gebhart/patrepeval huggingface dataset:
Single-stranded DNA oligomers stimulate error-prone alternative repair of DNA double-strand breaks through hijacking Ku protein (2015)

In humans, DNA double-strand breaks (DSBs) are repaired by two mutually-exclusive mechanisms, homologous recombination or end-joining. Among end-joining mechanisms, the main process is classical non-homologous end-joining (C-NHEJ) which relies on Ku binding to DNA ends and DNA Ligase IV (Lig4)-mediated ligation. Mostly under Ku- or Lig4-defective conditions, an alternative end-joining process (A-EJ) can operate and exhibits a trend toward microhomology usage at the break junction. Homologous recombination relies on an initial MRN-dependent nucleolytic degradation of one strand at DNA ends. This process, named DNA resection generates 3' single-stranded tails necessary for homologous pairing with the sister chromatid. While it is believed from the current literature that the balance between joining and recombination processes at DSBs ends is mainly dependent on the initiation of resection, it has also been shown that MRN activity can generate short single-stranded DNA oligonucleotides (ssO) that may also be implicated in repair regulation. Here, we evaluate the effect of ssO on end-joining at DSB sites both in vitro and in cells. We report that under both conditions, ssO inhibit C-NHEJ through binding to Ku and favor repair by the Lig4-independent microhomology-mediated A-EJ process.
Application of dopant segregation to metal-germanium-metal photodetectors and its dark current suppression mechanism (2008)

We report the mechanism of dopant-segregation (DS) technique as applied in metal-germanium-metal photodetectors (MGM-PDs) for dark current suppression. Photodetectors with various dopant-segregation strategies were designed, fabricated, and characterized. Results show that asymmetric MGM-PD, with n- and p-type dopants segregated separately in two NiGe electrodes, is the optimized scheme in terms of dark current and responsivity. It shows a dark current of 10−6A at −1V, which is two to three orders of magnitude lower than that of MGM-PD without DS. n-type dopant (As) segregation in NiGe barrier increases the hole Schottky barrier height to 0.5eV and, thus, plays a crucial role in dark current suppression.
Human Motion Modeling using DVGANs (2018)

We present a novel generative model for human motion modeling using Generative Adversarial Networks (GANs). We formulate the GAN discriminator using dense validation at each time-scale and perturb the discriminator input to make it translation invariant. Our model is capable of motion generation and completion. We show through our evaluations the resiliency to noise, generalization over actions, and generation of long diverse sequences. We evaluate our approach on Human 3.6M and CMU motion capture datasets using inception scores.
NF-κB, inflammation and pancreatic carcinogenesis: NF-κB as a chemoprevention target (Review) (2006)

Pancreatic cancer is the most deadly of all gastrointestinal malignancies with near zero five-year survival. This review summarizes our understanding of the potentially important role of inflammation in cancer in general and pancreatic cancer in particular. Nuclear factor kappaB (NF-kappaB), a mediator of inflammatory responses, plays a significant role in carcinogenesis and is now emerging as a link between inflammation and cancer. NF-kappaB is activated in over two thirds of human pancreatic cancers; participates in early events of pancreatic carcinogenesis through its interactions with signaling pathways; and suppression of its activation restores pancreatic cell kinetics, mainly normalizing the suppressed apoptosis of pancreatic cancer. NF-kappaB is an excellent target for chemoprevention and its modulation for pancreatic cancer prevention appears promising. The next few years will likely expand our understanding of NF-kappaB biology; solidify NF-kappaB's role as a major link between chronic inflammation and pancreatic carcinogenesis; and witness the development of NF-kappaB-based approaches to pancreatic cancer prevention.
INTERFERON-α MIMICS EFFECTS OF OVINE TROPHOBLAST PROTEIN 1 ON PROSTAGLANDIN AND PROTEIN SECRETION BY OVINE ENDOMETRIAL CELLS IN VITRO (1988)

Ovine endometrial cells were isolated from ovariectomized oestrogen and progesterone-treated ewes and maintained in primary culture. In-vitro treatment with human interferon-alpha 2 (Roferon, Hoffman La Roche) (5, 50 IU/ml) or purified ovine trophoblast protein 1 (oTP-1, 30 ng/ml) significantly attenuated PGF2 alpha (25 +/- 17, 29 +/- 17, 28 +/- 9% +/- SEM of control [no in-vitro treatment = 100%] respectively, N = 4 ewes) and PGE (11 +/- 4, 16 +/- 4, 16 +/- 5% of control) release from the cultured cells. Fluorography of two dimensional polyacrylamide gel electrophoretic analyses of proteins secreted by the cells following 35S-methionine incorporation, revealed that synthesis and secretion of the same "pregnancy-related" proteins was stimulated by both interferon-alpha 2 and oTP-1. Thus, interferon-alpha 2 (which has sequence homology with oTP-1) acts on the ovine endometrium, eliciting similar biological responses to those of oTP-1.
On the Naive Bayes Model for Text Categorization. (2003)

This paper empirically compares the performance of four probabilistic models for text classification- Poisson, Bernoulli, Multinomial and Negative Binomial. We examine the &amp;quot;naive Bayes&amp;quot; assumption in the four models and show that the multinomial model is a modified naive Bayes Poisson model that assumes independence of document length and document class. Despite the fact that this last assumption might not be correct in many situations, we find that, in general, relaxing it does not change the performance of the classifier.
Seppuku and Autoimmunity (1992)

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On the equivalence of minimum time input shaping with traditional time-optimal control (2002)

Investigates the constant amplitude nature of several time-optimal input shaping designs for controlling flexible structures. The authors first discuss the equivalence of the time-optimal zero-vibration shaper with the traditional time-optimal control problem. Then the authors show that several robust time-optimal shaper designs for flexible systems are equivalent to the time-optimal controls for different systems. This equivalence allows properties and numerical methods for time-optimal control problems to be applied to minimum time input shaping design.
Intravenous Immune Globulin for the Prevention of Nosocomial Infection in Low-Birth-Weight Neonates (1992)

For premature infants weighing between 500 and 1750 g at birth, treatment with intravenous infusions of immune globulin is safe and reduces the risk of nosocomial infection.
Regulatory role of BMP2 and BMP7 in spermatogonia and Sertoli cell proliferation in the immature mouse (2004)

We have demonstrated a stimulatory action of BMP2 and BMP7 in spermatogonia and Sertoli cell proliferation respectively. ActRIIB is the type II receptor expressed most in spermatogonia, whereas Sertoli cells specifically expressed BMPRIIB, in addition to ActRIIB. By contrast, the presence of ActRIIA was undetectable in either germ or somatic cells. The type I receptors ActRIA, ActRIB and BMPRIA were all found in both cell types, indicating that the observed effect of BMP2 and BMP7 on testicular cell proliferation may be mediated by a number of combinatorial interactions in the receptor complexes. These findings suggest that BMPs are involved in physiological paracrine signalling during the first wave of spermatogenesis.
Molecular recognition of ternary complexes: a new dimension in the structure-guided design of chemical degraders (2017)

Molecular glues and bivalent inducers of protein degradation (also known as PROTACs) represent a fascinating new modality in pharmacotherapeutics: the potential to knockdown previously thought 'undruggable' targets at sub-stoichiometric concentrations in ways not possible using conventional inhibitors. Mounting evidence suggests these chemical agents, in concert with their target proteins, can be modelled as three-body binding equilibria that can exhibit significant cooperativity as a result of specific ligand-induced molecular recognition. Despite this, many existing drug design and optimization regimens still fixate on binary target engagement, in part due to limited structural data on ternary complexes. Recent crystal structures of protein complexes mediated by degrader molecules, including the first PROTAC ternary complex, underscore the importance of protein-protein interactions and intramolecular contacts to the mode of action of this class of compounds. These discoveries have opened the door to a new paradigm for structure-guided drug design: borrowing surface area and molecular recognition from nature to elicit cellular signalling.
Cancer Immunology (2008)

This review is a comprehensive account of the current status of tumor immunology, beginning with the identification of human tumor antigens and ending with a summary of clinical applications of what we know about the immunology of tumors.
Adjustable Fragmentation in Laser Desorption/Ionization from Laser-Induced Silicon Microcolumn Arrays (2006)

Laser-induced silicon microcolumn arrays (LISMA) were developed as matrix-free substrates for soft laser desorption/ionization mass spectrometry (SLDI-MS). When low-resistivity silicon wafers were irradiated in air, sulfur hexafluoride, or water environment with multiple pulses from a 3 x omega mode-locked Nd:YAG laser, columnar structures were formed on the surface. The radii of curvature of the column tips varied with the processing environment, ranging from approximately 120 nm in water, to <1 mum in SF6, and to approximately 2 mum in air. In turn, these microcolumn arrays were used as matrix-free soft laser desorption substrates. In SLDI-MS experiments with a nitrogen laser, the microcolumn arrays obtained in water environment readily produced molecular ions for peptides and synthetic polymers at low laser fluence. These surfaces demonstrated the best ion yield among the three arrays. The threshold laser fluence and ion yield were comparable to those observed in matrix-assisted laser desorption/ionization. Low-femtomole sensitivity and approximately 6000 Da mass range were achieved. At elevated laser fluence, efficient in-source decay was observed and extensive peptide sequence information was extracted from the resulting mass spectra. The versatility of LISMA was attributed to confinement effects due to the submicrometer morphology and to the surface, thermal, and optical properties of processed silicon.
Molecular cloning and chromosomal localization of a human gene encoding D-amino-acid oxidase. (1992)

Genomic clones covering the entire sequence of the gene encoding human D-amino-acid oxidase (DAO) (EC 1.4.3.3), one of the principal and characteristic flavoenzymes of peroxisomes, were isolated from human placental genomic libraries with the aid of a previously cloned cDNA for human DAO as a probe. Nucleotide sequence analysis revealed that the gene, present as a single copy in the human genome, comprises 11 exons and spans 20 kilobase pairs. The protein sequences containing the catalytically important residues, Tyr-228 and His-307, are coded for by separate exons. Heterologous transcription initiation sites were identified by primer extension analysis, and the sequence of the 5'-flanking region of the DAO gene was found to show some features common to other mammalian genes, such as those of glucocorticoid and the cAMP-responsive element. An additional noteworthy feature is the presence of promoter-like sequences in the first intron of the gene. In addition, two sequences of alternating pyrimidine and purine nucleotides, (CA)20 and (CA)17, are also present in the first intron. Such sequences may play some role in the expression of the DAO gene in human tissues. With the use of genomic DNAs prepared from human and Chinese hamster somatic hybrid cells as templates for the polymerase chain reaction, the gene for DAO was localized to human chromosome 12.
Micromosaic Immunoassays (2000)

Immunoassays are widely used for medical diagnostics and constitute the principal method of detecting pathogenic agents and thus of diagnosing many diseases. These assays, which are most often performed in well plates, would be greatly improved by a practical method to pattern a series of antigens on a flat surface and to localize their binding to many analytes. But no obvious method exists to expose a planar surface successively to a series of antigens and analytes. Here, we present miniaturized mosaic immunoassays based on patterning lines of antigens onto a surface by means of a microfluidic network (muFN). Solutions to be analyzed are delivered by the channels of a second muFN across the pattern of antigens. Specific binding of the target antibodies with their immobilized antigens on the surface results in a mosaic of binding events that can readily be visualized in one screening using fluorescence. It is thus possible to screen solutions for antibodies in a combinatorial fashion with great economy of reagents and at a high degree of miniaturization. Such mosaic-format immunoassays are compatible with the sensitivity and reliability required for immunodiagnostic methods.
Functional antioxidant responsive elements (1997)

Exposure of human and rodent cells to a wide variety of chemoprotective compounds confers resistance against a broad set of carcinogens. For a subset of the chemoprotective compounds, protection is generated by an increase in the abundance of protective enzymes like glutathione S-transferases (GST). Antioxidant responsive elements (AREs) mediate the transcriptional induction of a battery of genes which comprise much of this chemoprotective response system. Past studies identified a necessary ARE "core" sequence of RTGACnnnGC, but this sequence alone is insufficient to mediate induction. In this study, the additional sequences necessary to define a sufficient, functional ARE are identified through systematic mutational analysis of the murine GST Ya ARE. Introduction of the newly identified necessary nucleotides into the regions flanking a nonresponsive, ARE-like, GST-Mu promoter sequence produced an inducible element. A screen of the GenBank database with the newly identified ARE consensus identified 16 genes which contained the functional ARE consensus sequence in their promoters. Included within this group was an ARE sequence from the murine ferritin-L promoter that mediated induction when tested. In an electrophoretic mobility-shift assay, the ferritin-L ARE was bound by ARE-binding protein 1, a protein previously identified as the likely mediator of the chemoprotective response. A three-level ARE classification system is presented to account for the distinct induction strengths observed in our mutagenesis studies. A model of the ARE as a composite regulatory site, where multiple transcription factors interact, is presented to account for the complex characteristics of ARE-mediated chemoprotective gene expression.
Regulation of p53 stability and p53-dependent apoptosis by NADH quinone oxidoreductase 1 (2001)

The tumor suppressor gene wild-type p53 encodes a labile protein that accumulates in cells after different stress signals and can cause either growth arrest or apoptosis. One of the p53 target genes, p53-inducible gene 3 (PIG3), encodes a protein with significant homology to oxidoreductases, enzymes involved in cellular responses to oxidative stress and irradiation. This fact raised the possibility that cellular oxidation-reduction events controlled by such enzymes also may regulate the level of p53. Here we show that NADH quinone oxidoreductase 1 (NQO1) regulates p53 stability. The NQO1 inhibitor dicoumarol caused a reduction in the level of both endogenous and gamma-irradiation-induced p53 in HCT116 human colon carcinoma cells. This reduction was prevented by the proteasome inhibitors MG132 and lactacystin, suggesting enhanced p53 degradation in the presence of dicoumarol. Dicoumarol-induced degradation of p53 also was prevented in the presence of simian virus 40 large T antigen, which is known to bind and to stabilize p53. Cells overexpressing NQO1 were resistant to dicoumarol, and this finding indicates the direct involvement of NQO1 in p53 stabilization. NQO1 inhibition induced p53 degradation and blocked wild-type p53-mediated apoptosis in gamma-irradiated normal thymocytes and in M1 myeloid leukemic cells that overexpress wild-type p53. Dicoumarol also reduced the level of p53 in its mutant form in M1 cells. The results indicate that NQO1 plays an important role in regulating p53 functions by inhibiting its degradation.
ES-8891, an orally active inhibitor of human renin. (1990)

A newly synthesized orally active renin inhibitor, N-morpholinoacetyl-(1-naphthyl)-L-alanyl-(4-thiazolyl)-L-alanyl (3S,4S)-4-amino-3-hydroxy-5-cyclohexylpentanoyl-n-hexylamide (ES-8891), was found to be a highly potent competitive inhibitor of human renin with an inhibition constant of 1.1 nM. This inhibitor was also active against monkey renin, although there was less inhibition of renin in pig, rabbit, and rat. ES-8891 did not inhibit cathepsin D, pepsin, trypsin, chymotrypsin, angiotensin converting enzyme, and urinary kallikrein at a concentration of 10(-5) M. A single oral administration of ES-8891 (10 or 30 mg/kg) to conscious, sodium-depleted marmosets caused a dose-related decrease in plasma renin activity and blood pressure. ES-8891 (30 mg/kg) produced an 80% inhibition of plasma renin activity, which lasted for more than 6 hours. Kidney renin messenger RNA was not significantly changed 6 hours after oral administration of ES-8891 (30 mg/kg). A single oral administration of 240 mg ES-8891 to healthy human volunteers (n = 6) produced a significant inhibition of plasma renin activity (75% inhibition at 0.5 and 1 hour, 50% inhibition at 2 hours) with a good correlation of plasma levels of ES-8891. There were no significant changes in blood pressure or heart rate, and no adverse effects were observed. These results suggest that ES-8891 is an orally active human renin inhibitor that may be clinically useful.
The feasibility and clinical efficacy of intravenous iron administration for preoperative anaemia in patients with colorectal cancer (2014)

IVI can be administered preoperatively in the outpatient clinic to colorectal cancer patients with anaemia, with associated reduction in ARBT use and increase in Hb levels.
Proteome Analysis of Metabolically Engineered Escherichia coli Producing Poly(3-Hydroxybutyrate) (2001)

Recombinant Escherichia coli strains harboring heterologous polyhydroxyalkanoate (PHA) biosynthesis genes were shown to accumulate unusually large amounts of PHA. In the present study, integrated cellular responses of metabolically engineered E. coli to the accumulation of poly(3-hydroxybutyrate) (PHB) in the early stationary phase were analyzed at the protein level by two-dimensional gel electrophoresis. Out of 20 proteins showing altered expression levels with the accumulation of PHB, 13 proteins were identified with the aid of mass spectrometry. Three heat shock proteins, GroEL, GroES, and DnaK, were significantly up-regulated in PHB-accumulating cells. Proteins which play essential roles in protein biosynthesis were unfavorably influenced by the accumulation of PHB. Cellular demand for the large amount of acetyl coenzyme A and NADPH for the PHB biosynthesis resulted in the increased synthesis of two enzymes of the glycolytic pathway and one enzyme of the Entner-Doudoroff pathway. The expression of the yfiD gene encoding a 14.3-kDa protein, which is known to be produced at low pH, was greatly induced with the accumulation of PHB. Therefore, it could be concluded that the accumulation of PHB in E. coli acted as a stress on the cells, which reduced the cells' ability to synthesize proteins and induced the expression of various protective proteins.
SafeTrip 21 initiative : networked traveler foresighted driving field experiment, final report. (2011)

This report describes the SafeTrip-21, Networked Traveler Foresighted Driving Field Experiment conducted as part of the US DOT’s SafeTrip-21 initiative. This experiment developed and evaluated an Advanced Driver Assistance System providing soft-safety or situational awareness alerts regarding “Slow Traffic Ahead” when driving on a freeway. The Networked Traveler system detects slow traffic or queues at several thousand locations in the Bay area, monitors the locations and speeds of its test subjects as they drive, and determines if the driver is approaching the slow traffic fast enough to warrant an alert. If so, the system alerts the driver through an auditory interface. The desired outcome is a foresighted reduction in speed, resulting in a smoother overall transition into the oncoming traffic queue. The system aims to reduce the likelihood of end-of-queue crashes on freeways, this being a subset of the class of rear-end crashes. The hypothesis is tested by computing measures representing the Root Mean Square (RMS) Error of Speed, Peak Deceleration Rate, Mean Deceleration Rate, Deceleration Due to Braking, Pre-Braking Deceleration, and Time before the start of braking. Amongst these, the RMS Error of Speed across all subjects most clearly confirms the test hypothesis -enhanced situational awareness results in smoother driving.
Allogeneic marrow transplantation in patients positive for hepatitis B surface antigen (1991)

Twenty patients who were positive for hepatitis B surface antigen (HBsAg) underwent allogeneic marrow transplant for malignancy or other underlying hematologic disease between 1975 and 1986. After transplant, one patient had serologic evidence of hepatitis B virus (HBV) reactivation whereas three patients had evidence of an immune response to HBV. Among four patients with serologic follow-up of 1 year or more, three remained positive for HBsAg and one became HBsAg negative. Six patients (30%) developed clinical evidence of venocclusive disease and seven patients (35%) developed acute graft-versus-host disease involving the liver, but the incidence of these complications was similar to that expected among patients who are not carriers of HBsAg. Three patients died with hepatorenal failure, but all three had venocclusive disease and the contribution of HBV infection to liver failure was unclear. Available liver specimens obtained at autopsy (six patients) or biopsy (two patients) all showed either HBsAg (one specimen) or hepatitis B core antigen (four specimens) or both (three specimens) by immunoperoxidase staining. Although HBV reactivation leading to hepatic failure has been reported among allogeneic marrow transplant recipients as well as other immunocompromised patients, we did not observe an increase in the incidence of severe liver disease after transplant among these 20 patients positive for HBsAg at the time of transplant, and do not consider positivity for HBsAg to be a contraindication to allogeneic marrow transplantation.
Experimental evaluation of a spherical aberration-corrected TEM and STEM (2005)

We have successfully developed a spherical aberration (Cs)-corrected electron microscope for probe- and image-forming systems using hexapole correctors. The performance of the microscope has been evaluated experimentally. The point resolution attained using the image-forming Cs-corrector is better than 0.12 nm. For scanning transmission electron microscopy, the Ronchigram flat area was >40 mrad in half-angle using the probe-forming Cs-corrector.