gebhart/patrepeval huggingface dataset:
Surface plasmon resonance spectroscopy in the study of membrane‐mediated cell signalling (2003)

Peptide-membrane interactions contribute to many important biological processes such as cellular signaling, protein trafficking and ion-channel formation. During receptor-mediated signalling, activated intracellular signalling molecules are often recruited into receptor-induced signaling complexes at the cytoplasmic surface of the cell membrane. Such recruitment can depend upon protein-protein and protein-lipid interactions as well as protein acylation. A wide variety of biophysical techniques have been combined with the use of model membrane systems to study these interactions and have provided important information on the relationship between the structure of these proteins involved in cell signalling and their biological function. More recently, surface plasmon resonance (SPR) spectroscopy has also been applied to the study of biomembrane-based systems using both planar mono- or bilayers or liposomes. This article provides an overview of these recent applications, which demonstrate the potential of SPR to enhance our molecular understanding of membrane-mediated cellular signalling.
Early Insulin Use in Type 2 Diabetes (2009)

It is generally recognized that type 2 diabetes is one of the major challenges of the 21st century. Its prevalence is growing rapidly worldwide, particularly in developing countries (1). It remains the first cause of blindness, end-stage renal disease, and nontraumatic lower-limb amputation and one of the major causes of cardiovascular disease (2,3). Because of its high morbidity and excess mortality, it has become a tremendous burden on health care cost (4).

In the last decade, a number of interventions have been shown to be effective in the prevention of diabetes in high-risk populations with impaired glucose tolerance and/or impaired fasting glucose (5–7). Yet, few countries have adopted policies for the screening and strategies for treating subjects with pre-diabetes. Furthermore, despite the development of newer therapies for treatment of diabetes, the disease is still associated with a high incidence of microangiopathy and macrovascular complications. Any new strategies that could help to curtail the burden of diabetes would be greatly appreciated.

More recently, it was postulated that early insulin replacement in type 2 diabetes, and perhaps even in pre-diabetes, may reduce cardiovascular risk and may even offer protection for the β-cell (8,9). However, a closer look at the available data does not support the hypothesis. The Outcome Reduction with an Initial Glargine Intervention (ORIGIN) study is still ongoing and therefore does not allow any conclusion in pre-diabetes. In type 2 diabetes, however, the published data support neither a beneficial effect of insulin therapy per se on microvascular complications, nor on cardiovascular events and mortality. In addition, the data suggesting that insulin therapy can improve the β-cell response to a glucose challenge could just as well be interpreted as being due to the improvement in glycemic control, rather than to the insulin therapy. And finally, …
Glucocorticoid activity, inactivity and the osteoblast (1999)

Although excess circulating glucocorticoids have detrimental effects on bone health, the processes underlying these effects are not well understood. We review what is currently known about the effects of glucocorticoids on osteoblast proliferation and differentiation, with particular emphasis on osteoblast expression of glucocorticoid metabolic enzymes as a mechanism for regulating corticosteroid activity in bone. The adverse effects on bone of increased circulating concentrations of endogenous glucocorticoids have been recognised since Harvey Cushing’s original description of Cushing’s disease (Cushing 1912). The increasing use of synthetic glucocorticoids for inflammatory diseases has increased the pressure to understand, and ultimately modify, the processes underlying their deleterious effects on bone. The clinical impact of the problem is reflected both by a doubling of the overall fracture risk in patients taking prednisolone (7·5 mg for 6 months) and the development of low bone mineral density in 50% of patients taking higher doses of glucocorticoid (Eastell 1995). Several mechanisms have been proposed for these effects, including reduction in endogenous sex steroid production, decreased muscle mass, and altered gastrointestinal and renal calcium handling causing secondary hyperparathyroidism (Canalis 1996). However, it appears increasingly likely that the most important effect of glucocorticoids is to alter the proliferation and differentiation of cells of the osteoblast lineage. Bone formation in vivo is clearly a complex dynamic process, involving the actions of multiple morphogens, growth factors and hormones. Glucocorticoids could affect any part of the differentiation pathway from initial skeletal patterning and mesoderm induction, commitment of primitive multipotent mesodermal progenitor cells to the osteoblast lineage, or the proliferation and differentiation of preosteoblasts through to mature osteoblasts, to bone-lining cells and osteocytes (Fig. 1). All these stages are likely to occur in normal bone turnover and during fracture healing. For each of these stages, the effects of glucocorticoids, their mechanisms of action and, equally important, the reasons for their lack of action, upon other osteoblasts within the bone microenvironment require explanation. These are outlined in the following review, with particular emphasis on osteoblast expression of glucocorticoid metabolic enzymes as a mechanism for regulating steroid activity in bone.
Characterization of a mammalian Golgi-localized protein complex, COG, that is required for normal Golgi morphology and function (2002)

Multiprotein complexes are key determinants of Golgi apparatus structure and its capacity for intracellular transport and glycoprotein modification. Three complexes that have previously been partially characterized include (a) the Golgi transport complex (GTC), identified in an in vitro membrane transport assay, (b) the ldlCp complex, identified in analyses of CHO cell mutants with defects in Golgi-associated glycosylation reactions, and (c) the mammalian Sec34 complex, identified by homology to yeast Sec34p, implicated in vesicular transport. We show that these three complexes are identical and rename them the conserved oligomeric Golgi (COG) complex. The COG complex comprises four previously characterized proteins (Cog1/ldlBp, Cog2/ldlCp, Cog3/Sec34, and Cog5/GTC-90), three homologues of yeast Sec34/35 complex subunits (Cog4, -6, and -8), and a previously unidentified Golgi-associated protein (Cog7). EM of ldlB and ldlC mutants established that COG is required for normal Golgi morphology. "Deep etch" EM of purified COG revealed an approximately 37-nm-long structure comprised of two similarly sized globular domains connected by smaller extensions. Consideration of biochemical and genetic data for mammalian COG and its yeast homologue suggests a model for the subunit distribution within this complex, which plays critical roles in Golgi structure and function.
[State of health of children and structure of morbidity in the region of catastrophe of oil producing plant]. (2006)

On September 9, 2004 in Sagarejo region, Ninotsminda village an ecologic catastrophe took place. As a result of explosion at the oil-producing plant there was an oil spill in the surrounding soil, which caused the pollution of the environment. Among children living in Ninotsminda village (the main zone) 370 children were investigated for evaluation of the state of their health and nosological structure of the morbidity. The observation was performed by stages. 1st stage: study of the zone 1 year before the catastrophe. 2(nc) stage: quarterly dynamic control over the state of health of the children in both zones for the purpose of comparison of definition of the absolute number of morbidity index. It was found that after the catastrophe the absolute number of diseases in the main zone increased 10.8 times, and in the control one significant alterations did not appear. According to the nosological structure of the morbidity the predominance of pathology of pulmonary-respiratory system was revealed.
Thermal degradation of polymers at low rates (1959)

I n meas uring the rates of thermal degradation of polym e rs at constant tempe rat u res in the r ange of 200 0 to 500 0 C, one encoun ters a distortion of t he initial p arts of t he rate cur ves during the time required to h eat the sp ecimen to t he p yrolys is tempe raL ure . This distortion has been largely overcome b y using a new apparatus, based o n an elecLronie ba lance, in which the d egradat ion of t he specimen is carried out at very low rates. The apparatus is eq uipped with an electronic thermostat that con trols t he temperature Lo within O.lo C, and also wi th an a u tomatic recorder t hat m easures both the temperatu re and the loss of weight of t he specimen . P yrolysis experimen ts were carri ed out in a vacuum in t his apparatus on pure specimens of poly styrene, p oly (a-meth ylsty rene), polyme thyle ne, high-molecula r-weigh t polyet hylene, and low-molecula r-weight polyethyle ne. T he ini tial rates of d egradation, in percent of sample p er minu te, varied fr o m 0.008 to 0.095. Except for the initial parts of the rate curves, in some cases up to about 30 percent loss of weight, t he r ate curves at low rates res emble closely t hose previously obtained at h igh rates of degradation .
Tetrazole Synthesis via the Palladium‐Catalyzed Three Component Coupling Reaction. (2004)

Abstract For Abstract see ChemInform Abstract in Full Text.
Determination of anisotropy of spatial correlation structure in a three‐dimensional permeability field accompanied by shallow faults (2002)

Structural planes, such as fractures, bedding planes, schistosity, and so on, induce heterogeneity of permeability field in geologic bodies. One of the ways to demonstrate the heterogeneity is to geostatistically infer the spatial correlation structure. This paper presents a newly developed geostatistical technique for estimating the three‐dimensional heterogeneous permeability field. In the presented method, the plane‐directional anisotropy of spatial correlation structure of the three‐dimensional permeability field is determined by estimating semivariograms in multiplane directions, using limited in situ measurement data of basement rock permeability. A case study of a dam site shows that the spatial correlation of permeability in the direction parallel to the fault planes is greater than that perpendicular to it. Direction of the largest anisotropy of the spatial correlation of the permeability field is concordant with the strike of the major faults.
Direct visualization of enzyme inhibitors using a portion mixing inhibitor library containing a quenched fluorogenic peptide substrate. Part 1. Inhibitors for subtilisin Carlsberg (1995)

A PEGA-resin was derivatized with a 2 : 1 mixture of 4-hydroxymethylbenzoic acid and Fmoc-Lys(Boc)-OH and the fluorogenic substrate Ac-Y(NO2)FQPLAVK(ABz)-PEGA was assembled using the active ester approach. Following esterification of the 4-hydroxymethylbenzoic acid with Fmoc-Val-OH a library X1X2X3-x4-X5X6V was assembled by the portion mixing method. The library was subjected to extensive hydrolysis by subtilisin Carlsberg and the rate of hydrolysis was highly dependent on the potential inhibitor contained in each bead. The most persistently dark beads were collected and sequenced to yield repeatedly highly lipophilic peptides. Some of these were synthesized and found to be strong inhibitors of subtilisin Carlsberg in solution.
Sequence analysis and relationships between meningococcal class 3 serotype proteins and other porins from pathogenic and non-pathogenic Neisseria species (1992)

The presence of highly conserved regions within previously determined porin gene sequences from Neisseria meningitidis and Neisseria gonorrhoeae permitted the construction of oligonucleotide primers for PCR amplification of other neisserial porin genes. Although two separate porin genes (porA and porB) are present in N. meningitidis only a single fragment, corresponding to porB, could be amplified from this species. The amplified porB genes from four different meningococcal serotypes, which express the class 3 outer membrane protein, were sequenced. Amplified fragments corresponding to porin genes from N. lactamica and N. sicca were also sequenced. In common with the known neisserial porins, models of the organisation of the predicted proteins indicated trans-membrane structures with eight surface exposed loops. In the meningococcal class 3 proteins the main regions of sequence variation, which must be responsible for serotype specificity, were located on loops 5 and 7. A phylogenetic analysis of the family of porins from the Neisseria confirmed the close relationship of the meningococcal class 3 protein with the gonococcal PIA protein, while the gonococcal PIB protein was shown to be closely related to the N. lactamica porin. The close relationship seen between porins of the pathogenic and non-pathogenic Neisseriae identified no obvious virulence-associated regions in the proteins, but did suggest that the current nomenclature for neisserial porin genes may need reviewing.
Maternity leave for practicing family physicians. (1992)

Women family physicians expressed strong interest in the development of maternity leave guidelines for their specialty. Guideline components are outlined.
Age does not affect contractile responses of the isolated rhesus monkey ciliary muscle to muscarinic agonists (1993)

In primates, ciliary muscle contraction causes accommodation and facilitates aqueous outflow. In living rhesus monkeys, accommodative, outflow facility, and ciliary muscle movement responses to cholinergic agonists all decline with age. We developed an apparatus to determine in vitro whether the latter is related to intra- or extra-ciliary muscle factors, and whether ciliary muscle contraction in the coronal (putatively more accommodation-relevant) and longitudinal (putatively more facility-relevant) vectors can be dissociated pharmacologically. In fresh ciliary muscle strips, carbachol and aceclidine each induced dose-dependent contraction in the longitudinal and coronal vectors. With neither drug was there any apparent dissociation of the responses in the two vectors. Atropine pretreatment completely prevented a supramaximal dose of carbachol from inducing ciliary muscle contraction in either vector. Ciliary muscle strips responded to several cholinergic agonists as well on day 2 (24-32 hours post-enucleation) as on day 1 (1-9 hours post-enucleation) when kept in a cell culture medium at 4 degrees C. By light microscopy, the general architecture of the ciliary muscle, the muscle bundles, and the single muscle cells appeared normal; however, cellular and nuclear swelling were apparent following the 32-hour culturing period. Contractile responses to near-maximal doses of carbachol and aceclidine did not vary markedly with age in either vector, suggesting that the age-related decrease in ciliary muscle mobility in vivo is due to extra-muscular restrictive factors rather than diminished muscular contractility.
Auction Performance Evaluation in Deregulated Electricity Markets (2005)

In a deregulated electricity market, auction serves as a primary pricing tool in various segments of the market including day-ahead, real time, ancillary services markets, and Financial Transmission Rights (FTRs) market. Deregulated power markets around the world use different auction strategies that exist in the literature, since very little comparative guidelines exist as to the relative merits of these strategies. In this thesis, a computational methodology and its solution framework are developed to evaluate the impact of an auction strategy on the equilibrium prices in a constrained network with multiple generators at nodes, and where transactions are settled using the optimal power flow (OPF) program.\nThe methodology is tested on a power market represented by a sample 12-bus IEEE network available in the MATPOWER software, which is reconfigured to allow multiple generators to supply power at a bus. The network is used as a platform to comprehensively assess the performance of uniform price auction, discriminatory auction, and second-price uniform auction. Auction rules are used to update generator costs, which are then introduced into the OPF program for obtaining optimal price and quantity allocations. This Auction-OPF procedure is embedded within a game theoretic model that obtains the equilibrium bidding strategies and the corresponding prices and quantities for the network.\nA detailed comparison of the auction mechanisms is carried out using different measures of performance such as revenue, average prices, and quantity weighted average prices. The comparison shows that there is, perhaps, an appreciable difference among the auction mechanisms. However, to statistically confirm the impact of auction choices, a mixed level factorial experiment is designed with auction strategy, network load, and congestion as three different factors and a closeness measure (defined as the difference between average total revenue and the average total cost of generators in the network per hour) as the responsible variable. An analysis of variance conducted on the experimental outcomes indicates that the load level and the auction strategy significantly affect the network performance. The presence market power under the auction strategies is examined through two well known indices, Herfindahl-Hirschmann Index (HHI) and Lerners Index. It is concluded from the HHI values that all three auction strategies allow the market to be moderately competitive. The Lerners index values show that, while discriminatory auction results in highest bid markup, second price uniform auction induces bidding at or close to the marginal cost.
Gene transfer of a secretable form of IL-15 in murine adenocarcinoma cells: Effects on tumorigenicity, metastatic potential and immune response (2000)

IL-15 is an immunostimulatory cytokine with IL-2-like activities. To exploit the potential role of IL-15 in cancer immuno-/gene therapy, we engineered murine TS/A cells with different IL-15 cDNA constructs. Significant IL-15 secretion was achieved only by the use of a modified cDNA encoding for an IL-15 pre-protein bearing the IgK light chain signal peptide. Different TS/A clones (TS/A IL-15 C6, C23, C29) producing 390 to 1,600 pg/ml biologically active IL-15 showed reduced tumorigenicity when implanted s.c. in syngeneic mice and significantly reduced metastatic potential by i.v. injection. Tumorigenicity of s.c. TS/A IL-15 was restored in animals depleted of CD8(+) lymphocytes or of natural killer cells and partially in CD4(+)-depleted mice. TS/A IL-15 cells displayed a significantly reduced growth rate by s.c. implant in nude mice. Also, >50% syngeneic animals rejecting TS/A IL-15 were resistant to a subsequent rechallenge with wild-type tumor (TS/Apc), indicating induction of protective immunity against TS/A tumor-associated antigens (TAAs). Cytolytic T lymphocyte (CTL) activity, specifically inhibited by anti-CD3 antibodies, was inducible in the splenocytes of TS/A IL-15-immunized animals by mixed lymphocyte/tumor culture (MLTC), and IFN-gamma was released in the supernatant of MLTC, mainly by CD8(+) cells. Immunohistochemistry of the TS/A IL-15 tumor area revealed the presence of an inflammatory infiltrate with predominant natural killer, macrophage, and granulocyte components and expression of IFN-gamma as a distinctive secondary cytokine. Use of TS/A IL-15 mitomycin-treated cells for therapeutic vaccination in experimental TS/A metastasis was effective in 60% of animals treated; these animals showed no metastatic tumor growth.
Not Innocent: Verdict from Ab Initio Multiconfigurational Second-Order Perturbation Theory on the Electronic Structure of Chloroiron Corrole (2008)

From a suitably broad perspective, transition metal corroles may be viewed as stable, synthetic analogues of high-valent heme protein intermediates such as compounds I and II. Against this backdrop, the electronic structure of chloroiron corrole has provoked a lively debate in recent years. Thus, whereas NMR spectroscopy and DFT calculations suggest an S = 3/2 Fe(III) corrole (*2-) radical description, certain researchers have favored an Fe(IV) formulation. These two descriptions are indistinguishable as far as DFT calculations are concerned. Ab initio CASSCF/CASPT2 calculations provide unambiguous support for the former description. In addition, they rule out any Fe(IV) state, whether high- or low-spin, within 1.5 eV of the ground state.
Tumor Hypoxia Has Independent Predictor Impact Only in Patients With Node-Negative Cervix Cancer (2002)

PURPOSE: This prospective clinical study was begun in 1994 to validate the independent prognostic impact of tumor hypoxia in patients with cervix cancer treated with definitive radiation therapy. PATIENTS AND METHODS: Between May 1994 and January 1999, 106 eligible patients with epithelial cervix cancer had tumor oxygen pressure (PO 2 ) measured using the Eppendorf probe. Oxygenation data are presented as the hypoxic proportion, defined as the percentage of PO 2 readings less than 5 mm/Hg (abbreviated as HP 5 ) and the median PO 2 . RESULTS: The median HP 5 in individual patients was 48%, and the median PO 2 was HP 5 . Progression-free survival (PFS) for patients with hypoxic tumors (HP 5 &gt; 50%) was 37% at 3 years versus 67% in those patients with better oxygenated tumors (P = .004). In multivariate analysis, only tumor size (risk ratio [RR], 1.33; P = .0003) and evidence of pelvic nodal metastases on imaging studies (RR, 2.52; P = .0065) were predictive of PFS. However, an interaction between nodal status and oxygenation was observed (P = .006), and further analysis indicated that HP 5 was an independent predictor of outcome in patients with negative nodes on imaging (P = .007). There was a significant increase in the 3-year cumulative incidence of distant metastases in the hypoxic group (41% v 15% in those with HP 5 &lt; 50%; P = .0023), but not in pelvic relapse (37% v 27%; P = .12). CONCLUSION: Tumor hypoxia is an independent predictor of poor PFS only in patients with node-negative cervix cancer, in addition to tumor size. Its impact appears to be related to an increased risk of distant metastases rather than to an effect on pelvic control.
Variance aware optimization of parameterized queries (2010)

Parameterized queries are commonly used in database applications. In a parameterized query, the same SQL statement is potentially executed multiple times with different parameter values. In today's DBMSs the query optimizer typically chooses a single execution plan that is reused for multiple instances of the same query. A key problem is that even if a plan with low average cost across instances is chosen, its variance can be high, which is undesirable in many production settings. In this paper, we describe techniques for selecting a plan that can better address the trade-off between the average and variance of cost across instances of a parameterized query. We show how to efficiently compute the skyline in the average-variance cost space. We have implemented our techniques on top of a commercial DBMS. We present experimental results on benchmark and real-world decision support queries.
The state of the World's Antibiotics 2015. (2015)

Since their introduction into medicine in the 1940s, antibiotics have been central to modern healthcare. Their role has expanded from treating serious infections to preventing infections in surgical patients, protecting cancer patients and people with compromised immune systems, and promoting growth and preventing disease in livestock and other food animals.