gebhart/patrepeval huggingface dataset:
Molecular Design and Functional Organization of the RecA Protein (2003)

The bacterial RecA protein participates in a remarkably diverse set of functions, all of which are involved in the maintenance of genomic integrity. RecA is a central component in both the catalysis of recombinational DNA repair and the regulation of the cellular SOS response. Despite the mechanistic differences of its functions, all require formation of an active RecA/ATP/DNA complex. RecA is a classic allosterically regulated enzyme, and ATP binding results in a dramatic increase in DNA binding affinity and a cooperative assembly of RecA subunits to form an ordered, helical nucleoprotein filament. The molecular events that underlie this ATP-induced structural transition are becoming increasingly clear. This review focuses on descriptions of our current understanding of the molecular design and allosteric regulation of RecA. We present a comprehensive list of all published recA mutants and use the results of various genetic and biochemical studies, together with available structural information, to develop ideas regarding the design of RecA functional domains and their catalytic organization.
A distinct hematopoietic stem cell population for rapid multilineage engraftment in nonhuman primates (2017)

Hematopoietic reconstitution after bone marrow transplantation is thought to be driven by committed multipotent progenitor cells followed by long-term engrafting hematopoietic stem cells (HSCs). We observed a population of early-engrafting cells displaying HSC-like behavior, which persisted long-term in vivo in an autologous myeloablative transplant model in nonhuman primates. To identify this population, we characterized the phenotype and function of defined nonhuman primate hematopoietic stem and progenitor cell (HSPC) subsets and compared these to human HSPCs. We demonstrated that the CD34<sup>+</sup>CD45RA<sup>-</sup>CD90<sup>+</sup> cell phenotype is highly enriched for HSCs. This population fully supported rapid short-term recovery and robust multilineage hematopoiesis in the nonhuman primate transplant model and quantitatively predicted transplant success and time to neutrophil and platelet recovery. Application of this cell population has potential in the setting of HSC transplantation and gene therapy/editing approaches.
Defects in Silicon Crystals and Their Impact on DRAM Device Characteristics (2002)

Polished p-wafers from vacancy-rich silicon crystals are used as substrates for many device applications and, in particular, for memory devices. Octahedral vacancy aggregates, the so-called crystal originated pits, are found in these wafers with sizes of 150 nm and densities of To meet the design rule requirements of 0.13 μm and below, a reduction of defect size and density is required. The approaches to achieve silicon with nearly no intrinsic point defect aggregates are the growth of so-called perfect crystals, the growth of nitrogen-doped crystals with very fast cooling rates and subsequent high temperature wafer annealing, and epitaxy of wafers. In addition, new concepts like wafers with a thin refinement layer grown on a cost and bulk optimized substrate (so-called fLASH! wafers) will allow further cost reduction. © 2002 The Electrochemical Society. All rights reserved.
Statistical model for whole genome sequencing and its application to minimally invasive diagnosis of fetal genetic disease (2009)

There is currently great interest in the development of methods for the minimally invasive diagnosis of fetal genetic disease using cell-free DNA from maternal plasma samples obtained in the first trimester of pregnancy. With the rapid development of high-throughput sequencing technology, the possibility of detecting the presence of trisomy fetal genomes in the maternal plasma DNA sample has recently been explored. The major concern of this whole genome sequencing approach is that, while detecting the karyotype of the fetal genome from the maternal plasma requires extremely high accuracy of copy number estimation, the majority of the available high-throughput sequencing technologies require polymerase chain reaction (PCR) and are subject to the substantial bias that is inherent to the PCR process. We introduce a novel and sophisticated statistical model for the whole genome sequencing data, and based on this model, develop a highly sensitive method of Minimally Invasive Karyotyping (MINK) for the diagnosis of the fetal genetic disease. Specifically we demonstrate, by applying our statistical method to ultra high-throughput whole sequencing data, that trisomy 21 can be detected in a minor ('fetal') genome when it is mixed into a major ('maternal') background genome at frequencies as low as 5%. This observation provides additional proof of concept and justification for the further development of this method towards its eventual clinical application. Here, we describe the statistical and experimental methods that illustrate this approach and discuss future directions for technical development and potential clinical applications.
Dichotomy of astrocytoma migration and proliferation (1996)

Astrocytomas often show high rates of local invasion that lead to local recurrence of the disease. Histologically, the most highly invasive astrocytoma cells are detected in isolation rather than as nests of tumor. Our study attempted to determine whether the migratory response to extracellular substrates influences the proliferative behavior of these highly invasive cells. The preferential and specific migratory response of human astrocytoma cells to extracellular matrix proteins was assessed by a microliter scale migration assay. Growth curve studies on protein ligands permissive (merosin) for cell migration indicated that the lag phase was protracted compared with cells seeded on non-permissive proteins (vitronectin). Once a certain cell density was reached, logarithmic proliferation was indistinguishable on the different proteins. The proliferation index of populations of cells migrating on merosin and vitronectin was measured by both BrdU incorporation and MIB-1 immunocytochemistry labeling. Cells seeded on vitronectin showed higher proliferation throughout the population than cells seeded on merosin. On merosin, the more migratory cells at the periphery were less proliferative than non-migratory cells in the central region of that population. The integrin-associated signal transduction protein, p125FAK, was heavily localized in the membrane of non-migrating cells and largely absent in migrating astrocytoma cells. We conclude that temporally, proliferation and migration are mutually exclusive behaviors. Cell density or non-permissive substrates that inhibit cell motility favor a more proliferative phenotype. Conversely, active migration suppresses cell proliferation.
Optimal execution of portfolio transactions (2001)

The authors consider the execution of portfolio transactions with the aim of minimizing a combination of volatility risk and transaction costs arising from permanent and temporary market impact. In the space of time-dependent liquidation strategies, the efficient frontier consists of strategies having the lowest expected execution cost for a given level of uncertainty; with a linear cost model this frontier can be explicitly constructed. It is then possible to select particular optimal strategies either by minimizing a quadratic utility function or by minimizing value-at-risk (VaR). The latter choice leads to the concept of liquidity-adjusted VaR, or L-VAR, which explicitly considers the best tradeoff between volatility risk and liquidation costs.
Developmental Biology Protocols (1999)

The molecular biology revolution has transformed developmental biology into one of the most exciting and fruitful fields in experimental biomedical research today. In Developmental Biology Protocols, established leaders in this field demonstrate this achievement with a comprehensive collection of cutting-edge protocols for studying and analyzing the events of embryonic development. Drawing on state-of-the-art cellular and molecular techniques, as well as new and sophisticated imaging and information technologies, this first volume of three presents readily reproducible methods for establishing and characterizing several widely used experimental model systems, for both the study of developmental patterns and morphogenesis, and the examination of embryo structure and function.
Playing only one instrument may be not enough: Limitations and future of the antiangiogenic treatment of cancer (2007)

Angiogenesis plays an essential role in tumor growth, invasion and metastasis. After initial pessimism about the usefulness of the antiangiogenic therapeutic approach for cancer, interest has increased in the development of antiangiogenic compounds after the first clinical approval of an antiangiogenic therapy. The anti-vascular endothelial growth factor (VEGF) antibody bevacizumab has recently been approved for use in combination with chemotherapy for the treatment of metastatic colorectal and non-small cell lung cancer patients. However, no survival benefit has been demonstrated in anti-VEGF monotherapy trials, probably due to the high complexity of tumor angiogenesis regulation. Experimental and clinical data, including the approval of the multitargeted drugs sunitinib and sorafenib, indicate that exciting results, including tumor regression, can be expected from the combined targeting of different pathways in the tumor angiogenesis scenario. Several obstacles, including the high cost of new molecular targeted drugs make this therapeutic approach difficult.
Addition of Mild Electrophiles to a Mo≡N Triple Bond and Nitrile Synthesis via Metal-Mediated N-Atom Transfer to Acid Chlorides (2008)

The addition of mild electrophiles to the anionic terminal Mo-nitride {[(t)BuOCO]Mo[triple bond]N]Na(DMF)}(2) (1) and the synthesis of nitriles via metal-mediated N-atom transfer is reported. The X-ray structure of a pivaloylimido intermediate indicates the presence of a weakly coordinated DMF molecule. Kinetic studies confirm that cyclometalation and DMF dissociation occur prior to nitrile extrusion.
Prognostic significance of urinary antigen analysis by enzyme-linked immunosorbent assay in melanoma patients. (1983)

Urine samples collected from normal donors and melanoma patients were analyzed for the presence of tumor-associated antigen by competitive inhibition in the enzyme-linked immunosorbent assay (ELISA) using an allogeneic melanoma serum as the source of antibody and partially purified urine from the same donor as the target antigen. The results were expressed as antigen units (ng antigen protein/mg creatinine). The antigen levels in urine of melanoma patients (median = 56.5, N = 56) were significantly higher (P less than 0.05) than those of normal donors (median = 1.9, N = 56). The 90th percentile for the normal group was 34.3 antigen units. Using this value as the criterion for positivity, 36 of 56 (64%) urine samples of melanoma group were positive for the antigen as opposed to only 6 of 56 (11%) of normal donors. Subsequently, a retrospective analysis of 58 melanoma patients paired on the basis of disease recurrence and no recurrence after lymphadenectomy revealed a median antigen level of 68 units for the recurrent group and 18.9 for the nonrecurrent group. Eighteen of 29 (62%) melanoma patients who had recurrence of their disease and 9 of 29 (31%) patients who remained disease free were urinary antigen positive. These incidences were significantly different (P less than 0.005). The results of this investigation suggest that assessment of urinary antigen in stage I and II melanoma patients may prognosticate recurrence of the disease.
A Phase I study of LGD1069 in adults with advanced cancer. (1999)

LGD1069 [Targretin; 4-[1-(5,6,7,8-tetrahydro-3,5,5,8,8-pentamethyl-2-naphtalenyl) propenyl] benzoic acid] is a novel synthetic retinoid X receptor-selective retinoid that has been recently identified. The goals of this study were to determine the safety, toxicity, pharmacokinetics (PKs), and metabolic profile of LGD1069 in advanced cancer patients. Sixty patients received oral LGD1069 at doses ranging from 5-1000 mg/m2/day with PK sampling performed on days 1 and 15. No dose-limiting toxicities (DLTs) were observed up to the 500 mg/m2/day dose level. DLT observed at and above 650 mg/m2/day included skin desquamation, hyperbilirubinemia, transaminase elevation, leukopenia, and diarrhea. Asymptomatic, dose-related alterations in lipid and thyroid metabolism were also observed. DLTs frequently observed with retinoic acid receptor-selective retinoids and pan agonists, including headache, mucocutaneous toxicity, and hypercalcemia, were not dose-limiting with LGD1069. Day 1 LGD1069 Cmax and area under the curve values increased dose-proportionately up to 800 mg/m2/day. Repeat-dose (day 15) area under the curve values varied between 25 and 105% of day 1 values. Although no objective tumor responses were observed, tumor progression may have been substantially arrested or delayed in non-small cell lung cancer (5 of 16) and in head and neck cancer (1 of 5), as well as other tumor types. At the higher dose levels, the molar concentration of LGD1069 was up to 10-fold higher than observed with other retinoids, yet toxicity was minimal. LGD1069 is an retinoid X receptor-selective retinoid agonist with a more favorable PK and toxicity profile than previously studied retinoids and merits further investigation as a chemopreventive and anticancer agent. On the basis of this Phase I trial, the recommended Phase II dose is 500 mg/m2/day.
Thymic stem cells in mouse bone marrow (1994)

There is still controversy concerning the nature of the stem cells from bone marrow that colonize the thymus during embryogenesis and continually throughout life. To identify the bone marrow stem cells that home to and populate the thymus, we screened murine bone marrow cells for the presence of a population of surface phenotype similar to the earliest known intrathymic precursor. We have identified a population characterized by expression of an intermediate level of heat stable antigen, a very low level of Thy-1, and high levels of CD44 and class I major histocompatibility complex antigens. It is negative for B- cell, granulocyte, macrophage, and erythrocyte markers (B220, Gr-1, Mac- 1, and TER 119). All these markers are common to the intrathymic precursors and bone marrow stem cells. However, this new bone marrow population is Sca-2+, similar to the intrathymic precursor, which makes a clear distinction from the Sca-2- bone marrow hematopoietic stem cells previously characterized. The frequency of the new population in the normal mouse bone marrow is about 0.25%. When transferred intrathymically or intravenously to lethally irradiated mice, it has a higher expansion potential (2 x 10(5)) than has been found for the intrathymic precursors (10(3)), but less than was found for the Sca-2- multipotent stem cell (10(7)). These transfer studies also showed that it was pluripotent, in that its precursor activity was not restricted to the production of T or B lymphocytes. However, it gave a reduced spleen colony number and smaller colonies (day-12 colony-forming unit spleen) when compared with multipotent stem cells. Thus, the cell we have identified appears to be the latest pluripotent cells so far identified in bone marrow and is therefore a good candidate for a bone marrow prothymocyte, but it appears not to be T-cell-committed.
Species differences in the localization of cGMP‐producing and NO‐responsive elements in the mouse and rat hippocampus using cGMP immunocytochemistry (2004)

The aim of the study was to compare the localization of the nitric oxide (NO)-cGMP pathway in hippocampus of mice and rats using cGMP- and soluble guanylyl cyclase (GC) immunocytochemistry and in situ hybridization of the cGMP-hydrolysing phosphodiesterase types 2, 5 and 9. In vitro incubation of hippocampus slices in the absence of a guanylyl cyclase stimulator or a phosphodiesterase inhibitor resulted in cGMP-positive astrocytes mainly in the CA1 area in mouse slices. In contrast, no cGMP immunoreactivity was observed under these conditions in the rat hippocampus. Treatment with an NO synthase inhibitor or inhibitors of soluble or particulate GC did not abolish cGMP immunoreactivity in astrocytes. Incubation with the NO donors sodium nitroprusside or diethylamino NONOate, or with the NO-independent activators of soluble GC, YC-1 and BAY 41-2272, in combination with phosphodiesterase inhibitors, resulted in an increase in cGMP immunoreactivity in numerous astrocytes throughout the mouse hippocampus. In contrast, under these conditions cGMP immunoreactivity was primarily observed in varicose fibers in rat hippocampus. Comparison of the cellular localization of the beta1 subunit of soluble GC and the mRNAs of PDE2, PDE5 and PDE9 revealed that in both species the beta1 subunit was observed in pyramidal and granule cells, which also expressed the mRNAs of the three phosphodiesterase families. Although the beta1 subunit was observed in astrocytes, none of the phosphodiesterases were detected in these cells. We conclude that, although the expression profiles of the soluble GC beta1 subunit and cGMP-hydrolysing phosphodiesterase mRNAs were identical, the cellular patterns of cGMP immunoreactivity differ between rat and mouse hippocampus.
Biologic basis for interleukin-1 in disease (1996)

To understand the role of the proinflammatory cytokine interleukin-1 (IL-1) in disease, investigators have studied how production of the different members of the IL-1 family is controlled, the various biologic activities of IL-1, the distinct and various functions of the IL-1 receptor (IL-1R) family, and the complexity of intracellular signaling. Mice deficient in IL-1Beta, IL-1Beta converting enzyme, and IL-1R type I have also been studied. Humans have been injected with IL-1 (either IL-1alpha or IL-1beta) for enhancing bone marrow recovery and for cancer treatment. The IL-1-specific receptor antagonist (IL-1Ra) has also been tested in clinical trials. The topics discussed in this review include production and activities of IL-1 and IL-1Ra molecules, the effects of IL-1 on gene expression, functions of cell-bound and soluble IL-1 receptors, the importance of the IL-1R accessory protein, newly discovered signal transduction pathways, naturally occurring cytokines limiting IL-1 production or activity, the effects of blocking cyclooxygenase and nitric oxide, and the outcomes of IL-1 and IL-1 Ra in human trials. Special attention is paid to IL-1beta converting enzyme and programmed cell death. The roles of IL-1 in hematopoiesis, leukemia, atherosclerosis, and growth of solid tumors are also discussed. This is a lengthy review, with 586 citations chosen to illustrate specific areas of interest rather than a compendium of references. At the end of each section, a short commentary summarizes what the author considers established or controversial topics linking the biology of IL-1 to mechanisms of disease.
Alternative multiple spanning tree protocol (AMSTP) for optical Ethernet backbones (2005)

The availability and affordable cost of Gigabit and 10 Gigabit Ethernet switches has impacted the deployment of metropolitan area networks (MAN) and campus networks. This paper presents a new protocol, the alternative multiple spanning tree protocol (AMSTP), that uses multiple source based spanning trees for backbones using Ethernet switches. It provides minimum paths and more efficient usage of optical backbone infrastructure than currently proposed protocols such as resilient packet ring and rapid spanning tree. The protocol exhibits features similar to MAC routing protocols like Link State Over MAC (LSOM) such as optimum path and effective infrastructure usage, without requiring MAC routing due to the use of the spanning tree protocol paradigm. AMSTP is not restricted to specific topologies such as ring or tree, but performs efficiently in arbitrary topologies. Among the application areas are optical backbones of campus and MANs.
Depression and the Course of Coronary Artery Disease (1998)

Literature and folk wisdom have long linked depression and death; however, only recently have scientific studies examined the relation between them. Beginning in the 1970s, investigators compared mortality among patients treated for major depression and the general population. Nine of ten studies found an increased mortality from cardiovascular disease among depressed patients. However, such studies confound the relation between depression and its treatment. Community surveys circumvent this difficulty, but as these studies began to appear, other investigations revealed the strong association between depression and cigarette smoking, which made obvious a need to control for smoking. The first study to do this appeared in 1993, and not only did a relation between depression and mortality persist, but a relation between depression and the development of ischemic disease was revealed. In the past 2 years, six more community surveys have followed populations initially free of disease, and five have observed an increased risk of ischemic heart disease among depressed persons. Another research strategy is to start with subjects who have preexisting cardiovascular disease. Here, too, depression has consistently been associated with a worse outcome. In one well-designed study, patients with depression in the period immediately after a myocardial infarction were 3.5 times more likely to die than nondepressed patients. The basis of this association remains speculative. However, it is likely that the changes in the autonomic nervous system and platelets that are seen in depression account for a substantial portion of the association.
Fourier transform method for automatic processing of moire´ deflectograms (1999)

In this work, a Fourier transform technique for automatic analysis of moire deflectograms is presented. A squared grating is used to multiplex the information of the deflection in two orthogonal directions in one image. This procedure avoids the necessity of rotating the gratings to obtain the complete deflection information. With this method only two fringe patterns. reference and distorted, are needed to determine the complete deflection information. To deal with irregularly shaped processing areas, a Gerchberg extrapolation method is used. The automatic determination of the carrier as well as the size and position of the reconstruction windows permit the complete and automatic measurement of the deflection produced by an ophthalmic lens in two orthogonal directions. Afterwards, the refractive power maps can be obtained, Experimental results obtained with a progressive addition lens are presented and comparison with measurements obtained with a commercial focimeter are shown showing a good agreement.