gebhart/patrepeval huggingface dataset:
Identification of cIAP1 as a candidate target gene within an amplicon at 11q22 in esophageal squamous cell carcinomas. (2001)

Amplification of chromosomal DNA is thought to be one of the mechanisms that activate cancer-related genes in tumors. In a recent study, we identified high copy-number amplification at 11q21-q23 in cell lines derived from esophageal squamous cell carcinomas (ESCs) using comparative genomic hybridization. Because 11q21-q23 amplification has been reported in tumors of various other types as well, gene(s) associated with tumor progression may lie within this chromosomal region. To identify the most likely target(s) for amplification at 11q21-q23, we determined the extent of the amplicon by fluorescence in situ hybridization and then analyzed ESC cell lines for expression levels of 11 known genes and one uncharacterized transcript present within the 1.8-Mb commonly amplified region. Only cIAP1, a member of the IAP (antiapoptotic) gene family, was consistently overexpressed in cell lines that showed amplification. Additionally, the cIAP1 protein was overexpressed in the primary tumors from which those cell lines had been established. The ESC cell lines with cIAP1 amplification were resistant to apoptosis induced by chemotherapeutic reagents. An increase in cIAP1 copy number was also detected in 4 of 42 (9.5%) primary ESC tumors that were not related to the cell lines examined. Because inhibition of apoptosis seems to be an important feature of carcinogenesis, cIAP1 is likely to be a target for 11q21-23 amplification and may be involved in the progression of ESC, as well as other malignancies.
ROLE OF COLLOIDAL OATMEAL IN DERMATOLOGIC TREATMENT OF THE AGED (1953)

SKIN PROBLEMS of the aged are receiving greater attention<sup>1</sup>since this age group comprises an increasing proportion of the total population. Many of the skin problems presented by the aged may be encountered in the younger age groups as well. Their occurrence, however, in a geriatric patient presents certain problems. Blood vessels of the aging skin exhibit varying degrees of sclerosis, which interferes with the circulation of the organ. Atrophy of the epidermis occurs, which results in a flattening of the epidermodermal junction and in a slower regeneration of the epidermal cells. A modification of the subcutaneous tissue and varying degrees of atrophy of the cutaneous appendages occur. There is a loss of the elastic fibers and a degeneration of the collagen tissue, resulting in a thinner corium with less resilience. Wrinkles are the clinical manifestation of these changes. Accompanying these histopathologic changes is a modified skin physiology.
Use of synthetic peptides for the detection of antibodies against the nef reguating protein in sera of HIV-infected patients (1989)

Human sera were tested for the presence of anti-nef antibodies by radioimmunoassay (RIA), with recombinant radiolabelled nef expressed in E. coli. Of the 300 HIV-positive sera tested by RIA, 70 +/- 5.3% were found to be anti-nef positive. Anti-nef antibodies bound to nef with a high affinity (K 0.5 = 2.2 x 10(-9) M). In 31 of the sera, the specificity of anti-nef antibodies was further analysed by enzyme-linked immunosorbent assay (ELISA) with large synthetic peptides ranging from 31 to 66 amino acid residues and spanning the total sequence of nef from HIV-1. The results obtained showed that the immunodominant antigenic sites of nef were located close to the N- and C-terminal regions of the molecule.
Molecular and cellular mediators of Alzheimer's disease inflammation (2001)

A wide range of inflammatory mediators has been demonstrated in the Alzheimer’s disease (AD) brain during the past 15 years (for previous reviews, see [6, 279,298,340,343]). Questions nonetheless remain, including even the designation of AD inflammatory mechanisms as a true inflammatory response. Like multiple sclerosis, the cardinal signs of peripheral inflammation, the “rubor et tumor cum calore et dolore” (redness and swelling with heat and pain) that Cornelius Celsus defined as criteria 2000 years ago, are not present in AD. Indeed, AD inflammation does not appear to include even cell-mediated humoral lymphocyte responses, as multiple sclerosis clearly does. Rather, our current understanding of AD inflammation suggests that it is an endogenously-mediated, localized reaction, an innate inflammatory response similar to that mounted in the periphery when localized tissue damage and the chronic deposition of highly insoluble, abnormal material occurs. Such primarily macrophagemediated reactions have been classed as inflammatory for over a century, and that designation, with glia as the brain intermediaries, certainly should hold for AD. Henry Wisniewski, who we honor by this special journal issue, was one of the first to come to grips with these simple principles of AD inflammation, and to apply them to other brain disorders. If we understand that localized brain inflammation is likely to arise wherever there is localized brain damage and deposits of highly insoluble, abnormal material, then prion diseases be-
Hepatocyte growth factor affects satellite cell activation and differentiation in regenerating skeletal muscle (2000)

Hepatocyte growth factor (HGF) is the only known growth factor that activates quiescent satellite cells in skeletal muscle. We hypothesized that local delivery of HGF may enhance regeneration after trauma by increasing the number of myoblasts available for restoring normal tissue architecture. Injection of HGF into muscle at the time of injury increases myoblast number but does not enhance tissue repair as determined using quantitative histological analyses. Rather, depending on the dose and the timing of HGF administration relative to the injury, regeneration can be inhibited. The greatest inhibitory effect is observed when HGF is administered on the day of injury and continued for 3 days, corresponding to the time when satellite cell activation, proliferation, and early differentiation normally occur. To establish a mechanism for this inhibition, we show that HGF can act directly on primary muscle cells to block differentiation. These results demonstrate that 1) exogenous HGF synergizes with factors in damaged muscle to increase myoblast number, 2) regeneration is not regulated solely by myoblast number, and 3) HGF inhibits muscle differentiation both in vitro and in vivo.
Anemia and Chronic Renal Failure: A Therapeutical Approach by Reduced Glutathione Parenteral Administration (1992)

Authors report on the effect of reduced glutathione parenterally administered on the anemic status in patients suffering from chronic renal failure and undergoing hemodialysis. Twenty patients were studied for 180 days and were divided into two age- and sex-matched groups. The first group (10 patients) received placebo, the second group (10 patients) received the treatment (1,200 mg of reduced glutathione). Reduced glutathione and placebo were given for 120 days in a randomized double-blind fashion and the following measurements were performed: red blood cells reduced and oxidized glutathione, plasma reduced and oxidized glutathione, hematocrit, hemoglobin, reticulocytes, serum iron, transferrin, indirect bilirubin, urea, creatinine, calcium, phosphate, parathyroid hormone and alkaline phosphatase. In the treated group, during the supplementation period, there was an increase in the levels of red blood cells and plasma reduced glutathione, hematocrit and hemoglobin and a concomitant decrease in plasma oxidized glutathione and reticulocytes with a maximum effect on the 120th day of therapy. In the placebo-treated group there were no significant variations of the parameters considered during the study period. When the therapy, on patients undergoing treatment, was terminated there was a drop in the analyzed parameters, which fell to pretreatment values at the subsequent controls. These findings seem to indicate that reduced glutathione could represent a useful drug in the treatment and management of anemia in patients affected by chronic renal failure.
IL-7 Enhances Thymic Human T Cell Development in “Human Immune System” Rag2−/−IL-2Rγc−/− Mice without Affecting Peripheral T Cell Homeostasis (2009)

IL-7 is a central cytokine in the development of hematopoietic cells, although interspecies discrepancies have been reported. By coculturing human postnatal thymus hematopoietic progenitors and OP9-huDL1 stromal cells, we found that murine IL-7 is approximately 100-fold less potent than human IL-7 for supporting human T cell development in vitro. We investigated the role of human IL-7 in newborn BALB/c Rag2(-/-)gamma(c)(-/-) mice transplanted with human hematopoietic stem cells (HSC) as an in vivo model of human hematopoiesis using three approaches to improve IL-7 signaling: administration of human IL-7, ectopic expression of human IL-7 by the transplanted human HSC, or enforced expression of a murine/human chimeric IL-7 receptor binding murine IL-7. We show that premature IL-7 signaling at the HSC stage, before entrance in the thymus, impeded T cell development, whereas increased intrathymic IL-7 signaling significantly enhanced the maintenance of immature thymocytes. Increased thymopoiesis was also observed when we transplanted BCL-2- or BCL-x(L)-transduced human HSC. Homeostasis of peripheral mature T cells in this humanized mouse model was not improved by any of these strategies. Overall, our results provide evidence for an important role of IL-7 in human T cell development in vivo and highlight the notion that IL-7 availability is but one of many signals that condition peripheral T cell homeostasis.
Intracellular Stress Signaling Pathways Activated During Human Islet Preparation and Following Acute Cytokine Exposure (2004)

Pancreatic islet transplantation may successfully restore normoglycemia in type 1 diabetic patients. However, successful grafting requires transplantation of a sufficient number of islets, usually requiring two or more donors. During the isolation process and following clinical transplantation, islets are subjected to severe adverse conditions that impair survival and ultimately contribute to graft failure. Here, we have mapped the major intracellular stress-signaling pathways that may mediate human islet loss during isolation and following cytokine attack. We found that the isolation procedure potently recruits two pathways consisting of |mitogen-activated protein kinase kinase (MKK)7 --> Jun NH(2)-terminal kinase (JNK)/p38 --> c-fos| and the |nuclear factor-kappaB (NF-kappaB) --> iNOS| module. Cytokines activate the |NF-kappaB --> iNOS| and |MKK4/MKK3/6 --> JNK/p38| pathways without recruitment of c-fos. Culturing the islets for 48 h after isolation allows for the activated pathways to return to background levels, with expression of MKK7 becoming undetectable. These data indicate that isolation and cytokines recruit different death pathways. Therefore, strategies might be rationally developed to avoid possible synergistic activation of these pathways in mediating islet loss during isolation and following grafting.
Cloning, functional expression and characterization of a human olfactory receptor. (1999)

The human olfactory system can recognize and discriminate a large number of different odorant molecules. The detection of chemically distinct odorants begins with the binding of an odorant ligand to a specific receptor protein on the olfactory neuron cell surface. To address the problem of olfactory perception at a molecular level, we have cloned, functionally expressed and characterized the first human olfactory receptor (OR 17-40). Application of a mixture of hundred different odorants elicited a transient increase in intracellular calcium at HEK 293-cells which were transfected with a plasmid containing the receptor encoding DNA and a membrane import sequence. By subdividing the odorant mixture in smaller groups we could identify a single component which represented the only effective substance: helional. Testing some structurally closely related molecules we found only one other compound which also could activate the receptor: heliotropyl acetone. All other compounds tested were completely ineffective. These findings represent the beginning of molecular understanding of odorant recognition in humans.
Seismic capacity of infilled frames using neural networks (2009)

The applicability of neural networks, trained on compiled experimental database, for prediction of the seismic behavior and capacity of reinforced-concrete infilled frames is explored. The work was motivated due to a great deal of uncertainty in the estimation of the seismic capacity of infilled frames and evaluation of complex infill effect. Despite a big number of experimental studies on infilled frames there is still a lack of understanding between the behavior and the geometric parameters such as ratio of height to length of frame, reinforcement ratio of frame elements, material properties of frame (reinforced - concrete) and infill (masonry), loading histories, etc. An experimental database used in this study has been compiled from the available literature and includes data from the laboratory test carried out on one story, one bay reinforced - concrete frames infilled with unreinforced masonry infill. Neural networks simulate human's brain ability to classify patterns or to make predictions or decisions based upon past experience using data sets. The network consists of input layer, hidden neurons and output layer. The inputs of the created neural networks are geometrical and material properties of frame and infill, reinforcement ratios of frame elements and loading. Output variables, which have an important role in performance evaluation, are deformation capacity in terms of drift, shear strength and failure modes of infilled frames. The main goal of this paper is to make a contribution towards the quantitative determination of the performance capability of specific structural elements – reinforced/concrete infilled frames, whose behavior depends on many variables and is often unpredictable. Their performance, expressed in terms of shear strength and deformation capacity is of vital importance for the evaluation of the seismic performance of existing buildings as well as for the design of earthquake resistant reinforced concrete buildings.
Fumigant activity of (E)‐anethole identified in Illicium verum fruit against Blattella germanica (2001)

The insecticidal activities of materials derived from the fruit of star anise, Illicium verum, against adults of Blattella germanica were examined by direct contact application and fumigation methods, and compared with those of DDVP, deltamethrin and hydramethylnon. The biologically active constituent of the Illicium fruit was characterized as the phenylpropene, (E)-anethole, by spectroscopic analysis. In a filter paper diffusion test with females, (E)-anethole caused 80.3% mortality at 0.159 mg cm-2 at 1 and 3 days after treatment (DAT), whereas 16.7% mortality at 3 DAT was achieved at 0.079 mg cm-2. DDVP and deltamethrin gave > 90% mortality at 0.019 mg cm-2 at 1 DAT. At 0.009 mg cm-2, DDVP and deltamethrin showed 73.3 and 60% mortality at 1 DAT, respectively, but 93.3 and 76.7% mortality at 3 DAT. Hydramethylnon exhibited 0 and 93.3% mortality at 0.159 mg cm-2 at 1 and 3 DAT, respectively, whereas 6.7% mortality at 3 DAT was observed at 0.079 mg cm-2. In a fumigation test with females, (E)-anethole was much more effective in closed cups than in open ones, indicating that the insecticidal activity of the compound was largely attributable to fumigant action. (E)-Anethole and DDVP caused 100% mortality at 0.398 and 0.051 mg cm-2 4 and 1 h after treatment, respectively. (E)-Anethole showed 46.7% mortality at 0.199 mg cm-2 at 3 DAT, whereas deltamethrin and hydramethylnon at 0.796 mg cm-2 was ineffective for 3-day period. As naturally occurring insect-control agents, the I verum fruit-derived materials described could be useful for managing populations of B germanica.
DNA Sequence-Based „Bar Codes” for Tracking the Origins of Expressed Sequence Tags from a Maize cDNA Library Constructed Using Multiple mRNA Sources (2003)

To enhance gene discovery, expressed sequence tag (EST) projects often make use of cDNA libraries produced using diverse mixtures of mRNAs. As such, expression data are lost because the origins of the resulting ESTs cannot be determined. Alternatively, multiple libraries can be prepared, each from a more restricted source of mRNAs. Although this approach allows the origins of ESTs to be determined, it requires the production of multiple libraries. A hybrid approach is reported here. A cDNA library was prepared using 21 different pools of maize (Zea mays) mRNAs. DNA sequence "bar codes" were added during first-strand cDNA synthesis to uniquely identify the mRNA source pool from which individual cDNAs were derived. Using a decoding algorithm that included error correction, it was possible to identify the source mRNA pool of more than 97% of the ESTs. The frequency at which a bar code is represented in an EST contig should be proportional to the abundance of the corresponding mRNA in the source pool. Consistent with this, all ESTs derived from several genes (zein and adh1) that are known to be exclusively expressed in kernels or preferentially expressed under anaerobic conditions, respectively, were exclusively tagged with bar codes associated with mRNA pools prepared from kernel and anaerobically treated seedlings, respectively. Hence, by allowing for the retention of expression data, the bar coding of cDNA libraries can enhance the value of EST projects.
Phylogenetic relationships among prokaryotic and eukaryotic catalases (1997)

Seventy-four catalase protein sequences, including 29 bacterial, 8 fungal, 7 animal, and 30 plant sequences, were compiled, and 70 were used for phylogenetic reconstruction. The core of the resulting tree revealed unique, separate groups of plant and animal catalases, two groups of fungal catalases, and three groups of bacterial catalases. The only overlap of kingdoms occurred within one branch and involved fungal and bacterial large-subunit enzymes. The other fungal branch was closely linked to the group of animal enzymes. Group I bacterial catalases were more closely related to the plant enzymes and contained such diverse taxa as the Gram-positive Listeria seeligeri, Deinocococcus radiodurans, and gamma-proteobacteria. Group III bacterial sequences were more closely related to fungal and animal sequences and included enzymes from a broad range of bacteria including high- and low-GC Gram positives, proteobacteria, and a bacteroides species. Group II was composed of large-subunit catalases from diverse sources including Gram positives (low-GC Bacilli and high-GC Mycobacteria), proteobacteria, and species of the filamentous fungus Aspergillus. These data can be interpreted in terms of two gene duplication events that produced a minimum of three catalase gene family members that subsequently evolved in response to environmental demands. Horizontal gene transfer may have been responsible for the group II mixture of bacterial and fungal large-subunit catalases.
Total synthesis of natural (levo) and enantiomeric (dextro) forms of prostaglandin E1 (1969)

1 newly-discovered method of synthesizing PGE1 (prostaglandin E1) is explained and diagrammed chemically. Recrystallization of the synthetic product produced material identical in all respects with natural PGE1. The synthetic product showed the same infrared spectrum and chromatographic values as racemic and natural forms of PGE1. The biological activity of the synthetic product was found to be .1% of that of the naturally-occurring PGE1 in the stimulation of smooth muscle contraction. This is the 1st report of a total synthesis of PGE1. Research continues on improvements in this synthesizing method and on discovering other synthetic approaches to PGs.
Molecular evidence for a clonal relationship between multiple lesions in patients with unknown primary adenocarcinoma (2008)

Unknown primary adenocarcinoma (UPA) comprises a group of heterogeneous cancers of great clinical and biological interest. UPA presents as metastatic disease without a detectable primary site after medical workup. Here we investigated whether or not a clonal relationship exists between multiple tumors within individual UPA patients. A molecular resemblance would argue for an early clonal outgrowth of tumor cells from the primary lesion, a mutual feature observed within this group of neoplasms. In 14 patients with UPA multiple tumors, obtained at autopsy, were analyzed by molecular allelotyping and immunohistochemistry. In addition, tumors of 4 patients could be analyzed by comparative genomic hybridization (CGH). Similar genetic and phenotypic profiles were used as indicator for a clonal relationship, whereas different profiles implicate independent tumors. The molecular data indicated that the multiple lesions in the 14 UPA patients, including the primary tumors, are clonally related. In agreement with the theory of tumor progression, some metastatic lesions showed additional genetic alterations besides the characteristics that were shared with the primary tumor. Furthermore, 8 UPA patients had tumors with a high frequency of allelic loss and/or imbalance (FALI; 43-71%), while 6 patients demonstrated a lower FALI (14-29%), suggesting the occurrence of chromosomal instability in the former group. Our data provide molecular evidence for a clonal relationship between multiple metastases and the primary tumor within individual UPA patients, independent of the anatomical origin of the cancer. This finding is in agreement with the suggestion that tumor progression is rapid in UPA patients, limiting the chance of clonal divergence. The identification of 2 groups of UPAs with either a high or low FALI indicates that chromosomal instability is not the only driving force behind early tumor cell dissemination. Thus, other molecular mechanisms must underlie the common biology of these tumors.
Structural role for a conserved region in the CTP synthetase glutamine amide transfer domain (1987)

Site-directed mutations were introduced into a conserved region of the Escherichia coli CTP synthetase glutamine amide transfer domain. The amino acid replacements, valine 349 to serine, glycine 351 to alanine, glycine 352 to proline, and glycine 352 to cysteine, all increased the lability of CTP synthetase. The proline 352 replacement abolished the capacity to form the covalent glutaminyl-cysteine 379 catalytic intermediate, thus preventing glutamine amide transfer function; NH3-dependent CTP synthetase activity was retained. In CTP synthetase (serine 349), both glutamine and NH3-dependent activities were increased approximately 30% relative to that of the wild type. CTP synthetase mutants alanine 351 and cysteine 352 were not overproduced because of apparent instability and proteolytic degradation. We conclude that the conserved region between residues 346 and 355 in the CTP synthetase glutamine amide transfer domain has an important structural role.
Mechanism of nanoblister formation in Ga+ self-ion implanted GaN nanowires (2005)

The formation of voids and bubbles during ion implantation is an important area of material research. Void and bubble formation can result in swelling and embrittlement of metallic or semiconducting materials, and increase catalytic effects in the nanopores of the bubble. Here, we report the observation of metallic nanoblister formation in GaN nanowires under self-ion implantation using a Ga+ focused ion beam. The mechanism of the blister formation was resolved using high-resolution transmission electron microscopy equipped with electron energy loss spectroscopy and plasmon imaging.