gebhart/patrepeval huggingface dataset:
Reversible azoospermia in a patient treated with triazolam (1996)

This is a report of a 26-year-old schizophrenic man treated with triazolam, levomepromazine, trifluoperazine and biperiden, who showed complete absence of spermatozoa in seminal analysis with normal plasma hormone levels. Sperm count reached 151 x 10(6)/ml after 6 months of triazolam withdrawal. A reversible effect of triazolam is suggested at the level of the germinal cells which are differentiating, without affecting the stem cells.
A New Human Selenium-containing Protein (1998)

Selenium which occurs in proteins as the amino acid, selenocysteine, is essential for numerous biological processes and for human health. A prominent 75Se-labeled protein detected in human T-cells migrated as a 15-kDa band by SDS-polyacrylamide gel electrophoresis. This protein subunit was purified and subjected to tryptic digestion and peptide sequence analyses. Sequences of tryptic peptides derived from the protein corresponded to a human placental gene sequence containing an open reading frame of 162 residues and a readthrough in-frame TGA codon. Three different peptide sequences of the 15-kDa protein corresponded to a nucleotide sequence located downstream of this codon, suggesting that the T-cell 15-kDa selenoprotein contains a selenocysteine residue encoded by TGA. Post-translational processing of the N-terminal portion of the predicted gene product to give the 15-kDa protein was suggested on the basis of molecular mass, amino acid analysis, and immunoblot assays of the purified protein. The 3'-untranslated region (UTR) of the gene encoding the 15-kDa protein contained a sequence that is very similar to the canonical selenocysteine-inserting sequence element. Computer analysis of transcript map data bases indicated that this gene was located on human chromosome 1. Its coding sequence showed no homology to known protein-encoding genes. The 15-kDa protein gene was expressed as mRNA in a wide range of tissues, with increased levels in the thyroid, parathyroid, and prostate-derived cells as evidenced by searches of partial cDNA sequences in public data bases. Genes corresponding to the 15-kDa selenocysteine-containing protein were found in mice and rats, while the corresponding genes in Caenorhabditis elegans and Brugia malayi contained a cysteine codon in place of TGA. The discovery of a new human selenoprotein provides an additional example of the role of selenium in mammalian systems.
Antileukemic activity of nuclear export inhibitors that spare normal hematopoietic cells (2012)

Drugs that target the chief mediator of nuclear export, chromosome region maintenance 1 protein (CRM1) have potential as therapeutics for leukemia, but existing CRM1 inhibitors show variable potencies and a broad range of cytotoxic effects. Here, we report the structural analysis and antileukemic activity of a new generation of small-molecule inhibitors of CRM1. Designated selective inhibitors of nuclear export (SINE), these compounds were developed using molecular modeling to screen a small virtual library of compounds against the nuclear export signal (NES) groove of CRM1. The 2.2-Å crystal structure of the CRM1-Ran-RanBP1 complex bound to KPT-251, a representative molecule of this class of inhibitors, shows that the drug occupies part of the groove in CRM1 that is usually occupied by the NES, but penetrates much deeper into the groove and blocks CRM1-directed protein export. SINE inhibitors exhibit potent antileukemic activity, inducing apoptosis at nanomolar concentrations in a panel of 14 human acute myeloid leukemia (AML) cell lines representing different molecular subtypes of the disease. When administered orally to immunodeficient mice engrafted with human AML cells, KPT-251 had potent antileukemic activity with negligible toxicity to normal hematopoietic cells. Thus, KPT-SINE CRM1 antagonists represent a novel class of drugs that warrant further testing in AML patients.
Comparative study of anthocyanin composition, antimicrobial and antioxidant activity in bilberry (Vaccinium myrtillus L.) and blueberry (Vaccinium corymbosum L.) fruits. (2009)

Simultaneous comparison of bilberry (Vaccinium myrtillus L.) and blueberry (Vaccinium corymbosum L) fruits for their anthocyanin composition, antimicrobial and antioxidant activity is reported. The aim of this study was to investigate and to compare anthocyanin composition, antimicrobial and antioxidant activity in bilberry and blueberry fruits and their skins. The investigations revealed that the highest amount of total anthocyanins was observed in fruits skins of blueberry cultivars. The results, obtained by chromatographic analysis, indicated that cyanidin is a dominant anthocyanidin in bilberry and malvidin in blueberry samples. Extracts of "Herbert", "Coville", "Toro" blueberry cultivars and bilberry fruits revealed antimicrobial properties. Citrobacter freundii (ATCC 8090) and Enterococcus faecalis (ATCC29212) were the most sensitive among eight tested Gram-negative and Gram-positive bacteria. Significant differences between berry and skin extracts were not established. Studies with fruits showed that the strongest antioxidant activity possesses blueberry cultivar "Berkeley" (82.13 +/- 0.51%). Meanwhile, the amount of quenched free radicals in bilberry samples was 63.72 +/- 1.11%, respectively. The lowest antioxidant activity was estimated in blueberry cultivar "Coville". Accordingly, the strongest antiradical properties were estimated in blueberry cultivar "Ama" fruit skins. Bilberry fruit skin samples possess strong antiradical activity as well (82.69 +/- 0.37%).
Studies on the structure and regulation of the human hepatic interleukin‐6 receptor (1990)

Affinity cross-linking of 125I-labeled recombinant human interleukin-6 (IL-6) to human hepatoma cells (HepG2) allowed the detection of three IL-6-containing complexes with molecular masses of 100 kDa, 120 kDa and 200 kDa. Treatment of HepG2 cells with dexamethasone led to a time- and dose-dependent up-regulation of IL-6-receptor mRNA levels. By the use of cross-linking this effect was also seen at the protein level, where all three IL-6-binding complexes increased upon incubation of HepG2 cells with dexamethasone. Under conditions of IL-6-receptor up-regulation by dexamethasone, gamma-fibrinogen mRNA induction by IL-6 is stronger and occurs earlier than without dexamethasone. We propose therefore that the expression of the IL-6 receptor might be a rate-limiting step in acute-phase-protein induction.
Redifferentiation, cellular elongation and the cell surface during lens regeneration (1977)

ABSTRACT Dorsal irises from normal and lentectomized eyes of the newt Notophthalmus viridescens were cultured in vitro in the presence of colchicine (1·25 × 10−3 to 2·5 × 10−6 M), vinblastine sulfate (4·4 × 10−8) and cytochalasin B (20 μg/ml). Explants were treated for 24 h and implanted into host eyes of previously lentectomized newts. In regenerates treated with colchicine at stages prior to the onset of lens fiber formation, cellular elongation was inhibited or considerably delayed. Cytochalasin B has no effect on lens fiber differentiation when compared with regenerates treated with its solvent, dimethyl sulfoxide. Colchicine-treated regenerates showed no detectable fluorescence when stained with anti-newt lens fluorescent antibodies, suggesting that cells in which cellular elongation was inhibited were unable to synthesize lens specific proteins. Ultrastructural observations of elongating lens regenerate cells showed microtubules present in the cytoplasm parallel to the axis of elongation. Microtubules were not observed in depigmented cells from colchicine-treated regenerates. Characteristic vinblastine-induced microtubule crystals were present in depigmented cells from vinblastine-treated regenerates. Experiments using cell electrophoresis showed that neuraminidase-sensitive groups were detectable at the ionic double layer of cells from implanted regenerates at stages where lens fiber differentiation occurs. Cells from colchicine-treated regenerates showed no significant reduction of their electrophoretic mobility after neuraminidase treatment. This suggests that the appearance of some cell surface components in the redifferentiated cell may also be colchicine sensitive and probably mediated by microtubules.
A new harmonic analyser (1932)

Recent troubles with harmonic voltages have rendered a simple electrical harmonic analyser necessary. The following notes outline the available methods of measuring harmonic values, compare their merits and indicate their weaknesses.
Role of leukocytes and endothelial cells in the development of angiogenesis in inflammation and wound healing. (2001)

The basic signs and symptoms of inflammation and wound healing have been appreciated for thousands of years. However, the specific cells involved and their roles in this complex environment are still being elucidated today. In 1926, the origin of the phagocytic mononuclear ameboid wandering cell (macrophage) had not been determined. One popular theory was that the cells were differentiated from the endothelial cells of the nearby blood vessels, whereas others believed that the cells came from the peripheral blood or resting wandering cells. The purpose of this article is to review the seminal article published by Lang regarding this topic nearly 75 years ago. In addition, this article will review what is now known with regard to the role of the macrophage and endothelial cells in the development of angiogenesis, which is arguably the most critical component of successful inflammatory process or wound healing.
Simplified Microneutralization Test for Serotyping Adenovirus Isolates (2001)

A simplified microneutralization procedure is described that uses an empirically determined virus challenge dose, a single dilution of antiserum, and observation of cytopathic effect to determine the adenovirus serotype. The simplified test has faster turnaround time and was 96% concordant with a confirmatory test using serial dilutions of type-specific sera. This method will find utility in high-volume serotyping work.
HtrA3 as an Early Marker for Preeclampsia: Specific Monoclonal Antibodies and Sensitive High-Throughput Assays for Serum Screening (2012)

Mammalian HtrA3 (high temperature requirement A3) is a serine protease of the HtrA family. It has two isoforms [long (HtrA3-L) and short (HtrA3-S)] and is important for placental development and cancer progression. Recently, HtrA3 was identified as a potential diagnostic marker for early detection of preeclampsia, a life-threatening pregnancy-specific disorder. Currently there are no high-throughput assays available to detect HtrA3 in human serum. In this study we generated and fully tested a panel of five HtrA3 mouse monoclonal antibodies (mAbs). Three mAbs recognised both HtrA3-L and HtrA3-S and the other two detected HtrA3-L only. All five mAbs were highly specific to HtrA3 and applicable in western blotting and immunohistochemical analysis of endogenous HtrA3 proteins in the mouse and human tissues. Amplified luminescent proximity homogeneous assays-linked immunosorbent assays (AlphaLISAs), were developed to detect HtrA3 isoforms in picomolar levels in serum. The HtrA3 AlphaLISA detected significantly higher serum levels of HtrA3 in women at 13-14 weeks of gestation who subsequently developed preeclampsia compared to gestational-age matched controls. These HtrA3 mAbs are valuable for the development of immunoassays and characterisation of HtrA3 isoform-specific biology. The newly developed HtrA3 AlphaLISA assays are suitable for large scale screening of human serum.
Gene therapy for ocular diseases (2010)

The eye is an easily accessible, highly compartmentalised and immune-privileged organ that offers unique advantages as a gene therapy target. Significant advancements have been made in understanding the genetic pathogenesis of ocular diseases, and gene replacement and gene silencing have been implicated as potentially efficacious therapies. Recent improvements have been made in the safety and specificity of vector-based ocular gene transfer methods. Proof-of-concept for vector-based gene therapies has also been established in several experimental models of human ocular diseases. After nearly two decades of ocular gene therapy research, preliminary successes are now being reported in phase 1 clinical trials for the treatment of Leber congenital amaurosis. This review describes current developments and future prospects for ocular gene therapy. Novel methods are being developed to enhance the performance and regulation of recombinant adeno-associated virus- and lentivirus-mediated ocular gene transfer. Gene therapy prospects have advanced for a variety of retinal disorders, including retinitis pigmentosa, retinoschisis, Stargardt disease and age-related macular degeneration. Advances have also been made using experimental models for non-retinal diseases, such as uveitis and glaucoma. These methodological advancements are critical for the implementation of additional gene-based therapies for human ocular diseases in the near future.
Electrical characterization of carbon nanotube field-effect transistors with SiNx passivation films deposited by catalytic chemical vapor deposition (2008)

SiN x passivation films were deposited on carbon nanotube field-effect transistors (CNTFETs) by catalytic chemical vapor deposition (Cat-CVD) at low substrate temperatures. Deposition at 330°C induced many defects in the CNT channels. The measurement of electrical properties revealed that p-type CNTFETs were converted to n-type CNTFETs after deposition at 270°C. Air-stable p-type top-gated CNTFETs with SiNx passivation films deposited at 65°C were operated. Thus, Cat-CVD is highly suitable for depositing high-quality SiNx passivation films on CNTFETs and the fabrication of n- or p-type CNTFETs can be controlled by changing the deposition temperature of SiNx passivation films.
Highly effective induction therapy for stage 4 neuroblastoma in children over 1 year of age. (1994)

The N6 approach reliably achieves significant cytoreduction against stage 4 neuroblastoma. This may eventuate in an improved cure rate, since consolidative treatments using myeloablative therapy, immunotherapy, or biologic response modifiers such as cis-retinoic acid are most likely to be effective against minimal residual disease.
The HMGB1 Receptor RAGE Mediates Ischemic Brain Damage (2008)

In ischemic stroke, the necrotic core is surrounded by a zone of inflammation, in which delayed cell death aggravates the initial insult. Here, we provide evidence that the receptor for advanced glycation end products (RAGE) functions as a sensor of necrotic cell death and contributes to inflammation and ischemic brain damage. The RAGE ligand high mobility group box 1 (HMGB1) was elevated in serum of stroke patients and was released from ischemic brain tissue in a mouse model of cerebral ischemia. A neutralizing anti-HMGB1 antibody and HMGB1 box A, an antagonist of HMGB1 at the receptor RAGE, ameliorated ischemic brain damage. Interestingly, genetic RAGE deficiency and the decoy receptor soluble RAGE reduced the infarct size. In vitro, expression of RAGE in (micro)glial cells mediated the toxic effect of HMGB1. Addition of macrophages to neural cultures further enhanced the toxic effect of HMGB1. To test whether immigrant macrophages in the ischemic brain mediate the RAGE effect, we generated chimeric mice by transplanting RAGE(-/-) bone marrow to wild-type mice. RAGE deficiency in bone marrow-derived cells significantly reduced the infarct size. Thus, HMGB1-RAGE signaling links necrosis with macrophage activation and may provide a target for anti-inflammatory therapy in stroke.
Vacuum level alignment in organic guest-host systems (2002)

Using a combination of ultraviolet and x-ray photoelectron spectroscopies, we have studied the relative energy level alignment of two phosphorescent guest molecules, 2,3,7,8,12,13,17,18-octaethyl-21H,23H-porphine platinum (PtOEP) and tris(2-phenylpyridine)iridium (Ir(ppy)3), doped in an electron transport host, tris(8-hydroxyquinolinato) aluminum (III) (Alq3), and in a hole transport host, 4,4′-bis(carbazol-9-yl)biphenyl. In each of the guest–host systems, we find that the vacuum levels of the guest and the host molecules align, and that the position of the highest occupied molecular orbital of the phosphorescent guest is independent of the guest molecule concentration (0.8%–56% by mass). The vacuum level alignment implies free movement of the Fermi level within the gaps of the guest and the host molecules manifesting the intrinsic nature of these organic semiconductors. These results give insights into the role that the phosphorescent molecules play in trapping and transporting charges within the emissive layer of an organic light-emitting device.
EML4-ALK Mutations in Lung Cancer That Confer Resistance to ALK Inhibitors (2010)

The EML4 (echinoderm microtubule-associated protein-like 4)-ALK (anaplastic lymphoma kinase) fusion-type tyrosine kinase is an oncoprotein found in 4 to 5% of non-small-cell lung cancers, and clinical trials of specific inhibitors of ALK for the treatment of such tumors are currently under way. Here, we report the discovery of two secondary mutations within the kinase domain of EML4-ALK in tumor cells isolated from a patient during the relapse phase of treatment with an ALK inhibitor. Each mutation developed independently in subclones of the tumor and conferred marked resistance to two different ALK inhibitors. (Funded by the Ministry of Health, Labor, and Welfare of Japan, and others.).
Deconvolution of atomic force microscopy data for cellular and molecular imaging (2006)

The restoration of image features in cellular and molecular images is a crucial problem in nanobiological investigations. Scanning probe microscopy (SPM) offers the potential for direct investigative capability at nanometer resolution necessary for imaging biological units and macromolecular protein control blocks. The distortion of the measured image due to tip-sample interaction is a major challenge for nanoscale metrology, and signal processing solutions are needed for increasing the accuracy and reliability of the data. Two candidate approaches have been described in detail in this article for modeling the tip-sample interaction from a topographical perspective, which is then used for reconstructing the sample surface from known tip geometry. When the aspect ratio of a feature is comparable with that of the tip, the two methods produce similar results, but when the aspect ratio is larger than that of the tip, the MM method produces a sharper estimate than the LT method. When the tip geometry is not known, blind-tip estimations methods are needed for iterative estimations of tip and sample surfaces
Selective blockade of inhibitory Fcγ receptor enables human dendritic cell maturation with IL-12p70 production and immunity to antibody-coated tumor cells (2005)

The final differentiation or maturation of dendritic cells (DCs) in response to environmental stimuli influences their ability to both initiate immunity and determine the quality of the response to antigens. Circulating immune complexes and cell-bound immunoglobulins present in normal human sera represent a potential stimulus for inadvertent DC activation in the steady state and during autoimmunity. Here, we show that selective blockade of the inhibitory Fcγ receptor (FcγR) FcγRIIb with recently developed monoclonal antibodies leads to maturation of human monocyte-derived DCs, which depends on the presence of IgG in normal human plasma. Plasma, in the presence of an FcγRIIb blockade, caused the DCs to up-regulate the expression of costimulatory molecules and to produce the inflammatory mediator IL-12p70. FcγRIIb blockade of DCs loaded with tumor cells led to increased tumor-specific T cell immunity without the need for exogenous stimuli other than human plasma. Therefore, the activation status of DCs in the presence of normal human serum depends on the balance between activating and inhibitory FcγRs and can be enhanced by new antibodies that react selectively with FcγRIIb. These data suggest an approach for modifying this balance to enhance immunity to immune complexes and antibody-coated tumor cells and to silence DC activation by immune complexes in autoimmune states.
Mutations and polymorphisms in the human peripherin-RDS gene and their involvement in inherited retinal degeneration (1996)

The RDS gene codes for the protein peripherin-RDS, which is an integral membrane glycoprotein found in the outer segment of both rod and cone photoreceptor cells. It is thought to function as a structural protein involved in the maintenance of the flattened form of the disc lamellae. The RDS gene has been implicated in the mouse phenotype retinal degeneration slow, and mutations in the human homologue are now known to be associated with both central and peripheral retinal degenerations. In all, 43 sequence variants have been described in the human gene, including 30 missense mutations, two single base substitutions producing termination codons, 7 small in-frame deletions, and 4 insertion/ deletion events, which break the reading frame. Of these, 39 are associated with retinal phenotypes, which can be grouped into four broad categories: dominant retinitis pigmentosa, progressive macular degeneration, digenic RP, and pattern dystrophies. The mutations underlying dominant RP and severe macular degeneration are largely missense or small in-frame deletions in a large intradiscal loop between the third and fourth transmembrane domains. In contrast, those associated with the milder pattern phenotypes or with digenic RP are scattered more evenly through the gene and are often nonsense mutations. This observation correlates with the hypothesis that the large loop is an important site of interaction between RDS molecules and other protein components in the disc.
Colloidal LaF3:Yb,Er, LaF3:Yb,Ho and LaF3:Yb,Tm nanocrystals with multicolor upconversion fluorescence (2005)

The IR-to-visible upconversion fluorescent nanocrystals, Yb–Er, Yb–Ho and Yb–Tm co-doped LaF3 were chemically synthesized and investigated. The ligand-capped nanocrystals were easily dispersed in organic solutions and subsequently formed a transparent colloidal solution. Under 980 nm IR excitation, green, red and blue emission bands were observed from these colloidal solutions, respectively. Compared with the recently reported colloidal NaYF4:Yb,Er nanocrystals, our nanocrystals produced a fluorescence output which was 5 times higher. These nanocrystals have potential applications as bio-probes and displays.
BIDE: efficient mining of frequent closed sequences (2004)

Previous studies have presented convincing arguments that a frequent pattern mining algorithm should not mine all frequent patterns but only the closed ones because the latter leads to not only more compact yet complete result set but also better efficiency. However, most of the previously developed closed pattern mining algorithms work under the candidate maintenance-and-test paradigm which is inherently costly in both runtime and space usage when the support threshold is low or the patterns become long. We present, BIDE, an efficient algorithm for mining frequent closed sequences without candidate maintenance. We adopt a novel sequence closure checking scheme called bidirectional extension, and prunes the search space more deeply compared to the previous algorithms by using the BackScan pruning method and the Scan-Skip optimization technique. A thorough performance study with both sparse and dense real-life data sets has demonstrated that BIDE significantly outperforms the previous algorithms: it consumes order(s) of magnitude less memory and can be more than an order of magnitude faster. It is also linearly scalable in terms of database size.