gebhart/patrepeval huggingface dataset:
Homozygous mutation of MYBPC3 associated with severe infantile hypertrophic cardiomyopathy at high frequency among the Amish (2008)

Homozygous mutations in the MYBPC3 gene have been identified as the cause of severe infantile HCM among the Amish population.
A systematic review of electrical stimulation for pressure ulcer prevention and treatment in people with spinal cord injuries (2014)

The methodological quality of the studies was poor, in particular for prevention studies. A significant effect of ES on enhancement of PU healing is shown in limited Grade I evidence. The great variability in ES parameters, stimulating locations, and outcome measure leads to an inability to advocate any one standard approach for PU therapy or prevention. Future research is suggested to improve the design of ES devices, standardize ES parameters, and conduct more rigorous trials.
Inhibition of c‐Jun N‐terminal kinase decreases cardiomyocyte apoptosis and infarct size after myocardial ischemia and reperfusion in anaesthetized rats (2004)

1 Myocardial ischemia/reperfusion is associated with inflammation, apoptosis and necrosis. During this process, c-jun N-terminal kinase is activated in cardiac myocytes resulting in apoptosis. 2 This study investigates the effects of AS601245, a nonpeptide ATP competitive JNK inhibitor, on infarct size caused by myocardial ischemia/reperfusion in anaesthetized rats. The left descending coronary artery of anaesthetized rats was occluded for 30 min and then reperfused for 3 h. AS601245 was administered 5 min before the end of the ischemia period as an i.v. bolus (1.5, 4.5 or 15 mg kg(-1) i.v.) followed by continuous i.v. infusion (18, 55 and 183 microg kg(-1) min(-1), respectively) during reperfusion. Controls received saline only. 3-Aminobenzamide, a poly(ADP-ribose) polymerase inhibitor, was used as reference compound at 10 mg kg(-1) i.v. bolus plus 0.17 mg kg(-1) min(-1) continuous infusion. 3 AS601245 significantly reduced infarct size at 4.5 mg kg(-1) (-44%; P<0.001) and 15 mg kg(-1) i.v. (-40.3%; P<0.001) similarly to 3-aminobenzamide (-44.2%; P<0.001). This protective effect was obtained without affecting hemodynamics or reducing ST-segment displacement. 4 The beneficial effects on infarct size correlated well with the reduction of c-jun phosphorylation (-85%; P<0.001 versus control) and of TUNEL-positive cells (-82.1%; P<0.001) in post-ischemic cardiomyocytes. No change in the phosphorylation state of p38 MAPK and ERK in post-ischemic heart was observed in the presence of AS601245 in comparison to the vehicle-treated group. 5 These results demonstrate that blocking the JNK pathway may represent a novel therapeutic approach for treating myocardial ischemia/reperfusion-induced cardiomyocyte death.
The expanded tomato fruit volatile landscape (2013)

The present review aims to synthesize our present knowledge about the mechanisms implied in the biosynthesis of volatile compounds in the ripe tomato fruit, which have a key role in tomato flavour. The difficulties in identifiying not only genes or genomic regions but also individual target compounds for plant breeding are addressed. Ample variability in the levels of almost any volatile compound exists, not only in the populations derived from interspecific crosses but also in heirloom varieties and even in commercial hybrids. Quantitative trait loci (QTLs) for all tomato aroma volatiles have been identified in collections derived from both intraspecific and interspecific crosses with different wild tomato species and they (i) fail to co-localize with structural genes in the volatile biosynthetic pathways and (ii) reveal very little coincidence in the genomic regions characterized, indicating that there is ample opportunity to reinforce the levels of the volatiles of interest. Some of the identified genes may be useful as markers or as biotechnological tools to enhance tomato aroma. Current knowledge about the major volatile biosynthetic pathways in the fruit is summarized. Finally, and based on recent reports, it is stressed that conjugation to other metabolites such as sugars seems to play a key role in the modulation of volatile release, at least in some metabolic pathways.
Antitumor activity of TZT-1027 (Soblidotin). (2006)

Because its growth-inhibitory and antitumor activities were superior to those of the other drugs tested, including the tubulin inhibitors paclitaxel, docetaxel and vincristine, TZT-1027 should be useful in the chemotherapy of tumors that are not responsive to other tubulin inhibitors.
Antibodies : a laboratory manual (2014)

"The focus of Antibodies: A Laboratory Manual, 2nd Edition, will be unchanged from the original edition by Ed Harlow and David Lane and will cover both the production and use of antibodies in a way that is accessible to the nonimmunologist. The emphasis will be on contemporary, essential antibody-based methods that are tried, true, necessary, and useful to a broad population of life scientists. The manual will provide up-to-date protocols that work reproducibly, along with explanations as to how and why methods work and how to choose between alternative approaches. Methods that have become research staples since the manual was originally published will be included at the same level of detail and organization as the existing topics"--
Identification and Characterization of Newsworthy Verbs in World News (2015)

We present a data-driven technique for acquiring domain-level importance of verbs from the analysis of abstract/article pairs of world news articles. We show that existing lexical resources capture some the semantic characteristics for important words in the domain. We develop a novel characterization of the association between verbs and personal story narratives, which is descriptive of verbs avoided in summaries for this domain.
Reduction of Vertebral Fracture Risk in Postmenopausal Women With Osteoporosis Treated With Raloxifene<SUBTITLE>Results From a 3-Year Randomized Clinical Trial</SUBTITLE> (1999)

In postmenopausal women with osteoporosis, raloxifene increases bone mineral density in the spine and femoral neck and reduces risk of vertebral fracture.
Docking in Metal-Organic Frameworks (2009)

The use of metal-organic frameworks (MOFs) so far has largely relied on nonspecific binding interactions to host small molecular guests. We used long organic struts (approximately 2 nanometers) incorporating 34- and 36-membered macrocyclic polyethers as recognition modules in the construction of several crystalline primitive cubic frameworks that engage in specific binding in a way not observed in passive, open reticulated geometries. MOF-1001 is capable of docking paraquat dication (PQT2+) guests within the macrocycles in a stereoelectronically controlled fashion. This act of specific complexation yields quantitatively the corresponding MOF-1001 pseudorotaxanes, as confirmed by x-ray diffraction and by solid- and solution-state nuclear magnetic resonance spectroscopic studies performed on MOF-1001, its pseudorotaxanes, and their molecular strut precursors. A control experiment involving the attempted inclusion of PQT2+ inside a framework (MOF-177) devoid of polyether struts showed negligible uptake of PQT2+, indicating the importance of the macrocyclic polyether in PQT2+ docking.
CD4+ T cells in cancer stroma, not CD8+ T cells in cancer cell nests, are associated with favorable prognosis in human non‐small cell lung cancers (2003)

We investigated intratumoral tumor-infiltrating lymphocytes (TILs), including CD4(+) and CD8(+) T cells, in non-small cell lung cancers (NSCLCs) and their relationships with clinicopathological variables and post-operative survival. Tumor specimens from 178 NSCLCs were consecutively obtained by surgery at the Hokkaido University Medical Hospital between 1976 and 1994. CD8(+) T cells, CD4(+) T cells and Ki-67/CD8(+) T cells were visualized immunohistochemically, and counted within cancer cell nests and in cancer stroma. CD8(+) T cells and CD4(+) T cells were observed at higher frequencies within cancer cell nests in moderately and poorly differentiated tumors compared with well differentiated tumors (P < 0.01), and in tumors with high Ki-67 expression compared with low Ki-67 expression (P < 0.01), that showed severe cellular atypia and a higher growth rate. Patients with higher numbers of CD8(+) T cells within cancer cell nests showed significantly shorter survival times compared to those with lower numbers of CD8(+) T cells within cancer cell nests (5-year survival rates, 47% and 60%, respectively; P = 0.03). Moreover, patients with higher labeling index of Ki-67/CD8(+) T cells showed significantly shorter survival than those with lower labeling index of Ki-67/CD8(+) T cells within cancer cell nests (5-year survival rates, 41% and 69%, respectively; P = 0.02), and the labeling index of Ki-67/CD8(+) T cells within cancer cell nests was found to be a significant and independent unfavorable prognostic factor by multivariate analysis (P = 0.01). On the other hand, higher numbers of CD4(+) T cells in cancer stroma, but not within cancer cell nests, were correlated with longer survival times in patients with NSCLC (5-year survival rates, 64% and 43%, respectively; P = 0.04). CD4(+) T cells in cancer stroma might reflect immune responses against cancer cells, while CD8(+) T cells do not appear to work as effectors in tumor tissues of NSCLC. Moreover, the higher labeling index of Ki-67/CD8(+) T cells within cancer cell nests is a strong indicator of unfavorable clinical outcome.
Comparative Effects of Alpha-2 and DA-2 Agonists on Intraocular Pressure in Pigmented and Nonpigmented Rabbits (1993)

Alpha-2 and DA2 adrenoceptor agonists produce ocular hypotension in cats, rabbits, monkeys and humans. In this study, the effects of topical, unilateral administration of medetomidine (MED), an alpha-2 agonist, and Ha-118 (HA), a DA2 agonist, were compared on intraocular pressure (IOP) in normal, unilaterally sympathectomized (SX), and ocular hypertensive (oral water loaded) Dutch Belted (DB) and New Zealand White (NZW) rabbits. MED (75 micrograms) produced bilateral ocular hypotensive effects in both DB and NZW normal rabbits; however, HA (250 micrograms) lowered IOP unilaterally in NZW rabbits only. MED (25 micrograms) inhibited the rise in IOP caused by oral water loading in both DB and NZW rabbits; HA, on the other hand, was effective only in NZW rabbits. Topical bilateral pretreatment with metoclopramide, a DA2 antagonist, inhibited the ocular antihypertensive effect of HA in NZW rabbits. The IOP lowering effects of MED were absent in the SX eyes of DB and NZW rabbits, but hypotensive responses to MED were present in normal (contralateral) eyes of both strains. In contrast, HA was effective only in the treated, normal eyes of SX NZW rabbits. These data support pharmacodynamic roles for alpha-2 and DA2 receptors in modulating IOP. The lack of activity by HA in DB rabbit eyes suggests a possible absence of DA2 receptors or excessive binding of HA to pigment in the anterior segment of DB rabbit eyes.
Growth hormone secretagogue MK-677 (2008)

Despite evidence of target engagement as indicated by an increase in serum insulin-like growth factor-1, the human growth hormone secretagogue MK-677 25 mg was ineffective at slowing the rate of progression of Alzheimer disease.
MAUB Is a New Mucin Antigen Associated with Bladder Cancer (1996)

The M344 tumor-associated antigen, expressed in 70% of superficial bladder tumors, is a sialylated carbohydrate present on a high molecular mass thiol-reducible secreted mucin, which we named MAUB for mucin antigen of the urinary bladder. Herein we studied the relationship between MAUB and other known mucins in the MGH-U3 bladder cancer line where MAUB expression is modulated by culture conditions. Northern blots, immunoradiometric assays, and Western blots showed that only MUC1 and MUC2 are expressed in this MAUB-positive cell line. MUC1 differs from MAUB by its molecular mass and its non-oligomeric nature, while MUC2 has similar molecular mass and response to culture conditions. However, in double determinant immunoradiometric assays, MAUB and MUC2 did not cross-react. Moreover, confocal microscopy showed different subcellular localization of the two antigens. Treatment of MGH-U3 cells with MUC2 antisense oligodeoxynucleotides resulted in decreased expression of MUC2 and increased expression of MAUB, ruling out the possibility that monoclonal antibody M344 recognizes a different glycosylated form of MUC2. In addition, we identified a tumor specimen expressing MAUB but no MUC2 antigen or mRNA. Together, these results suggest that there is expression of at least three mucins in MGH-U3 cells and that MAUB is a cancer-associated mucin distinct from those identified so far.
Functional analysis of protein N-myristoylation: metabolic labeling studies using three oxygen-substituted analogs of myristic acid and cultured mammalian cells provide evidence for protein-sequence-specific incorporation and analog-specific redistribution. (1990)

Covalent attachment of myristic acid (C14:0) to the NH2-terminal glycine residue of a number of cellular, viral, and oncogene-encoded proteins is essential for full expression of their biological function. Substitution of oxygen for methylene groups in this fatty acid does not produce a significant change in chain length or stereochemistry but does result in a reduction in hydrophobicity. These heteroatom-containing analogs serve as alternative substrates for mammalian myristoyl-CoA:protein N-myristoyltransferase (EC 2.3.1.97) and offer the opportunity to explore structure/function relationships of myristate in N-myristoyl proteins. We have synthesized three tritiated analogs of myristate with oxygen substituted for methylene groups at C6, C11, and C13. Metabolic labeling studies were performed with these compounds and (i) a murine myocyte cell line (BC3H1), (ii) a rat fibroblast cell that produces p60v-src (3Xsrc), or (iii) NIH 3T3 cells that have been engineered to express a fusion protein consisting of an 11-residue myristoylation signal from the Rasheed sarcoma virus (RaSV) gag protein linked to c-Ha-ras with a Cys----Ser-186 mutation. This latter mutation prevents isoprenylation and palmitoylation of ras. Two-dimensional gel electrophoresis of membrane and soluble fractions prepared from cell lysates revealed different patterns of incorporation of the analogs into cellular N-myristoyl proteins (i.e., protein-sequence-specific incorporation). In addition, proteins were identified that underwent redistribution from membrane to soluble fractions after incorporating one but not another analog (analog-specific redistribution). Comparable studies using the model RaSV-ras chimeric protein also demonstrated analog-specific differences in incorporation, varying from approximately 25% of the total RaSV-ras chimeric protein with 5-octyloxypentanoate to greater than 50% with 12-methoxydodecanoate. Modification by this latter compound was so extensive that the amount of membrane-associated N-myristoylated protein was decreased. Incorporation of each of the analogs caused a dramatic redistribution to the soluble fraction, comparable to that seen when myristoylation was completely blocked by mutating the protein's site of myristate attachment (glycine) to an alanine residue. The demonstration that these analogs differ in the extent to which they are incorporated and in their ability to cause redistribution of any single protein suggests that they may also have sufficient selectivity to be of potential therapeutic value.
Structure Evolution During Processing of Polycrystalline Films (2000)

▪ Abstract Polycrystalline films have wide variety of applications in which their grain structures affect their performance and reliability. Thin film growth techniques and growth conditions affect grain shapes, the distribution of grain sizes, and the distribution of the crystallographic orientations of grains. Variations in these structural properties are affected by the conditions under which grain nucleation, growth, coarsening, coalescence, and thickening occur. General trends in structural evolution in polycystalline films, as a function of processing conditions and materials class, are discussed in terms of these fundamental kinetic processes.
SciMiner: web-based literature mining tool for target identification and functional enrichment analysis (2009)

Supplementary data are available at Bioinformatics online.
PARP1 Is Overexpressed in Nasopharyngeal Carcinoma and Its Inhibition Enhances Radiotherapy (2013)

Nasopharyngeal carcinoma is a rare but highly invasive cancer. As options of agents for effective combination chemoradiotherapy for advanced nasopharyngeal carcinoma are limited, novel therapeutic approaches are desperately needed. The ubiquitin ligase CHFR is known to target PARP1 for degradation and is epigenetically inactivated in nasopharyngeal carcinoma. We present evidence that PARP1 protein is indeed overexpressed in nasopharyngeal carcinoma cells in comparison with immortalized normal nasopharyngeal epithelial cells. Tissue microarray analysis also indicated that PARP1 protein is significantly elevated in primary nasopharyngeal carcinoma tissues, with strong correlation with all stages of nasopharyngeal carcinoma development. We found that the PARP inhibitor AZD2281 (olaparib) increased DNA damage, cell-cycle arrest, and apoptosis in nasopharyngeal carcinoma cells challenged with ionizing radiation or temozolomide. Isobologram analysis confirmed that the cytotoxicity triggered by AZD2281 and DNA-damaging agents was synergistic. Finally, AZD2281 also enhanced the tumor-inhibitory effects of ionizing radiation in animal xenograft models. These observations implicate that PARP1 overexpression is an early event in nasopharyngeal carcinoma development and provide a molecular basis of using PARP inhibitors to potentiate treatment of nasopharyngeal carcinoma with radio- and chemotherapy.
Characterization of wild-type and an active-site mutant in Escherichia coli of short-chain acyl-CoA dehydrogenase from Megasphaera elsdenii (1993)

The objective of this work is to determine the molecular mechanism and regulation of short-chain acyl-CoA dehydrogenase (SCAD) from Megasphaera elsdenii. To achieve this, the gene coding for SCAD from M. elsdenii was cloned and sequenced. Site-directed mutagenesis was then used to identify an amino acid residue that is required for the proposed mechanism. To clone the gene, the amino acid sequence of the 50 N-terminal residues of SCAD from M. elsdenii was determined. This sequence information was utilized to synthesize two sets of mixed oligonucleotide primers which were then used to generate a 120-bp specific probe from M. elsdenii DNA by the polymerase chain reaction (PCR) method. The 120-bp probe was used to screen a M. elsdenii genomic DNA library cloned into Escherichia coli. The gene encoding M. elsdenii SCAD was identified from this library, sequenced, and expressed. The cloned SCAD gene contained an open reading frame which revealed a high degree of sequence identity with an open reading frame protein sequence of the human SCAD and the rat medium-chain acyl-CoA dehydrogenase (MCAD) (44% and 36% identical residues in paired comparisons for human SCAD and rat MCAD, respectively). Recombinant SCAD expressed from a pUC119 vector accounted for 35% of the cytosolic protein in the Escherichia coli crude extract. The expressed protein had similar activity, redox potential properties, and nearly identical amino acid composition to native M. elsdenii SCAD. In addition, a site-directed Glu367 Gln mutant of SCAD expressed from a pUC119 vector was shown to have minimal reductive and oxidative pathway activity with butyryl-CoA and crotonyl-CoA, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Peptidomimetic Inhibitors of the Human Cytomegalovirus Protease (1997)

The development of peptidomimetic inhibitors of the human cytomegalovirus (HCMV) protease showing sub-micromolar potency in an enzymatic assay is described. Selective substitution of the amino acid residues of these inhibitors led to the identification of tripeptide inhibitors showing improvements in inhibitor potency of 27-fold relative to inhibitor 39 based upon the natural tetrapeptide sequence. Small side chains at P1 were well tolerated by this enzyme, a fact consistent with previous observations. The S2 binding pocket of HCMV protease was very permissive, tolerating lipophilic and basic residues. The substitutions tried at P3 indicated that a small increase in inhibitor potency could be realized by the substitution of a tert-leucine residue for valine. Substitutions of the N-terminal capping group did not significantly affect inhibitor potency. Pentafluoroethyl ketones, alpha,alpha-difluoro-beta-keto amides, phosphonates and alpha-keto amides were all effective substitutions for the activated carbonyl component and gave inhibitors which were selective for HCMV protease. A slight increase in potency was observed by lengthening the P1' residue of the alpha-keto amide series of inhibitors. This position also tolerated a variety of groups making this a potential site for future modifications which could modulate the physicochemical properties of these molecules.
Amelioration of epidermolysis bullosa by transfer of wild-type bone marrow cells (2008)

The recessive dystrophic form of epidermolysis bullosa (RDEB) is a disorder of incurable skin fragility and blistering caused by mutations in the type VII collagen gene (Col7a1). The absence of type VII collagen production leads to the loss of adhesion at the basement membrane zone due to the absence of anchoring fibrils, which are composed of type VII collagen. We report that wild-type, congenic bone marrow cells homed to damaged skin, produced type VII collagen protein and anchoring fibrils, ameliorated skin fragility, and reduced lethality in the murine model of RDEB generated by targeted Col7a1 disruption. These data provide the first evidence that a population of marrow cells can correct the basement membrane zone defect found in mice with RDEB and offer a potentially valuable approach for treatment of human RDEB and other extracellular matrix disorders.
Changes of Sugar Kind and Its Content in the Fruit of Watermelon during Its Development and after Harvest. (1991)

To be of high quality the flesh of watermelon must be red in color, of crisp texture, and sweet. Especially sweetness of fruit, which is outcome of sugar content, is most important.
Long-Term Survival in Patients with Glioblastoma Multiforme (1993)

FEW PATIENTS WITH glioblastoma multiforme survive more than 5 years. To identify the factors associated with long-term survival, patients with primary supratentorial glioblastoma multiforme diagnosed between 1969 and 1985 were identified from our computer data base. Twenty-two (5%) of the 449 patients identified survived at least 5 years after surgical diagnosis. There were 12 female and 10 male patients, with a mean age of 39.2 years (range, 15 to 63 yr). Twenty patients had a subtotal resection, and 2 had a gross total resection. The median duration of survival was 9.4 years. As of August 1, 1992, 10 patients were alive 5.2 to 13.6 years after diagnosis, and 1 patient was lost to follow-up after 9.4 years. Ten patients died from their tumors; 2 patients with stable tumors died, 1 from a ruptured intracranial aneurysm and 1 from erythromycin-induced hepatitis. Unusual sequelae were noted in irradiated areas in several cases. One patient had a scalp sarcoma and a basal cell carcinoma, and three patients had strokes; each of these events occurred more than 5 years after diagnosis. We conclude that among patients with glioblastoma multiforme, long-term survival is most likely for those who have a long disease-free interval after the initial diagnosis and receive multimodal therapy, including aggressive tumor removal. Other factors associated with long-term survival were younger age and high Karnofsky scores.