gebhart/patrepeval huggingface dataset:
Degradation of halogenated aliphatic compounds utilizing sequential anaerobic/aerobic treatments (2003)

The objective of this research was to determine if either methanogenic or sulfidogenic reductive dechlorination could survive an alternating anaerobic/aerobic sequence to biologically transform halogenated aliphatic hydrocarbons (HACs), specifically tetrachloroethylene (PCE), trichloroethylene (TCE), cis-1,2 dichloroethylene (cDCE), trans-1,2 dichloroethylene (tDCE), 1,1 dichloroethylene (1, 1DCE) and vinyl chloride (VC). This ability was considered to be a necessary prerequisite for complete anaerobic/aerobic mineralization of halogenated aliphatic hydrocarbons by a single microbial consortia. Chlorinated solvents, which are among the most common groundwater contaminants, have been partially dechlorinated using single-stage anaerobic environmental treatment strategies. Various types of bacteria typically reductively dechlorinate PCE and TCE to cDCE and VC in an anaerobic environment, including methanogens, sulfidogens, and homoacetogens. The problem lies in the fact that reductive dechlorination typically leads to an accumulation of daughter compounds (cDCE, VC) which are more toxic than their parent compounds (PCE, TCE). Furthermore, PCE and (to a lesser extent) TCE, are resistant to dechlorination in aerobic environments. In contrast, VC and cDCE are readily oxidized co-metabolically in an aerobic environment by methanotrophic bacteria, and others using oxygenases (e.g. toluene oxidizers). Results from this research showed that both methanogenic and sulfidogenic reductive dechlorination could resume after transient exposures to both oxygen and hydrogen peroxide (H2O2). In fact, for cycles as frequent as 10 days between aerobic treatment cycles, reductive dechlorination was observed to resume at rates at least as rapid as microcosms not exposed to aerobic treatments.
What is the most relevant standard of success in assisted reproduction?: Redefining success in the context of elective single embryo transfer: evidence, intuition and financial reality (2004)

Treatment-related multiple pregnancy poses the biggest threat to the safety of IVF. Despite a double embryo transfer (DET) policy in most European centres, twin rates continue to be unacceptably high, at 20-35%. Elective single embryo transfer (SET) is an effective way to minimize twin pregnancies, but the debate surrounding its routine clinical use continues. A review of the literature was undertaken in order to seek evidence about the effectiveness of SET, and identify barriers to its acceptance in clinical practice. Data from randomized controlled trials (RCTs) indicate that SET results in lower live birth rates per fresh IVF cycle (odds ratio 0.53; 95% confidence interval 0.31-0.89; P = 0.02) in comparison with DET. Data on cumulative live birth rates are unavailable from RCTs, although the expectation is that these are comparable in the two groups. SET is unlikely to be suitable for all women undergoing IVF and outcomes may be sensitive to different laboratory protocols. The perceived effectiveness of SET is influenced by the way existing evidence is interpreted. Other factors affecting the routine use of SET include laboratory techniques, individual preferences and funding issues.
[Expression of P27 protein in odontogenic tumors]. (1998)

The expression of P27 protein was investigated in 40 cases of odontogenic tumors by immunohistochemical S-P assay. The results showed that P27 expression varied in different types of odontogenic tumors. Positive signals were present in 17/20 (85.0%) of the malignant odontogenic tumors, but in 6/20 (30.3%) of the benign ones (P < 0.005). It was suggested that P27 protein had certain practical value in the differentiation diagnosis of odontogenic tumors.
Bone Marrow NK1.1− and NK1.1+ T Cells Reciprocally Regulate Acute Graft versus Host Disease (1999)

Sorted CD4(+) and CD8(+) T cells from the peripheral blood or bone marrow of donor C57BL/6 (H-2(b)) mice were tested for their capacity to induce graft-versus-host disease (GVHD) by injecting the cells, along with stringently T cell-depleted donor marrow cells, into lethally irradiated BALB/c (H-2(d)) host mice. The peripheral blood T cells were at least 30 times more potent than the marrow T cells in inducing lethal GVHD. As NK1.1(+) T cells represented <1% of all T cells in the blood and approximately 30% of T cells in the marrow, the capacity of sorted marrow NK1.1(-) CD4(+) and CD8(+) T cells to induce GVHD was tested. The latter cells had markedly increased potency, and adding back marrow NK1.1(+) T cells suppressed GVHD. The marrow NK1.1(+) T cells secreted high levels of both interferon gamma (IFN-gamma) and interleukin 4 (IL-4), and the NK1.1(-) T cells secreted high levels of IFN-gamma with little IL-4. Marrow NK1.1(+) T cells obtained from IL-4(-/-) rather than wild-type C57BL/6 donors not only failed to prevent GVHD but actually increased its severity. Together, these results demonstrate that GVHD is reciprocally regulated by the NK1.1(-) and NK1.1(+) T cell subsets via their differential production of cytokines.
Smooth muscle α‐actin expression and myofibroblast differentiation by TGFβ are dependent upon MK2 (2006)

Fibroblasts play a major role in processes such as wound repair, scarring, and fibrosis. Differentiation into myofibroblasts, characterized by upregulation of smooth muscle alpha-actin (smalpha) in response to profibrotic agents such as TGFbeta is believed to be an important step in fibrosis. Therefore, elucidating mechanisms of myofibroblast differentiation might reveal novel targets in treating diseases such as idiopathic pulmonary fibrosis (IPF). MK2 is a kinase substrate of p38 MAP kinase that mediates some effects of p38 activation on the actin cytoskeleton. Using mouse embryonic fibroblasts (MEF) from MK2 knockout (MK2(-/-)) mice, we demonstrate that disrupting expression of MK2 expression reduces filamentous actin and stress fibers. It also causes MK2(-/-) MEF to express less smalpha than their corresponding wild-type (WT) MEF at baseline and in response to TGFbeta. Furthermore, TGFbeta causes downregulation of smalpha in MK2(-/-) MEF, instead of upregulation observed in WT MEF. Expression of other fibroblast markers, such as collagen, is not altered in MK2(-/-) MEF. Our results further suggest that downregulation of smalpha in MK2(-/-) MEF is not due to lack of activation of serum responsive promoter elements, but probably due to reduced smalpha message stability in these cells. These results indicate that MK2 plays a key role in regulation of smalpha expression, and that targeting MK2 might present a therapeutic approach in managing conditions such as pulmonary fibrosis.
Structural determinants of ligand binding selectivity between the peroxisome proliferator-activated receptors (2001)

The peroxisome proliferator-activated receptors (PPARs) are transcriptional regulators of glucose, lipid, and cholesterol metabolism. We report the x-ray crystal structure of the ligand binding domain of PPAR alpha (NR1C1) as a complex with the agonist ligand GW409544 and a coactivator motif from the steroid receptor coactivator 1. Through comparison of the crystal structures of the ligand binding domains of the three human PPARs, we have identified molecular determinants of subtype selectivity. A single amino acid, which is tyrosine in PPAR alpha and histidine in PPAR gamma, imparts subtype selectivity for both thiazolidinedione and nonthiazolidinedione ligands. The availability of high-resolution cocrystal structures of the three PPAR subtypes will aid the design of drugs for the treatments of metabolic and cardiovascular diseases.
Targeting the Nogo Receptor Complex in Diseases of the Central Nervous System (2011)

After injury to the central nervous system intrinsic factors such as myelin associated inhibitory factors inhibit cellular and axonal regeneration resulting in permanent disability. Three of these factors (Nogo-A, oligodendrocyte myelin glycoprotein, myelin-associated glycoprotein) bind to a common receptor: the Nogo-66 receptor (NgR1). NgR1 is expressed mainly on neurons and is usually associated in a trimolecular complex. The second member of the complex, LINGO-1, is often connected to NgR1 function and is further found to function independently as a negative regulator of oligodendrocyte proliferation and differentiation. The third member of the NgR complex is either the p75 neurotrophin receptor, TROY, or an as yet unidentified co-receptor. Targeting of factors contained in this complex has been described to lead to the promotion of neurite outgrowth, oligodendrocyte proliferation and differentiation and inhibition of cell death. In the current review, we aim to describe the mechanisms of action of the chemical and biological compounds used in targeting NgR1 and LINGO-1. This will be achieved using three examples: blocking of ligand binding to NgR1 in treatment of spinal cord injury, antibody-mediated inhibition of LINGO-1 to promote oligodendrocyte differentiation in multiple sclerosis, and the use of soluble NgR1 to sequester Abeta peptide in the periphery in Alzheimer's disease.
Proposal of Ultrahigh Density Optical Disk System Using a Vertical Cavity Surface Emitting Laser Array (1998)

An ultrahigh density optical disk system of Tera bit/inch 2 is described. This system utilizes a vertical cavity surface emitting laser (VCSEL) diode array as a parallel optical beam source which can make the disk system more useful at a high data transfer rate and bit density using evanescent waves from each laser cavity. In order to avoid the diffraction limited restriction to the optical beam the near-field optics is adopted to the parallel beam optical head. 1 bit size on the surface of the disk is 10–20 nm in diameter. A polished glass disk substrate is deposited by either phase change medium or photon mode optical medium. The medium thickness of the disk is approximately 10–20 nm. The optical gap size between the surface of the medium and laser output windows of a VCSEL array head is controlled within 20 nm using contact head technology.
Frequency Comb Vernier Spectroscopy for Broadband, High-Resolution, High-Sensitivity Absorption and Dispersion Spectra (2007)

A femtosecond frequency comb provides a vast number of equidistantly spaced narrow band laser modes that can be simultaneously tuned and frequency calibrated with 15 digit accuracy. Our Vernier spectrometer utilizes all of theses modes in a massively parallel manner to rapidly record both absorption and dispersion spectra with a sensitivity that is provided by a high finesse broadband optical resonator and a resolution that is only limited by the frequency comb line width while keeping the required setup simple.
What is the cell surface receptor(s) for the different serotypes of botulinum neurotoxin? (1999)

The first step in the interaction of botulinum neurotoxin (BoNT) with target cells is its adherence to the cell surface. While the cell surface receptor(s) has not been unequivocably identified it does appear that different serotypes of BoNT may recognize different receptor(s). Gangliosides were the first molecules identified as potential BoNT receptors. However, more recent observations indicated that while gangliosides might affect binding they might not be the specific receptor. A protein component, either alone or in combination with gangliosides, may also be necessary. Evidence for the interaction of BoNT with specific cell surface molecules is presented and suggestions for future work to more completely define the receptor(s) are presented. Identification of the receptor(s) could lead to 1) development of inhibitors of the interaction, 2) better use of BoNT in the treatment of dystonias, and 3) use of BoNT in the targeting of drugs to the neuromuscular junction.
Structural, Electrochemical, and Photophysical Properties of Gallium(III) 5,10,15-Tris(pentafluorophenyl)corrole (2000)

High quantum yields are found for the prototype metallocorrole 1, which is readily prepared from GaCl3 and tris(pentafluorophenyl)corrole. The crystallographic and electronic structures of 1 are reported as well as the simple generation of its π-cation radical complex by chemical oxidation and the characteristic spectroscopic features of this ion.
Cyclosporine for Plaque-Type Psoriasis (1991)

Cyclosporine therapy leads to a rapid and thorough clearing of psoriasis; an initial dose of 5 mg per kilogram per day seems to be appropriate. However, the safety of cyclosporine for the long-term treatment of psoriasis remains to be determined.
Lactoferrin, a Potent Tryptase Inhibitor, Abolishes Late-Phase Airway Responses in Allergic Sheep (1997)

Tryptase, a serine protease released exclusively from activated mast cells, has been implicated as a potential causative agent in asthma. Enzymatically active tryptase is comprised of four subunits, and heparin stabilizes the associated tetramer. Lactoferrin, a cationic protein released from activated neutrophils, binds tightly to heparin, therefore we investigated lactoferrin as an inhibitor of tryptase and found that it is both a potent (Ki' is 24 nM) and selective inhibitor. Size exclusion chromatography studies revealed that lactoferrin disrupted the quaternary structure of active tryptase. Lactoferrin was tested in an allergic sheep model of asthma; aerosolized lactoferrin (10 mg in 3 ml phosphate-buffered saline, 0.5 h before as well as 4 and 24 h after inhalation challenge by Ascaris suum) abolished both late-phase bronchoconstriction (no significant increase in specific lung resistance 4 to 8 h following provocation, p < 0.05 versus vehicle treatment) and airway hyperresponsiveness (no detectable increase in airway sensitivity to carbachol challenge 24 h after antigen challenge, p < 0.05 versus vehicle). These data suggest tryptase involvement in both late-phase bronchoconstriction and airway hyperreactivity and furthermore suggest that a physiological function of neutrophil lactoferrin is the inhibition of tryptase released from mast cells.
Characterization of cardiac troponin subunit release into serum after acute myocardial infarction and comparison of assays for troponin T and I (1998)

We examined the release of cardiac troponin T (cTnT) and I (cTnI) into the blood of patients after acute myocardial infarction (AMI). Three postAMI serum samples were applied in separate analytical runs onto a calibrated gel filtration column (Sephacryl S-200), and the proteins were separated by molecular weight. Using commercial cTnT and cTnI assays measured on collected fractions, we found that troponin was released into blood as a ternary complex of cTnT-I-C, a binary complex of cTnI-C, and free cTnT, with no free cTnI within the limits of the analytical methodologies. The serum samples were also examined after incubation with EDTA and heparin. EDTA broke up troponin complexes into individual subunits, whereas heparin had no effect on the assays tested. We added free cTnC subunits to 24 AMI serum samples and found no marked increase in the total cTnI concentrations, using an immunoassay that gave higher values for the cTnI-C complex than free cTnI. To characterize the cross-reactivity of cTnT and cTnI assays, purified troponin standards in nine different forms were prepared, added to serum and plasma pools, and tested in nine quantitative commercial and pre-market assays for cTnI and one approved assay for cTnT. All nine cTnI assays recognized each of the troponin I forms (complexed and free). In five of these assays, the relative responses for cTnI were nearly equimolar. For the remainder, the response was substantially greater for complexed cTnI than for free cTnI. Moreover, there was a substantial difference in the absolute concentration of results between cTnI assays. The commercial cTnT assay recognized binary and ternary complexes of troponin on a near equimolar basis. We conclude that all assays are useful for detection of cardiac injury. However, there are differences in absolute cTnI results due to a lack of mass standardization and heterogeneity in the cross-reactivities of antibodies to various troponin I forms.
In Vitro Production and Screening of DNA Polymerase η Mutants for Catalytic Diversity (2002)

Mutant DNA polymerases have become an increasingly important tool in biotechnology. The ability to examine the activity and specific properties of enzymes has a crucial role in the characterization of the enzyme. We have developed several systems for characterizing DNA polymerases that combine random mutagenesis with in vivo selection systems. However in vivo screening systems for specific properties are sometimes unavailable. The ability to quickly screen for polymerase activity has many applications, including the identification of compounds that can inhibit polymerase activity, identifying the properties of newly discovered polymerases, and engineering new biological properties into existing polymerases. These applications can both expand the knowledge of the basic science of polymerases and can further industrial efforts to identify new drugs that specifically target polymerase activity. Here we present a high-throughput in vitro assay to select for active polymerases. We show the applicability of this assay by measuring the level of activity for a set of in vitro synthesized polymerase mutants and by screening for the incorporation of a fluorescent nucleotide analog by DNA polymerases.
8-Chloro-1-methyl-6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepines with substituents at C-4 (1980)

A series of 8-chloro-1-methyl-6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepines with substituents at C-4 was prepared and evaluated for antianxiety potential. It was found that substitution at this position generally decreased the activity in this series.
Synthesis and Structure–Activity Relationships of FAAH Inhibitors: Cyclohexylcarbamic Acid Biphenyl Esters with Chemical Modulation at the Proximal Phenyl Ring (2005)

Fatty acid amide hydrolase (FAAH) is a serine hydrolase that catalyzes the intracellular hydrolysis of fatty acid ethanolamides such as anandamide and oleoylethanolamide. Targeting this enzyme may have important therapeutic potentials owing to the multiple physiological roles of these amides. Cyclohexylcarbamic acid biphenyl-3-yl ester (URB524) was one of the most promising FAAH inhibitors so far described. We report the modulation of the electronic and steric features of the proximal phenyl ring of this compound by introducing a series of substituents at the ortho and para positions. pIC50 values were found to correlate with molecular features thought to be involved in the recognition step such as steric hindrance and hydrogen-bonding ability. Derivatives with small polar groups at the para position of the proximal phenyl ring were slightly better FAAH inhibitors than the parent compound URB524.
Performance of MIMO systems with channel inversion (2003)

The paper discusses channel inversion which is a spatial equalization technique when channel state information is available at the transmitter. Channel inversion is a straightforward concept without iterations and it might be useful when the data transmission is critical with time e.g. high data rate applications. We discuss performance degradation caused by channel estimation errors, clipping due to the limited range of the transmitted power and the effect of cochannel interference. These results give an insight into the technical constraints of this transmission technique and show how these critical issues can be limited or reduced.
Identification of linear epitopes on Semliki Forest virus E2 membrane protein and their effectiveness as a synthetic peptide vaccine (1991)

Semliki Forest virus (SFV) infection of mice was used as a model to study the applicability of synthetic peptides containing only linear epitopes as viral vaccines. The identification of linear epitopes with vaccine potential on the E2 membrane protein of SFV was based on the binding of SFV-specific antibodies to a set of overlapping synthetic hexapeptides (Pepscan) representing the whole E2 amino acid sequence. The 14 available E2-specific monoclonal antibodies which were protective in vivo proved to be unsuitable for the identification of linear epitopes because they recognized only conformational epitopes, as indicated by their lack of reactivity with unfolded, reduced E2 protein on immunoblots. Three epitopes were detected with polyclonal anti-SFV serum at amino acid positions 135 to 141, 177 to 185 and 240 to 246 of the E2 protein. Synthetic peptides containing these epitopes were coupled to a carrier protein and tested as a vaccine. Mice immunized with the peptide containing amino acids 240 to 255 of protein E2 were protected against a challenge with virulent SFV but protection of mice immunized with the peptides containing amino acids 126 to 141 or 178 to 186 was only marginally better than that of controls. The prechallenge sera of most peptide-immunized mice reacted with SFV-infected cells but none of these sera neutralized the virus in vitro. However, protection of mice correlated well with SFV-specific antibody titre, suggesting antibody-mediated protection.
A Proteoglycan Related to the Urinary Trypsin Inhibitor (UTI) Links the two Heavy Chains of Inter-α-Trypsin Inhibitor (1989)

cDNA studies have suggested that inter-alpha-trypsin inhibitor (ITI) is a complex of several different peptide chains; the sequence of the inhibitory part of ITI is in excellent agreement with that of the urinary trypsin inhibitor (UTI). The present report demonstrates that a compound immunologically related to UTI is released by digestion with porcine pancreatic elastase or human leucocyte elastase. Since UTI has been shown to be a proteoglycan, ITI has been treated by chondroitinase. In these conditions, ITI is dissociated and gives rise to two heavy chains (78 and 85 kDa) and one light chain (26 kDa) immunologically related to UTI and which in PAGE moves close to UTIc (produced by chondroitinase treatment of UTI). We suggest that ITI is a non-covalent complex comprising two heavy chains and one light chain immunologically related to UTI and which is also a proteoglycan.
Chemotherapy targeted to tumor vasculature (1998)

Vasculature-targeted chemotherapy--the destruction of tumor blood vessels with cytotoxic agents--makes use of biochemical differences between angiogenic and resting blood vessels. This approach may minimize or eliminate some of the problems associated with conventional solid-tumor targeting, such as poor tissue penetration and drug resistance. Experiments with antiangiogenic and thrombotic factors have shown that eliminating tumor blood supply has dramatic antitumor effects in mice. Targeting chemotherapeutic agents to the tumor vasculature combines the blood vessel destruction with the usual antitumor activities of the drug, resulting in increased efficacy and reduced toxicity in experiments with tumor-bearing mice. Human clinical trials, which are soon to follow, will determine the final value of this approach.