gebhart/patrepeval huggingface dataset:
The history of the International Journal of Technology Assessment in Health Care (2009)

The 1970s and early 1980s was the period in which high technology medicine became dominant. It had begun in the late 1950s with the introduction of effective artificial respiratory technology. This gave physicians, patients, and families the hope that the threats to fundamental life processes such as breathing could be countered by technology, and the dilemma of both meeting its costs and the ethical challenges of how to remove it when its use no longer produced benefits.
A hyaluronidase activity of the sperm plasma membrane protein PH-20 enables sperm to penetrate the cumulus cell layer surrounding the egg. (1994)

A typical mammalian egg is surrounded by an outer layer of about 3,000 cumulus cells embedded in an extracellular matrix rich in hyaluronic acid. A current, widely proposed model is that the fertilizing sperm, while it is acrosome intact, passes through the cumulus cell layer and binds to the egg zona pellucida. This current model lacks a well-supported explanation for how sperm penetrate the cumulus layer. We report that the sperm protein PH-20 has a hyaluronidase activity and is present on the plasma membrane of mouse and human sperm. Brief treatment with purified, recombinant PH-20 can release all the cumulus cells surrounding mouse eggs. Acrosome intact mouse sperm incubated with anti-PH-20 antibodies can not pass through the cumulus layer and thus can not reach the zona pellucida. These results, indicating that PH-20 enables acrosome intact sperm to penetrate the cumulus barrier, reveal a mechanism for cumulus penetration, and thus provide the missing element in the current model.
Synthesis of Star Polymers by A New “Core-First” Method:  Sequential Polymerization of Cross-Linker and Monomer (2008)

Star polymers containing a highly cross-linked core and many arms were synthesized by sequential polymerization of cross-linker and monomer. This novel method, termed as “star from in situ generated core”, belongs to the category of “core-first” method and presents an alternative strategy for star synthesis when compared to the traditional “arm-first” method, in which monomer is polymerized first before cross-linker. To illustrate this new concept for the synthesis of star polymers by using controlled radical polymerization techniques, atom transfer radical polymerization was applied for homopolymerization of ethylene glycol diacrylate (EGDA) to generate a multifunctional cross-linked core (nanogel). At high cross-linker conversion, monovinyl monomers were added into the system and polymerized from the polyEGDA nanogel macroinitiator (MI) to form the star arms. By use of different acrylate monomers, including methyl acrylate, n-butyl acrylate, and tert-butyl acrylate, star polymers with different arm chemical compositions were successfully synthesized. Several parameters affected the star structures, such as the initial concentration of cross-linker, the molar ratio of cross-linker to initiator, and the addition moment of monovinyl monomer. The star polymers preserved the initiating sites at the chain ends, and they were further used as star MIs for arm extension by polymerization of a second monovinyl monomer to form a star block copolymer.
All‐Optical Integrated Logic Operations Based on Chemical Communication between Molecular Switches (2008)

Molecular logic gates process physical or chemical "inputs" to generate "outputs" based on a set of logical operators. We report the design and operation of a chemical ensemble in solution that behaves as integrated AND, OR, and XNOR gates with optical input and output signals. The ensemble is composed of a reversible merocyanine-type photoacid and a ruthenium polypyridine complex that functions as a pH-controlled three-state luminescent switch. The light-triggered release of protons from the photoacid is used to control the state of the transition-metal complex. Therefore, the two molecular switching devices communicate with one another through the exchange of ionic signals. By means of such a double (optical-chemical-optical) signal-transduction mechanism, inputs of violet light modulate a luminescence output in the red/far-red region of the visible spectrum. Nondestructive reading is guaranteed because the green light used for excitation in the photoluminescence experiments does not affect the state of the gate. The reset is thermally driven and, thus, does not involve the addition of chemicals and accumulation of byproducts. Owing to its reversibility and stability, this molecular device can afford many cycles of digital operation.
Synthesis and evaluation of N,N'-bis(arylsulfonyl)hydrazines as antineoplastic agents (1985)

Several N,N'-bis(arylsulfonyl)hydrazines, with the potential to function as biological methylating agents, were synthesized and evaluated for antineoplastic activity against the L1210 leukemia and other transplanted rodent tumors. In general, the N-methyl-N,N'-bis(arylsulfonyl)hydrazines that possess the capacity to generate an alkylating species under physiological conditions showed significant antineoplastic activity, while N,N'-bis(phenylsulfonyl)-hydrazine and N-methyl-N,N'-dibenzoylhydrazine were inactive.
Regulation of Airway and Alveolar Epithelial Cell Apoptosis by p53-Induced Plasminogen Activator Inhibitor-1 during Cigarette Smoke Exposure Injury (2012)

Increased expression of tumor suppressor protein p53 and of plasminogen activator inhibitor (PAI)-1 is associated with cigarette smoke (CS) exposure-induced lung epithelial injury. p53 induces PAI-1 through mRNA stabilization in lung epithelial cells. However, it is unclear how this process affects lung epithelial damage. Here, we show that CS induces p53 and PAI-1 expression and apoptosis in cultured Beas2B and primary alveolar type (AT)II cells. CS exposure augmented binding of p53 protein with PAI-1 mRNA. Inhibition of p53 from binding to PAI-1 mRNA through expression of p53-binding 70 nt PAI-1 mRNA 3'UTR sequences suppressed CS-induced PAI-1 expression. Treatment of Beas2B cells with caveolin-1 scaffolding domain peptide (CSP) suppressed p53 expression and p53-PAI-1 mRNA interaction. These changes were associated with parallel inhibition of CS-induced PAI-1 expression and apoptosis in Beas2B cells. Wild-type mice exposed to passive CS likewise show augmented p53 and PAI-1 with parallel induction of ATII cell apoptosis, whereas mice deficient for p53 or PAI-1 expression resisted apoptosis of ATII cells. CSP suppressed CS-induced ATII cell apoptosis in wild-type mice and abrogated p53-PAI-1 mRNA interaction with parallel inhibition of p53 and PAI-1 expression. The protection against ATII cell apoptosis by CSP involves inhibition of passive CS-induced proapoptotic Bax and Bak expression and restoration of the prosurvival proteins Bcl-X(L). These observations demonstrate that inhibition of p53 binding to PAI-1 mRNA 3'UTR attenuates CS-induced ATII cell apoptosis. This presents a novel link between p53-mediated PAI-1 expression and CS-induced ATII cell apoptosis.
An experimental 2-bit/cell storage DRAM for macro cell or memory-on-logic application (2003)

A novel multiple-level storage DRAM (dynamic random-access memory) technique which obtains fairly fast access time is presented. The RAM area, especially the cell-array area, which is highly defect-sensitive, is reduced with this technique. Reasonable yield can thus be achieved. An experimental 1-Mb DRAM has been fabricated, and the 2-bit/cell storage technique has been verified to be suitable for macro-cell or memory-on-logic application.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Prevalence of Methicillin-ResistantStaphylococcus aureusin a Combat Support Hospital in Iraq (2011)

Methicillin-resistant Staphylococcus aureus (MRSA) in health-care settings results in life-threatening infections. We examined the incidence of MRSA at the combat support hospital located at the Ibn Sina Hospital in Baghdad, Iraq. We compiled isolate data from 2005 to 2009 characterizing antibiotic susceptibilities, annual trends, patient populations, infection sites, and hospital locations. Approximately 46.1% of S. aureus were MRSA, with increase in numbers of yearly isolates. MRSA was isolated in higher numbers from U.S. military personnel. Non-U.S. patient isolates displayed higher antibiotic susceptibility compared to U.S. military personnel isolates. Outpatient clinic, forward operating bases, and intermediate care ward 1 isolated the most MRSA. Common isolation sites were wound and skin cultures. Community-acquired MRSA was likely present in 291 out of 303 isolates based on antibiotic susceptibility. Our data suggests that most MRSA were community-acquired with limited nosocomial spread. We recommend increases in combat support hospital molecular lab capability to rapidly identify both MRSA categories.
ChemInform Abstract: Stereospecific Nucleophilic Addition Reaction of Thiophenol to α,β‐Unsaturated Esters. (1990)

Abstract The unsaturated esters and lactones (I) react with excess thiophenol (II) in the presence of lithium thiophenoxide to yield predominantly the trans‐adducts (III).
Molecular composition and biological activity of commercial birch pollen allergen extracts (2009)

Commercial birch pollen extracts exhibit a considerable variability regarding allergen contents and hence deliver varying in vivo test results. These problems might be overcome with recombinant allergen-based preparations.
The heparin-binding domain of extracellular superoxide dismutase C and formation of variants with reduced heparin affinity. (1992)

A fundamental property of the secretory tetrameric extracellular superoxide dismutase (EC-SOD) is its affinity for heparin and analogues, in vivo, mediating attachment to heparan sulfate proteoglycans located on cell surfaces and in the connective tissue matrix. EC-SOD is in vivo heterogeneous with regard to heparin affinity and can be divided into subclasses; A which lacks heparin affinity, B with intermediate affinity, and C with strong heparin affinity. The EC-SOD C subunits contain 222 amino acids and among the last 20 carboxyl-terminal amino acids, 10 are positively charged and six of these are located in a cluster in positions 210-215. To analyze if this local accumulation of basic amino acids is responsible for heparin binding we produced three series of recombinant EC-SOD (rEC-SOD) variants, six containing amino acid exchanges in the carboxyl-terminal end, four with truncations, and two with both truncations and substitutions. Exchange of positively or negatively charged amino acids on the carboxyl-terminal side of the cluster results in only minor modifications in heparin affinity, whereas substitution of three of the amino acids in the cluster abrogates the heparin binding. Insertions of stop codons at different positions resulted in either C or A but not B class EC-SOD. In an attempt to produce EC-SODs with intermediate heparin affinities, plasmids defining C and A class EC-SOD were cotransfected into Chinese hamster ovary cells. In addition to the parental A and C class EC-SOD forms, two variants with intermediate heparin affinities were formed. Coincubation of EC-SOD C and A resulted in the appearance of one heterotetramer with intermediate affinity for heparin. We conclude that the cluster of six basic amino acids forms the essential part of the heparin-binding domain and that the composition of the four subunits in the EC-SOD tetramer determines the affinity for heparin. This domain is different from heparin-binding domains of other proteins, and its localization allows the distribution of EC-SOD in vivo to be regulated by proteolytic processing.
Persistence of platelet thrombus formation in arterioles of mice lacking both von Willebrand factor and fibrinogen (2000)

We used intravital microscopy to observe the formation of platelet plugs in ferric chloride-injured arterioles of live mice. With this model, we evaluated thrombus growth in mice lacking von Willebrand factor (vWF) and fibrinogen (Fg), the two key ligands known to mediate platelet adhesion and aggregation. In vWF(-/-) mice, despite the presence of arterial shear, delayed platelet adhesion occurred and stable thrombi formed. In many mice, a persisting high-shear channel never occluded. Abundant thrombi formed in Fg(-/-) mice, but they detached from the subendothelium, which ultimately caused downstream occlusion in all cases. Surprisingly, mice deficient in both vWF and Fg successfully formed thrombi with properties characteristic of both mutations, leading to vessel occlusion in the majority of vessels. Platelets of these doubly deficient mice specifically accumulated fibronectin in their alpha-granules, suggesting that fibronectin could be the ligand supporting the platelet aggregation.
HLA-A2.1–restricted Education and Cytolytic Activity of CD8+ T Lymphocytes from β2 Microglobulin (β2m) HLA-A2.1 Monochain Transgenic H-2Db β2m Double Knockout Mice (1997)

Three different HLA-A2.1 monochains were engineered in which either the human or mouse beta2-microglobulin (beta2m) is covalently linked to the NH2 terminus of the heavy chain by a 15- amino acid long peptide: HHH, entirely human, HHD, with the mouse H-2Db alpha3, transmembrane, and cytoplasmic domains, and MHD, homologous to HHD but linked to the mouse beta2mb. The cell surface expression and immunological capacities of the three monochains were compared with transfected cells, and the selected HHD construct was introduced by transgenesis in H-2Db-/- beta2m-/- double knockout mice. Expression of this monochain restores a sizable peripheral CD8(+) T cell repertoire essentially educated on the transgenic human molecule. Consequently, infected HHD, H-2Db-/- beta2m-/- mice generate only HLA-A2.1-restricted CD8(+) CTL responses against influenza A and vaccinia viruses. Interestingly, the CTL response to influenza A virus is mostly, if not exclusively, directed to the 58-66 matrix peptide which is the HLA-A2.1-restricted immunodominant epitope in humans. Such mice might constitute a versatile animal model for the study of HLA-A2.1-restricted CTL responses of vaccine interest.
Abrogation of an S-phase checkpoint and potentiation of camptothecin cytotoxicity by 7-hydroxystaurosporine (UCN-01) in human cancer cell lines, possibly influenced by p53 function. (1997)

7-Hydroxystaurosporine (UCN-01) is a selective protein kinase C inhibitor in clinical trial for cancer treatment. In this study, we found that nanomolar concentrations of camptothecin (CPT), a topoisomerase I inhibitor, arrest or delay cell cycle progression during the S and G2 phases in p53 mutant human colon carcinoma HT29 cells and that UCN-01 abrogates the S-phase arrest or delay induced by CPT. Under these conditions, CPT increased cyclin A levels and cyclin A/cyclin-dependent kinase 2 activity. UCN-01 prevented the increase of cyclin A/cyclin-dependent kinase 2 activity induced by CPT and enhanced Cdc2 kinase activity. Replication protein A (RPA2) was hyperphosphorylated after CPT treatment, and this effect was also abrogated by UCN-01. UCN-01 potentiated the cytotoxicity of CPT and reduced by 6-fold the concentration of CPT required to kill 50% of the HT-29 cells, as determined by clonogenic assays. This effect was observed at concentrations of UCN-01 that alone were not cytotoxic and had no detectable effect on cell cycle progression. UCN-01 markedly potentiated the cytotoxicity of CPT also in HCT116/E6 and MCF-7/ADR cells defective for p53 function, whereas significantly less potentiation was observed in p53-wild-type HCT116 and MCF-7 cells. These results suggest the existence of an S-phase checkpoint that delays replication and that may extend the time available for DNA repair. Thus, pharmacological abrogation of CPT-induced S- and G2-phase checkpoints by UCN-01 may provide an effective strategy for enhancing the chemotherapeutic activity of CPT, particularly against p53-defective tumors.
Wavelength-tunable optical filters: applications and technologies (1989)

The authors review noncoherent, frequency-tunable filter (receiver) technologies. They describe three basic mechanisms of wavelength filtering: filters that are based on the wavelength dependence of interferometric phenomena, with emphasis on Fabry-Perot interferometer filters; filters that are based on the wavelength dependence of coupling between optical fields (modes) induced by external perturbations (both acoustooptic and electrooptic filters are described); and filters that are based on resonant amplification of optical signals in semiconductor laser diode devices (these devices provide gain in addition to wavelength selectivity). For each technology the authors explain briefly the principles of operation and quantify the relevant system parameters: tuning range, channel separation, number of channels, crosstalk isolation, gain and distortion, speed of wavelength tuning, and complexity. They present a unified picture of filtering mechanisms in an appendix.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Optical chromatography. A new tool for separation of particles (1998)

n 1906 Tswett reported on a separation technique which is now called ch ro m at ograp hy This classical ch romatography involves the adsorption (or extraction) of a substance to the stationary phase. The analyte can then be eluted from the stationary phase by passing a solvent, which desorbs the analyte from the support , t h e reby affecting a s ep a ration. Chro m at ograp hy has been studied and widely used by many researchers. In practical analysis, chromatography is frequently employed for purification of the sample and for separation of the components before spectrometric determination. Chromatography, however, has several limitations that have not yet been overcome.
Potential of using lactic acid bacteria for therapy and immunomodulation in man (1993)

There is in 1993 no proven medical indication of lactic acid bacteria (LAB) for therapy or immunomodulation in man. However, within the bulk of publications, rigorous trials have now opened rational fields of research on beneficial effects of LAB. These include lactose digestion, cholesterol metabolism, diarrheal disorders, prophylaxis of intestinal or urogenital infections, immunomodulation or even oral vaccination. We try here to analyse these studies, considering LAB as pharmacological agents, and conclude that pursuit of research could be promising for ecological therapy of mucosal diseases, and for development of original and flexible vectors for targeting in the gastrointestinal tract.
Detection of P2Y14 protein in platelets and investigation of the role of P2Y14 in platelet function in comparison with the EP3 receptor (2008)

mRNA encoding the recently discovered P2Y(14) receptor has been reported in platelets, but the presence of P2Y(14) receptor protein and its functionality have not been studied. If P2Y(14) is expressed along with P2Y(1) and P2Y(12) receptors it may have a role in haemostasis. It was the objective of this study to investigate the presence of the P2Y(14) receptor in platelets and its role in platelet function. The effects of the agonist UDP-glucose were compared with those of sulprostone, a selective EP(3) receptor agonist. Expression of P2Y(14) receptor was investigated by immunoblotting and confocal microscopy. Platelet aggregation in platelet-rich plasma (PRP) and whole blood was measured using light absorbance and platelet counting. VASP phosphorylation was investigated using flow cytometry. Immunoblotting provided evidence for P2Y(14) receptor protein and microscopy confirmed its presence on platelets. Despite this, UDP-glucose (up to 100 muM) did not induce platelet aggregation in either PRP or whole blood, and did not potentiate aggregation induced by other agonists. P2Y(14) did not substitute for P2Y(12) in experiments using the P2Y(12) antagonist AR-C69931. No effect of UDP-glucose was seen on adenylate cyclase activity as measured by VASP phosphorylation. In contrast, sulprostone acting via the EP(3) receptor promoted platelet aggregation with effects on adenylate cyclase activity. EP(3) also partially substituted for P2Y(12) receptor. We have demonstrated the presence of P2Y(14) receptor protein in platelets, but no contribution of this receptor to several measures of platelet function has been observed. Further studies are necessary to determine whether the P2Y(14) receptor in platelets has any functionality.
Wrong-path instruction prefetching (1996)

Instruction cache misses can severely limit the performance of both superscalar processors and high speed sequential machines. Instruction prefetch algorithms attempt to reduce the performance degradation by bringing lines into the instruction cache before they are needed by the CPU fetch unit. There have been several algorithms proposed to do this, most notably next line prefetching and target prefetching. We propose a new scheme called wrong-path prefetching which combines next-line prefetching with the prefetching of all control instruction targets regardless of the predicted direction of conditional branches. The algorithm substantially reduces the cycles lost to instruction cache misses while somewhat increasing the amount of memory traffic. Wrong-path prefetching performs better than the other prefetch algorithms studied in all of the cache configurations examined while requiring little additional hardware. For example, the best wrong-path prefetch algorithm can result in a speed up of 16% when using an 8 K instruction cache. In fact, an 8 K wrong-path prefetched instruction cache is shown to achieve the same miss rate as a 32 K non-prefetch cache. Finally, it is shown that wrong-path prefetching is applicable to both multi-issue and long L1 miss latency machines.
Selective inhibition of mutant Ha-ras mRNA expression by antisense oligonucleotides. (1992)

A biological reporter gene assay was employed to determine the crucial parameters for maximizing selective targeting of a Ha-ras codon 12 point mutation (G----T) using phosphorothioate antisense oligonucleotides. We have tested a series of oligonucleotides ranging in length between 5 and 25 bases, each centered around the codon 12 point mutation. Our results indicate that selective targeting of this point mutation can be achieved with phosphorothioate antisense oligonucleotides, but this selectivity is critically dependent upon oligonucleotide length and concentration. The maximum selectivity observed in antisense experiments, 5-fold for a 17-base oligonucleotide, was closely predicted by a simple thermodynamic model that relates the fraction of mutant to wild type target bound as a function of oligonucleotide concentration and affinity. These results suggest thermodynamic analysis of oligonucleotide/target interactions is useful in predicting the specificity that can be achieved by an antisense oligonucleotide targeted to a single base point mutation.