gebhart/patrepeval huggingface dataset:
Observations on the anemia and neutropenia of human copper deficiency (1977)

Following extensive bowel resection, a young woman experienced severe malnutrition; subsequent administration of parenteral nutrition precipitated the copper deficiency syndrome. This consisted of hypocupremia, subnormal ceruloplasmin levels, anemia, and severe neutropenia. The bone marrow was megaloblastic, vacuolated, and sideroblastic; granulocytic maturation was not observed beyond the myelocyte stage. Copper sulfate therapy was followed by a marked reticulocytosis, increase in hematocrit, and recovery of neutrophils. Additional studies indicated that both serum and urinary erythropoietin values were low; serum activity increased after copper supplementation. Abnormal granulopoiesis was demonstrated using the in vitro granulocyte colony assay. The patient's granulcoytic stem cells were normal on two occasions; however, mixing studies showed that culture of the patient's copper-deficient marrow with her copper-deficient serum yielded significantly reduced numbers of granulocyte colonies. Thus, copper appears to be a necessary element for normal hematopoiesis; lack of this trace element may result in ineffective erythropoiesis and granulopoiesis.
Specific Inhibition of c-Raf Activity by Semapimod Induces Clinical Remission in Severe Crohn’s Disease (2005)

There is a substantial need for novel treatment strategies in Crohn's disease (CD), a chronic relapsing inflammatory disease of the gut. In an earlier study, we reported clinical efficacy of a 2-wk treatment with semapimod (CNI-1493) in 12 patients with therapy resistant CD. The aim of this study was to identify the cellular target underlying semapimod action. In vitro experiments with murine macrophages showed impaired MAPK signaling and decreased cytokine production due to semapimod treatment. In vitro kinase assays revealed c-Raf as a direct molecular target of semapimod, and semapimod did not affect b-Raf enzymatic activity. Immunohistochemistry performed on paired colon biopsies obtained from CD patients (n = 6) demonstrated increased expression of phospho-MEK, the substrate of Raf. Strikingly, phospho-MEK levels were significantly decreased in patients with a good clinical response to semapimod, but no decrease in phospho-MEK expression was observed in a clinically nonresponsive patient. In conclusion, this study identifies c-Raf as a molecular target of semapimod action and suggests that decreased c-Raf activity correlates with clinical benefit in CD. Our observations indicate that c-Raf inhibitors are prime candidates for the treatment of CD.
An Assessment of the Utility of Tissue Smears in Rapid Cancer Profiling with Desorption Electrospray Ionization Mass Spectrometry (DESI-MS) (2016)

Mass spectrometry imaging with desorption electrospray ionization mass spectrometry (DESI-MS) is used to characterize cancer from ex vivo slices of tissues. The process is time-consuming. The use of tissue smears for DESI-MS analysis has been proposed as it eliminates the time required to snap-freeze and section the tissue. To assess the utility of tissue smears for rapid cancer characterization, principal component analysis (PCA) was performed to evaluate the concordance between DESI-MS profiles of breast cancer from tissue slices and smears prepared on various surfaces. PCA suggested no statistical discrimination between DESI-MS profiles of tissue sections and tissue smears prepared on glass, polytetrafluoroethylene (PTFE), and porous PTFE. However, the abundances of cancer biomarker ions varied between sections and smears, with DESI-MS analysis of tissue sections yielding higher ion abundances of cancer biomarkers compared with smears. Coefficient of variance (CV) analysis suggests DESI-MS profiles from tissue smears are as reproducible as the ones from tissue sections. The limit of detection with smear samples from single pixel analysis is comparable to tissue sections that average the signal from a tissue area of 0.01 mm<sup>2</sup>. The smears prepared on the PTFE surface possessed a higher degree of homogeneity compared with the smears prepared on the glass surface. This allowed single MS scans (~1 s) from random positions across the surface of the smear to be used in rapid cancer typing with good reproducibility, providing pathologic information for cancer typing at speeds suitable for clinical utility. Graphical Abstract ᅟ.
Fabrication of 5-20 nm thick β-W films (2014)

A technique to fabricate 5 to 20 nm thick sputter deposited β W films on SiO2 and Si substrates is presented. This is achieved by growing tungsten on a 5 nm SiO2 layer or in an oxygen controlled environment by flowing 2 sccm of O2 during deposition. Resistivity, X-ray photoelectron spectroscopy, X-ray diffraction and reflectivity studies were performed to determine the phase and thickness of tungsten films. These results demonstrate a technique to grow this film on bare Si or a SiO2 substrate, which can enable growth on the bottom of a write unit in a non-volatile spin logic device.
c-MET mutational analysis in small cell lung cancer: novel juxtamembrane domain mutations regulating cytoskeletal functions. (2003)

Small cell lung cancer (SCLC) is an aggressive cancer, and most patients present with cancer already spread beyond the lung. The receptor tyrosine kinase (RTK) c-MET has been implicated in various solid tumors, including SCLC, and is involved in mediating tumorigenesis, cell motility, scattering, invasion and metastasis. Mutations of c-Met have been described in renal papillary carcinoma and gastrointestinal cancers including hepatocellular carcinoma. The sequence of c-MET was examined for possible mutations in the 10 SCLC cell lines and 32 paired-SCLC/normal tissues. Novel c-MET alterations were identified among 3 of 10 separate SCLC cell lines and in 4 of 32 SCLC tumor tissue samples. These include two different c-MET missense mutations in the juxtamembrane (JM) domain (R988C found in NCI-H69 and H249 cell lines; and T1010I in SCLC tumor sample T31). Also, there are one Sema domain missense mutation (E168D in SCLC tumor sample T5), two-base-pair insertional mutations (IVS13- (52-53)insCT in both SCLC tumor samples T26 and T27) within the pre-JM intron 13, as well as an alternative transcript involving exon 10 (H128 cell line). c-MET receptors are expressed at various levels among the 10 SCLC cell lines studied (high expression: H69, H345, H510, and H526; medium-expression: H128 and H146; and low/no-expression: H82, H209, H249, and H446). The level of c-MET expression does not have any apparent correlation with presence or absence of mutations of c-MET in the cell lines. We show that the two identified JM mutations (R988C and T1010I), when introduced into the interleukin-3 (IL-3)-dependent BaF3 cell line, regulated cell proliferation resulting in a small but significant growth factor independence. When introduced into a SCLC cell line (H446, with minimal endogenous wild-type c-MET expression), the JM mutations also regulated cell morphology and adhesion, as well as causing enhanced tumorigenicity by both increases in focus-formation and soft-agar colony-formation assays. Both of the JM mutations also increased cell motility and migration evident in wound healing assay and time-lapse video-microscopy speed analysis. The JM mutations also altered the c-MET RTK signaling, resulting in preferentially increased constitutive tyrosine phosphorylation of various cellular proteins, including the key focal adhesion protein paxillin on tyrosine residue Y31 (first CRKL-binding site), correlating with increased motility. These results suggest a novel and unique role of the JM domain in c-MET signaling in SCLC with significant implications in cytoskeletal functions and metastatic potential. The novel JM gain-of-function somatic mutations described are the first to be reported in SCLC, and may be associated with a more aggressive phenotype. It would now be useful to study the inhibition of c-MET as a therapeutic target against SCLC.
Expression of a novel gene product by transplants of genetically modified primary fibroblasts in the central nervous system (1991)

Primary fibroblasts initiated from skin biopsies of Wistar rats were transfected with a plasmid that encodes the human growth hormone and the neomycin resistance genes. Cell clones selected for G418 resistance and expressing high levels of human growth hormone were propagated in vitro and subsequently transplanted into the cerebral cortex of adult allogeneic rats. Grafts were examined by immunocytochemistry at weekly intervals up to 2 months. Fibroblasts in the transplants survived and expressed growth hormone clearly up to 4 weeks, but showed reduced expression at 6 to 8 weeks. Significant levels of human growth hormone were also detected by radioimmunoassay in the serum of the host rats up to 1 month. The experiments demonstrate that primary fibroblasts can be genetically modified to deliver a new gene product into the central nervous system, and the gene product can pass the blood-brain barrier to enter the systemic circulation. This model illustrates the potential to introduce desired products into the brain through the genetic alteration of autologous primary fibroblasts.
Gene isolation with human T lymphocyte probes. Isolation of a gene that expresses an epitope recognized by T cells specific for Mycobacterium bovis BCG and pathogenic mycobacteria. (1988)

We have used human CD4+ T lymphocyte clones as primary probes to identify and isolate lambda gt11 rDNA clones that express epitopes recognized by T cells. The method that we describe here permits a direct survey of T cell epitope coding sequences in genomic DNA or cDNA libraries. A lambda gt11 library of Mycobacterium leprae DNA was screened with M. leprae-reactive human T cell clones as probes, allowing the isolation of a M. leprae DNA clone encoding the unidentified Ag. This DNA clone differs in restriction maps from those previously identified by antibody probes and encodes an epitope that is unique to vaccine strains of Mycobacterium bovis bacillus Calmette-Guérin and pathogenic mycobacteria. This method is generally applicable and should expedite the study of Ag and epitopes important to the T cell response in infections and in autoimmune diseases.
Minireview: Role of the Growth Hormone/Insulin-Like Growth Factor System in Mammalian Aging (2005)

The important role of IGF and insulin-related signaling pathways in the control of longevity of worms and insects is very well documented. In the mouse, several spontaneous or experimentally induced mutations that interfere with GH biosynthesis, GH actions, or sensitivity to IGF-I lead to extended longevity. Increases in the average life span in these mutants range from approximately 20-70% depending on the nature of the endocrine defect, gender, diet, and/or genetic background. Extended longevity of hypopituitary and GH-resistant mice appears to be due to multiple mechanisms including reduced insulin levels, enhanced insulin sensitivity, alterations in carbohydrate and lipid metabolism, reduced generation of reactive oxygen species, enhanced resistance to stress, reduced oxidative damage, and delayed onset of age-related disease. There is considerable evidence to suggest that the genetic and endocrine mechanisms that influence aging and longevity in mice may play a similar role in other mammalian species, including the human.
A historical perspective of CSTA (1996)

Computer-supported telecommunications applications (CSTA) is one of the more important standards for computer-telecommunications interfaces, addressing service and protocol definitions used to provide a link between computers and telecommunications systems. The services provided on a CSTA link between a telecommunications and computer network work much like the services that telecommunication network provides to a user at an access point. At the point of attachment to a telecommunications network, the "phone numbers" are sufficient to describe the desired object for involvement with a service. If a new object were created for the purposes of CSTA (e.g., a monitoring group), an identifier which would work like a phone number in that network would be assigned to that object. Additional handle-identifiers are created and provided after a service is initiated to differentiate between instances of the service being provided. To show this relationship, a functional model was created.
Chemical synthesis and structural characterization of the RGD‐protein decorsin: A potent inhibitor of platelet aggregation (1998)

Decorsin is a 39-residue RGD-protein crosslinked by three disulfide bridges isolated from the leech Macrobdella decora belonging to the family of GPIIb-IIIa antagonists and acting as a potent inhibitor of platelet aggregation. Here we report the solid-phase synthesis of decorsin using the Fmoc strategy. The crude polypeptide was purified by reverse-phase HPLC in its reduced form and allowed to refold in the presence of glutathione. The homogeneity of the synthetic oxidized decorsin was established by reverse-phase HPLC and capillary zone electrophoresis. The results of amino acid analysis after acid hydrolysis of the synthetic protein, NH2-terminal sequencing and mass determination (4,377 Da) by electrospray mass spectrometry were in full agreement with this theory. The correct pairing of the three disulfide bridges in synthetic decorsin was determined by a combined approach of both peptide mapping using proteolytic enzymes and analysis of the disulfide chirality by CD spectroscopy in the near-UV region. Synthetic decorsin inhibited human platelet aggregation with an IC50 of approximately 0.1 microM, a figure quite similar to that determined utilizing decorsin from natural source. In particular, the synthetic protein was 2,000-fold more potent than a model RGD-peptide (e.g., Arg-Gly-Asp-Ser) in inhibiting platelet aggregation. Thermal denaturation experiments of synthetic decorsin, monitored by CD spectroscopy, revealed its high thermal stability (Tm approximately 74 degrees C). The features of the oxidative refolding process of reduced decorsin, as well as the thermal stability of the oxidized species, were compared with those previously determined for the NH2-terminal core domain fragment 1-41 or 1-43 from hirudin. This fragment shows similarity in size, pairing of the three disulfides and three-dimensional structure with those of decorsin, even if very low sequence similarity. It is suggested that the less efficient oxidative folding and the enhanced thermal stability of decorsin in respect to those of hirudin core domain likely can be ascribed to the presence of the six Pro residues in the decorsin chain, whereas none is present in the hirudin domain. The results of this study indicate that decorsin can be obtained by solid-phase methodology in purity and quantities suitable for structural and functional studies and thus open the way to prepare by chemical methods novel decorsin derivatives containing unusual amino acids or even non-peptidic moieties.
[Low affinity human IgE receptor: cloning cDNA from B-lymphocytes of cell line 1B and study of its expression in peripheral blood B-cells]. (1995)

Previously, the cDNA coding for human low-affinity receptor for IgE (FcERII/CD23) was cloned by three independent groups. Using oligonucleotide probes corresponding to the published cDNA sequence of CD23, we have isolated cDNA clones encoding FcERII from the cDNA library of B-lymphoblastoid cell line 1B obtained in our laboratory. Cloned nucleotide sequences of FcERII were shown to be identical to those from the RPMI8866 cell line. Using a DNA fragment containing the full-length cDNA copy of CD23 as a probe, CD23 expression in highly purified peripheral blood B lymphocytes was shown to be induced by recombinant human IL4 in a clearly dose-dependent manner.
Overspill of Catheter Locking Solution: Safety and Efficacy Aspects (2003)

Avoidance of clotting in catheter lumens between treatments usually entails locking with an anticoagulant solution such as heparin. Catheter manufacturers specify internal volume of the catheters, and it is commonly assumed that injection of this precise filling volume is safe and efficient. However, it has been shown that activated partial thromboplastin time (aPTT) increases after instillation of the heparin lock volume specified by the manufacturer. We have investigated this phenomenon in vitro using dye and saline dilution and found that injection of the catheter volume results in spillage of up to 15% of the catheter volume into the patient's blood. Depending on fluid dynamics of the instillation process and catheter compliance, the concentration of the locking solution at the catheter tip is much reduced. As a consequence of this overshoot, the mean concentration at the tip is reduced to approximately 90%. In conclusion, the injection volume must exceed 120% of the catheter lumen for achieving the full strength of the locking solution at the tip. The overshoot may have clinical consequences, (e.g., bleeding if highly concentrated heparin is used).
Crystal structure of human T cell leukemia virus type 1 gp21 ectodomain crystallized as a maltose-binding protein chimera reveals structural evolution of retroviral transmembrane proteins (1999)

Retroviral entry into cells depends on envelope glycoproteins, whereby receptor binding to the surface-exposed subunit triggers membrane fusion by the transmembrane protein (TM) subunit. We determined the crystal structure at 2.5-A resolution of the ectodomain of gp21, the TM from human T cell leukemia virus type 1. The gp21 fragment was crystallized as a maltose-binding protein chimera, and the maltose-binding protein domain was used to solve the initial phases by the method of molecular replacement. The structure of gp21 comprises an N-terminal trimeric coiled coil, an adjacent disulfide-bonded loop that stabilizes a chain reversal, and a C-terminal sequence structurally distinct from HIV type 1/simian immunodeficiency virus gp41 that packs against the coil in an extended antiparallel fashion. Comparison of the gp21 structure with the structures of other retroviral TMs contrasts the conserved nature of the coiled coil-forming region and adjacent disulfide-bonded loop with the variable nature of the C-terminal ectodomain segment. The structure points to these features having evolved to enable the dual roles of retroviral TMs: conserved fusion function and an ability to anchor diverse surface-exposed subunit structures to the virion envelope and infected cell surface. The structure of gp21 implies that the N-terminal fusion peptide is in close proximity to the C-terminal transmembrane domain and likely represents a postfusion conformation.
Efficient Immunoglobulin Gene Disruption and Targeted Replacement in Rabbit Using Zinc Finger Nucleases (2011)

Rabbits are widely used in biomedical research, yet techniques for their precise genetic modification are lacking. We demonstrate that zinc finger nucleases (ZFNs) introduced into fertilized oocytes can inactivate a chosen gene by mutagenesis and also mediate precise homologous recombination with a DNA gene-targeting vector to achieve the first gene knockout and targeted sequence replacement in rabbits. Two ZFN pairs were designed that target the rabbit immunoglobulin M (IgM) locus within exons 1 and 2. ZFN mRNAs were microinjected into pronuclear stage fertilized oocytes. Founder animals carrying distinct mutated IgM alleles were identified and bred to produce offspring. Functional knockout of the immunoglobulin heavy chain locus was confirmed by serum IgM and IgG deficiency and lack of IgM(+) and IgG(+) B lymphocytes. We then tested whether ZFN expression would enable efficient targeted sequence replacement in rabbit oocytes. ZFN mRNA was co-injected with a linear DNA vector designed to replace exon 1 of the IgM locus with ∼1.9 kb of novel sequence. Double strand break induced targeted replacement occurred in up to 17% of embryos and in 18% of fetuses analyzed. Two major goals have been achieved. First, inactivation of the endogenous IgM locus, which is an essential step for the production of therapeutic human polyclonal antibodies in the rabbit. Second, establishing efficient targeted gene manipulation and homologous recombination in a refractory animal species. ZFN mediated genetic engineering in the rabbit and other mammals opens new avenues of experimentation in immunology and many other research fields.
Impurity‐Associated Colour Centres in Mg‐ and Ca‐Doped Al2O3 Single Crystals (1981)

Abstract In Mg‐ and Ca‐doped α‐Al 2 O 3 crystals irradiated by X‐rays at 80 K new paramagnetic colour centres are observed having an absorption band at about 255 nm and an emission band at 310 nm. The hyperfine structure of the EPR spectrum indicates that the unpaired electron spin interacts mainly with two Al 27 nuclei. The optical and EPR spectra are consistent with the model of a centre involving one electron trapped at an anion vacancy adjoining the substitutional divalent ion (F Mg or F Ca ). The luminescence band at 290 nm observed in the TSL peak at 225 K is suggested to result from the recombination of the holes with the F Mg (F Ca ) centres.
The Preparation and Properties of Amorphous Silicon (1969)

A radio‐frequency glow discharge is used to deposit films of amorphous silicon from silane gas on to substrates at 25°–650°C. These films have resistivities at 21°C of up to 1014 ohm‐cm and have large temperature coefficients of resistivity. A photoconductive effect is observed which reaches a maximum for films deposited at 300°C, and a sample is compared with a cell. The effects of heat‐treatment, ageing, and doping on the properties of amorphous silicon are reported. The variation of properties with deposition temperature is related to the structural changes with temperature that have been observed for this material.
ENERGY CONVERSION OF CONCENTRATED NEAR INFRARED RADIATION IN A SOLAR GREENHOUSE (2007)

The aim of this investigation was to develope a new type of greenhouse with an integrated filter.The filter reflects and concentrates the near infrared radiation (NIR) which is then converted to electric power by means of TPV cells.In northern countries, with colder winter climate conditions, energy saving is an important issue.Moreover, during the summer, cooling by natural ventilation is needed to remove excess energy.In the southern countries with high global radiation and outdoor temperatures during the summer, cooling of greenhouses is even more important [1].An important issue is the concentration potential of the integrated reflector.In this study several approaches were investigated and a circular trough reflector appeared to be most suitable.The most important properties concerning concentration capabilities were investigated to come to an optimal concept regarding generated power, constructional limits and growing conditions.With the concept presented in this paper, cooling can be combined with power generation up to a an electric output of about 20 kWh annually per m greenhouse on a yearly base.The produced electricity can be used for energy supply and/or for extra cooling with a pad and fan system and/or a desalination system.The concept will be worked out to an operating prototype.
Adenovirus-mediated transfer of a wild-type p53 gene and induction of apoptosis in cervical cancer. (1996)

In most cervical cancers, the function of p53 is down regulated. To explore the potential use of p53 in gene therapy for cervical cancer, we introduced wild-type p53 into cervical cancer cell lines via a recombinant adenoviral vector, Ad5CMV-p53, and analyzed its effects on cell and tumor growth. The transduction efficiencies of all cell lines were 100% at a multiplicity of infection of 100 or greater. The p53 protein was detected in Ad5CMV-p53-infected cells. Protein expression peaked at day 3 after infection and lasted 15 days. The Ad5CMV-p53-infected cells underwent apoptosis, and cell growth was greatly suppressed. The Ad5CMV-p53 treatment significantly reduced the volumes of established s.c. tumors in vivo. These results indicate that transfection of cervical cancer cells with the wild-type p53 gene via Ad5CMV-p53 is a potential novel approach to the therapy of cervical cancer.