gebhart/patrepeval huggingface dataset:
Directed evolution of λ integrase activity and specificity by genetic derepression (2015)

Advances in genome engineering are attendant on the development of novel enzyme variants with programed substrate specificities and improved activity. We have devised a novel selection method, wherein the activity of a recombinase deletes the gene encoding an inhibitor of an enzyme conferring a selectable phenotype. By using β-lactamase and the β-lactamase inhibitor protein, the selection couples recombinase activity to Escherichia coli survival in the presence of ampicillin. Using this method, we generated λ integrase variants displaying improved in vitro recombination of a non-cognate substrate present in the human genome. One generalist integrase variant displaying enhanced catalytic activity was further used in a facile, single-step transformation method to introduce transgenes up to 8.5 kb into the unique endogenous attB site of common laboratory E.coli strains.
Chitosan Biosynthesis and Virulence in the Human Fungal Pathogen Cryptococcus gattii (2019)

<i>Cryptococcus gattii</i> R265 is a hypervirulent fungal strain responsible for the recent outbreak of cryptococcosis in Vancouver Island of British Columbia in Canada. It differs significantly from <i>Cryptococcus neoformans</i> in its natural environment, its preferred site in the mammalian host, and its pathogenesis. Our previous studies of <i>C. neoformans</i> have shown that the presence of chitosan, the deacetylated form of chitin, in the cell wall attenuates inflammatory responses in the host, while its absence induces robust immune responses, which in turn facilitate clearance of the fungus and induces a protective response. The results of the present investigation reveal that the cell wall of <i>C. gattii</i> R265 contains a two- to threefold larger amount of chitosan than that of <i>C. neoformans</i> The genes responsible for the biosynthesis of chitosan are highly conserved in the R265 genome; the roles of the three chitin deacetylases (CDAs) have, however, been modified. To deduce their roles, single and double <i>CDA</i> deletion strains and a triple <i>CDA</i> deletion strain were constructed in a R265 background and were subjected to mammalian infection studies. Unlike <i>C. neoformans</i> where Cda1 has a discernible role in fungal pathogenesis, in strain R265, Cda3 is critical for virulence. Deletion of either <i>CDA3</i> alone or in combination with another CDA (<i>cda1Δ3</i>Δ or <i>cda2Δ3Δ</i>) or both (<i>cda1Δ2Δ3Δ</i>) rendered the fungus avirulent and cleared from the infected host. Moreover, the <i>cda1</i>Δ<i>2</i>Δ<i>3</i>Δ strain of R265 induced a protective response to a subsequent infection with R265. These studies begin to illuminate the regulation of chitosan biosynthesis of <i>C. gattii</i> and its subsequent effect on fungal virulence.<b>IMPORTANCE</b> The fungal cell wall is an essential organelle whose components provide the first line of defense against host-induced antifungal activity. Chitosan is one of the carbohydrate polymers in the cell wall that significantly affects the outcome of host-pathogen interaction. Chitosan-deficient strains are avirulent, implicating chitosan as a critical virulence factor. <i>C. gattii</i> R265 is an important fungal pathogen of concern due to its ability to cause infections in individuals with no apparent immune dysfunction and an increasing geographical distribution. Characterization of the fungal cell wall and understanding the contribution of individual molecules of the cell wall matrix to fungal pathogenesis offer new therapeutic avenues for intervention. In this report, we show that the <i>C. gattii</i> R265 strain has evolved alternate regulation of chitosan biosynthesis under both laboratory growth conditions and during mammalian infection compared to that of <i>C. neoformans</i>.
SAMP32, a Testis-Specific, Isoantigenic Sperm Acrosomal Membrane-Associated Protein1 (2002)

To identify novel human sperm membrane antigens, we analyzed two-dimensional gels of sperm extracts containing hydrophobic proteins that partitioned into Triton X-114. Four protein spots with isoelectric points (pIs) ranging from 4.5 to 5.5 and apparent molecular weights from 32 to 34 kDa were sequenced by mass spectrometry and found to contain common peptide sequences. Cloning the corresponding cDNA revealed that these protein spots were products of a single gene (SAMP32), encoding a protein of 32 kDa with a predicted pI of 4.57. SAMP32 has a potential transmembrane domain in the carboxyl terminus and is phosphorylated in vivo on serine 256. Northern blotting of eight human tissues and RNA dot blotting of 76 human tissues showed that SAMP32 expression was testis specific. SAMP32 contained an amino terminal domain homologous to the major malarial circumsporozoite surface protein and a domain similar to that of Krp1 from Schizosaccharomyces pombe in its carboxyl terminus. The SAMP32 locus consists of seven exons on chromosome 6q15-16.2. Antiserum against recombinant SAMP32 recognized protein spots originally cored from a two-dimensional gel. This antiserum strongly stained the equatorial segment and faintly stained the acrosome cap of ejaculated human spermatozoa by immunofluorescence. Immunoelectron microscopy showed that SAMP32 was associated with the inner acrosomal membrane in the principal and the equatorial segments of the sperm acrosome. By immunostaining enzyme-dissociated testicular cells, SAMP32 was localized to Golgi phase round spermatids and subsequent stages of acrosome biogenesis. Recombinant SAMP32 reacted with serum from an infertile man, suggesting that it is isoantigenic. Antibodies against recombinant SAMP32 inhibited both the binding and the fusion of human sperm to zona-free hamster eggs.
Rapid prototyping of a novel and flexible paper based oxygen sensing patch via additive inkjet printing process (2019)

A novel and flexible oxygen sensing patch was successfully developed for wearable, industrial, food packaging, pharmaceutical and biomedical applications using a cost-efficient and rapid prototypable additive inkjet print manufacturing process. An oxygen sensitive ink was formulated by dissolving ruthenium dye and ethyl cellulose polymer in ethanol in a 1 : 1 : 98 (w/w/w) ratio. The patch was fabricated by depositing the oxygen sensitive ink on a flexible parchment paper substrate using an inkjet printing process. A maximum absorbance from 430 nm to 480 nm and a fluorescence of 600 nm was observed for the oxygen sensitive ink. The capability of the oxygen sensitive patch was investigated by measuring the fluorescence quenching lifetime of the printed dye for varying oxygen concentration levels. A fluorescence lifetime decay (τ) from ≈4 μs to ≈1.9 μs was calculated for the printed oxygen sensor patch, for oxygen concentrations varying from ≈5 mg L−1 to ≈25 mg L−1. A sensitivity of 0.11 μs mg L−1 and a correlation coefficient of 0.9315 was measured for the printed patches. The results demonstrated the feasibility of employing an inkjet printing process for the rapid prototyping of flexible and moisture resistant oxygen sensitive patches which facilitates a non-invasive method for monitoring oxygen and its concentration levels.
Characterization of a 96-kilodalton thermostable polypeptide antigen of Plasmodium falciparum related to protective immunity in the squirrel monkey (1987)

Protective immunity against Plasmodium falciparum malaria in the squirrel monkey (Saimiri sciureus) is, in part, antibody mediated. We have previously shown that polypeptides of 41, 76, and 96 kilodaltons (kDa) are specifically immunoprecipitated with monkey sera which are protective in passive transfer experiments. We report here that three different 96-kDa polypeptides, of pI 5.15, 5.25, and 5.35, can be visualized when parasite extracts are analyzed in bidimensional gels. Only one of them (of pI 5.25) was stable after being heated at 100 degrees C for 5 min. The 96-kDa thermostable polypeptide of pI 5.25 was immunoprecipitated by protective monkey sera and by sera from adult humans living in hyperendemic areas and thus seems to be correlated with humoral protective immunity. This antigen was found in culture supernatants at the time of schizont rupture. It was synthesized during the schizont stage and is apparently not a glycoprotein.
A large scale machine learning system for recommending heterogeneous content in social networks (2011)

The goal of the Facebook recommendation engine is to compare and rank heterogeneous types of content in order to find the most relevant recommendations based on user preference and page context. The challenges for such a recommendation engine include several aspects: 1) the online queries being processed are at very large scale; 2) with new content types and new user-generated content constantly added to the system, the candidate object set and underlying data distribution change rapidly; 3) different types of content usually have very distinct characteristics, which makes generic feature engineering difficult; and 4) unlike a search engine that can capture intention of users based on their search queries, our recommendation engine needs to focus more on users' profile and interests, past behaviors and current actions in order to infer their cognitive states. In this presentation, we would like to introduce an effective, scalable, online machine learning framework we developed in order to address the aforementioned challenges. We also want to discuss the insights, approaches and experiences we have accumulated during our research and development process.
Synthesis Of Metastable Superconductors By High Dynamic Pressure (1988)

High dynamic pressure is used to synthesize metastable superconducting materials and to process superconductors into practical form. Specimens are subjected to shock pressures in the range 0.1-1 Mbar, temperatures up to several 1000 K and quenches at rates up to 1012 bar/s and 109 K/s. Shock waves are generated by impact of projectiles accelerated up to 3.5 km/s by the LLNL two-stage light-gas gun. Recovered specimens are characterized for superconductivity and structural properties. The gas gun, specimen recovery fixture, and phenomenology of the technique are described. Results are reviewed and include a quenched solid-solid phase transition (A15 Nb3Si); amorphous, fine-grained, and multiphase materials produced by shock-induced melting of powders and subsequent rapid solidification; and the shock-compaction in a metal matrix of thin powder layers of high-Tc oxides mixed with metal. The latter is a potential method for fabricating superconducting wire, which could be scaled to long lengths using explosives.
Microbiota/Host Crosstalk Biomarkers: Regulatory Response of Human Intestinal Dendritic Cells Exposed to Lactobacillus Extracellular Encrypted Peptide (2012)

The human gastrointestinal tract is exposed to a huge variety of microorganisms, either commensal or pathogenic; at this site, a balance between immunity and immune tolerance is required. Intestinal dendritic cells (DCs) control the mechanisms of immune response/tolerance in the gut. In this paper we have identified a peptide (STp) secreted by Lactobacillus plantarum, characterized by the abundance of serine and threonine residues within its sequence. STp is encoded in one of the main extracellular proteins produced by such species, which includes some probiotic strains, and lacks cleavage sites for the major intestinal proteases. When studied in vitro, STp expanded the ongoing production of regulatory IL-10 in human intestinal DCs from healthy controls. STp-primed DC induced an immunoregulatory cytokine profile and skin-homing profile on stimulated T-cells. Our data suggest that some of the molecular dialogue between intestinal bacteria and DCs may be mediated by immunomodulatory peptides, encoded in larger extracellular proteins, secreted by commensal bacteria. These peptides may be used for the development of nutraceutical products for patients with IBD. In addition, this kind of peptides seem to be absent in the gut of inflammatory bowel disease patients, suggesting a potential role as biomarker of gut homeostasis.
Controlled Load and Speed Transitions in a Multicylinder Recompression HCCI Engine (2014)

A model-based control strategy to track combustion phasing during load and speed transitions in the homogeneous charge compression ignition (HCCI) operating region of a multimode combustion engine is presented in this paper. HCCI transitions can traverse regions of high cyclic variability (CV), even if the steady state transition end points are stable with low CV. A control-oriented HCCI model for both the stable, low CV region and the oscillatory, high CV, late phasing region is used to design a controller that uses valve and fuel injection timings to track combustion phasing. Novel aspects of the controller include nonlinear model-inversion-based feedforward and gain scheduled feedback based on unburned fuel that reduces transient CV. Transitions tested on a multicylinder HCCI engine include load transitions at fixed engine speeds, simultaneous load, and speed transitions, and select FTP75 drive-cycle transitions with high load slew rates. Good combustion phasing tracking performance is demonstrated, and misfires are prevented.
All-optical XOR gate using semiconductor optical amplifiers without additional input beam (2002)

The novel design of an all-optical XOR gate by using cross-gain modulation of semiconductor optical amplifiers has been suggested and demonstrated successfully at 10 Gb/s. Boolean AB~ and A~B of the two input signals A and B have been obtained and combined to achieve the all-optical XOR gate. No additional input beam such as a clock signal or continuous wave light is used in this new design, which is required in other all-optical XOR gates.
ChemInform Abstract: ANTIHYPERTENSIVE 5,6‐DIARYLPYRIDAZIN‐3‐ONES (1981)

Abstract Die Aldehyde (I) reagieren mit Cyanid zu den Benzoinen (II), die über die Diketone (III) direkt bzw. über deren Hydrazone in die Diarylpyridazinone (IV) umgewandelt werden.
MicroRNA‐Based Therapeutic Strategies for Targeting Mutant and Wild Type RAS in Cancer (2015)

MicroRNAs (miRs) have been causally implicated in the progression and development of a wide variety of cancers. miRs modulate the activity of key cell signaling networks by regulating the translation of pathway component proteins. Thus, the pharmacological targeting of miRs that regulate cancer cell signaling networks, either by promoting (using miR-supplementation) or by suppressing (using antisense oligonucleotide-based strategies) miR activity is an area of intense research. The RAS-extracellular signal regulated kinase (ERK) pathway represents a major miR-regulated signaling network that endows cells with some of the classical hallmarks of cancer, and is often inappropriately activated in malignancies by somatic genetic alteration through point mutation or alteration of gene copy number. In addition, recent progress indicates that many tumors may be deficient in GTPase activating proteins (GAPs) due to the collaborative action of oncogenic miRs. Recent studies also suggest that in tumors harboring a mutant RAS allele there is a critical role for wild type RAS proteins in determining overall RAS-ERK pathway activity. Together, these two advances comprise a new opportunity for therapeutic intervention. In this review, we evaluate miR-based therapeutic strategies for modulating RAS-ERK signaling in cancers; in particular for more direct modulation of RAS-GTP levels, with the potential to complement current strategies to yield more durable treatment responses. To this end, we discuss the potential for miR-based therapies focused on three prominent miRs including the pan-RAS regulator let-7 and the GAP regulator comprised of miR-206 and miR-21 (miR-206/21).
Experimental infection in turkeys and chickens with Ornithobacterium rhinotracheale. (1997)

Ornithobacterium rhinotracheale was found to cause growth retardation in both turkeys and chickens after experimental intra-air sac administration and to cause growth retardation together with airsacculitis and pneumonia after aerosol administration. Both turkey and chicken isolates of O. rhinotracheale were able to induce the same kind of respiratory inflammations and weight-gain losses in chickens as well as turkeys. Turkey rhinotracheitis virus was found to have a triggering effect on the O. rhinotracheale infection in turkeys, and Newcastle disease virus and to a lesser extent infectious bronchitis virus showed triggering effects on the O. rhinotracheale infection in chickens. Ornithobacterium rhinotracheale could be reisolated from affected organs of experimentally infected birds.
Method of sealing. [Patent application] (1977)

Metabolomics, the systematic investigation of all metabolites present within a biologic system, is used in biomarker development for many human diseases, including cancer. In this review, we investigate the current role of mass spectrometry-based metabolomics in cancer research. A literature review was carried out within the databases PubMed, Embase, and Web of Knowledge. We included 106 studies reporting on 21 different types of cancer in 7 different sample types. Metabolomics in cancer research is most often used for case-control comparisons. Secondary applications include translational areas, such as patient prognosis, therapy control and tumor classification, or grading. Metabolomics is at a developmental stage with respect to epidemiology, with the majority of studies including less than 100 patients. Standardization is required especially concerning sample preparation and data analysis. In the second part of this review, we reconstructed a metabolic network of patients with cancer by quantitatively extracting all reports of altered metabolites: Alterations in energy metabolism, membrane, and fatty acid synthesis emerged, with tryptophan levels changed most frequently in various cancers. Metabolomics has the potential to evolve into a standard tool for future applications in epidemiology and translational cancer research, but further, large-scale studies including prospective validation are needed.
Epoxyeicosatrienoic acid analogue lowers blood pressure through vasodilation and sodium channel inhibition (2014)

Epoxyeicosatrienoic acids (EETs) contribute to haemodynamics, electrolyte homoeostasis and blood pressure regulation, leading to the concept that EETs can be therapeutically targeted for hypertension. In the present study, multiple structural EET analogues were synthesized based on the EET pharmacophore and vasodilator structure-activity studies. Four EET analogues with 91-119% vasodilatory activity in the isolated bovine coronary artery (EC50: 0.18-1.6 μM) were identified and studied for blood-pressure-lowering in hypertension. Two EET analogues in which the COOH group at carbon 1 of the EET pharmacophore was replaced with either an aspartic acid (EET-A) or a heterocyclic surrogate (EET-X) were administered for 14 days [10 mg/kg per day intraperitoneally (i.p.)]. Both EET-A and EET-X lowered blood pressure in spontaneously hypertensive rats (SHRs) and in angiotensin II (AngII) hypertension. On day 14, the mean arterial pressures in EET analogue-treated AngII-hypertensive and SHRs were 30-50 mmHg (EET-A) and 15-20 mmHg (EET-X) lower than those in vehicle-treated controls. These EET analogues (10 mg/kg per day) were further tested in AngII hypertension by administering orally in drinking water for 14 days and EET-A lowered blood pressure. Additional experiments demonstrated that EET-A inhibits epithelial sodium channel (ENaC) activity in cultured cortical collecting duct cells and reduced renal expression of ENaC subunits in AngII hypertension. In conclusion, we have characterized EET-A as an orally active antihypertensive EET analogue that protects vascular endothelial function and has ENaC inhibitory activity in AngII hypertension.
Generalization of Dual-Porosity-System Representation and Reservoir Simulation of Hydraulic Fracturing-Stimulated Shale Gas Reservoirs (2011)

Abstract Recently, we have developed a new methodology to model hydraulic fracturing-induced fracture networks and subsequently simulate a shale gas reservoir as a dual-porosity system. The reservoir geological, geophysical and petrophysical characteristic data are integrated to build geological framework and property models. Microseismic responses are used to delineate stimulated reservoir volumes. Microseismic events and/or natural fracture intensity are utilized to estimate the initial intensity of this induced fracture network. The fracture intensity is further calibrated using hydraulic fracturing job data and reservoir geomechanical properties through a fracture propagation mechanism. In this paper, we show a significant extension of the modeling methodology to handle more general scenarios of stimulated shale reservoirs. We introduce a superposition technique to process the overlapping of microseismic mapping responses from different stages of "simul-frac" and/or "zipper-frac" operations in a single well or in multiple wells. The improved method takes into account different fracture network geometries. Various models for volume expansion by stimulation are investigated for proppant placement estimations. In the ideal viscous fluid-proppant transportation scenario, proppant and fracture conductivity distributions can be calculated with mass conservation corresponding to different fracture network geometries and volume expansion models. Both fracture intensity and fracture network conductivity are used to create dual porosity simulation model inputs. Considering that for most shale gas wells there is no microseismic data, we introduce a modeling procedure incorporating treatment data and geomechanical parameters in which the fracture network geometry can be specified based on well completion data and field experience. We also present the general workflow through a demo case from data input, fracture network geometry configuration, calibration and calculations, and output of dual-porosity model parameters for reservoir simulation. This extended methodology can be efficiently applied not only to modeling of singlewell shale gas reservoir but also to modeling of multiple wells where their drainage volumes are inter-connected. A field example demonstrates the applications of the new modeling methodology, which provides a unique, effective means for modeling and simulation study as well as history-matching calibration of stimulated shale gas reservoirs.
A Structure−Affinity Relationship Study on Derivatives of <i>N</i>-[2-[4-(4-Chlorophenyl)piperazin-1-yl]ethyl]-3-methoxybenzamide, a High-Affinity and Selective D<sub>4</sub> Receptor Ligand (1999)

N-[2-[4-(4-Chlorophenyl)piperazin-1-yl]ethyl]-3-methoxybenzamide (1), a high-affinity and selective dopamine D(4) receptor ligand, was chosen as a lead, and structural modifications were done on its amide bond and on its alkyl chain linking the benzamide moiety to the piperazine ring and by preparing some semirigid analogues. The binding profile at dopamine D(4) and dopamine D(2), serotonin 5-HT(1A), and adrenergic alpha(1) receptors of 16 new compounds was determined. From the results emerged that the modification of the amide bond and the elongation of the intermediate alkyl chain caused a decrease in dopamine D(4) receptor affinity. All prepared semirigid analogues displayed D(4) receptor affinity values in the same range of the opened counterparts.
Beam quality improvements in surface-emitting distributed feedback lasers (1990)

Recent work on surface-emitting distributed feedback laser devices is reported. New developments include the incorporation of index guides for a more stable lateral mode and higher efficiency as well as tailored gratings for improved beam quality.