gebhart/patrepeval huggingface dataset:
Response to Rituximab: Has the Original Hypothesis Been Confirmed? (2014)

Before the use of rituximab, the strongest accepted evidence for an association between B-cells and rheumatoid arthritis (RA) was that clinical disease was associated with serum autoantibodies. The ability to remove B-cells with rituximab has also revealed the relative importance of the different immunological parameters that underlie the clinical symptoms of RA. First, seropositive patients have a significantly more predictable and favorable clinical response to rituximab than seronegative patients. Second, the kinetics of the clinical response, with a delay of weeks or months after depletion, suggest that it is a B-cell product (autoantibody) and not B-cells per se that need to be reduced for remission to occur. Third, removal of B-cells from joints may not be closely associated with clinical improvement, although maintenance of plasma cell counts in joints has been associated with poorer responses. The requirement of 'new' B-cells generated from the bone marrow for relapse to occur suggests that selection of autoreactive B-cell clones in the periphery may also be necessary for their survival and differentiation into autoantibody-producing cells. The initial hypothesis suggested that the autoimmune response underlying the pathogenesis of RA was self-sustaining. This would seem to be confirmed, as relapse inevitably follows a variable period of reduced clinical symptoms induced by rituximab. In addition, a dominant role for autoantibodies seems to have strong support from clinical practice. In addition to their possible role in the pathogenesis of RA in the form of immune complexes, further investigation is necessary to determine whether autoantibodies contribute to perpetuation of changes in central B-cell tolerance in these patients.
Perspectives in Alkaline Phosphatase Research (1992)

Gene cloning and site-directed mutagenesis have had a profound effect on alkaline phosphatase research. Four distinct structural genes encoding placental, intestinal, and tissue-nonspecific isoenzymes have been cloned, sequenced, and mapped to human chromosomes. Differences in properties between the respective gene products are due to variations in primary structure involving only one, or a few, key amino acid residues. Recognition that alkaline phosphatase belongs to the category of molecules that are localized to cell membranes through a COOH-terminal glycan-phosphatidylinositol anchor provides a basis for understanding the generation of isoforms observed in plasma in disease. Isoforms produced by differential cleavage or preservation of the glycan-phosphatidylinositol anchor may offer new correlations with disease that are of diagnostic value. However, a more important contribution of alkaline phosphatase research to clinical chemistry may prove to be an increased understanding of disease processes at the molecular level.
T Cell Receptor-Independent Basal Signaling via Erk and Abl Kinases Suppresses RAG Gene Expression (2003)

Signal transduction pathways guided by cellular receptors commonly exhibit low-level constitutive signaling in a continuous, ligand-independent manner. The dynamic equilibrium of positive and negative regulators establishes such a tonic signal. Ligand-independent signaling by the precursors of mature antigen receptors regulates development of B and T lymphocytes. Here we describe a basal signal that controls gene expression profiles in the Jurkat T cell line and mouse thymocytes. Using DNA microarrays and Northern blots to analyze unstimulated cells, we demonstrate that expression of a cluster of genes, including RAG-1 and RAG-2, is repressed by constitutive signals requiring the adapter molecules LAT and SLP-76. This TCR-like pathway results in constitutive low-level activity of Erk and Abl kinases. Inhibition of Abl by the drug STI-571 or inhibition of signaling events upstream of Erk increases RAG-1 expression. Our data suggest that physiologic gene expression programs depend upon tonic activity of signaling pathways independent of receptor ligation.
Enhanced Rate Response Algorithm for Orthostatic Compensation Pacing (2000)

Upon orthostatic stress after a period of rest, the heart rate increases rapidly to maintain cardiac output and minimize the fall in arterial pressure. Pacemaker patients are often prone to a deficient response to orthostatic stress. This may cause lightheadedness and, in rare patients with autonomic dysfunction, syncope. To alleviate these undesirable consequences, an enhanced rate response algorithm was developed using an accelerometer. The pacemaker generates two signals from its accelerometer: instantaneous activity level (Act) and long-term change in activity level (ActVar). Low values of both Act and ActVar indicate a resting state. An increase in Act while ActVar remains low indicates the onset of motion after prolonged rest. Upon detecting this transition, the algorithm increases the pacing rate to a programmable orthostatic compensation rate for a programmable duration. A taped-on pacemaker with this algorithm was evaluated in three healthy women and two healthy men, 36 +/- 8 years of age. Electrocardiogram and ventricular pacing pulses were recorded by a 24-hour ambulatory system. Each trigger of the orthostatic compensation rate was verified against a > 10 beats/min increase in heart rate, a response classified as appropriate. The overall specificity of the algorithm among the five subjects was 78%. The nocturnal specificity (10 PM to 7 AM) was 98%, considerably higher than during daytime (72%). In conclusion, a pacing algorithm to alleviate orthostatic stress was developed, which was highly specific during the night hours.
Underdetermined Convolutive Blind Source Separation via Frequency Bin-Wise Clustering and Permutation Alignment (2010)

This paper presents a blind source separation method for convolutive mixtures of speech/audio sources. The method can even be applied to an underdetermined case where there are fewer microphones than sources. The separation operation is performed in the frequency domain and consists of two stages. In the first stage, frequency-domain mixture samples are clustered into each source by an expectation-maximization (EM) algorithm. Since the clustering is performed in a frequency bin-wise manner, the permutation ambiguities of the bin-wise clustered samples should be aligned. This is solved in the second stage by using the probability on how likely each sample belongs to the assigned class. This two-stage structure makes it possible to attain a good separation even under reverberant conditions. Experimental results for separating four speech signals with three microphones under reverberant conditions show the superiority of the new method over existing methods. We also report separation results for a benchmark data set and live recordings of speech mixtures.
Ligand-based targeted therapy: a novel strategy for hepatocellular carcinoma (2016)

Hepatocellular carcinoma (HCC) is the most common primary liver cancer with high morbidity and mortality worldwide. Chemotherapy is recommended to patients with intermediate or advanced stage cancer. However, the conventional chemotherapy yields low desired response rates due to multidrug resistance, fast clearance rate, nonspecific delivery, severe side effects, low drug concentration in cancer cells, and so on. Nanoparticle-mediated targeted drug delivery system can surmount the aforementioned obstacles through enhanced permeability and retention effect and active targeting as a novel approach of therapeutics for HCC in recent years. The active targeting is triggered by ligands on the delivery system, which recognize with and internalize into hepatoma cells with high specificity and efficiency. This review focuses on the latest targeted delivery systems for HCC and summarizes the ligands that can enhance the capacity of active targeting, to provide some insight into future research in nanomedicine for HCC.
Evaluation of antiviral drugs and neutralizing antibodies to human immunodeficiency virus by a rapid and sensitive microtiter infection assay (1988)

A 96-well microtiter infection assay for the human immunodeficiency virus (HIV) is described. The assay utilizes human T-cell lymphotropic virus type I-immortalized MT-2 cells as targets for infection and requires only 4 to 5 days for completion. Cytolysis was quantitated by vital dye uptake of poly-L-lysine-adhered cells as an endpoint for infection. The assay's efficacy was proven by the sensitive and accurate assessment of several known anti-HIV agents including two inhibitors of reverse transcription (3'-azido-3'-deoxythymidine and 2',3'-dideoxycytidine), three biological response modifiers (recombinant interferons alpha and beta and mismatched double-stranded RNA), a direct inactivator of HIV virions (amphotericin B), and neutralizing antibodies from two HIV-positive human subjects. Evaluation of data was facilitated by computer-assisted analysis. This assay provides a means for rapid, sensitive, and inexpensive large-scale in vitro testing of potential anti-HIV therapeutic regimens and quantitation of HIV-neutralizing antibody titers.
Performance of ultra-wideband communications in the presence of interference (2002)

We analyze the performance of ultra-wideband (UWB) communications in the presence of interference. Closed-form expressions are provided for the jam resistance of UWB with binary pulse position modulation utilizing rectangular pulses. A simple approximation is obtained for the special case of tone interference. The jam resistance analysis is extended to more practical UWB waveforms such as Gaussian and Rayleigh monocycles. A comparison between the interference suppression capabilities of UWB and direct-sequence spread-spectrum (DS-SS) is carried out under conditions similar to both systems. It is shown that in most cases, the jam suppression of UWB is superior to that of DS-SS.
Distribution and properties of fructosyl amino acid oxidase in fungi (1995)

Fructosyl amino acid oxidase, and enzyme that can be used for the determination of glycated proteins in blood samples from diabetic patients, was used to screen cultures in our microorganism culture collection. Fructosyl amino acid oxidase was found only in the strains of four genera of fungi, Aspergillus, Fusarium, Gibberella, and Penicillium and exhibited different substrate specificities against fructosyl valine and N epsilon-fructosyl N alpha-Z-lysine. A fructosyl valine-specific enzyme from Penicillium janthinellum AKU3413 was monomeric (M(r), 49,000), was most active at 35 degrees C and pH 8.0, and had a covalently bound flavin adenine dinucleotide as a prosthetic group.
Safety and Efficacy of Adalimumab (D2E7) in Crohn's Disease Patients with an Attenuated Response to Infliximab (2005)

Our preliminary data suggest that adalimumab may be a safe and effective therapy for patients with CD who have experienced an attenuated response to infliximab.
A major immunogenic 36,000-molecular-weight antigen from Mycobacterium leprae contains an immunoreactive region of proline-rich repeats (1990)

The 36,000-molecular-weight antigen (36K antigen) of Mycobacterium leprae is a major immunogenic protein carrying common and specific antigenic determinants recognized by antibodies and T cells in leprosy patients. Recombinant DNA clones containing the complete gene coding for the 36 K antigen, designated in this paper as PRA, were isolated from both lambda gt11 and cosmid libraries of the M. leprae genome. The DNA sequence of the pra gene coded for a polypeptide of 249 amino acids with a predicted molecular mass of 26,299 daltons. The deduced amino acid sequence revealed a proline-rich (42%) amino-terminal region containing a number of repeated sequences similar or identical to the sequence PGGSYPPPPP. The reactivity of four monoclonal antibodies (F47-9, F67-1, F67-5, and F126-5) was directed to this proline-rich region of the PRA protein. DNA sequence and immunological data indicated that the lambda gt11 recombinant Y3180, which was previously isolated by using antibody F47-9 (R. A. Young, V. Mehra, D. Sweetser, T. Buchanan, J. Clark-Curtiss, R. W. Davis, and B. R. Bloom, Nature (London) 316:450-452, 1985), specifies a fusion protein unrelated to PRA but containing a similar epitope recognized by F47-9.
Quest for high brightness, monochromatic noble gas ion sources (2005)

Focused ion beam (FIB) machines are key tools for state-of-the art sample preparation in electron microscopy, for characterization and repair in material sciences, for the semiconductor industry and for nanotechnology in general. Liquid-metal ion sources (LMIS) are widely used in FIB machines because they meet the minimum ion source requirements such as source brightness and reliability. However, in FIB machines, noble gas ion sources are favorable for sputtering, beam-induced etching and deposition, because the implanted ions do not change the electrical behavior of the substrate significantly. There are several efforts by various researchers to develop noble gas ion sources that can be used in FIB machines instead of LMIS. The gas ion sources could not meet the minimum ion source requirements. Therefore, LMIS are still a popular choice among FIB machine users. This review article takes a critical look at the reported efforts in the literature to develop noble gas ion sources for FIB machines.
Investigation of the Acid-Catalysed Alkylation of Lignins by Means of NMR Spectroscopic Methods (1987)

Abstracting & Indexing
Nuclear Technology and Canadian Oil Sands: Integration of Nuclear Power with In-Situ Oil Extraction (2006)

This report analyzes the technical aspects and the economics of utilizing nuclear reactors to provide the energy needed for a Canadian oil sands extraction facility using Steam-Assisted Gravity Drainage (SAGD) technology. The energy from the nuclear reactor would replace the energy supplied by natural gas, which is currently burned at these facilities. There are a number of concerns surrounding the continued use of natural gas, including carbon dioxide emissions and increasing gas prices. Three scenarios for the use of the reactor are analyzed:(1) using the reactor to produce only the steam needed for the SAGD process; (2) using the reactor to produce steam as well as electricity for the oil sands facility; and (3) using the reactor to produce steam, electricity, and hydrogen for upgrading the bitumen from the oil sands to syncrude, a material similar to conventional crude oil. Three reactor designs were down-selected from available options to meet the expected mission demands and siting requirements. These include the Canadian ACR- 700, Westinghouse's AP 600 and the Pebble Bed Modular Reactor (PBMR). The report shows that nuclear energy would be feasible, practical, and economical for use at an oil sands facility. Nuclear energy is two to three times cheapermore » than natural gas for each of the three scenarios analyzed. Also, by using nuclear energy instead of natural gas, a plant producing 100,000 barrels of bitumen per day would prevent up to 100 mega-tonnes of CO{sub 2} per year from being released into the atmosphere. (authors)« less
Studies on Xylanase from Microorganisms (1969)

As xylanase-producing microorganisms, 64 strains belonging to the genus Streptomyces were isolated from the barn-yard manures, silages and litters collected in Hokkaido district. Among these isolates the strain 102–1–4, which was found to be a new species under taxonomical studies and named Streptomyces xylophagus nov. sp., had the most outstanding ability for the enzyme production. In addition to the isolates, 38 strains of Streptomyces and 480 strains of filamentous fungi which have been preserved in our culture collection were also examined on their ability to produce the enzyme. 1) Among the strains of Streptomyces tested, only two strains, St. albogriseolus IAM 0031 and St. olivaceus IAM 0025 were found to have the ability, but their abilities were less than that of St. xylophagus nov. sp. 2) Out of 480 strains of fungi tested, Chaetomium, Schyzophyllum, Trametes, Echinodontium, Alternaria, Cepharosporium, Cercospora, Gibberella, Glomerella and Macrosporium produced the enzyme. Especially, Ch. trilateral 2264 was the most excellent.
Absence of tektin 4 causes asthenozoospermia and subfertility in male mice (2007)

Sperm flagellar motion is the outcome of a dynamic interplay between the axonemal cytoskeleton, the peri-axonemal accessory structures, and multiple regulatory networks that coordinate to produce flagellar beat and waveform. Tektins are conserved components of the flagellar proteome in evolutionarily diverse species and are believed to play essential roles in the mechanics of sperm motility. Using database mining, we identified multiple new paralogs of previously annotated tektins, including tektin 4 (TEKT4), which shares 77.1% identity with its nearest human homologue. Mouse Tekt4 is a germ cell-enriched gene, most abundantly expressed in haploid round spermatids in the testis, and the protein is localized to the sperm flagella. Male mice lacking TEKT4 on a 129S5/SvEvBrd inbred background are subfertile. Tekt4-null sperm exhibit drastically reduced forward progressive velocity and uncoordinated waveform propagation along the flagellum. In Tekt4-null sperm, flagellar ultrastructure is grossly unaltered as revealed by transmission electron microscopy. However, the ineffective flagellar strokes lead to approximately 10-fold higher consumption of intracellular ATP in Tekt4-null sperm as compared to wild-type, and null spermatozoa rapidly lose progressive motility when incubated for > or = 1.5 h. Our studies demonstrate that TEKT4 is necessary for the proper coordinated beating of the sperm flagellum and male reproductive physiology.
Dechlorination from Sulphate Aqueous Solutions of Zinc Electrolysis by Electrochemical Method (2018)

To remove chlorine from zinc electrolysis solutions, the electrochemical method was carried out in this research. Copper electrodes with a purity of 99.99% were employed as the anode and cathode. In addition, the effect of applied potential, agitation rate, and reaction temperature on the efficiency of chlorine removal was investigated and dechlorination mechanism was explored. Scanning electron microscopy (SEM) was used to observe the evolution of the chlorine species on the anode surface. Based on the obtained results, the efficiency of dechlorination from electrolysis solution with a Cl − concentration of 295 mg.L −1 in constant values of pH = 5 and reaction time of 4 h and under optimal applied potential of 0.8 V, agitation rate of 200 rpm, and the reaction temperature of 25°C turned out to be 42.6%.
Intracrinology: role of the family of 17 beta-hydroxysteroid dehydrogenases in human physiology and disease (2000)

In women and men, an important proportion of estrogens and androgens are synthesized locally at their site of action in peripheral target tissues. This new field of endocrinology has been called intracrinology. In postmenopausal women, 100% of active sex steroids are synthesized in peripheral target tissues from inactive steroid precursors while, in adult men, approximately 50% of androgens are made locally in intracrine target tissues. The last and key step in the formation of all estrogens and androgens is catalyzed by members of the family of 17beta-hydroxysteroid dehydrogenases (17 beta-HSDs) while different 17 beta-HSDs inactivate these steroids in the same cell where synthesis takes place. To date, seven human 17 beta-HSDs have been cloned, sequenced and characterized. The 17 beta-HSDs provide each cell with the means of precisely controlling the intracellular concentration of each sex steroid according to local needs.
Cluster Headache (1985)

Cocainization of the sphenopalatine fossa region has been shown to abort acute cluster headaches rapidly. Whether this response occurs by sympathomimetic action or via local anesthetic effect has been unknown. In this study, lidocaine hydrochloride was given as a therapeutic abortive agent to patients with cluster headache to elucidate cocaine's mechanism of action in relieving symptoms and to search for a safe, nonaddicting agent for self-administration. Using a 4% lidocaine solution applied to the sphenopalatine fossa, four of five patients obtained rapid relief of nitrate-induced cluster headaches and associated signs. Lidocaine was also effective in relieving spontaneous attacks. These results indicated that anesthetic rather than sympathomimetic effects are responsible for cocaine-medicated abortion of cluster headache, that transmission of pain in cluster headache likely occurs via the sphenopalatine fossa, and that topical lidocaine is effective in rapidly aborting acute cluster headache.
Advances in the Development of Inactivated Virus Vaccines (2006)

Vaccine discovery stands out as one of the public health interventions that has achieved the greatest impact in world's health. Vaccination is the most effective means of disease prevention, especially for viral infections. Starting with the use of smallpox vaccine by Jenner in the late 1700s, the technology for vaccine development has seen numerous advances. Currently, vaccines available for human viral illness are based on live attenuated (e.g. measles, mumps, and rubella), inactivated (e.g. hepatitis A) and recombinant (e.g. hepatitis B) viruses. Among these, inactivated vaccines are known for their easy production and safety. The present article reviews the literature and patents related to the mechanisms used for viral inactivation, mainly chemical and physical procedures, including the novel strategies that are currently being explored and that have been recently patent protected.
p-, o-η4-Benzoquinone and the Related η6-Hydroquinone, η6-Catechol Complexes of Pentamethylcyclopentadienyliridium:  Synthesis, Structures, and Reactivity (1998)

Treatment of hydroquinone with [Cp*Ir(solvent)3][BF4]2 (1) in acidic medium afforded the stable π-bonded complex [Cp*Ir(η6-hydroquinone)][BF4]2 (2) in 93% yield. Complex 2 can be easily deprotonated by a base to give the related [Cp*Ir(η5-semiquinone)][BF4] (3) and [Cp*Ir(η4-p-benzoquinone)] (4) compounds, identified by spectroscopic methods. Further, the X-ray molecular structure of p-benzoquinone iridium complex 4 is reported; such compounds are rare in the literature. Complex 4 reacts with an excess of HBF4·Et2O to give the starting material 2 quantitatively. Interestingly, the chemical transformations from 2 to 4 and vice versa occur with facile reversible changes of the oxidation state from Ir(III) to Ir (I). On the other hand, the oxo−dienyl iridium complex [Cp*Ir(η5-2,6-dimethoxy-C6H3O)][BF4] (5), identified by spectroscopic methods and X-ray analysis, reacts with NaOMe in methanol to give unexpectedly but reproducibly the substituted o-benzoquinone iridium compound [Cp*Ir{η4-(3-methoxy)-o-benzoquinone}] (6). The solution behavior and the reactivity of 6, as well as a rationale explaining its formation, is advanced.
Isolation and properties of a nitrile hydratase from the soil fungus Myrothecium verrucaria that is highly specific for the fertilizer cyanamide and cloning of its gene. (1991)

A protein was purified from crude extracts of the soil fungus Myrothecium verrucaria by gel filtration and hydrophobic chromatography to homogeneity; this protein catalyzed the stoichiometric hydration of the fertilizer cyanamide to urea with high substrate specificity. This cyanamide hydratase (urea hydro-lyase; EC 4.2.1.69) contained zinc and consisted of six identical subunits with Mr = 27,700. It was partially sequenced. The protein was detectable only when the fungus was grown on cyanamide as the sole nitrogen source. Genomic DNA from the fungus was cloned, and the gene encoding the enzyme was mapped with an oligonucleotide probe derived from the amino acid sequence within a 25,800-base-pair DNA region. The subunit of the enzyme is encoded by a 795-base-pair DNA sequence containing a 63-base-pair intron. A cDNA clone containing the intronless gene with an open reading frame encoding a sequence of 244 amino acids expressed the enzyme in active form in Escherichia coli with excellent yield.