bluuebunny/crossref_metadata_2025 huggingface dataset:
Gene Therapy for Vascular Smooth Muscle Cell Proliferation After Arterial Injury
Authors: Ohno Takeshi , Gordon David , San Hong , Pompili Vincent J. , Imperiale Michael J. , Nabel Gary J. , Nabel Elizabeth G.
Published: October 2006

Accumulation of vascular smooth muscle cells as a consequence of arterial injury is a major feature of vascular proliferative disorders. Molecular approaches to the inhibition of smooth muscle cell proliferation in these settings could potentially limit intimal expansion. This problem was approached by introducing adenoviral vectors encoding the herpesvirus thymidine kinase (tk) into porcine arteries that had been injured by a balloon on a catheter. These smooth muscle cells were shown to be infectable with adenoviral vectors, and introduction of the tk gene rendered them sensitive to the nucleoside analog ganciclovir. When this vector was introduced into porcine arteries immediately after a balloon injury, intimal hyperplasia decreased after a course of ganciclovir treatment. No major local or systemic toxicities were observed. These data suggest that transient expression of an enzyme that catalyzes the formation of a cytotoxic drug locally may limit smooth muscle cell proliferation in response to balloon injury.
Parallel Computing in Biomedical Research
Authors: Martino Robert L. , Johnson Calvin A. , Suh Edward B. , Trus Benes L. , Yap Tieng K.
Published: October 2006

Scalable parallel computer architectures provide the computational performance needed for advanced biomedical computing problems. The National Institutes of Health have developed a number of parallel algorithms and techniques useful in determining biological structure and function. These applications include processing electron micrographs to determine the three-dimensional structure of viruses, calculating the solvent-accessible surface area of proteins to help predict the three-dimensional conformation of these molecules from their primary structures, and searching for homologous DNA or amino acid sequences in large biological databases. Timing results demonstrate substantial performance improvements with parallel implementations compared with conventional sequential systems.
Calcineurin Inhibition of Dynamin I GTPase Activity Coupled to Nerve Terminal Depolarization
Authors: Liu Jun-Ping , Sim Alistair T. R. , Robinson Phillip J.
Published: October 2006

Dynamin I is a nerve terminal phosphoprotein with intrinsic guanosine triphosphatase (GTPase) activity that is required for endocytosis. Upon depolarization and synaptic vesicle recycling, dynamin I undergoes a rapid dephosphorylation. Dynamin I was found to be a specific high-affinity substrate for calcineurin in vitro. At low concentrations, calcineurin dephosphorylated dynamin I that had been phosphorylated by protein kinase C. The dephosphorylation inhibited dynamin I GTPase activity in vitro and after depolarization of nerve terminals. The effect in nerve terminals was prevented by the calcineurin inhibitor cyclosporin A. This suggests that in nerve terminals, calcineurin serves as a Ca
2+
-sensitive switch for depolarization-evoked synaptic vesicle recycling.
Disparate Rates of Molecular Evolution in Cospeciating Hosts and Parasites
Authors: Hafner Mark S. , Sudman Philip D. , Villablanca Francis X. , Spradling Theresa A. , Demastes James W. , Nadler Steven A.
Published: October 2006

DNA sequences for the gene encoding mitochondrial cytochrome oxidase I in a group of rodents (pocket gophers) and their ectoparasites (chewing lice) provide evidence for cospeciation and reveal different rates of molecular evolution in the hosts and their parasites. The overall rate of nucleotide substitution (both silent and replacement changes) is approximately three times higher in lice, and the rate of synonymous substitution (based on analysis of fourfold degenerate sites) is approximately an order of magnitude greater in lice. The difference in synonymous substitution rate between lice and gophers correlates with a difference of similar magnitude in generation times.
A Specific Inhibitor of the Epidermal Growth Factor Receptor Tyrosine Kinase
Authors: Fry David W. , Kraker Alan J. , McMichael Amy , Ambroso Linda A. , Nelson James M. , Leopold Wilbur R. , Connors Richard W. , Bridges Alexander J.
Published: October 2006

A small molecule called PD 153035 inhibited the epidermal growth factor (EGF) receptor tyrosine kinase with a 5-pM inhibition constant. The inhibitor was specific for the EGF receptor tyrosine kinase and inhibited other purified tyrosine kinases only at micromolar or higher concentrations. PD 153035 rapidly suppressed autophosphorylation of the EGF receptor at low nanomolar concentrations in fibroblasts or in human epidermoid carcinoma cells and selectively blocked EGF-mediated cellular processes including mitogenesis, early gene expression, and oncogenic transformation. PD 153035 demonstrates an increase in potency over that of other tyrosine kinase inhibitors of four to five orders of magnitude for inhibition of isolated EGF receptor tyrosine kinase and three to four orders of magnitude for inhibition of cellular phosphorylation.
Generation of Lymphohematopoietic Cells from Embryonic Stem Cells in Culture
Authors: Nakano Toru , Kodama Hiroaki , Honjo Tasuku
Published: October 2006

An efficient system was developed that induced the differentiation of embryonic stem (ES) cells into blood cells of erythroid, myeloid, and B cell lineages by coculture with the stromal cell line OP9. This cell line does not express functional macrophage colony-stimulating factor (M-CSF). The presence of M-CSF had inhibitory effects on the differentiation of ES cells to blood cells other than macrophages. Embryoid body formation or addition of exogenous growth factors was not required, and differentiation was highly reproducible even after the selection of ES cells with the antibiotic G418. Combined with the ability to genetically manipulate ES cells, this system will facilitate the study of molecular mechanisms involved in development and differentiation of hematopoietic cells.
Direct Inhibition of the Yeast Cyclin-Dependent Kinase Cdc28-Cln by Far1
Authors: Peter Matthias , Herskowitz Ira
Published: October 2006

Cell cycle arrest of
Saccharomyces cerevisiae
in G
1
by the antimitogen α-factor is mediated by activation of a signal transduction pathway that results in inhibition of the cyclin-dependent kinase Cdc28-Cln. The Far1 protein is required for cell cycle arrest and associates with the Cdc28-Cln complex. The kinase activity of Cdc28-Cln was directly inhibited by Far1 both in vivo and in vitro, thus demonstrating that Far1 acts at the final step in the α-factor response pathway by inhibiting a G
1
cyclin-dependent kinase.
Direct Observation of Enzyme Activity with the Atomic Force Microscope
Authors: Radmacher Manfred , Fritz Monika , Hansma Helen G. , Hansma Paul K.
Published: October 2006

The height fluctuations on top of the protein lysozyme adsorbed on mica were measured locally with an atomic force microscope operated in tapping mode in liquid. Height fluctuations of an apparent size of 1 nanometer that lasted for about 50 milliseconds were observed over lysozyme molecules when a substrate (oligoglycoside) was present. In the presence of the inhibitor chitobiose, these height fluctuations decreased to the level without the oligoglycoside. The most straightforward interpretation of these results is that the height fluctuations correspond to the conformational changes of lysozyme during hydrolysis. It is also possible, however, that the height fluctuations are, at least in part, the result of a different height or elasticity of the transient complex of lysozyme plus the substrate.
iaglu
, a Gene from
Zea mays
Involved in Conjugation of Growth Hormone Indole-3-Acetic Acid
Authors: Szerszen Jedrzej B. , Szczyglowski Krzysztof , Bandurski Robert S.
Published: October 2006

Plants contain most of the growth hormone indole-3-acetic acid (IAA) in conjugated forms believed to be inactive in promoting growth. The
iaglu
gene, which controls the first step in the biosynthesis of the IAA conjugates of
Zea mays
, encodes (uridine 5′-diphosphate-glucose:indol-3-ylacetyl)- β-D-glucosyl transferase. Protein synthesized by
Escherichia coli
that contained cloned 1-
O
-β-D-indol-3-ylacetyl-glucose complementary DNA (cDNA) was catalytically active. The predicted amino acid sequence of the cDNA was confirmed by amino-terminal sequencing of the purified enzyme. Homologous nucleotide sequences were found in all plants tested. The blockage or enhancement of
iaglu
expression may permit regulation of plant growth.
Stimulatory Effects of Yeast and Mammalian 14-3-3 Proteins on the Raf Protein Kinase
Authors: Irie Kenji , Gotoh Yukiko , Yashar Beverly M. , Errede Beverly , Nishida Eisuke , Matsumoto Kunihiro
Published: October 2006

Intracellular signaling from receptor tyrosine kinases in mammalian cells results in activation of a signal cascade that includes the guanine nucleotide-binding protein Ras and the protein kinases Raf, MEK [mitogen-activated protein kinase (MAPK) or extracellular signal-regulated kinase (ERK) kinase], and MAPK. MAPK activation that is dependent on the coupling of Ras and Raf was reconstituted in yeast. Yeast genes were isolated that, when overexpressed, enhanced the function of Raf. One of them is identical to
BMH1
, which encodes a protein similar to members of the mammalian 14-3-3 family. Bacterially synthesized mammalian 14-3-3 protein stimulated the activity of Raf prepared from yeast cells expressing c-Raf-1. Thus, the 14-3-3 protein may participate in or be required for activation of Raf.
Control of Thalamocortical Afferent Rearrangement by Postsynaptic Activity in Developing Visual Cortex
Authors: Hata Yoshio , Stryker Michael P.
Published: October 2006

The formation of specific connections in the developing central nervous system is thought to result from mechanisms that increase the strengths of synapses at which pre- and postsynaptic activity are correlated and decrease it otherwise. In the visual cortex, initially widespread inputs normally sort out into eye-specific patches during early life. If only one eye can see during this period, its patches are much larger than normal, and patches from the occluded eye become much smaller. Anatomical experiments here show that closed-eye inputs expand within a region of cortex that is silenced, establishing that inhibition of common target cells gives less active inputs a competitive advantage.
Laminar Comparison of Somatosensory Cortical Plasticity
Authors: Diamond Mathew E. , Huang Wei , Ebner Ford F.
Published: October 2006

During tactile learning there is a transformation in the way the primary somatosensory cortex integrates, represents, and distributes information from the skin. To define this transformation, the site of earliest modification has been identified in rat somatosensory cortex after a change in sensory experience. Afferent activity was manipulated by clipping all except two whiskers on one side of the snout ("whisker pairing"), and the receptive fields of neurons at different cortical depths were mapped 24 hours later. Neurons in layer IV, the target of the primary thalamic pathway, were unaltered, whereas neurons located above and below layer IV showed significant changes. These changes were similar to those that occur in layer IV after longer periods of whisker pairing. The findings support the hypothesis that the layers of cortex contribute differently to plasticity. Neurons in the supragranular and infragranular layers respond rapidly to changes in sensory experience and may contribute to subsequent modification in layer IV.
Genetic Dissection of Complex Traits
Authors: Lander Eric S. , Schork Nicholas J.
Published: October 2006

Medical genetics was revolutionized during the 1980s by the application of genetic mapping to locate the genes responsible for simple Mendelian diseases. Most diseases and traits, however, do not follow simple inheritance patterns. Geneticists have thus begun taking up the even greater challenge of the genetic dissection of complex traits. Four major approaches have been developed: linkage analysis, allele-sharing methods, association studies, and polygenic analysis of experimental crosses. This article synthesizes the current state of the genetic dissection of complex traits—describing the methods, limitations, and recent applications to biological problems.
Complete Nucleotide Sequence of
Saccharomyces cerevisiae
Chromosome VIII
Authors: Johnston M. , Andrews S. , Brinkman R. , Cooper J. , Ding H. , Dover J. , Du Z. , Favello A. , Fulton L. , Gattung S. , Geisel C. , Kirsten J. , Kucaba T. , Hillier L. , Jier M. , Johnston L. , Langston Y. , Latreille P. , Louis E. J. , Macri C. , Mardis E. , Menezes S. , Mouser L. , Nhan M. , Rifkin L. , Riles L. , St. Peter H. , Trevaskis E. , Vaughan K. , Vignati D. , Wilcox L. , Wohldman P. , Waterston R. , Wilson R. , Vaudin M.
Published: October 2006

The complete nucleotide sequence of
Saccharomyces cerevisiae
chromosome VIII reveals that it contains 269 predicted or known genes (300 base pairs or larger). Fifty-nine of these genes (22 percent) were previously identified. Of the 210 novel genes, 65 are predicted to encode proteins that are similar to other proteins of known or predicted function. Sixteen genes appear to be relatively recently duplicated. On average, there is one gene approximately every 2 kilobases. Although the coding density and base composition across the chromosome are not uniform, no regular pattern of variation is apparent.
Age of the Earliest Known Hominids in Java, Indonesia
Authors: Swisher C. C. , Curtis G. H. , Jacob T. , Getty A. G. , Suprijo A. , Widiasmoro
Published: October 2006

40
Ar/
39
Ar laser-incremental heating of hornblende separated from pumice recovered at two hominid sites in Java, Indonesia, has yielded well-defined plateaus with weighted mean ages of 1.81 ± 0.04 and 1.66 ± 0.04 million years ago (Ma). The hominid fossils, a juvenile calvaria of
Pithecanthropus
and a partial face and cranial fragments of
Meganthropus
, commonly considered part of the Asian
Homo erectus
hypodigm, are at least 0.6 million years older than fossils referred to as
Homo erectus
(OH-9) from Olduvai Gorge, Tanzania, and comparable in age with the oldest Koobi Fora
Homo cf. erectus
(
Homo ergaster
) in Kenya. These ages lend further credence to the view that
Homo erectus
may have evolved outside of Africa. If the ancestor of
Homo erectus
ventured out of Africa before 1.8 Ma, the dispersal would have predated the advent of the Acheulean culture at 1.4 Ma, possibly explaining the absence of these characteristic stone cleavers and hand axes in East Asia.
Fusion of a Kinase Gene,
ALK
, to a Nucleolar Protein Gene,
NPM
, in Non-Hodgkin's Lymphoma
Authors: Morris Stephan W. , Kirstein Mark N. , Valentine Marcus B. , Dittmer Kristopher G. , Shapiro David N. , Saltman David L. , Look A. Thomas
Published: October 2006

The 2;5 chromosomal translocation occurs in most anaplastic large-cell non-Hodgkin's lymphomas arising from activated T lymphocytes. This rearrangement was shown to fuse the
NPM
nucleolar phosphoprotein gene on chromosome 5q35 to a previously unidentified protein tyrosine kinase gene,
ALK
, on chromosome 2p23. In the predicted hybrid protein, the amino terminus of nucleophosmin (NPM) is linked to the catalytic domain of anaplastic lymphoma kinase (ALK). Expressed in the small intestine, testis, and brain but not in normal lymphoid cells, ALK shows greatest sequence similarity to the insulin receptor subfamily of kinases. Unscheduled expression of the truncated ALK may contribute to malignant transformation in these lymphomas.
Neuronal Plasticity That Underlies Improvement in Perceptual Performance
Authors: Zohary Ehud , Celebrini Simona , Britten Kenneth H. , Newsome William T.
Published: October 2006

The electrophysiological properties of sensory neurons in the adult cortex are not immutable but can change in response to alterations of sensory input caused by manipulation of afferent pathways in the nervous system or by manipulation of the sensory environment. Such plasticity creates great potential for flexible processing of sensory information, but the actual effects of neuronal plasticity on perceptual performance are poorly understood. The link between neuronal plasticity and performance was explored here by recording the responses of directionally selective neurons in the visual cortex while rhesus monkeys practiced a familiar task involving discrimination of motion direction. Each animal experienced a short-term improvement in perceptual sensitivity during daily experiments; sensitivity increased by an average of 19 percent over a few hundred trials. The increase in perceptual sensitivity was accompanied by a short-term improvement in neuronal sensitivity that mirrored the perceptual effect both in magnitude and in time course, which suggests that improved psychophysical performance can result directly from increased neuronal sensitivity within a sensory pathway.
Regulation of Melanin Biosynthesis in the Human Epidermis by Tetrahydrobiopterin
Authors: Schallreuter Karin U. , Wood John M. , Pittelkow Mark R. , Gütlich Markus , Lemke K. Regina , Rödl Wolfgang , Swanson Norma N. , Hitzemann Karen , Ziegler Irmgard
Published: October 2006

The participation of (6R) 5,6,7,8-tetrahydrobiopterin (6-BH
4
) in regulating the tyrosine supply for melanin biosynthesis was investigated by the examination of human keratinocytes, melanocytes, and epidermal suction blisters from normal human skin and from patients with the depigmentation disorder vitiligo. Cells, as well as total epidermis, contained high phenylalanine hydroxylase activities and also displayed the capacity to synthesize and recycle 6-BH
4
, the essential cofactor for this enzyme. In vitiligo, 4a-hydroxy-BH
4
dehydratase activity was extremely low or absent, yielding an accumulation of the nonenzymatic by-product 7-tetrahydrobiopterin (7-BH
4
) at concentrations up to 8 × 10
-6
M in the epidermis. This by-product is a potent competitive inhibitor in the phenylalanine hydroxylase reaction with an inhibition constant of 10
-6
M. Thus, 6-BH
4
seems to control melanin biosynthesis in the human epidermis, whereas 7-BH
4
may initiate depigmentation in patients with vitiligo.
Functional Polymers and Dendrimers: Reactivity, Molecular Architecture, and Interfacial Energy
Authors: Fréchet Jean M. J.
Published: October 2006

The interaction of polymers with their environment depends largely on the functional groups they carry. Interfaces between different polymers or between polymers and other surfaces can be strengthened through the design of molecular interactions such as hydrogen bonding and through the control of polymer architecture. The placement of functional groups at polymer chain ends or in well-defined segments can determine the ultimate properties. Three-dimensional synthetic polymers such as dendrimers can be fashioned to encapsulate reactive sites or provide highly controlled surfaces and interfaces.
New Challenges in Biomaterials
Authors: Peppas Nicholas A. , Langer Robert
Published: October 2006

Significant opportunities and challenges exist in the creation and characterization of biomaterials. Materials have been designed for contact with blood, as replacements for soft and hard tissues, as adhesives, and as dental materials. Current methods of synthesis and characterization of these materials are outlined. Approaches for controlling the interface between tissue and biomaterials and ways in which the engineered materials may contribute to medicine are considered.
The
Drosophila
saxophone
Gene: a Serine-Threonine Kinase Receptor of the TGF-β Superfamily
Authors: Xie Ting , Finelli Alyce L. , Padgett Richard W.
Published: October 2006

The
Drosophila decapentaplegic
(
dpp
) gene encodes a transforming growth factor-β (TGF-β)-like protein that plays a key role in several aspects of development. Transduction of the DPP signal was investigated by cloning of serine-threonine kinase transmembrane receptors from
Drosophila
because this type of receptor is specific for the TGF-β-like ligands. Here evidence is provided demonstrating that the
Drosophila saxophone
(
sax
) gene, a previously identified female sterile locus, encodes a TGF-β-like type I receptor. Embryos from
sax
mothers and
dpp
embryos exhibit similar mutant phenotypes during early gastrulation, and these two loci exhibit genetic interactions, which suggest that they are utilized in the same pathway. These data suggest that
sax
encodes a receptor for
dpp
.
Mutational Isolation of a Sieve for Editing in a Transfer RNA Synthetase
Authors: Schmidt Eric , Schimmel Paul
Published: October 2006

Editing reactions are essential for the high fidelity of information transfer in processes such as replication, RNA splicing, and protein synthesis. The accuracy of interpretation of the genetic code is enhanced by the editing reactions of aminoacyl transfer RNA (tRNA) synthetases, whereby amino acids are prevented from being attached to the wrong tRNAs. Amino acid discrimination is achieved through sieves that may overlap with or coincide with the amino acid binding site. With the class I
Escherichia coli
isoleucine tRNA synthetase, which activates isoleucine and occasionally misactivates valine, as an example, a rationally chosen mutant enzyme was constructed that lacks entirely its normally strong ability to distinguish valine from isoleucine by the initial amino acid recognition sieve. The misactivated valine, however, is still eliminated by hydrolytic editing reactions. These data suggest that there is a distinct sieve for editing that is functionally independent of the amino acid binding site.
Stimulation of Human γδ T Cells by Nonpeptidic Mycobacterial Ligands
Authors: Constant Patricia , Davodeau François , Peyrat Marie-Alix , Poquet Yannick , Puzo Germain , Bonneville Marc , Fournié Jean-Jacques
Published: October 2006

Most human peripheral blood γδ T lymphocytes respond to hitherto unidentified mycobacterial antigens. Four ligands from
Mycobacterium tuberculosis
strain H37Rv that stimulated proliferation of a major human γδ T cell subset were isolated and partially characterized. One of these ligands, TUBag4, is a 5′ triphosphorylated thymidine-containing compound, to which the three other stimulatory molecules are structurally related. These findings support the hypothesis that some γδ T cells recognize nonpeptidic ligands.
Telomere-Led Premeiotic Chromosome Movement in Fission Yeast
Authors: Chikashige Yuji , Ding Da-Qiao , Funabiki Hironori , Haraguchi Tokuko , Mashiko Shinro , Yanagida Mitsuhiro , Hiraoka Yasushi
Published: October 2006

The movement of chromosomes that precedes meiosis was observed in living cells of fission yeast by fluorescence microscopy. Further analysis by in situ hybridization revealed that the telomeres remain clustered at the leading end of premeiotic chromosome movement, unlike mitotic chromosome movement in which the centromere leads. Once meiotic chromosome segregation starts, however, centromeres resume the leading position in chromosome movement, as they do in mitosis. Although the movement of the telomere first has not been observed before, the clustering of telomeres is reminiscent of the bouquet structure of meiotic-prophase chromosomes observed in higher eukaryotes, which suggests that telomeres perform specific functions required for premeiotic chromosomal events generally in eukaryotes.
Resistance to Antibiotics Mediated by Target Alterations
Authors: Spratt Brian G.
Published: October 2006

The development of resistance to antibiotics by reductions in the affinities of their enzymatic targets occurs most rapidly for antibiotics that inactivate a single target and that are not analogs of substrate. In these cases of resistance (for example, resistance to rifampicin), numerous single amino acid substitutions may provide large decreases in the affinity of the target for the antibiotic, leading to clinically significant levels of resistance. Resistance due to target alterations should occur much more slowly for those antibiotics (penicillin, for example) that inactivate multiple targets irreversibly by acting as close analogs of substrate. Resistance to penicillin because of target changes has emerged, by unexpected mechanisms, only in a limited number of species. However, inactivating enzymes commonly provide resistance to antibiotics that, like penicillin, are derived from natural products, although such enzymes have not been found for synthetic antibiotics. Thus, the ideal antibiotic would be produced by rational design, rather than by the modification of a natural product.
Adhesion Forces Between Individual Ligand-Receptor Pairs
Authors: Florin Ernst-Ludwig , Moy Vincent T. , Gaub Hermann E.
Published: October 2006

The adhesion force between the tip of an atomic force microscope cantilever derivatized with avidin and agarose beads functionalized with biotin, desthiobiotin, or iminobiotin was measured. Under conditions that allowed only a limited number of molecular pairs to interact, the force required to separate tip and bead was found to be quantized in integer multiples of 160 ± 20 piconewtons for biotin and 85 ± 15 piconewtons for iminobiotin. The measured force quanta are interpreted as the unbinding forces of individual molecular pairs.
The Role of Interleukin-6 in Mucosal IgA Antibody Responses in Vivo
Authors: Ramsay Alistair J. , Husband Alan J. , Ramshaw lan A. , Bao Shisan , Matthaei Klaus I. , Koehler Georges , Kopf Manfred
Published: October 2006

In mice with targeted disruption of the gene that encodes interleukin-6 (IL-6), greatly reduced numbers of immunoglobulin A (IgA)-producing cells were observed at mucosae and grossly deficient local antibody responses were recorded after mucosal challenge with either ovalbumin or vaccinia virus. The IgA response in the lungs was completely restored after intranasal infection with recombinant vaccinia viruses engineered to express IL-6. These findings demonstrate a critical role for IL-6 in vivo in the development of local IgA antibody responses and illustrate the effectiveness of vector-directed cytokine gene therapy.
A Genetic Linkage Map for the Zebrafish
Authors: Postlethwait John H. , Johnson Stephen L. , Midson Clare N. , Talbot William S. , Gates Michael , Ballinger Eric W. , Africa Dana , Andrews Rebecca , Carl Tim , Eisen Judith S. , Horne Sally , Kimmel Charles B. , Hutchinson Mark , Johnson Michele , Rodriguez Andre
Published: October 2006

To facilitate molecular genetic analysis of vertebrate development, haploid genetics was used to construct a recombination map for the zebrafish
Danio
(
Brachydanio
)
rerio
. The map consists of 401 random amplified polymorphic DNAs (RAPDs) and 13 simple sequence repeats spaced at an average interval of 5.8 centimorgans. Strategies that exploit the advantages of haploid genetics and RAPD markers were developed that quickly mapped lethal and visible mutations and that placed cloned genes on the map. This map is useful for the position-based cloning of mutant genes, the characterization of chromosome rearrangements, and the investigation of evolution in vertebrate genomes.
Specification of Pore Properties by the Carboxyl Terminus of Inwardly Rectifying K
+
Channels
Authors: Taglialatela Maurizio , Wible Barbara A. , Caporaso Roberta , Brown Arthur M.
Published: October 2006

Inwardly rectifying potassium (K
+
) channels (IRKs) maintain the resting membrane potential of cells and permit prolonged depolarization, such as during the cardiac action potential. Inward rectification may result from block of the ion conduction pore by intracellular magnesium (Mg
i
2+
). Two members of this family, IRK1 and ROMK1, which share 40 percent amino acid identity, differ markedly in single-channel K
+
conductance and sensitivity to block by Mg
i
2+
. The conserved H
5
regions were hypothesized to determine these pore properties because they have this function in voltage-dependent K
+
channels and in cyclic nucleotide-gated channels. However, exchange of the H
5
region between IRK1 and ROMK1 had no effect on rectification and little or no effect on K
+
conductance. By contrast, exchange of the amino- and carboxyl-terminal regions together transferred Mg
2+
blockade and K
+
conductance of IRK1 to ROMK1. Exchange of the carboxyl but not the amino terminus had a similar effect. Therefore, the carboxyl terminus appears to have a major role in specifying the pore properties of IRKs.
How Nature Builds the Pigments of Life: the Conquest of Vitamin B
12
Authors: Battersby Alan R.
Published: October 2006

In part because humans cannot synthesize vitamin B
12
and must obtain it from organisms that produce it and because B
12
deficiency leads to pernicious anemia, it has been important to understand how microorganisms build this quite complex substance. As shown here, an interdisciplinary attack was needed, which combined the strengths of genetics, molecular biology, enzymology, chemistry, and spectroscopy. This allowed the step-by-step synthetic pathway of B
12
to be elucidated, and this approach has acted as a model for future research on the synthesis of substances in living organisms. One practical outcome of such an approach has been the improved availability of B
12
for animal feedstuffs and human health.
Molecular Genetic Analyses of the Tyrolean Ice Man
Authors: Handt Oliva , Richards Martin , Trommsdorff Marion , Kilger Christian , Simanainen Jaana , Georgiev Oleg , Bauer Karin , Stone Anne , Hedges Robert , Schaffner Walter , Utermann Gerd , Sykes Bryan , Pääbo Svante
Published: October 2006

An approximately 5000-year-old mummified human body was recently found in the Tyrolean Alps. The DNA from tissue samples of this Late Neolithic individual, the so-called "Ice Man," has been extracted and analyzed. The number of DNA molecules surviving in the tissue was on the order of 10 genome equivalents per gram of tissue, which meant that only multi-copy sequences could be analyzed. The degradation of the DNA made the enzymatic amplification of mitochondrial DNA fragments of more than 100 to 200 base pairs difficult. One DNA sequence of a hypervariable segment of the mitochondrial control region was determined independently in two different laboratories from internal samples of the body. This sequence showed that the mitochondrial type of the Ice Man fits into the genetic variation of contemporary Europeans and that it was most closely related to mitochondrial types determined from central and northern European populations.
Catalytic Activity of an RNA Domain Derived from the U6-U4 RNA Complex
Authors: Yang Jing-Hua , Cedergren Robert , Nadal-Ginard Bernardo
Published: October 2006

U6 RNA contains two regions that are essential for proper splicing of nuclear precursor messenger RNA (pre-mRNA). A comparison of putative secondary structures of the U6-U4 RNA complexes from different phyla revealed a conserved domain that is similar to the catalytic hammerhead RNA motif. Although no catalytic activity was detected in the mammalian U6-U4 RNA complexes, two nucleotide changes in U6 RNA and one in U4 RNA conferred cleavage activity to the complex. Furthermore, the highly conserved domain of the wild-type complex, without the accompanying flanking regions, cleaved an RNA substrate and exhibited other characteristics of the hammerhead ribozyme. The possible involvement of this structure in pre-mRNA splicing is also discussed.
Routes to Catalysis: Structure of a Catalytic Antibody and Comparison with Its Natural Counterpart
Authors: Haynes Matthew R. , Stura Enrico A. , Hilvert Donald , Wilson lan A.
Published: October 2006

The three-dimensional structure of a catalytic antibody (1F7) with chorismate mutase activity has been determined to 3.0 Å resolution as a complex with a transition state analog. The structural data suggest that the antibody stabilizes the same conformationally restricted pericyclic transition state as occurs in the uncatalyzed reaction. Overall shape and charge complementarity between the combining site and the transition state analog dictate preferential binding of the correct substrate enantiomer in a conformation appropriate for reaction. Comparison with the structure of a chorismate mutase enzyme indicates an overall similarity between the catalytic mechanism employed by the two proteins. Differences in the number of specific interactions available for restricting the rotational degrees of freedom in the transition state, and the lack of multiple electrostatic interactions that might stabilize charge separation in this highly polarized metastable species, are likely to account for the observed 10
4
times lower activity of the antibody relative to that of the natural enzymes that catalyze this reaction. The structure of the 1F7 Fab′-hapten complex provides confirmation that the properties of an antibody catalyst faithfully reflect the design of the transition state analog.
Population Policy Options in the Developing World
Authors: Bongaarts John
Published: October 2006

The population of the developing world is currently expanding at the unprecedented rate of more than 800 million per decade, and despite anticipated reductions in growth during the 21st century, its size is expected to increase from 4.3 billion today to 10.2 billion in 2100. Past efforts to curb this growth have almost exclusively focused on the implementation of family planning programs to provide contraceptive information, services, and supplies. These programs have been partially successful in reducing birth rates. Further investments in them will have an additional but limited impact on population growth; therefore, other policy options, in particular measures to reduce high demand for births and limit population momentum, are needed.
Promoter-Selective Transcriptional Defect in Cell Cycle Mutant ts13 Rescued by hTAF
II
250
Authors: Wang Edith H. , Tjian Robert
Published: October 2006

The TAF
II
250 subunit of the human transcription factor IID (TFIID) rescues the temperature-sensitive hamster cell line ts13 and overcomes a G
1
arrest. Investigation of the transcriptional properties of ts13 nuclear extracts in vitro showed that activation by the site-specific regulators Sp1 and Gal4VP16 is temperature sensitive in ts13 extracts, whereas basal transcription remains unaffected. This transcriptional defect can be rescued by purified human TFIID or by expression of wild-type TAF
II
250 in ts13 cells. Expression from the cyclin A but not c-fos promoter is temperature sensitive in these mutant cells. Thus, the mutation in TAF
II
250 appears to have gene-specific effects that may lead to the ts13 cell cycle phenotype.
Magnetic Field Effects on B
12
Ethanolamine Ammonia Lyase: Evidence for a Radical Mechanism
Authors: Harkins Timothy T. , Grissom Charles B.
Published: October 2006

A change in radical pair recombination rates is one of the few mechanisms by which a magnetic field can interact with a biological system. The kinetic parameter V
max
/K
m
(where K
m
is the Michaelis constant) for the coenzyme B
12
-dependent enzyme ethanolamine ammonia lyase was decreased 25 percent by a static magnetic field near 0.1 tesla (1000 gauss) with unlabeled ethanolamine and decreased 60 percent near 0.15 tesla with perdeuterated ethanolamine. This effect is likely caused by a magnetic field-induced change in intersystem crossing rates between the singlet and triplet spin states in the [cob(II)alamin:5′-deoxyadenosyl radical} spin-correlated radical pair.
Identification and Characterization of a Major Cell Wall-Associated Iron-Regulated Envelope Protein (Irep-28) in
Mycobacterium tuberculosis
Authors: Yeruva Veena C. , Duggirala Sridevi , Lakshmi V. , Kolarich Daniel , Altmann Friedrich , Sritharan Manjula
Published: October 2006

Iron limitation and the expression of mycobactin and carboxymycobactin by
Mycobacterium tuberculosis
are known. Here, we report how iron regulated the coordinate expression of these two siderophores and a 28-kDa cell wall-associated iron-regulated protein (Irep-28). Irep-28 is identified as the DNA-binding HU homologue HupB protein (
hupB
[Rv2986c]). Antibodies to this protein were detected in sera from tuberculosis patients. The location of the protein in the cell wall makes it a potential drug target.
RESONANCE AND THE LATE COEFFICIENTS IN THE SCATTERED FIELD OF A DIELECTRIC CIRCULAR CYLINDER
Authors: DUNSTER T. M. , YEDLIN MATTHEW , LAM KIM
Published: October 2006

The classical modal expansion for the scattered field of a plane wave from a circular dielectric cylinder is studied. A new uniform asymptotic approximation is presented for the late coefficients in this expansion, in the case of a fixed relative dielectric constant εr, both real and complex. These new approximations for the mode values are not based on the scattering matrix but rather the classical WKBJ approximations for the Bessel functions, and are valid for the entire region exterior to the cylinder, including the transition region. Furthermore, a precise asymptotic form for the location of a certain critical Regge pole is obtained. It is shown that this pole can lead to at least one dramatic resonant modal term at certain critical values, and the exponential nature of the mode in question is determined explicitly. This is followed by an extension to complex values of εrwith new uniform asymptotic approximations for the modes also being obtained, and these in turn demonstrate a heavy damping of the resonant mode.
Present Status and Future Prospect of Widegap Semiconductor High-Power Devices
Authors: Okumura Hajime
Published: October 2006

High-power device technology is a key technological factor for wireless communication, which is one of the information network infrastructures in the 21st century, as well as power electronics innovation, which contributes considerably to solving the energy saving problem in the future energy network. Widegap semiconductors, such as SiC and GaN, are strongly expected as high-power high-frequency devices and high-power switching devices owing to their material properties. In this paper, the present status and future prospect of these widegap semiconductor high-power devices are reviewed, in the context of applications in wireless communication and power electronics.
A New 600 V Punch Through-Insulated Gate Bipolar Transistor with the Monolithic Fault Protection Circuit Using the Floating p-Well Voltage Detection
Authors: Ji In-Hwan , Jeon Byung-Chul , Choi Young-Hwan , Ha Min-Woo , Han Min-Koo
Published: October 2006

A new fault sensing scheme of the insulated gate bipolar transistor (IGBT) employing the floating p-well, which detects the over-voltage of the floating p-well under the short circuit fault condition, is proposed and implemented by fabricating the main IGBT and gate voltage pull-down circuit using the widely used planar IGBT process. The floating p-well structure also improves the avalanche energy of IGBT in addition to detecting the fault signal. The detection of fault and gate voltage pull-down operation is achieved by the proposed fault protection scheme employing the floating p-well voltage detection. The proposed fault protection circuit was measured under the hard switching fault (HSF) and fault under load (FUL) conditions. The normal switching behavior of the main IGBT with the proposed protection circuit was also investigated under inductive load switching conditions.
High-Speed Uni-Traveling-Carrier Photodiodes Monolithically Integrated with InP Heterojunction Bipolar Transistors using Be Ion Implantation
Authors: Kashio Norihide , Yamahata Shoji , Ida Minoru , Kurishima Kenji , Sano Kimikazu
Published: October 2006

Uni-traveling-carrier photodiodes (UTC-PDs) can be monolithically integrated with InP heterojunction bipolar transistors (HBTs) using Be ion implantation and rapid thermal annealing (RTA) for an activation of implanted Be. UTC-PDs share the base and collector layers of the HBTs; the photoabsorption layer of the UTC-PD is formed by selectively doping the collector with Be. The fabricated UTC-PDs exhibit an output voltage of over 0.5 V and a 3-dB bandwidth of 100 GHz. The HBTs fabricated on the same wafer provide a peak f
t of 150 GHz and a peak f
max of 250 GHz at a collector current density of 1 mA/µm2. The RTA used to fabricate the UTC-PDs does not seriously degrade the current gain of the HBTs. These results indicate that Be ion implantation is a promising technique for integrating UTC-PDs and InP HBTs on the same wafer.
Sharp, Long Wavelength Cathodoluminescence Emission from Undoped Semi-insulating GaAs
Authors: Radhakrishnan J. K. , Salviati G.
Published: October 2006

Cathodoluminescence investigations on bulk undoped semi-insulating GaAs (SI GaAs) samples taken from different sources reveal the presence of a sharp, long wavelength emission at 0.9 eV (at 10 K), with a very narrow full-width at half-maximum of 7 meV, which shows a redshift and thermal broadening upon increasing the temperature. At 10 K, the liquid encapsulated Czokralski grown undoped SI GaAs samples show an additional lower energy emission at 0.89 eV, which is absent in the vertical gradient freeze grown undoped SI GaAs samples. Systematic temperature dependent and beam parameter dependent studies indicate that, the probable origin for the 0.9 eV emission maybe some quantum-dot/nano-cluster like structures present inside the SI GaAs crystal lattice.
Temperature Effect on Current–Voltage Characteristics of Molecular Organic Tris(8-hydroxyquinoline) Aluminium Complex
Authors: Kumar Pankaj , Misra Aparna , Kamalasanan M. N. , Jain S. C. , Srivastava R. , Kumar Vikram
Published: October 2006

The temperature effect on the electron transport in organic semiconducting molecule tris(8-hydroxyquinoline) aluminium (Alq3) diodes has been investigated. The current–voltage (J–V) characteristics have been measured in single layer electron only devices with Alq3 sandwitched between two aluminium electrodes. J–V characteristics have been studied at different temperatures from 295 to 83 K. At high-applied bias and temperatures from 295 to 219 K, our experimental data fits well to the theory where charge transport is determined by exponential traps and J∝V

l+1, where l=T
c/T, T
c is the characteristic temperature of traps distribution. A characteristic trap depth (E
t) of 0.19 eV, has been obtained by a temperature dependent analysis of J–V characteristics. However it was not possible to fit the low temperature data below 219 K, with exponential trap theory, without some unacceptable changes. A numerical analysis of mobility model, in which the mobility has field and temperature dependence, has been found in a good agreement to the data below 219 K.
Source of Surface Morphological Defects Formed on 4H–SiC Homoepitaxial Films
Authors: Okada Tatsuya , Ochi Kengo , Kawahara Hiroyuki , Tomita Takuro , Matsuo Shigeki , Yamaguchi Makoto , Higashimine Kouichi , Kimoto Tsunenobu
Published: October 2006

Plan-view transmission electron microscopy (TEM) was carried out to investigate the source of morphological defects formed on the surface of 4H–SiC homoepitaxial films. The source at the substrate/epifilm interface consisted of an inclusion and partial dislocations emerging from it. Selected-area diffraction pattern analysis, energy dispersive X-ray spectroscopy and micro-Raman spectroscopy revealed that the chemical composition of the inclusion was ZrO2. From the comparison between TEM images and calculated images, it was suggested that the partial dislocations were sheared Frank dislocations with the Burgers vector of the (1/12)<4403> type.
Application of the Ag-Based Ohmic Contact to the Realization of Thermally-Stable InAlAs/InGaAs/InP High Electron Mobility Transistors
Authors: Zhao Weifeng , Mohammed Fitih M. , Adesida Ilesanmi
Published: October 2006

Auger electron spectroscopy analysis of Ag-based Ge/Ag/Ni ohmic contacts on InAlAs/InGaAs/InP revealed that the in-diffusion of the Ag down to the semiconductor layers was necessary for the formation of excellent ohmic contact. Atomic force microscopy characterization of the surface morphology showed that the root mean square roughness of the ohmic contact after annealing was as small as 3.0 nm. High electron mobility transistors with a gate length of 0.2 µm fabricated utilizing Ag-based ohmic contact showed excellent DC and RF characteristics including: g
m,max of 835 mS/mm, I
D,max of 813 mA/mm, f
T of 156 GHz, and f
max of 245 GHz. Due to the stable property of the Ag-based source and drain ohmic contacts, these devices were shown to be thermally stable through preliminary thermal storage tests at 215 °C.
Evaluation of Errors in Feedback Control Based on Persistence Prediction in Model-Based Process Controller System for Deep Sub-100 nm Gate Fabrication
Authors: Goto Takeshi K. , Makabe Toshiaki
Published: October 2006

Using model-based advanced process control (APC) in the gate etching process, gate linewidth variations that are caused by variations in the photo resist linewidth are reduced by feedforward control of the photo resist linewidth that is obtained by a critical dimension (CD) measurement tool. Both long-term process drift in the etching process and long-term instability of the CD measurement tool lead to variations in the process model for APC. These process model variations result in gate linewidth variations and are attenuated by feedback control using the etch CD bias from the previously processed lot. We used a lot-to-lot model-based APC system and a critical dimension scanning electron microscope (CD-SEM) in a deep sub-100 nm gate fabrication line to investigate long-term variations in the process model over a period of six months, and to study how much the variations are reduced by feedback control based on persistence prediction methods using the etch CD bias for the pilot wafer from the currently processed lot. The process model uses the linear relationship between the etch CD bias and the gas mixture ratio at the gate linewidth plasma trimming step, and the gradient is almost constant over the term. The spread in the long-term variation in the process model was 8.12 nm. The variation mainly included process drift in the plasma etcher, and the persistence of the etch CD bias in the lot after processing was significantly lost beyond approximately one week. When using feedback control based on the persistence prediction method using the etch CD bias for the pilot wafer from the currently processed lot, the standard deviation of the feedback error was 0.50 nm of 1σ. On the other hand, when calculating feedback control with the lot-mean etch CD bias from the lot processed immediately before the currently processed lot, the standard deviation of the feedback error was estimated to be 0.82 nm of 1σ. When performing feedback with the etching shift value of the pilot wafers, the percentage of lots whose post etch CD value fell within the range of ±1 nm from the target value was higher by 20% than the simulated value of the percentage of lots in which feedback was calculated with the etch CD bias of the previously processed lots.
Electroluminescent and Electrical Characteristics of Polar and Nonpolar InGaN/GaN Light-Emitting Diodes at Low Temperature
Authors: Masui Hisashi , Schmidt Mathew C. , Chakraborty Arpan , Nakamura Shuji , DenBaars Steven P.
Published: October 2006

Three types of InGaN multiple quantum-well light-emitting diodes (LEDs) were subjected to electroluminescent and electrical characterization at low temperatures and results were compared. Characterized samples included (0001) c-plane InGaN LEDs, (1120) a-plane InGaN LEDs, and AlInGaP LEDs. While electroluminescence from the (1120) InGaN LEDs and AlInGaP LEDs extinguished and became highly electrically resistive at low temperature, the (0001) InGaN LEDs emitted light down to 7 K. This result suggested the continued presence of electrical carriers in the (0001) InGaN LEDs at low temperatures. A carrier-generation mechanism is proposed by examining the energy band diagram with polarization-induced internal electric fields taken into account. Polarization fields in the (0001) InGaN LEDs give rise to local field emission, hole-trapping potential, and interface states, which assist hole injection. It is believed that (0001) InGaN LED operation was possible at low temperatures because of these effects.