gebhart/patrepeval huggingface dataset:
Language modeling with sum-product networks (2014)

Sum product networks (SPNs) are a new class of deep probabilistic models. They can contain multiple hidden layers while keeping their inference and training times tractable. An SPN consists of interleaving layers of sum nodes and product nodes. A sum node can be interpreted as a hidden variable, and a product node can be viewed as a feature capturing rich interactions among an SPN’s inputs. We show that the ability of SPN to use hidden layers to model complex dependencies among words, and its tractable inference and learning times, make it a suitable framework for a language model. Even though SPNs have been applied to a variety of vision problems [1, 2], we are the first to use it for language modeling. Our empirical comparisons with six previous language models indicate that our SPN has superior performance.
Pairwise comparisons of mitochondrial DNA sequences in stable and exponentially growing populations. (1991)

We consider the distribution of pairwise sequence differences of mitochondrial DNA or of other nonrecombining portions of the genome in a population that has been of constant size and in a population that has been growing in size exponentially for a long time. We show that, in a population of constant size, the sample distribution of pairwise differences will typically deviate substantially from the geometric distribution expected, because the history of coalescent events in a single sample of genes imposes a substantial correlation on pairwise differences. Consequently, a goodness-of-fit test of observed pairwise differences to the geometric distribution, which assumes that each pairwise comparison is independent, is not a valid test of the hypothesis that the genes were sampled from a panmictic population of constant size. In an exponentially growing population in which the product of the current population size and the growth rate is substantially larger than one, our analytical and simulation results show that most coalescent events occur relatively early and in a restricted range of times. Hence, the "gene tree" will be nearly a "star phylogeny" and the distribution of pairwise differences will be nearly a Poisson distribution. In that case, it is possible to estimate r, the population growth rate, if the mutation rate, mu, and current population size, N0, are assumed known. The estimate of r is the solution to ri/mu = ln(N0r) - gamma, where i is the average pairwise difference and gamma approximately 0.577 is Euler's constant.
Embryonic expression and cloning of the murine GATA-3 gene (1994)

We describe the embryonic expression pattern as well as the cloning and initial transcriptional regulatory analysis of the murine (m) GATA-3 gene. In situ hybridization shows that mGATA-3 mRNA accumulation is temporally and spatially regulated during early development: although found most abundantly in the placenta prior to 10 days of embryogenesis, mGATA-3 expression becomes restricted to specific cells within the embryonic central nervous system (in the mesencephalon, diencephalon, pons and inner ear) later in gestation. GATA-3 also shows a restricted expression pattern in the peripheral nervous system, including terminally differentiating cells in the cranial and sympathetic ganglia. In addition to this distinct pattern in the nervous system, mGATA-3 is also expressed in the embryonic kidney and the thymic rudiment, and further analysis showed that it is expressed throughout T lymphocyte differentiation. To begin to investigate how this complex gene expression pattern is elicited, cloning and transcriptional regulatory analyses of the mGATA-3 gene were initiated. At least two regulatory elements (one positive and one negative) appear to be required for appropriate tissue-restricted regulation after transfection of mGATA-3-directed reporter genes into cells that naturally express GATA-3 (T lymphocytes and neuroblastoma cells). Furthermore, this same region of the locus confers developmentally appropriate expression in transgenic mice, but only in a subset of the tissues that naturally express the gene.
Viral Multiplex Quantitative PCR Assays for Tracking Sources of Fecal Contamination (2010)

Human and animal fecal pollution of the environment presents a risk to human health because of the presence of pathogenic viruses and bacteria. To distinguish between human and animal sources of pollution, we designed specific real-time reverse transcription (RT)-PCR assays for human and animal enteric viruses, including norovirus genogroups I, II, and III; porcine adenovirus types 3 and 5; ovine adenovirus; atadenovirus; and human adenovirus species C and F, which are excreted by infected humans, pigs, cattle, sheep, deer, and goats, and for the detection of F+ RNA bacteriophage genogroups I to IV, which are associated with human and animal wastes. The sensitivity of this viral toolbox (VTB) was tested against 10-fold dilution series of DNA plasmids that carry the target sequences of the respective viruses and was shown to detect at least 10 plasmid copies for each assay. A panel of human and animal enteric and respiratory viruses showed these assays to be highly sensitive and specific to their respective targets. The VTB was used to detect viruses in fecal and environmental samples, including raw sewage and biosolids from municipal sewage treatment plants, abattoir sewage, and fecally contaminated shellfish and river water, which were likely to contain animal or human viruses.
Sensing Tissue Ischemia (2004)

This study provides the first functional evidence that ischemic stimulation of cardiac spinal afferent nerves is mediated through VR1s. The VR1 on the cardiac sensory nerve may function as a molecular sensor to detect tissue ischemia and activate cardiac nociceptors.
Quantification in Proteomics through Stable Isotope Coding: A Review (2004)

This review focuses on techniques for quantification and identification in proteomics by stable isotope coding. Methods are examined for analyzing expression, post-translational modifications, protein:protein interactions, single amino acid polymorphism, and absolute quantification. The bulk of the quantification literature in proteomics focuses on expression analysis, where a wide variety of methods targeting different features of proteins are described. Methods for the analysis of post-translational modification (PTM) focus primarily on phosphorylation and glycosylation, where quantification is achieved in two ways, either by substitution or tagging of the PTM with an isotopically coded derivatizing agent in a single process or by coding and selecting PTM modified peptides in separate operations. Absolute quantification has been achieved by age-old internal standard methods, in which an isotopically labeled isoform of an analyte is synthesized and added to a mixture at a known concentration. One of the surprises is that isotope coding can be a valuable aid in the examination of intermolecular association of proteins through stimulus:response studies. Preliminary efforts to recognize single amino acid polymorphism are also described. The review ends with the conclusion that (1) isotope ratio analysis of protein concentration between samples does not necessarily relate directly to protein expression and rate of PTM and (2) that multiple new methods must be developed and applied simultaneously to make existing stable isotope quantification methods more meaningful. Although stable isotope coding is a powerful, wonderful new technique, multiple analytical issues must be solved for the technique to reach its full potential as a tool to study biological systems.
Diffraction culling for virtual-acoustic simulations. (2009)

Acoustic simulations of complex virtual environments typically are created with geometrical-acoustics techniques. Such simulations can be augmented with edge diffraction modeling for improved accuracy, but not without a significant increase in processing time due to the additional propagation paths which must be considered and the computational complexity of the diffraction calculations. However, for a given modeling scenario, the contribution of a diffracted path to the overall impulse response can vary over a large range, suggesting that certain diffracted paths can be ignored, or culled, to reduce processing time with a limited effect on the accuracy of the simulation. In this talk, we first analyze the effects of diffraction culling through a precomputed, amplitude-based ranking scheme. We then describe a simple procedure for identifying and culling insignificant diffraction components during a virtual-acoustic simulation which approximates the performance of the precomputed ranking. Through numerical and subjective analysis, we show that a significant percentage of diffracted paths can be ignored if the retained paths are those which lead to the highest-amplitude diffraction components, although the audible effects of such diffraction culling are dependent on the input signal.
IL-12 antagonism induces T helper 2 responses, yet exacerbates cardiac allograft rejection. Evidence against a dominant protective role for T helper 2 cytokines in alloimmunity (1996)

IL-12 promotes Th1 development and inhibits the generation of Th2 by inducing IFN-gamma production. In several experimental models, Th2 are preferentially induced in the absence of IL-12. It was proposed that the preferential induction of Th2 by IL-12 antagonism would inhibit Th1-driven rejection responses, thereby promoting allograft acceptance. To test this possibility, mouse cardiac allograft recipients were treated with either anti-IL-12 Abs, or with the IL-12 receptor antagonist p40 homodimer. Unmodified rejection is characterized by a Th1-dominated response, with Th2 cytokines being absent or only weakly expressed within the allograft. Though both forms of IL-12 antagonism induced Th2 cytokine expression within the allograft, these treatments surprisingly exacerbated graft rejection relative to control animals. Interestingly, IL-12 antagonism did not inhibit IFN-gamma gene expression or in vivo sensitization of IFN-gamma-producing cells. Similar observations were made when IL-12 p40 knockout mice were used as allograft donors and recipients, verifying that IL-12 was not required for Th1 development. Further, IL-12 antagonism was associated with strong expression of p40 and weak expression of p35 within the graft. Neither p35 nor p40 mRNAs were detectable in control allografts. These data indicate that while IL-12 antagonism does induce Th2 cytokine expression within cardiac allografts, Th2 cytokines do not play a dominant protective role in the rejection process. Further, the Th2-inducing activity of IL-12 antagonism is not related to decreased IFN-gamma production, but may reflect altered regulation of IL-12 itself.
Active Site of Chondroitin AC Lyase Revealed by the Structure of Enzyme−Oligosaccharide Complexes and Mutagenesis, (2001)

The crystal structures of Flavobacterium heparinium chondroitin AC lyase (chondroitinase AC; EC 4.2.2.5) bound to dermatan sulfate hexasaccharide (DS(hexa)), tetrasaccharide (DS(tetra)), and hyaluronic acid tetrasaccharide (HA(tetra)) have been refined at 2.0, 2.0, and 2.1 A resolution, respectively. The structure of the Tyr234Phe mutant of AC lyase bound to a chondroitin sulfate tetrasaccharide (CS(tetra)) has also been determined to 2.3 A resolution. For each of these complexes, four (DS(hexa) and CS(tetra)) or two (DS(tetra) and HA(tetra)) ordered sugars are visible in electron density maps. The lyase AC DS(hexa) and CS(tetra) complexes reveal binding at four subsites, -2, -1, +1, and +2, within a narrow and shallow protein channel. We suggest that subsites -2 and -1 together represent the substrate recognition area, +1 is the catalytic subsite and +1 and +2 together represent the product release area. The putative catalytic site is located between the substrate recognition area and the product release area, carrying out catalysis at the +1 subsite. Four residues near the catalytic site, His225, Tyr234, Arg288, and Glu371 together form a catalytic tetrad. The mutations His225Ala, Tyr234Phe, Arg288Ala, and Arg292Ala, revealed residual activity for only the Arg292Ala mutant. Structural data indicate that Arg292 is primarily involved in recognition of the N-acetyl and sulfate moieties of galactosamine, but does not participate directly in catalysis. Candidates for the general base, removing the proton attached to C-5 of the glucuronic acid at the +1 subsite, are Tyr234, which could be transiently deprotonated during catalysis, or His225. Tyrosine 234 is a candidate to protonate the leaving group. Arginine 288 likely contributes to charge neutralization and stabilization of the enolate anion intermediate during catalysis.
The genetic basis of ataxia. (1995)

The inherited ataxias can now be classified on the basis of genotype rather than phenotype. Clinical expression of the various disorders overlap one another, making a diagnostic classification based on phenotype inaccurate in many instances. A genomic classification as outlined here has provided order and clarity in this group of disorders previously classified on the basis of clinical features. It is expected that in the near future the abnormal gene products for these ataxias, the ataxins, will be identified and provide molecular insights for effective therapies.
Function of HAb18G/CD147 in Invasion of Host Cells by Severe Acute Respiratory Syndrome Coronavirus (2005)

To identify the function of HAb18G/CD147 in invasion of host cells by severe acute respiratory syndrome (SARS) coronavirus (CoV), we analyzed the protein-protein interaction among HAb18G/CD147, cyclophilin A (CyPA), and SARS-CoV structural proteins by coimmunoprecipitation and surface plasmon resonance analysis. Although none of the SARS-CoV proteins was found to be directly bound to HAb18G/CD147, the nucleocapsid (N) protein of SARS-CoV was bound to CyPA, which interacted with HAb18G/CD147. Further research showed that HAb18G/CD147, a transmembrane molecule, was highly expressed on 293 cells and that CyPA was integrated with SARS-CoV. HAb18G/CD147-antagonistic peptide (AP)-9, an AP of HAb18G/CD147, had a high rate of binding to 293 cells and an inhibitory effect on SARS-CoV. These results show that HAb18G/CD147, mediated by CyPA bound to SARS-CoV N protein, plays a functional role in facilitating invasion of host cells by SARS-CoV. Our findings provide some evidence for the cytologic mechanism of invasion by SARS-CoV and provide a molecular basis for screening anti-SARS drugs.
Expression and Properties of Two Types of Protein Kinase C: Alternative Splicing from a Single Gene (1987)

Two complementary DNA's, encoding the complete sequences of 671 and 673 amino acids for subspecies of rat brain protein kinase C, were expressed in COS 7 cells. The complementary DNA sequence analysis predicted that the two enzymes are derived from different ways of splicing and differ from each other only in the short ranges of their carboxyl-terminal regions. Both enzymes showed typical characteristics of protein kinase C that responded to Ca2+, phospholipid, and diacylglycerol. The enzymes showed practically identical physical and kinetic properties and were indistinguishable from one of the several subspecies of protein kinase C that occurs in rat brain but not in untransfected COS 7 cells. Partial analysis of the genomic structure confirmed that these two subspecies of protein kinase C resulted indeed from alternative splicing of a single gene.
Recent Developments in the Field of Anticancer Platinum Complexes (2006)

Cisplatin, carboplatin and oxaliplatin continue to be among the most efficient anticancer drugs in world-wide clinical use so far. In particular, cisplatin has shown a remarkable therapeutic efficacy in a broad spectrum of solid tumors and outstanding activity against metastatic testicular germ-cell cancer with cure rates of about 90% of cases. Nevertheless, the dose-limiting severe toxic side-effects of platinum-based chemotherapy, the problem of inherent or therapy-induced resistance, the limited activity in a range of tumors, and the meager tumor selectivity are the motivation for tremendous efforts and inventions in the development of novel anticancer platinum drugs. This article reviews the most recent patents in this field of research, covering the following strategies in the design of promising anticancer platinum complexes: (i) synthesis of new anticancer platinum complexes, using combinatorial chemistry and high throughput synthesis and screening, (ii) activation of platinum complexes in the tumor tissue, (iii) accumulation of platinum complexes at the tumor site, (iv) novel platinum complexes, displaying activity against cisplatin resistant cells and as inhibitors of specific biological functions, and (v) direct derivatives of classical anticancer platinum drugs in clinical use.
Synthesis of an Asparagine-Linked Heptasaccharide − Basic Structure ofN-Glycans (2000)

Galβ(1−4)GlcNAcβ(1−2)Manα(1−3)[Manα(1−6)]Manβ(1−4)GlcNAcβ(1−4)GlcNAcβ(1−N)Asn (1) was disconnected into building blocks 2−6. N-Dimethylmaleoyl (DMM) protected glucosamine 3 was readily obtained from glucosamine. Transformation of 3 into 4-O-unprotected glucosamine derivatives 9, 14, and 18 furnished the intermediates required for the incorporation of the three differently linked glucosamine residues. Thus, disaccharide 20 was obtained from acceptor 9 and glucosyl donor 19 and converted into protected Manβ(1−4)GlcNAc disaccharide donor 5 by inversion of the configuration at C-2 of the glucose residue. Glycosylation of acceptor 18 with known galactosyl donor 26 afforded protected lactosamine donor 6. The synthesis of asparagine building block 2 and of mannosyl donor 4 has already been reported. With building blocks 2−6 in hand, the synthesis of 1 was accomplished. Glycosylation of acceptor 14 with donor 5 gave trisaccharide 29 which was transformed into acceptor 30. Treatment of 30 with glycosyl donor 4 provided tetrasaccharide intermediate 31. Its transformation into 2d-O-unprotected acceptor 33 and then reaction with disaccharide donor 6 furnished hexasaccharide 34. Removal of the 4c,6c-O-benzylidene group gave 4c,6c-O-unprotected acceptor 35 which, on glycosylation with donor 4, led to heptasaccharide 36. Replacement of the N-DMM groups by N-acetyl groups and removal of all O-acyl groups, followed by transformation of the C-1a azido group into an amino group, and attachment of asparagine building block 2 led to the desired heptasaccharide β-linked to asparagine 39. Hydrogenolysis of all O-benzyl groups afforded target molecule 1.
Paleolithic Population Growth Pulses Evidenced by Small Animal Exploitation (1999)

Variations in small game hunting along the northern and eastern rims of the Mediterranean Sea and results from predator-prey simulation modeling indicate that human population densities increased abruptly during the late Middle Paleolithic and again during the Upper and Epi-Paleolithic periods. The demographic pulses are evidenced by increasing reliance on agile, fast-reproducing partridges, hares, and rabbits at the expense of slow-reproducing but easily caught tortoises and marine shellfish and, concurrently, climate-independent size diminution in tortoises and shellfish. The results indicate that human populations of the early Middle Paleolithic were exceptionally small and highly dispersed.
Developing combinatorial multi-component therapies (CMCT) of drugs that are more specific and have fewer side effects than traditional one drug therapies (2007)

Drugs designed for a specific target are always found to have multiple effects. Rather than hope that one bullet can be designed to hit only one target, nonlinear interactions across genomic and proteomic networks could be used to design Combinatorial Multi-Component Therapies (CMCT) that are more targeted with fewer side effects. We show here how computational approaches can be used to predict which combinations of drugs would produce the best effects. Using a nonlinear model of how the output effect depends on multiple input drugs, we show that an artificial neural network can accurately predict the effect of all 215 = 32,768 combinations of drug inputs using only the limited data of the output effect of the drugs presented one-at-a-time and pairs-at-a-time.
Synthesis and Processing of Ovine Trophoblast Protein-1 and Bovine Trophoblast Protein-1, Conceptus Secretory Proteins Involved in the Maternal Recognition of Pregnancy* (1988)

Ovine and bovine trophoblast protein-1 (oTP-1 and bTP-1) are newly discovered proteins produced by embryonic tissues for a limited period in early gestation. They appear to act as agents that prevent regression of the corpus luteum during early pregnancy in the ewe and cow. Ovine TP-1 [mol wt (Mr), 17,000] consists of three or four isoelectric variants (pI 5.4-5.7), whereas bTP-1, which cross-reacts with antiserum to oTP-1, is found as two predominant Mr classes (Mr, 22,000 and 24,000), each with several isoelectric variants (in the pI range 6.3-6.8). Cell-free translation of ovine conceptus mRNA yields pre-oTP-1 also consists of three or four isoelectric variants, assumed to have arisen by translation of multiple mRNA species. Ovine TP-1 is not glycosylated. When bovine conceptus mRNA is translated, a group of four or five isoforms of pre-bTP-1 are generated, each with a Mr of 19,000. In the presence of microsomes the Mr shifts upward to about 21,500. Bovine conceptuses cultured in presence of either [3H]glucosamine or [3H]mannose incorporate label into both size classes of bTP-1 (Mr, 22,000 and 24,000). Culture in presence of [35S]methionine and tunicamycin gave rise to a nonglycosylated form of bTP-1 with an apparent Mr of 18,000. Treatment of [35S]methionine-labeled bTP-1 with either endoglycosidase-H or peptide:N-glycosidase F yielded products with Mr of 17,000 and 16,000, respectively. bTP-1, although functionally and structurally related to oTP-1, appears to be a glycoprotein carrying at least two Asn-linked oligosaccharides. The two Mr classes of bTP-1 arise as a result of differences in either the number or structure of the carbohydrate chains. Like oTP-1, bTP-1 is probably translated from multiple mRNA species.
Oxidative C−H Activation/C−C Bond Forming Reactions:  Synthetic Scope and Mechanistic Insights (2005)

This paper describes a new palladium-catalyzed method for C-H activation/carbon-carbon bond formation with hypervalent iodine arylating agents. This transformation has been applied to a variety of arene and benzylic substrates containing different directing groups (pyridines, quinolines, oxazolidinones, and amides) and proceeds with high levels of regiocontrol. Mechanistic experiments provide preliminary evidence in support of an unusual mechanism for this transformation involving a Pd(II)/Pd(IV) catalytic cycle.