gebhart/patrepeval huggingface dataset:
DEPLETED AND NATURAL URANIUM: CHEMISTRY AND TOXICOLOGICAL EFFECTS (2004)

Depleted uranium (DU) is a by-product from the chemical enrichment of naturally occurring uranium. Natural uranium is comprised of three radioactive isotopes: (238)U, (235)U, and (234)U. This enrichment process reduces the radioactivity of DU to roughly 30% of that of natural uranium. Nonmilitary uses of DU include counterweights in airplanes, shields against radiation in medical radiotherapy units and transport of radioactive isotopes. DU has also been used during wartime in heavy tank armor, armor-piercing bullets, and missiles, due to its desirable chemical properties coupled with its decreased radioactivity. DU weapons are used unreservedly by the armed forces. Chemically and toxicologically, DU behaves similarly to natural uranium metal. Although the effects of DU on human health are not easily discerned, they may be produced by both its chemical and radiological properties. DU can be toxic to many bodily systems, as presented in this review. Most importantly, normal functioning of the kidney, brain, liver, and heart can be affected by DU exposure. Numerous other systems can also be affected by DU exposure, and these are also reviewed. Despite the prevalence of DU usage in many applications, limited data exist regarding the toxicological consequences on human health. This review focuses on the chemistry, pharmacokinetics, and toxicological effects of depleted and natural uranium on several systems in the mammalian body. A section on risk assessment concludes the review.
Novel, Chimpanzee Serotype 68-Based Adenoviral Vaccine Carrier for Induction of Antibodies to a Transgene Product (2002)

An E1-deletion-containing adenoviral recombinant based on the chimpanzee serotype 68 (AdC68) was developed to express the rabies virus glycoprotein. Mice immunized with this construct (AdC68rab.gp) developed antibodies to rabies virus and remained resistant to challenge with an otherwise lethal dose of rabies virus. In naïve mice immunized intranasally, the rabies virus-specific antibody responses elicited by AdC68rab.gp were comparable with regard to both titers and isotype profiles to those induced by an adenoviral recombinant based on human serotype 5 (Adhu5) expressing the same transgene product. In contrast, subcutaneous immunization with the AdC68rab.gp vaccine resulted in markedly lower antibody responses to the rabies virus glycoprotein than the corresponding Adhu5 vaccine. Antibodies from AdC68rab.gp-immunized mice were strongly biased towards the immunoglobulin G2a isotype. The antibody response to the rabies virus glycoprotein presented by Adhu5rab.gp was severely compromised in animals preexposed to the homologous adenovirus. In contrast, the rabies virus-specific antibody response to the AdC68rab.gp vaccine was at most marginally affected by preexisting immunity to common human adenovirus serotypes, such as 2, 4, 5, 7, and 12. This novel vaccine carrier thus offers a distinct advantage over adenoviral vaccines based on common human serotypes.
Immunization of ovarian cancer patients with a synthetic Lewisy-protein conjugate vaccine: A phase 1 trial (2000)

As the initial step in developing carbohydrate-based vaccines for the treatment of ovarian cancer patients in an adjuvant setting, 25 patients were immunized with a Lewis(y) pentasaccharide (Le(y))-keyhole limpet hemocyanin (KLH)-conjugate vaccine together with the immunological adjuvant QS-21. Four different doses of the vaccine, containing 3, 10, 30, and 60 microg of carbohydrate were administered s.c. at 0, 1, 2, 3, 7, and 19 weeks to groups of 6 patients. Sera taken from the patients at regular intervals were assayed by ELISA for reactivity with naturally occurring forms of Le(y) (Le(y)-ceramide and Le(y) mucin) and by flow cytometry and a complement-dependent cytoxicity assay for reactivity with Le(y)-expressing tumor cells. The majority of the patients (16/24) produced anti-Le(y) antibodies as assessed by ELISA, and a proportion of these had strong anti-tumor cell reactivity as assessed by flow cytometry and complement-dependent cytotoxicity. One serum, analyzed in detail, was shown to react with glycolipids but not with glycoproteins or mucins expressed by ovarian cancer cell line OVCAR-3. The vaccine was well tolerated and no gastrointestinal, hematologic, renal, or hepatic toxicity related to the vaccine was observed. On the basis of this study, Le(y)-KLH should be a suitable component for a polyvalent vaccine under consideration for the therapy of epithelial cancers.
Anti-inflammatory effects of carprofen, carprofen enantiomers, and NG-nitro-L-arginine methyl ester in sheep (2002)

Rac-CPF and S(+)CPF inhibited serum thromboxane2 (TXB2) and exudate prostaglandin (PG)E2 generation significantly for 32 hours. Maximal inhibitory effect for serum TXB2 was 79+/-3% for Rac-CPF and 68+/-6% for S(+)CPF. The Rac-CPF and S(+)CPF induced 50 to 98% reversible inhibitory effect for exudate PGE2 generation during a 4- to 32-hour period. The R(-)CPF and LNAME attenuated serum TXB2 generation significantly. The R(-)CPF did not affect exudate PGE2 production, whereas L-NAME potentiated exudate, PGE2 generation by 30% during 4 to 32 hours. The S(+)CPF and LNAME increased leukotriene B4 generation and WBC recruitment in exudate although significance was achieved only at a few time points. Increase in skin temperature over inflammatory cages was effectively inhibited by Rac-CPF and S(+)CPF but not by R(-)CPF CONCLUSIONS AND CLINICAL RELEVANCE: Carprofen is a potent cyclooxygenase inhibitor in vivo in sheep, and its anti-inflammatory effects are attributable only to S(+)CPF in Rac-CPF. Nitric oxide may enhance eicosanoid production and accelerate the acute inflammatory process.
Enhancement of Sindbis Virus Self-Replicating RNA Vaccine Potency by Linkage of Mycobacterium tuberculosis Heat Shock Protein 70 Gene to an Antigen Gene (2001)

Recently, self-replicating RNA vaccines (RNA replicons) have emerged as an effective strategy for nucleic acid vaccine development. Unlike naked DNA vaccines, RNA replicons eventually cause lysis of transfected cells and therefore do not raise the concern of integration into the host genome. We evaluated the effect of linking human papillomavirus type 16 E7 as a model Ag to Mycobacterium tuberculosis heat shock protein 70 (HSP70) on the potency of Ag-specific immunity generated by a Sindbis virus self-replicating RNA vector, SINrep5. Our results indicated that this RNA replicon vaccine containing an E7/HSP70 fusion gene generated significantly higher E7-specific T cell-mediated immune responses in vaccinated mice than did vaccines containing the wild-type E7 gene. Furthermore, our in vitro studies demonstrated that E7 Ag from E7/HSP70 RNA replicon-transfected cells can be processed by bone marrow-derived dendritic cells and presented more efficiently through the MHC class I pathway than can wild-type E7 RNA replicon-transfected cells. More importantly, the fusion of HSP70 to E7 converted a less effective vaccine into one with significant potency against E7-expressing tumors. This antitumor effect was dependent on NK cells and CD8(+) T cells. These results indicated that fusion of HSP70 to an Ag gene may greatly enhance the potency of self-replicating RNA vaccines.
An islet amyloid peptide is derived from an 89-amino acid precursor by proteolytic processing. (1988)

Amyloid deposits occurring in the islets of Langerhans in patients with noninsulin-dependent diabetes mellitus and some insulinomas contain a 37-amino acid peptide that is structurally related to calcitonin gene-related peptide. We have identified three cDNA clones encoding islet amyloid polypeptide (IAPP) or diabetes-associated peptide (DAP) by oligonucleotide screening of a lambda gt10 human insulinoma cDNA library. Two of the three cDNAs contained a domain encoding IAPP/DAP but had an intron-like sequence in their 5' region. The other cDNA contained an open reading frame encoding an 89-amino acid precursor having a typical signal peptide followed by a small prohormone-like sequence containing within it the IAPP/DAP peptide bracketed at its NH2 and COOH termini by Lys-Arg and Gly-Lys-Arg, respectively. These data indicate that this amyloid peptide is generated by proteolytic processing similar to that for proinsulin and other islet prohormones and also that the peptide may be carboxyamidated. The isolation of cDNA clones having 5'-unprocessed intron-like sequences suggests that inefficient or alternative splicing of this mRNA occurred in the insulinoma.
X-Linked Cutis Laxa (1980)

We studied several members of a family with an X-linked form of cutis laxa; the affected males have mild skin laxity, a characteristic facies, skeletal abnormalities, structural abnormalities of the genitourinary tract, and low serum copper levels. The activity of lysyl oxidase, a copper-dependent enzyme involved in cross-link formation in collagen, was decreased in skin-biopsy specimens (13 to 26 per cent of normal) and in culture medium from cells to two affected males (15 to 20 per cent of normal). Immunoreactive lysyl oxidase from skin of both patients was virtually undetectable by immunodiffusion assay. The amounts of lysyl-derived aldehydes (the product formed in collagen and elastin by lysyl oxidase) and of cross-links formed from these products were decreased in dermal fibroblasts in culture. Collagen extractability from these cells was increased in culture. These findings suggest that lysyl oxidase deficiency provides the biochemical basis of the X-linked form of cutis laxa.
INTRASPECIFIC VARIATION IN THE DINOFLAGELLATEGAMBIERDIZSCUS TOXICUS(DINOPHYCEAE). I. ISOZYME ANALYSIS (1997)

ABSTRACT Intraspecific variation among 19 isolates of the ciguatera‐causing dinoflagellate Gambierdiscus toxicus Adachi &amp; Fukuyo (Dinophyceae) collected from French Polynesia, New Caledonia, and the French West Indies was investigated by isozyme analysis. Comparison of their cell sizes and growth rates revealed that significant variation exists among these clones. Comparison of electrophoretic patterns for seven enzyme systems indicated that G. toxicus is comprised of numerous biochemically distinct strains. Isolates from Tubuai and Hao appeared to be the most distantly related. Tahitian strains of G. toxicus also showed a remarkably low degree of similarity with the Tubuai isolates. The latter, which were taken from the same locale in Tubuai, also exhibited highly heterogeneous electrophoretic Profiles when compared to each other, suggesting a multiclonal origin. The single isolate analyzed from the Atlantic Ocean was most closely related to Tahitian isolates, despite their geographic separation. Finally, no clear relationship was found between the electrophoretic profiles of these isolates and their capacity to produce ciguatoxic compounds .
Macromolecular binding (1975)

Abstract Formulas for the free energy of binding to a macromolecule are obtained by thermodynamic and statistical mechanical methods, and it is shown that the free energy of binding is intimately related with the binding polynomial and Wyman's binding potential. The expression for the free energy of binding is applied to a number of cases of ligand‐induced conformational changes, cooperativity, association reactions, etc.
Molecular Bases of Cutaneous and Uveal Melanomas (2011)

Intensive research in recent years has begun to unlock the mysteries surrounding the molecular pathogenesis of melanoma, the deadliest of skin cancers. The high-penetrance, low-frequency susceptibility gene CDKN2A produces tumor suppressor proteins that function in concert with p53 and retinoblastoma protein to thwart melanomagenesis. Aberrant CDKN2A gene products have been implicated in a great many cases of familial cutaneous melanoma. Sporadic cases, on the other hand, often involve constitutive signal transduction along the mitogen-activated protein kinase (MAPK) pathway, with particular focus falling upon mutated RAS and RAF protooncogenes. The proliferative effects of the MAPK pathway may be complemented by the antiapoptotic signals of the PI3K/AKT pathway. After skin, melanoma most commonly affects the eye. Data for the constitutive activation of the MAPK pathway in uveal melanoma exists as well, however, not through mutations of RAS and RAF. Rather, evidence implicates the proto-oncogene GNAQ. In the following discussion, we review the major molecular pathways implicated in both familial and sporadic cutaneous melanomagenesis, the former accounting for approximately 10% of cases. Additionally, we discuss the molecular pathways for which preliminary evidence suggests a role in uveal melanomagenesis.
An Integrated System for 3D Gaze Recovery and Semantic Analysis of Human Attention (2013)

This work describes a computer vision system that enables pervasive mapping and monitoring of human attention. The key contribution is that our methodology enables full 3D recovery of the gaze pointer, human view frustum and associated human centered measurements directly into an automatically computed 3D model in real-time. We apply RGB-D SLAM and descriptor matching methodologies for the 3D modeling, localization and fully automated annotation of ROIs (regions of interest) within the acquired 3D model. This innovative methodology will open new avenues for attention studies in real world environments, bringing new potential into automated processing for human factors technologies.
Necroptosis-Inducing Rhenium(V) Oxo Complexes (2015)

Rhenium(V) oxo complexes of general formula [ReO(OMe)(N^N)Cl2], where N^N = 4,7-diphenyl-1,10-phenanthroline, 1, or 3,4,7,8-tetramethyl-1,10-phenanthroline, 2, effectively kill cancer cells by triggering necroptosis, a non-apoptotic form of cell death. Both complexes evoke necrosome (RIP1-RIP3)-dependent intracellular reactive oxygen species (ROS) production and propidium iodide uptake. The complexes also induce mitochondrial membrane potential depletion, a possible downstream effect of ROS production. Apparently, 1 and 2 are the first rhenium complexes to evoke cellular events consistent with programmed necrosis in cancer cells. Furthermore, 1 and 2 display low acute toxicity in C57BL/6 mice and reasonable stability in fresh human blood.
The possible role of hydrogen sulfide as an endogenous neuromodulator (1996)

Hydrogen sulfide (H2S), which is well known as a toxic gas, is produced endogenously from L-cysteine in mammalian tissues. H2S is present at relatively high levels in the brain, suggesting that it has a physiological function. Two other gases, nitric oxide and carbon monoxide, are also endogenously produced and have been proposed as neuronal messengers in the brain. In this work we show the following: (1) an H2S-producing enzyme, cystathionine beta-synthase (CBS), is highly expressed in the hippocampus; (2) CBS inhibitors hydroxylamine and amino-oxyacetate suppress the production of brain H2S; and (3) a CBS activator, S-adenosyl-L-methionine, enhances H2S production, indicating that CBS contributes to the production of endogenous H2S. We also show that physiological concentrations of H2S selectively enhance NMDA receptor-mediated responses and facilitate the induction of hippocampal long-term potentiation. These observations suggest that endogenous H2S functions as a neuromodulator in the brain.
The Chemical Synthesis and Antiviral Properties of an Acyclovir-phospholipid Conjugate. (1985)

The synthesis of acyclovir-phospholipid conjugate (2) is reported through an unambiguous one-step preparation of L-alpha-dimyristoyl phosphatidic acid triethylammonium salt (5). The biological activity of 2 as an antiviral drug has also been investigated.
An analysis package comparing PID anti-windup strategies (1995)

This article describes software developed in SIMULINK that enables the behavior of feedback control systems with actuator saturation and PID controllers to be evaluated. The software, which is part command- and part menu-driven, allows a choice of four PID controllers using different integral wind-up strategies and transfer function entry of the actuator and plant dynamics. Most realistic control systems contain nonlinearities of some form. One nonlinearity commonly found in control systems is a saturating element. If integral control is applied to such a system to eliminate steady state error, an undesired side effect known as integrator windup may occur when large setpoint changes are made. This effect leads to a characteristic step response with a large overshoot and a very high settling time. To avoid this situation, many different anti-windup strategies have been suggested. This article discusses a software package that has been developed in the SIMULINK/MATLAB environment to investigate and compare the performance of four different anti-windup implementations for PI or PID controllers. The software is partially menu-driven and enables the user to easily enter his own actuator and plant transfer functions to study the performance with the different controllers.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Constitutive expression of the Wilms tumor suppressor gene (WT1) in renal cell carcinoma (1998)

The expression of the Wilms tumor suppressor gene WT1 is largely restricted to elements of the developing urogenital system. In the fetal kidney, WT1 transcripts are present at low levels in the condensing mesenchyme and at much higher levels in differentiating glomerular epithelium and are not detected in other mesenchymal-derived epithelial structures such as the proximal and distal tubules. However, WT1 expression is observed in tubule-like elements found in some Wilms tumors. As renal cell carcinoma (RCC) of the clear cell type is one of the most prevalent adult tumors of the kidney, and is thought to originate from the epithelial cells of the proximal tubules, we studied WT1 expression in RCCs. Despite the absence of WT1 in normal primary epithelial cells derived from proximal tubules, RCC tumors and tumor-derived cell lines expressed WT1 RNA. Immunocytochemical analyses of tumor cryosections showed widespread expression throughout the poorly differentiated epithelial components of the tumor. Immunoblots of RCC samples detected a normal size WT I protein and reciprocal antibody immunoprecipitations of RCC cell extracts indicated that WT I interacts with p53 as has been demonstrated for normal human fetal kidney. The aberrant expression of functional WT1 in RCC may represent a reversion to a more de-differentiated phenotype and may contribute to the tumorigenic phenotype by inappropriately activating or repressing genes involved in growth regulation.
CD40 Ligand and MCP-1 as Predictors of Cardiovascular Events in Diabetic Patients with Stroke (2009)

Up-regulation of inflammatory molecules, such as CD40L and MCP-1, is involved in the advanced stage of atherosclerotic cerebro-vascular disease and is associated with increased risk of recurrence of cardiovascular events.
Polyphenol–caffeine complexation (1986)

Crystal structures of complexes of caffeine (1) with methyl gallate (2), m-nitrobenzoic acid (3), and potassium chlorogenate (4) are described; the results are used to comment on possible modes of association of natural polyphenols with substrates such as proteins.
Transforming growth factor-beta 1 overproduction in prostate cancer: effects on growth in vivo and in vitro. (1992)

We found previously that transforming growth factor-beta 1 (TGF beta 1) mRNA levels are markedly elevated in rat prostate cancer (Dunning R3327 sublines) compared to levels in normal prostate. Our goal was to determine whether elevated expression of TGF beta 1 is biologically relevant to prostate cancer growth in vivo. We chose as our model the R3327-MATLyLu prostate cancer epithelial cell line, which produces metastatic anaplastic tumors when reinoculated in vivo. Our approach was to stably transfect MATLyLu cells with an expression vector that codes for latent TGF beta 1 and to isolate subclones of cells that over-expressed TGF beta 1 mRNA. We also isolated a subclone of MATLyLu cells transfected with a control vector lacking the TGF beta 1 cDNA insert. We then studied the growth of these cells in vivo and in vitro. Twenty days after sc inoculation of 10(6) cells in vivo, TGF beta 1-overproducing MATLyLu tumors were 50% larger, markedly less necrotic, and produced more extensive metastatic disease (lung metastases in 73% of all lobes and lymph node metastases in 88% of animals) compared to control MATLyLu tumors (lung metastases, 21%; lymph node metastases, 7%). Thus, TGF beta 1 produced in vivo is biologically active and can promote prostate cancer growth, viability, and aggressiveness, perhaps via effects on the host and/or on the tumor cells themselves. When followed in vitro, TGF beta 1-overproducing cells became growth inhibited, but this effect was transient as cells subsequently resumed proliferating. Growth inhibition was due to TGF beta, because it could be prevented by TGF beta-neutralizing antibody. Therefore, prostate cancer cells can activate and respond to secreted latent TGF beta 1, and although the cells are transiently inhibited in vitro, there is no net inhibition of growth. The ability of the cells to respond to endogenously produced TGF beta 1 suggests that TGF beta 1 overexpression enhances tumor growth in vivo at least in part via an effect of TGF beta 1 on the tumor cells themselves.
The Endogenous Hallucinogen and Trace Amine N,N-Dimethyltryptamine (DMT) Displays Potent Protective Effects against Hypoxia via Sigma-1 Receptor Activation in Human Primary iPSC-Derived Cortical Neurons and Microglia-Like Immune Cells (2016)

N,N-dimethyltryptamine (DMT) is a potent endogenous hallucinogen present in the brain of humans and other mammals. Despite extensive research, its physiological role remains largely unknown. Recently, DMT has been found to activate the sigma-1 receptor (Sig-1R), an intracellular chaperone fulfilling an interface role between the endoplasmic reticulum (ER) and mitochondria. It ensures the correct transmission of ER stress into the nucleus resulting in the enhanced production of antistress and antioxidant proteins. Due to this function, the activation of Sig-1R can mitigate the outcome of hypoxia or oxidative stress. In this paper we aimed to test the hypothesis that DMT plays a neuroprotective role in the brain by activating the Sig-1R. We tested whether DMT can mitigate hypoxic stress in in vitro cultured human cortical neurons (derived from induced pluripotent stem cells), and in monocyte-derived macrophages and dendritic cells. Here we report that DMT robustly increases the survival of these cell types in severe hypoxia (0.5% O2) through the Sig-1R. Furthermore, this phenomenon is associated with the decreased expression and function of the alpha subunit of the hypoxia-inducible factor 1 (HIF-1) suggesting that DMT-mediated Sig-1R activation may alleviate hypoxia-induced cellular stress and increase survival in a HIF-1-independent manner. Our results reveal a novel and important role of DMT in human cellular physiology. We postulate that this compound may be endogenously generated in situations of stress, ameliorating the adverse effects of hypoxic/ischemic insult to the brain.