gebhart/patrepeval huggingface dataset:
SDF-1/CXCR4 and VLA-4 interaction regulates homing in Waldenstrom macroglobulinemia (2008)

Waldenstrom macroglobulinemia (WM) is characterized by widespread involvement of the bone marrow at the time of diagnosis, implying continuous homing of WM cells into the marrow. The mechanisms by which trafficking of the malignant cells into the bone marrow has not been previously elucidated. In this study, we show that WM cells express high levels of chemokine and adhesion receptors, including CXCR4 and VLA-4. We showed that CXCR4 was essential for the migration and trans-endothelial migration of WM cells under static and dynamic shear flow conditions, with significant inhibition of migration using CXCR4 knockdown or the CXCR4 inhibitor AMD3100. Similarly, CXCR4 or VLA-4 inhibition led to significant inhibition of adhesion to fibronectin, stromal cells, and endothelial cells. Decreased adhesion of WM cells to stromal cells by AMD3100 led to increased sensitivity of these cells to cytotoxicity by bortezomib. To further investigate the mechanisms of CXCR4-dependent adhesion, we showed that CXCR4 and VLA-4 directly interact in response to SDF-1, we further investigated downstream signaling pathways regulating migration and adhesion in WM. Together, these studies demonstrate that the CXCR4/SDF-1 axis interacts with VLA-4 in regulating migration and adhesion of WM cells in the bone marrow microenvironment.
Ab initio studies of quasi-one-dimensional pentagon and hexagon ice nanotubes (2003)

Ab initio plane-wave total-energy calcuation is carried out to study the relative stability of the quasi-one-dimensional (Q1D) pentagon and hexagon ice nanotubes. Electronic structure calculations indicate the two Q1D ice nanotubes have nearly the same band structures and energy bandgap as those of proton-ordered bulk ice Ih. Ab initio molecular-orbital and density-functional theory calculations, as well as three classical potential models of water, are also employed to investigate the relative stability of the pentagon and hexagon water clusters (H2O)30, (H2O)60, and (H2O)120. Clusters of this kind can serve to bridge the gap between the small polygonal water rings and the infinitely long Q1D polygon ice nanotubes. It is found that the polygon water prisms with the size (H2O)120 begin to show the relative energetic behavior of the infinitely long polygon ice nanotubes.
Strategies for Discovery of Small Molecule Radiation Protectors and Radiation Mitigators (2012)

Mitochondrial targeted radiation damage protectors (delivered prior to irradiation) and mitigators (delivered after irradiation, but before the appearance of symptoms associated with radiation syndrome) have been a recent focus in drug discovery for (1) normal tissue radiation protection during fractionated radiotherapy, and (2) radiation terrorism counter measures. Several categories of such molecules have been discovered: nitroxide-linked hybrid molecules, including GS-nitroxide, GS-nitric oxide synthase inhibitors, p53/mdm2/mdm4 inhibitors, and pharmaceutical agents including inhibitors of the phosphoinositide-3-kinase pathway and the anti-seizure medicine, carbamazepine. Evaluation of potential new radiation dose modifying molecules to protect normal tissue includes: clonogenic radiation survival curves, assays for apoptosis and DNA repair, and irradiation-induced depletion of antioxidant stores. Studies of organ specific radioprotection and in total body irradiation-induced hematopoietic syndrome in the mouse model for protection/mitigation facilitate rational means by which to move candidate small molecule drugs along the drug discovery pipeline into clinical development.
Guam Amyotrophic Lateral Sclerosis-Parkinsonism-Dementia Linked to a Plant Excitant Neurotoxin (1987)

The decline in the high incidence of amyotrophic lateral sclerosis, parkinsonism, and Alzheimer-type dementia among the Chamorro population of the western Pacific islands of Guam and Rota, coupled with the absence of demonstrable viral and hereditable factors in this disease, suggests the gradual disappearance of an environmental factor selectively associated with this culture. One candidate is seed of the neurotoxic plant Cycas circinalis L., a traditional source of food and medicine which has been used less with the Americanization of the Chamorro people after World War II. Macaques were fed the Cycas amino acid beta-N-methylamino-L-alanine, a low-potency convulsant that has excitotoxic activity in mouse brain, which is attenuated by N-methyl-D-aspartate receptor antagonists. These animals developed corticomoto-neuronal dysfunction, parkinsonian features, and behavioral anomalies, with chromatolytic and degenerative changes of motor neurons in cerebral cortex and spinal cord. In concert with existing epidemiological and animal data, these findings support the hypothesis that cycad exposure plays an important role in the etiology of the Guam disease.
The Clinical Development of &#947;-Hydroxybutyrate (GHB) (2006)

The discovery of gamma-hydroxybutyrate (GHB) over 40 years ago led to its immediate use as a general anesthetic agent. Subsequent research demonstrated that GHB is an endogenous compound in the mammalian brain and current research suggests that GHB is a probable neurotransmitter. In the United States, reports of anabolic effects lead to its misuse among body builders during the 1980's while the intoxicating properties of the drug lead to its popularization as a substance of abuse during the 1990's. GHB became associated with reports of drug-facilitated sexual assault and cases of physical dependence and withdrawal. Efforts to ban GHB caused increased use of GHB analogues and pro-drugs. Against this backdrop, GHB was being developed for the treatment of narcolepsy, leading to the approval of Xyrem (sodium oxybate) oral solution in 2002 for the treatment of cataplexy in patients with narcolepsy. A risk management program permits the safe handling and distribution of the approved product, minimizes the risk for diversion, provides professional and patient education about the risks and benefits of sodium oxybate, and includes physician and patient registries. Post-marketing surveillance indicates sodium oxybate has an acceptable safety profile and presents minimal risk for the development of physical dependence.
Surface enhancement of local optical fields and the lightning-rod effect (1993)

The increase in the local field Eloc due to the "lightning-rod effect" has been studied theoretically (in a model of a small ellipsoid) and experimentally (by a method of surface-enhanced second-harmonic generation on a surface with protruding needles). Algorithms are proposed for resolving the overall electromagnetic amplification of Eloc into resonant and nonresonant components, both in the model and experimentally. The model predicts a limitation on the nonresonant local-field enhancement because of the modulus of the dielectric constant of the metal. This prediction has been confirmed experimentally.
Molecular Phylogeny and Proposed Classification of the Simian Picornaviruses (2002)

The simian picornaviruses were isolated from various primate tissues during the development of general tissue culture methods in the 1950s to 1970s or from specimens derived from primates used in biomedical research. Twenty simian picornavirus serotypes are recognized, and all are presently classified within the Enterovirus genus. To determine the phylogenetic relationships among all of the simian picornaviruses and to evaluate their classification, we have determined complete VP1 sequences for 19 of the 20 serotypes. Phylogenetic analysis showed that A13, SV19, SV26, SV35, SV43, and SV46 are members of human enterovirus species A, a group that contains enterovirus 71 and 11 of the coxsackie A viruses. SA5 is a member of human enterovirus species B, which contains the echoviruses, coxsackie B viruses, coxsackievirus A9, and enterovirus 69. SV6, N125, and N203 are related to one another and, more distantly, to species A human enteroviruses, but could not be definitely assigned to a species. SV4 and SV28 are closely related to one another and to A-2 plaque virus, but distinct from other enteroviruses, suggesting that these simian viruses are members of a new enterovirus species. SV2, SV16, SV18, SV42, SV44, SV45, and SV49 are related to one another but distinct from viruses in all other picornavirus genera, suggesting that they may comprise a previously unknown genus in Picornaviridae. Several simian virus VP1 sequences (N125 and N203; SV4 and SV28; SV19, SV26, and SV35; SV18 and SV44; SV16, SV42, and SV45) are greater than 75% identical to one another (and/or greater than 85% amino acid identity), suggesting that the true number of distinct serotypes among the viruses surveyed is less than 20.
Purification and Some Characteristics of the Human Coagulation Factor VII (1979)

1. A purification procedure for factor VII (proconvertin) from human plasma is described. The procedure involves barium sulphate adsorption and elution. DEAE-Sephadex column chromatography, barium sulphate adsorption and elution, heparin-Sepharose column chromatography, preparative disc gel electrophoresis and finally adsorption with antiserum to prothrombin coupled to Sepharose and antiserum to albumin coupled to Sepharose. This procedure gave an approximately 8 . 10(5)-fold purification. 2. The factor VII obtained from the electrophoresis step was mainly a single-chain protein with an apparent molecular weight of 53000 +/- 2000. 3. After the final purification step, additional forms of factor VII, resulting from a fragmentation of the factor VII molecule were detected. 4. Amino acid composition data of the purified factor VII are given. 5. Antisera were raised in two different rabbits by injection of the purified factor VII. The antisera obtained gave a good titre against the factor VII activity and were not directed against any of the three other vitamin-K-dependent coagulation factors.
Monoclonal Antibodies That Distinguish Between Two Related Digitalis Glycosides, Ouabain and Digoxin (1999)

The exogenous digitalis glycosides, ouabain and digoxin, have been widely used in humans to treat congestive heart failure and cardiac arrhythmias. Several reports have also pointed to the existence of endogenous ouabain- and digoxin-like compounds, but their precise roles in mammalian physiology and various disorders of the circulation are not clear. In an attempt to produce specific Abs for the purification and identification of endogenous ouabain-like compounds, somatic cell fusion was used to produce mAbs specific for ouabain. Our attempts to produce ouabain-specific mAbs were unsuccessful when ouabain was coupled to exogenous proteins such as bovine gamma-globulins, BSA, and human serum albumin. However, when ouabain was coupled to an Ab of A/J mice origin and the same strain of mouse was used for immunization with ouabain-Ab conjugate, three Abs (1-10, 5A12, and 7-1) specific for ouabain were obtained. In assays of fluorescence quenching and saturation equilibrium with tritiated ouabain, Ab 1-10 exhibited 200 nM affinity for ouabain. These three mAbs are distinguished from existing Abs to ouabain and digoxin by their specificity for ouabain and lack of cross-reactivity with digoxin. Specificity studies showed that the loss of cross-reactivity was correlated with the presence of a hydroxyl group at either position 12beta (digoxin) or 16beta (gitoxin) of the steroid ring. These Abs can be used to develop assays for detection and characterization of ouabain-like molecules in vivo.
Mesenchymal stromal cells are more effective than the MSC secretome in diminishing injury and enhancing recovery following ventilator-induced lung injury (2015)

The immunomodulating and/or reparative effect of MSCs is evident early after VILI in this model. MSC-conditioned medium was not as effective as the cells themselves in diminishing injury and restoring lung structure and function.
Computer-aided model-building strategies for protein design (1986)

Model-building strategies for protein modification and design are developed. These strategies emphasize simple geometric aspects of protein structure, use local coordinate systems defined at particular residues, and systematically consider a large number of alternative sequences and conformations. We have written a computer program, PROTEUS, to implement these search methods. PROTEUS has been used to find positions where disulfide bonds could be added to the N-terminal domain of the lambda repressor and to predict how a loop on the surface of repressor could be shortened.
Steric Accessibility of the HIV-1 gp41 N-trimer Region (2005)

During human immunodeficiency virus entry, gp41 undergoes a series of conformational changes that induce membrane fusion. Immediately prior to fusion, gp41 exists in a prehairpin intermediate in which the N- and C-peptide regions of gp41 are exposed. Rearrangement of this intermediate into a six-helix bundle composed of a trimeric coiled coil from the N-peptide region (N-trimer) surrounded by three peptides from the C-peptide region provides the driving force for membrane fusion, whereas prevention of six-helix bundle formation inhibits viral entry. Because of its central role in mediating viral entry, the N-trimer region of gp41 is a key vaccine target. Extensive efforts to discover potent and broadly neutralizing antibodies (Abs) against the N-trimer region have, thus far, been unsuccessful. In this study, we attached a potent C-peptide inhibitor that binds to the N-trimer region to cargo proteins of various sizes to examine the steric accessibility of the N-trimer during fusion. These inhibitors show a progressive loss of potency with increasing cargo size. Extension of the cargo/C-peptide linker partially restores inhibitory potency. These results demonstrate that the human immunodeficiency virus defends its critical hairpin-forming machinery by steric exclusion of large proteins and may explain the current dearth of neutralizing Abs against the N-trimer. In contrast, previous results suggest the C-peptide region is freely accessible during fusion, demonstrating that the N- and C-peptide regions are in structurally distinct environments. Based on these results, we also propose new strategies for the generation of neutralizing Abs that overcome this steric block.
Resonant-cavity InGaN quantum-well blue light-emitting diodes (2000)

We describe progress in blue resonant-cavity light-emitting diodes, based on InGaN/GaN quantum-well heterostructures. We have fabricated vertical-microcavity devices in which either one or both mirrors forming the cavity are patterned, high-reflectivity dielectrics Bragg reflectors. The results suggest that a blue vertical-cavity diode laser may be feasible by this approach.
Self-Aligned U-Gate Carbon Nanotube Field-Effect Transistor with Extremely Small Parasitic Capacitance and Drain-Induced Barrier Lowering (2011)

A novel self-aligned U-gate structure for carbon nanotube (CNT) field-effect transistors (FETs) is introduced and shown to yield excellent dc properties and high reproducibility that are comparable with that of the best CNT FETs based on the previously developed self-aligned device structures. In particular the subthreshold swing of the U-gate FET is 75 mV/dec and the drain-induced barrier lowering is effectively zero, indicating that the electrostatic potential of the whole CNT channel is most efficiently controlled by the U-gate and that the CNT device is a well-behaved FET. Moreover the high-frequency response of the U-gate FET is investigated, and the parasitic capacitance of the device is measured and shown to be one magnitude smaller than that of the previously developed self-aligned device structures. Direct frequency domain measurements show that the U-gate CNT FETs can operate up to 800 MHz, which is also higher than previously reported values. The large improvement in the device high-frequency behavior is largely due to the replacement of the high-κ dielectric material between the source/drain and the gate by a vacant space with κ ≈ 1, and the significant reduction in the device parasitic capacitance renders the U-gate CNT FETs promising for rf applications.
Age-Associated Increase in BMP Signaling Inhibits Hippocampal Neurogenesis (2014)

Hippocampal neurogenesis, the product of resident neural stem cell proliferation and differentiation, persists into adulthood but decreases with organismal aging, which may contribute to the age-related decline in cognitive function. The mechanisms that underlie this decrease in neurogenesis are not well understood, although evidence in general indicates that extrinsic changes in an aged stem cell niche can contribute to functional decline in old stem cells. Bone morphogenetic protein (BMP) family members are intercellular signaling proteins that regulate stem and progenitor cell quiescence, proliferation, and differentiation in various tissues and are likewise critical regulators of neurogenesis in young adults. Here, we establish that BMP signaling increases significantly in old murine hippocampi and inhibits neural progenitor cell proliferation. Furthermore, direct in vivo attenuation of BMP signaling via genetic and transgenic perturbations in aged mice led to elevated neural stem cell proliferation, and subsequent neurogenesis, in old hippocampi. Such advances in our understanding of mechanisms underlying decreased hippocampal neurogenesis with age may offer targets for the treatment of age-related cognitive decline.
Three‐Component Bimetallic (Pd/In) Mediated Cascade Allylation of C=X Functionality. Part 1. Scope and Class 1 Examples with Aldehydes and Ketones. (2004)

Abstract For Abstract see ChemInform Abstract in Full Text.
Resonant Absorption of the 14.4-kevγRay from 0.10-μsecFe57 (1959)

Received 23 November 1959DOI:https://doi.org/10.1103/PhysRevLett.3.554©1959 American Physical Society
A systematic review of the importance of milk TGF‐β on immunological outcomes in the infant and young child (2009)

Cytokines in milk like transforming growth factor-beta (TGF-beta) have been shown to induce oral tolerance in experimental animal studies. However, human studies are less consistent with these findings. The primary objective of this review was to conduct a systematic review of published studies on the association between TGF-beta identified in human milk and immunological outcomes in infancy and early childhood. Human prospective clinical studies were identified through MEDLINE, CAB Abstracts, Biological Abstracts and Scopus. Selection criteria included: well described populations of mothers and infants, time of milk sampling, immunological outcome measures and analytical methods of TGF-beta determination. We considered a wide range of immunological outcomes in infancy and early childhood, such as wheeze, atopy, eczema and the immunoglobulin switch. Twelve human studies were included in the review and 67% showed a positive association with TGF-beta1 or TGF-beta2 demonstrating protection against allergy-related outcomes in infancy and early childhood. High variability in concentrations of TGF-beta was noted between and within studies, some of it explained by maternal history of atopy or by consumption of probiotics. Human milk TGF-beta appears to be essential in developing and maintaining appropriate immune responses in infants and may provide protection against adverse immunological outcomes, corroborating findings from experimental animal studies. Further large clinical studies in diverse human populations are indicated to confirm these results.
NF-κB-dependent Induction of Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL) and Fas/FasL Is Crucial for Efficient Influenza Virus Propagation (2004)

Activation of the transcription factor NF-kappaB is a hallmark of infections by viral pathogens including influenza viruses. Because gene expression of many proinflammatory and antiviral cytokines is controlled by this factor, the concept emerged that NF-kappaB and its upstream regulator IkappaB kinase are essential components of the innate antiviral immune response to infectious pathogens. In contrast to this common view we report here that NF-kappaB activity promotes efficient influenza virus production. On a molecular level this is due to NF-kappaB-dependent viral induction of the proapoptotic factors tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and FasL, which enhance virus propagation in an autocrine and paracrine fashion. Thus, NF-kappaB acts both proapoptotically and provirally in the context of an influenza virus infection.
Alpha-1-antitrypsin mutant Z protein content in individual hepatocytes correlates with cell death in a mouse model (2007)

These data, combined with previous work, permit for the first time the construction of a hypothetical hepatocellular injury cascade for this disease involving mitochondrial injury, caspase activation, and apoptosis, which takes into account the heterogeneous nature of the mutant Z protein accumulation within the liver. Further development of this hypothetical cascade will focus future research on this and other metabolic liver diseases.
Opportunistic beamforming using dumb antennas (2003)

An important means to cope with fading in wireless channels is the use of diversity. Diversity can be obtained over time (interleaving of coded bits), frequency (combining of multipaths in CDMA systems) and space (multiple antennas). The basic idea is to improve performance by creating several independent signal paths between the transmitter and the receiver. In this paper, we propose a scheme that induces random fading when the environment has little scattering and/or the fading is slow. We focus on the downlink of a cellular system. We use multiple antennas at the base-station to transmit the same signal from each antenna modulated by a gain whose phase and magnitude is changing in time in a controlled but pseudo random fashion.
The Ski oncoprotein interacts with the Smad proteins to repress TGFbeta signaling (1999)

Smad proteins are critical signal transducers downstream of the receptors of the transforming growth factor-beta (TGFbeta) superfamily. On phosphorylation and activation by the active TGFbeta receptor complex, Smad2 and Smad3 form hetero-oligomers with Smad4 and translocate into the nucleus, where they interact with different cellular partners, bind to DNA, regulate transcription of various downstream response genes, and cross-talk with other signaling pathways. Here we show that a nuclear oncoprotein, Ski, can interact directly with Smad2, Smad3, and Smad4 on a TGFbeta-responsive promoter element and repress their abilities to activate transcription through recruitment of the nuclear transcriptional corepressor N-CoR and possibly its associated histone deacetylase complex. Overexpression of Ski in a TGFbeta-responsive cell line renders it resistant to TGFbeta-induced growth inhibition and defective in activation of JunB expression. This ability to overcome TGFbeta-induced growth arrest may be responsible for the transforming activity of Ski in human and avian cancer cells. Our studies suggest a new paradigm for inactivation of the Smad proteins by an oncoprotein through transcriptional repression.
Impacts of doping on thermal and thermoelectric properties of nanomaterials (2010)

Thermal transport in nanoscale structures has attracted an increasing interest in the last two decades. On the one hand, the low dimensional nanostructured materials are platforms for testing novel phonon transport theories. On the other hand, nanomaterials are promising candidates for nanoscale on-chip coolers. This review is focused on the thermal conductance, thermoelectric property, and impacts of doping on these properties.