gebhart/patrepeval huggingface dataset:
Mammalian sperm interaction with extracellular matrices of the egg. (1989)

One conclusion that may be drawn from the foregoing discussion is that examination of mammalian gamete interaction at a molecular level is underway. As yet, however, it would be premature to suggest a detailed molecular model to account fully for acrosomal exocytosis. Too many possibilities exist at present, not just for sperm but for virtually all other exocytotic systems studied. It is evident, however, that many elements of typical signal transduction pathways are present in sperm, and recent work supports the idea that such pathways may be used in AR triggering. Investigations at the cellular level provide sufficient data to formulate a sequence of gamete interactions that may apply generally to mammals. This sequence is summarized in Fig. 8.2. It is suggested that the cumulus ECM functions to restrict access of only primed (i.e., capacitated) sperm to the egg. Those sperm that undergo a spontaneous AR in the midst of the cumulus ECM are prevented from further participation in fertilization by adherence to cumulus cells. Thus, a select population of capacitated, acrosome-intact sperm arrive at the zona pellucida surface under the normal conditions of fertilization. Binding to the zona pellucida is initiated by plasma membrane receptors interacting with ZP3. This primary binding results in receptor clustering, which itself is the triggering event for acrosomal exocytosis. The signal is transmitted intracellularly via G proteins to effect fusion between the plasma and outer acrosomal membranes. As a result, proacrosin is exposed. Direct evidence for specific use of ZP2 in secondary binding has not yet been reported, but is inferred from results with mouse (Bleil and Wassarman 1986), and procine (Brown and Jones 1987; Jones et al. 1988; Topfer-Petersen and Henschen 1987, 1988) gametes. This secondary binding between ZP2 and proacrosin occurs together with pH-dependent autoactivation of proacrosin to acrosin. Limited proteolysis of the zona pellucida matrix by acrosin causes digestion and increases the affinity of freshly exposed proacrosin for the zona pellucida. This cycle continues, eventually generating the narrow penetration slit through the zona pellucida. Undoubtedly, other factors are at play here, particularly motility, and it is assumed that vigorously active ('hyperactive') sperm are the cells that participate in these events. This scheme can account for the many diverse observations made in different species if two factors, kinetics and affinity, are considered. In some species, FTU aggregation may occur spontaneously at a rate faster than in others, leading to a higher level of spontaneously acrosome-reacted sperm.(ABSTRACT TRUNCATED AT 400 WORDS)
The Biosynthesis and Synthesis of Shikimic Acid, Chorismic Acid, and Related Compounds (1993)

This review considers recent progress in the interpretation of the reaction mechanisms involved in the conversion of glucose into shikimic acid and chorismic acid en route to aromatic compounds. Its main thrust, however, is a detailed survey of the chemical syntheses of shikimic acid and chorismic acid and their derivatives which have been announced in the last decade. 1. The Shikimate Pathway 1.1. Introduction 1.2. The Common Pathway 1.3. The Role of Quinic Acid 1.4. Branch Point Metabolism 2. Syntheses of Shikimic Acid 2.1. Campbell, Sainsbury et al. 2.2. Sunderland et al. 2.3. Rodrigo et al. 2.4. Birch et al. 2.5. Koizumi et al. 2.6. Koreeda et al. 2.7. Koreeda et al. 2.8. Fleet et al. 2.9. Mirza et al. 3. Synthesis of Later Intermediates in the Shikimate Pathway 3.1. Shikimic Acid 3-Phosphate 3.2. 5-Enolpyruvylshikimate-3-phosphate (5-EPS-3-P) 3.3. Chorismic Acid 4. Synthesis of Enzyme Inhibitors 4.1. Synthesis of 5-EPS-3-P Synthase Inhibitors 4.2. Knowles-Anderson
Genetic analysis of a plasmid-encoded, host genotype-specific enhancement of bacterial fitness (1994)

In the absence of antibiotics, carriage of pACYC184 reduces the competitive fitness of an Escherichia coli B genotype that was not previously selected for plasmid carriage, relative to that of an isogenic plasmid-free competitor. However, a host genotype propagated with the plasmid for 500 generations evolved an unexpected competitive advantage from plasmid carriage, relative to its own isogenic plasmid-free segregant. We manipulated the pACYC184 genome in order to identify the plasmid-encoded function that was required for the enhancement of the coevolved host genotype's competitive fitness. Inactivation of the plasmid-encoded tetracycline resistance gene, by deletion of either the promoter region or the entire gene, eliminated the beneficial effect of plasmid carriage for the coevolved host. This beneficial effect for the coevolved host was also manifest with pBR322, which contains a tetracycline resistance gene identical to that of pACYC184 but is otherwise heterologous.
Inductor design for low loss with complex waveforms (2012)

An inductor design which uses solid and litz wire in order to attain high efficiency for waveforms with low- and high-frequency components is presented. In previous designs, leakage inductance can increase the portion of the low-frequency component that flows in the litz-wire winding, and thus increase loss. A capacitor in series with the litz-wire winding is proposed to eliminate this effect. An inductor prototype has been built and measurement results verify the benefits of the proposed concept. Both model results and measurements show that loss can be reduced by as much as 20% through adding the capacitor or by 30% compared to a solid-wire winding alone. For design optimization including cost considerations a software tool has been written in MATLAB based on the derived loss model offering a simple step-by-step process for designers.
Redox and Activation Status of Monocytes from Human Immunodeficiency Virus-Infected Patients: Relationship with Viral Load (1999)

Monocytes are precursors of tissue macrophages, which are major targets of human immunodeficiency virus type 1 (HIV-1) infection. Although few blood monocytes are infected, their resulting activation could play a key role in the pathogenesis of HIV disease by modulating their transendothelial migration and inducing the production of reactive oxygen species (ROS). ROS participate in chronic inflammation, HIV replication, and the apoptosis of immune system cells seen in HIV-infected subjects. Published data on monocyte activation are controversial, possibly because most studies have involved monocytes isolated from their blood environment by various procedures that may alter cell responses. We therefore used flow cytometry to study, in whole blood, the activation and redox status of monocytes from HIV-infected patients at different stages of the disease. We studied the expression of adhesion molecules, actin polymerization, and cellular levels of H2O2, Bcl-2, and thioredoxin. Basal H2O2 production correlated with viral load and was further enhanced by bacterial N-formyl peptides and endotoxin. The enhanced H2O2 production by monocytes from asymptomatic untreated patients with CD4(+) cell counts above 500/microliter was associated with a decrease in the levels of Bcl-2 and thioredoxin. In contrast, in patients with AIDS, Bcl-2 levels returned to normal and thioredoxin levels were higher than in healthy controls. Restoration of these antioxidant and antiapoptotic molecules might explain, at least in part, why monocyte numbers remain relatively stable throughout the disease. Alterations of adhesion molecule expression and increased actin polymerization could play a role in transendothelial migration of these activated monocytes.
Mammalian tyrosinase. A comparison of tyrosine hydroxylation and melanin formation (1976)

1. Melanosomal tyrosinase was isolated from normal C57B1 mice, and a comparison of the tyrosine-hydroxylation and dopa (3,4-dihydroxyphenylalanine)-oxidation activities of this enzyme was made. 2. The results indicate that in the absence of dopa cofactor, this enzyme is capable of tyrosine hydroxylation, but with very little subsequent dopa oxidation and melanin formation. 3. This mechanism of enzyme action may play an important role in the intracellular regulation of melanin formation. 4. Further, dopa appears to act as a positive allosteric effector for tyrosine hydroxylation by tyrosinase, in addition to its known activity as a hydrogen donor for the reaction.
ChemInform Abstract: SYNTHESIS OF THE TWO EPIMERIC 5′‐METHYLCYTIDINES, THEIR 5′‐PHOSPHATES AND (5‐3H)‐5′‐PYROPHOSPHATES, AND THE TWO 5′‐METHYLDEOXYCYTIDINES. A NOVEL CYSTOSINE ANHYDRONUCLEOSIDE WITH TWO OXYGEN BRIDGES BETWEEN THE BASE AND THE SUGAR (1982)

Abstract Das aus dem β‐D‐allo‐Zuckerderivat (Ia) erhältliche Benzoylderivat (Ib) wird a) in das Tribenzoat (Ic) bzw. b) in das Dibenzoat (Id) [ im Gemisch mit dem Isomeren (Ie); Ausb.‐Optimierung durch Isomerisierung (siedendes Toluol) von (Ie)] übergeführt.
Tissue Inhibitor of Metalloproteinase-1 Protects Human Breast Epithelial Cells Against Intrinsic Apoptotic Cell Death via the Focal Adhesion Kinase/Phosphatidylinositol 3-Kinase and MAPK Signaling Pathway (2003)

Tissue inhibitor of metalloproteinase (TIMP-1) is a natural protease inhibitor of matrix metalloproteinases (MMPs). Recent studies revealed a novel function of TIMP-1 as a potent inhibitor of apoptosis in mammalian cells. However, the mechanisms by which TIMP-1 exerts its anti-apoptotic effect are not understood. Here we show that TIMP-1 activates cell survival signaling pathways involving focal adhesion kinase, phosphatidylinositol 3-kinase, and ERKs in human breast epithelial cells to TIMP-1. TIMP-1-activated cell survival signaling down-regulates caspase-mediated classical apoptotic pathways induced by a variety of stimuli including anoikis, staurosporine exposure, and growth factor withdrawal. Consistently, down-regulation of TIMP-1 expression greatly enhances apoptotic cell death. In a previous study, substitution of the second amino acid residue threonine for glycine in TIMP-1, which confers selective MMP inhibition, was shown to obliterate its anti-apoptotic activity in activated hepatic stellate cells suggesting that the anti-apoptotic activity of TIMP-1 is dependent on MMP inhibition. Here we show that the same mutant inhibits apoptosis of human breast epithelial cells, suggesting different mechanisms of TIMP-1 regulation of apoptosis depending on cell types. Neither TIMP-2 nor a synthetic MMP inhibitor protects breast epithelial cells from intrinsic apoptotic cell death. Furthermore, TIMP-1 enhances cell survival in the presence of the synthetic MMP inhibitor. Taken together, the present study unveils some of the mechanisms mediating the anti-apoptotic effects of TIMP-1 in human breast epithelial cells through TIMP-1-specific signal transduction pathways.
A Sensitive HPLC Method for the Determination of Terfenadine and Its Metabolite in Human Plasma (1994)

Abstract A sensitive and selective HPLC assay with fluorescence detection was developed for the analysis of terfenadine and its acid metabolite in human plasma. The compounds were isolated from plasma by liquid extraction with methyl-t-butyl ether:isopropyl alcohol (95:5% v/v). The chromatographic separation was carried on cyanopropylsilane column (15 cm × 4,6 mm) with a mobile phase consisting of 0.001 M acetate buffer, pH 4.0 : acetonitrile (25:75% v/v). The eluent was monitored at 230 nm excitation and 300 nm emission wavelengths with a 270 nm cut-off filter. The range of quantification was 2 to 1000 ng/ml for terfenadine and 5 to 1000 ng/ml for acid metabolite, respectively. The assay showed linearity over the range of quantification (r2 > 0.998). This method has been applied to the analysis of human plasma samples.
An improved method for precise quantitation of cellular and tissue apolipoprotein A-I mRNA levels by use of an internal standard. (1990)

We have developed a method for the quantitation of apolipoprotein A-I (apoA-I) mRNA by using a variation of traditional S1 nuclease analysis. This method uses an internal standard RNA that allows a level of precision not obtainable with traditional S1 nuclease analysis. The internal standard RNA is synthesized in vitro using the T7 promoter from the transcription vector, pApoAI, which contains the full length apoA-I cDNA. This RNA molecule is identical to authentic apoA-I mRNA except for the addition of 48 bases at the 5'-end which are derived from the vector. A labeled ssDNA probe is produced from pApoAI in such a way that solution hybridization of the probe to a mixture of total RNA and internal standard RNA followed by S1 nuclease digestion results in the protection of DNA fragments from authentic and internal standard RNA, which differ in size by 48 bases. The DNA fragments can be resolved by gel electrophoresis and quantitated. The addition of internal standard RNA to each hybridization reaction allows for correction of variations in hybridization and other sources of experimental error. Using this method we demonstrate a sevenfold increase in precision (the 90% confidence interval was reduced from +/- 186% to +/- 26% of the mean value) when compared to traditional S1 nuclease analysis of apoA-I mRNA in liver biopsies and hepatocytes in culture. The internal standard/S1 nuclease method can be adapted to the analysis of any mRNA.
Performance of the Genotype MTBDR Line Probe Assay for Detection of Resistance to Rifampin and Isoniazid in Strains of Mycobacterium tuberculosis with Low- and High-Level Resistance (2006)

We assessed the performance of the Genotype MTBDR line probe assay that offers the simultaneous identification of Mycobacterium tuberculosis and its resistance to rifampin (RIF) and isoniazid (INH) by detecting the most commonly found mutations in the rpoB and katG genes. One hundred thirteen M. tuberculosis isolates were tested. The nucleotide sequences of the katG and inhA genes and the mabA-inhA promoter region were also determined. The MTBDR assay detected 100% and 67% (n = 64) of the strains resistant to RIF and INH, respectively. Among the latter, 62 strains carried a Ser315Thr mutation in katG, 59 of them displaying a high level of resistance to INH. Two strains with a low level of INH resistance had a Ser315Asn mutation. No mutation was found by the MTBDR assay for 31 INH-resistant strains (33%), of which 24 showed a low level of resistance. By DNA sequencing, we found among them various mutations in the KatG protein for 7 strains, a C-->T mutation in position -15 of the mabA-inhA promoter in 17 strains, and a Ser94Ala mutation in InhA for 7 strains. In conclusion, the MTBDR assay, which fits easily in the workflow of a routine laboratory, enabled the detection of 100% of the RIF-resistant strains and 89% of the INH-resistant strains with a high level of resistance but only 17% of the strains characterized by a low level of INH resistance, indicating that the test can be used as a rapid method to detect in the same experiment the rifampin-resistant and the high-level isoniazid-resistant strains of M. tuberculosis.
IDH2 Mutations in Patients with d -2-Hydroxyglutaric Aciduria (2010)

Heterozygous somatic mutations in the genes encoding isocitrate dehydrogenase-1 and -2 (IDH1 and IDH2) were recently discovered in human neoplastic disorders. These mutations disable the enzymes' normal ability to convert isocitrate to 2-ketoglutarate (2-KG) and confer on the enzymes a new function: the ability to convert 2-KG to d-2-hydroxyglutarate (D-2-HG). We have detected heterozygous germline mutations in IDH2 that alter enzyme residue Arg(140) in 15 unrelated patients with d-2-hydroxyglutaric aciduria (D-2-HGA), a rare neurometabolic disorder characterized by supraphysiological levels of D-2-HG. These findings provide additional impetus for investigating the role of D-2-HG in the pathophysiology of metabolic disease and cancer.
ArrayTrack: a fine-grained indoor location system (2013)

With myriad augmented reality, social networking, and retail shopping applications all on the horizon for the mobile handheld, a fast and accurate location technology will become key to a rich user experience. When roam-ing outdoors, users can usually count on a clear GPS sig-nal for accurate location, but indoors, GPS often fades, and so up until recently, mobiles have had to rely mainly on rather coarse-grained signal strength readings. What has changed this status quo is the recent trend of dramat-ically increasing numbers of antennas at the indoor ac-cess point, mainly to bolster capacity and coverage with multiple-input, multiple-output (MIMO) techniques. We thus observe an opportunity to revisit the important prob-lem of localization with a fresh perspective. This paper presents the design and experimental evaluation of Ar-rayTrack, an indoor location system that uses MIMO-based techniques to track wireless clients at a very fine granularity in real time, as they roam about a building. With a combination of FPGA and general purpose com-puting, we have built a prototype of the ArrayTrack sys-tem. Our results show that the techniques we propose can pinpoint 41 clients spread out over an indoor office envi-ronment to within 23 centimeters median accuracy, with the system incurring just 100 milliseconds latency, mak-ing for the first time ubiquitous real-time, fine-grained location available on the mobile handset. 1
Thermal Management of Batteries in Advanced Vehicles Using Phase-Change Materials (2008)

Hybrid electric vehicles (HEVs) and plug-in hybrid electric vehicles (PHEVs) are promising technologies to help reduce the amount of petroleum consumed for transportation. In both HEVs and PHEVs, the battery pack is a key component to enabling their fuel savings potential. The battery is also one of the most expensive components in the vehicle. One of the most significant factors impacting both the performance and life of a battery is temperature. In particular, operating a battery at elevated temperatures reduces its life. It is therefore important to design and implement effective battery thermal management systems. This paper analyzes the suitability of phase-change material (PCM) for battery thermal management in HEV and PHEV systems. A prototype PCM/graphite matrix module (that was not fully optimized for HEV applications) was evaluated experimentally under geometric and vehicle-simulation-based drive cycles. The results were used to validate a thermal model. The model was then used to explore the benefits and limitations of PCM thermal management. This study suggests that PCM can provide a peak-temperature-limiting benefit in vehicle applications, but the overall battery thermal management solution must rely on active cooling or on limiting the battery’s power output (or both) to avoid high temperatures during continuous cycling. Ultimately, vehicle designers will need to weigh the potential increase in mass and cost associated with adding PCM to the thermal management system against the anticipated benefits: a smaller active cooling system, less need to limit battery power output in high-temperature conditions, and/or potentially reduced exposure to momentary or localized high cell temperatures.
Random noise attenuation using local signal-and-noise orthogonalization (2015)

ABSTRACT We have developed a novel approach to attenuate random noise based on local signal-and-noise orthogonalization. In this approach, we first removed from a seismic section using one of the conventional denoising operators and then applied a weighting operator to the initially denoised section to predict the signal-leakage energy, as well as retrieve it from the initial noise section. The weighting operator was obtained by solving a least-squares minimization problem via shaping regularization with a smoothness constraint. Next, the initially denoised section and the retrieved signal were combined to form the final denoised section. The proposed denoising approach corresponded to orthogonalizing the initially denoised signal and noise in a local manner. We evaluated the denoising performance using local similarity. To test the orthogonalization property of the estimated signal and noise, we calculated the local similarity map between the denoised signal section and removed noise section. Low values of local similarity indicated a good orthogonalization and thus a good denoising performance. Synthetic and field data examples revealed the effectiveness of the proposed approach in applications to noise attenuation for conventional and simultaneous-source seismic data.
Integrated cell and process engineering for improved transient production of a “difficult‐to‐express“ fusion protein by CHO cells (2015)

Based on an optimized electroporation protocol, we designed a rapid, milliliter-scale diagnostic transient production assay to identify limitations in the ability of Chinese hamster ovary (CHO) cells to produce a model "difficult-to-express" homodimeric Fc-fusion protein, Sp35Fc, that exhibited very low volumetric titer and intracellular formation of disulfide-bonded oligomeric aggregates post-transfection. As expression of Sp35Fc induced an unfolded protein response in transfected host cells, we utilized the transient assay to compare, in parallel, multiple functionally diverse strategies to engineer intracellular processing of Sp35Fc in order to increase production and reduce aggregation as two discrete design objectives. Specifically, we compared the effect of (i) co-expression of ER-resident molecular chaperones (BiP, PDI, CypB) or active forms of UPR transactivators (ATF6c, XBP1s) at varying recombinant gene load, (ii) addition of small molecules known to act as chemical chaperones (PBA, DMSO, glycerol, betaine, TMAO) or modulate UPR signaling (PERK inhibitor GSK2606414) at varying concentration, (iii) a reduction in culture temperature to 32°C. Using this information, we designed a biphasic, Sp35Fc-specific transient manufacturing process mediated by lipofection that utilized CypB co-expression at an optimal Sp35Fc:CypB gene ratio of 5:1 to initially maximize transfected cell proliferation, followed by addition of a combination of PBA (0.5 mM) and glycerol (1% v/v) at the onset of stationary phase to maximize cell specific production and eliminate Sp35Fc aggregation. Using this optimal, engineered process transient Sp35Fc production was significantly increased sixfold over a 12 day production process with no evidence of disulfide-bonded aggregates. Finally, transient production in clonally derived sub-populations (derived from parental CHO host) screened for a heritably improved capability to produce Sp35Fc was also significantly improved by the optimized process, showing that protein-specific cell/process engineering can provide a solution that exceeds the limits of genetic/functional diversity within heterogeneous host cell populations. .
A transmission gate physical unclonable function and on-chip voltage-to-digital conversion technique (2013)

A physical unclonable function (PUF) is an embedded integrated circuit (IC) structure that is designed to leverage naturally occurring variations to produce a random bitstring. In this paper, we evaluate a PUF which leverages resistance variations which occur in transmission gates (TGs) of ICs. We also investigate a novel on-chip technique for converting the voltage drops produced by TGs into a digital code, i.e., a voltage-to-digital converter (VDC). The analysis is carried out on data measured from chips subjected to temperature variations over the range of -40°C to +85°C and voltage variations of +/- 10% of the nominal supply voltage. The TG PUF and VDC produce high quality bitstrings that perform exceptionally well under statistical metrics including stability, randomness and uniqueness.