gebhart/patrepeval huggingface dataset:
Noninvasive chemical enucleation of mouse oocytes (1993)

Abstract A noninvasive method of enucleating mouse oocytes has been developed and evaluated. Strong chromosome to chromosome binding was induced by culturing early metaphase I oocytes in etoposide supplemented medium. Subsequent expulsion of the entire chromosome complex during polar body extrusion was facilitated by exposing the etoposide treated oocytes to a combination of cycloheximide and etoposide during anaphase and telophase. This simple two‐step chemical enucleation procedure yields fully enucleated mouse oocytes in 96% of cases. Chemically enucleated oocytes do not contain maturation promoting factor (MPF) at the end of etoposide‐cycloheximide enucleation. MPF levels are, however, restored during subsequent incubation in drug‐free medium and, after 15 h of post‐enucleation culture, the cytoplasts regain their full capacity for parthenogenetic activation and nuclear remodelling. We believe that this novel enucleation technique will greatly facilitate the research in nuclear transplantation. © 1993 Wiley‐Liss, Inc.
Utilizing the Ultraviolet (UV Detect) Camera to Enhance the Appearance of Photodamage and Other Skin Conditions (1997)

The UV camera should become an integral part of sun damage detection both in the physician's office and in the community. Not only does the camera document pigmentary changes but it also demonstrates improvement after therapeutic intervention.
Arachidonic Acid Metabolites and the Interactions between Platelets and Blood-Vessel Walls (1979)

PROSTAGLANDINS are potent vasoactive agents with a wide variety of other actions that depend on the species and organ tested and the prostaglandin used. They are synthesized from 20-carbon polyunsaturated fatty acids containing three, four or five double bonds. These fatty acids are present in the phospholipids of the cell membranes of all mammalian tissues. The main precursor of prostaglandins in man is eicosatetraenoic or arachidonic acid (four double bonds), which gives rise to the prostaglandins (PG's) containing two double bonds (PGE2, PGF2α, PGD2, prostacyclin and thromboxane A2). PGE2 and PGF . . .
What makes a good graphene-binding peptide? Adsorption of amino acids and peptides at aqueous graphene interfaces (2015)

Investigation of the non-covalent interaction of biomolecules with aqueous graphene interfaces is a rapidly expanding area. However, reliable exploitation of these interfaces in many applications requires that the links between the sequence and binding of the adsorbed peptide structures be clearly established. Molecular dynamics (MD) simulations can play a key role in elucidating the conformational ensemble of peptides adsorbed at graphene interfaces, helping to elucidate these rules in partnership with experimental characterisation. We apply our recently-developed polarisable force-field for biomolecule-graphene interfaces, GRAPPA, in partnership with advanced simulation approaches, to probe the adsorption behaviour of peptides at aqueous graphene. First we determine the free energy of adsorption of all twenty naturally occurring amino acids (AAs) via metadynamics simulations, providing a benchmark for interpreting peptide-graphene adsorption studies. From these free energies, we find that strong-binding amino acids have flat and/or compact side chain groups, and we relate this behaviour to the interfacial solvent structuring. Second, we apply replica exchange with solute tempering simulations to efficiently and widely sample the conformational ensemble of two experimentally-characterised peptide sequences, P1 and its alanine mutant P1A3, in solution and adsorbed on graphene. For P1 we find a significant minority of the conformational ensemble possesses a helical structure, both in solution and when adsorbed, while P1A3 features mostly extended, random-coil conformations. In solution this helical P1 configuration is stabilised through favourable intra-peptide interactions, while the adsorbed structure is stabilised via interaction of four strongly-binding residues, identified from our metadynamics simulations, with the aqueous graphene interface. Our findings rationalise the performance of the P1 sequence as a known graphene binder.
Maximal bite force and its association with signs and symptoms of craniomandibular disorders in young Finnish non-patients (1995)

Maximal bite force values and subjective symptoms and clinical signs of craniomandibular disorders (CMD) were recorded for a non-patient sample of 129 young adults, 56 men and 73 women. The signs and symptoms of CMD were classified on the basis of Helkimo's clinical dysfunction index. The two genders reported equally frequently subjective symptoms of CMD, but women had significantly more severe clinical signs of CMD than did men. Mean maximal bite force values for men were 909 N (SD, 177) in the molar region and 382 N (SD, 133) in the incisal region and thus significantly higher than corresponding figures for women, 777 N (SD, 168) in the molar, 325 N (SD, 116) in the incisal region, suggesting that separate evaluation of the genders would be advisable in future studies involving bite force assessments. Neither subjective symptoms nor clinical signs of CMD correlated significantly with maximal bite force values. The bite force values measured were in line with theoretical calculations.
Physical Assay and Growth Cycle Studies of a Defective Adeno-Satellite Virus (1967)

Electron microscopic particle counting of the defective adeno-satellite virus (ASV), by use of pseudoreplication and negative staining with phosphotungstic acid, was shown to be a reproducible quantitative assay procedure. Particles of satellite type 4 that were counted in fluids from infected cultures had the same morphology as particles that banded at a buoyant density of 1.43 g/cc in cesium chloride. Other satellite virus serotypes examined in the same manner had a buoyant density of 1.37 to 1.38 g/cc. A comparison of satellite titers obtained by complement fixation and by particle counting demonstrated that an increase in satellite particles resulted in a corresponding increase in CF titers; however, electron microscopy was at least 10 times more sensitive than complement fixation for detecting satellite virus. Growth cycle studies of satellite virus in cells co-infected with adenovirus, as assayed by particle counting, indicated that the kinetics of satellite virus production closely followed the kinetics of its helper adenovirus production, with an eclipse period of 12 to 16 hr. The eclipse period of the satellite remained the same when cultures were preinfected with satellite 24 hr prior to adenovirus inoculation. However, when cultures were infected with adenovirus 12 hr before satellite virus, the eclipse period of the satellite was shortened to between 4 and 6 hr. Thus, satellite virus replication seems dependent upon a relatively late event in the adenovirus replication cycle. When cells were co-infected with adenovirus and its defective satellite, the yield of adenovirus was markedly reduced from that obtained in cells singly infected with adenovirus.
Eilat virus, a unique alphavirus with host range restricted to insects by RNA replication (2012)

Most alphaviruses and many other arboviruses are mosquito-borne and exhibit a broad host range, infecting many different vertebrates including birds, rodents, equids, humans, and nonhuman primates. Consequently, they can be propagated in most vertebrate and insect cell cultures. This ability of arboviruses to infect arthropods and vertebrates is usually essential for their maintenance in nature. However, several flaviviruses have recently been described that infect mosquitoes but not vertebrates, although the mechanism of their host restriction has not been determined. Here we describe a unique alphavirus, Eilat virus (EILV), isolated from a pool of Anopheles coustani mosquitoes from the Negev desert of Israel. Phylogenetic analyses placed EILV as a sister to the Western equine encephalitis antigenic complex within the main clade of mosquito-borne alphaviruses. Electron microscopy revealed that, like other alphaviruses, EILV virions were spherical, 70 nm in diameter, and budded from the plasma membrane of mosquito cells in culture. EILV readily infected a variety of insect cells with little overt cytopathic effect. However, in contrast to typical mosquito-borne alphaviruses, EILV could not infect mammalian or avian cell lines, and viral as well as RNA replication could not be detected at 37 °C or 28 °C. Evolutionarily, these findings suggest that EILV lost its ability to infect vertebrate cells. Thus, EILV seems to be mosquito-specific and represents a previously undescribed complex within the genus Alphavirus. Reverse genetic studies of EILV may facilitate the discovery of determinants of alphavirus host range that mediate disease emergence.
Antiangiogenic Agents in Combination with Chemotherapy in Patients with Advanced Non-Small Cell Lung Cancer (2011)

Most patients with non-small cell lung cancer (NSCLC) present with advanced disease requiring systemic chemotherapy. Treatment with the antiangiogenic agent bevacizumab in combination with standard platinum-based doublet chemotherapy has been shown to improve outcomes in patients with advanced NSCLC. Several multitargeted antiangiogenic tyrosine kinase inhibitors (e.g., sorafenib, sunitinib, cediranib, vandetanib, BIBF 1120, pazopanib, and axitinib) are also being evaluated in combination with standard chemotherapy. Here we review current clinical data with combination therapy involving antiangiogenic agents and cytotoxic chemotherapy in patients with advanced NSCLC.
Purification and Properties of an Enzyme in Human Blood and Rat Liver Microsomes Catalyzing the Formation and Hydrolysis of γ-Lactones (1966)

Abstract Calcium ions have been found to activate and stabilize γ-lactonase specifically. Hydrolytic activity at pH 8.6 requires 10 µm calcium ions, while the lactonization rate at pH 6.0 is maximal with 10 mm calcium. At pH 6.0, hydrolysis is increased proportionally with synthesis upon the addition of calcium, indicating that the metal ion interacts with the enzyme and not the substrate. Calcium ion, 1 mm, serves to stabilize γ-lactonase prepared from rat liver microsomes. Zn++, Cu++, Mn++, Mg++, Fe+++, Ni++, Co++, Hg++, Na+, and K+ either inhibit γ-lactonase or are without effect, depending upon the pH of the assay and the particular metal ion involved. Magnesium appears to inhibit specifically only the hydrolytic activity of γ-lactonase without affecting its lactonizing function. Ethylenediaminetetraacetate-calcium chelates can replace calcium in activation of the enzyme, indicating a very high affinity constant for the lactonase-calcium complex. Four- to eight-carbon lactones are effective substrates for the enzymes, with Km values ranging from 1 to 13 mm. The values for the corresponding γ-hydroxy acids as substrates for lactone synthesis run about 4-fold higher. The enzyme preparations from liver microsomes and human plasma have similar, but not identical, kinetic properties. Equilibrium constants at near neutral pH values and 27° have been determined for the 4- to 8-carbon lactone-hydroxy acid couples, with the use of γ-lactonase. Except for the 4-carbon substrate, a sizeable fraction of these compounds exists in the lactone form at equilibrium (10 to 20%).
Proposal to reclassify Propionibacterium acnes type I as Propionibacterium acnes subsp. acnes subsp. nov. and Propionibacterium acnes type II as Propionibacterium acnes subsp. defendens subsp. nov. (2016)

Recently, it has been proposed that strains of Propionibacterium acnes from the type III genetic division should be classified as P. acnessubsp. elongatum subsp. nov., with strains from the type I and II divisions collectively classified as P. acnessubsp. acnes subsp. nov. Under such a taxonomic re-appraisal, we believe that types I and II should also have their own separate rank of subspecies. In support of this, we describe a polyphasic taxonomic study based on the analysis of publicly available multilocus and whole-genome sequence datasets, alongside a systematic review of previously published phylogenetic, genomic, phenotypic and clinical data. Strains of types I and II form highly distinct clades on the basis of multilocus sequence analysis (MLSA) and whole-genome phylogenetic reconstructions. In silico or digital DNA-DNA similarity values also fall within the 70-80 % boundary recommended for bacterial subspecies. Furthermore, we see important differences in genome content, including the presence of an active CRISPR/Cas system in type II strains, but not type I, and evidence for increasing linkage equilibrium within the separate divisions. Key biochemical differences include positive test results for β-haemolytic, neuraminidase and sorbitol fermentation activities with type I strains, but not type II. We now propose that type I strains should be classified as P. acnessubsp. acnes subsp. nov., and type II as P. acnessubsp. defendens subsp. nov. The type strain of P. acnessubsp. acnes subsp. nov. is NCTC 737T (=ATCC 6919T=JCM 6425T=DSM 1897T=CCUG 1794T), while the type strain of P. acnessubsp. defendens subsp. nov. is ATCC 11828 (=JCM 6473=CCUG 6369).
Rapamycin Inhibits α 1 -Adrenergic Receptor–Stimulated Cardiac Myocyte Hypertrophy but Not Activation of Hypertrophy-Associated Genes (1997)

The 70-kD S6 kinase (p70S6K) has been implicated in the regulation of protein synthesis in many cell types and in the angiotensin II-stimulated hypertrophy of cardiac myocytes. Our purpose was to determine whether p70S6K plays a role in cardiomyocyte hypertrophy induced by the alpha 1-adrenergic receptor (alpha 1-AR) agonist phenylephrine (PE). PE stimulated the activity of p70S6K > 3-fold, and this increase was blocked by rapamycin, an immunosuppressant macrolide that selectively inhibits p70S6K. When administered for 3 days, PE stimulated a 30% increase in total protein content, a 2-fold increase in the incorporation of [14C]phenylalanine (14C-Phe) into protein, and a 50% increase in two-dimensional myocyte area. Rapamycin pretreatment (> or = 500 pg/mL) significantly inhibited each of these PE-stimulated changes. Two days of PE treatment resulted in a 1.6-fold increase in total RNA yield per dish, a 2-fold increase in incorporation of [14C]uridine into myocyte RNA, and increases in relative mRNA levels of the hypertrophy-associated atrial natriuretic factor (ANF, 2.1-fold) and skeletal alpha-actin (SK, 2.2-fold) genes. Although rapamycin abolished the PE-stimulated increases in total RNA and incorporation of [14C]uridine, it had no effect on the induction of the ANF and SK genes. LY294002, a specific inhibitor of phosphatidylinositol 3-kinase (PI3-K) activity, inhibited PE-stimulated increases in p70S6K activity and the incorporation of labeled precursors into myocyte protein and RNA. These results demonstrate that p70S6K is activated by the hypertrophic agent PE and that a PI3-K or PI3-K-like activity is required for p70S6K activation and myocyte hypertrophy. The data suggest that p70S6K activation may be required for PE-stimulated hypertrophy of cardiac myocytes. Our results demonstrate that intracellular signaling pathways responsible for transcriptional and translational responses diverge early after alpha 1-AR stimulation in cardiac myocytes.
Dysfunctional kynurenine pathway metabolism in the R6/2 mouse model of Huntington’s disease (2010)

Elevated concentrations of neurotoxic metabolites of the kynurenine pathway (KP) of tryptophan degradation may play a causative role in Huntington's disease (HD). The brain levels of one of these compounds, 3-hydroxykynurenine (3-HK), are increased in both HD and several mouse models of the disease. In the present study, we examined this impairment in greater detail using the R6/2 mouse, a well-established animal model of HD. Initially, mutant and age-matched wild-type mice received an intrastriatal injection of (3)H-tryptophan to assess the acute, local de novo production of kynurenine, the immediate bioprecursor of 3-HK, in vivo. No effect of genotype was observed between 4 and 12 weeks of age. In contrast, intrastriatally applied (3)H-kynurenine resulted in significantly increased neosynthesis of (3)H-3-HK, but not other tritiated KP metabolites, in the R6/2 striatum. Subsequent ex vivo studies in striatal, cortical and cerebellar tissue revealed substantial increases in the activity of the biosynthetic enzyme of 3-HK, kynurenine 3-monooxygenase and significant reductions in the activity of its degradative enzyme, kynureninase, in HD mice starting at 4 weeks of age. Decreased kynureninase activity was most evident in the cortex and preceded the increase in kynurenine 3-monooxygenase activity. The activity of other KP enzymes showed no consistent brain abnormalities in the mutant mice. These findings suggest that impairments in its immediate metabolic enzymes jointly account for the abnormally high brain levels of 3-HK in the R6/2 model of HD.
Streptozotocin at low doses induces apoptosis and at high doses causes necrosis in a murine pancreatic ß cell line, INS-1 (1996)

The ability of beta cells to endure assaults by various environmental agents, including toxins and viruses, may be relevant to the development of diabetes. We have examined the mode of cell death caused by streptozotocin (STZ) in a murine pancreatic beta cell line, INS-1. Apoptosis was identified by detection of initial endonuclease-mediated DNA strand breaks by DNA gel electrophoresis. Apoptosis and necrosis were distinguished morphologically by light and electron microscopy. Higher rates of apoptosis, as compared to necrosis, were observed when cells were exposed to 15 mM STZ for 1 hr followed by a 24 hrs recovery period. Higher doses of STZ (30 mM) caused the cells to undergo necrosis (22%) as well as apoptosis (17%). These results suggest that the cytotoxic effect of STZ, at low doses, on beta cells involves the activation of the apoptotic pathway, whereas, at high doses, the mode of beta cell death is predominantly necrosis.
Digestive disease week and american diabetes association: digestive disease week. (2008)

A twice-daily formulation of balsalazide tablets (Colazal, Salix) improved signs and symptoms of mild-to-moderate ulcerative colitis, according to phase 3 clinical trial results presented by Dr. Bosworth. The reduced-dosing regimen, he stated, “has the potential for higher compliance with self-administered treatment.” Poor compliance with the currently approved formulation of three doses per day, he added, is a major problem for these patients.

Dr. Bosworth and co-investigators for the double-blind, placebo-controlled, multicenter trial enrolled 249 adults with symptoms of mild-to-moderate active ulcerative colitis with Modified Mayo Disease Activity Index (MMDAI) scores of 6 to 10 at baseline. Subjects had subscale ratings of 2 or higher for both rectal bleeding and mucosal appearance.

Patients were randomly assigned to three 1,100-mg bal-salazide tablets (n = 166) twice daily or three matching placebo tablets (n = 83) twice daily for eight weeks. Colonoscopy or sigmoidoscopy screening was conducted up to seven days before randomization and at the study’s end.

Dr. Bosworth reported benefits for the balsalazide group across a wide range of endpoints. A significantly larger proportion of balsalazide patients achieved improvements in total MMDAI scores at the end of the study (67% vs. 47%, respectively; P = 0.004), and mean decreases in total MMDAI scores from baseline to week eight were significantly larger with balsalazide than with placebo (−3.4 ± 3.0 vs. −2.3 ± 3.0; P = 0.002).

Benefits among the balsalazide subjects, compared with the patients receiving placebo, were also reported for rectal bleeding (59% vs. 42%, respectively; P = 0.01); Physician Global Assessment (PGA) scores (60% vs. 36%; P = 0.0004); mucosal appearance (53% vs. 37%; P = 0.02); and improvements in bowel frequency (49% vs. 37%; P = 0.08).

Dr. Bosworth concluded: “As assessed by the MMDAI, balsalazide tablets, administered as 3.3 g twice daily, are effective in improving the signs and symptoms of mild-to-moderate ulcerative colitis. This new tablet formulation reduces both pill and dosing burden in patients with active ulcerative colitis and may improve patient compliance.”
Effect of Liposomal Encapsulation of <i>cis</i>-Platinum Diamminodichloride in the Treatment of Ehrlich Ascites Carcinoma (1983)

cis-Platinum diamminodichloride (II) encapsulated in neutral liposomes has been used to enhance the activity of the drug on Ehrlich ascites carcinoma in mice. Both in vitro and in vivo experiments have revealed that better regression in tumor growth and cure, could be achieved with a lower dose, having apparently no toxic effect, by liposomal encapsulation of the drug.
MicroRNA Let-7f Inhibits Tumor Invasion and Metastasis by Targeting MYH9 in Human Gastric Cancer (2011)

Our study demonstrated that overexpression of let-7f in gastric cancer could inhibit invasion and migration of gastric cancer cells through directly targeting the tumor metastasis-associated gene MYH9. These data suggest that let-7f may be a novel therapeutic candidate for gastric cancer, given its ability to reduce cell invasion and metastasis.
The TCP domain: a motif found in proteins regulating plant growth and development (1999)

The cycloidea (cyc) and teosinte branched 1 (tb1) genes code for structurally related proteins implicated in the evolution of key morphological traits. However, the biochemical function of CYC and TB1 proteins remains to be demonstrated. To address this problem, we have analysed the predicted secondary structure of regions conserved between CYC and TB1, and looked for related proteins of known function. One of the conserved regions is predicted to form a non-canonical basic-Helix-Loop-Helix (bHLP) structure. This domain is also found in two rice DNA-binding proteins, PCF1 and PCF2, where it has been shown to be involved in DNA-binding and dimerization. This indicates that the conserved domain most probably defines a new family of transcription factors, which we have termed the TCP family after its first characterised members (TB1, CYC and PCFs). Other plant proteins of unknown function also belong to this family. We have studied two of these in Arabidopsis and have shown that they are expressed in rapidly growing floral primordia. This, together with the proposed involvement of cyc and tb1 in influencing meristem growth, suggests that many members of the TCP family may affect cell division. Some of these genes may have been recruited during plant evolution to generate new morphological traits.
Mn3O4−Graphene Hybrid as a High-Capacity Anode Material for Lithium Ion Batteries (2010)

We developed two-step solution-phase reactions to form hybrid materials of Mn(3)O(4) nanoparticles on reduced graphene oxide (RGO) sheets for lithium ion battery applications. Selective growth of Mn(3)O(4) nanoparticles on RGO sheets, in contrast to free particle growth in solution, allowed for the electrically insulating Mn(3)O(4) nanoparticles to be wired up to a current collector through the underlying conducting graphene network. The Mn(3)O(4) nanoparticles formed on RGO show a high specific capacity up to ∼900 mAh/g, near their theoretical capacity, with good rate capability and cycling stability, owing to the intimate interactions between the graphene substrates and the Mn(3)O(4) nanoparticles grown atop. The Mn(3)O(4)/RGO hybrid could be a promising candidate material for a high-capacity, low-cost, and environmentally friendly anode for lithium ion batteries. Our growth-on-graphene approach should offer a new technique for the design and synthesis of battery electrodes based on highly insulating materials.