gebhart/patrepeval huggingface dataset:
Using Limited Dependence Sequential Expansion for Decompressing Test Vectors (2006)

Existing techniques that incorporate decompressor constraints in the ATPG search/backtrace (e.g., Illinois scan) are based on combinational expansion in which each scan slice must be encoded using only the free-variables arriving from the tester in the current clock cycle. Sequential expansion is more powerful as it allows free-variables across multiple clock cycles to be used, however conventional approaches for sequential expansion that are based on linear finite state machines (LFSRs) and ring generators are not amenable to including the constraints in the ATPG backtrace because the constraints are too complex. This paper investigates the use of limited dependence sequential expansion to combine the benefits of sequential decompression with the benefits of incorporating the decompressor constraints in the ATPG backtrace. Analytical and experimental results are presented showing the benefits of the proposed approach
The commercialization of migration. (1989)

International migration is not new to the Philippines. In the recent outflow of contract workers to the Middle East, there is a shift from individual and family initiated migrations to the more organized, highly commercial variety. While profit-taking intermediaries have played some role in the past, the increase in the number and influence of these intermediaries has altered the story of migration decision-making. In 1975, the signing of the bilateral labor agreement between the governments of Iran and the Philippines signalled the rising demand for Filipino contract workers. From 1970 to 1975, the number of Asian migrant workers in the Gulf countries rose from about 120,000 to 370,000. These figures rose dramatically to 3.3 million in 1985. The growing share of organized and commercialized migration has altered migration decision making. Primarily, intermediaries are able to broaden access to foreign job and high wage opportunities. Commercialization effectively raises the transaction costs for contract migration. Studies on recruitment costs and fees show that self-solicited foreign employment costs less than employment obtained through recruitment agents and intermediaries. The difference in the 2 prices is due, not only to overhead costs of intermediation, but more importantly to the rent exacted by agents from having job information and placement rights. In the Philippines in October 1987 the average placement fee was P8000, greatly exceeding the mandated maximum fee level of P5000. This average is understated because the computation includes the 17% who do not pay any fees. The widespread and popular view of recruitment intermediaries is negative, dominated by images of abuses and victims. Private intermediaries and the government bureaucracy need each other. Intermediaries need government; their consistent demand for incentives and protection is indicative. On the other hand, government expands its supervision of control of overseas employment via the intermediaries. For both the community at large and the government, more can be gained in endeavors assisting workers and their families to make choices based on the widest available information. The most valuable program is that of providing correct information on recruitment charges and costs, on work and living conditions at the job site, on family and social consequences.
Combining evidence using p-values: application to sequence homology searches. (1998)

In sequence analysis, two or more (approximately) independent measures of the membership of a sequence (or sequence region) in some class are often available. We would like to estimate the likelihood of the sequence being a member of the class in view of all the available evidence. An example is estimating the significance of the observed match of a macromolecular sequence (DNA or protein) to a set of patterns (motifs) that characterize a biological sequence family. An intuitive way to do this is to express each piece of evidence as a p-value, and then use the product of these p-values as the measure of membership in the family. We derive a formula and algorithm (QFAST) for calculating the statistical distribution of the product of n independent p-values. We demonstrate that sorting sequences by this p-value effectively combines the information present in multiple motifs, leading to highly accurate and sensitive sequence homology searches.
Suppression of Diacylglycerol Acyltransferase-2 (DGAT2), but Not DGAT1, with Antisense Oligonucleotides Reverses Diet-induced Hepatic Steatosis and Insulin Resistance (2007)

Nonalcoholic fatty liver disease (NAFLD) is a major contributing factor to hepatic insulin resistance in type 2 diabetes. Diacylglycerol acyltransferase (Dgat), of which there are two isoforms (Dgat1 and Dgat2), catalyzes the final step in triglyceride synthesis. We evaluated the metabolic impact of pharmacological reduction of DGAT1 and -2 expression in liver and fat using antisense oligonucleotides (ASOs) in rats with diet-induced NAFLD. Dgat1 and Dgat2 ASO treatment selectively reduced DGAT1 and DGAT2 mRNA levels in liver and fat, but only Dgat2 ASO treatment significantly reduced hepatic lipids (diacylglycerol and triglyceride but not long chain acyl CoAs) and improved hepatic insulin sensitivity. Because Dgat catalyzes triglyceride synthesis from diacylglycerol, and because we have hypothesized that diacylglycerol accumulation triggers fat-induced hepatic insulin resistance through protein kinase C epsilon activation, we next sought to understand the paradoxical reduction in diacylglycerol in Dgat2 ASO-treated rats. Within 3 days of starting Dgat2 ASO therapy in high fat-fed rats, plasma fatty acids increased, whereas hepatic lysophosphatidic acid and diacylglycerol levels were similar to those of control rats. These changes were associated with reduced expression of lipogenic genes (SREBP1c, ACC1, SCD1, and mtGPAT) and increased expression of oxidative/thermogenic genes (CPT1 and UCP2). Taken together, these data suggest that knocking down Dgat2 protects against fat-induced hepatic insulin resistance by paradoxically lowering hepatic diacylglycerol content and protein kinase C epsilon activation through decreased SREBP1c-mediated lipogenesis and increased hepatic fatty acid oxidation.
Design, Synthesis, and Biological Evaluation of a Series of Benzo[de][1,7]naphthyridin-7(8H)-ones Bearing a Functionalized Longer Chain Appendage as Novel PARP1 Inhibitors (2013)

A series of benzo[de][1,7]naphthyridin-7(8H)-ones possessing a functionalized long-chain appendage have been designed and evaluated as novel PARP1 inhibitors. The initial effort led to the first-generation PARP1 inhibitor 26 bearing a terminal phthalazin-1(2H)-one framework and showing remarkably high PARP1 inhibitory activity (0.31 nM) but only moderate potency in the cell. Further effort generated the second-generation lead 41, showing high potency against both the PARP1 enzyme and BRCA-deficient cells, especially for the BRCA1-deficient MDA-MB-436 cells (CC50 < 0.26 nM). Mechanistic studies revealed that the new PARP1 inhibitors significantly inhibited H2O2-triggered PARylation in SKOV3 cells, induced cellular accumulation of DNA double-strand breaks, and impaired cell-cycle progression in BRCA2-deficient cells. Significant potentiation on the cytotoxicity of Temozolomide was also observed. The unique structural character and exceptionally high potency of 41 made it stand out as a promising drug candidate worthy for further evaluation.
Fertilin β and other ADAMs as integrin ligands: insights into cell adhesion and fertilization (2001)

One of the most important cell-cell interactions is that of the sperm with the egg. This interaction, which begins with cell adhesion and culminates with membrane fusion, is mediated by multiple molecules on the gametes. One of the best-characterized of these molecules is fertilin beta, a ligand on mammalian sperm and one of the first ADAMs (A Disintegrin and A Metalloprotease domain) to be identified. Fertilin beta (also known as ADAM2) participates in sperm-egg membrane binding, and it has long been hypothesized that this function is achieved through the interaction of the disintegrin domain of fertilin beta with an integrin on the egg surface. There are now approximately 30 members of the ADAM family and, to date, five different ADAMs (fertilin beta, ADAM9, ADAM12, ADAM15, ADAM23) have been described to interact with integrins (specifically alpha(6)beta(1), alpha(v)beta(3), alpha(9)beta(1), alpha(v)beta(5), and/or alpha(5)beta(1)). This field will be discussed with respect to what is known about specific ADAMs and the integrins with which they interact, and what the implications are for sperm-egg interactions and for integrin function. These data will also be discussed in the context of recent knockout studies, which show that eggs lacking the alpha(6) integrin subunit can be fertilized, and eggs lacking the integrin-associated tetraspanin protein CD9 fail to fertilize. Key issues in cell adhesion that pertain to gametes and fertilization will also be highlighted.
Isolation of a hamster cDNA clone coding for a function involved in methotrexate uptake. (1994)

A clone has been isolated from a Chinese hamster ovary cell cDNA expression library that complements mutant cells defective in the uptake of the folate analogue methotrexate. When transfected with this clone, the mutant cells regain the ability to bind and transport the drug and, as a consequence, become sensitive to its cytotoxic action. The clone is 2314 base pairs long and has an open reading frame of 1557 base pairs that codes for a putative protein of 58 kDa. This novel putative protein has a high content of hydrophobic residues and has a large part of its predicted secondary structure in the form of beta-sheets. In the wild-type cell line and in one of the mutant cell lines, this clone detects an mRNA of 2.5 kilobases, while in another mutant cell line, this message is absent. The data are consistent with this clone encoding either the reduced folate transporter or an auxiliary function that interacts with this transporter. This is the first report of a cDNA coding for a function, other than folate-binding protein, that is involved in the transport of methotrexate.
Block Polycationic Oligonucleotide Derivative:  Synthesis and Inhibition of Herpes Virus Reproduction (1996)

The block polycationic oligonucleotide (oligo) consisting of a phosphodiester 12-mer linked to the polycation chain at the 3'-end and cholesteryl group at the 5'-end was synthesized. The polycation chain was grown on the solid support using the monomer, H-phosphonate of 1-O-(4,4'-dimethoxytrityl)-1,3-butanediol. Amino groups were introduced in the polymer backbone using 1,4-diaminobutane, and then the oligo chain was formed at the free end of the polymer. The last stage of the synthesis was the attachment of the cholesteryl group to the 5'-end of the oligo prior to cleavage and deprotection of the copolymer. The nucleotide sequence of this copolymer, CGTTCCTCCTGC, was complementary to the splicing site of immediate early (IE) mRNA 4 and 5 of herpes simplex virus type 1 (HSV-1). The stability of the duplexes formed between the copolymer and the complementary 12-mer was similar to that of unmodified oligo. The stability of the block polycationic oligo against phosphodiesterase digestion was significantly increased compared to that of the unmodified oligo. The block polycationic oligo inhibited the reproduction of HSV-1 in Vero cells; however, the effect was significantly less than the effect of 12-mer oligo modified with cholesterol at the 5'-end. The decreased antiviral activity of the copolymer is explained by the polycation-induced stimulation of the virus infection.
Spontaneous Rejection of Poorly Immunogenic P1.HTR Tumors by Stat6-Deficient Mice (2000)

Experimental evidence suggests that a type 1 T cell response may result in optimal tumor rejection in vivo. This phenotype is determined in part by cytokines that influence T cell differentiation. In transplantable tumor models such as P1.HTR, tumors grow progressively despite expression of defined tumor Ags. We hypothesized that this failure to reject may be due to poor generation of a type 1 phenotype, through a dominant influence of the type 2-promoting cytokines IL-4 and/or IL-13. This hypothesis was tested by implanting P1.HTR tumors into mice deficient in Stat6. In contrast to progressive growth of P1.HTR tumors in wild-type mice, and aggressive growth even of IL-12-transfected P1.HTR in Stat1(-/-) mice, P1.HTR was spontaneously rejected by Stat6(-/-) mice. Rejection was accompanied by augmented tumor-specific IFN-gamma production and CTL activity. These results suggest that pharmacologic inhibition of Stat6 signaling could potentiate anti-tumor immunity in vivo.
P450BM3(CYP102A1): connecting the dots (2011)

P450(BM3) (CYP102A1), a fatty acid hydroxylase from Bacillus megaterium, has been extensively studied over a period of almost forty years. The enzyme has been redesigned to catalyse the oxidation of non-natural substrates as diverse as pharmaceuticals, terpenes and gaseous alkanes using a variety of engineering strategies. Crystal structures have provided a basis for several of the catalytic effects brought about by mutagenesis, while changes to reduction potentials, inter-domain electron transfer rates and catalytic parameters have yielded functional insights. Areas of active research interest include drug metabolite production, the development of process-scale techniques, unravelling general mechanistic aspects of P450 chemistry, methane oxidation, and improving selectivity control to allow the synthesis of fine chemicals. This review draws together the disparate research themes and places them in a historical context with the aim of creating a resource that can be used as a gateway to the field.
Deep neural networks are robust to weight binarization and other non-linear distortions (2016)

Recent results show that deep neural networks achieve excellent performance even when, during training, weights are quantized and projected to a binary representation. Here, we show that this is just the tip of the iceberg: these same networks, during testing, also exhibit a remarkable robustness to distortions beyond quantization, including additive and multiplicative noise, and a class of non-linear projections where binarization is just a special case. To quantify this robustness, we show that one such network achieves 11% test error on CIFAR-10 even with 0.68 effective bits per weight. Furthermore, we find that a common training heuristic--namely, projecting quantized weights during backpropagation--can be altered (or even removed) and networks still achieve a base level of robustness during testing. Specifically, training with weight projections other than quantization also works, as does simply clipping the weights, both of which have never been reported before. We confirm our results for CIFAR-10 and ImageNet datasets. Finally, drawing from these ideas, we propose a stochastic projection rule that leads to a new state of the art network with 7.64% test error on CIFAR-10 using no data augmentation.
Embedded noninteractive continuous bot detection (2008)

Multiplayer online computer games are quickly growing in popularity, with millions of players logging in every day. While most play in accordance with the rules set up by the game designers, some choose to utilize artificially intelligent assistant programs, a.k.a. bots, to gain an unfair advantage over other players. In this article we demonstrate how an embedded noninteractive test can be used to prevent automatic artificially intelligent players from illegally participating in online game-play. Our solution has numerous advantages over traditional tests, such as its nonobtrusive nature, continuous verification, and simple noninteractive and outsourcing-proof design.
A study on IN basic call state model for packet switched network (2002)

The advanced IN enables various network services to be provided quickly and efficiently. The functions and protocols of the advanced IN were standardized as Capability Set 1, CS-1, by the ITU-T in 1993. The main target of the advanced IN has been circuit switched networks. Packet switched networks, which are widely used for data communications, also provide various services that should be provided quickly and efficiently. One approach to meeting this requirement is to apply the advanced IN concept to packet switched networks. In the ITU-T recommendations for the advanced IN, call control in a circuit switched network is achieved by controlling the call-state transition based on the basic call state model, or BCSM, which is in the call control function, CCF. We propose also using the BCSM for packet switched networks. The advanced IN call-control mechanism could then be applied to packet switched networks.
Cumulative Toll-Like Receptor Activation in Human Macrophages Treated with Whole Bacteria (2003)

Purified components from bacteria selectively activate Toll-like receptors (TLR), leading to shared and unique responses in innate immune cells. Whole bacteria contain agonists for multiple TLR and induce a common macrophage activation program of transcription. It is not known, however, whether the stimulation of specific TLR by whole bacteria results in differential activation of the innate immune system. We evaluated gene expression data from human macrophages and found a unique gene expression profile induced by Gram-negative bacteria. In contrast, Gram-positive bacteria evoked few specific alterations in gene expression. LPS, a TLR4-specific ligand, was sufficient to elicit the distinct expression profile observed with Gram-negative bacteria. TLR4 activation regulated gene expression by both an IFN-dependent and an IFN-independent mechanism, illustrated by I-TAC and IL-12 p70, respectively. IL-12 p70 was produced by cells in whole blood exposed to Gram-negative bacteria, demonstrating faithful reproduction of the macrophage response in mixed populations of cells and identifying a potential diagnostic marker of infection. Our results show that the macrophage response to bacteria is dominated by the accumulated input from multiple TLR. For macrophages exposed to Gram-negative bacteria, gene expression changes encompass those induced by Gram-positive bacteria plus a distinct TLR4 response. This distinct TLR4 response may provide the basis to diagnose clinical Gram-negative infections.
Self‐Assembly of Cyclic Metal–DNA Nanostructures using Ruthenium Tris(bipyridine)‐Branched Oligonucleotides (2004)

A discrete cyclic nanostructure was obtained through the self-assembly of oligonucleotide-branched metal complexes. The picture shows the metal–DNA nanostructure, which contains two DNA double-helical arms and two relatively rigid redox- and photoactive [Ru(bpy)3]2+ vertices. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2004/z460255_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Increased manganese superoxide dismutase expression suppresses the malignant phenotype of human melanoma cells. (1993)

Introduction of a normal human chromosome 6 into human melanoma cell lines results in suppression of tumorigenicity. This suggests that a gene(s) on chromosome 6 controls the malignant phenotype of human melanoma. Because antioxidants can suppress the tumor-promotion phase of carcinogenesis, and because the antioxidant enzyme manganese superoxide dismutase (MnSOD) has been localized to a region of chromosome 6 frequently lost in melanomas, we have examined the effect of transfecting sense and antisense human MnSOD cDNAs into melanoma cell lines. Cell lines expressing abundant (+)-sense MnSOD-5 cDNAs significantly altered their phenotype in culture and lost their ability to form colonies in soft agar and tumors in nude mice. In contrast, the introduction of antisense MnSOD or +psv2neo had no effect on melanoma tumorigenicity. These findings indicate that stable transfection of MnSOD cDNA into melanoma cell lines exerts a biological effect that mimics that observed after introduction of an entire human chromosome 6.
Part I of GANNET53: A multicenter phase I/II trial of the Hsp90 inhibitor ganetespib (G) combined with weekly paclitaxel (P) in women with high-grade serous, high-grade endometrioid, or undifferentiated, platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal cancer. (2015)

5578 Background: Stabilized mutant p53 protein (mutp53) is a novel target in epithelial ovarian cancer (EOC). Due to aberrant conformation, mutp53 proteins depend on folding support by the Hsp90 chaperone. Hsp90 blockade induces degradation of mutp53, resulting in tumor cell cytotoxicity and increased sensitivity to chemotherapeutics. Preclinical synergy of the Hsp90 inhibitor G combined with P provided the rationale for testing the combination in relapsed platinum resistant EOC patients (pts) in the GANNET53 trial (EUDRACT 2013-003868-31). Methods: Eligiblepts had platinum resistant EOC. Pts with > 4 prior chemotherapy and low grade carcinoma were not eligible. Weekly P (80 mg/m²) and increasing doses of G (100, 150 mg/m²) were given i.v. on days 1, 8, 15 in a 28 days cycle until disease progression or unacceptable toxicity. End points were safety and determination of phase II dose. Dose limiting toxicity (DLT) was defined as grade (gr) 4 toxicity (with exceptions) occurring in cycles 1 & 2. Results: Ten pts (median age 57 years; range 43-70) were enrolled. No DLT occurred in cohort 1 (4 pts treated with P + G 100 mg/m²), nor in cohorts 2 and 3 (6 pts treated with P + G 150mg/m²). The most common adverse events (AEs) related to G were transient gr 1/2 diarrhea (n = 9). The most frequent gr 1/2 AEs were diarrhea (n = 9), nausea (n = 5), anemia (n = 6), fatigue (n = 4), headache (n = 5), and QTc prolongation (n = 6). AEs ≥ gr 3 were anemia (n = 3), neutropenia (n = 2), and acute cardiac failure (n = 1). There was 1 death on study (after DLT period) due to digestive tract hemorrhage from duodenal ulcer. Two pts discontinued due to SAEs (digestive hemorrhage n = 1, cardiac failure n = 1), 4 due to progressive disease, one due to physicians decision. Three pts are still on study at time of abstract submission. Conclusions: The combination of ganetespib 150 mg/m² with paclitaxel 80 mg/m² once weekly for 3 out of 4 weeks was generally well tolerated with no DLTs, and therefore chosen for the planned randomized phase II trial. Clinical trial information: 2013-003868-31.