gebhart/patrepeval huggingface dataset:
Assembly of large genomes using second-generation sequencing (2010)

Second-generation sequencing technology can now be used to sequence an entire human genome in a matter of days and at low cost. Sequence read lengths, initially very short, have rapidly increased since the technology first appeared, and we now are seeing a growing number of efforts to sequence large genomes de novo from these short reads. In this Perspective, we describe the issues associated with short-read assembly, the different types of data produced by second-gen sequencers, and the latest assembly algorithms designed for these data. We also review the genomes that have been assembled recently from short reads and make recommendations for sequencing strategies that will yield a high-quality assembly.
Increased Frequency of Surface IgA-Positive Plasma Cells in the Intestinal Lamina Propria and Decreased IgA Excretion in Hyper IgA (HIGA) Mice, a Murine Model of IgA Nephropathy with Hyperserum IgA (2000)

Because abnormalities of mucosal immunity have been suggested in human IgA nephropathy, we examined the involvement of mucosal immunity in IgA deposition to the kidney in hyper IgA (HIGA) mice, which was established as a mouse model for human IgA nephropathy with hyperserum IgA. The number of surface IgA+B220- lymphocytes in the intestinal lamina propria (LP) of HIGA mice increased 2.7-fold at 30 wk of age as compared with those at 10 wk of age, whereas normal mice did not show such increase. The surface IgA+B220- LP lymphocytes spontaneously secreted IgA in culture. Morphological studies showed that the surface IgA+B220- lymphocytes of murine intestinal LP are identical with plasma cells (PCs). About 20% of IgA+B220- PC in LP expressed both Mac-1 and CD19, suggesting that they may derive from peritoneal B-1 cells. Cell cycle study on intestinal IgA-PCs using bromodeoxyuridine revealed no difference between HIGA mice and normal mice, suggesting that the high frequency of IgA-producing PCs in HIGA mice is not due to enhanced proliferation or prolonged survival of IgA-producing PCs in LP. In addition, IgA secretion into the gut lumen of HIGA mice decreased drastically (to one forth) with aging. These data suggest that the increased number of intestinal IgA-producing PCs and the down-regulation of IgA excretion into the intestinal lumen might synergistically contribute to the hyperserum IgA in HIGA mice and resultant IgA deposition to the kidney.
Structural Basis of Preexisting Immunity to the 2009 H1N1 Pandemic Influenza Virus (2010)

The 2009 H1N1 swine flu is the first influenza pandemic in decades. The crystal structure of the hemagglutinin from the A/California/04/2009 H1N1 virus shows that its antigenic structure, particularly within the Sa antigenic site, is extremely similar to those of human H1N1 viruses circulating early in the 20th century. The cocrystal structure of the 1918 hemagglutinin with 2D1, an antibody from a survivor of the 1918 Spanish flu that neutralizes both 1918 and 2009 H1N1 viruses, reveals an epitope that is conserved in both pandemic viruses. Thus, antigenic similarity between the 2009 and 1918-like viruses provides an explanation for the age-related immunity to the current influenza pandemic.
Alterations in pulsatile insulin secretion in the Zucker diabetic fatty rat (1994)

Insulin secretion from the isolated perfused pancreas is characterized by pulses occurring every 5-15 min. The present experiments were performed to explore the role of glucose in regulating these pulses. The pancreata from 12 Wistar (W), 12 Zucker diabetic fatty (ZDF), and 6 nondiabetic lean Zucker control (ZC) male rats were isolated and perfused at 37 degrees C with an oxygenated Krebs Ringer solution containing bovine serum albumin and glucose. In W and ZDF, insulin secretion was pulsatile during constant glucose, as assessed by pulse analysis (ULTRA). The pulse period in W was significantly shorter than in ZDF (7.1 +/- 0.6 vs. 14.7 +/- 1.0 min; P < 0.001), whereas the median relative pulse amplitude was not different. When glucose was administered as a series of 10-min sine waves, spectral analysis showed that the normalized spectral power at 10 min was greater in W and ZC compared with ZDF (34.2 +/- 5.9 and 32.9 +/- 2.9 vs. 3.2 +/- 0.9; P < 0.0001), demonstrating entrainment of the insulin pulses to the exogenous glucose oscillations in W and ZC but not in ZDF. Furthermore, in ZDF, the insulin secretory rates were not higher when 28 mM rather than 7 mM glucose were used. In additional studies, islets of Langerhans from one W, three ZDF, and three ZC rats were isolated and perifused using an oscillatory glucose concentration. Single and groups of islets were studied. Islets from diabetic rats demonstrated the same lack of entrainment by glucose seen in the perfused pancreas, suggesting that the defect is at the cellular level.(ABSTRACT TRUNCATED AT 250 WORDS)
Guanylyl cyclase C agonists regulate progression through the cell cycle of human colon carcinoma cells (2001)

The effects of Escherichia coli heat-stable enterotoxin (ST) and uroguanylin were examined on the proliferation of T84 and Caco2 human colon carcinoma cells that express guanylyl cyclase C (GC-C) and SW480 human colon carcinoma cells that do not express this receptor. ST or uroguanylin inhibited proliferation of T84 and Caco2 cells, but not SW480 cells, in a concentration-dependent fashion, assessed by quantifying cell number, cell protein, and [(3)H]thymidine incorporation into DNA. These agonists did not inhibit proliferation by induction of apoptosis, assessed by TUNEL (terminal deoxynucleotidyl transferase-mediated dNTP-biotin nick end labeling of DNA fragments) assay and DNA laddering, or necrosis, assessed by trypan blue exclusion and lactate dehydrogenase release. Rather, ST prolonged the cell cycle, assessed by flow cytometry and [(3)H]thymidine incorporation into DNA. The cytostatic effects of GC-C agonists were associated with accumulation of intracellular cGMP, mimicked by the cell-permeant analog 8-Br-cGMP, and reproduced and potentiated by the cGMP-specific phosphodiesterase inhibitor zaprinast but not the inactive ST analog TJU 1-103. Thus, GC-C agonists regulate the proliferation of intestinal cells through cGMP-dependent mechanisms by delaying progression of the cell cycle. These data suggest that endogenous agonists of GC-C, such as uroguanylin, may play a role in regulating the balance between epithelial proliferation and differentiation in normal intestinal physiology. Therefore, GC-C ligands may be novel therapeutic agents for the treatment of patients with colorectal cancer.
Vaccination With Irradiated, Autologous Melanoma Cells Engineered to Secrete Granulocyte-Macrophage Colony-Stimulating Factor by Adenoviral-Mediated Gene Transfer Augments Antitumor Immunity in Patients With Metastatic Melanoma (2003)

Vaccination with irradiated, autologous melanoma cells engineered to secrete GM-CSF by adenoviral-mediated gene transfer augments antitumor immunity in patients with metastatic melanoma.
Pharmacological Strategies to Overcome HER2 Cross-Talk and Trastuzumab Resistance (2012)

Approximately 20-30% of breast cancers show increased expression of the HER2 receptor tyrosine kinase. Trastuzumab (Herceptin) is a clinically approved anti-HER2 monoclonal antibody. Many patients with HER2-overexpressing metastatic breast cancer respond to trastuzumab; however, a subset display primary drug resistance. In addition, many patients who initially respond to trastuzumab ultimately develop disease progression. Multiple molecular mechanisms contributing to trastuzumab resistance have been proposed in the literature. These mechanisms include cross-signaling from related HER/erbB receptors and compensatory signaling from receptors outside of the HER/erbB family, including receptors for insulin-like growth factor-I, vascular endothelial growth factor, and transforming growth factor beta. The major downstream signaling pathway activated by HER2 cross-talk is PI3K/mTOR, and a potential integrator of receptor cross-talk is Src-focal adhesion kinase (FAK) signaling. PI3K, Src, and FAK have independently been implicated in trastuzumab resistance. In this review, we will discuss pharmacological inhibition of HER2 cross-talk as a strategy to treat trastuzumab-refractory HER2-overexpresssing breast cancer.
Novel and efficient bridged bis(N‐heterocyclic carbene)palladium(II) catalysts for selective carbonylative Suzuki–Miyaura coupling reactions to biaryl ketones and biaryl diketones (2020)

Bridged N , N ′‐substituted bisbenzimidazolium bromide salts (L1, L2, and L3) were synthesized and fully characterized. Reactions of palladium acetate with L1, L2, and L3 afforded corresponding new bridged bis( N ‐heterocyclic carbene)palladium(II) complexes (C1, C2, and C3) in high yields. The X‐ray structure of complex C1 showed that the Pd(II) ion is bonded to the two carbon atoms of the bis( N ‐heterocyclic carbene) and two bromido ligands are in the cis position, resulting in a distorted square planar geometry. The three Pd(NHC) 2 Br 2 complexes C1, C2, and C3 were evaluated in carbonylative Suzuki–Miyaura coupling reactions of aryl boronic acids with aryl halides and displayed high catalytic activity with low catalyst loading. The coupling reactions of aryl bromides were selective towards the carbonylation product at higher carbon monoxide pressure.
Simultaneous production of IL-2, IL-4, and IFN-gamma by activated human CD4+ and CD8+ T cell clones. (1988)

In the present study, we have investigated the ability of human T cells to secrete IL-2, IL-4, and IFN-gamma. IL-4 and IFN-gamma were quantified with enzymatic immunoassays and IL-2 with a biologic assay by using the murine IL-2-dependent cell line CTLL-2. PBL, stimulated with Con A or with a combination of the phorbol ester 13-O-tetradecanoylphorbol-12-acetate and the Ca2+ ionophore A23187 secreted IL-2, IL-4, and IFN-gamma. The kinetics of the secretion of the three lymphokines was investigated with two CD4+ clones; one (GEO-2) that produced IL-2, IL-4, and IFN-gamma and another (HY640), that produced only IL-2 and IFN-gamma. Significant IL-2, IL-4, and IFN-gamma production was observed after only 8 h of activation. Maximal levels of IL-2 and IL-4 were found 20 h after the onset of the stimulation which subsequently decreased. In contrast, IFN-gamma levels continued to increase in a period up to 40 h and then leveled off. In spite of these differences in secretion, the kinetics of accumulation of mRNA did not differ. The IL-2, IL-4, and IFN-gamma mRNA were detectable 2 h after stimulation and continued to accumulate for a period up to 20 h. In a series of 22 CD4+ clones, 21 were able to secrete all three lymphokines upon stimulation. Almost all CD8+ clones were able to produce IL-2 and IFN-gamma, but only six of the 23 CD8+ T cell clones secreted IL-4. In addition, five CD4+ (allo)antigen-specific T cell clones were tested for IL-2, IL-4, and IFN-gamma secretion upon specific stimulation. Two alloantigen-specific and two tetanus toxoid-specific T cell clones secreted IL-2, IL-4, and IFN-gamma simultaneously, whereas one alloantigen-specific T cell clone secreted IL-2 and IFN-gamma, but not IL-4. A supernatant of the CD4+ T cell clone GEO-2, that contained high levels of IFN-gamma and IL-4, was unable to induce the low affinity receptor for IgE, CD23, on a Burkitt lymphoma cell line. However, after separation of IL-4 from IFN-gamma by using HPLC, the IL-4-containing fraction-induced CD23, which could be blocked by the fraction that contained IFN-gamma and by a polyclonal rabbit anti-IL-4 antiserum. Finally, the partly purified IL-4, that was devoid of IL-2, promoted the growth of the clone GEO-2.
Programmable Periodicity of Quantum Dot Arrays with DNA Origami Nanotubes (2010)

To fabricate quantum dot arrays with programmable periodicity, functionalized DNA origami nanotubes were developed. Selected DNA staple strands were biotin-labeled to form periodic binding sites for streptavidin-conjugated quantum dots. Successful formation of arrays with periods of 43 and 71 nm demonstrates precise, programmable, large-scale nanoparticle patterning; however, limitations in array periodicity were also observed. Statistical analysis of AFM images revealed evidence for steric hindrance or site bridging that limited the minimum array periodicity.
Potent and conditional redirected T cell killing of tumor cells using Half DVD-Ig (2017)

Novel biologics that redirect cytotoxic T lymphocytes (CTLs) to kill tumor cells bearing a tumor associated antigen hold great promise in the clinic. However, the ability to safely and potently target CD3 on CTL toward tumor associated antigens (TAA) expressed on tumor cells remains a challenge of both technology and biology. Herein we describe the use of a Half DVD-Ig format that can redirect CTL to kill tumor cells. Notably, Half DVD-Ig molecules that are monovalent for each specificity demonstrated reduced non-specific CTL activation and conditional CTL activation upon binding to TAA compared to intact tetravalent DVD-Ig molecules that are bivalent for each specificity, while maintaining good drug like properties and appropriate PK properties.
Production of Site-Specific Antibody–Drug Conjugates Using Optimized Non-Natural Amino Acids in a Cell-Free Expression System (2014)

Antibody-drug conjugates (ADCs) are a targeted chemotherapeutic currently at the cutting edge of oncology medicine. These hybrid molecules consist of a tumor antigen-specific antibody coupled to a chemotherapeutic small molecule. Through targeted delivery of potent cytotoxins, ADCs exhibit improved therapeutic index and enhanced efficacy relative to traditional chemotherapies and monoclonal antibody therapies. The currently FDA-approved ADCs, Kadcyla (Immunogen/Roche) and Adcetris (Seattle Genetics), are produced by conjugation to surface-exposed lysines, or partial disulfide reduction and conjugation to free cysteines, respectively. These stochastic modes of conjugation lead to heterogeneous drug products with varied numbers of drugs conjugated across several possible sites. As a consequence, the field has limited understanding of the relationships between the site and extent of drug loading and ADC attributes such as efficacy, safety, pharmacokinetics, and immunogenicity. A robust platform for rapid production of ADCs with defined and uniform sites of drug conjugation would enable such studies. We have established a cell-free protein expression system for production of antibody drug conjugates through site-specific incorporation of the optimized non-natural amino acid, para-azidomethyl-l-phenylalanine (pAMF). By using our cell-free protein synthesis platform to directly screen a library of aaRS variants, we have discovered a novel variant of the Methanococcus jannaschii tyrosyl tRNA synthetase (TyrRS), with a high activity and specificity toward pAMF. We demonstrate that site-specific incorporation of pAMF facilitates near complete conjugation of a DBCO-PEG-monomethyl auristatin (DBCO-PEG-MMAF) drug to the tumor-specific, Her2-binding IgG Trastuzumab using strain-promoted azide-alkyne cycloaddition (SPAAC) copper-free click chemistry. The resultant ADCs proved highly potent in in vitro cell cytotoxicity assays.
Membrane phospholipid asymmetry as a determinant of erythrocyte recognition by macrophages. (1986)

To assess the role of transbilayer phospholipid distribution in the recognition and phagocytosis of erythrocytes by macrophages, human erythrocytes with either a symmetric or asymmetric distribution of membrane phospholipids were prepared by hypotonic hemolysis and then incubated with cultures of human monocyte-derived macrophages. Erythrocytes with an abnormal, symmetric distribution were phagocytosed 4 times more readily than their counterparts with an asymmetric distribution or than normal, asymmetric intact erythrocytes. This enhanced phagocytosis correlated with two biophysical properties of the membrane: the spacing of phospholipids, as assessed by binding of the dye merocyanine 540, and the relative hydrophobicity, as measured by aqueous two-phase polymer partitioning. These results suggest a mechanism by which loss of membrane asymmetry is translated into recognition by macrophages and provide guidelines in loading erythrocytes that may be useful in manipulating the mode of delivery when erythrocytes are used as drug carriers in vivo.
Understanding the Key Drivers in User Loyalty Toward Mobile Data Services (2008)

Given the rapid growth and large investments in mobile data services (MDS), it has become important to examine how to enhance satisfaction with MDS (M-satisfaction) and how to build loyalty toward MDS (M-loyalty).This paper develops an integrated model to deeply understand the antecedents of M-loyalty through constructs prescribed by two established research streams on information system (IS) success, namely user satisfaction and information technology (IT) motivation.The research model was tested by using survey data collected from 747 users who have experience with MDS.Analysis results show that the proposed model provides a significant explanation of the variance of M-loyalty, indicating that the unified perspective it provides helps enhance our knowledge of how to build Mloyalty.This study should help MDS researchers and practitioners better understand user behavior in MDS.
Entrapment of an Organometallic Complex within a Metal: A Concept for Heterogeneous Catalysis (2008)

A novel family of composite materials, organically doped metals, has been recently introduced. Here, we demonstrate their use as a new platform for heterogeneous catalysis, namely the doping of a metal with a catalytic organometallic complex. Specifically, a rhodium(I) catalyst, (RhCl(COD)(Ph2P(C6H4SO3Na))), ([Rh]), was physically entrapped within silver, thus creating a new type of catalytic material: [Rh]@Ag. Several aspects were demonstrated with the development of this heterogeneous catalyst: a metal can be used as a support for heterogenizing a homogeneous catalyst; the homogeneous catalyst is stabilized by the entrapment within the metal; the products of the composite catalyst are different compared to those obtained from the homogeneous one; and the adsorption of [Rh] on the surface of Ag and its entrapment are very different processes only the latter provided appreciable catalytic activity. Thus, while homogeneous [Rh] was entirely destroyed after converting styrene to ethylbenzne at 50%, [Rh]@Ag remained active after effecting the same reaction to a yield of 85% (compared to only 7% for [Rh] adsorbed on Ag), and while homogeneous [Rh] hydrogenated diphenylacetylene to bibenzyl (and was completely deactivated after one cycle) with no trace of cis-stilbene, [Rh]@Ag afforded that compound as the main product and could be reused.
Immunological and clinical profile of adult patients with selective immunoglobulin subclass deficiency: response to intravenous immunoglobulin therapy (2009)

Selective immunoglobulin (Ig)G3 subclass deficiency in adults, especially its immunological profile, has not been described previously in detail. Therefore, a retrospective chart review was conducted to characterize the immune profile and clinical manifestations in adult patients with selective IgG3 deficiency. We reviewed the charts of 17 adult patients attending our subspeciality immunology clinic with a diagnosis of selective IgG3 deficiency. The following immunological test results were recorded: lymphocyte subsets, proliferative response to mitogens (phytohaemagglutinin, concanavalin A, pokeweed mitogen) and soluble antigens (mumps, Candida albicans, tetanus toxoid), specific antibody response to tetanus toxoid and pneumococcal antigens, neutrophil oxidative burst and natural killer cell cytotoxicity. In addition, we recorded information about the types of infections and other associated diseases, and response to intravenous immunoglobulin therapy (IVIG). In the majority of patients, lymphocyte subsets were normal. Proliferative responses to mitogens and antigens were decreased in 33% and 40% of patients, respectively. Specific antibody responses to tetanus were normal; however, responses to various pneumococcal serotypes were impaired in a subset of patients. Patients suffered from recurrent upper respiratory tract infections, which usually decreased in frequency and severity following treatment with IVIG. The majority of these patients also had concurrent atopic diseases in the form of allergic rhinitis or asthma. Selective IgG3 subclass deficiency should be considered in adults with recurrent upper respiratory tract infections with or without allergic rhinitis or asthma, who may have normal levels of total IgG. IVIG appears to be an effective therapy.
Transcatheter arterial chemoembolization therapy for hepatocellular carcinoma using polylactic acid microspheres containing aclarubicin hydrochloride. (1989)

Transcatheter arterial chemoembolization therapy using polylactic acid microspheres containing aclarubicin hydrochloride (ACR) was performed in 62 patients with primary hepatocellular carcinoma. These microspheres were about 200 microns in diameter and contained 10% (w/w) aclarubicin. A single dose of polylactic acid microspheres containing ACR (50-100 mg of ACR) was administered 1 to 8 times with a mean of 2.2 doses (a total of 160 treatments) in 62 patients. Antitumor effects were observed from the decrease in serum alpha-fetoprotein levels (82.1% of the patients) and in two dimensional size of tumor on computed tomography (93.6%). The cumulative survival rate was 54.3% at 1 year, 24.6% at 2 years, and 19.2% at 3 years, respectively, among 59 patients with unresectable tumors. In 3 resected liver specimens, there was a significant accumulation of ACR in the tumor, and severe necroses of the tumors were observed histologically. Systemic toxicity was mild and all patients tolerated this treatment. These results suggest that transcatheter arterial chemoembolization with the use of polylactic acid microspheres containing ACR is a useful tumor-targeting chemotherapy and is effective in the treatment of hepatocellular carcinoma.
Defective internalization of insulin and its receptor in cells expressing mutated insulin receptors lacking kinase activity. (1987)

The internalization and degradation of insulin was assessed in Chinese hamster ovary cell lines expressing either the wild-type receptor or mutated receptors lacking kinase activity. The mutated receptors included receptors which differed from the wild-type receptor by a single amino acid (substitution of an arginine for lysine at position 1030, a site critical for ATP binding) as well as receptors which had a deletion of 112 amino acids at the carboxyl terminus. Cells expressing mutated receptors lacking kinase activity were found to internalize and degrade insulin at about half the rate of cells expressing wild-type receptors with kinase activity. Moreover, insulin was found incapable of inducing the internalization of the mutated receptors, whereas it could stimulate the internalization of the wild-type receptor. Finally, the constitutive rate of receptor internalization was found to be the same for the mutant and wild-type receptors. These results implicate the intrinsic tyrosine-specific kinase activity of the insulin receptor in the ligand-induced, but not the constitutive, internalization of this receptor.