gebhart/patrepeval huggingface dataset:
Adjuvant effects of CpG oligodeoxynucleotides on responses against T‐independent type 2 antigens (2001)

Oligodeoxynucleotides containing CpG motifs (CpG-ODN) are potent in vitro B-cell activators and they have been successfully used to increase in vivo antibody responses to T-dependent peptide and protein antigens. In contrast, the use of CpG-ODN to enhance in vivo antibody responses to various T-independent type 2 (TI-2) antigens has recently generated contradictory results. In this study, we compared the CpG-ODN stimulatory effect on antibody responses of adult and young BALB/c mice to trinitrophenylaminoethyl-carboxymethyl (TNP) -Ficoll and to polysaccharides (PS) from several distinct serotypes of Streptococcus pneumoniae (SPn). CpG-ODN co-administration significantly enhanced antigen-specific immunoglobulin M (IgM), IgG, IgG1 and IgG2a titres to TNP-Ficoll. The depletion of CD4+ cells by monoclonal antibodies (GK1.5) identified their essential role in CpG-ODN-mediated enhancement of antibody responses. In contrast to TNP-Ficoll, CpG-ODN failed to enhance IgM and IgG responses to any of the 18 SPnPS serotypes tested. Providing T-cell epitopes by the conjugation of SPnPS to the carrier protein tetanus toxoid again allowed CpG-ODN to mediate enhancement of IgG, IgG2a and IgG3 responses to most SPnPS serotypes. Thus, antigen-presenting cell/T-cell interaction appears to largely mediate the in vivo influence of CpG-ODN on antibody responses to TI-2 antigens. In early life, additional factors limit CpG-ODN modulation of antibody responses to TI-2 antigens.
Type I and type IV pili of Xylella fastidiosa affect twitching motility, biofilm formation and cell–cell aggregation (2007)

Xylella fastidiosa, an important phytopathogenic bacterium, causes serious plant diseases including Pierce's disease of grapevine. It is reported here that type I and type IV pili of X. fastidiosa play different roles in twitching motility, biofilm formation and cell-cell aggregation. Type I pili are particularly important for biofilm formation and aggregation, whereas type IV pili are essential for motility, and also function in biofilm formation. Thirty twitching-defective mutants were generated with an EZ : : TN transposome system, and several type-IV-pilus-associated genes were identified, including fimT, pilX, pilY1, pilO and pilR. Mutations in fimT, pilX, pilO or pilR resulted in a twitch-minus phenotype, whereas the pilY1 mutant was twitching reduced. A mutation in fimA resulted in a biofilm-defective and twitching-enhanced phenotype. A fimA/pilO double mutant was twitch minus, and produced almost no visible biofilm. Transmission electron microscopy revealed that the pili, when present, were localized to one pole of the cell. Both type I and type IV pili were present in the wild-type isolate and the pilY1 mutant, whereas only type I pili were present in the twitch-minus mutants. The fimA mutant produced no type I pili. The fimA/pilO double mutant produced neither type I nor type IV pili.
T-Cell Lymphoma and the Virus-Associated Hemophagocytic Syndrome (1992)

A 20-month-old girl had a disorder that by both clinical and histologic criteria resembled the virus-associated hemophagocytic syndrome in the setting of Epstein-Barr virus infection. Subsequent investigation revealed histologic evidence of disseminated T-cell lymphoma. DNA hybridization studies displayed a monoclonal T-cell receptor beta chain rearrangement, in the absence of clonal immunoglobulin gene rearrangement, and a single band in the analysis for the fused termini of the Epstein-Barr virus genome. These results suggest the presence of a monoclonal population of T lymphocytes infected with Epstein-Barr virus. The diagnosis of lymphoma was confirmed at autopsy. The authors discuss the association of Epstein-Barr virus infection with the development of T-cell lymphoma and propose that the previous reports of virus-associated hemophagocytic syndrome include cases of unrecognized T-cell lymphoma.
Thermal illuminators for far-infrared and submillimeter astronomical instruments (2005)

Astronomical instruments operating in the infrared-millimeter region often require internal sources for detector monitoring, instrument calibration, and health checking. We describe the design, modeling, and experimental evaluation of thermal emitters with a fast speed of response and low-power dissipation, suitable for the far-infrared-submillimeter region. The development of an internal illuminator for the Herschel Spectral and Photometric Imaging Receiver (SPIRE) satellite instrument is used as an example of the optimization of the design to meet particular requirements. A prototype illuminator design for SPIRE has been developed that, for a power dissipation of 1.5 mW, provides an equivalent blackbody temperature of 45 K with a 90% settling time of 220 ms.
UDP-N-acetylglucosamine:glycoprotein N-acetylglucosamine-1-phosphotransferase. Proposed enzyme for the phosphorylation of the high mannose oligosaccharide units of lysosomal enzymes. (1981)

The recognition marker for the targeting of lysosomal enzymes contains mannose 6-phosphate. The recent discovery of phosphate in diester linkage between N-acetylglucosamine (GlcNAc) and mannose in newly synthesized beta-glucuronidase led to the proposal that the phosphate might be acquired via N-acetylglucosamine-phosphate transfer from UDP-GlcNAc (Tabas, I., and Kornfeld, S. (1980) J. Biol. Chem. 255, 6633-6639). We describe the synthesis of [beta-32P]UDP-[3H]GlcNAc and the use of this compound to demonstrate a UDP-GlcNAc:glycoprotein N-acetylglucosamine-1-phosphotransferase. The basis of the enzyme assay is the incorporation of 32P and 3H into glycopeptides with a high affinity for Concanavalin A-Sepharose. This membrane-associated transferase is neither inhibited by tunicamycin nor stimulated by dolichol-phosphate, indicating that the reaction does not proceed via a dolichylpyrophosphoryl-N-acetylglucosamine intermediate. Characterization of the enzyme reaction products (derived from either endogenous or exogenous acceptors) demonstrated that alpha-linked N-acetylglucosamine 1-phosphate is transferred en bloc to the 6-hydroxyl of mannose in high mannose oligosaccharides of glycoproteins. We propose that the function of this enzyme is to donate N-acetylglucosamine 1-phosphate to mannose residues of newly synthesized lysosomal enzymes.
Improved Treatment of Ligands and Coupling Effects in Empirical Calculation and Rationalization of p<i>K</i><sub>a</sub> Values (2011)

The new empirical rules for protein pKa predictions implemented in the PROPKA3.0 software package (Olsson et al. J. Chem. Theory Comput.2010, 7, 525-537) have been extended to the prediction of pKa shifts of active site residues and ionizable ligand groups in protein-ligand complexes. We present new algorithms that allow pKa shifts due to inductive (i.e., covalently coupled) intraligand interactions, as well as noncovalently coupled interligand interactions in multiligand complexes, to be included in the prediction. The number of different ligand chemical groups that are automatically recognized has been increased to 18, and the general implementation has been changed so that new functional groups can be added easily by the user, aided by a new and more general protonation scheme. Except for a few cases, the new algorithms in PROPKA3.1 are found to yield results similar to or better than those obtained with PROPKA2.0 (Bas et al. Proteins: Struct., Funct., Bioinf.2008, 73, 765-783). Finally, we present a novel algorithm that identifies noncovalently coupled ionizable groups, where pKa prediction may be especially difficult. This is a general improvement to PROPKA and is applied to proteins with and without ligands.
Diagnosis and management of angioedema with abdominal involvement: A gastroenterology perspective (2010)

Abdominal involvement in angioedema is often a challenge to diagnose. Acute onset abdominal pain is its most common presenting symptom, and misdiagnosis may lead to unnecessary surgical intervention. Familiarity with the types and presentations of angioedema can be invaluable to clinicians as they consider the differential diagnoses of a patient presenting with abdominal pain. Detailed personal and family histories, careful physical examination of the patient, combined with knowledge of angioedema types, can help clinicians perform their diagnostic evaluation. An accurate diagnosis is essential in order to provide appropriate treatment to patients with angioedema. Depending upon the diagnosis, treatment may be the avoidance of provoking factors (such as allergens or medications), inhibiting histamine-provoked reactions, or treating C1 esterase inhibitor deficiency.
Beta Cell Replacement Therapy (2011)

Type 1 Diabetes mellitus (T1D) is an autoimmune disorder caused by destruction of pancreatic beta cells which produce insulin. Current estimates have shown that T1D affects about 0.4 to 0.8% of the population worldwide accounting for 5-10% of all diabetes cases (Stock and Bluestone, 2004). It is seen as an increasing health hazard. For T1D, exogenous insulin administration is the most widely used treatment. However, this treatment has several limitations including development of secondary health complications over time. There are several approaches already in practice to replace the damaged beta cells in T1D. They include whole organ pancreas or isolated islet cell transplantation. Several novel approaches are currently in development such as expansion of adult beta cells and stem/progenitor cells which can be transformed into beta cells. This review summarizes recent progress made in beta cell replacement therapy for T1D. Diabetes mellitus has been known for thousands of years. Diabetes comes from an ancient Greek word coined by Arataeus of Cappadocia, and mellitus from the Latin word honey associated with sweet urine. (Medvei, 1993). The pathogenesis of T1D has been attributed to an autoimmune response. Currently the mechanism that triggers this disease is still unknown, but it seems to be a combination of environmental and genetic factors. T-cells in the host’s body become sensitized to protein that naturally occurs in the beta cells of the pancreas and the immune system begins to mount a specific attack leading to destruction of the islets of Langerhans. Several candidate proteins have been identified including GAD65, insulin, and ZnT8 (Harlan et al., 2009, Shapiro et al., 2003). Reducing the autoimmune effect in beta cell replacement is very important, but before moving onto the strategies for beta cell replacement therapy it is important to describe the standard therapy for T1D and how it falls short of providing for all the needs of diabetic patients. Exogenous insulin therapy continues to be the leading therapy for T1D today, but there are several complications associated with it. However, even intensive monitoring of blood glucose and injection of insulin is not enough to halt the secondary complications of diabetes (Harlan et al., 2009). Diabetes mellitus can decrease patients’ lifespan, especially in severe cases. Lowered blood sugar levels, which can result if too much insulin is administered, can also lead to a hypoglycemic episode (Cooke and Plotnick, 2008). These episodes are typified by ketoacidosis, where in an effort to find energy, the body burns fatty acids leading to the production of acidic ketones that can be detected by an alcoholic smell on the breath. Hypoglycemic episodes can lead to coma and even death, and is considered
Adenosine‐ and α,β‐methylene ATP‐induced differential inhibition of cholinergic and non‐cholinergic neurogenic responses in rat urinary bladder (1991)

1. The effects of adenosine and alpha,beta-methylene adenosine triphosphate (alpha,beta-Me ATP) on single pulse-induced neurogenic responses and contractions caused by exogenously applied acetylcholine (ACh) and adenosine triphosphate (ATP) were examined in rat urinary bladder. 2. Application of single pulse stimulation (1 ms; 80 V) evoked a biphasic contractile response (abolished by tetrodotoxin, 0.5 x 10(-7) M) consisting of a fast (time to peak: 1.02 +/- 0.07 s) and a slow component (time to peak: 4.92 +/- 1.6 s). The selective inhibition of the slow component by atropine (3 x 10(-6) M) suggests the participation of both cholinergic and non-cholinergic neurotransmitters. 3. alpha,beta-Me ATP (5 x 10(-6) M) abolished ATP (10(-4) M)-induced contractions without altering those to ACh (10(-6) M). Further, the selective inhibition of the fast component of the neurogenic response by alpha,beta-Me ATP is suggestive of the contribution of endogenous ATP to the non-cholinergic component. 4. Adenosine (10(-8) M to 10(-4) M) caused dose-related differential inhibition of the fast (IC50, 1.04 +/- 0.25 x 10(-5) M) and slow (IC50, 2.18 +/- 0.69 x 10(-6) M) components, thereby further supporting two modes of neurotransmission in bladder. 5. Theophylline (10(-4) M) antagonized the inhibitory effects of adenosine on the non-cholinergic component, thereby implicating the participation of P1-purinoceptors in neuromodulation. In contrast, theophylline at this concentration enhanced the adenosine-induced inhibition of the cholinergic component. component. 6. The magnitude of ATP (10-4M)- and ACh (10-8M)-induced contractions were almost identical to those of the fast and slow components of the neurogenic response, respectively. Comparable reduction of ATP (30.2 + 3.4%) and ACh (100%) contractions to those of fast (44.2 + 6.5%) and slow (88.2 + 5.5%) components suggests the involvement of a postjunctional mechanism in adenosine-induced differential inhibition of neurogenic responses. 7. The lack of effect of erythro-6-amino-9-(2-hydroxy-3-nonyl) adenosine hydrochloride (10-6M) and dipyridamole (10-6M) suggests that endogenous adenosine plays little part in modulation of single pulseinduced neurogenic response. 8. The results of the present study suggest that fast and slow components of neurogenic response are mediated through ATP and ACh, respectively, possibly co-released from the same neurone in the rat bladder.
Quartz-Seq: a highly reproducible and sensitive single-cell RNA sequencing method, reveals non-genetic gene-expression heterogeneity (2013)

Development of a highly reproducible and sensitive single-cell RNA sequencing (RNA-seq) method would facilitate the understanding of the biological roles and underlying mechanisms of non-genetic cellular heterogeneity. In this study, we report a novel single-cell RNA-seq method called Quartz-Seq that has a simpler protocol and higher reproducibility and sensitivity than existing methods. We show that single-cell Quartz-Seq can quantitatively detect various kinds of non-genetic cellular heterogeneity, and can detect different cell types and different cell-cycle phases of a single cell type. Moreover, this method can comprehensively reveal gene-expression heterogeneity between single cells of the same cell type in the same cell-cycle phase.
Characterization of MarR, the repressor of the multiple antibiotic resistance (mar) operon in Escherichia coli (1995)

The marRAB operon is one of two operons in the mar locus of Escherichia coli that are divergently transcribed from a central regulatory region, marO. The marRAB operon, transcribed from marOII, controls intrinsic resistance or susceptibility to multiple antibiotics and is inducible by structurally unrelated compounds such as tetracycline and chloramphenicol (S. P. Cohen, H. Hachler, and S. B. Levy, J. Bacteriol. 175:1484-1492, 1993). To clarify the role of the operon in response to environmental signals, its transcription was studied under different conditions, using a marOII-lacZ transcriptional fusion introduced into the chromosome of wild-type or mar-deleted cells. In wild-type cells, uncoupling agents (such as carbonyl cyanide m-chlorophenylhydrazone) and different redox-cycling compounds (e.g., menadione and plumbagin) induced expression from the marOII-lacZ fusion two- to sevenfold. In the mar-deleted strain, LacZ expression from the fusion was 10-fold higher than in wild-type cells. This activity was temperature sensitive (3-fold lower at 42 than at 30 degrees C) and decreased 20-fold with the introduction of the gene for MarR. Structurally different compounds which induce the mar operon in wild-type cells reversed the MarR repression of marOII-lacZ expression. To determine the size of MarR, it was fused to MalE as a MarR fusion protein of 144 amino acids [MarR(144)] or of 125 amino acids (deleted of 19 amino acids at the N terminus) [MarR(125)]. Only the MarR(144) fusion showed repressor ability. The purified MarR(144) fusion, but not the MarR(125) fusion, bound specifically to marO in vitro, as revealed by gel retardation, with an apparent dissociation constant of 5 x 10(-9) M. MarR, therefore, controls expression of the marRAB operon presumably by binding to marO. MarR repression in cells can be reversed by different compounds, facilitating the response of bacteria to multiple environmental stress conditions.
Hypermethylation of Tachykinin-1 Is a Potential Biomarker in Human Esophageal Cancer (2007)

TAC1 promoter hypermethylation is a common event in both major histologic types of human esophageal carcinoma, occurs early, correlates with other progression risk factors in esophageal adenocarcinogenesis, and is a tissue biomarker of a poor prognosis in ESCC. Circulating methylated TAC1 promoter DNA also offers potential as a biomarker for the diagnosis of EAC.
Highly accurate two-gene classifier for differentiating gastrointestinal stromal tumors and leiomyosarcomas (2007)

Gastrointestinal stromal tumor (GIST) has emerged as a clinically distinct type of sarcoma with frequent overexpression and mutation of the c-Kit oncogene and a favorable response to imatinib mesylate [also known as STI571 (Gleevec)] therapy. However, a significant diagnostic challenge remains in the differentiation of GIST from leiomyosarcomas (LMSs). To improve on the diagnostic evaluation and to complement the immunohistochemical evaluation of these tumors, we performed a whole-genome gene expression study on 68 well characterized tumor samples. Using bioinformatic approaches, we devised a two-gene relative expression classifier that distinguishes between GIST and LMS with an accuracy of 99.3% on the microarray samples and an estimated accuracy of 97.8% on future cases. We validated this classifier by using RT-PCR on 20 samples in the microarray study and on an additional 19 independent samples, with 100% accuracy. Thus, our two-gene relative expression classifier is a highly accurate diagnostic method to distinguish between GIST and LMS and has the potential to be rapidly implemented in a clinical setting. The success of this classifier is likely due to two general traits, namely that the classifier is independent of data normalization and that it uses as simple an approach as possible to achieve this independence to avoid overfitting. We expect that the use of simple marker pairs that exhibit these traits will be of significant clinical use in a variety of contexts.
Multiple Taq I RFLPs at tbe human manganese superoxide dismutase (S0D2) locus on chromosome 6 (1987)

The probe is an 827 bp insert from phMnSOD4 (vector-pBR327) which encodes the 222 amino acid human MnSOD precursor, 91 and 21 bp of 5' and 3' untranslated region, respectively, and poly A tract.
Site-Specific PEGylation of Hemoglobin at Cys-93(β):  Correlation between the Colligative Properties of the PEGylated Protein and the Length of the Conjugated PEG Chain (2003)

Increasing the molecular size of acellular hemoglobin (Hb) has been proposed as an approach to reduce its undesirable vasoactive properties. The finding that bovine Hb surface decorated with about 10 copies of PEG5K per tetramer is vasoactive provides support for this concept. The PEGylated bovine Hb has a strikingly larger molecular radius than HbA (1). The colligative properties of the PEGylated bovine Hb are distinct from those of HbA and even polymerized Hb, suggesting a role for the colligative properties of PEGylated Hb in neutralizing the vasoactivity of acellular Hb. To correlate the colligative properties of surface-decorated Hb with the mass of the PEG attached and also its vasoactivity, we have developed a new maleimide-based protocol for the site-specific conjugation of PEG to Hb, taking advantage of the unusually high reactivity of Cys-93(beta) of oxy HbA and the high reactivity of the maleimide to protein thiols. PEG chains of 5, 10, and 20 kDa have been functionalized at one of their hydroxyl groups with a maleidophenyl moiety through a carbamate linkage and used to conjugate the PEG chains at the beta-93 Cys of HbA to generate PEGylated Hbs carrying two copies of PEG (of varying chain length) per tetramer. Homogeneous preparations of (SP-PEG5K)(2)-HbA, (SP-PEG10K)(2)-HbA, and (SP-PEG20K)(2)-HbA have been isolated by ion exchange chromatography. The oxygen affinity of Hb is increased slightly on PEGylation, but the length of the PEG-chain had very little additional influence on the O(2) affinity. Both the hydrodynamic volume and the molecular radius of the Hb increased on surface decoration with PEG and exhibited a linear correlation with the mass of the PEG chain attached. On the other hand, both the viscosity and the colloidal osmotic pressure (COP) of the PEGylated Hbs exhibited an exponential increase with the increase in PEG chain length. In contrast to the molecular volume, viscosity, and COP, the vasoactivity of the PEGylated Hbs was not a direct correlate of the PEG chain length. There appeared to be a threshold for the PEG chain length beyond which the protection against vasoactivity is decreased. These results suggest that the modulation of the vasoactivity of Hb by PEG could be a function of the surface shielding afforded by the PEG, the latter being a function of the disposition of the PEG chain on the protein surface, which in turn is a function of the length of the PEG chain. Thus, the biochemically homogeneous PEGylated Hbs described in the present study, surface-decorated with PEG chains of appropriate size, could serve as potential candidates for Hb-based oxygen carriers.
New Compound in the System La <sub>2</sub> O <sub>3</sub> ‐Al <sub>2</sub> O <sub>3</sub> (1985)

A new compound, 5La 2 O 3 ‐2Al 2 O 3 , is formed from an amorphous material prepared by the simultaneous hydrolysis of lanthanum and aluminurn alkoxides. It has an orthorhombic unit cell with a=0.9704 nm, b=0.5967 nm, and c=1.5473 nm. The structure contains tetrahedral AlO 4 groups and octahedral AlO 6 groups.
A Skin Chamber Technique as a Human Model for Studies of Aseptic Inflammatory Reactions (2007)

Using a combination of induced skin blistering and collection chambers permits dynamic studies of the aseptic inflammatory reaction in humans. Blisters filled with interstitial fluid can be generated by applying negative pressure to normal skin for up to 2 h. The blisters are subsequently denuded to form superficial "skin windows" that are well defined with regard to area and depth. The denuded areas are covered with a separate collection chamber filled with a suitable medium and left for 18-24 h. During this period, neutrophils and inflammatory agents accumulate in the chamber medium, and sequential events in the inflammatory process can be studied by repeated sampling. Inactive medium or isolated peripheral blood cells from the same individual can be used as controls for both cellular functions and the pro-/anti-inflammatory mediators that are generated or released.