gebhart/patrepeval huggingface dataset:
Arabidopsis SON1 Is an F-Box Protein That Regulates a Novel Induced Defense Response Independent of Both Salicylic Acid and Systemic Acquired Resistance (2002)

One of several induced defense responses in plants is systemic acquired resistance (SAR), which is regulated by salicylic acid and in Arabidopsis by the NIM1/NPR1 protein. To identify additional components of the SAR pathway or other genes that regulate SAR-independent resistance, we performed genetic suppressor screens of mutagenized nim1-1 seedlings, which are highly susceptible to infection by Peronospora parasitica. We isolated the son1 (suppressor of nim1-1) mutant, which shows full restoration of pathogen resistance without the induction of SAR-associated genes and expresses resistance when combined with a salicylate hydroxylase (nahG) transgene. These features indicate that son1-mediated resistance is distinct from SAR. Resistance is effective against both the virulent oomycete Peronospora and the bacterial pathogen Pseudomonas syringae pv tomato strain DC3000. We cloned SON1 and found it to encode a novel protein containing an F-box motif, an element found within the specificity determinant in the E3 ubiquitin-ligase complex. We propose the existence of a novel defense response that is independent of SAR and negatively regulated in Arabidopsis by SON1 through the ubiquitin-proteosome pathway.
Tpl2 kinase regulates FcγR signaling and immune thrombocytopenia in mice (2013)

The MAPK3 Tpl2 controls innate and adaptive immunity by regulating TLR, TNF-α, and GPCR signaling in a variety of cell types. Its ablation gives rise to an anti-inflammatory phenotype characterized by resistance to LPS-induced endotoxin shock, DSS-induced colitis, and TNF-α-induced IBD. Here, we address the role of Tpl2 in autoimmunity. Our data show that the ablation and the pharmacological inhibition of Tpl2 protect mice from antiplatelet antibody-induced thrombocytopenia, a model of ITP. Thrombocytopenia in this model and in ITP is caused by phagocytosis of platelets opsonized with antiplatelet antibodies and depends on FcγR activation in splenic and hepatic myeloid cells. Further studies explained how Tpl2 inhibition protects from antibody-induced thrombocytopenia, by showing that Tpl2 is activated by FcγR signals in macrophages and that its activation by these signals is required for ERK activation, cytoplasmic Ca(2+) influx, the induction of cytokine and coreceptor gene expression, and phagocytosis.
Solution structure of the antiapoptotic protein bcl-2 (2001)

The structures of two isoforms of Bcl-2 that differ by two amino acids have been determined by NMR spectroscopy. Because wild-type Bcl-2 behaved poorly in solution, the structures were determined by using Bcl-2/Bcl-x(L) chimeras in which part of the putative unstructured loop of Bcl-2 was replaced with a shortened loop from Bcl-x(L). These chimeric proteins have a low pI compared with the wild-type protein and are soluble. The structures of the two Bcl-2 isoforms consist of 6 alpha-helices with a hydrophobic groove on the surface similar to that observed for the homologous protein, Bcl-x(L). Comparison of the Bcl-2 structures to that of Bcl-x(L) shows that although the overall fold is the same, there are differences in the structural topology and electrostatic potential of the binding groove. Although the structures of the two isoforms of Bcl-2 are virtually identical, differences were observed in the ability of the proteins to bind to a 25-residue peptide from the proapoptotic Bad protein and a 16-residue peptide from the proapoptotic Bak protein. These results suggest that there are subtle differences in the hydrophobic binding groove in Bcl-2 that may translate into differences in antiapoptotic activity for the two isoforms.
Cryptosporidiosis in Patients Infected with the Human Immunodeficiency Virus (1992)

Infection caused by Cryptosporidium species has proved to be one of the most taxing and frustrating conditions faced by clinicians caring for patients with AIDS. Unfortunately, this unique organism, which was identified as a human pathogen only shortly before the AIDS epidemic began to manifest itself, has received only minimal attention during the past decade. Dr. Carolyn Petersen, an assistant professor of medicine at the University of California, San Francisco, and a member of the Division of Infectious Diseases at San Francisco General Hospital, is a molecular parasitologist whose investigative career is focused on elucidating the biology of Cryptosporidium species. In this AIDS Commentary Dr. Petersen provides an update on recent developments in this field.
Novel Clostridium difficile Anti-Toxin (TcdA and TcdB) Humanized Monoclonal Antibodies Demonstrate In Vitro Neutralization across a Broad Spectrum of Clinical Strains and In Vivo Potency in a Hamster Spore Challenge Model (2016)

Clostridium difficile (C. difficile) infection (CDI) is the main cause of nosocomial antibiotic-associated colitis and increased incidence of community-associated diarrhea in industrialized countries. At present, the primary treatment of CDI is antibiotic administration, which is effective but often associated with recurrence, especially in the elderly. Pathogenic strains produce enterotoxin, toxin A (TcdA), and cytotoxin, toxin B (TcdB), which are necessary for C. difficile induced diarrhea and gut pathological changes. Administration of anti-toxin antibodies provides an alternative approach to treat CDI, and has shown promising results in preclinical and clinical studies. In the current study, several humanized anti-TcdA and anti-TcdB monoclonal antibodies were generated and their protective potency was characterized in a hamster infection model. The humanized anti-TcdA (CANmAbA4) and anti-TcdB (CANmAbB4 and CANmAbB1) antibodies showed broad spectrum in vitro neutralization of toxins from clinical strains and neutralization in a mouse toxin challenge model. Moreover, co-administration of humanized antibodies (CANmAbA4 and CANmAbB4 cocktail) provided a high level of protection in a dose dependent manner (85% versus 57% survival at day 22 for 50 mg/kg and 20 mg/kg doses, respectively) in a hamster gastrointestinal infection (GI) model. This study describes the protective effects conferred by novel neutralizing anti-toxin monoclonal antibodies against C. difficile toxins and their potential as therapeutic agents in treating CDI.
Developments in CMOS camera technology (1994)

This paper gives an overview of developments in CMOS camera technology and sensor related products at VLSI Vision Ltd.
Enzymatic formation of prostaglandin F2 alpha from prostaglandin H2 and D2. Purification and properties of prostaglandin F synthetase from bovine lung. (1985)

Prostaglandin F synthetase from bovine lung was purified 540-fold to apparent homogeneity, as assessed by polyacrylamide gel electrophoreses and ultracentrifugation. The purified enzyme proved to be a monomeric protein with a molecular weight of about 30,500. The enzyme catalyzed not only the reduction of the 11-keto group of prostaglandin D2 but also the reduction of 9,11-endoperoxide of prostaglandin H2 and various carbonyl compounds (e.g. phenanthrenequinone). Experiments using column chromatography, polyacrylamide gel electrophoreses, immunotitration using antibody against the purified enzyme, and heat treatment indicated that three enzyme activities resided in a single protein. Although phenanthrenequinone and prostaglandin D2 competitively inhibited the prostaglandin D2 and phenanthrenequinone reductase activities, respectively, these two substrates were all but ineffective on the prostaglandin H2 (at the Km value) reductase activity up to 14-fold of those Km values. These results suggest that a single enzyme protein purified from the bovine lung catalyzes the reduction of prostaglandin D2, prostaglandin H2, and various carbonyl compounds and that prostaglandin D2 and prostaglandin H2 are metabolized at two different active sites, yielding prostaglandin F2 alpha as the reaction product.
Phase I/II Trial of the Type I Soluble Recombinant Human Interleukin-1 Receptor in HIV-1-Infected Patients (1998)

Interleukin-1 (IL-1) produced in peripheral blood mononuclear cell (PBMC) cultures or added exogenously has been shown to upregulate HIV expression in vitro. Inhibition of IL-1 in HIV-infected individuals may inhibit HIV activation and slow disease progression. Recombinant human IL-1 receptor (rHu-IL-1R), the soluble extracellular portion of the human type I IL-1 receptor, inhibits HIV expression in acutely infected primary PBMCs and in the chronically infected promonocytic cell line, U1. We, therefore, conducted a phase I/II trial of the soluble rHu-IL-1R in HIV-1-infected individuals with CD4 T cell counts <300/microl to evaluate its safety and activity. Twelve evaluable patients were enrolled at three rHu-IL-1R dose levels:125 (n=3), 500 (n=3), and 1250 (n=6) microg/m2 per dose by subcutaneous (s.c.) injection three times a week for 8 weeks, followed by a 4 week observation period. rHu-IL-1R was safe and well tolerated. There were no deaths, no treatment-related grade 3/4 events, and no premature study discontinuations because of adverse events. The maximum tolerated dose was not reached. Seven patients reported improvements in one or more symptoms, including weight gain (3), improved energy level (4), decreased diarrhea (1), decreased night sweats (1), improvement in psoriatic arthritis (1), and improvement in a nonspecific chronic diffuse skin rash (1). Of 3 evaluable patients with Kaposi's sarcoma, 1 remained stable and 2 showed minimal progression. No consistent trends in absolute CD4 counts or percentages, quantitative HIV cultures, or serum p24 antigen, beta2-microglobulin, or triglyceride levels were observed. rHu-IL-1R is safe and well tolerated at the doses tested but induced no consistent changes in objective markers of HIV disease. Symptomatic improvements will require confirmation in randomized, placebo-controlled trials.
The MMSET protein is a histone methyltransferase with characteristics of a transcriptional corepressor (2007)

MMSET, identified by its fusion to the IgH locus in t(4;14)-associated multiple myeloma, possesses domains found within chromatin regulators, including the SET domain. MMSET protein is overexpressed and highly associated with chromatin in myeloma cell lines carrying t(4;14). MMSET possesses methyltransferase activity for core histone H3 lysine 4 and histone 4 lysine 20, whereas MMSET made in cells only modified H4. Segments of MMSET fused to the Gal4 DNA binding domain repressed transcription of a chromatin-embedded Gal4 reporter gene. MMSET-mediated repression was associated with increased H4K20 methylation gene and loss of histone acetylation. Consistent with this repressive activity, MMSET could form a complex with HDAC1 and HDAC2, mSin3a, and the histone demethylase LSD1, suggesting that it is a component of corepressor complexes. Furthermore, MMSET coexpression enhances HDAC1- and HDAC2-mediated repression in transcriptional reporter assays. Finally, shRNA-mediated knockdown of MMSET compromised viability of a myeloma cell line, suggesting a biologic role for the protein in malignant cell growth. Collectively, these data suggest that, by acting directly as a modifier of chromatin as well as through binding of other chromatin-modifying enzymes, MMSET influences gene expression and potentially acts as a pathogenic agent in multiple myeloma.
Isothermal nucleic acid amplification technologies for point-of-care diagnostics: a critical review (2012)

Nucleic Acid Testing (NAT) promises rapid, sensitive and specific diagnosis of infectious, inherited and genetic disease. The next generation of diagnostic devices will interrogate the genetic determinants of such conditions at the point-of-care, affording clinicians prompt reliable diagnosis from which to guide more effective treatment. The complex biochemical nature of clinical samples, the low abundance of nucleic acid targets in the majority of clinical samples and existing biosensor technology indicate that some form of nucleic acid amplification will be required to obtain clinically relevant sensitivities from the small samples used in point-of-care testing (POCT). This publication provides an overview and thorough review of existing technologies for nucleic acid amplification. The different methods are compared and their suitability for POCT adaptation are discussed. Current commercial products employing isothermal amplification strategies are also investigated. In conclusion we identify the factors impeding the integration of the methods discussed in fully automated, sample-to-answer POCT devices.
Dosimetric verification of a commercial inverse treatment planning system (1999)

A commercial three-dimensional (3D) inverse treatment planning system, Corvus (Nomos Corporation, Sewickley, PA), was recently made available. This paper reports our preliminary results and experience with commissioning this system for clinical implementation. This system uses a simulated annealing inverse planning algorithm to calculate intensity-modulated fields. The intensity-modulated fields are divided into beam profiles that can be delivered by means of a sequence of leaf settings by a multileaf collimator (MLC). The treatments are delivered using a computer-controlled MLC. To test the dose calculation algorithm used by the Corvus software, the dose distributions for single rectangularly shaped fields were compared with water phantom scan data. The dose distributions predicted to be delivered by multiple fields were measured using an ion chamber that could be positioned in a rotatable cylindrical water phantom. Integrated charge collected by the ion chamber was used to check the absolute dose of single- and multifield intensity modulated treatments at various spatial points. The measured and predicted doses were found to agree to within 4% at all measurement points. Another set of measurements used a cubic polystyrene phantom with radiographic film to record the radiation dose distribution. The films were calibrated and scanned to yield two-dimensional isodose distributions. Finally, a beam imaging system (BIS) was used to measure the intensity-modulated x-ray beam patterns in the beam's-eye view. The BIS-measured images were then compared with a theoretical calculation based on the MLC leaf sequence files to verify that the treatment would be executed accurately and without machine faults. Excellent correlation (correlation coefficients ) was found for all cases. Treatment plans generated using intensity-modulated beams appear to be suitable for treatment of irregularly shaped tumours adjacent to critical structures. The results indicated that the system has potential for clinical radiation treatment planning and delivery and may in the future reduce treatment complexity.
Primer-Free Aptamer Selection Using A Random DNA Library (2010)

Aptamers are highly structured oligonucleotides (DNA or RNA) that can bind to targets with affinities comparable to antibodies (1). They are identified through an in vitro selection process called Systematic Evolution of Ligands by EXponential enrichment (SELEX) to recognize a wide variety of targets, from small molecules to proteins and other macromolecules (2-4). Aptamers have properties that are well suited for in vivo diagnostic and/or therapeutic applications: Besides good specificity and affinity, they are easily synthesized, survive more rigorous processing conditions, they are poorly immunogenic, and their relatively small size can result in facile penetration of tissues. Aptamers that are identified through the standard SELEX process usually comprise approximately 80 nucleotides (nt), since they are typically selected from nucleic acid libraries with approximately 40 nt long randomized regions plus fixed primer sites of approximately 20 nt on each side. The fixed primer sequences thus can comprise nearly approximately 50% of the library sequences, and therefore may positively or negatively compromise identification of aptamers in the selection process (3), although bioinformatics approaches suggest that the fixed sequences do not contribute significantly to aptamer structure after selection (5). To address these potential problems, primer sequences have been blocked by complementary oligonucleotides or switched to different sequences midway during the rounds of SELEX (6), or they have been trimmed to 6-9 nt (7, 8). Wen and Gray (9) designed a primer-free genomic SELEX method, in which the primer sequences were completely removed from the library before selection and were then regenerated to allow amplification of the selected genomic fragments. However, to employ the technique, a unique genomic library has to be constructed, which possesses limited diversity, and regeneration after rounds of selection relies on a linear reamplification step. Alternatively, efforts to circumvent problems caused by fixed primer sequences using high efficiency partitioning are met with problems regarding PCR amplification (10). We have developed a primer-free (PF) selection method that significantly simplifies SELEX procedures and effectively eliminates primer-interference problems (11, 12). The protocols work in a straightforward manner. The central random region of the library is purified without extraneous flanking sequences and is bound to a suitable target (for example to a purified protein or complex mixtures such as cell lines). Then the bound sequences are obtained, reunited with flanking sequences, and re-amplified to generate selected sub-libraries. As an example, here we selected aptamers to S100B, a protein marker for melanoma. Binding assays showed Kd s in the 10(-7) - 10(-8) M range after a few rounds of selection, and we demonstrate that the aptamers function effectively in a sandwich binding format.
Results of a Phase 2 Efficacy and Safety Study with SB204, an Investigational Topical Nitric Oxide-releasing Drug for the Treatment of Acne Vulgaris. (2016)

When compared to vehicle, both SB204 1% and SB204 4% significantly decreased the percentage of noninflammatory lesions and SB204 4% also significantly decreased the percentage of inflammatory lesions in subjects with acne vulgaris treated for 12 weeks. Treatment with SB204 1% and SB204 4% was safe and well-tolerated. Registry: clinicaltrials.gov (NCT01844752).
Fasting inhibits colorectal cancer growth by reducing M2 polarization of tumor-associated macrophages (2017)

Dietary restriction has been recognized as a healthy and natural therapy for cancer. It is reported that different forms of dietary restriction can promote anti-tumor immunity. However, it is not clear how fasting affects tumor-associated macrophages (TAMs). This study aims to investigate the relationship between fasting and antitumor immunity in terms of tumor-associated macrophages. <i>In vivo,</i> the results showed that alternate day fasting for 2 weeks inhibitted the tumor growth of mice without causing a reduction of body weight. Meanwhile, M2 polarization of tumor-associated macrophages in tumor tissues of alternate day fasting group was also decreased. <i>In vitro</i>, fasting induced the autophagy of CT26 cells, decreased the generation of extracellular adenosine by supressing the expression of CD73 in CT26 cells. Decreasing adenosine inhibitted M2 polarization of RAW264.7 cells through inactivating JAK1/STAT3 signal pathway in fasting condition. Eventually, the proliferation of CT26 cancer cells declined on account of fasting-facilitated antitumor immunity. These results suggested that fasting suppressed M2 polarization of tumor-associated macrophages to inhibit tumor growth through decreasing the level of adenosine in the tumor microenvironment both <i>in vivo</i> and <i>in vitro</i>. This process was associated with increasing autophagy of tumor cells.
Synthesis of Functionalized Vinyl Boronates via Ruthenium-Catalyzed Olefin Cross-Metathesis and Subsequent Conversion to Vinyl Halides (2003)

Functionalized vinyl pinacol boronates suitable for Suzuki cross-coupling reactions are synthesized using ruthenium-catalyzed olefin cross-metathesis of 1-propenyl pinacol boronate and various alkenes, including functionalized and 1,1-disubstituted alkenes. The resultant boronate cross products are stereoselectively transformed into predominantly Z-vinyl bromides and E-vinyl iodides. The vinyl bromides may be synthesized in a two-step, one-pot synthesis from a variety of olefins, resulting in a Z-selective formal vinyl bromide cross-metathesis reaction.
Clinical Usefulness of theCrithida luciliaeTest for Antibodies to Native DNA (1979)

The Crithidia luciliae assay (CL-IF) for antibodies to native DNA was found to be significantly more sensitive and specific for systemic lupus erythematosus (SLE) than the Farr radioimmunoassay (RIA). High titers of antibodies to native DNA were seen exclusively in patients wtih SLE using the CL-IF test. The titers correlated with the activity of SLE and nephritis, in that the highest titers occurred in patients with active disease and severe nephritis, the lowest in patients with inactive lupus and normal renal function. Favorable responses to therapy were associated with decreases in CL-IF titers. The CL-IF assay can detect complement-fixing antibodies to native DNA. Their presence correlated with the disease activity and nephritis in SLE patients. The simple and inexpensive CL-IF test could either replace the RIA in clinical laboratories or be used in conjunction with the RIA as a confirmatory test for antibodies to native DNA.
Symptomatic suspected gluten exposure is common among patients with coeliac disease on a gluten‐free diet (2016)

Reactions to suspected gluten exposure are common among patients with coeliac disease on a gluten-free diet. Eating at restaurants and other peoples' homes remain a risk for unintentional gluten exposure. When following individuals with coeliac disease, clinicians should include questions regarding reactions to gluten as part of their assessment of gluten-free diet adherence.