gebhart/patrepeval huggingface dataset:
Vlsi Custom Microelectronics Digital, Analog And Mixed- Signal (1998)

From the Publisher:
This innovative reference/text focuses on the design and production of integrated circuits specifically designed for particular applications from original-equipment manufacturers. Containing over 900 references, tables, equations, and figures, VLSI Custom Microelectronics is a versatile reference for electrical, electronics, design, computer, mechanical, and control engineers; computer architects and scientists; and circuit and systems designers; and an excellent text for upper-level undergraduate and graduate students in these disciplines.
Chiral porous metal-organic frameworks with dual active sites for sequential asymmetric catalysis (2012)

Metal-organic frameworks (MOFs) are a class of organic–inorganic hybrid materials built from metal-connecting nodes and organic-bridging ligands. They have received much attention in recent years owing to the ability to tune their properties for potential applications in various areas. Properly designed MOFs with uniform, periodically aligned active sites have shown great promise in catalysing shape-, size-, chemo-, regio- and stereo-selective organic transformations. This study reports the synthesis and characterization of two chiral MOFs (CMOFs 1 and 2 ) that are constructed from Mn-salen-derived dicarboxylic acids [salen is ( R , R )- N , N ′-bis(5- tert -butylsalicylidene)-1,2-cyclohexanediamine], bis(4-vinylbenzoic acid)-salen manganese(III) chloride (H 2 L 4 ) or bis(benzoic acid)-salen manganese(III) chloride (H 2 L 3 ) and [Zn 4 (μ 4 -O)(O 2 CR) 6 ] or [Zn 5 (H 2 O) 2 (μ 3 -OH) 2 (O 2 CR) 8 ] secondary building units (SBUs), respectively. The SBUs in CMOF- 1 are connected by the linear ditopic Mn-salen-derived linkers to construct a fourfold interpenetrated isoreticular MOF (IRMOF) structure with pcu topology. In CMOF- 2 , the Mn-salen centres dimerize in a cross-linking way to form a diamondoid structure with threefold interpenetration. CMOF- 1 was examined for highly regio- and stereo-selective tandem alkene epoxidation/epoxide ring-opening reactions by using the Mn-salen andZn 4 (μ 4 -O)(carboxylate) 6 active sites, respectively. Our work demonstrated the potential utility of chiral MOFs with multiple active sites in the efficient synthesis of complex molecules with excellent regio- and stereo-controls
Age as a prognostic factor in breast cancer (1986)

The influence of age on survival was studied in an unselected series of 31,594 females with breast cancer reported to The Cancer Registry of Norway during 1955-1980. The prognosis was best in patients aged 35 to 49 years, and poorest in the older (greater than or equal to 75 years) and the younger patients (less than or equal to 34 years). These trends were present in all stages and periods of diagnosis. The poor outcome among the older patients may, in part, be related to less aggressive treatment, while differences in treatment procedures hardly explain the poor prognosis among the younger patients.
Ultrasound Elastography: A Dynamic Programming Approach (2008)

This paper introduces a 2-D strain imaging technique based on minimizing a cost function using dynamic programming (DP). The cost function incorporates similarity of echo amplitudes and displacement continuity. Since tissue deformations are smooth, the incorporation of the smoothness into the cost function results in reduced decorrelation noise. As a result, the method generates high-quality strain images of freehand palpation elastography with up to 10% compression, showing that the method is more robust to signal decorrelation (caused by scatterer motion in high axial compression and nonaxial motions of the probe) in comparison to the standard correlation techniques. The method operates in less than 1 s and is thus also potentially suitable for real time elastography.
Elucidation of the Selectivity of Proton-Dependent Electrocatalytic CO2 Reduction by fac-Re(bpy)(CO)3Cl (2013)

A complete mechanism for the proton-dependent electrocatalytic reduction of CO2 to CO by fac-Re(bpy)(CO)3Cl that is consistent with experimental observations has been developed using first principles quantum chemistry. Calculated one-electron reduction potentials, nonaqueous pKa's, reaction free energies, and reaction barrier heights provide deep insight into the complex mechanism for CO2 reduction as well as the origin of selectivity for this catalyst. Protonation and then reduction of a metastable Re-CO2 intermediate anion precedes Brønsted-acid-catalyzed C-O cleavage and then rapid release of CO at negative applied potentials. Conceptually understanding the mechanism of this rapid catalytic process provides a useful blueprint for future work in artificial photosynthesis.
Rapamycin Reverses Elevated mTORC1 Signaling in Lamin A/C–Deficient Mice, Rescues Cardiac and Skeletal Muscle Function, and Extends Survival (2012)

Mutations in LMNA, the gene that encodes A-type lamins, cause multiple diseases including dystrophies of the skeletal muscle and fat, dilated cardiomyopathy, and progeria-like syndromes (collectively termed laminopathies). Reduced A-type lamin function, however, is most commonly associated with skeletal muscle dystrophy and dilated cardiomyopathy rather than lipodystrophy or progeria. The mechanisms underlying these diseases are only beginning to be unraveled. We report that mice deficient in Lmna, which corresponds to the human gene LMNA, have enhanced mTORC1 (mammalian target of rapamycin complex 1) signaling specifically in tissues linked to pathology, namely, cardiac and skeletal muscle. Pharmacologic reversal of elevated mTORC1 signaling by rapamycin improves cardiac and skeletal muscle function and enhances survival in mice lacking A-type lamins. At the cellular level, rapamycin decreases the number of myocytes with abnormal desmin accumulation and decreases the amount of desmin in both muscle and cardiac tissue of Lmna(-/-) mice. In addition, inhibition of mTORC1 signaling with rapamycin improves defective autophagic-mediated degradation in Lmna(-/-) mice. Together, these findings point to aberrant mTORC1 signaling as a mechanistic component of laminopathies associated with reduced A-type lamin function and offer a potential therapeutic approach, namely, the use of rapamycin-related mTORC1 inhibitors.
Heteronuclear three-dimensional NMR spectroscopy of the inflammatory protein C5a (1989)

The utility of three-dimensional heteronuclear NMR spectroscopy for the assignment of 1H and 15N resonances of the inflammatory protein C5a (MW 8500), uniformly labeled with 15N, is demonstrated at a protein concentration of 0.7 mM. It is shown that dramatic simplification of the 2D nuclear Overhauser effect spectrum (NOESY) is obtained by editing with respect to the frequency of the 15N heteronucleus in a third dimension. The improved resolution in the 3D experiment largely facilitates the assignment of protein NMR spectra and allows for the determination of distance constraints from otherwise overlapping NOE cross peaks for purposes of 3D structure determination. The results show that 15N heteronuclear 3D NMR can facilitate the structure determination of small proteins and promises to be a useful tool for the study of larger systems that cannot be studied by conventional 2D NMR techniques.
Question Answering and Question Generation as Dual Tasks (2017)

We study the problem of joint question answering (QA) and question generation (QG) in this paper. Our intuition is that QA and QG have intrinsic connections and these two tasks could improve each other. On one side, the QA model judges whether the generated question of a QG model is relevant to the answer. On the other side, the QG model provides the probability of generating a question given the answer, which is a useful evidence that in turn facilitates QA. In this paper we regard QA and QG as dual tasks. We propose a training framework that trains the models of QA and QG simultaneously, and explicitly leverages their probabilistic correlation to guide the training process of both models. We implement a QG model based on sequence-to-sequence learning, and a QA model based on recurrent neural network. As all the components of the QA and QG models are differentiable, all the parameters involved in these two models could be conventionally learned with back propagation. We conduct experiments on three datasets. Empirical results show that our training framework improves both QA and QG tasks. The improved QA model performs comparably with strong baseline approaches on all three datasets.
Matrix Metalloproteinases (2002)

Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes responsible for myocardial extracellular protein degradation. Several MMP species identified within the human myocardium may be dysregulated in congestive heart failure (CHF). For example, MMPs that are expressed at very low levels in normal myocardium, such as collagenase-3 (MMP-13) and the membrane-type-1 MMPs, are substantially upregulated in CHF. However, MMP species are not uniformly increased in patients with end-stage CHF, suggesting that a specific portfolio of MMPs are expressed in the failing myocardium. With the use of animal models of CHF, a mechanistic relationship has been demonstrated with respect to myocardial MMP expression and the left ventricular (LV) remodeling process. The tissue inhibitors of the MMPs (TIMPs) are locally synthesized proteins that bind to active MMPs and thereby regulate net proteolytic activity. However, there does not appear to be a concomitant increase in myocardial TIMPs during the LV remodeling process and progression to CHF. This disparity between MMP and TIMP levels favors a persistent MMP activation state within the myocardium and likely contributes to the LV remodeling process in the setting of developing CHF. The elucidation of upstream signaling mechanisms that contribute to the selective induction of MMP species within the myocardium as well as strategies to normalize the balance between MMPs and TIMPs may yield some therapeutic strategies by which to control myocardial extracellular remodeling and thereby slow the progression of the CHF process.
Comparison of sputum processing techniques in cystic fibrosis (1996)

Sputum analysis is a useful technique for the study of airway inflammation. In asthma, dithiothreitol (DTT) is used to disperse cells from surrounding mucus; however, the applicability of these processing methods to cystic fibrosis (CF) sputum is unknown. In order to compare two methods for processing sputum of patients with CF, sputum was obtained from 11 subjects with CF (8 female, aged 9-21 years). The sample was split into 2 portions and sputum dispersal using DTT was compared with an enzyme mixture (E) of deoxyribonuclease, hyaluronidase, and galactosidase. Outcomes assessed were sample quality, cell viability (percent cells excluding trypan blue), total cell count (TCC), neutrophil count, and elastase immunoreactivity (percent cells positive). Sample quality (enzymes vs. DTT, 8.3 +/- 0.3 vs 7.6 +/- 0.4, mean +/- SEM) and cell viability (enzymes vs. DTT, 75.0% vs. 68.0%, median) were similar for both methods. Sputum total cell count (20.5 x 10(6)/ml vs. 12.0 x 10(6)/ml, median; P = 0.01) and neutrophil count (13.4 x 10(6)/ml vs. 5.5 > 10(6)/ml, median; P = 0.02) were significantly higher with E. Elastase immunoreactivity was lost after processing with E (19.0% vs. 39.5%, median; P = 0.04). When purified peripheral blood neutrophils were incubated with DTT and E, there was no reduction in neutrophil viability, suggesting that the reduced neutrophil number in CF sputum was not due to a toxic effect of DTT but rather incomplete dispersal. We conclude that published sputum processing methods for asthma using DTT give false results when applied to CF sputum, which should be processed using an enzyme mixture.
An engineered intersubunit disulfide enhances the stability and DNA binding of the N-terminal domain of .lambda. repressor (1986)

Site-directed mutagenesis has been used to replace Tyr-88 at the dimer interface of the N-terminal domain of lambda repressor with cysteine. Computer model building had suggested that this substitution would allow formation of an intersubunit disulfide without disruption of the dimer structure [Pabo, C. O., & Suchanek, E. G. (1986) Biochemistry (preceding paper in this issue)]. We find that the Cys-88 protein forms a disulfide-bonded dimer that is very stable to reduction by dithiothreitol and has increased operator DNA binding activity. The covalent Cys88-Cys88' dimer is also considerably more stable than the wild-type protein to thermal denaturation or urea denaturation. As a control, Tyr-85 was replaced with cysteine. A Cys85-Cys85' disulfide cannot form without disrupting the wild-type structure, and we find that this disulfide bond reduces the DNA binding activity and stability of the N-terminal domain.
Flow cytometric analysis of inflammatory markers in KCS: 6-month treatment with topical cyclosporin A. (2001)

Flow cytometry provided an objective technique to monitor the effects of topical cyclosporin A on immune- and apoptosis-related markers in the conjunctival epithelium of patients with KCS enrolled in a large multicenter trial. Topical cyclosporin A strikingly reduced HLA DR and to a lesser extent, other inflammatory and apoptotic markers, whereas the vehicle, used as a control tear substitute, had almost no effect. This study confirms that cyclosporin A may be efficient in reducing conjunctival inflammation in moderate to severe KCS and is consistent with clinical results in this indication.
The RAD3 gene of Saccharomyces cerevisiae encodes a DNA-dependent ATPase. (1987)

The RAD3 gene of the yeast Saccharomyces cerevisiae is required for excision repair of damaged DNA and for cell viability. A protein of approximately equal to 89 kDa was purified to near homogeneity from yeast strains harboring multicopy plasmids that overproduce RAD3 protein; this protein corresponds closely to the expected size of the RAD3 protein and cross-reacts with the antiserum raised against a truncated RAD3 protein produced in Escherichia coli. The purified RAD3 protein shows a single-stranded DNA-dependent ATPase activity that catalyzes hydrolysis of ATP to ADP and Pi. The ATPase activity was coincident with the RAD3 protein during purification and is inhibited by anti-RAD3 antibodies, indicating that the RAD3 gene encodes this activity.
High ponderal index at birth predicts high estradiol levels in adult women (2005)

Inter-individual variation in levels of sex hormones results from differences in genetic, developmental, and environmental factors. We tested a hypothesis that programming of the fetal neuroendocrine axis may predispose some women to produce higher levels of steroid hormones during their menstrual cycles as adults. One hundred forty-five regularly menstruating 24- to 36- year-old women collected daily saliva samples for one menstrual cycle. Data on women's birth weights and birth lengths were obtained from medical records. A positive relationship was observed between ponderal index at birth (an indicator of nutritional status, calculated as birth weight/(birth length)(3)) and levels of estradiol (E2) in menstrual cycles, after controlling for potential confounding factors. Mean E2 was 16.4 pmol/l in the low ponderal index tertile, 17.3 pmol/l in the moderate ponderal index tertile, and 19.6 pmol/l in the high ponderal index tertile (the high ponderal index group had significantly higher E2 than both low and moderate ponderal index groups, P=0.0001). This study shows a positive association between ponderal index recorded for women at birth and levels of E2 measured during their menstrual cycles as adults. This suggests that conditions during fetal life influence adult production of reproductive hormones and may contribute to inter-individual variation in reproductive function. In addition, because large size at birth is one of the factors linked with an increased risk of breast cancer, our findings provide a physiological link for the observed positive relationship between indicators of energetic conditions during fetal growth and breast cancer in women.
A direct role for IFN-γ in regulation of Th1 cell development (1996)

IL-12 has been identified as a major cytokine influencing the differentiation of CD4 cells to a Th1 phenotype, whereas a role for IFN-gamma is controversial. We investigated the interrelationship between IL-12 and IFN-gamma in promoting Th1 responses using naive CD4 cells reactive with pigeon cytochrome c from TCR transgenics and memory CD4 cells derived by in vivo priming with KLH. Without exogenous rIL-12 or rIFN-gamma, primary and memory effectors induced by Ag or anti-CD3 and anti-CD28 secreted variable levels of IL-2 and IFN-gamma. The level of IFN-gamma secreted by effectors correlated with endogenous IFN-gamma produced in primary cultures, and anti-IFN-gamma largely inhibited the development of effectors producing IFN-gamma. With optimal TCR stimulation and costimulation, endogenous IFN-gamma, without IL-12, was sufficient to elicit Th1 cells via an autocrine mechanism, whereas with suboptimal stimulation, exogenous rIFN-gamma or rIL-12 was required for Th1 development. However, rIL-12 was more effective than rIFN-gamma, partially because rIL-12 greatly enhanced autocrine production of IFN-gamma, and optimal development of the Th1 phenotype was mediated by the synergistic actions of both cytokines. Thus, both IFN-gamma and IL-12 can independently regulate Th1 development, but because of IFN-gamma-mediated feedback, their relative contributions are determined by the conditions of T cell stimulation. The extent of differentiation to a Th1 phenotype may, therefore, depend on the availability of both APC-derived IL-12 and autocrine IFN-gamma consequent to the overall strength of T cell stimulation.
Characterization of ligand binding by the human p55 tumour‐necrosis‐factor receptor (1994)

Two soluble tumour-necrosis-factor-alpha(TNF)-binding proteins are derived from the extracellular domains of the p55 and p75 TNF receptors. They are considered to play a pivotal regulatory role in TNF-mediated inflammatory processes, including diseases such as rheumatoid arthritis, by competing with the cell surface receptors for TNF and lymphotoxin (LT, tumour-necrosis factor beta). The extracellular domains of the two receptors each contain four similar cysteine-rich repeats of about 40 amino acids, in common with several other cell surface proteins including the p75 nerve-growth-factor receptor and the CD40 and Fas antigens. The aim of this study was to characterize the involvement of the four cysteine-rich repeats of the human p55 TNF receptor in TNF and LT binding by both membrane-bound and soluble forms of the receptor. Individual repeats were systematically deleted by PCR mutagenesis and the variants transiently expressed in COS cells. Immunoprecipitated receptor variants exhibited the expected sizes on SDS/PAGE gels, and bound a panel of conformation-dependent anti-(TNF receptor) antibodies. Binding of TNF by the four soluble derivatives was compared with binding by the wild-type soluble receptor using a TNF-affinity column and a BIAcore Biosensor, by measurement of their ability to inhibit TNF cytotoxicity on WEHI cells, and 125I-TNF binding to U937 cells. delta 4, which lacks the fourth cysteine-rich repeat, bound TNF comparably with the full-length soluble receptor. TNF-binding affinity was unaltered by deletion of the fourth membrane-proximal cysteine-rich repeat, as determined by Scatchard analysis of the transmembrane derivatives. We conclude that the fourth cysteine-rich repeat is not required for TNF binding. In contrast, both the soluble and the transmembrane derivatives lacking any one of the first, second or third repeats failed to bind TNF. Although we cannot entirely exclude the possibility that this may be due to indirect conformational change, rather than the removal of essential epitopes, our results suggest that the first three repeats are each required for TNF binding by both the soluble and the cell-surface receptor.
Selective amplification of periportal transitional cells precedes formation of hepatocellular carcinoma in SV40 large tag transgenic mice. (1991)

In a major urinary protein (MUP)-promoter/simian virus 40 (SV40)Tag transgenic mouse line (MT-D2) the liver-directed, androgen-regulated transgene expression leads to synchronized pathology resulting in a stepwise progression to multiple hepatocellular carcinomas. SV40Tag-activated replication gives rise to two different preneoplastic alterations in hepatocytes, which are characterized in detail: 1) dysplasia and finally cell death in the original hepatocyte population and 2) amplification of periportal transitional hepatocytes leading to multifocal hyperplasia and hepatocellular carcinoma. Multifocal hyperplasia, most probably the equivalent of SV40Tag-immortalization, grows confluent and leads to hepatomegaly. SV40Tag-independent, secondary events are necessary for the tumor development from confluent hyperplasia. This allows further investigation of the steps involved in malignant transformation and progression during hepatocarcinogenesis in vivo.
125I radioimmunoassay of delta-9-tetrahydrocannabinol in blood and plasma with a solid-phase second-antibody separation method. (1981)

In this sensitive and specific radioimmunoassay for delta-9-tetrahydrocannabinol, an iodinated tracer with high specific activity and a solid-phase separation are used. Within-run coefficients of variation for 5.0 and 30.0 microgram/L concentrations were 7.8 and 4.2% for plasma and 14 and 10.6% for hemolyzed blood specimens, respectively. Day-to-day coefficients of variations ranged from 7.3 to 13.6% (for 7.6 to 33.0 microgram/L concentrations) for plasma and 13.4 to 18.1% (3.0 to 52.1 microgram/L) for hemolyzed blood specimens. Data for time after start of smoking of a standard THC-containing cigarette vs the concentration of delta-9-tetrahydrocannabinol in the plasma were similar to those obtained by others. Positive plasma specimens from the smoking study were analyzed by gas chromatography-mass spectrometry and by our radioimmunoassay. Nonparametric statistical comparison and linear regression (r2 = 0.972) showed that results by the two methods of analysis correlate well. The sensitivity of the assay was at least 0.3 microgram/L for plasma, 1.1 microgram/L for hemolyzed blood.
Calcium‐sensing receptor expression and signalling in human parathyroid adenomas and primary hyperplasia (2000)

The study shows that the activation of the calcium sensing receptors expressed in adenomatous parathyroid glands modulates intracellular effectors in a similar way to those operating in the normal parathyroid. Although a reduction of calcium sensing receptor expression is probably involved in the poor inhibition of PTH release induced by [Ca2+]o, this is not the only factor altering [Ca2+]o sensing in parathyroid adenomas, since tumours characterized by different in vitro sensitivity to [Ca2+]o showed similar CaSR levels. The low content of G proteins of the Gq subfamily might represent an additional alteration leading to a defective [Ca2+]o sensing.