bluuebunny/crossref_metadata_2025 huggingface dataset:
The gold-ammonia bonding patterns of neutral and charged complexes Aum±1–(NH3)n. I. Bonding and charge alternation
Authors: Kryachko E. S. , Remacle F.
Published: November 2007

The gold-ammonia bonding patterns of the complexes which are formed between the ammonia clusters (NH3)1⩽n⩽3 and gold clusters of different sizes that range from one gold atom to the tri-, tetra-, and 20-nanogold clusters are governed by two basic and fundamentally different ingredients: the anchoring Au–N bond and the nonconventional N–H⋯Au hydrogen bond. The latter resembles, by all features, a conventional hydrogen bond and is formed between a typical conventional proton donor N–H group and the gold cluster that behaves as a nonconventional proton acceptor. We provide strong computational evidence that the gold-ammonia bonding patterns exhibit distinct characteristics as the Z charge state of the gold cluster varies within Z=0,±1. The analysis of these bonding patterns and their effects on the N–H⋯N H-bonded ammonia clusters are the subject of this paper.
Computational modeling of nanorod growth
Authors: Grochola Gregory , Snook Ian K. , Russo Salvy P.
Published: November 2007

In this computational study, we used molecular dynamics and the embedded atom method to successfully reproduce the growth of gold nanorod morphologies from starting spherical seeds in the presence of model surfactants. The surfactant model was developed through extensive systematic attempts aimed at inducing nonisotropic nanoparticle growth in strictly isotropic computational growth environments. The aim of this study was to identify key properties of the surfactants which were most important for the successful anisotropic growth of nanorods. The observed surface and collective dynamics of surfactants shed light on the likely growth phenomena of real nanoprods. These phenomena include the initial thermodynamically driven selective adsorption, segregation, and orientation of the surfactant groups on specific crystallographic surfaces of spherical nanoparticle seeds and the kinetic elongation of unstable surfaces due to growth inhibiting surfactants on those surfaces. Interestingly, the model not only reproduced the growth of nearly all known nanorod morphologies when starting from an initial fcc or fivefold seed but also reproduced the experimentally observed failure of nanorod growth when starting from spherical nanoparticles such as the Ih morphology or morphologies containing a single twinning plane. Nanorod morphologies observed in this work included fivefold nanorods, fcc crystalline nanorods in the [100] direction and [112] directions and the more exotic “dumbell-like” nanorods. Non-nanorod morphologies observed included the Ih and the nanoprism morphology. Some of the key properties of the most successful surfactants seemed to be suggestive of the important but little understood role played by silver ions in the growth process of real nanorods.
Local strain measurements in shallow trench insulator structures using near-ultraviolet Raman spectroscopy: Simulation and experiment
Authors: Latu-Romain Eddy , Mermoux Michel , Crisci Alexandre , Delille Dominique , Kwakman Laurens F. Tz.
Published: November 2007

Shallow trench insulator (STI) stress induced in active lines has been investigated both by near-ultraviolet (UV) Raman spectroscopy and mechanical modelization. Two different STI processes have been compared. The influence of the linewidth is also studied. After adjusting some instrumental and material parameters, all components of the stress tensors have been determined accurately. The polarization of the incoming light is discussed, showing that the selection rules are no longer respected at the edges of the STIs. Some of the limitations in spatial resolution of the Raman spectroscopy have been overcome, making use of the mechanical model and taking benefit from the higher spatial resolution of the UV excitation. In turn, the mechanical model has been refined from comparisons with experiments. It is therefore suggested that coupling these techniques may provide a relevant method to measure stress in the silicon for the integrated circuit industry. From a practical viewpoint, it is demonstrated that the use of the subatmospheric chemical vapor deposition process allows significant reduction of the compressive stress in the center of the active lines.
Ghost imaging in Fourier space
Authors: Liu Honglin , Cheng Jing , Han Shensheng
Published: November 2007

In experimentation we first find that a ghost diffraction image exists even when the coherent length on the object plane is larger than the character size of the object, and we explain the phenomenon in Fourier space. The analysis indicates that the resolution of the far-field diffraction image is determined by the coherent length on the back-focus plane, and the distribution of the wave vector of the illumination on the object determines the range of information of a pixel detector collecting in the signal arm.
Experimental verification of backward wave propagation at photonic crystal surfaces
Authors: Foteinopoulou S. , Kenanakis G. , Katsarakis N. , Tsiapa I. , Kafesaki M. , Economou E. N. , Soukoulis C. M.
Published: November 2007

Backward wave propagation is the true manifestation of left-handed electromagnetism and not negative refraction which occurs also at the interface of right-handed systems. Here we experimentally demonstrate in a direct fashion the backward wave propagation phenomenon, which takes place at the surface of a properly designed photonic crystal. Our microwave experiment could open other venues for the verification of left-handed behavior in optical metamaterials.
Simultaneous growth of a GaN p∕n lateral polarity junction by polar selective doping
Authors: Collazo R. , Mita S. , Rice A. , Dalmau R. F. , Sitar Z.
Published: November 2007

Differences in surface energy between the Ga-polar orientation and the N-polar orientation of GaN translate into a completely different behavior for the incorporation of intentional and unintentional impurities. Oxygen is found to be an impurity with higher concentrations in N-polar films than in Ga-polar films and is the cause for the high n-type carrier concentration observed in N-polar films. We fabricated a lateral p∕n junction in GaN by the simultaneous growth of p- and n-type regions, utilizing the doping selectivity of the two different polar domains. The N-polar domains were n type with a carrier concentration of 1.7×1019cm−3, predominantly due to high oxygen incorporation, while Ga-polar domains were p type with a carrier concentration of 1.7×1017cm−3. No significant difference in Mg incorporation was observed between the two polar domains. This junction showed the characteristics that define a p∕n junction: current rectification, electroluminescence, and the photovoltaic effect.
Measurement of the anisotropy constant of antiferromagnets in metallic polycrystalline exchange biased systems
Authors: Vallejo-Fernandez G. , Fernandez-Outon L. E. , O’Grady K.
Published: November 2007

A method for the measurement of the anisotropy constant of the antiferromagnet (AF) KAF in exchange biased systems has been developed. This has been achieved by measurement of the median blocking temperature ⟨TB⟩ of a CoFe∕IrMn bilayer. In thermal activation-free conditions, this is the temperature at which equal volumes of the AF are oriented in opposite senses. Hence, for a grain size dependent model, the critical volume for thermal activation at this point is equal to the median volume of the grain size distribution. A value of (5.5±0.5)×106erg∕cc has been obtained at room temperature for a 4nm thick IrMn layer.
Magnetodielectric coupling in core/shell BaTiO3∕γ-Fe2O3 nanoparticles
Authors: Koo Y. S. , Bonaedy T. , Sung K. D. , Jung J. H. , Yoon J. B. , Jo Y. H. , Jung M. H. , Lee H. J. , Koo T. Y. , Jeong Y. H.
Published: November 2007

We report an intriguing magnetodielectric coupling in BaTiO3∕γ-Fe2O3 dielectric core/ferrimagnetic shell nanoparticles. The dielectric constant steeply increases with magnetic field, and the frequency dependent magnetodielectric curve shows a resonancelike peak at high temperatures, while it decreases smoothly with field and no peak appears in the frequency dependent magnetodielectric curve at low temperatures. We attribute the observed magnetodielectric coupling to the Maxwell-Wagner effect combined with magnetoresistance at high temperatures and to possible spin-lattice coupling and its modification near interfaces at low temperatures.
Constellations of Identity: Place-Ma(r)King beyond Heritage
Authors: Pollock Venda Louise , Sharp Joanne P
Published: November 2007

In this paper we will critically consider the different ways in which history and belonging have been treated in artworks situated in the Citadel development in Ayr on the west coast of Scotland. We will focus upon one artwork, Constellation by Stephen Hurrel, as an alternative to the more conventional landscapes of heritage which are adjacent, in order to examine the relationship between personal history and place history and argue the primacy of participatory process in the creation of place and of any artwork therein. Through his artwork, Hurrel has attempted to adopt a material process through which place can be created performatively but, in part due to its nonrepresentational form, it proves problematic, aesthetically and longitudinally, in wholly engaging the community. We will suggest that, through variants of ‘new genre public art’ such as this, personal and place histories can be actively recreated through the redevelopment of contemporary urban landscapes, but we will also highlight the complexities and indeterminacies involved in the relationship between artwork, people, and place.
Weed management on grazing properties: a survey of livestock producers in New South Wales and Victoria
Authors: van der Meulen A. W. , Reeve I. J. , Sindel B. M.
Published: November 2007

Social research was conducted to explore factors influencing weed management on grazing properties in southern Australia. Face-to-face interviews were held with 122 livestock producers, 94 written questionnaires were returned and 90 grazing properties were visited and rated for weed incidence and management effort. Segmentation techniques revealed three groups, on the basis of farmer demographics and farm characteristics. These groups varied significantly in the range of control methods used, weed management effort, difficulties encountered with weed control and attitudes towards weed control. Respondents were also grouped into four categories with respect to weed control methods: minimal control, mechanical control, grazing control and maximal control. Control groups differed significantly in terms of the number and complexity of methods used, difficulties encountered with weed control, levels of weed awareness and the value placed on various sources of information about weed control. Characteristics of effective weed managers were considered and three factors were identified as underpinning success with weed control. These are referred to as the three ‘Ds’: diligence, diversity and deliberation. These factors have been used to define a three dimensional framework, within which the diversity of approaches towards weed control can be understood.
Impact of voltage unbalance on the performance of three-phase induction motor
Authors: Kini P Giridhar , Bansal R C , Aithal R S
Published: November 2007

Availability of quality power has become an important issue for industrial utilities due to frequent performance variations in process industries. Increase in the generating capacity has not kept up pace of power demand, which results into shortage of power supply and power system network is normally subjected to varying and unequal loads across the three phases. Continuous variation of single-phase loads on the power system network leads to voltage variation and unbalance, most importantly; the three-phase voltages tend to become asymmetrical in nature. Application of asymmetrical voltages to induction motor driven systems severely affects its working performance. This paper presents the effects of voltage variation and unbalance on the performance of an induction motor driven centrifugal pump with a case study.
Transformation of hematopoietic cells and activation of JAK2-V617F by IL-27R, a component of a heterodimeric type I cytokine receptor
Authors: Pradhan Anuradha , Lambert Que T. , Reuther Gary W.
Published: November 2007

From a patient with acute myeloid leukemia (AML), we have identifiedIL-27Ra(also known asTCCRandWSX1) as a gene whose expression can induce the transformation of hematopoietic cells. IL-27Ra (IL-27R) is a type I cytokine receptor that functions as the ligand binding component of the receptor for IL-27 and functions with the glycoprotein 130 (gp130) coreceptor to induce signal transduction in response to IL-27. We show that IL-27R is expressed on the cell surface of the leukemic cells of AML patients. 32D myeloid cells transformed by IL-27R contain elevated levels of activated forms of various signaling proteins, including JAK1, JAK2, STAT1, STAT3, STAT5, and ERK1/2. Inhibition of JAK family proteins induces cell cycle arrest and apoptosis in these cells, suggesting the transforming properties of IL-27R depend on the activity of JAK family members. IL-27R also transforms BaF3 cells to cytokine independence. Because BaF3 cells lack expression of gp130, this finding suggests that IL-27R-mediated transformation of hematopoietic cells is gp130-independent. Finally, we show that IL-27R can functionally replace a homodimeric type I cytokine receptor in the activation of JAK2-V617F, a critical JAK2 mutation in various myeloproliferative disorders (MPDs). Our data demonstrate that IL-27R possesses hematopoietic cell-transforming properties and suggest that, analogous to homodimeric type I cytokine receptors, single-chain components of heterodimeric receptors can also enhance the activation of JAK2-V617F. Therefore, such receptors may play unappreciated roles in MPDs.
Integrated genetic and epigenetic analysis identifies three different subclasses of colon cancer
Authors: Shen Lanlan , Toyota Minoru , Kondo Yutaka , Lin E , Zhang Li , Guo Yi , Hernandez Natalie Supunpong , Chen Xinli , Ahmed Saira , Konishi Kazuo , Hamilton Stanley R. , Issa Jean-Pierre J.
Published: November 2007

Colon cancer has been viewed as the result of progressive accumulation of genetic and epigenetic abnormalities. However, this view does not fully reflect the molecular heterogeneity of the disease. We have analyzed both genetic (mutations of BRAF, KRAS, and p53 and microsatellite instability) and epigenetic alterations (DNA methylation of 27 CpG island promoter regions) in 97 primary colorectal cancer patients. Two clustering analyses on the basis of either epigenetic profiling or a combination of genetic and epigenetic profiling were performed to identify subclasses with distinct molecular signatures. Unsupervised hierarchical clustering of the DNA methylation data identified three distinct groups of colon cancers named CpG island methylator phenotype (CIMP) 1, CIMP2, and CIMP negative. Genetically, these three groups correspond to very distinct profiles. CIMP1 are characterized by MSI (80%) and BRAF mutations (53%) and rare KRAS and p53 mutations (16% and 11%, respectively). CIMP2 is associated with 92% KRAS mutations and rare MSI, BRAF, or p53 mutations (0, 4, and 31% respectively). CIMP-negative cases have a high rate of p53 mutations (71%) and lower rates of MSI (12%) or mutations of BRAF (2%) or KRAS (33%). Clustering based on both genetic and epigenetic parameters also identifies three distinct (and homogeneous) groups that largely overlap with the previous classification. The three groups are independent of age, gender, or stage, but CIMP1 and 2 are more common in proximal tumors. Together, our integrated genetic and epigenetic analysis reveals that colon cancers correspond to three molecularly distinct subclasses of disease.
Separate functions for nuclear and cytoplasmic cryptochrome 1 during photomorphogenesis ofArabidopsisseedlings
Authors: Wu Guosheng , Spalding Edgar P.
Published: November 2007

Cryptochrome blue-light receptors mediate many aspects of plant photomorphogenesis, such as suppression of hypocotyl elongation and promotion of cotyledon expansion and root growth. The cryptochrome 1 (cry1) protein ofArabidopsisis present in the nucleus and cytoplasm of cells, but how the functions of one pool differ from the other is not known. Nuclear localization and nuclear export signals were genetically engineered into GFP-tagged cry1 molecules to manipulate cry1 subcellular localization in a cry1-null mutant background. The effectiveness of the engineering was confirmed by confocal microscopy. The ability of nuclear or cytoplasmic cry1 to rescue a variety ofcry1phenotypes was determined. Hypocotyl growth suppression by blue light was assessed by standard end-point analyses and over time with high resolution by a custom computer-vision technique. Both assays indicated that nuclear, rather than cytoplasmic, cry1 was the effective molecule in these growth inhibitions, as was the case for the mechanistically linked membrane depolarization, which occurs within several seconds of cry1 activation. Petiole elongation also was inhibited by nuclear, but not cytoplasmic, cry1. Conversely, primary root growth and cotyledon expansion in blue light were promoted by cytoplasmic cry1 and inhibited by nuclear cry1. Anthocyanin production in response to blue light was strongly stimulated by nuclear cry1 and, to a lesser extent, by cytoplasmic cry1. An important step toward elucidation of cry1 signaling pathways is the recognition that different subcellular pools of the photoreceptor have different functions.
Neuroglobin attenuates β-amyloid neurotoxicity
in vitro
and transgenic Alzheimer phenotype
in vivo
Authors: Khan Adil A. , Mao Xiao Ou , Banwait Surita , Jin Kunlin , Greenberg David A.
Published: November 2007

Neuroglobin (Ngb), a vertebrate globin expressed primarily in neurons, is induced by and protects against neuronal hypoxia and cerebral ischemia. To investigate the spectrum and mechanism of Ngb's neuroprotective action, we studied the effect of transgenic overexpression of Ngb on NMDA and β-amyloid (Aβ) toxicity in murine cortical neuron cultures
in vitro
and on the phenotype of Alzheimer's disease (AD) transgenic (APP
Sw,Ind
) mice. Compared with cortical neuron cultures from wild-type mice, cultures from Ngb-overexpressing transgenic (Ngb-Tg mice) were resistant to the toxic effects of NMDA and Aβ(25–35), as measured by polarization of cell membrane lipid rafts, mitochondrial aggregation, lactate dehydrogenase release, and nuclear fragmentation. In addition, compared with APP
Sw,Ind
mice, double-transgenic (Ngb-Tg × APP
Sw,Ind
) mice showed reductions in thioflavin-S-stained extracellular Aβ deposits, decreased levels of Aβ(1–40) and Aβ(1–42), and improved behavioral performance in a Y-maze test of spontaneous alternations. These findings suggest that the spectrum of Ngb's neuroprotective action extends beyond hypoxic–ischemic insults. Ngb may protect neurons from NMDA and Aβ toxicity by inhibiting the formation of a death-signaling membrane complex, and interventions that increase Ngb expression could have therapeutic application in AD and other neurodegenerative disorders.
Mapping hydration dynamics around a protein surface
Authors: Zhang Luyuan , Wang Lijuan , Kao Ya-Ting , Qiu Weihong , Yang Yi , Okobiah Oghaghare , Zhong Dongping
Published: November 2007

Protein surface hydration is fundamental to its structure and activity. We report here the direct mapping of global hydration dynamics around a protein in its native and molten globular states, using a tryptophan scan by site-specific mutations. With 16 tryptophan mutants and in 29 different positions and states, we observed two robust, distinct water dynamics in the hydration layer on a few (≈1–8 ps) and tens to hundreds of picoseconds (≈20–200 ps), representing the initial local relaxation and subsequent collective network restructuring, respectively. Both time scales are strongly correlated with protein's structural and chemical properties. These results reveal the intimate relationship between hydration dynamics and protein fluctuations and such biologically relevant water–protein interactions fluctuate on picosecond time scales.
Free-surface microfluidic control of surface-enhanced Raman spectroscopy for the optimized detection of airborne molecules
Authors: Piorek Brian D. , Lee Seung Joon , Santiago Juan G. , Moskovits Martin , Banerjee Sanjoy , Meinhart Carl D.
Published: November 2007

We present a microfluidic technique for sensitive, real-time, optimized detection of airborne water-soluble molecules by surface-enhanced Raman spectroscopy (SERS). The method is based on a free-surface fluidic device in which a pressure-driven liquid microchannel flow is constrained by surface tension. A colloidal suspension of silver nanoparticles flowing through the microchannel that is open to the atmosphere absorbs gas-phase 4-aminobenzenethiol (4-ABT) from the surrounding environment. As surface ions adsorbed on the colloid nanoparticles are substituted by 4-ABT, the colloid aggregates, forming SERS “hot spots” whose concentrations vary predictably along the microchannel flow. 4-ABT confined in these hot spots produces SERS spectra of very great intensity. An aggregation model is used to account quantitatively for the extent of colloid aggregation as determined from the variation of the SERS intensity measured as a function of the streamwise position along the microchannel, which also corresponds to nanoparticle exposure time. This allows us to monitor simultaneously the nanoparticle aggregation process and to determine the location at which the SERS signal is optimized.
On anti-portfolio effects in science and technology with application to reaction kinetics, chemical synthesis, and molecular biology
Authors: Vlad Marcel O. , Corlan Alexandru Dan , Popa Vlad T. , Ross John
Published: November 2007

The portfolio effect is the increase of the stability of a system to random fluctuations with the increase of the number of random state variables due to spreading the risk among these variables; many examples exist in various areas of science and technology. We report the existence of an opposite effect, the decrease of stability to random fluctuations due to an increase of the number of random state variables. For successive industrial or biochemical processes of independent, random efficiencies, the stability of the total efficiency decreases with the increase of the number of processes. Depending on the variables considered, the same process may display both a portfolio as well as an anti-portfolio behavior. In disordered kinetics, the activation energy of a reaction or transport process is the result of a sum of random components. Although the total activation energy displays a portfolio effect, the rate coefficient displays an anti-portfolio effect. For random-channel kinetics, the stability of the total rate coefficient increases with the average number of reaction pathways, whereas the stability of the survival function has an opposite behavior: it decreases exponentially with the increase of the average number of reaction pathways (anti-portfolio effect). In molecular biology, the total rate of a nucleotide substitution displays a portfolio effect, whereas the probability that no substitutions occur displays an anti-portfolio effect, resulting in faster evolutionary processes due to fluctuations. The anti-portfolio effect emerges for products of random variables or equations involving multiplicative convolution products.
A tensor higher-order singular value decomposition for integrative analysis of DNA microarray data from different studies
Authors: Omberg Larsson , Golub Gene H. , Alter Orly
Published: November 2007

We describe the use of a higher-order singular value decomposition (HOSVD) in transforming a data tensor of genes × “
x
-settings,” that is, different settings of the experimental variable
x
× “
y
-settings,” which tabulates DNA microarray data from different studies, to a “core tensor” of “eigenarrays” × “
x
-eigengenes” × “
y
-eigengenes.” Reformulating this multilinear HOSVD such that it decomposes the data tensor into a linear superposition of all outer products of an eigenarray, an
x
- and a
y
-eigengene, that is, rank-1 “subtensors,” we define the significance of each subtensor in terms of the fraction of the overall information in the data tensor that it captures. We illustrate this HOSVD with an integration of genome-scale mRNA expression data from three yeast cell cycle time courses, two of which are under exposure to either hydrogen peroxide or menadione. We find that significant subtensors represent independent biological programs or experimental phenomena. The picture that emerges suggests that the conserved genes
YKU70
,
MRE11
,
AIF1
, and
ZWF1
, and the processes of retrotransposition, apoptosis, and the oxidative pentose phosphate pathway that these genes are involved in, may play significant, yet previously unrecognized, roles in the differential effects of hydrogen peroxide and menadione on cell cycle progression. A genome-scale correlation between DNA replication initiation and RNA transcription, which is equivalent to a recently discovered correlation and might be due to a previously unknown mechanism of regulation, is independently uncovered.
3-Hydroxyanthranilic acid inhibits PDK1 activation and suppresses experimental asthma by inducing T cell apoptosis
Authors: Hayashi Tomoko , Mo Ji-Hun , Gong Xing , Rossetto Cyprian , Jang Angela , Beck Lucinda , Elliott Gregory I. , Kufareva Irina , Abagyan Ruben , Broide David H. , Lee Jongdae , Raz Eyal
Published: November 2007

3-Hydroxyanthranilic acid (HAA), a compound generated during tryptophan metabolism initiated by indoleamine 2,3-dioxygenase, is known to induce T cell death, but its molecular target is not known. Here we report that HAA inhibits NF-κB activation upon T cell antigen receptor engagement by specifically targeting PDK1. Inhibition of NF-κB by HAA leads to dysfunction and cell death of activated Th2 cells, which in turn suppresses experimental asthma. Inhibition of NF-κB and induction of apoptosis is specific to CD4 T cells because HAA does not inhibit NF-κB activation or induce cell death upon Toll-like receptor 4 stimulation in dendritic cells. Thus, HAA is a natural inhibitor that restrains T cell expansion and activation.
Aberrant expression of zinc transporter ZIP4 (SLC39A4) significantly contributes to human pancreatic cancer pathogenesis and progression
Authors: Li Min , Zhang Yuqing , Liu Zijuan , Bharadwaj Uddalak , Wang Hao , Wang Xinwen , Zhang Sheng , Liuzzi Juan P. , Chang Shou-Mei , Cousins Robert J. , Fisher William E. , Brunicardi F. Charles , Logsdon Craig D. , Chen Changyi , Yao Qizhi
Published: November 2007

Zinc is an essential trace element and catalytic/structural component used by many metalloenzymes and transcription factors. Recent studies indicate a possible correlation of zinc levels with the cancer risk; however, the exact role of zinc and zinc transporters in cancer progression is unknown. We have observed that a zinc transporter, ZIP4 (SLC39A4), was substantially overexpressed in 16 of 17 (94%) clinical pancreatic adenocarcinoma specimens compared with the surrounding normal tissues, and ZIP4 mRNA expression was significantly higher in human pancreatic cancer cells than human pancreatic ductal epithelium (HPDE) cells. This indicates that aberrant ZIP4 up-regulation may contribute to the pancreatic cancer pathogenesis and progression. We studied the effects of ZIP4 overexpression in pancreatic cancer cell proliferation
in vitro
and pancreatic cancer progression
in vivo
. We found that forced expression of ZIP4 increased intracellular zinc levels, increased cell proliferation by 2-fold
in vitro
, and significantly increased tumor volume by 13-fold in the nude mice model with s.c. xenograft compared with the control cells. In the orthotopic nude mice model, overexpression of ZIP4 not only increased the primary tumor weight (7.2-fold), it also increased the peritoneal dissemination and ascites incidence. Moreover, increased cell proliferation and higher zinc content were also observed in the tumor tissues that overexpressed ZIP4. These data reveal an important outcome of aberrant ZIP4 expression in contributing to pancreatic cancer pathogenesis and progression. It may suggest a therapeutic strategy whereby ZIP4 is targeted to control pancreatic cancer growth.
Tissue entrainment by feedback regulation of insulin gene expression in the endoderm of
Caenorhabditis elegans
Authors: Murphy Coleen T. , Lee Seung-Jae , Kenyon Cynthia
Published: November 2007

How are the rates of aging of different tissues coordinated? In
Caenorhabditis elegans
, decreasing insulin/IGF-1 signaling extends lifespan by activating the transcription factor DAF-16/FOXO. If DAF-16 levels are experimentally increased in one tissue, such as the intestine, DAF-16 activity in other tissues rises. Here we test the hypothesis that this “FOXO-to-FOXO” signaling occurs via feedback regulation of
ins-7
insulin gene expression. We find that DAF-16 regulates
ins-7
expression in the intestine, and that preventing this regulation blocks FOXO-to-FOXO signaling from the intestine to other tissues. Our findings show that feedback regulation of insulin gene expression coordinates DAF-16 activity among the tissues, and they establish the intestine, which is the animal's entire endoderm, as an important insulin-signaling center.
Differential natural killer cell–mediated inhibition of HIV-1 replication based on distinct KIR/HLA subtypes
Authors: Alter Galit , Martin Maureen P. , Teigen Nickolas , Carr William H. , Suscovich Todd J. , Schneidewind Arne , Streeck Hendrik , Waring Michael , Meier Angela , Brander Christian , Lifson Jeffrey D. , Allen Todd M. , Carrington Mary , Altfeld Marcus
Published: November 2007

Decline of peak viremia during acute HIV-1 infection occurs before the development of vigorous adaptive immunity, and the level of decline correlates inversely with the rate of AIDS progression, implicating a potential role for the innate immune response in determining disease outcome. The combined expression of an activating natural killer (NK) cell receptor, the killer immunoglobulin-like receptor (KIR) 3DS1, and its presumed ligand, human leukocyte antigen (HLA)–B Bw4-80I, has been associated in epidemiological studies with a slow progression to AIDS. We examined the functional ability of NK cells to differentially control HIV-1 replication in vitro based on their KIR and HLA types. NK cells expressing KIR3DS1 showed strong, significant dose- and cell contact–dependent inhibition of HIV-1 replication in target cells expressing HLA-B Bw4-80I compared with NK cells that did not express KIR3DS1. Furthermore, KIR3DS1+ NK cells and NKLs were preferentially activated, and lysed HIV-1 infected target cells in an HLA-B Bw4-80I–dependent manner. These data provide the first functional evidence that variation at the KIR locus influences the effectiveness of NK cell activity in the containment of viral replication.
Multiple Pathways Differentially Regulate Global Oxidative Stress Responses in Fission Yeast
Authors: Chen Dongrong , Wilkinson Caroline R.M. , Watt Stephen , Penkett Christopher J. , Toone W. Mark , Jones Nic , Bähler Jürg
Published: November 2007

Cellular protection against oxidative damage is relevant to ageing and numerous diseases. We analyzed the diversity of genome-wide gene expression programs and their regulation in response to various types and doses of oxidants in Schizosaccharomyces pombe. A small core gene set, regulated by the AP-1–like factor Pap1p and the two-component regulator Prr1p, was universally induced irrespective of oxidant and dose. Strong oxidative stresses led to a much larger transcriptional response. The mitogen-activated protein kinase (MAPK) Sty1p and the bZIP factor Atf1p were critical for the response to hydrogen peroxide. A newly identified zinc-finger protein, Hsr1p, is uniquely regulated by all three major regulatory systems (Sty1p-Atf1p, Pap1p, and Prr1p) and in turn globally supports gene expression in response to hydrogen peroxide. Although the overall transcriptional responses to hydrogen peroxide and t-butylhydroperoxide were similar, to our surprise, Sty1p and Atf1p were less critical for the response to the latter. Instead, another MAPK, Pmk1p, was involved in surviving this stress, although Pmk1p played only a minor role in regulating the transcriptional response. These data reveal a considerable plasticity and differential control of regulatory pathways in distinct oxidative stress conditions, providing both specificity and backup for protection from oxidative damage.
Uniformization for sampling realizations of Markov processes: applications to Bayesian implementations of codon substitution models
Authors: Rodrigue Nicolas , Philippe Hervé , Lartillot Nicolas
Published: November 2007

Motivation: Mapping character state changes over phylogenetic trees is central to the study of evolution. However, current probabilistic methods for generating such mappings are ill-suited to certain types of evolutionary models, in particular, the widely used models of codon substitution.

Results: We describe a general method, based on a uniformization technique, which can be utilized to generate realizations of a Markovian substitution process conditional on an alignment of character states and a given tree topology. The method is applicable under a wide range of evolutionary models, and to illustrate its usefulness in practice, we embed it within a data augmentation-based Markov chain Monte Carlo sampler, for approximating posterior distributions under previously proposed codon substitution models. The sampler is found to be more efficient than the conventional pruning-based sampler with the decorrelation times between draws from the posterior reduced by a factor of 20 or more.

Contact:  nicolas.rodrigue@umontreal.ca
Electronic properties and the quantum Hall effect in bilayer graphene
Authors: Fal'ko Vladimir I
Published: November 2007

In this paper, I review the quantum Hall effect (QHE) and far-infra red (FIR) absorption properties of bilayer graphene in a strong magnetic field. This includes a derivation of the effective low-energy Hamiltonian for this system and the consequences of this Hamiltonian for the sequencing of the Landau levels in the material: the form of this effective Hamiltonian gives rise to the presence of a level with doubled degeneracy at zero energy. The effect of a potential difference between the layer of a bilayer is also investigated. It is found that there is a density-dependent gap near the
K
points in the band structure. The consequences of this gap on the QHE are then described. Also, the magneto-absorption spectrum is investigated and an experiment proposed to distinguish between model groundstates of the bilayer QHE system based on the different absorption characteristics of right- and left-handed polarization of FIR light. Finally, the effects of trigonal warping are taken into account in the absorption picture.
Electron scattering on microscopic corrugations in graphene
Authors: Katsnelson M.I , Geim A.K
Published: November 2007

We discuss various scattering mechanisms for Dirac fermions in single-layer graphene. It is shown that scattering on a short-range potential (e.g. due to neutral impurities) is mostly irrelevant for electronic quality of graphene, which is likely to be controlled by charged impurities and ripples (microscopic corrugations of a graphene sheet). The latter are an inherent feature of graphene due to its two-dimensional nature and can also be an important factor in defining the electron mean-free path. We show that certain types of ripples create a long-range scattering potential, similar to Coulomb scatterers, and result in charge-carrier mobility practically independent of carrier concentration, in agreement with experimental observations.
Gene activities that mediate increased life span of C. elegans insulin-like signaling mutants
Authors: Samuelson Andrew V. , Carr Christopher E. , Ruvkun Gary
Published: November 2007

Genetic and RNA interference (RNAi) screens for life span regulatory genes have revealed that the daf-2 insulin-like signaling pathway plays a major role in Caenorhabditis elegans longevity. This pathway converges on the DAF-16 transcription factor and may regulate life span by controlling the expression of a large number of genes, including free-radical detoxifying genes, stress resistance genes, and pathogen resistance genes. We conducted a genome-wide RNAi screen to identify genes necessary for the extended life span of daf-2 mutants and identified ∼200 gene inactivations that shorten daf-2 life span. Some of these gene inactivations dramatically shorten daf-2 mutant life span but less dramatically shorten daf-2; daf-16 mutant or wild-type life span. Molecular and behavioral markers for normal aging and for extended life span in low insulin/IGF1 (insulin-like growth factor 1) signaling were assayed to distinguish accelerated aging from general sickness and to examine age-related phenotypes. Detailed demographic analysis, molecular markers of aging, and insulin signaling mutant test strains were used to filter progeric gene inactivations for specific acceleration of aging. Highly represented in the genes that mediate life span extension in the daf-2 mutant are components of endocytotic trafficking of membrane proteins to lysosomes. These gene inactivations disrupt the increased expression of the DAF-16 downstream gene superoxide dismutase sod-3 in a daf-2 mutant, suggesting trafficking between the insulin-like receptor and DAF-16. The activities of these genes may normally decline during aging.
Novel pro- and anti-recombination activities of the Bloom’s syndrome helicase
Authors: Bugreev Dmitry V. , Yu Xiong , Egelman Edward H. , Mazin Alexander V.
Published: November 2007

Bloom’s syndrome (BS) is an autosomal recessive disorder characterized by a strong cancer predisposition. The defining feature of BS is extreme genome instability. The gene mutated in Bloom’s syndrome, BLM, encodes a DNA helicase (BLM) of the RecQ family. BLM plays a role in homologous recombination; however, its exact function remains controversial. Mutations in the BLM cause hyperrecombination between sister chromatids and homologous chromosomes, indicating an anti-recombination role. Conversely, other data show that BLM is required for recombination. It was previously shown that in vitro BLM helicase promotes disruption of recombination intermediates, regression of stalled replication forks, and dissolution of double Holliday junctions. Here, we demonstrate two novel activities of BLM: disruption of the Rad51-ssDNA (single-stranded DNA) filament, an active species that promotes homologous recombination, and stimulation of DNA repair synthesis. Using in vitro reconstitution reactions, we analyzed how different biochemical activities of BLM contribute to its functions in homologous recombination.
A burst of protein sequence evolution and a prolonged period of asymmetric evolution follow gene duplication in yeast
Authors: Scannell Devin R. , Wolfe Kenneth H.
Published: November 2007

It is widely accepted that newly arisen duplicate gene pairs experience an altered selective regime that is often manifested as an increase in the rate of protein sequence evolution. Many details about the nature of the rate acceleration remain unknown, however, including its typical magnitude and duration, and whether it applies to both gene copies or just one. We provide initial answers to these questions by comparing the rate of protein sequence evolution among eight yeast species, between a large set of duplicate gene pairs that were created by a whole-genome duplication (WGD) and a set of genes that were returned to single-copy after this event. Importantly, we use a new method that takes into account the tendency for slowly evolving genes to be retained preferentially in duplicate. We show that, on average, proteins encoded by duplicate gene pairs evolved at least three times faster immediately after the WGD than single-copy genes to which they behave identically in non-WGD lineages. Although the high rate in duplicated genes subsequently declined rapidly, it has not yet returned to the typical rate for single-copy genes. In addition, we show that although duplicate gene pairs often have highly asymmetric rates of evolution, even the slower members of pairs show evidence of a burst of protein sequence evolution immediately after duplication. We discuss the contribution of neofunctionalization to duplicate gene preservation and propose that a form of subfunctionalization mediated by coding region activity-reducing mutations is likely to have played an important role.
Genome-wide patterns of gene flow across a house mouse hybrid zone
Authors: Teeter Katherine C. , Payseur Bret A. , Harris Leslie W. , Bakewell Margaret A. , Thibodeau Lisa M. , O’Brien Janelle E. , Krenz James G. , Sans-Fuentes Maria A. , Nachman Michael W. , Tucker Priscilla K.
Published: November 2007

Hybrid zones between closely related species or subspecies provide useful settings for studying the genetic architecture of speciation. Using markers distributed throughout the mouse genome, we use a hybrid zone between two recently diverged species of house mice (Mus musculus and Mus domesticus) as a natural mapping experiment to identify genomic regions that may be involved in reproductive isolation. Using cline analysis we document a nearly 50-fold variation in level of introgression among markers. Some markers have extremely narrow cline widths; these genomic regions may contribute to reproductive isolation. Biological processes associated with these narrow clines include physiological and immune responses to the environment as well as physiological and behavioral aspects of reproduction. Other autosomal markers exhibit asymmetrically broad clines, usually with high frequencies of M. domesticus alleles on the M. musculus side of the hybrid zone. These markers identify genome regions likely housing genes with alleles that are spreading from one species to the other. Biological processes associated with these wide clines include cell signaling, olfaction, and pheromone response. These processes play important roles in survival and reproduction, and associated genes are likely targets of selection. Patterns of linkage disequilibrium in the center of the hybrid zone suggest that isolation may be caused by multiple epistatic interactions between sets of genes. These data highlight the complex genetic architecture underlying speciation even at early stages of divergence and point to some of the biological processes that may govern this architecture.
Computational design of the Fyn SH3 domain with increased stability through optimization of surface charge–charge interactions
Authors: Schweiker Katrina L. , Zarrine‐Afsar Arash , Davidson Alan R. , Makhatadze George I.
Published: November 2007

Computational design of surface charge–charge interactions has been demonstrated to be an effective way to increase both the thermostability and the stability of proteins. To test the robustness of this approach for proteins with predominantly β‐sheet secondary structure, the chicken isoform of the Fyn SH3 domain was used as a model system. Computational analysis of the optimal distribution of surface charges showed that the increase in favorable energy per substitution begins to level off at five substitutions; hence, the designed Fyn sequence contained four charge reversals at existing charged positions and one introduction of a new charge. Three additional variants were also constructed to explore stepwise contributions of these substitutions to Fyn stability. The thermodynamic stabilities of the variants were experimentally characterized using differential scanning calorimetry and far‐UV circular dichroism spectroscopy and are in very good agreement with theoretical predictions from the model. The designed sequence was found to have increased the melting temperature, ΔTm = 12.3 ± 0.2°C, and stability, ΔΔG(25°C) = 7.1 ± 2.2 kJ/mol, relative to the wild‐type protein. The experimental data suggest that a significant increase in stability can be achieved through a very small number of amino acid substitutions. Consistent with a number of recent studies, the presented results clearly argue for a seminal role of surface charge–charge interactions in determining protein stability and suggest that the optimization of surface interactions can be an attractive strategy to complement algorithms optimizing interactions in the protein core to further enhance protein stability.
INTRAINDUSTRY SPECIALIZATION AND THE UNITED STATES–CENTRAL AMERICA–DOMINICAN REPUBLIC FREE TRADE AGREEMENT
Authors: CLARK Don P.
Published: November 2007

This paper examines changes in intraindustry specialization indicators over the 1992–2004 period to assess the potential for structural adjustment problems that may arise in the United States with growth in trade resulting from the United States–Central America–Dominican Republic Free Trade Agreement (CAFTA‐DR) between the United States and six Central American countries—Guatemala, Honduras, El Salvador, Nicaragua, Costa Rica, and the Dominican Republic. CAFTA‐DR will expand market access for US exporters. Few US industries are likely to encounter structural adjustment problems. Given the relatively large size of the US economy, and the small number of industries that face potential adjustment pressures, the United States should have liberalized all trade immediately. When potential adjustment pressures are indicated, long tariff phaseouts, complex rules of origin, and import safeguards are used to delay factor adjustments in import‐sensitive industries.
Self‐administration of drugs in animals and humans as a model and an investigative tool
Authors: Panlilio Leigh V. , Goldberg Steven R.
Published: November 2007

Aim  To review briefly the methods, assumptions, models, accomplishments, drawbacks and future directions of research using drug self‐administration in animals and humans.

Background  The use of drug self‐administration to study addiction is based on the assumption that drugs reinforce the behavior that results in their delivery. A wide range of drug self‐administration techniques have been developed to model specific aspects of addiction. These techniques are highly amenable to being combined with a wide variety of neuroscience techniques.

Conclusions  The identification of drug use as behavior that is reinforced by drugs has contributed greatly to the understanding and treatment of addiction. As part of a program of pre‐clinical research that also involves screening with a variety of simpler behavioral techniques, drug self‐administration procedures can provide an important last step in testing potential treatments for addiction. There is currently a concerted effort to develop self‐administration procedures that model the extreme nature of the behavior engendered by addiction. As advances continue to be made in neuroscience techniques, self‐administration should continue to provide a means of applying these techniques within a sophisticated and valid model of human drug addiction.