gebhart/patrepeval huggingface dataset:
PIK3R1 (p85α) Is Somatically Mutated at High Frequency in Primary Endometrial Cancer (2011)

Phosphoinositide 3-kinase (PI3K) is an important therapeutic target. Mutations in PIK3CA, which encodes p110α, the catalytic subunit of PI3K, occur in endometrioid endometrial cancers (EEC) and nonendometrioid endometrial cancers (NEEC). The goal of this study was to determine whether PIK3R1, which encodes p85α, the inhibitory subunit of PI3K, is mutated in endometrial carcinoma. We carried out exonic sequencing of PIK3R1 from 42 EECs and 66 NEECs. The pattern of PIK3R1 mutations was compared with the patterns of PIK3CA, PTEN, and KRAS mutations. The biochemical effect of seven PIK3R1 mutations was examined by stable expression in U2OS cells, followed by coimmunoprecipitation analysis of p110α, and Western blotting of phospho-AKT(Ser473) (p-AKT(Ser473)). We found that PIK3R1 was somatically mutated in 43% of EECs and 12% of NEECs. The majority of mutations (93.3%) were localized to the p85α-nSH2 and -iSH2 domains. Several mutations were recurrent. PIK3R1 mutations were significantly (P = 0.0015) more frequent in PIK3CA-wild type EECs (70%) than in PIK3CA mutant EECs (18%). Introduction of wild-type p85α into U2OS cells reduced the level of p-AKT(Ser473) compared with the vector control. Five p85α mutants, p85αdelH450-E451, p85αdelK459, p85αdelY463-L466, p85αdelR574-T576, and the p85αN564D positive control, were shown to bind p110α and led to increased levels of p-AKT(Ser473). The p85αR348X and p85αK511VfsX2 mutants did not bind p110α and showed no appreciable change in p-AKT(Ser473) levels. In conclusion, our study has revealed a new mode of PI3K alteration in primary endometrial tumors and warrants future studies to determine whether PIK3R1 mutations correlate with clinical outcome to targeted therapies directed against the PI3K pathway in EEC and NEEC.
Dietary magnesium supplements improve B-cell response to glucose and arginine in elderly non-insulin dependent diabetic subjects (1989)

Hypomagnesemia and low erythrocyte magnesium content are both common findings in non-insulin-dependent diabetic subjects. Moreover, intracellular magnesium may play a crucial role in modulating B-cell response to glucose by interfering with potassium permeability. Eight elderly, moderately obese, non-insulin-dependent diabetic subjects were treated with either magnesium supplementation (3 g/day) to the diet or placebo. Both treatment schemes lasted 4-weeks and were separated by a 'wash-out' of 3 weeks. At the end of each treatment period, in glucose test (0.33 g/kg for 3 min) and an iv arginine (5 g) test were performed to determine the B-and A-cell responses. Dietary magnesium supplementation vs placebo produced a slight but significant decrease in basal plasma glucose (8.6 +/- 0.3 vs 8.0 +/- 0.1 mmol/l, p less than 0.05) and an increase in acute insulin response after iv glucose (3.7 +/- 2.3 vs - 14.7 +/- 0.9 pmol.l 1. (10 min)-1, p less than 0.01) and after iv arginine (151 +/- vs 81 +/- 15 pmol.l-1. (10 min)-1, p less than 0.01), respectively. Plasma glucagon levels were unaffected by chronic dietary magnesium supplementation as well under basal conditions as in response to arginine. Net increase in acute insulin response after iv glucose and after iv arginine was significantly correlated to the net increase in erythrocyte magnesium content after dietary magnesium supplementation. We conclude that magnesium administration may be a useful adjuvant to the classic hypoglycemic agents in the treatment of non-insulin-dependent diabetic subjects.
Stimulation of Pig Growth Performance by Porcine Growth Hormone and Growth Hormone-Releasing Factor (1986)

The current study was undertaken to determine the effects of human growth hormone-releasing factor [hpGRF-(1-44)-NH2] on growth performance in pigs and whether this response was comparable to exogenous porcine growth hormone (pGH) treatment. Preliminary studies were conducted to determine if GRF increased plasma GH concentration after iv and im injection and the nature of the dose response. Growth hormone-releasing factor stimulated the release of pGH in a dose-dependent fashion, although the individual responses varied widely among pigs. The results from the im study were used to determine the dose of GRF to use for a 30-d growth trial. Thirty-six Yorkshire-Duroc barrows (initial wt 50 kg) were randomly allotted to one of three experimental groups (C = control, GRF and pGH). Pigs were treated daily with 30 micrograms of GRF/kg body weight by im injection in the neck. Pigs treated with pGH were also given 30 micrograms/kg body weight by im injection. Growth rate was increased 10% by pGH vs C pigs (P less than .05). Growth rate was not affected by GRF; however, hot and chilled carcass weights were increased 5% vs C pigs (P less than .05). On an absolute basis, adipose tissue mass was unaffected by pGH or GRF. Carcass lipid (percent of soft-tissue mass) was decreased 13% by GRF (P less than .05) and 18% by pGH (P less than .05). Muscle mass was significantly increased by pGH but not by GRF. There was a trend for feed efficiency to be improved by GRF; however, this was not different from control pigs. In contrast, pGH increased feed efficiency 19% vs control pigs (P less than .05). Chronic administration of GRF increased anterior pituitary weight but did not affect pituitary GH content or concentration. When blood was taken 3 h post-injection, both GRF- and pGH-treated pigs had lower blood-urea nitrogen concentrations. Serum glucose was significantly elevated by both GRF and pGH treatment. This was associated with an elevation in serum insulin. These results indicate that increasing the GH concentration in blood by either exogenous GH or GRF enhances growth performance. The effects of pGH were more marked than for GRF. Further studies are needed to determine the optimal dose of GRF to administer in growth trials and the appropriate pattern of GRF administration in order to determine whether GRF will enhance pig growth performance to the extent that exogenous pGH does.
Aggregation of deoxyhemoglobin subunits (1976)

The formation of deoxyhemoglobin was examined by measuring the heme spectral change that accompanies the aggregation of isolated alpha and beta chains. At low hemeconcentrations (less than 10(-5) M), tetramer formation can be described by two consecutive, second order reactions representing the aggregation of monomers followed by the association of alphabeta dimers. At neutral pH, the rates of monomer and dimer aggregation are roughly the same, approximately 5 X 10(5) M(-1) X(-1) at 20 degrees. Raising or lowering the pH results in a uniform decrease of both aggregation rates due presumably to repulsion of positively charged subunits at acid pH and repulsion of negatively charged subunits at alkaline pH. Addition of p-hydroxymercuribenzoate to alpha chains lowers the rate of monomer aggregation whereas addition of mercurials to the beta subunits appears to lower both the rate of monomer and the rate of dimer aggregation. At high heme concentrations (greater than 10(-5) M) or in the presence of organic phosphates, the rate of chain aggregation becomes limited, in part, by the slow dissociation of beta chain tetramers. In the case of inositol hexaphosphate, the rate of hemoglobin formation exhibits a bell-shaped dependence on phosphate concentration. When intermediate concentrations of inositol hexaphosphate (approximately 10(-4 M) are preincubated with beta subunits, a slow first order time course is observed and exhibits a half-time of about 8 min. As more inositol hexaphosphate is added, the chain aggregation reaction begins to occur more rapidly. Eventually at about 10(-2) M inositol hexaphospate, the time course becomes almost identical to that observed in the absence of phosphates. The increase in the velocity of the chain aggregation reaction at high phosphate concentrations suggests strongly that inositol hexaphosphate binds to beta monomers and, if added in sufficiently large amounts, promotes beta4 dissociation. A quantitative analysis of these results showed that the affinity of beta monomers for inositol hexaphosphate is the same as that of alphabeta dimers. Only when tetramers are formed, either alpha2beta2 or beta4, is a marked increase in affinity for inositol hexaphosphate observed.
A (2005)

This chapter contains sections titled: Abrasion treatment Accelerated ageing Acid–base interactions: introduction Acid–base surface energy parameters Acids Acrylic adhesives Adhesion Adhesion – fundamental and practical Adhesion in dentistry: orthodontics and prosthodontics Adhesion in dentistry: restorative materials Adhesion in medicine Adhesive classification Adhesives – historical perspective Adhesives for textile fibre bonding Adhesives in textile coating, laminating and printing Adhesives in the textile industry Adsorption theory of adhesion Aerospace applications of adhesives Alkyl-2-cyanoacrylates Anaerobic adhesives Animal glues and technical gelatins Anodizing Atomic force microscopy Auger electron spectroscopy Automotive applications Autophoretic primers
Spectroscopic properties of ethidium monoazide: a fluorescent photoaffinity label for nucleic acids (1978)

The non-covalent binding of ethidium monoazide to nucleic acids is entirely analogous to that of ethidium (binding constant approximately 2-3 X 10(5) M). The ethidium monoazide can be photochemically covalently linked to nucleic acids in high yield, up to 75%, by long wavelength light. The fluorescence of ethidium monoazide and ethidium crosslinked to nucleic acids show the same environmental sensitivity as does the fluorescence of ethidium. These properties of ethidium monoazide indicate its use as a fluorescent photoaffinity label for nucleic acids. Ethidium diazide can be photochemically linked to nucleic acids but appears to have properties substantially different from those of ethidium.
Determinants of Antileukemia Effects of Allogeneic NK Cells (2004)

In HLA-nonidentical bone marrow transplantation, we studied the characteristics of donor NK cells, recipient leukemia cells, and the cytokine environment that predict the antileukemia effects of allogeneic NK cells. We found that the risk of relapse in pediatric patients with hematologic malignancies was best predicted by a model taking into consideration the presence of inhibitory killer cell Ig-like receptors (KIRs) on the donor's NK cells and the absence of corresponding KIR ligand in the recipient's HLA repertoire (a receptor-ligand model). The risk of relapse was prognosticated less precisely by the Perugia donor-recipient KIR ligand-ligand mismatch model or by a natural cytotoxicity model. In contrast to the ligand-ligand model, we found that the new receptor-ligand model was accurate when analysis was applied to patients with lymphoid malignancy. These findings corroborate our observations that the recipient's KIR repertoire, which was derived from highly purified, HLA-disparate CD34+ cells, resumed a donor-specific pattern within 3 mo of transplantation, but did not correlate evidently with the donor or recipient ligand repertoire. In an in vitro assay and an in vivo mouse model, human NK cell cytotoxicity toward human leukemia cells with 11q23 chromosomal rearrangement increased with the number of receptor-ligand mismatch pairs or prestimulation with IL-12 and IL-18. These findings provide new insights into the determinants of antileukemia effects of allogeneic NK cells and therapeutic strategies.
Recent Patents on MicroRNA-Induced Pluripotent Stem Cell Generation (2012)

Regenerative medicine using pluripotent stem cells represents the future for curing developmental abnormalities, degenerative disorders and aging-related illnesses. However, today’s regenerative medicine faces two major challenges with respect to stem cells: their shortage in supply and uncertain safety in clinical therapy. The recent discovery of induced pluripotent stem cells (iPS cells or iPSCs) derived from patients’ somatic cells presents a possible solution for the supply shortage problem. Yet, iPSC generation with the enforced overexpression of previously defined four factors Oct4– Sox2-Klf4-c-Myc (OSKM) also causes oncogenic stimulation, which leads to potential tumorigenicity. The more recent development of miR302-mediated iPSC generation may further solve this problem since miR-302, a tiny 23-nucleotide non-coding microRNA (miRNA), is able to replace all four OSKM in mediating iPSC formation while preventing the onset of stem cell tumorigenicity. MiR-302-reprogrammed iPSCs (mirPSCs) not only possess a highly demethylated genome but also share >92% gene expression similarity with human embryonic stem cells (hESCs). Transplantation of mirPSCs into immunocompromised mice leads to the formation of relatively organized tissue cysts containing various cell types derived from all three embryonic germ layers (ectoderm, mesoderm and endoderm), providing a potential tool for regenerative medicine. Hence, this novel iPSC technology offers a simple, effective and safe method for not only reprogramming somatic cells to hESC-like pluripotent stem cells but also maintaining stem cell pluripotency in tumor-free conditions. Conceivably, mirPSCs present a more suitable choice of iPSCs based on current Food and Drug Administration (FDA) regulations. Due to the novelty of this recent technology, a majority of patent applications are still pending and are mainly led by two major research groups, Lin et al. (WJWU & LYNN Institute - 7 filings) and Yamanaka et al. (Kyoto University - 3 filings). This review will summarize all relevant patent applications and describe the mechanisms underlying this new miRNA-mediated iPSC generation technology.
Increased MDR1 Expression in Normal and Malignant Peripheral Blood Mononuclear Cells Obtained from Patients Receiving Depsipeptide (FR901228, FK228, NSC630176) (2006)

The increased expression of markers associated with a differentiated phenotype, such as P-glycoprotein (Pgp), follows treatment with histone deacetylase inhibitors. Because depsipeptide (FR901228, FK228, NSC630176) is a substrate for Pgp, up-regulation of the gene that encodes it, MDR1, would mean that depsipeptide induces its own mechanism of resistance. To examine the effect of depsipeptide on expression of ATP-binding cassette transporters associated with multidrug resistance, the kidney cancer cell lines 108, 121, 127, and 143 were treated with depsipeptide and evaluated by quantitative reverse transcription-PCR. Increased levels of MDR1 (1.3- to 6.3-fold) and ABCG2 (3.2- to 11.1-fold) but not MRP1 (0.9- to 1.3-fold) were observed. The induced Pgp transported the fluorescent substrates rhodamine 123, bisantrene, calcein-AM, BODIPY-vinblastine, and BODIPY-paclitaxel. In normal peripheral blood mononuclear cells (PBMC) and circulating tumor cells obtained from patients receiving depsipeptide, increased levels of histone H3 acetylation were found. We next examined MDR1 levels in normal and malignant PBMCs obtained from 15 patients enrolled in clinical trials with depsipeptide and detected up to a 6-fold increase in normal PBMCs and up to an 8-fold increase in circulating tumor cells after depsipeptide administration. In one patient with Sézary syndrome, increased MDR1 gene expression was accompanied by increased cell surface Pgp expression in circulating Sézary cells as determined by measurement of MRK-16 staining by flow cytometry. These studies suggest that depsipeptide induces its own mechanism of resistance and thus provide a basis for clinical trials evaluating depsipeptide in combination with a Pgp inhibitor.
The endothelium and vascular inflammation in diabetes (2007)

The endothelium releases multiple mediators, not only regulators of vasomotor function but also important physiological and pathophysiological inflammatory mediators. Endothelial dysfunction is caused by chronic exposure to various stressors such as oxidative stress and modified low-density lipoprotein (LDL) cholesterol, resulting in impaired nitric oxide (NO) production and chronic inflammation. Biomechanical forces on the endothelium, including low shear stress from disturbed blood flow and hypertension, are also important causes of endothelial dysfunction. These processes seem to be augmented in patients with diabetes. In states of insulin resistance and in type 2 diabetes insulin signalling is impaired. Increased vascular inflammation, including enhanced expression of interleukin- 6 (IL-6), vascular cellular adhesion molecule-1 (VCAM-1) and monocyte chemoattractant protein (MCP- 1) are observed, as is a marked decrease in NO bioavailability. Furthermore, hyperglycaemia leads to increased formation of advanced glycation end products (AGE), which quench NO and impair endothelial function. In summary, during the development of diabetes a number of biochemical and mechanical factors converge on the endothelium, resulting in endothelial dysfunction and vascular inflammation. In the presence of insulin resistance, these processes are potentiated and they provide a basis for the macrovascular disease seen in diabetes.
Acute Graft-versus-Host Disease in Pancreas Transplantation: A Comparison of Two Case Presentations and a Review of the Literature (2006)

As a complication of solid organ transplantation, acute graft-versus-host disease (GVHD) is most associated with small bowel and liver transplants. We present two cases of acute GVHD following pancreas transplantation. Case 1 was a 27-year-old female who underwent cadaveric pancreas transplant 9 months after a successful live donor kidney transplant. Case 2 was a 38-year-old male who received a simultaneous cadaveric pancreas and live donor kidney transplant. Both patients presented within 30 days of transplant with nonspecific symptoms. Rejection and infection were ruled out. Both subjects had progressive decline in mentation associated with pancytopenia and hyperbilirubinemia. Rash was not present until late in their hospital course. Skin biopsies demonstrated mixed chimerism with pancreas donor DNA diagnostic of GVHD. Acute GVHD is a rare, often fatal, complication of pancreas transplantation, and its presentation appears to differ from acute GVHD associated with stem cell transplantation.
Mice with a disrupted IFN-γ gene are susceptible to the induction of experimental autoimmune encephalomyelitis (EAE) (1996)

Abstract Experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis, is an autoimmune disorder seen in mice and rats following immunization with myelin basic protein (MBP) or MBP-derived peptides. IFN-γ, a cytokine produced by a variety of cells, is involved in many inflammatory and immune regulatory events. Contradictory results concerning exacerbations and the disease course were seen comparing injections of IFN-γ in humans suffering from multiple sclerosis to studies using anti-IFN-γ Abs in mice with EAE. To study the role of IFN-γ and IFN-γ-producing cells in EAE, we crossed IFN-γ knockout mice (H-2b) (unable to produce IFN-γ due to the disruption of the IFN-γ gene) with an EAE-susceptible mouse strain, B10.PL (H-2u). EAE was seen in IFN-γ knockout mice, heterozygotic (IFN-γ +/-) mice, as well as wild-type littermates following immunization with MBP. Histologic analyses of the central nervous system of IFN-γ knockout mice with EAE revealed massive infiltrates composed of lymphocytes, macrophages, and granulocytes. We conclude that the presence of IFN-γ is not crucial to the induction or the clinical course of EAE.
Active recognition: using uncertainty to reduce ambiguity (1996)

Scene ambiguity, due to noisy measurements and uncertain object models, can be quantified and actively used by an autonomous agent to efficiently gather new data and improve its information about the environment. In this work an information-based utility measure is used to derive from a learned classification of shape models an efficient data collection strategy, specifically aimed at increasing classification confidence when recognizing uncertain shapes.
Transfer printing of flexible hybrid inductor-capacitor filters via pre-etched silicon-on-insulator mother wafer (2012)

An approach for the processing of flexible electronics is presented. To protect the functional insulator in the structure, hybrid inductor-capacitor (LC) filters were fabricated on the pre-etched silicon-on-insulator wafer, where the selectively patterned semi-stable Si-supporting membranes were sufficiently robust to support the entire device fabrication process, yet flexible enough to facilitate the subsequent transfer printing via adhesive stamp. When the LC filters were transferred to an elastomeric substrate, 20% compressibility was achieved, giving rise to “wavy” deformation of the devices and up to 9% variation in the electronic properties. Beyond the 20% strain, local delamination of the films resulted in mechanical instability.
Catalytic Carbonylation of β-Lactones to Succinic Anhydrides (2004)

A well-defined, highly active and selective catalyst for the synthesis of succinic anhydrides from CO and beta-lactones is reported. At 200 psi of CO, the catalyst [(N,N'-bis(3,5-di-tert-butylsalicylidene)phenylenediamino)Al(THF)2][Co(CO)4] carbonylates beta-propiolactones to succinic anhydrides in high yield. (R)-beta-Butyrolactone is carbonylated to (S)-methylsuccinic anhydride with clean inversion of stereochemistry, while cis-2,3-dimethyl-beta-propiolactone yields exclusively trans-2,3-dimethylsuccinic anhydride. These data are consistent with a mechanism involving nucleophilic attack by [Co(CO)4]- on the beta carbon of the lactone, followed by CO insertion and anhydride formation.
Structure-based drug design (1998)

Most of the techniques used in structure-based drug design have experienced significant improvements in the past few years, resulting in a marked enhancement of the speed and the efficacy of this approach. At the same time, it was thought that the future of drug design lay in strategies involving solely combinatorial chemistry. It is becoming evident, however, that the development of future drugs will use a combination of methods that will contain a major component of structure-based design.
Palliative use of a stent for colonic obstruction caused by adenocarcinoma in two cats (2006)

Abstract Case Description —Two adult male castrated cats were evaluated because of a history of constipation, tenesmus, or intermittent vomiting. Clinical Findings —Radiography and ultrasonography revealed luminal narrowing in the colon of 1 cat and a colonic mass in the other. A histopathologic diagnosis of colonic adenocarcinoma was made in both cats. Treatment and Outcome —Under fluoroscopic guidance, a self-expanding metallic stent was advanced over a wire and across the area of colonic stenosis and deployed. One cat had progressive weight loss but maintained a normal appetite, energy, and a high quality of life. Fecal continence was maintained, and tenesmus was rarely observed. The cat was euthanized because of tumor metastasis 274 days after the colonic stent was placed. The other cat retained fecal continence, and the owners reported subjective improvement in the severity of tenesmus, compared with that prior to stent placement. The cat was euthanized 19 days after stent placement because of perceived decreased quality of life. Clinical Relevance —The use of self-expanding metallic stents for alleviation of colonic obstruction secondary to adenocarcinoma in cats appears to be effective. This technique provides a simple, quick, nonsurgical option for palliation in cats with advanced metastatic or systemic disease in which surgical resection may not be possible or warranted.
Inhibition of Accelerated Atherosclerosis in Vein Grafts by Placement of External Stent in ApoE*3-Leiden Transgenic Mice (2002)

Extravascular stent placement results in strong inhibition of accelerated vein graft atherosclerosis in hypercholesterolemic transgenic mice and thereby provides a perspective for therapeutic intervention in vein graft diseases.