gebhart/patrepeval huggingface dataset:
Factors Affecting Transformation of Bacillus licheniformis (1966)

Thorne, Curtis B. (Fort Detrick, Frederick, Md.), and Harold B. Stull. Factors affecting transformation of Bacillus licheniformis. J. Bacteriol. 91:1012-1020. 1966.-Transformation systems involving two types of transformable mutants of Bacillus licheniformis 9945A were compared. Each system required its specific growth medium, but a single transformation medium could be used for both. Cells from a culture of optimal age were not competent, at least to any great extent, but they developed competence during incubation in a transformation medium. With each system, 3 to 5% of the recipient cells were transformed upon exposure to wild-type deoxyribonucleic acid (DNA) for 2 to 3 hr. When competent cells were exposed to DNA for 30 min, 1 to 2% of them were transformed. The data are interpreted to mean that cells were heterogeneous with respect to development of competence, and when properly grown cells were incubated in transformation medium some of them gained competence, whereas others lost it. If DNA was present during the entire period, the cells were transformed as they became competent and the transformants accumulated. However, during any short period of exposure to DNA, only those cells that were competent at the time were potential transformants. The high frequencies of transformation obtained in these studies made it feasible to prepare marked strains by transforming markers into recipient cells. These experiments demonstrated that the characteristics of the two transformation systems could not be attributed to specific nutritional markers. Presumably, each of the two series of highly transformable auxotrophic mutants also carried at least one other mutation that resulted in development of competence under the specific conditions.
Potentiation of paclitaxel activity by the HSP90 inhibitor 17-allylamino-17-demethoxygeldanamycin in human ovarian carcinoma cell lines with high levels of activated AKT (2006)

Activation of the phosphatidylinositol-3-kinase (PI3K)/AKT survival pathway is a mechanism of cytotoxic drug resistance in ovarian cancer, and inhibitors of this pathway can sensitize to cytotoxic drugs. The HSP90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) depletes some proteins involved in PI3K/AKT signaling, e.g., ERBB2, epidermal growth factor receptor (EGFR), and phosphorylated AKT (p-AKT). 17-AAG and paclitaxel were combined (at a fixed 1:1 ratio of their IC(50)) in four ovarian cancer cell lines that differ in expression of p-AKT, EGFR, and ERBB2. The EGFR-overexpressing A431 and KB epidermoid cell lines were also included. Combination indices (CI) were calculated using the median-effect equation and interpreted in the context of 17-AAG-mediated inhibition of PI3K signaling. Synergy was observed in IGROV-1- and ERBB2-overexpressing SKOV-3 ovarian cancer cells that express a high level of constitutively activated p-AKT [CI at fraction unaffected (fu)(0.5) = 0.50 and 0.53, respectively]. Slight synergy was observed in A431 cells (moderate p-AKT/overexpressed EGFR; CI at fu(0.5) = 0.76) and antagonism in CH1 (moderate p-AKT), HX62 cells (low p-AKT), and KB cells (low p-AKT/overexpressed EGFR; CI at fu(50) = 3.0, 3.5, and 2.0, respectively). The observed effects correlated with changes in the rate of apoptosis induction. 17-AAG induced a decrease in HSP90 client proteins (e.g., C-RAF, ERBB2, and p-AKT) or in downstream markers of their activity (e.g., phosphorylated extracellular signal-regulated kinase or p-AKT) in SKOV-3, IGROV-1, and CH1 cells at IC(50) concentrations. A non-growth-inhibitory concentration (6 nmol/L) reduced the phosphorylation of AKT (but not extracellular signal-regulated kinase) and sensitized SKOV-3 cells to paclitaxel. In conclusion, 17-AAG may sensitize a subset of ovarian cancer to paclitaxel, particularly those tumors in which resistance is driven by ERBB2 and/or p-AKT.
A flexible distributed authorization protocol (2002)

While there has been considerable effort in creating a single sign-on solution for interoperability among authentication methods, such interoperability across authorization methods has received little attention. This paper presents a flexible distributed authorization protocol that provides the full generality of restricted proxies while supporting the functionality of and interoperability with existing authorization models including OSF DCE and SESAME V2. Our authorization protocol includes a delegation method that is well suited for certain electronic commerce applications.
A steroid-inducible promoter for the controlled overexpression of cloned genes in eukaryotic cells. (1993)

Previous studies have shown that members of the steroid receptor family of transcriptional regulators can function synergistically when bound to multiple arrays of specific DNA binding sites known as hormone response elements, usually located upstream of target genes. We have constructed a mammalian expression vector containing a synthetic promoter composed of five high-affinity glucocorticoid response elements (termed GRE5) placed upstream of the adenovirus 2 major late promoter "TATA" region. In transiently transfected HeLa cells in the presence of dexamethasone, the GRE5 promoter was at least 50-fold more efficient than the mouse mammary tumor virus long terminal repeat in expressing bacterial chloramphenicol acetyltransferase activity. When the GRE5 vector was introduced stably into the HeLa cell genome, chloramphenicol acetyltransferase activity was induced from 10- to >50-fold by dexamethasone in six of eight responsive clones. The levels of both basal and induced expression varied from one clone to the next, probably due to an effect of chromosomal location on promoter activity. When propagated stably in HeLa cells in an Epstein-Barr virus episomal vector, the GRE5 promoter was > 50-fold inducible and its activity was strictly dependent on the presence of dexamethasone. We also show that the GRE5 promoter stably propagated in HeLa cells is inducible by progesterone in the presence of a transiently transfected progesterone receptor expression vector. The GRE5 promoter should be widely applicable for the strictly controlled high-level expression of target genes in eukaryotic cells that contain either the glucocorticoid or progesterone receptors.
Phase I Trial of M7824 (MSB0011359C), a Bifunctional Fusion Protein Targeting PD-L1 and TGFβ, in Advanced Solid Tumors (2018)

<b>Purpose:</b> M7824 (MSB0011359C) is an innovative first-in-class bifunctional fusion protein composed of a mAb against programmed death ligand 1 (PD-L1) fused to a TGFβ "trap."<b>Experimental Design:</b> In the 3+3 dose-escalation component of this phase I study (NCT02517398), eligible patients with advanced solid tumors received M7824 at 1, 3, 10, or 20 mg/kg once every 2 weeks until confirmed progression, unacceptable toxicity, or trial withdrawal; in addition, a cohort received an initial 0.3 mg/kg dose to evaluate pharmacokinetics/pharmacodynamics, followed by 10 mg/kg dosing. The primary objective is to determine the safety and maximum tolerated dose (MTD); secondary objectives include pharmacokinetics, immunogenicity, and best overall response.<b>Results:</b> Nineteen heavily pretreated patients with ECOG 0-1 have received M7824. Grade ≥3 treatment-related adverse events occurred in four patients (skin infection secondary to localized bullous pemphigoid, asymptomatic lipase increase, colitis with associated anemia, and gastroparesis with hypokalemia). The MTD was not reached. M7824 saturated peripheral PD-L1 and sequestered any released plasma TGFβ1, -β2, and -β3 throughout the dosing period at >1 mg/kg. There were signs of efficacy across all dose levels, including one ongoing confirmed complete response (cervical cancer), two durable confirmed partial responses (PR; pancreatic cancer; anal cancer), one near-PR (cervical cancer), and two cases of prolonged stable disease in patients with growing disease at study entry (pancreatic cancer; carcinoid).<b>Conclusions:</b> M7824 has a manageable safety profile in patients with heavily pretreated advanced solid tumors. Early signs of efficacy are encouraging, and multiple expansion cohorts are ongoing in a range of tumors. <i>Clin Cancer Res; 24(6); 1287-95. ©2018 AACR</i>.
Grosmomoside I, a new cucurbitane triterpenoid glycoside from fruits of Momordica grosvenori (2005)

2005-2006 > Academic research: refereed > Publication in refereed journal
Surface Recognition among Oral Bacteria: Multigeneric Coaggregations and their Mediators (1989)

Nearly all human oral bacteria participate in intergeneric coaggregation, which is defined as cell-to-cell recognition and adherence between bacterial pairs from different genera.’ It is becoming increasingly clear that coaggregation is a critical factor in bacterial colonization and accretion on oral surface~.~.~ Furthermore, the concept of multigeneric coaggregates,6 interacting bacterial networks composed of coaggregating cells of three or more genera, is central to understanding the accumulation of dental plaque on teeth. While the recent studies of initial adherence by bacteria to oral surfaces are briefly covered here, the major focus of this article is the potential role of multigeneric coaggregations in the bacterial ecology of the oral cavity. Their relevance to (1) a lotic or flowing environment; (2) sequential addition6 or accretion of bacteria on teeth; (3) temporal changes in bacterial populations that accompany progressively more severe stages of periodontal disease;’-I9 and (4) interactive cellular arrangements that illustrate bacterial competitions,2’.22 and rosettesU are discussed. Excepting conjugation systems, reports of intergeneric bacteria-bacteria interactions outside of the oral microflora are few, and the adherence properties of the participating cell types have not been de~cribed.~’~’ Some of these appear to involve nutritiona128*3 or predatory”32 relationships. Ecosystems where coaggregation might be expected to play a role are the large cellular aggregations of metabolic consortia found in anaerobic digestors that convert organic matter into CH, and C02.33.y Although direct cell-to-cell contact between these synmphic organisms has not been reported, it has been proposed that metabolic communication within the extracellular biopolymer matrix occurs by interspecies juxtapositioning rather than between separate clusters of the Merent types of cells.3s In contrast, studies of metabolic communication among the obligately anaerobic methanogenic human oral bacteria in dental plaque are just beginning,19’ and their involvement in coaggregation has not been investigated. Because the bacterial composition of subgingival dental plaque is in a constant state of flux, a recurring theme in this review is the apparent relationship of coaggregating partnerships to their temporal appearance in this ecosystem. Subgingival bacteria that are found in the environment of normal healthy gingiva tend to form coaggregating pairs, whereas those bacteria that predominate in more advanced stages of periodontal disease tend not to recognize the early colonizers.’% Instead, they coaggregate with other bacteria
Regulation of the H+/e− stoichiometry of cytochrome c oxidase from bovine heart by intramitochondrial ATP/ADP ratios (1996)

This paper describes the effect of intramitochondrial ATP/ADP ratios on the H+/e- stoichiometry of reconstituted cytochrome c oxidase (COX) from bovine heart. At 100% intraliposomal ATP the H+/e- stoichiometry of the reconstituted enzyme is decreased to half of the value measured below 98% intraliposomal ATP (above 2% ADP), while it remains constant up to 100% ADP. The decrease is obtained with different COX preparations, independent of the absolute value of the H+/e- stoichiometry. Decrease of H+/e- stoichiometry is prevented by preincubation of the enzyme with a tissue-specific monoclonal antibody to subunit VIa-H (heart type). Tissue-specific regulation of the efficiency of energy transduction in COX of muscle mitochondria could have a physiological function in maintaining the body temperature at rest or sleep, i.e. at low ATP expenditure.
Prenatal diagnosis of beta-thalassaemia using fetal erythroblasts enriched from maternal blood by a novel gradient (2000)

We have assessed a new technique for the isolation of fetal erythroblasts from maternal blood for the non-invasive prenatal diagnosis of pregnancies at risk of beta-thalassaemia. This method relies on the separation of erythroblasts from maternal nucleated cells by a novel step gradient and high speed centrifugation. In four of the six cases examined, single erythroblasts were identified by immunohistochemistry for zeta (zeta) globin. These were individually micromanipulated and analysed by single cell polymerase chain reaction (PCR) and subsequent sequencing of the region of beta-globin locus where the mutations most common to the region of Puglia, Italy, are clustered. In each of the four instances where fetal erythroblasts were identified by antibody staining, the fetal beta-globin genotype was correctly determined. To date, this represents the largest series of non-invasive prenatal diagnoses performed for this haemoglobinopathy.
In vitro scanning electron microscopic study on the effect of doxycycline and vancomycin on enterococcal induced biofilm. (2010)

We can conclude that vancomycin had greater efficacy than doxycycline for inhibiting and reducing E. faecalis biofilms growth in root canals. However, it failed to completely eliminate biofilm formation.
Downregulation of cytoplasmic DNases is implicated in cytoplasmic DNA accumulation and SASP in senescent cells (2018)

Accumulating evidence indicates that the senescence-associated secretory phenotype (SASP) contributes to many aspects of physiology and disease. Thus, controlling the SASP will have tremendous impacts on our health. However, our understanding of SASP regulation is far from complete. Here, we show that cytoplasmic accumulation of nuclear DNA plays key roles in the onset of SASP. Although both DNase2 and TREX1 rapidly remove the cytoplasmic DNA fragments emanating from the nucleus in pre-senescent cells, the expression of these DNases is downregulated in senescent cells, resulting in the cytoplasmic accumulation of nuclear DNA. This causes the aberrant activation of cGAS-STING cytoplasmic DNA sensors, provoking SASP through induction of interferon-β. Notably, the blockage of this pathway prevents SASP in senescent hepatic stellate cells, accompanied by a decline of obesity-associated hepatocellular carcinoma development in mice. These findings provide valuable new insights into the roles and mechanisms of SASP and possibilities for their control.
Bis(dithienothiophene) organic field-effect transistors with a high ON/OFF ratio (1997)

A conjugated, fused-thiophene oligomer, bis(dithienothiophene) (BDT), has been synthesized and deposited by vacuum sublimation as the active layer in organic thin film transistors (TFTs). The TFTs show exceptionally high ON/OFF ratios up to 108 between accumulation and depletion with sharp turn-on characteristics comparable to that of amorphous silicon TFTs (subthreshold slope S=0.6 V/decade). Field-effect mobilities are 0.02–0.05 cm2/V s. The good performance is explained by the relatively high π-π* gap of the short-chain BDT molecule and the favorable coplanar π-π stacking in BDT, differing from the herringbone stacking in the oligothiophenes.
Attention Deficit Hyperactivity Disorder (ADHD) and 5-HT2C receptor: A slight increase in the transmission of Cys23 to ADHD cases (1999)

Recent evidence suggests that interaction with and balancebetween serotonergicand dopaminergic neurotransmissionis important in the mediation of hyperactive behaviour.Animal model studies have ?rmly implicated the genes of theserotonergic system in predisposing to ADHD. Serotoninexerts its effects via a heterogenous family of receptors ofwhich there are at least 14 distinct subtypes.The non-speci?c serotonin receptor agonist (m-chlorophenylpiperazine)is known to suppress locomotion in normalmice. However, when administered to mice bearing amutated 5-HTR2C gene, it induces hyperactivity in theseanimals (Lora et al., 2000). This effect was blocked by pretreatmentwith 5HT1B receptor antagonist, indicating thatthe behavioural consequences of the mCPP-induced 5HT1Breceptor stimulation are unmasked in animals devoid of5HT2C receptor function. A Cysteine to Serine substitutionat amino acid 23 of the 5HT2C has been identi?ed whichmay in ?uence the receptor folding thereby hindering the formation of a normal hydrophobic pocket and subsequentlythe binding of bulky ligands. In a family based associationstudy design, we analysed the Cys-Ser polymorphism at the5HT2C receptor gene in 60 Irish ADHD trios using transmissiondisequilibrium test (TDT). We observed a slightincrease in the transmission of the Cysteine allele to theaffected ADHD cases (Chi-square ?1.8, P ? 0.26). Thismay suggest the involvement of 5HT2C gene in predisposingto ADHD.
Formaldehyde, Formalin, Paraformaldehyde And Glutaraldehyde: What They Are And What They Do (2000)

Abstract Aldehydes are the most commonly used fixatives. They serve to stabilize the fine structural details of cells and tissues prior to examination by light or electron microscopy. Research workers, technicians, pathologists and others who regularly use aldehyde fixatives frequently do not appreciate the nature and properties of these compounds or the reasons for choosing to fix a specimen in formaldehyde, glutaraldehyde or a mixture of the two. Misconceptions are widespread also about formalin and paraformaldehyde, the commercial products from which formaldehyde-containing solutions are made.
Design of sealed cavity microstructures formed by silicon wafer bonding (1993)

Three fabrication issues related to the design and fabrication of micromechanical devices using sealed cavities within bonded silicon wafers are discussed. The first concerns the resultant residual gas pressure within a sealed cavity between two bonded wafers after bonding and a high-temperature anneal. The second concerns the prediction of plastic deformation in capping layers of single-crystal silicon over sealed cavities. Exposure of sealed cavity structures to a high-temperature environment causes the trapped residual gas to expand, which can result in the plastic deformation of the capping layer. A model for analytically predicting the occurrence of plastic deformatio in these silicon capping layers has been developed. The third fabrication issue concerns the prediction of the resultant height of plastically deformed capping layers of silicon after cooling. A model which gives a lower and an upper bound on the height, based on an analytical spherical shell membrane stress equation, has been developed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Kriging interpolation in simulation: a survey (2004)

Many simulation experiments require much computer time, so they necessitate interpolation for sensitivity analysis and optimization. The interpolating functions are 'metamodels' (or 'response surfaces') of the underlying simulation models. Classic methods combine low-order polynomial regression analysis with fractional factorial designs. Modern Kriging provides 'exact' interpolation, i.e., predicted output values at inputs already observed equal the simulated output values. Such interpolation is attractive in deterministic simulation, and is often applied in computer aided engineering. In discrete-event simulation, however, Kriging has just started. Methodologically, a Kriging metamodel covers the whole experimental area; i.e., it is global (not local). Kriging often gives better global predictions than regression analysis. Technically, Kriging gives more weight to 'neighboring' observations. To estimate the Kriging metamodel, space filling designs are used; for example, latin hypercube sampling (LHS). This paper also presents novel, customized (application driven) sequential designs based on cross-validation and bootstrapping.
Environmental Advances in Drilling Fluids and Waste Operations Applying Novel Technology for Fluid Recovery and Recycling (2006)

Abstract This paper presents a concept designed to meet and be compliant with the environmental legislation requirements of managing drilling fluids, completion fluids and waste from the oil and gas industry in the arctic and Barents Sea region. Data will be presented in this paper to document the reduction in direct environmental impact, reduced risk as well as the profitable returns; like cost savings for the operators and the drilling fluid supplier as a result from applying these novel technologies. A total drilling fluid and waste management concept for drilling and well operations was developed to merge the operators cost reduction strategies and reduced environmental impact with the fluids and equipment supplier's technology and business incentives. Key elements in this concept was; (1) the development of both water based and oil based environmental friendly drilling fluids for challenging arctic conditions, (2) the EnviroUnit for separation, recovery and recycling on location, (3) CleanCut for enclosed cuttings containment completely reliable with no operational downtime or due to harsh weather conditions when drilling operations are distant from shore and finally (4) the onshore EnviroCenter with capacity and technology to receive, treat, store, manufacture and deliver drilling fluids and related liquid and cuttings waste streams. Presented data show oil based drilling special waste reduction of over 90%. All recovered oil based drilling fluid has been recycled, upgraded and reused. A reduction in the new oil based drilling fluid consumption has been experienced reducing manufacturing, transport and storage cost. All separated waste water has been cleaned to well within the approved discharge regulations. Whenever possible, the total fluids and waste management concept should be applied. Oil recovered from cuttings transported onshore and processed via thermal treatment has been successfully recycled as drilling fluid base oil. This total fluids and waste management concept has been established as a business "standard". The success is however closely linked to the close team-work with the operator and across the traditional service lines of fluids; solids control, waste management, associated waste handling logistics, processing, treatment and disposal. It will achieve full environmental impact and benefit when applied to large-scale operation.
Low-Field Magnetic Separation of Monodisperse Fe 3 O 4 Nanocrystals (2006)

Magnetic separations at very low magnetic field gradients (<100 tesla per meter) can now be applied to diverse problems, such as point-of-use water purification and the simultaneous separation of complex mixtures. High-surface area and monodisperse magnetite (Fe3O4) nanocrystals (NCs) were shown to respond to low fields in a size-dependent fashion. The particles apparently do not act independently in the separation but rather reversibly aggregate through the resulting high-field gradients present at their surfaces. Using the high specific surface area of Fe3O4 NCs that were 12 nanometers in diameter, we reduced the mass of waste associated with arsenic removal from water by orders of magnitude. Additionally, the size dependence of magnetic separation permitted mixtures of 4- and 12-nanometer-sized Fe3O4 NCs to be separated by the application of different magnetic fields.