
in the 1930s but not realized until 1960, an insulating layer is
placed between the gate electrode and the conducting channel,
preventing any current flow between them. The insulated-gate
field-effect transistor is sometimes called a "surface field-
effect transistor", since the effective conducting channel is the
semiconductor surface. (In contrast, the JFET, in which the bulk
of the semiconductor is the current carrier, is sometimes called
a "bulk field-effect transistor".)
     In general, an ambipolar transistor is a transistor which
depends for its action on two types of charge carrier (electrons
and holes), while a unipolar transistor is a transistor which
depends for its action primarily on one type of charge carrier
(either electrons or holes). All bipolar junction transistors are
ambipolar; some field-effect transistors are ambipolar, while
other field-effect transistors are unipolar.
     In general, an "exciton" is an electron paired with a hole
in a crystalline solid. The electron has gained sufficient energy
to be in an excited state and is bound by electrostatic
attraction to the positive hole. The exciton may migrate through
the solid, and eventually the hole and electron recombine with
emission of a photon.
     In this context, the term "coherent light" refers to light
in which radiation waves are in phase both spatially and
temporally, e.g., as in a laser.
     In general, an "organic semiconductor" is an organic
material having unusually high conductivity and other properties
associated with semiconductors, e.g., anthracene.
... ... J.H. Schoen et al (3 authors at Bell Laboratories, US)
report on a new light-emitting field-effect transistor, the
authors making the following points:
     1) The authors point out that field-effect transistors are
generally unipolar devices in which minority carrier effects are
negligible. However, ambipolar field-effect transistors, which
operate as either n- or p-channel devices, depending on the
polarity if the gate voltage (gate bias), can operate in a mixed
or bipolar mode, in which both electron and hole currents are
injected into the device at separate electrodes. Ambipolar field-
effect transistors have been realized with amorphous silicon,
organic semiconductor heterostructures, and organic single
crystals.
     2) The authors present data on the structure and operating
characteristics of an ambipolar light-emitting field-effect
transistor based on single crystals of the organic semiconductor
alpha-sexithiophene. In this device, electrons and holes are
injected from the source and drain electrodes, respectively, and
the concentrations of electrons and holes are controlled by the
applied gate and drain-source voltages. Excitons are generated,
leading to radiative electron-hole recombination. Moreover, above
a remarkably low threshold current, coherent light is
spontaneously emitted (amplified spontaneous emission). The
authors thus suggest "this three-terminal device is the basis of
a very promising architecture for electrically driven laser
action in organic semiconductors."
-----------
J.H. Schoen et al: A light-emitting field-effect transistor.
(Science 3 Nov 00 290:963)
QY: J.H. Schoen: hendrik@lucent.com
-------------------
Summary by SCIENCE-WEEK http://scienceweek.com 1Dec00
For more information: http://scienceweek.com/swfr.htm
-------------------
Related Background:
ON THE FOUNDATION OF THE SILICON AGE
This is the 50th anniversary of the invention of the transistor,
and many periodicals and journals are offering reviews of the
people involved, the event, and the consequences. Essentially,
the transistor is a valve that controls the flow of current
carriers (electrical charges in motion) through a semiconductor
crystal material. It is this ability to control current carriers
and their associated voltages that made the transistor perhaps
the most useful single entity in post World War II technology.
But the antecedents of the transistor were in place before that.
A rectifier is a device for changing alternating current into
direct current. The first use of a crystal semiconductor as a
rectifier in electrical circuits occurred during the early days
of radio. A point contact diode is a semiconductor rectifier that
uses the barrier formed between a specially prepared semi-
conductor surface and a metal point to produce the rectifying
action. Point contact diodes (germanium diodes) were used during
World War II in radar and other high-frequency applications. The
transistor essentially consists of a small block of semiconductor
material to which at least three electrical contacts are made,
two of which are closely spaced rectifying contacts. A junction
transistor is a transistor involving a special junction between
two semiconductor materials possessing opposite current carrier
properties. The first point contact transistor was announced in
1948, and this was followed by the development of the junction
diode and the junction transistor in 1949. There were many
researchers involved in the physics of semiconductors and
transistors in the early years of transistor invention and
development, but the three people most often mentioned are
William Shockley, John Bardeen, and Walter H. Brattain, who
jointly received the Nobel Prize in Physics for their work in
1956. Concerning the question of who did what, we will let John
Bardeen provide the answer (Handbook of Physics, 1967): "It was a
fundamental research program on semiconductors initiated just
after the war at the Bell Telephone Laboratories and under the
general direction of W. Shockley that led to the invention of the
transistor by Brattain and [Bardeen]..." In a review of the
invention of the transistor and the first decade of transistor
research, Ian Ross (AT&T Bell Labs, US), who with George Dacey
fabricated the first working field-effect transistor (a
transistor whose junction behavior is modulated by an applied
electric field) in 1952, points out that the transistor was the
product of basic research with a clear technological goal, but
the revolutionary impact of the new technology was not
anticipated.
-----------
(Physics Today December 1997) (ScienceWeek 12 Dec 97)
For more information: http://scienceweek.com/swfr.htm

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7. IN FOCUS: ON THE MEANING OF QUANTUM THEORY
"To some extent, I myself am not deeply troubled by the prospect
of a reality which is not independent of the observer or the
measuring device. However, I do not share the uncompromising
views characteristic of the positivist. I am convinced that the
desire to relate their theories to elements of an independent
reality is part of the psychological make-up of many scientists.
They feel it is necessary to try continually to go beyond the
symbols in a mathematical equation and attach a deeper meaning to
them. Without this continual attempt to penetrate to an
underlying reality, science would be a sterile, passive, and
rather unemotional activity. This it certainly is not. Like all
acts of faith, the search for an independent reality involves
striving for a goal that can never be reached. This does not mean
that the effort is any less worthwhile. On the contrary, it is
through this process of striving for the unachievable that
progress in science is made. With regard to quantum theory, my
personal view is that we still do not yet know enough about the
physical world to make a sound judgment about its meaning. The
positivist says that the theory is all there is, but the realist
says: Look again, we do not yet have the whole story. As to where
we might look, my recommendation is to watch _time_ closely: we
do not yet seem to have a good explanation of it. This is not to
say that a better understanding of time will automatically solve
all the conceptual problems of quantum theory. Time, I suppose,
will tell. I am reasonably certain of one thing. The
unquestioning acceptance of the Copenhagen interpretation of
quantum theory has, in the last 40 years or so, held back
progress on the development of alternative theories. It has been
very difficult for the voices raised against the orthodox
interpretation to be heard. Remember that it was John Bell -- an
opponent of the dogmatic Copenhagen view -- whose curiosity and
determination led to Bell's theorem and ultimately to new
experimental tests. Blind acceptance of the orthodox position
cannot produce the challenges needed to push the theory
eventually to its breaking point. And break it will, probably in
a way no one can predict to produce a theory no one can imagine.
The arguments about reality will undoubtedly persist, but at
least we will have a better theory."
-----------
Jim Baggott: _The Meaning of Quantum Theory_
(Oxford University Press, Oxford UK, p.210)
-------------------
SCIENCE-WEEK http://scienceweek.com 1Dec00

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8. FROM THE SCIENCEWEEK ARCHIVE:
ON FRAUD IN SCIENCE
There are two prevalent myths concerning scientific fraud: The
first myth states that since most scientific experiments are
replicated by other laboratories, science is self-correcting
because the discovery of fraud involving the fabrication of data
is inevitable. The second myth is that scientific papers
involving fabrication of data are extremely rare, with only a few
fraudulent papers published in any one year. Concerning the first
myth, it is not true that all or even most published experiments
are sooner or later replicated. What is true is that research
results that are of apparent great significance will probably be
replicated, but not other research results. These days, in the
front lines of fast-moving fields in science, few laboratory
heads are inclined to waste precious manpower and funds simply
replicating the work of others: the most successful research
strategy is to assume the relevant published product of other
laboratories is honest and take the next step, or better yet the
step after that, in the push to solve a hot problem. Concerning
the second myth, the evidence that exists suggests the number of
scientific papers involving fabricated data published each year
may involve hundreds and perhaps thousands of publications. For
example, the Office of Research Integrity of the US National
Institutes of Health (NIH) found that between 1993 and 1997, 61
researchers receiving its grants were involved in the fabrication
of data. The total number of NIH grants during the same period
was approximately 150,000. These figures produce a fabrication
rate for published papers of 0.0004, assuming each research grant
produced on average the same number of papers. This fabrication
rate concerns the biomedical sciences in the US (the area with
which NIH is concerned), but there is no evidence of a lower rate
in other areas of science. In 1998, the top 5600 scientific
journals published approximately 1 million articles, and it is
estimated this is approximately one-tenth of the total world
output. Considering only the top 1 million publications and
applying the fabrication rate derived from the NIH evidence, we
find the expected number of publications each year in all
scientific fields involving fabricated data is approximately 400
papers for the top 5600 journals, and perhaps as much as 10 times
that if all scientific journals are considered. It is certainly
true that these estimates involve some assumptions; it is also
true that a small fabrication rate applied to a large number of
published articles will yield a significant number of fraudulent
publications. In general, the idea that only a few fraudulent
scientific papers are published each year is probably a complete
fallacy. ... ... Alison Abbott (_Nature_) presents an extensive
review of official handling of the problem of scientific
misconduct (especially the problem of scientific fraud), the
author making the following points: 1) Although the incidence of
proven scientific fraud remains low, several high-profile cases
have convinced the research community of the need for effective
action, in particular by enforcing codes of good laboratory
practice. 2) The extent of scientific misconduct of the
"fabrication-falsification-plagiarism" type is hotly debated in
both the US and Europe. Some scientists fear that publicized
cases are merely the tip of an iceberg. Others remain convinced
that the overall incidence remains low, and even those with
direct experience of misconduct cases are often optimistic. 3) In
one survey, published in _American Scientist_ in 1993, between 6
and 9 percent of respondents said they were personally aware of
results that had been plagiarized or fabricated within their
faculties. 4) Many journal editors believe that breaches of the
traditional ethics of scientific publication are increasing, but
few editors are confident of how they should react. 5) Last year,
two foundations in Germany set up a project to determine how many
of the 550 journal papers and 80-odd book chapters written by two
German cancer researchers, Friedhelm Herrmann and Marion Brach
(see SW background material below), and some of their former
colleagues, included apparently fabricated data. Investigating
committees have already identified 58 papers by Herrmann and
Brach that involve apparently fabricated data, but investigation
of the publications is only 20 percent finished. The
investigation will take months to complete, and the intention is
to publish the results in an international journal.
-----------
Alison Abbott: Science comes to terms with the lessons of fraud.
(Nature 4 Mar 99 398:13)
Alison Abbott: a.abbott@nature.com
-------------------
Summary by SCIENCE-WEEK http://scienceweek.com 30Apr99
-------------------
Related Background:
RESEARCH FRAUD SCANDAL IN GERMANY: AN UPDATE
What has been called in Germany and elsewhere "Germany's biggest
ever scientific fraud" is apparently still without closure. The
essence of the case (details are provided in the attached
background material) is the involvement of 2 molecular
biologists, Marion Brach and Friedhelm Herrmann (who both worked
and lived together during their scientific collaboration at
Harvard, Freiburg, and Berlin), in an alleged systematic
fabrication of data in 37 publications over a 9 year period
ending in 1996. It is now nearly 2 years after the affair was
first revealed, but no case has yet been brought to court.
Prosecutors in Germany are evidently finding it more difficult
than expected to bring charges against the two scientists
involved, both of whom achieved full professorships on the basis
of the apparently fraudulent research reports. After being
dismissed as full professor at the University of Lubeck in 1997
(she assumed the post in 1996), Brach evidently left Germany and
she is now reported to be working in New York. Herrmann resigned
his professorship at the University of Ulm and now works in
private medical practice in Munich. Herrmann continues to deny
any involvement in misconduct, and says the failure to bring
charges against him is proof of his innocence. Meanwhile
Germany's main university research funding agency, Deutsche
Forschungsgemeinschaft, has set up a task force to determine the
"full extent of any scientific damage" caused by the alleged
fraudulent publications.
-----------
A. Abbott (*Nature*)
German scientists may escape fraud trial.
(Nature 8 Oct 98 395:532)
QY: Alison Abbot: a.abbott@nature.com
-------------------
Summary by SCIENCE-WEEK http://scienceweek.com 6Nov98
-------------------
Related Background:
ABDERHALDEN'S FRAUD REVISITED
Last year was not a good year for German biological and medical
science, since 1997 was marked by a major fraud scandal involving
two full professors apparently involved in the fabrication of
data published in dozens of scientific papers during a 9-year
period. That story is not yet finished (see background material
below). Now from Germany comes the publication of a "commentary"
by two scientists, U. Deichmann and B. Muller-Hill, the
commentary revisiting what has come to be considered the
fraudulent career of German scientist Emil Abderhalden
(1877-1950). Abderhalden was a biochemist involved in designing
tests for various clinical disease entities, the tests involving
what he called "defense enzymes" (Abwehrfermente), enzymes which
he claimed to have identified, and which according to his
analyses were specific proteases produced when humans were
challenged by foreign proteins. During the years 1912 to 1950,
Abderhalden enjoyed the status of one of the most eminent
scientists in Germany, was professor of physiology and
physiological chemistry at Halle University, president of the
oldest German academy of science (the Leopoldina), editor of
several journals, and author of several books and more than 1000
research papers -- and all of this notwithstanding, the consensus
today is that nearly all of his research on the so-called
"defense enzymes" was completely fraudulent, with scores of
colleagues and underlings either explicitly or implicitly
colluding in the fraud over a period of decades. It is an ugly
story with political tangents (e.g., Joseph Mengele, the
notorious Auschwitz doctor, was one of Abderhalden's proteges).
In their commentary, Deichmann and Muller-Hill conclude: "The
elite of today [the biomedical elite in Germany] are loyal
students of the old elite, and they have learned and internalized
the old values. Has medical, clinical science in Germany today
really changed that much? We doubt it. The Brach-Herrmann-
Mertelsmann affair provides a brief glimpse into the abyss of
medical science in Germany. Will it be soon forgotten by the
German medical elite, or will there be real change in the spirit
of true science?" [Editor's note: Roland Mertelsmann, Professor
Herrmann's department head, was co-author of 25 suspected papers
produced by Herrmann, but has pleaded non-involvement in the
research.]
QY: Ute Deichmann, Institute of Genetics, Cologne University,
Weyertal 121, 50931, Koeln, DE.
(Nature 14 May 98 393:109) (Science-Week 5 Jun 98)
-------------------
Related Background:
GERMAN RESEARCHER ADMITS FRAUD AND CHARGES ACADEMIC COVER-UP
Producing another chapter in the scientific fraud case that has
caused an apparent sensation in Germany, Marion A. Brach, one of
the accused scientists, has published a letter in the journal
*Nature* in which she points out the following: 1) She has
confessed to falsifying scientific papers; 2) she has resigned
her position as a full professor at the University of Lubeck; 3)
she does not believe further victimization is appropriate; 4) she
has concluded that the various German investigating commissions
met only with the intention of limiting damage to the German
academic community rather than with the intention of discovering
the full extent of culpability; 5) the German government has
reneged on its legal agreement to provide her with severance pay
following her early confession and resignation; 6) official
bodies have found it expedient to imply that she was the major or
only culprit in the affair.
QY: Marion A. Brach, c/o Walter F. Kalthoff, Pacellistr. 14,
D-80333, Muenchen, DE.
(Nature 2 Apr 98) (Science-Week 17 Apr 98)
-------------------
Related Background:
MORE DEVELOPMENTS IN GERMAN SCIENTIFIC FRAUD CASE
The scientific fraud case that has been shocking the German
intellectual community these past months, and which is claimed to
be the worst case of scientific fraud in that country since 1945,
continues to be a public spectacle. The scandal involves two
German molecular biologists, Marion Brach (who has resigned as a
Professor at Lubeck University), and Friedhelm Herrmann (a
suspended Professor at Ulm University). Brach has admitted
falsifying published data while she worked under the supervision
of Herrmann at the Max Delbruck Center for Molecular Medicine a
few years ago. Herrmann claims he is only a clinician and had
nothing to do with the laboratory bench work. Herrmann is a
prominent hematologist and a leading genetic therapy researcher.
The two biologists had worked together for some time, and each
received professorships on the basis of that work. (Herrmann's
salary was apparently US$278,000 per year). Now it has been
announced that Herrmann is suing various academic investigators
in the case for DM10 million (US5.6 million) in compensation for
damage to his career. In addition, there is now a claim by a new
investigation team that the two accused researchers also
published falsified data earlier in their careers.
(Nature 11 Sep) (Science-Week 26 Sep 97)
-------------------
AN UPROAR OVER SCIENTIFIC FRAUD IN GERMANY
The German scientific community was rocked by scandal this
spring, and the resulting repercussions are apparently not yet
complete. The brouhaha involves two German molecular biologists,
Marion Brach (recently resigned as a Professor at Lubeck
University), and Friedhelm Herrmann (a suspended Professor at Ulm
University). Brach has admitted falsifying published data while
she worked under the supervision of Herrmann at the Max Delbruck
Center for Molecular Medicine a few years ago. Herrmann claims he
is only a clinician and had nothing to do with the laboratory
bench work. Herrmann is a prominent hematologist and a leading
genetic therapy researcher. The two biologists have worked
together for some time, and each received professorships on the
basis of that work. All of that work is now being investigated,
and the German government has established a commission of
international scientific experts to discuss research standards
and the procedures for scientific oversight in German and
internationally.
(Science 11 Jul 97) (Science-Week 18 Jul 97) 


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The first issue of SCIENCE-WEEK appeared May 1, 1997, and it has
been published regularly each week since that date. SW is
designed to cross existing conceptual and linguistic barriers
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