gebhart/patrepeval huggingface dataset:
Selection of a Pseudomonas cepacia strain constitutive for the degradation of trichloroethylene (1992)

Tn5 insertion mutants of Pseudomonas cepacia G4 that were unable to degrade trichloroethylene (TCE), toluene, or phenol or to transform m-trifluoromethyl phenol (TFMP) to 7,7,7-trifluoro-2-hydroxy-6-oxo-2,4-heptadienoic acid (TFHA) were produced. Spontaneous reversion to growth on phenol or toluene as the sole source of carbon was observed in one mutant strain, G4 5223, at a frequency of approximately 1 x 10(-4) per generation. One such revertant, G4 5223-PR1, metabolized TFMP to TFHA and degraded TCE. Unlike wild-type G4, G4 5223-PR1 constitutively metabolized both TFMP and TCE without aromatic induction. G4 5223-PR1 also degraded cis-1,2-dichloroethylene, trans-1,2-dichloroethylene, and 1,1-dichloroethylene and oxidized naphthalene to alpha naphthol constitutively. G4 5223-PR1 exhibited a slight retardation in growth rate at TCE concentrations of > or = 530 microM, whereas G4 (which was unable to metabolize TCE under the same noninducing growth conditions) remained unaffected. The constitutive degradative phenotype of G4 5223-PR1 was completely stable through 100 generations of nonselective growth.
Designing small multiple-target artificial RNAs (2010)

MicroRNAs (miRNAs) are naturally occurring small RNAs that regulate the expression of several genes. MiRNAs' targeting rules are based on sequence complementarity between their mature products and targeted genes' mRNAs. Based on our present understanding of those rules, we developed an algorithm to design artificial miRNAs to target simultaneously a set of predetermined genes. To validate in silico our algorithm, we tested different sets of genes known to be targeted by a single miRNA. The algorithm finds the seed of the corresponding miRNA among the solutions, which also include the seeds of new artificial miRNA sequences potentially capable of targeting these genes as well. We also validated the functionality of some artificial miRNAs designed to target simultaneously members of the E2F family. These artificial miRNAs reproduced the effects of E2Fs inhibition in both normal human fibroblasts and prostate cancer cells where they inhibited cell proliferation and induced cellular senescence. We conclude that the current miRNA targeting rules based on the seed sequence work to design multiple-target artificial miRNAs. This approach may find applications in both research and therapeutics.
Mathematical modeling of transdermal drug delivery. (1987)

A dynamic mathematical model for transdermal drug delivery is developed on the basis of the bi-layer skin/twocompartment body model. The effects of metabolism reaction in the viable skin, the drug binding and reservoir function in the stratum corneum, and the solubility and diffusivity of the drug in the skin on the permeation ratetime profile are extensively simulated. The effects of the pharmacokinetic parameters on the plasma concentration profile are also analyzed. The present model is useful not only for analyzing the rate of skin permeation but also for predicting the plasma concentration after transdermal drug delivery.
Metformin and Pathologic Complete Responses to Neoadjuvant Chemotherapy in Diabetic Patients With Breast Cancer (2009)

Diabetic patients with breast cancer receiving metformin and neoadjuvant chemotherapy have a higher pCR rate than do diabetics not receiving metformin. Additional studies to evaluate the potential of metformin as an antitumor agent are warranted.
IL‐4 induces apoptosis of endothelial cells through the caspase‐3‐dependent pathway (2000)

The present study was designed to investigate the hypothesis that interleukin-4 (IL-4) can induce apoptosis of human endothelial cells and to study regulatory pathways of this process. Indeed, DNA ladder assay and flow cytometry study showed that IL-4 can induce apoptosis of endothelial cells in a time- and dose-dependent manner. In addition, IL-4 markedly increased activity of caspase-3, and inhibition of this enzyme suppressed IL-4-induced apoptosis in a dose-dependent manner. These results provide the first evidence that IL-4 can induce apoptosis of human endothelial cells. In addition, the data indicate that the caspase-3-dependent pathway is critically involved in this process.
A Systematic Review: The Role of Resident Memory T Cells in Infectious Diseases and Their Relevance for Vaccine Development (2018)

Although the role resident memory T cells play in providing immunity varies depending on the pathogen and anatomical location they resided in, the evidence overall suggests that these cells are vital for the timely and optimal protection against a number of infectious diseases. The induction of resident memory T cells should be further investigated and seriously considered when designing new vaccines.
Are catechins natural tyrosine kinase inhibitors? (2002)

Enhanced activity of tyrosine kinase receptors (RTKs) has been implicated as a contributing factor in the development of malignant and nonmalignant proliferative diseases such as cancer and atherosclerosis. Several growth factors traducing mitogenic signals through RTKs are implicated in the development of tumor and cardiovascular diseases. Therefore, in recent years many efforts have been made to develop RTK small molecule inhibitors for the treatment of tumor and cardiovascular diseases. Recently, catechins, the main compounds of green tea leafs, have been identified as potent natural inhibitors of several RTKs. Furthermore, there is increasing evidence that catechins possess antiangiogenic properties. In summary, several animal and cell culture studies suggest that catechins are potential candidates for the clinical therapy of cancer and cardiovascular diseases. (c) 2002 Prous Science. All rights reserved.
Chinese Redemptive Societies and Salvationist Religion: Historical Phenomenon or Sociological Category? (2011)

This paper outlines a conceptual framework for research on Chinese redemptive societies and salvationist religion. I begin with a review of past scholarship on Republican era salvationist movements and their contemporary communities, comparing their treatment in three bodies of scholarly literature dealing with the history and scriptures of ”popular sects” in the late imperial era, the history of ”secret societies” of the Republican period, and the ethnography of ”popular religion” in the contemporary Chinese world. I then assess Prasenjit Duara's formulation of ”redemptive societies” as a label for a constellation of religious groups active in the republican period, and, after comparing the characteristics of the main groups in question (such as the Tongshanshe, Daoyuan, Yiguandao and others), argue that an analytical distinction needs to be made between ”salvationist movements” as a sociological category, which have appeared throughout Chinese history and until today, and redemptive societies as one historical instance of a wave of salvationist movements, which appeared in the Republican period and bear the imprint of the socio-cultural conditions and concerns of that period. Finally, I discuss issues for future research and the significance of redemptive societies in the social, political and intellectual history of modern China, and in the modern history of Confucianism, Daoism, and Buddhism.
Constitutive NF-κB maintains high expression of a characteristic gene network, including CD40, CD86, and a set of antiapoptotic genes in Hodgkin/Reed-Sternberg cells (2001)

Constitutively activated nuclear factor (NF)-kappaB is observed in a variety of neoplastic diseases and is a hallmark of the malignant Hodgkin and Reed-Sternberg cells (H/RS) in Hodgkin lymphoma. Given the distinctive role of constitutive NF-kappaB for H/RS cell viability, NF-kappaB-dependent target genes were searched for by using adenoviral expression of the super-repressor IkappaBDeltaN. A surprisingly small but characteristic set of genes, including the cell-cycle regulatory protein cyclin D2, the antiapoptotic proteins Bfl-1/A1, c-IAP2, TRAF1, and Bcl-x(L), and the cell surface receptors CD86 and CD40 were identified. Thus, constitutive NF-kappaB activity maintains expression of a network of genes, which are known for frequent, marker-like expression in primary or cultured H/RS cells. Intriguingly, CD40, which is able to activate CD86 or Bcl-x(L) via NF-kappaB, is itself transcriptionally regulated by NF-kappaB through a promoter proximal binding site. NF-kappaB inhibition resulted in massive spontaneous and p53-independent apoptosis, which could be rescued by ectopic expression of Bcl-x(L), underscoring its dominant role in survival of H/RS cells. Hence, NF-kappaB controls a signaling network in H/RS cells, which promotes tumor cell growth and confers resistance to apoptosis.
Accuracy and efficiency define Bxb1 integrase as the best of fifteen candidate serine recombinases for the integration of DNA into the human genome (2013)

We conclude that the Bxb1 and φC31 integrases are the reagents of choice for genome engineering in vertebrate cells and that DNA damage repair is a major limitation upon the utility of this class of site-specific recombinase.
TCR stimulation with modified anti-CD3 mAb expands CD8+ T cell population and induces CD8+CD25+ Tregs (2005)

Modified anti-CD3 mAbs are emerging as a possible means of inducing immunologic tolerance in settings including transplantation and autoimmunity such as in type 1 diabetes. In a trial of a modified anti-CD3 mAb [hOKT3gamma1(Ala-Ala)] in patients with type 1 diabetes, we identified clinical responders by an increase in the number of peripheral blood CD8+ cells following treatment with the mAb. Here we show that the anti-CD3 mAb caused activation of CD8+ T cells that was similar in vitro and in vivo and induced regulatory CD8+CD25+ T cells. These cells inhibited the responses of CD4+ cells to the mAb itself and to antigen. The regulatory CD8+CD25+ cells were CTLA4 and Foxp3 and required contact for inhibition. Foxp3 was also induced on CD8+ T cells in patients during mAb treatment, which suggests a potential mechanism of the anti-CD3 mAb immune modulatory effects involving induction of a subset of regulatory CD8+ T cells.
Posttranslational activation, site‐directed mutation and phylogenetic analyses of the lysine biosynthesis enzymes α‐aminoadipate reductase Lys1p (AAR) and the phosphopantetheinyl transferase Lys7p (PPTase) from Schizosaccharomyces pombe (2004)

Alpha-aminoadipate reductase (AAR), the signature enzyme for lysine biosynthesis in fungi, catalyses the conversion of alpha-aminoadipate to alpha-aminoadipate-semiadehyde in the presence of ATP and NADPH. In Saccharomyces cerevisiae and Candida albicans, the LYS2-encoded AAR is posttranslationally activated by CoA and the LYS5-encoded PPTase. The fission yeast Schizosaccharomyces pombe is evolutionarily highly diverged from S. cerevisiae and C. albicans. We report here several unusual activation characteristics of Sz. pombe Lys1p and Lys7p, isofunctional to Lys2p (AAR) and Lys5p (PPTase), respectively. Unlike the Lys2p from S. cerevisiae and C. albicans, the Sz. pombe Lys1p was active when expressed in E. coli and exhibited significant AAR activity without the addition of CoA or the Sz. pombe Lys7p intron free PPTase. Somewhat higher AAR activity was obtained with the addition of CoA and the Sz. pombe Lys7p PPTase. Substitution of G910A, S913T or S913A in the Sz. pombe Lys1p activation domain (IGGHSI) resulted in no AAR activity. Similarly, substitutions of several amino acid residues in the Sz. pombe Lys7p PPTase domain (G79A, R80K and P81A in Core 1; F93W, D94E, F95W and N96D in Core 1a; G124A, V125I and D126E in Core 2; K172R, E173D and K177R in Core 3) also resulted in no activation of Lys1p and no AAR activity. The Sz. pombe Lys1p amino acid sequence showed a high degree of similarity to other fungal Lys2p proteins; however, the Lys7p amino acid sequence showed much less similarity to other bacterial, fungal and animal PPTases representing several phylogenetic groups.
A theoretical analysis of the laser melt-level monitoring system for the Czochralski crystal growing furnaces (1997)

This paper discusses the operating theory of a trigonometrical laser melt-level monitoring system as applied to Czochralski crystal pullers. The surface movement of the silicon melt is modeled with three-dimensional random harmonic waves. The effect of this motion on the spatial distribution of the laser signal is simulated and studied. Means of separating the laser signal from the noise caused by the background radiation from the melt is described. Statistical analysis is used to determine measurement accuracy. It has been found that with a relatively tranquil melt surface, characterized by a small wave amplitude to wavelength ratio and a large wavelength to laser beam size ratio, the laser signal is confined to a limited area, thus can be effectively acquired by a photo detector. The accurate measurement can then be achieved with statistical means. Experimental data generated with water and molten silicon surfaces are in good conformity with the theoretical results.
Sigh Improves Gas Exchange and Lung Volume in Patients with Acute Respiratory Distress Syndrome Undergoing Pressure Support Ventilation (2002)

The addition of 1 sigh per minute during PSV in patients with early ARDS improved gas exchange and lung volume and decreased the respiratory drive.
PALAEO-ENVIRONMENT, DIAGENESIS AND CHARACTERISTICS OF PERMIAN BLACK SHALES IN THE LOWER KAROO SUPERGROUP FLANKING THE CAPE FOLD BELT NEAR JANSENVILLE, EASTERN CAPE, SOUTH AFRICA: IMPLICATIONS FOR THE SHALE GAS POTENTIAL OF THE KAROO BASIN (2015)

Author: Geel, Claire et al.; Genre: Journal Article; Finally published : 2015; Title: Palaeo-environment, diagenesis and characteristics of Permian black shales in the Lower Karoo Supergroup<br/>flanking the Cape Fold Belt near Jansenville, eastern Cape, South Africa: Implications for the shale gas potential of the Karoo Basin
FGFR3 Translocations in Bladder Cancer: Differential Sensitivity to HSP90 Inhibition Based on Drug Metabolism (2014)

Pharmacologic blockade of the molecular chaperone HSP90 represents a promising approach for treating bladder tumors driven by oncogenic gene rearrangements of FGFR3. Furthermore, UDP-glucuronosyltransferase enzyme expression may serve as a predictive factor for clinical response to resorcinol-based HSP90 inhibitors.
Treating moderate to severe psoriasis – best use of biologics (2013)

This review focuses on the efficacy, safety and best use of biologic agents in moderate-to-severe psoriasis. Recommendations from two recent guidelines are summarised. The NICE Guidelines 2012 provide recommendations on best practice for prescribing biologics. The German S3 Guidelines are based on a systematic review of published studies and report the efficacy of biologics and guidelines for treatment. Data on the safety of biologics are available for up to 5 years in psoriasis and are on the whole reassuring. Registry data is evolving and will provide data on safety to help inform long-term monitoring of patients with psoriasis on biologics agents. New anti-interleukin-17 (IL17) and anti-IL17RA biologics are in Phase 3 clinical trials and may prove to be more effective than existing biologics.
Injectable DaxibotulinumtoxinA for the Treatment of Glabellar Lines: A Phase 2, Randomized, Dose-Ranging, Double-Blind, Multicenter Comparison With OnabotulinumtoxinA and Placebo (2017)

The 40U dose of daxibotulinumtoxinA was well tolerated (e.g., absence of ptosis) and had the most favorable risk: benefit profile. Compared with 20U onabotulinumtoxinA, it exhibited a significantly greater response rate and a significantly longer duration of response (median of 24 weeks vs 19 weeks; p = .030).
MECHANISMS OF INCREASED SURVIVAL AFTER LIPOPOLYSACCHARIDE-INDUCED ENDOTOXIC SHOCK IN MICE CONSUMING OLIVE OIL-ENRICHED DIET (2005)

We examined the impact of dietary fatty acid intake on lipopolysaccharide (LPS)-induced endotoxic shock. C57Bl/6J mice were fed for 6 weeks with a commercial laboratory chow (CC) or with test chows containing 7% (w/w) canola oil (CO), sesame oil (SeO), soybean oil (SO), or virgin olive oil (OO). The increase in body weight and energy consumption were similar for all diets tested. In the sixth week, mice were injected intraperitoneally with 400 microg of bacterial LPS to induce endotoxic shock. LPS induced a massive neutrophil infiltration into the peritoneal cavity and an increase in lipid body (LB) formation in leukocytes recovered from the peritoneal fluid of mice fed with CC, CO, SeO, or SO. In addition, there were increases in prostaglandin E(2) (PGE(2)), leukotriene B4 (LTB(4)), and cytokines IL-6, IL-10, and MCP-1 in peritoneal lavage, as well as in plasma TNF-alpha. In contrast, mice fed with OO exhibited reduced neutrophil accumulation and LB formation, and also had lower levels of PGE(2), LTB(4), MCP-1, and TNF-alpha. All mice fed with CC, CO, SeO, or SO died within 48 to 72 h after LPS injection. Interestingly, mice fed with the OO diet were resistant to endotoxic shock, with 60% survival at 168 h. These data indicate that intake of OO may have a beneficial role, reducing the magnitude of the inflammatory process triggered by endotoxic shock through modulation of LB formation and of the production of inflammatory mediators.
CoolMPS ™ : Advanced massively parallel sequencing using antibodies specific to each natural nucleobase (2020)

Abstract Massively parallel sequencing (MPS) on DNA nanoarrays provides billions of reads at relatively low cost and enables a multitude of genomic applications. Further improvement in read length, sequence quality and cost reduction will enable more affordable and accurate comprehensive health monitoring tests. Currently the most efficient MPS uses dye-labeled reversibly terminated nucleotides (RTs) that are expensive to make and challenging to incorporate. Furthermore, a part of the dye-linker (scar) remains on the nucleobase after cleavage and interferes with subsequent sequencing cycles. We describe here the development of a novel MPS chemistry (CoolMPS™) utilizing unlabeled RTs and four natural nucleobase-specific fluorescently labeled antibodies with fast (30 sec) binding. We implemented CoolMPS™ on MGI’s PCR-free DNBSEQ MPS platform using arrays of 200nm DNA nanoballs (DNBs) generated by rolling circle replication and demonstrate 3-fold improvement in signal intensity and elimination of scar interference. Single-end 100-400 base and pair-end 2×150 base reads with high quality were readily generated with low out-of-phase incorporation. Furthermore, DNBs with less than 50 template copies were successfully sequenced by strong-signal CoolMPS™ with 3-times higher accuracy than in standard MPS. CoolMPS™ chemistry based on natural nucleobases has potential to provide longer, more accurate and less expensive MPS reads, including highly accurate “4-color sequencing” on the most efficient dye-crosstalk-free 2-color imagers with an estimated sequencing error rate of 0.00058% (one error in 170,000 base calls) in a proof-of-concept demonstration.
Intersubunit contacts made by tryptophan 120 with biotin are essential for both strong biotin binding and biotin-induced tighter subunit association of streptavidin. (1995)

In natural streptavidin, tryptophan 120 of each subunit makes contacts with the biotin bound by an adjacent subunit through the dimer-dimer interface. To understand quantitatively the role of tryptophan 120 and its intersubunit communication in the properties of streptavidin, a streptavidin mutant in which tryptophan 120 is converted to phenylalanine was produced and characterized. The streptavidin mutant forms a tetrameric molecule and binds one biotin per subunit, as does natural streptavidin, indicating that the mutation of tryptophan 120 to phenylalanine has no significant effect on the basic properties of streptavidin. However, its biotin-binding affinity was reduced substantially, to approximately 10(8) M-1, indicating that the contact made by tryptophan 120 to biotin has a considerable contribution to the extremely tight biotin binding by streptavidin. The mutant retained bound biotin over a wide pH range or with the addition of urea up to 6 M at neutral pH. However, bound biotin was efficiently released by the addition of excess free biotin due, presumably, to exchange reactions. Electrophoretic analysis revealed that the intersubunit contact made by tryptophan 120 to biotin through the dimer-dimer interface is the major interaction responsible for the biotin-induced, tighter subunit association of streptavidin. In addition, the mutant has weaker subunit association than natural streptavidin even in the absence of biotin, indicating that tryptophan 120 also contributes to the subunit association of tetramers in the absence of biotin.
Tau protein liquid–liquid phase separation can initiate tau aggregation (2018)

The transition between soluble intrinsically disordered tau protein and aggregated tau in neurofibrillary tangles in Alzheimer's disease is unknown. Here, we propose that soluble tau species can undergo liquid-liquid phase separation (LLPS) under cellular conditions and that phase-separated tau droplets can serve as an intermediate toward tau aggregate formation. We demonstrate that phosphorylated or mutant aggregation prone recombinant tau undergoes LLPS, as does high molecular weight soluble phospho-tau isolated from human Alzheimer brain. Droplet-like tau can also be observed in neurons and other cells. We found that tau droplets become gel-like in minutes, and over days start to spontaneously form thioflavin-S-positive tau aggregates that are competent of seeding cellular tau aggregation. Since analogous LLPS observations have been made for FUS, hnRNPA1, and TDP43, which aggregate in the context of amyotrophic lateral sclerosis, we suggest that LLPS represents a biophysical process with a role in multiple different neurodegenerative diseases.
Major histocompatibility complex class II expression is required for posttransplant immunological but not hemopoietic reconstitution in mice. (1994)

We had previously shown in a canine model that the administration of anti-MHC class II monoclonal antibody (MAB) immediately after autologous marrow transplantation prevented hemopoietic reconstitution. Since MHC class II expression in mice differs from that in dogs we were interested in determining the effect of MHC class II manipulation on posttransplant hemopoietic and immunological recovery in mice. Three murine models including MHC class II knock-out mice were studied. BALB/c mice (I-E+, I-A+) given anti-MHC class II MAB H81.9 (anti-I-E; 1 mg/kg/day, days 0-4) after TBI and infusion of syngeneic marrow or infused with anti-I-E purged marrow both showed normal hemopoietic reconstitution. Similarly, C57B1/6 mice (I-E-, I-A+) transplanted with M5/114 (anti-I-A) purged marrow recovered normal hemopoiesis. MHC class II knock-out (C2D) mice, which lack class II completely, also recovered normal hemopoiesis after TBI and transplantation with either normal or class II-deficient (C2D) marrow, although the kinetics of platelet recovery as determined by megakaryocytopoiesis and platelet counts on day 14 were slightly delayed. C57B1/6 mice transplanted with C2D marrow recovered normally. Immunologic recovery, however, was abnormal both in C2D recipients and in normal mice transplanted with C2D marrow: While CD8+ T lymphocytes recovered normally, no (or only very few) CD4+ T cells were identified posttransplant. Treatment of normal mice with anti-MHC class II MAB in vivo or transplantation of MHC class II-purged marrow, however, did not interfere with complete immunological recovery, although T cell maturation was slightly delayed. Thus, complete immunological reconstitution requires the expression of MHC class II on marrow-derived precursor cells, while the expression of MHC class II antigens is not a requirement for hemopoietic reconstitution in mice.