gebhart/patrepeval huggingface dataset:
Reconstituting Telomerase Activity Using the Telomerase Catalytic Subunit Prevents the Telomere Shorting and Replicative Senescence in Human Osteoblasts (2001)

The rate of bone formation is largely determined by the number of osteoblasts, which in turn is determined by the rate of replication of progenitors and the life span of mature cells, reflecting the timing of death by apoptosis. However, the exact age-dependent changes of the cellular activity, replicative potential, and life span of osteoblasts have not been investigated to date. Here, we present evidence that the cellular activity, telomere lengths, and replicative life span of osteoblastic cells obtained from juxta-articular bone marrow gradually decrease with the advance of donor age. Recently, telomerase reverse transcriptase (hTERT) has been identified as a human telomerase catalytic subunit. We transfected the gene encoding hTERT into telomerase-negative human osteoblastic cells from donors and osteoblastic cell strain NHOst 54881 cells and showed that expression of hTERT induces telomerase activity in these osteoblastic cells. In contrast to telomerase-negative control cells, which exhibited telomere shortening and senescence after 10-15 population doublings, telomerase-expressing osteoblastic cells had elongated telomere lengths and showed continued alkaline phosphatase activity and procollagen I C-terminal propeptide (PICP) secretion for more than 30 population doublings. These results indicate that osteoblasts with forced expression of hTERT may be used in cell-based therapies such as ex vivo gene therapy, tissue engineering, and transplantation of osteoblasts to correct bone loss or osteopenia in age-related osteoporotic diseases.
Circuit technologies for 16Mb DRAMs (1987)

THIS PAPER WILL DESCRIBE circuit technologies not only necessary for submicron ULSl memories, but also for customized ULSIs including RAM blocks. Key circnlts proposed here are an on-chip error checking and correcting (ECC) circuit that induces little access penalty, and sense circuits suitable for fast data- sensing at 3.3V operation. A 16Mb CMOS dynamic RAM incorporating a main sub bitline structure and 4.9μp2 Isolation Merged Vertical Capacitor (IVEC) cells has been designed and fabricated using a 0.7μm CMOS process as a test vehicle for these circuits
Patent Practice: Strategies for Submitting Newly Discovered Prior Art After Allowance of an Application (1991)

problem of treating material references 2 discovered late in the prosecution 3 of a patent application, particularly, the problem of treating references discovered after the claims 4 have been allowed 5 or after the application has issued 6 as a patent.
Apolipoproteins C-I and C-III as important modulators of lipoprotein metabolism (2001)

Apolipoprotein (apo)C-I and apoC-III are constituents of HDL and of triglyceride-rich lipoproteins that slow the clearance of triglyceride-rich lipoproteins by a variety of mechanisms. ApoC-I is an inhibitor of lipoprotein binding to the LDL receptor, LDL receptor-related protein, and VLDL receptor. It also is the major plasma inhibitor of cholesteryl ester transfer protein, and appears to interfere directly with fatty acid uptake. ApoC-III also interferes with lipoprotein particle clearance, but its principal role is as an inhibitor of lipolysis, both through the biochemical inhibition of lipoprotein lipase and by interfering with lipoprotein binding to the cell-surface glycosaminoglycan matrix where lipolytic enzymes and lipoprotein receptors reside. Variation in the expression of apoC-III has been credibly documented to have an important role in hypertriglyceridemia. Variation in the expression of apoC-I may also be important for hypertriglyceridemia under certain circumstances.
Carotid artery stenosis: treatment with protected balloon angioplasty and stent placement. (1996)

Endovascular treatment can be considered for all types of carotid artery stenosis. Cerebral protection is mandatory to eliminate embolic complication in cases of atherosclerotic stenosis in the internal carotid artery or carotid bifurcation. Stent placement has eliminated the risk of immediate dissection and reduced the risk of delayed restenosis.
Differential Inhibition of Functional Dilation of Small Arterioles by Indomethacin and Glibenclamide (2001)

Indomethacin or glibenclamide treatments attenuate functional dilation of larger-diameter "feed" arterioles paired with venules in hamster cremaster muscle. We tested the hypothesis that release of cyclooxygenase products from venules is important for functional dilation of third- and fourth-order arterioles. We also tested whether ATP-sensitive potassium channels are important during functional dilation of smaller arterioles. The microcirculation of hamster cremaster muscle was visualized with in vivo video microscopy. We measured diameter responses of third- and fourth-order arterioles paired and unpaired with venules in response to 2 minutes of muscle field stimulation (40 microseconds, 10 V, 1 Hz). Control diameters of vessels were 31+/-2 (n=19), 13+/-1 (n=12), 12+/-2 (n=12), and 10+/-1 (n=12) for paired and unpaired third-order and paired and unpaired fourth-order arterioles, respectively. In all groups, field stimulation resulted in increases in mean control diameter of >80%. Indomethacin (28 micromol/L) superfused on the preparation was used to inhibit cyclooxygenase metabolism, or glibenclamide (10 micromol/L) was used to block ATP-sensitive potassium channels. Indomethacin attenuated arteriolar vasodilations to electrical stimulation in paired third-order vessels only, whereas glibenclamide attenuated this vasodilation in all 4 groups. These results support a role for ATP-sensitive potassium channels in functional dilation of arterioles of all sizes regardless of whether or not they are paired with venules. Conversely, a role for cyclooxygenase products is limited to larger "feed arterioles" paired with venules. This study provides further evidence that venules may be the source of prostaglandin release during functional hyperemia.
Effective Post-insult Neuroprotection by a Novel Ca2+/ Calmodulin-dependent Protein Kinase II (CaMKII) Inhibitor (2010)

Ca(2+)/calmodulin (CaM)-dependent protein kinase II (CaMKII) is a major mediator of physiological glutamate signaling involved in higher brain functions. Here, we show CaMKII involvement in pathological glutamate signaling relevant in stroke. The novel inhibitor tatCN21 was neuroprotective even when added hours after glutamate insults. By contrast, the "traditional" inhibitor KN93 attenuated excitotoxicity only when present during the insult. Both inhibitors efficiently blocked Ca(2+)/CaM-stimulated CaMKII activity, CaMKII interaction with NR2B and aggregation of CaMKII holoenzymes. However, only tatCN21 but not KN93 blocked the Ca(2+)-independent "autonomous" activity generated by Thr-286 autophosphorylation, the hallmark feature of CaMKII regulation. Mutational analysis further validated autonomous CaMKII activity as the drug target crucial for post-insult neuroprotection. Overexpression of CaMKII wild type but not the autonomy-deficient T286A mutant significantly increased glutamate-induced neuronal death. Maybe most importantly, tatCN21 also significantly reduced infarct size in a mouse stroke model (middle cerebral arterial occlusion) when injected (1 mg/kg intravenously) 1 h after onset of arterial occlusion. Together, these data demonstrate that inhibition of autonomous CaMKII activity provides a promising therapeutic avenue for post-insult neuro-protection after stroke.
Pathophysiologic Implications of Membrane Phospholipid Asymmetry in Blood Cells (1997)

MANY STUDIES HAVE led to the concept that membrane phospholipid asymmetry is ubiquitous. In general terms, the outer leaflet of eukaryotic plasma membranes is formed predominantly with the cholinephospholipids (sphingomyelin and phosphatidylcholine [PC]), whereas the majority of the
Prostate cancer risk-associated genetic markers and their potential clinical utility (2013)

Prostate cancer (PCa) is one of the most common cancers among men in Western developed countries and its incidence has increased considerably in many other parts of the world, including China. The etiology of PCa is largely unknown but is thought to be multifactorial, where inherited genetics plays an important role. In this article, we first briefly review results from studies of familial aggregation and genetic susceptibility to PCa. We then recap key findings of rare and high-penetrance PCa susceptibility genes from linkage studies in PCa families. We devote a significant portion of this article to summarizing discoveries of common and low-penetrance PCa risk-associated single-nucleotide polymorphisms (SNPs) from genetic association studies in PCa cases and controls, especially those from genome-wide association studies (GWASs). A strong focus of this article is to review the literature on the potential clinical utility of these implicated genetic markers. Most of these published studies described PCa risk estimation using a genetic score derived from multiple risk-associated SNPs and its utility in determining the need for prostate biopsy. Finally, we comment on the newly proposed concept of genetic score; the notion is to treat it as a marker for genetic predisposition, similar to family history, rather than a diagnostic marker to discriminate PCa patients from non-cancer patients. Available evidence to date suggests that genetic score is an objective and better measurement of inherited risk of PCa than family history. Another unique feature of this article is the inclusion of genetic association studies of PCa in Chinese and Japanese populations.
Transcatheter ablation of ectopic atrial tachycardia in young patients using radiofrequency current. (1992)

RF ablation appears to be a safe and effective therapeutic option for drug-resistant ectopic atrial tachycardia and may be the preferred first-line therapy for those patients with depressed ventricular function.
Synthesis of 2‐Deoxy‐2‐Fluoro‐2‐C‐Methyl‐D‐Ribofuranoses (2006)

Abstract The synthesis of methyl 3,5‐di‐O‐benzoyl‐2‐deoxy‐2‐fluoro‐2‐C‐methyl‐β‐D‐ribofuranoside and the conversion to the corresponding 1‐O‐acetyl‐3,5‐di‐O‐benzoyl‐2‐deoxy‐2‐fluoro‐2‐C‐methyl‐D‐ribofuranose and 1,3,5‐tri‐O‐benzoyl‐2‐deoxy‐2‐fluoro‐2‐C‐methyl‐D‐ribofuranose is reported. The key synthetic step is the fluorination of the tertiary center of methyl 3,5‐di‐O‐benzyl‐2‐C‐methyl‐β‐D‐arabinofuranoside to provide methyl 3,5‐di‐O‐benzyl‐2‐deoxy‐2‐fluoro‐2‐C‐methyl‐β‐D‐ribofuranoside. Keywords: SynthesisRibofuranosesFluorinationOligonucleotides Acknowledgement Dr. R. F. Schinazi is the principal founder and former consultant of Pharmasset Inc. His laboratory received no funding for this work. This paper is dedicated to the loving memory of our friend and colleague Dr. J. Christian Mason. Additional informationNotes on contributorsJ. Christian Mason Deceased April 2005.
Beef flavor: a review from chemistry to consumer (2015)

This paper briefly reviews research that describes the sensation, generation and consumer acceptance of beef flavor. Humans sense the five basic tastes in their taste buds, and receptors in the nasal and sinus cavities sense aromas. Additionally, trigeminal senses such as metallic and astringent are sensed in the oral and nasal cavities and can have an effect on the flavor of beef. Flavors are generated from a complex interaction of tastes, tactile senses and aromas taken collectively throughout the tongue, nasal, sinus and oral cavities. Cooking beef generates compounds that contribute to these senses and result in beef flavor, and the factors that are involved in the cookery process determine the amount and type of these compounds and therefore the flavor generated. A low-heat, slow cooking method generates primarily lipid degradation products, while high-heat, fast cookery generates more Maillard reaction products. The science of consumer acceptance, cluster analyses and drawing relationships among all flavor determinants is a relatively new discipline in beef flavor. Consumers rate beef that has lipid degradation products generated from a low degree of doneness and Maillard flavor products from fast, hot cookery the highest in overall liking, and current research has shown that strong relationships exist between beef flavor and consumer acceptability, even more so than juiciness or tenderness.
Cdk4 and Nek2 Signal Binucleation and Centrosome Amplification in a Her2+ Breast Cancer Model (2013)

Centrosome amplification (CA) is a contributor to carcinogenesis, generating aneuploidy, and chromosome instability. Previous work shows that breast adenocarcinomas have a higher frequency of centrosome defects compared to normal breast tissues. Abnormal centrosome phenotypes are found in pre-malignant lesions, suggesting an early role in breast carcinogenesis. However, the role of CA in breast cancers remains elusive. Identification of pathways and regulatory molecules involved in the generation of CA is essential to understanding its role in breast tumorigenesis. We established a breast cancer model of CA using Her2-positive cells. Our goal was to identify centrosome cycle molecules that are deregulated by aberrant Her2 signaling and the mechanisms driving CA. Our results show some Her2+ breast cancer cell lines harbor both CA and binucleation. Abolishing the expression of Cdk4 abrogated both CA and binucleation in these cells. We also found the source of binucleation in these cells to be defective cytokinesis that is normalized by downregulation of Cdk4. Protein levels of Nek2 diminish upon Cdk4 knockdown and vice versa, suggesting a molecular connection between Cdk4 and Nek2. Knockdown of Nek2 reduces CA and binucleation in this model while its overexpression further enhances centrosome amplification. We conclude that CA is modulated through Cdk4 and Nek2 signaling and that binucleation is a likely source of CA in Her2+ breast cancer cells.
Distributed dynamic programming (1981)

We consider distributed algorithms for solving dynamic programming problems whereby several processors participate simultaneously in the computation while maintaining coordination by information exchange via communication links. A model of asynchronous distributed computation is developed which requires very weak assumptions on the ordering of computations, the timing of information exchange, the amount of local information needed at each computation node, and the initial conditions for the algorithm. The class of problems considered is very broad and includes shortest path problems, and finite and infinite horizon stochastic optimal control problems. When specialized to a shortest path problem the algorithm reduces to the algorithm originally implemented for routing of messages in the ARPANET.
Performance and Photosensitization of Cattle Related to Forage Quality of Four Legumes1 (1987)

Alfalfa ( Medicago sativa L.) is a superior forage legume that has several shortcomings as a pasture species, including ruminant bloat potential. Our objective was to determine whether palatability differences among alfalfa and three nonbloat‐inducing alternative legume species would influence performance of grazing heifers ( Bos taurus ). Heifer performance was quantified on pure stands of the four legumes from 1982 through 1984 and of three legumes in 1985. Grazing pressure was controlled in pastures that had a Waukegan silt loam (fine‐silty over sandy, mixed, mesic Typic Hapludolls) soil. Heifers confined to cicer milkvetch ( Astragalus cicer L.), by far the least palatable species, usually gained less than those confined to either alfalfa, birdsfoot trefoil ( Lotus corniculatus L.), or sainfoin ( Onobrychis viciifolia Scop.). Mean average daily gains during 1983 and 1984 (long‐term grazing seasons) were 0.67, 0.81, 0.80, and 0.42 kg for alfalfa, birdsfoot trefoil, sainfoin, and cicer milkvetch, respectively. Measurements of nutritive value did not explain gain differences, but reduced intake and frequent photosensitization occurred in heifers that grazed cicer milkvetch. Heifer product per hectare was influenced more by daily gains than by legume carrying capacity. Birdsfoot trefoil is a promising alternative pasture legume because it provided excellent heifer gains and had better summer growth and persistence than sainfoin, although somewhat less persistence than alfalfa. The poor palatability of cicer milkvetch was associated with reduced intake, reduced gains by cattle, and possibly with the photosensitization problem; however, its excellent yield, persistence, and nutritive value indicate that cicer milkvetch deserves more research and breeding to overcome its antiquality traits.
Human melanoma‐specific oncofetal antigen defined by a mouse monoclonal antibody (1982)

140.240, an IgG2a mouse monoclonal antibody raised against a cultured human melanoma cell line, was highly specific for melanoma cells as determined by direct and absorption analyses in a mixed hemadsorption assay. Supernatants of doubly cloned hybridomas producing antibody 140.240 reacted with all cultured and fresh melanomas tested but failed to react with a variety of carcinomas, sarcomas, lymphomas, leukemias and other tumors of neuroectodermal origin. This antibody did not react with B-lymphoid cell lines, ruling out HLA-DR specificity. Non-reactivity of antibody 140.240 with peripheral blood lymphocytes obtained from the donor of the immunizing melanoma line excluded the possibility of detecting histocompatibility antigens. Nevus cells were also non-reactive. However, antibody 140.240 did identify an antigenic determinant on tissue homogenates prepared from fetuses of 10-14 weeks' gestation. The antigen involved was shed by cultured melanoma lines and, by immunoprecipitation analysis of radiolabelled lysates, had a molecular weight of approximately 87kdal. Thus, the structure identified by monoclonal antibody 140.240 is a melanoma-specific oncofetal antigen.
Molding CNNs for text: non-linear, non-consecutive convolutions (2015)

The success of deep learning often derives from well-chosen operational building blocks. In this work, we revise the temporal convolution operation in CNNs to better adapt it to text processing. Instead of concatenating word representations, we appeal to tensor algebra and use low-rank n-gram tensors to directly exploit interactions between words already at the convolution stage. Moreover, we extend the n-gram convolution to non-consecutive words to recognize patterns with intervening words. Through a combination of lowrank tensors, and pattern weighting, we can efficiently evaluate the resulting convolution operation via dynamic programming. We test the resulting architecture on standard sentiment classification and news categorization tasks. Our model achieves state-of-the-art performance both in terms of accuracy and training speed. For instance, we obtain 51.2% accuracy on the fine-grained sentiment classification task. 1
Effects of direct current on dog liver: Possible mechanisms for tumor electrochemical treatment (1997)

Mechanisms of tumor electrochemical treatment (ECT) were studied using normal dog liver. Five physical and chemical methods were used. Two platinum electrodes were inserted into an anesthetized dog's liver at 3 cm separation. A voltage of 8.5 V direct current (DC) at an average current of 30 mA was applied for 69 min; total charge was 124 coulombs. Concentrations of selected ions near the anode and cathode were measured. The concentrations of Na+ and K+ ions were higher around the cathode, whereas the concentration of Cl- ions was higher around the anode. Water contents and pH were determined near the anode and the cathode at the midpoint between the two electrodes and in an untreated area away from the electrodes. Hydration occurred around the cathode, and dehydration occurred around the anode. The pH values were 2.1 near the anode and 12.9 near the cathode. Spectrophotometric scans of the liver sample extract were obtained, and the released gases were identified by gas chromatography as chlorine at the anode and hydrogen at the cathode. These results indicate that a series of electrochemical reactions take place during ECT. The cell metabolism and its environment are severely disturbed. Both normal and tumor cells are rapidly and completely destroyed in this altered environment. We believe that the above reactions are the ECT mechanisms for treating tumors.
Structure-function studies of the BTB/POZ transcriptional repression domain from the promyelocytic leukemia zinc finger oncoprotein. (1999)

The evolutionarily conserved BTB/POZ domain from the promyelocytic leukemia zinc finger (PLZF) oncoprotein mediates transcriptional repression through the recruitment of corepressor proteins containing histone deacetylases in acute promyelocytic leukemia. We have determined the 2.0 A crystal structure of the BTB/POZ domain from PLZF (PLZF-BTB/POZ), and have carried out biochemical analysis of PLZF-BTB/POZ harboring site-directed mutations to probe structure-function relationships. The structure reveals a novel alpha/beta homodimeric fold in which dimer interactions occur along two surfaces of the protein subunits. The conservation of BTB/POZ domain residues at the core of the protomers and at the dimer interface implies an analogous fold and dimerization mode for BTB/POZ domains from otherwise functionally unrelated proteins. Unexpectedly, the BTB/POZ domain forms dimer-dimer interactions in the crystals, suggesting a mode for higher-order protein oligomerization for BTB/POZ-mediated transcriptional repression. Biochemical characterization of PLZF-BTB/POZ harboring mutations in conserved residues involved in protein dimerization reveals that the integrity of the dimer interface is exquisitely sensitive to mutation and that dimer formation is required for wild-type levels of transcriptional repression. Interestingly, similar mutational analysis of residues within a pronounced protein cleft along the dimer interface, which had been implicated previously for interaction with corepressors, has negligible effects on dimerization or transcriptional repression. Together, these studies form a structure-function framework for understanding BTB/POZ-mediated oligomerization and transcriptional repression properties.
Ligand Screening of Olfactory Receptors (2005)

Imaging Assay ...........................................................................95 4.4.2 cAMP Assay.......................................................................................97 4.4.3 Luciferase Reporter Gene Assay .......................................................99 4.4.4XenopusOocyte Assay.....................................................................100 4.4.4.1 Assays for Multiple G Protein-Mediated Signals............100 4.4.4.2 Measurement of Ion Currents with a Voltage ClampMethod ..............................................................................102 4.4.4.3 Measurement with Depolarization Step Pulses................103