gebhart/patrepeval huggingface dataset:
Effect of hydroxychloroquine treatment on pro-inflammatory cytokines and disease activity in SLE patients: data from LUMINA (LXXV), a multiethnic US cohort (2012)

Hydroxychloroquine therapy resulted in significant clinical improvement in SLE patients, which strongly correlated with reductions in IFN-α levels. This indicates an important role for the inhibition of endogenous TLR activation in the action of hydroxychloroquine in SLE and provides additional evidence for the importance of type I interferons in the pathogenesis of SLE. This study underscores the use of hydroxychloroquine in the treatment of SLE.
Onto-Tools, the toolkit of the modern biologist: Onto-Express, Onto-Compare, Onto-Design and Onto-Translate (2003)

Onto-Tools is a set of four seamlessly integrated databases: Onto-Express, Onto-Compare, Onto-Design and Onto-Translate. Onto-Express is able to automatically translate lists of genes found to be differentially regulated in a given condition into functional profiles characterizing the impact of the condition studied upon various biological processes and pathways. OE constructs functional profiles (using Gene Ontology terms) for the following categories: biochemical function, biological process, cellular role, cellular component, molecular function and chromosome location. Statistical significance values are calculated for each category. Once the initial exploratory analysis identified a number of relevant biological processes, specific mechanisms of interactions can be hypothesized for the conditions studied. Currently, many commercial arrays are available for the investigation of specific mechanisms. Each such array is characterized by a biological bias determined by the extent to which the genes present on the array represent specific pathways. Onto-Compare is a tool that allows efficient comparisons of any sets of commercial or custom arrays. Using Onto-Compare, a researcher can determine quickly which array, or set of arrays, covers best the hypotheses studied. In many situations, no commercial arrays are available for specific biological mechanisms. Onto-Design is a tool that allows the user to select genes that represent given functional categories. Onto-Translate allows the user to translate easily lists of accession numbers, UniGene clusters and Affymetrix probes into one another. All tools above are seamlessly integrated. The Onto-Tools are available online at http://vortex.cs.wayne.edu/Projects.html.
Amelioration of Collagen-Induced Arthritis by Blockade of Inducible Costimulator-B7 Homologous Protein Costimulation (2002)

B7 homologous protein (B7h)/B7-related protein 1 (B7RP-1) is a new member of the B7 family of costimulatory molecules that specifically interacts with inducible costimulator (ICOS) expressed on activated T cells. Collagen type II (CII)-induced arthritis (CIA) is an experimental model of arthritis that has been used to dissect the pathogenesis of human rheumatoid arthritis. In this study, we have investigated the effect of neutralizing anti-B7h mAb on the development and disease progression of CIA. Administration of anti-B7h mAb significantly ameliorated the disease as assessed by clinical arthritis score and histology in the joints, and a beneficial effect was also obtained by a delayed treatment after the onset of disease. Expression of ICOS and B7h was observed in the inflamed synovial tissue as well as in the draining lymph nodes (LNs) and expansion of ICOS(+) T cells in the LN was reduced by the anti-B7h mAb treatment. Expression of mRNA for proinflammatory cytokines such as TNF-alpha, IL-1beta, and IL-6 in the joints was inhibited by the treatment. Proliferative responses and production of IFN-gamma and IL-10 upon restimulation with CII in vitro were significantly inhibited in LN cells from the anti-B7h mAb-treated mice. Serum anti-CII IgG1, IgG2a, and IgG2b levels were also reduced. Our present results showed a beneficial effect of the B7h blockade on CIA through anti-inflammatory actions and inhibition of both Th1- and Th2-mediated immune responses, suggesting that the ICOS-B7h interaction plays an important role in the pathogenesis of CIA and thus the blockade of this pathway may be beneficial for the treatment of human rheumatoid arthritis.
Self-Renewing Human Bone Marrow Mesenspheres Promote Hematopoietic Stem Cell Expansion (2013)

Strategies for expanding hematopoietic stem cells (HSCs) include coculture with cells that recapitulate their natural microenvironment, such as bone marrow stromal stem/progenitor cells (BMSCs). Plastic-adherent BMSCs may be insufficient to preserve primitive HSCs. Here, we describe a method of isolating and culturing human BMSCs as nonadherent mesenchymal spheres. Human mesenspheres were derived from CD45- CD31- CD71- CD146+ CD105+ nestin+ cells but could also be simply grown from fetal and adult BM CD45--enriched cells. Human mesenspheres robustly differentiated into mesenchymal lineages. In culture conditions where they displayed a relatively undifferentiated phenotype, with decreased adherence to plastic and increased self-renewal, they promoted enhanced expansion of cord blood CD34+ cells through secreted soluble factors. Expanded HSCs were serially transplantable in immunodeficient mice and significantly increased long-term human hematopoietic engraftment. These results pave the way for culture techniques that preserve the self-renewal of human BMSCs and their ability to support functional HSCs.
An Inhibitor of Na+/H+Exchanger (NHE), Ethyl-Isopropyl Amiloride (EIPA), Diminishes Proliferation of MKN28 Human Gastric Cancer Cells by Decreasing the Cytosolic Cl-Concentration via DIDS-Sensitive Pathways (2012)

EIPA suppressed proliferation of MKN28 cells through up-regulation of p21 expression via reduction of [Cl(-)](c) as a result from DIDS-sensitive Cl(-)/HCO(3)(-) exchanger-mediated compensation for keeping pH(c) normal under an NHE-inhibited condition. This is the first study revealing that an NHE inhibitor suppressed the proliferation of cancer cells by reducing [Cl(-)](c) but not pH(c).
Ex Vivo Expansion and Prophylactic Infusion of CMV-pp65 Peptide-Specific Cytotoxic T-Lymphocytes following Allogeneic Hematopoietic Stem Cell Transplantation (2007)

Cytomegalovirus reactivation and infection post-allogeneic hematopoietic stem cell transplant continue to cause morbidity and mortality. Current pharmacologic therapies are limited by side effects. Adoptive transfer of ex vivo generated cytomegalovirus-specific T cells has the potential to restore immunity, prevent cytomegalovirus, and circumvent the need for pharmacologic therapies. We have generated donor-derived cytomegalovirus-specific cytotoxic T cells using dendritic cells pulsed with the HLA-A2 restricted nonapeptide NLVPMVATV (NLV) derived from the cytomegalovirus-pp65 protein. These cytotoxic T cells have been given prophylactically to 9 recipients aged 4 to 65 years on or after day 28 post-allogeneic hematopoietic stem cell transplant. Only 2 of 9 recipients received T cell depletion in vivo or in vitro. There were no immediate adverse reactions to the infusions. During 97-798 days of follow-up, 2 recipients developed cytomegalovirus reactivation; neither developed cytomegalovirus disease or required pharmacotherapy. Three recipients developed acute graft versus host disease after infusion. Two recipients died, 1 from thrombotic thrombocytopenia purpura secondary to cyclosporine, 1 from complications of graft versus host disease. A transient increase in numbers of cytomegalovirus-specific T cells demonstrated by NLV-tetramer binding was seen in 6 recipients. Prophylactic adoptive transfer of NLV-specific T cells is safe and may be effective in preventing cytomegalovirus reactivation.
Manufacturing Immunity to Disease in a Test Tube: The Magic Bullet Realized (2006)

Although it took over one hundred years, Ehrlich's concept of the magic bullet is now a reality. Today, therapeutic antibodies are, arguably, the most important class of new drugs for the treatment of illnesses ranging from Alzheimer's disease to cancer. The emergence of therapeutic antibodies had to wait for advances in immunochemistry that allowed construction of antibodies in vitro. The centerpiece of the new technology is the combinatorial antibody library, which essentially allows one to synthesize an artificial immune system with a diversity that exceeds that of the natural repertoire. The construction of such libraries was perceived to be difficult because, if the natural immune system was to be used as the starting material, construction of the libraries would entail protocols that are the opposite of usual cloning. In gene cloning one starts with complexity and reduces it to a singularity. In the generation of diversity by construction of combinatorial antibody libraries, one starts with a collection of clones, randomly expands their complexity, and then returns them to recoverable singularities. The methods developed to accomplish this seemingly formidable task now allow construction of antibodies in a test tube to any antigen. These synthetic antibodies may be qualitatively and quantitatively superior to those of nature.
Site-directed, recombination-mediated mutagenesis of a complex gene locus (1990)

We have generated a site-specific 17 bp insertion within a 38 kb chick globin gene cluster by employing the recombination abilities of Saccharomyces cerevisiae. This gene cluster contains four beta-type globin genes which share a high degree of sequence homology. In this procedure, a small fragment of beta A-globin DNA containing a 17 bp insertion is subcloned into a URA3-based yeast integrating vector (YIp). This mutated globin subclone is introduced into cells that carry the 38 kb globin cluster clone on a single-copy, circular vector derived from a yeast artificial chromosome (YAC). Insertion of the 17 bp oligomer is achieved by targeted integration of the Ylp subclone. The recombinant contains the normal beta A-globin gene, the mutant gene and Ylp vector sequences between the two copies. Excision of the vector sequences and one copy of the duplicated globin sequences by homologous recombination is required for cell survival when exposed to the selective agent 5-fluoroorotic acid, which is toxic to ura+ yeast cells. Depending upon the point of the cross-over, a ura- yeast cell bearing either a wild-type globin gene or a 17 bp insertion mutation will result. By restriction mapping and in vitro transcription analysis, the beta A-globin gene containing the 17 bp insert has no nonspecific mutations generated during the recombination and selection procedures. Specific mutations of regulatory regions, including protein-DNA binding sites, can be accurately targeted within extensive DNA clones by this method.
Human Monocyte–Derived Dendritic Cells Induce Naive T Cell Differentiation into T Helper Cell Type 2 (Th2) or Th1/Th2 Effectors (2000)

The subset of dendritic cells (DCs) and the nature of the signal inducing DC maturation determine the capacity of DCs to generate polarized immune responses. In this study, we show that the ability of human monocyte-derived DCs (myeloid DC(1)) to promote T helper type 1 (Th1) or Th2 differentiation was also found to be critically dependent on stimulator/responder ratio. At a low ratio (1:300), mature DCs that have been differentiated after inflammatory (Staphylococcus aureus Cowan 1 or lipopolysaccharide) or T cell-dependent (CD40 ligand) stimulation induced naive T cells to become Th2 (interleukin [IL]-4(+), IL-5(+), interferon gamma) effectors. Th2 differentiation was dependent on B7-CD28 costimulation and enhanced by OX40-OX40 ligand interactions. However, high DC/T cell ratio (1:4) favored a mixed Th1/Th2 cell development. Thus, the fact that the same DC lineage stimulates polarized Th1 or Th2 responses may be relevant since it allows the antigen-presenting cells to initiate an appropriate response for the signal received at the peripheral sites. Controlling the number and the rate of DC migration to the T cell areas in lymphoid tissues may be important for the therapeutic use of DCs.
Rate of occurrence of false-positive results from total coliform most-probable-number analysis of shellfish and estuaries (1980)

The incidence of confirmed test, false-positive coliform most-probable-number results was compared with environmental parameters and was found to be inversely related to water temperature. It is concluded that the completed coliform test must be done when water temperatures drop below 15 degrees C.
A small yeast RNA inhibits HCV IRES mediated translation and inhibits replication of poliovirusin vivo (2003)

IRES specific IRNA can inhibit HCV IRES mediated translation and poliovirus replication.
MCPC VSATs for rural network (1995)

The multiple channel per carrier very small aperture terminal (MCPC VSAT) is ideally suited for trunk connections between a large switching centre and small exchanges in rural/remote inaccessible areas on a point to point basis in star connectivity. Utilising low bit encoding techniques for voice, the MCPC VSAT network achieves economy in satellite resources while retaining circuit quality. The developments in VSATs have made it possible to provide basic telephone services to rural/remote areas. In India, about 80% of our population lives in rural, remote sparsely populated areas where presently there is no basic telephone service available. The geographic remoteness, hilly hostile terrain requires the installations of costly transmission lines to bring basic telephone services to these underdeveloped areas. The low population density and poor economic conditions makes it difficult for the service provider to justify the economic investment to bring basic telephone services to these areas. In the MCPC VSAT network as the name implies, several information channels are multiplexed and sent on a single satellite carrier frequency. In a rural environment, where a few information channels are required for communication, the MCPC VSATs network system would provide the best economy. This satellite based telecommunication network provides all the basic services such as telephone, fax and data transmission.
Clinical Pharmacology of Propofol: An Intravenous Anesthetic Agent (1989)

Propofol is a 2,6-diisopropylphenol with sedative-hypnotic properties. Because of its slight solubility in water, the drug is formulated as an emulsion for clinical use. It is highly lipophilic and distributes extensively in the body. The blood concentration-time profile of propofol after an iv bolus injection follows a three-compartment model with half-lives of 2-4 min, 30-45 min, and 3-63 h, respectively. Propofol is extensively metabolized by the liver prior to its elimination by the kidney. Following an iv dose of 2-2.5 mg/kg, loss of consciousness occurs in less than one minute and lasts for approximately five minutes. Hypnosis can be maintained by propofol blood concentrations of 1.5-6 micrograms/mL in the presence of N2O/O2 (60:40 ratio) or other anesthetic agents. During induction, propofol decreases the systolic and diastolic blood pressure by approximately 20-30 percent with minimal change in heart rate; apnea is also common. The cardiovascular and respiratory effects of propofol, however, should not cause major concern in otherwise healthy patients. By virtue of its pharmacokinetic profile, the drug lends itself to continuous infusion for maintenance of anesthesia. When used as the main anesthetic agent, it produces satisfactory anesthesia with rapid recovery and without major adverse effects in healthy individuals. In continuous infusion propofol can be used as an alternative to inhalation anesthetics.
Hint, Fhit, and GalT:  Function, Structure, Evolution, and Mechanism of Three Branches of the Histidine Triad Superfamily of Nucleotide Hydrolases and Transferases (2002)

HIT (histidine triad) proteins, named for a motif related to the sequence HphiHphiHphiphi (phi, a hydrophobic amino acid), are a superfamily of nucleotide hydrolases and transferases, which act on the alpha-phosphate of ribonucleotides, and contain a approximately 30 kDa domain that is typically either a homodimer of approximately 15 kDa polypeptides with two active-sites or an internally, imperfectly repeated polypeptide that retains a single HIT active site. On the basis of sequence, substrate specificity, structure, evolution, and mechanism, HIT proteins can be classified into the Hint branch, which consists of adenosine 5'-monophosphoramide hydrolases, the Fhit branch, which consists of diadenosine polyphosphate hydrolases, and the GalT branch, which consists of specific nucleoside monophosphate transferases, including galactose-1-phosphate uridylyltransferase, diadenosine tetraphosphate phosphorylase, and adenylyl sulfate:phosphate adenylytransferase. At least one human representative of each branch is lost in human diseases. Aprataxin, a Hint branch hydrolase, is mutated in ataxia-oculomotor apraxia syndrome. Fhit is lost early in the development of many epithelially derived tumors. GalT is deficient in galactosemia. Additionally, ASW is an avian Hint family member that has evolved to have unusual gene expression properties and the complete loss of its nucleotide binding site. The potential roles of ASW and Hint in avian sexual development are discussed elsewhere. Here we review what is known about biological activities of HIT proteins, the structural and biochemical bases for their functions, and propose a new enzyme mechanism for Hint and Fhit that may account for the differences between HIT hydrolases and transferases.
Blood—Brain Barrier Genomics and Cloning of a Novel Organic Anion Transporter (2007)

A novel organic anion transporter selectively expressed at the blood-brain barrier (BBB), originally designated BBB-specific anion transporter type 1 (BSAT1), and now classified as Slco1c1, has been cloned from a BBB genomics program as a partial cDNA; this study describes the cloning and expression of the full-length cDNA from a rat brain capillary cDNA library. Northern analysis revealed the selective expression of the transporter at the BBB, and the transporter was expressed after permanent transfection of human 293 cells with cDNA encoding either the full length or open reading frame mRNA. The full-length transporter cDNA was 2.6 kb, and the mRNA was highly expressed at the rat brain microvasculature, but not in kidney, liver, heart, or lung, or in glial cells or brain glial tumors. Blood-brain barrier-specific anion transporter type 1 expression in 293 cells was poor after the transfection of the full-length cDNA, whereas transporter expression in 293 cells was high after transfection of the open reading frame. The transporter showed asymmetric kinetic properties in comparison of the influx and efflux of model substrates, thyroxine (T4), triiodothyronine (T3), and estradiol-glucuronide (E2G). Thyroxine and T3 inhibited the influx of E2G, but E2G did not inhibit thyroxine influx, and T3 only weakly inhibited the influx of T4. Extracellular E2G stimulated the transefflux of intracellular T4. Blood-brain barrier-specific anion transporter type 1 is a novel organic anion transporter that is a sodium-independent exchanger that may participate in the active efflux of iodothyronines and steroid conjugates at the BBB.
Changes in subcellular distribution of protocadherin gamma proteins accompany maturation of spinal neurons (2003)

Protocadherins gamma (Pcdhgamma) are a family of transmembrane proteins in which variable extracellular domains are associated with an invariant cytoplasmic domain, potentially allowing these proteins to trigger common cellular responses through diverse extracellular signals. We studied the expression of the family by in situ hybridisation and immunohistochemistry for the conserved portion of the mRNA or protein. During mouse development, Pcdhgamma expression is highest in neural tissues, but is also present in some nonneural tissues. In the adult, Pcdhgamma expression is maintained at high levels in brain, in particular in hippocampus and in the Purkinje cells of the cerebellum, whereas it is downregulated in spinal cord. Using antibodies against the conserved cytoplasmic domain, we show that in cultured embryonic spinal cord neurons, Pcdhgamma protein is present initially in both axonal and dendritic growth cones. At later stages of differentiation in vitro, Pcdhgamma distribution becomes polarised to the somatodendritic compartment. We propose that members of the Pcdhgamma family may play roles in neuronal growth and maturation.
Comparison of the macroscopic and single channel conductance properties of colicin E1 and its COOH-terminal tryptic peptide. (1983)

A COOH-terminal tryptic fragment (Mr approximately equal to 20,000) of colicin E1 has been proposed to contain the membrane channel-forming domain of the colicin molecule. A comparison is made of the conductance properties of colicin E1 and its COOH-terminal fragment in planar bilayer membranes. The macroscopic and single channel properties of colicin E1 and its COOH-terminal tryptic fragment are very similar, if not indistinguishable, implying that the NH2-terminal, two-thirds of the colicin E1 molecule, does not significantly influence its channel properties. The channel-forming activity of both polypeptides is dependent upon the presence of a membrane potential, negative on the trans side of the membrane. The average single channel conductance of colicin E1 and the COOH-terminal fragment is 20.9 +/- 3.9 and 19.1 +/- 2.9 picosiemens, respectively. The rate at which both proteins form conducting channels increases as the pH is lowered from 7 to 5. Both molecules require negatively charged lipids for activity to be expressed, exhibit the same ion selectivity, and rectify the current to the same extent. Both polypeptides associate irreversibly with the membrane in the absence of voltage, but subsequent formation of conducting channels requires a negative membrane potential.
Optimizing a Lupus Autoantibody for Targeted Cancer Therapy (2015)

The specificity of binding by antibodies to target antigens is a compelling advantage to antibody-based cancer therapy, but most antibodies cannot penetrate cells to affect intracellular processes. Select lupus autoantibodies penetrate into cell nuclei, and the potential for application of these antibodies in cancer therapy is an emerging concept. Here, we show that a divalent lupus anti-DNA autoantibody fragment with enhancing mutations that increase its ability to penetrate cell nuclei and bind DNA causes accumulation of DNA double-strand breaks in and is highly and selectively toxic to cancer cells and tumors with defective homology-directed repair of DNA double-strand breaks. These findings provide proof of principle for the use of optimized lupus autoantibodies in targeted cancer therapy.