gebhart/patrepeval huggingface dataset:
The mechanism of cell-mediated cytotoxicity. I. Killing by murine cytotoxic T lymphocytes requires cell surface thiols and activated proteases. (1980)

Abstract Murine allogeneic cell-mediated lympholysis (CML) involves steps requiring cell surface sulfhydryl groups and separate steps that appear to require one or more cell surface proteases that become activated during the lytic process. Chloromethyl ketone derivatives of amino acids, which are specific irreversible inhibitors of isolated serine-dependent esterases, inhibit a variety of cellular functions including cell-mediated cytotoxicity. These reagents, such as the lysine derivative (TLCK), inhibited CML when the effectors were briefly treated and washed before the assay. However, the inhibition did not appear to result from inactivation of a serine-dependent esterase, because we found that TLCK inhibition was not reversed by including 10- to 30-fold molar excesses of protease substrates. Chloromethyl ketone derivatives are also alkylating agents that nonspecifically react with thiol groups. Iodoacetamide (IAcNH2), an alkylating agent with little reactivity for serine-dependent proteases, also inhibited CML. Furthermore, we showed that several other thiol-reactive compounds, including diamide, which penetrates cells, and oxidized glutathione and thiolyte monoquat, which do not penetrate cells, also inhibited CML. Therefore, a cell surface thiol group appeared involved in an obligatory step in CML. We obtained evidence in other experiments that proteases also appeared to participate in CML. CML was inhibited when low m.w. trypsin or chymotrypsin ester substrates or protein anti-proteases were included in the assay. Pretreatment of effector cells with serum α1AT, which irreversibly inactivates serine-dependent esterases, did not inhibit killing. Inhibition of CML by α1AT included in the assay increased as the assay time was lengthened. We interpreted these results to mean that CML involves one or more cell surface proteases that become activated as a consequence of effector-target interactions.
spr-2 , a suppressor of the egg-laying defect caused by loss of sel-12 presenilin in Caenorhabditis elegans , is a member of the SET protein subfamily (2000)

Presenilin plays critical roles in the genesis of Alzheimer's disease and in LIN-12/Notch signaling during development. Here, we describe a screen for genes that influence presenilin level or activity in Caenorhabditis elegans. We identified four spr (suppressor of presenilin) genes by reverting the egg-laying defective phenotype caused by a null allele of the sel-12 presenilin gene. We analyzed the spr-2 gene in some detail. We show that loss of spr-2 activity suppresses the egg-laying defective phenotype of different sel-12 alleles and requires activity of the hop-1 presenilin gene, suggesting that suppression is accomplished by elevating presenilin activity rather than by bypassing the need for presenilin activity. We also show that SPR-2 is a nuclear protein and is a member of a protein subfamily that includes human SET, which has been identified in numerous different biochemical assays and at translocation breakpoints associated with a subtype of acute myeloid leukemia.
Anti-Angiogenic Therapy as a Cancer Treatment Paradigm (2005)

The inhibition of angiogenesis is an emerging therapeutic strategy for cancer treatment. In contrast to conventional therapies, anti-angiogenic therapies primarily target tumor-associated endothelial cells which serve as a lifeline for tumor growth, progression and metastasis. By blocking the supply of essential nutrients and the removal of metabolites, anti-angiogenic therapies aim to delay both primary and metastastic tumor growth while overcoming the inherent cytotoxicities of classical chemotherapies. Indeed, tumor-related angiogenesis is a multi-step process initiated by a cascade of proangiogenic factors secreted from both the tumor and host tissues. These intricate processes involve a close interaction of tumor and associated endothelial cells as well as an intimate communication between proliferating endothelial cells, stromal cells and extracellular matrix components. Inhibition of these proangiogenic mechanisms has become a major challenge for the development of anti-cancer treatment modalities. In this regard, anti-angiogenic therapies embody a potentially powerful adjunct to traditional cancer therapies. In this review, we provide an overview of traditional anti-cancer drugs and discuss the fundamentals of anti-angiogenic therapies. While presenting the salient features of the anti-angiogenic agents targeting the individual phases of angiogenesis, we highlight the potential for specific agent development as novel anti-angiogenic therapeutics. Finally, we present and summarize emerging angiogenesis inhibitors.
Multiple growth factors are associated with lesions of atherosclerosis: Specificity or redundancy? (1996)

Within the last five years, a number of specific growth factors have been localized in developing lesions of atherosclerosis. This localization of growth factors that is not observed in normal vessels, together with the pleotrophic activities of growth factors, have suggested a role for growth factors in atherosclerotic lesion progression. However, based on in vitro studies, many of the growth factors identified in lesions have overlapping target cells and are derived from the same cellular sources. What is the relative role of the specific growth factors identified? How is the their activity altered by the local conditions in the vessel wall? How do different risk factors for atherosclerosis alter the balance between growth factors and their natural regulators? Evidence for the involvement of specific growth factors in the progression of lesions of atherosclerosis is discussed, as well as the multiple levels at which the activities of these growth factors may be regulated by the vessel wall.
Time‐resolved contrast‐enhanced imaging with isotropic resolution and broad coverage using an undersampled 3D projection trajectory (2002)

Time-resolved contrast-enhanced 3D MR angiography (MRA) methods have gained in popularity but are still limited by the tradeoff between spatial and temporal resolution. A method is presented that greatly reduces this tradeoff by employing undersampled 3D projection reconstruction trajectories. The variable density k-space sampling intrinsic to this sequence is combined with temporal k-space interpolation to provide time frames as short as 4 s. This time resolution reduces the need for exact contrast timing while also providing dynamic information. Spatial resolution is determined primarily by the projection readout resolution and is thus isotropic across the FOV, which is also isotropic. Although undersampling the outer regions of k-space introduces aliased energy into the image, which may compromise resolution, this is not a limiting factor in high-contrast applications such as MRA. Results from phantom and volunteer studies are presented demonstrating isotropic resolution, broad coverage with an isotropic field of view (FOV), minimal projection reconstruction artifacts, and temporal information. In one application, a single breath-hold exam covering the entire pulmonary vasculature generates high-resolution, isotropic imaging volumes depicting the bolus passage.
Obesity: A Risk Factor for Severe Acute Biliary and Alcoholic Pancreatitis (1998)

Obesity may predispose to a complicated course of AP, especially if it is secondary to alcohol or gallstones. Further studies are needed to establish the precise prognostic value of obesity in AP, as well as the pathogenic mechanisms involved in the process.
Evaluation of Stresses in Thin Device Wafer using Piezoresistive Stress Sensor (2008)

In this work, piezoresistive stress sensors have been used to evaluate the stresses in thin device wafer. For the evaluation, device wafers having piezoresistive stress sensors were fabricated. The stress sensors were then calibrated to determine the piezoresistive coefficients. The evaluation of stresses in device wafer was carried out after thinning the device wafers to three different thicknesses ranging from 400 ¿m to 100 ¿m. The thinning process was performed with the help of commercial wafer back-grinding machine and the complete thinning process included rough grinding, then fine grinding, and finally polishing. It is found that wafer back-grinding of device wafer generates a large amount of compressive stress at the device wafer surface and the amount of stress increases exponentially with the decrease in wafer thickness. The stresses were also evaluated after mounting the thin device wafers on dicing tape. It is found that the mounting on dicing tape generates tensile stress at the device wafer surface. These trends of stresses in the thin device wafers were confirmed with the bending profile of thin device wafers. A detailed explanation for the development of stresses in the thin device wafer is provided in the paper.
A Murine Model for Neuropsychiatric Disorders Associated with Group A β-Hemolytic Streptococcal Infection (2004)

A syndrome of motoric and neuropsychiatric symptoms comprising various elements, including chorea, hyperactivity, tics, emotional lability, and obsessive-compulsive symptoms, can occur in association with group A beta-hemolytic streptococcal (GABHS) infection. We tested the hypothesis that an immune response to GABHS can result in behavioral abnormalities. Female SJL/J mice were immunized and boosted with a GABHS homogenate in Freund's adjuvant, whereas controls received Freund's adjuvant alone. When sera from GABHS-immunized mice were tested for immunoreactivity to mouse brain, a subset was found to be immunoreactive to several brain regions, including deep cerebellar nuclei (DCN), globus pallidus, and thalamus. GABHS-immunized mice having serum immunoreactivity to DCN also had increased IgG deposits in DCN and exhibited increased rearing behavior in open-field and hole-board tests compared with controls and with GABHS-immunized mice lacking serum anti-DCN antibodies. Rearing and ambulatory behavior were correlated with IgG deposits in the DCN and with serum immunoreactivity to GABHS proteins in Western blot. In addition, serum from a GABHS mouse reacted with normal mouse cerebellum in nondenaturing Western blots and immunoprecipitated C4 complement protein and alpha-2-macroglobulin. These results are consistent with the hypothesis that immune response to GABHS can result in motoric and behavioral disturbances and suggest that anti-GABHS antibodies cross-reactive with brain components may play a role in their pathophysiology.
A randomized, double-blind, placebo-controlled, dose-escalation study of the safety and efficacy of INCB039110, an oral janus kinase 1 inhibitor, in patients with stable, chronic plaque psoriasis (2016)

INCB039110 produced significant improvements in sPGA, demonstrating proof of concept in chronic plaque psoriasis.
Expression of the extracellular matrix molecule thrombospondin inversely correlates with malignant progression in melanoma, lung and breast carcinoma cell lines (1994)

Thrombospondin (TSP) is a member of a family of extracellular matrix glycoproteins that may participate in multiple aspects of the metastatic cascade. We report an inverse correlation of steady-state Thbs-1 mRNA and protein expression with malignant progression among murine melanoma and human lung and breast carcinoma cell lines. Murine K-1735 melanoma cell lines of low metastatic potential, including K-1735 lines transfected with the murine nm23-1 cDNA, expressed higher TSP levels than related highly metastatic lines. In a model system of lung carcinoma malignant progression, immortalized human bronchial epithelial cells expressed higher TSP levels than v-Ki-ras, v-Ha-ras or n-ras transfectants, which in turn expressed higher TSP levels than tumor-derived, more aggressive variants. Among 3 unrelated breast carcinoma cell lines, Thbs-1 steady-state mRNA levels were greater in the 2 non-metastatic lines than the metastatic line. Our data show that malignant progression in some cell lines is associated with reduced TSP expression. The suppressive effects of nm23-1 transfection on metastatic potential are also associated with increased TSP expression; ras transfection, which results in increased tumorigenesis, is associated with decreased TSP expression.
Intranasal dexmedetomidine for sedation in children undergoing transthoracic echocardiography study—a prospective observational study (2015)

Sedation by intranasal dexmedetomidine at 3 mcg·kg(-1) is associated with acceptable success rate in children undergoing echocardiography with no adverse events in this cohort.
Structural and Chiroptical Properties of the Two Coordination Isomers of YbDOTA-Type Complexes (2005)

Studies of the structural, physical, and chemical properties of the lanthanide(III) complexes of DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) and related ligands are often complicated by the presence of two coordination isomers in solution. Since these coordination isomers are in exchange and cannot be separated, many techniques offer information only on the weighted average of the two isomers. Lanthanide ion complexes formed with the ligands S(RRRR)NO2BnDOTMA and S(SSSS)NO2BnDOTMA preferentially adopt only one of the two common coordination isomers in solution, so the ytterbium complexes of these ligands offer a unique opportunity to study the near-infrared circular dichroism (NIR-CD) characteristics of each coordination geometry in isolation. The spectra acquired support many of the conclusions and assumptions of previous studies and demonstrate that this spectroscopy is particularly sensitive to the distortion of the coordination polyhedron. This will have particularly relevant consequences when studying achiral YbDOTA-like systems forming labile adducts with (chiral) hosts and receptors.
Identification and synthesis of a major conserved antigenic epitope of Trypanosoma cruzi. (1992)

A gene sequence encoding an immunodominant protein with a repetitive epitope from the protozoan Trypanosoma cruzi, the causative agent of Chagas disease, was cloned and expressed. The identified 10-amino acid repeat is present within a high-molecular-weight trypomastigote antigen that appears specific to and conserved among T. cruzi isolates. More importantly, greater than 95% of T. cruzi infection sera, including both chronic and acute Chagas disease, contained elevated levels of antibody to a 15-amino acid synthetic peptide bearing the repetitive B-cell epitope. Considering the wide diversity of T. cruzi parasites, as well as the broad spectrum of clinical manifestations of Chagas disease, such a prevalent immune response among patients is significant and applicable to the control of Chagas disease through the diagnosis of T. cruzi infection.
Microstructured Optical Fibers as High-Pressure Microfluidic Reactors (2006)

Deposition of semiconductors and metals from chemical precursors onto planar substrates is a well-developed science and technology for microelectronics. Optical fibers are an established platform for both communications technology and fundamental research in photonics. Here, we describe a hybrid technology that integrates key aspects of both engineering disciplines, demonstrating the fabrication of tubes, solid nanowires, coaxial heterojunctions, and longitudinally patterned structures composed of metals, single-crystal semiconductors, and polycrystalline elemental or compound semiconductors within microstructured silica optical fibers. Because the optical fibers are constructed and the functional materials are chemically deposited in distinct and independent steps, the full design flexibilities of both platforms can now be exploited simultaneously for fiber-integrated optoelectronic materials and devices.
Simultaneous Humanization and Affinity Optimization of Monoclonal Antibodies (2003)

Monoclonal antibodies (MAbs) have broad therapeutic applications in cancer therapy, prevention and treatment of viral infection, immune suppression, etc. However, many well-characterized MAbs are derived from murine sources, and these antibodies have been shown to induce strong immunogenicity when administered into the human body. The ensuring human anti-mouse antibody (HAMA) response consequently can induce fast clearance of administered antibodies from serum resulting in significantly reduced efficacy. In addition, murine MAbs also have weak effector function in human, which is important for certain clinical applications. To overcome these shortcomings, humanization techniques are used to modify nonhuman MAbs for therapeutic use. Humanization can reduce and potentially eliminate the human immune response to administered foreign antibodies. It is a critical step in maximizing the usage of MAbs as therapeutic agents.
Transfer of chimeric receptor gene made of variable regions of tumor-specific antibody confers anticarbohydrate specificity on T cells. (1999)

The antitumor specificity of T cells can be induced by gene transfer using a recently developed therapeutic approach (T body). In this work, we genetically conferred anticarbohydrate specificity onto T cells using the variable regions of monoclonal antibody MLuC1, which binds the Lewis(Y) (LeY) tumor-associated antigen that is overexpressed on several human carcinomas. The variable regions of MLuC1, which are in a single-chain Fv (ScFv) configuration, were cloned and spliced in a eukaryotic expression vector with both the gene encoding the signal-transducing gamma-chain of the human Fcgamma receptor and a flexible hinge domain. The chimeric ScFv-gamma gene was expressed in a murine cytotoxic T-cell hybridoma. Transfectants receiving vector only served as a negative control (mock). Screening for functional transfectants was carried out using a tumor growth inhibition assay. The soluble form of MLuC1 ScFv was recovered from bacteria periplasm and tested for binding to LeY-expressing cells by the fluorescence-activated cell sorter analysis. Despite the low binding ability of the soluble MLuC1 ScFv, 7 of 13 genetically engineered cytotoxic T lymphocyte clones inhibited the growth of LeY-positive cells and did not affect growth of LeY-negative cells. None of the mock clones tested specifically inhibited tumor growth. These data indicate that, by chimeric MLuC1 ScFv-gamma gene transfer, it is possible to confer anticarbohydrate specificity onto T cells and extend the applicability of the T-body approach to tumor-associated antigens that are naturally not recognized by T cells.
MicroRNA in schizophrenia: Genetic and expression analysis of miR-130b (22q11) (2007)

MicroRNAs (miRNAs) are a class of small regulatory RNAs that control a level of expression of protein encoding genes. Their role in brain pathologies is unknown. We made a first attempt to carry out a genetic study coupled with gene expression analysis of microRNA in human neuropsychiatric pathology. Presumably, at least one third of known miRNA genes are expressed in the brain. Mutations disrupting MECP2 protein lead to abnormal development of the brain and resulting behavior. MiR-130b expressed in the brain and potentially targeting MECP2 is located in the susceptibility locus for schizophrenia (22q11). We performed a comparative analysis of the expression of miR-130b in 24 brain neocortex samples from schizophrenic and normal individuals. The stability and effective detection of mature microRNA in postmortem tissues using Real-time PCR have been shown. Screening for mutations has identified a population polymorphism in the 5 -upstream miR-130b gene region containing DNA elements for putative transcription factors. Genetic association analysis of 300 schizophrenia and 316 normal control individuals revealed no statistically significant association of any of the miR-130b allelic variants with schizophrenia. The data demonstrated feasibility and perspective of convergent genetic and expression analysis of human microRNA genes in testing their role in human diseases.
Ternäre Halogenide vom Typ A3MX6. III [1, 2]. Synthese, Strukturen und Ionenleitfähigkeit der Halogenide Na3MX6 (X = Cl, Br) (1995)

Abstract Die Bromide Na 3 MBr 6 kristallisieren im aufgefüllten LiSbF 6 ‐Typ (Typ I; M = SmGd) oder im Kryolith‐Typ (Typ II; M = GdLu). Die Strukturen wurden anhand von Einkristalldaten verfeinert (Na 3 SmBr 6 : trigonal, Raumgruppe R 3 , a = 740,8(2) pm, c = 1 998,9(8) pm, Z = 3; Na 3 YBr 6 : monoklin, Raumgruppe P2 1 /n, a = 721,3(4) pm, b = 769,9(2) pm, c = 1 074,8(4) pm, β = 90,60(4)°, Z = 2). Beide Strukturen sind reversibel ineinander umwandelbar. Die Umwandlungstemperaturen der Bromide wurden ebenso wie die der Chloride Na 3 MCl 6 (M = EuLu) bestimmt. An Na 3 GdBr 6 wurden beide Strukturen an Einkristallen bestimmt (I: trigonal, Raumgruppe R 3 , a = 737,1(5) pm, c = 1 887(2) pm, Z = 3; II: monoklin, Raumgruppe P2 1 /n, a = 725,2(1) pm, b = 774,1(3) pm, c = 1 080,1(3) pm, β = 90,76(3)°, Z = 2). Alle Verbindungen zeigen Natrium‐Ionenleitfähigkeit, die beim Übergang vom Typ I in den Typ II stark abnimmt. Die Bromide zeigen, verglichen mit den Chloriden, jeweils eine bessere Leitfähigkeit.
Multiple receptor systems promote CNS neural migration (1993)

To identify glial receptor systems in CNS migration, cerebellar granule neuron migration was assayed on glass fibers coated with polylysine, astroglial membranes (AM fibers), or the extracellular matrix proteins collagen (COLL fibers), fibronectin (FN fibers), and laminin (LAM fibers). By video microscopy, granule cells migrated along AM fibers with the cytology, neuron-fiber apposition, and dynamics seen on living glia. The demonstration that immobilized astroglial membranes support neural migration suggests that astroglial receptor systems, in combination with glial fiber geometry, promote CNS neural migration. Moreover, granule neurons migrated rapidly on LAM fibers, moved relatively slowly on FN fibers, and not at all on COLL fibers. Antibody perturbation analyses suggested that, whereas astrotactin provides the neural receptor for migration on astroglial membranes, integrin beta 1 provides the neural receptor for migration on LAM fibers. These results suggest that multiple receptor systems support CNS neural migration.
Use of Manganese in RT-PCR Eliminates PCR Artifacts Resulting from DNase I Digestion (1997)

The precise quantification of rare mRNA copies from intronless genes by reverse transcription polymerase chain reaction (RT-PCR) requires the complete removal of genomic DNA because discrimination of cDNA and DNA amplification products by differing sizes of PCR products is not possible. Elimination of DNA is achieved by treating the RNA sample with RNase-free DNase I before RT-PCR. The lack of a PCR product from DNase-treated RNA samples before RT is usually accepted as a proof of efficient DNA destruction. However, this may vary depending on the metal cofactor used in the DNase I cleavage. Treating DNA-contaminated RNA samples with DNase I and magnesium as a cofactor creates a negative PCR control after digestion without further RT. Paradoxically, after additional RT-PCR, the original intron-containing DNA fragment size may be produced again. In the presence of manganese as cofactor, RT-created DNA fragments do not appear. This is because in the presence of manganese, DNase I cleaves both DNA strands at approximately the same site, yielding DNA fragments that are blunt-ended or that have protruding termini of only one or two nucleotides in length. However, overlapping fragments with the potential to recombine are created by DNase digestion with magnesium as cofactor. Because one cannot differentiate between a PCR signal produced by RNA and one produced by recombined DNA after DNase I digestion and RT, all such DNase I assays should be performed with manganese instead of magnesium.