gebhart/patrepeval huggingface dataset:
Roles of Tetrodotoxin (TTX)-Sensitive Na+Current, TTX-Resistant Na+Current, and Ca2+Current in the Action Potentials of Nociceptive Sensory Neurons (2002)

Nociceptive sensory neurons are unusual in expressing voltage-gated inward currents carried by sodium channels resistant to block by tetrodotoxin (TTX) as well as currents carried by conventional TTX-sensitive sodium channels and voltage-dependent calcium channels. To examine how currents carried by each of these helps to shape the action potential in small-diameter dorsal root ganglion cell bodies, we voltage clamped cells by using the action potential recorded from each cell as the command voltage. Using intracellular solutions of physiological ionic composition, we isolated individual components of current flowing during the action potential with the use of channel blockers (TTX for TTX-sensitive sodium currents and a mixture of calcium channel blockers for calcium currents) and ionic substitution (TTX-resistant current measured by the replacement of extracellular sodium by N-methyl-D-glucamine in the presence of TTX, with correction for altered driving force). TTX-resistant sodium channels activated quickly enough to carry the largest inward charge during the upstroke of the nociceptor action potential (approximately 58%), with TTX-sensitive sodium channels also contributing significantly ( approximately 40%), especially near threshold, and high voltage-activated calcium currents much less (approximately 2%). Action potentials had a prominent shoulder during the falling phase, characteristic of nociceptive neurons. TTX-resistant sodium channels did not inactivate completely during the action potential and carried the majority (58%) of inward current flowing during the shoulder, with high voltage-activated calcium current also contributing significantly (39%). Unlike calcium current, TTX-resistant sodium current is not accompanied by opposing calcium-activated potassium current and may provide an effective mechanism by which the duration of action potentials (and consequently calcium entry) can be regulated.
Bacterial Plasminogen Receptors Utilize Host Plasminogen System for Effective Invasion and Dissemination (2012)

In order for invasive pathogens to migrate beyond the site of infection, host physiological barriers such as the extracellular matrix, the basement membrane, and encapsulating fibrin network must be degraded. To circumvent these impediments, proteolytic enzymes facilitate the dissemination of the microorganism. Recruitment of host proteases to the bacterial surface represents a particularly effective mechanism for enhancing invasiveness. Plasmin is a broad spectrum serine protease that degrades fibrin, extracellular matrices, and connective tissue. A large number of pathogens express plasminogen receptors which immobilize plasmin(ogen) on the bacterial surface. Surface-bound plasminogen is then activated by plasminogen activators to plasmin through limited proteolysis thus triggering the development of a proteolytic surface on the bacteria and eventually assisting the spread of bacteria. The host hemostatic system plays an important role in systemic infection. The interplay between hemostatic processes such as coagulation and fibrinolysis and the inflammatory response constitutes essential components of host defense and bacterial invasion. The goal of this paper is to highlight mechanisms whereby pathogenic bacteria, by engaging surface receptors, utilize and exploit the host plasminogen and fibrinolytic system for the successful dissemination within the host.
Human bone marrow stromal cells inhibit allogeneic T-cell responses by indoleamine 2,3-dioxygenase–mediated tryptophan degradation (2004)

Marrow stromal cells (MSCs) inhibit allogeneic T-cell responses, yet the molecular mechanism mediating this immunosuppressive effect of MSCs remains controversial. Recently, expression of indoleamine 2,3-dioxygenase (IDO), which is induced by interferon-gamma (IFN-gamma) and catalyzes the conversion from tryptophan to kynurenine, has been identified as a T-cell inhibitory effector pathway in professional antigen-presenting cells. Here we show that human MSCs express IDO protein and exhibit functional IDO activity upon stimulation with IFN-gamma. MSCs inhibit allogeneic T-cell responses in mixed lymphocyte reactions (MLRs). Concomitantly, IDO activity resulting in tryptophan depletion and kynurenine production is detected in MSC/MLR coculture supernatants. Addition of tryptophan significantly restores allogeneic T-cell proliferation, thus identifying IDO-mediated tryptophan catabolism as a novel T-cell inhibitory effector mechanism in human MSCs. As IDO-mediated T-cell inhibition depends on MSC activation, modulation of IDO activity might alter the immunosuppressive properties of MSCs in different therapeutic applications.
Targeted Deletion of the Epididymal Receptor HE6 Results in Fluid Dysregulation and Male Infertility (2004)

Human epididymal protein 6 (HE6; also known as GPR64) is an orphan member of the LNB-7TM (B(2)) subfamily of G-protein-coupled receptors. Family members are characterized by the dual presence of a secretin-like (type II) seven-transmembrane (7TM) domain and a long cell adhesion-like extracellular domain. HE6 is specifically expressed within the efferent ductules and the initial segment of the epididymis, ductal systems involved in spermatozoon maturation. Here, we report that targeted deletion of the 7TM domain of the murine HE6 gene results in male infertility. Mutant mice reveal a dysregulation of fluid reabsorbtion within the efferent ductules, leading to a backup of fluid accumulation in the testis and a subsequent stasis of spermatozoa within the efferent ducts. The fertility phenotype of HE6 knockout mice identifies this receptor as a potential nonsteroidal, nontesticular target for future male contraceptives and identifies an in vivo function for a member of this unusual gene family.
Reassembly of active 30S ribosomal subunits with an unmethylated in vitro transcribed 16S rRNA (1987)

A plasmid has been constructed, which contains the 16S ribosomal RNA gene of Escherichia coli immediately downstream from a phage T7 promoter. In vitro transcription of this gene by RNA polymerase of the T7 phage yielded an unmethylated 16S rRNA that could be used for the assembly of functional 30S subunits. These subunits when assayed in a poly(U)-directed translation assay, were as active as 30S subunits reconstructed with native 16S rRNA. This system opens the possibility of investigating the role of the methylations of the rRNA and the functional consequences of site-directed mutagenesis in a rRNA gene. An application of this system was provided by generating a 16S rRNA transcript shortened by about 30 nucleotides at the 3' end. This truncated rRNA could be reassembled into 30S subunits, about 70% as active as 30S subunits reconstructed with the full-length 16S rRNA transcript.
CCL2 (MCP-1) MEDIATES CHRONIC PELVIC PAIN THROUGH MAST CELLS IN EXPERIMENTAL AUTOIMMUNE CYSTITIS (2012)

Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic inflammatory bladder condition with unknown pathophysiology. Chronic pelvic pain is one of the most important and disturbing symptoms of IC/PBS, beside urinary frequency, urgency, and nocturia. Increased amounts of mast cells (MCs) and CCL2 have been found in bladder tissue and urine, respectively. Whether or not there is a causal relationship between CCL2, MCs, and pelvic pain in IC/PBS is unknown. Methods: Female BALB/c mice were immunized with a peptide consisting of residues 65-84 of the bladder urothelium-specific protein uroplakin 3A to induce experimental autoimmune cystitis (EAC), a model for human IC/PBS. Referred visceral pelvic pain was measured using von Frey monofilaments at different times after immunization. Lidocaine was instilled into the bladder, colon and uterus to locate the source of the pelvic pain. CCL2 expression in tissues was measured by qRT-PCR and ELISA, and MCs in the bladder were quantified by toluidine blue staining. An MC stabilizer (cromolyn sodium), histamine H1 receptor blocker (cetirizine), and histamine H2 receptor blocker (ranitidine) were administered orally to show the relation of MCs with the pain. CCL2-/- and CCR2-/- mice, and CCR2 (CCL2 receptor) antagonist treatment were used to delineate the causative effect of CCL2 on MC accumulation and chronic pelvic pain.Results: All mice immunized with the uroplakin 3A peptide developed pelvic pain within 5 days and up to 40 days after immunization. Lidocaine alleviated the pain only when it was installed into the bladder of EAC mice, confirming the bladder origin of the pain. The amounts of CCL2 mRNA and protein, and the numbers of MCs were markedly increased in bladder tissue up to 40 days after immunization with peptide compared with controls. Administrations of cromolyn sodium and ranitidine significantly decreased pelvic pain in the model. Moreover, immunization did not establish chronic pelvic pain or accumulation of MCs in MCP-1-/- or CCR2-/- mice, compar
The antipsoriatic dimethyl-fumarate suppresses interferon-gamma -induced ICAM-1 and HLA-DR expression on hyperproliferative keratinocytes. Quantification by a culture plate-directed APAAP-ELISA technique. (1999)

The derivatives of fumaric acid show antipsoriatic effects but details of the mechanism of action are largely unknown. The study focused on the effect of fumaric acid, dimethyl-fumarate, Zn-, Ca- and Mg-monoethyl-fumarate on the interferon-gamma (IFN-gamma)-induced expression of ICAM-1 and HLA-DR molecules on keratinocytes. Human hyperproliferative keratinocytes of the HaCaT cell line were exposed to IFN-gamma (10 U/ml) alone or in combination with fumaric acid and its derivatives for 48 hrs. The effect of fumarates was investigated semiquantitatively using the alkaline phosphatase-anti-alkaline phosphatase (APAAP) method. Subsequently, the effect of dimethyl-fumarate, the main component of "fumaric acid therapy", was evaluated quantitatively by means of an APAAP-ELISA technique. The semiquantitative evaluation revealed that in the micromolar dose range investigated only dimethyl-fumarate demonstrated substantial growth inhibition and down-regulation of the cell surface markers. In the quantitative evaluation, dimethyl-fumarate significantly (p</=0.05) suppressed the expression of ICAM-1 (84%) and HLA-DR (67%) on HaCaT keratinocytes at a subtoxic concentration of 4.0 microM as compared to untreated controls (100%). In contrast, concentrations of 4.0, 12 and 35 microM dimethyl-fumarate had no influence on the ICAM-1 and HLA-DR expression on IFN-gamma-exposed normal human epidermal keratinocytes in primary cultures. Thus, there is experimental evidence that dimethyl-fumarate may exert its antipsoriatic effect not only as an antiproliferative agent but also by down-regulation of ICAM-1 and HLA-DR molecules on hyperproliferative keratinocytes.
[Bioinformatic analysis of chronic myeloid leukemia progression and preliminary experimental verification]. (2014)

This study was aimed to explore the progression mechanism of chronic myeloid leukemia, so as to provide the new molecular markers for evaluation of CML clinical outcome and selection of treatment. The microarray data of genes related with progression from different phase of chronic myeloid leukemia (CML) were collected from public data depository GEO (Gene expression datasets). SAM analysis, fold change filtering, cross comparison were used to analyze the data and identify different genes. Moreover, MeV and pSTIING sofewares were used to analyze the key differential genes and signal pathways. At last, Q-PCR were used to confirm the predicted key gene. The results indicated that after comparison, 9 genes were differentially expressed from AP to BC, and the integrin-mediated cell adhesion , focal adhesion, regulation of actin cytoskeleton were the principal pathways during CML progression. Network construction analysis found that AP-related genes or pathways may be the original signals; and MLLT4, WDR35 and EPHB4 were the key genes for CML progression. EPHB4 was confirmed by Q-PCR in CML BC patients and CP patients. It is concluded that MLLT4, WDR35, EPHB4, integrin-mediated cell adhesion, focal adhesion and regulation of actin cytoskeleton are the principal genes and pathways during CML progression.
Molecular cloning of the actin gene from yeast Saccharomyces cerevisiae (1980)

Two overlapping DNA fragments from yeast Saccharomyces cerevisiae containing the actin gene have been inserted into pBR322 and cloned in E.coli. Clones were identified by hybridization to complementary RNA from a plasmid containing a copy of Dictyostelium actin mRNA. One recombinant plasmid obtained (pYA102) contains a 3.93-kb Hindlll fragment, the other (pYA208) a 5.1-kb Pstl fragment, both share a common 2.2-kb fragment harboring part of the actin gene. Cloned yeast actin DNA was identified by R-loop formation and translation of the hybridized actin mRNA and by DNA sequence analysis. Cytoplasmic actin mRNA has been estimated to be about 1250 nucleotides long. There is only one type of the actin gene in S.cerevisiae.
Pathogenesis of chronic allograft rejection. (2003)

Chronic allograft nephropathy (CAN) is, besides death of the recipient with graft function, the most common cause of renal transplant loss. It is characterized by loss of function and replacement of tissue by fibrotic material. The pathogenesis is not clear, but seems to be multifactorial and involves events both early and late after transplantation. Alloantigen-dependent mechanisms seem to be crucial for the development of chronic rejection (CR). Although modern immunosuppressive drugs have reduced the number and severity of acute rejection episodes, their effects on CR are less obvious. In this review we discuss the role of direct and indirect antigen presentation in the development of CR, and we will focus on the production of antibodies directed against HLA and non-HLA antigens on the graft and their influence on CR.
Cooling the Neck Region During Exercise in the Heat (2011)

Cooling the neck increased the time taken to reach volitional exhaustion by dampening the perceived levels of thermal strain.
On the determination of the crystalline fraction of isotactic polypropylene from x‐ray diffraction (1961)

Abstract A simple procedure for the determination of the crystalline fraction in isotactic polypropylene, suitable for routine work, is described. It gives lower figures for the crystalline fraction than the method recommended by N ATTA , C ORRADINI , and C ESARI in 1957. The correctness of the results (within the limitations inherent to the concept of crystallinity in polymers) is supported by the consistency of the results with those obtained by the recently published very remarkable quite elaborate and sophisticated procedure of W. R ULAND .
The allele encoding the mycobacterial Erp protein affects lung disease in mice (2003)

Erp (exported repetitive protein), also known as P36, Pirg and Rv3810, is a member of a mycobacteria-specific family of extracellular proteins. These proteins consist of three domains, the N- and C-terminal domains are similar in all mycobacterial species, however, the central domain contains a repeated PGLTS module and differs considerably between species. The erp knockout mutant of Mycobacterium tuberculosis displays very low levels of multiplication both in macrophage cell lines and in vivo in a mouse model of infection. The high interspecies variability of the central repeated region of the Erp protein led us to investigate whether these orthologous proteins were functionally equivalent in a mouse model of tuberculosis. We expressed a gene fusion with the erp gene of Mycobacterium smegmatis, Mycobacterium leprae or M. tuberculosis in trans in an erp-M. tuberculosis mutant and found that these three alleles restored multiplication to similar levels in the spleen of infected mice. However, these alleles gave different levels of colonization in the lung, for the early time-points. Quantitative histological analyses of the lungs of infected animals showed that the nature of the erp allele strongly affected the number and the size of lung lesions, demonstrating the importance of surface determinants for virulence and tissue damage.
CD30 expression by CD8+ T cells producing type 2 helper cytokines. Evidence for large numbers of CD8+CD30+ T cell clones in human immunodeficiency virus infection. (1994)

A large panel of CD8+ T cell clones generated from peripheral blood lymphocytes (PBL) of healthy donors or human immunodeficiency virus (HIV)-infected individuals were assessed for both cytokine secretion profile and CD30 expression and release. The great majority of CD8+ T cell clones generated from healthy individuals showed the ability to produce interferon gamma (IFN-gamma), but not interleukin 4 (IL-4), and none of them either expressed membrane CD30 or released substantial amounts of soluble CD30 (sCD30) in their supernatant. In contrast, high numbers of CD8+ T cell clones generated from HIV-infected individuals, which produced IL-4 (and IL-5) in addition to IFN-gamma or IL-4 (and IL-5) alone, expressed membrane CD30 and released detectable amounts of sCD30 in their supernatants. Indeed, CD30 expression appeared to be positively correlated with the ability of CD8+ T cell clones to produce IL-4 and IL-5 and inversely correlated with their ability to produce IFN-gamma, whereas no correlation between CD30 expression and production of IL-10 was observed. These data suggest that CD30 is a marker for CD8+ T cells that have switched to the production of type 2 helper cytokines.
Prospective Multicenter Study of Pegylated Liposomal Doxorubicin Treatment in Patients With Advanced or Refractory Mycosis Fungoides or Sézary Syndrome (2008)

This prospective study demonstrates the effectiveness of Caelyx in treating CTCL, with an overall response rate of 56% in spite of the high proportion of patients with advanced-stage disease. Responses were observed in 2 subpopulations of patients in which the prognosis is known to be poorer: Sézary syndrome (overall response rate, 60%) and transformed CTCL (overall response rate, 50%). Moreover, this study shows that dose escalation to 40 mg/m(2) does not seem to improve the effectiveness but increases toxic effects (especially hematologic toxic effects) compared with the dose previously tested of 20 mg/m(2).
Pyoderma Gangrenosum (1980)

Fifteen consecutive patients with PG have been studied during the period 1971-78. Systemic disease was found in 13 of the patients and preceded the skin disease in 10 patients by 1-25 years. Only two patients had ulcerative colitis. One patient had paroxysmal nocturnal hemoglobinuria and three patients had an IgA myeloma. Eight patients had polyarthritis; this was classical seropositive rheumatoid arthritis in two patients, and a seronegative inflammatory polyarthritis in six patients. Four patients had an unusual progressive erosive seronegative polyarthritis without evidence of granulomatous bowel disease, psoriasis, genital, urinary tract or eye disease. In three of these four patients the arthritis preceded the PG. Synovial fluid analysis showed depressed complement levels and in one patient deposits of immunoglobulins and complement were demonstrated in the synovial membrane. The course of the arthritis was progressive with development of disabling joint deformities and erosive destruction of joints, despite treatment with penicillamine, corticosteroids and nonsteroidal anti-inflammatory drugs. One other patient had severe degenerative joint disease and chondrocalcinosis in association with a seronegative inflammatory polyarthritis, and another patient had ulcerative proctitis and severe degenerative joint disease secondary to chronic seronegative inflammatory polyarthritis. None of the patients had colitic arthritis, but in view of the association between PG and ulcerative colitis, some patients previously reported with PG and joint disease may have been suffering from the arthritis of ulcerative colitis. PG developed at the site of skin trauma in six patients. The natural history of the skin disease ran one of two courses: an acute, progressive course in which the ulcers rapidly enlarged until arrested by treatment; and a chronic course in which the lesions extended slowly and which after a period of weeks began to show signs of spontaneous healing. In only the patients with ulcerative colitis was there any correlation between the activity of the associated disease and the onset and progression of the skin disease. Serum complement levels were normal and no circulating cryoprecipitable immune complexes were found. Skin histology showed no evidence of vasculitis and direct immunofluorescence examination of involved skin was negative for IgG, IgM, IgA and C3. No consistent abnormality of cell-mediated immunity or neutrophil function was found and no significantly increased prevalence of any HLA antigen type was noted. Twelve patients have been treated with systemic corticosteroids. Six of these patients developed serious steroid complications and four patients have died, all from complications of steroid therapy.
Expression of most matrix metalloproteinase family members in breast cancer represents a tumor-induced host response. (1996)

Matrix metalloproteinase (MMP) family members have been associated with advanced-stage cancer and contribute to tumor progression, invasion, and metastasis as determined by inhibitor studies. In situ hybridization was performed to analyze the expression and localization of all known MMPs in a series of human breast cancer biopsy specimens. Most MMPs were localized to tumor stroma, and all MMPs had very distinct expression patterns. Matrilysin was expressed by morphologically normal epithelial ducts within tumors and in tissue from reduction mammoplasties, and by epithelial-derived tumor cells. Many family members, including stromelysin-3, gelatinase A, MT-MMP, interstitial collagenase, and stromelysin-1 were localized to fibroblasts of tumor stroma of invasive cancers but in quite distinct, and generally widespread, patterns. Gelatinase B, collagenase-3, and metalloelastase expression were more focal; gelatinase B was primarily localized to endothelial cells, collagenase-3 to isolated tumor cells, and metalloelastase to cytokeratin-negative, macrophage-like cells. The MMP inhibitor, TIMP-1, was expressed in both stromal and tumor components in most tumors, and neither stromelysin-2 nor neutrophil collagenase were detected in any of the tumors. These results indicate that there is very tight and complex regulation in the expression of MMP family members in breast cancer that generally represents a host response to the tumor and emphasize the need to further evaluate differential functions for MMP family members in breast tumor progression.
A framework for Response Surface Methodology for simulation optimization (2000)

We develop a framework for automated optimization of stochastic simulation models using Response Surface Methodology. The framework is especially intended for simulation models where the calculation of the corresponding stochastic response function is very expensive or time-consuming. Response Surface Methodology is frequently used for the optimization of stochastic simulation models in a non-automated fashion. In scientific applications there is a clear need for a standardized algorithm based on Response Surface Methodology. In addition, an automated algorithm is less time-consuming, since there is no need to interfere in the optimization process. In our framework for automated optimization we describe the many choices that have to be made in constructing such an algorithm.