gebhart/patrepeval huggingface dataset:
Roles of Cyclophilins in Cancers and Other Organ Systems (2005)

Cyclophilins are originally identified as cellular binding proteins for the immunosuppressive drug cyclosporin A. Many cyclophilins, including CypA, CypB, CypC, CypD, and Cyp40, have been discovered and shown to be ubiquitously distributed in many types of cells and organ systems. Recent investigations have uncovered many important properties and functions for cyclophilins including peptidyle-prolyl-isomerase activity and protein folding/repair; maintaining mitochondrial functions and involvement in apoptosis; roles in regulation of T-cell function and inflammation; interaction with CD147; and pathogenesis of vascular disease, human immunodeficiency virus infection, and rheumatoid arthritis. Furthermore, the expression and functions of cyclophilins may be correlated with tumor biology of several types of cancers including pancreatic carcinoma. Molecular mechanisms of cyclophilin-mediated biologic events and future directions of research are discussed in this review. Understanding the roles of cyclophilins in cancers and other organ systems will be crucial in determining clinical applications for the treatment or diagnosis of human diseases.
Direct Interaction between Ras and the Kinase Domain of Mitogen-activated Protein Kinase Kinase Kinase (MEKK1) (1995)

Mitogen-activated protein kinase kinase kinase (MEKK1) is a serine-threonine kinase that regulates sequential protein kinase pathways involving stress-activated protein kinases and mitogen-activated protein kinases. MEKK1 is activated in response to growth factor stimulation of cells and by expression of activated Ras. We demonstrate that the kinase domain of MEKK1 (MEKKCOOH) binds to GST-RasV12 in a GTP-dependent manner. Purified bacterially expressed MEKKCOOH binds to GST-RasV12(GTP gamma S) (GTP gamma S is guanosine 5'-3-O-(thio)triphosphate), demonstrating a direct interaction of the two proteins. A Ras effector domain peptide blocks the binding of MEKKCOOH to GST-RasV12(GTP gamma S). MEKKCOOH complexed with GST-RasV12(GTP gamma S) is capable of phosphorylating MEK1. These findings indicate that MEKK1 directly binds Ras.GTP. Thus, Ras interacts with protein kinases of both the Raf and MEKK families.
The fluorescent probe BCECF has a heterogenous distribution in sea urchin eggs (1990)

Sea urchin eggs were loaded with the pH-sensitive fluorescent probe BCECF. Homogenization of these eggs, followed by centrifugation, resulted in 25% of the total homogenate fluorescence remaining with the pellet. Fluorescence microscopy revealed brightly fluorescing punctate organelles whose fluorescence was not quenched by acidification. The excitation spectrum of intracellular BCECF was markedly red-shifted compared to probe calibrated in buffer. Model excitation spectra based on a two compartment model mimicked the intracellular BCECF spectrum, therefore, supporting the possibility that organelles in sea urchin eggs accumulate large amounts of BCECF in a relatively pH-insensitive form.
A Module System for Harvesting Tree Prunings (1985)

A system for moduling tree prunings was constructed and field tested. The system included a heavy-duty module builder, a specially designed module cutter, and a tub grinder. 904 modules of almond tree prunings were made over two pruning seasons. Average time to make one module was 0.35 h. Average module density was 89 kg/m3 (5.6 lb/ft3). Wood in the modules dried from 30% to 10% moisture content wet basis over a period of 4 months. A cutter was developed to cut the modules into two or three sections to fit a 3 m (10 ft) diameter tub grinder. Throughput capacity of the tub grinder with cut modules was two to three times higher than with loose brush. Total estimated cost to module, grind, and transport tub ground brush 50 km was $31.45/t ($28.50/ton) dry basis.
Modulation of signaling via the B cell antigen receptor by CD21, the receptor for C3dg and EBV. (1994)

CD21 is the receptor for C3dg and EBV. Several reports have shown that these CD21 ligands, and certain anti-CD21 mAb, trigger B cell activation, particularly when combined with Ag receptor ligation. However, the characteristics, biologic functions, and importance of this CD21-signaling pathway are unknown. We have used a model we recently developed to study B cell activation induced by complex particulate Ag, such as immune complexes and viruses, to begin to examine these questions. In the current studies, we incubated purified small resting B cells with 100-nm latex beads bearing various combinations of CD21 ligands and mAbs to CD19, CD35, and the Ag receptor. CD21, CD19, and CD35 have all been implicated in modulating membrane IgM initiated signaling. Beads coated with mAb to the C3dg/EBV-binding portion of CD21, but not mAb to other portions of the CD21 molecule, triggered B cell homotypic aggregation. Beads coated with the same CD21 ligands, although inactive alone, synergized with anti-IgM mAb in greatly increasing (20- to 180-fold) mRNA levels of the c-fos nuclear proto-oncogene. Signaling via CD21 was tyrosine kinase dependent. Levels of c-myc mRNA were not altered by CD21 ligands. Anti-CD19 and anti-CD35 mAb did not augment signaling via membrane IgM as assessed by changes in c-fos mRNA levels. These findings indicate that CD21 ligands binding to the C3dg/EBV-binding site of CD21 markedly augment B cell activation initiated by Ag receptor ligation via a selective, c-fos-dependent signaling pathway.
Assessment of pain: types, mechanism and treatment. (2013)

Pain is the most common symptom of disease, which accompanies us from an early age. It is a protective mechanism to which the body responds to harmful stimulus. The definition of pain states that it is a subjective sensory and emotional experience. It is connected to the stimulus that it invokes and is also based on the observation of psychological interpretation of the phenomena taking place. Pain is individual for each person. Pain affects both our previous experience of pain and psychosomatic conditions, depending on the relationship between the psyche and the body. Pain is always an unpleasant sensation. The feeling of pain can be caused by irritation of pain receptors, which can be found in the skin, joints and many internal organs. The cause of pain may also be damage to the nervous system, both the peripheral nerves, brain and spinal cord. Pain can also occur without damage to tissues, although the patient refers to it (psychogenic pain). The process of pain is a complex phenomenon. Experience of pain depends on the strength of the stimulus, individual susceptibility and individual resistance to pain. Pain receptors are sensitive to mechanical, thermal or chemical stimuli. The operation of noxious stimulus to these receptors results in the processing into an electrical signal. This impulse is conducted by nerve fibress into the spinal cord and then to the brain. At this point, there is the realization that something hurts us. Pain is not only somatic in nature, associated with the condition of the body, but it is a multidimensional phenomenon. Therefore, in addition to the physiological process of pain, its subjective perception is also important, which is decided by the central nervous system. It consists of the emotional aspects: suffering and attitude towards pain and pain expression. A review of pain physiology is essential to fully understand the principles of pain management.
Difficulties in Classifying Diabetes at Presentation in the Young Adult (1993)

All newly diagnosed diabetic patients in Sweden aged 15-34 years have been registered since 1983. In this study the clinical characteristics initially and after 2.5-3 years were evaluated by a questionnaire to the patient's physician and by non-fasting C-peptide. The study comprised patients registered 1983-84, and for 281 patients (37%), complete information was obtained. At diagnosis 75% were classified as Type 1, 19% as Type 2, and 6% as secondary diabetes or as uncertain by their physician. Twenty patients (7.1%) were reported to have ketoacidosis. Seventy-five percent were treated with insulin, 7% with oral hypoglycaemic agents (OHG), and 18% with diet alone. At follow-up 71% were classified as Type 1, 21% as Type 2, and 8% as secondary or uncertain while treatment was 82% insulin, 8% OHG, and 9% diet. During the follow-up period 42% of the initially non-insulin-treated patients were put on insulin whereas only a few stopped insulin treatment. Patients treated with diet or OHG at follow-up were older, had higher percent desirable weight, and lower blood glucose at diagnosis than patients treated with insulin. All except one patient had measurable random C-peptide at follow-up and mean values were for patients treated with insulin 0.55, OHG 1.41 and diet alone 1.29 nmol l-1. Random blood glucose results were similar. In conclusion the majority of newly diagnosed patients in the age group 15-34 years have the characteristics of Type 1 diabetes and Type 2 diabetes is rare before 25-30 years of age.(ABSTRACT TRUNCATED AT 250 WORDS)
Genomic Organization and Localization of the Human CRMP-1 Gene (1998)

The Collapsin Response Mediator Protein-1 (CRMP-1) is a brain specific protein considered to be involved in the collapsin-induced growth cone collapse during neural development. CRMP-1 belongs to the Unc-33 gene family. Here we report the genomic structure and the localization of the human CRMP-1 gene to chromosome 4p16.1. Sequence analysis revealed that the human CRMP-1 gene consists of 14 exons. We have also established sequencing assays for all its coding exons. This should permit the rapid screening for mutations to assess CRMP-1 role in genetic disorders mapped in the 4p16.1 region.
Differentiation-on-a-chip: A microfluidic platform for long-term cell culture studies (2004)

Here we demonstrate a microfluidic perfusion system suitable for a long-term (>2 week) culture of muscle cells spanning the whole process of differentiation from myoblasts to myotubes. Cell-adhesive surface microdomains alternating with a robust cell-repellent coating mimic in vivo spatial cues for muscle cell assembly and allow for confining the fusion of myoblasts into aligned, isolated multinucleated myotubes. The microfluidic system provides accurate control of the perfusion rates and biochemical composition of the environment surrounding the cells. Comparing muscle cell-specific differentiation markers and the timing of fusion, we observed no differences in differentiation between microfluidic and traditional cultures. All differentiation assays were fully microfluidic, i.e. they were performed by sequentially changing the fluids in the micro-channels. By delivering fluorescent markers using heterogeneous laminar flows, it was possible to confine a membrane receptor labeling assay to a region smaller than a myotube. Our method can serve as an improved in vitro model for studying muscle cell differentiation and for characterizing extracellular molecules and mechanisms involved in neuromuscular differentiation.
Context sensitive flying interface (1997)

The requirement to change scale frequently is common to many 2D and 3D applications.
The human myelin basic protein gene is included within a 179-kilobase transcription unit: expression in the immune and central nervous systems. (1993)

Two human Golli (for gene expressed in the oligodendrocyte lineage)-MBP (for myelin basic protein) cDNAs have been isolated from a human oligodendroglioma cell line. Analysis of these cDNAs has enabled us to determine the entire structure of the human Golli-MBP gene. The Golli-MBP gene, which encompasses the MBP transcription unit, is approximately 179 kb in length and consists of 10 exons, seven of which constitute the MBP gene. The human Golli-MBP gene contains two transcription start sites, each of which gives rise to a family of alternatively spliced transcripts. At least two Golli-MBP transcripts, containing the first three exons of the gene and one or more MBP exons, are produced from the first transcription start site. The second family of transcripts contains only MBP exons and produces the well-known MBPs. In humans, RNA blot analysis revealed that Golli-MBP transcripts were expressed in fetal thymus, spleen, and human B-cell and macrophage cell lines, as well as in fetal spinal cord. These findings clearly link the expression of exons encoding the autoimmunogen/encephalitogen MBP in the central nervous system to cells and tissues of the immune system through normal expression of the Golli-MBP gene. They also establish that this genetic locus, which includes the MBP gene, is conserved among species, providing further evidence that the MBP transcription unit is an integral part of the Golli transcription unit and suggest that this structural arrangement is important for the genetic function and/or regulation of these genes.
Deep surface relief grating in azobenzene-containing materials using a low-intensity 532 nm laser (2019)

The inscription of deep surface relief grating (SRG) in glassy monomeric azobenzene materials using a low intensity diode pumped solid state (DPSS) laser operating at 532 nm is demonstrated. Previously developed epoxy-based star-like azobenzene-containing material was applied. Both deep SRG and multi-dimensional structures can be fabricated using this cheap, effective material in combination with a low cost laser source. The dependencies of the SRG performance (amplitude, inscription rate, stability) on exposure conditions (time, intensity) and layer thickness are presented. The replication of the inscribed gratings using polydimethylsiloxane is demonstrated. The results show that effective all-optical fabrication of surface relief master-gratings can be realized using low cost chemistry and widely used low-intensity coherent light source operating at 532 nm.
Aerosolized Human Neutrophil Elastase Induces Airway Constriction and Hyperresponsiveness With Protection by Intravenous Pretreatment With Half-Length Secretory Leukoprotease Inhibitor (1996)

This study was designed to determine the effects of inhaled human neutrophil elastase (HNE) on airway constriction and airway responsiveness, and to examine the protection by an intravenous recombinant half-length secretory leukoprotease inhibitor, r1/2SLPI in guinea pigs. Aerosol inhalation of HNE (250 microgram/ml, for 3 min) caused a transient but significant airway constriction, in which lung resistance (RL) increased from 194 +/- 18 (mean +/- SEM) to 461 +/- 42 cm H2O/L/s (p < 0.001). Thirty minutes after the end of HNE inhalation, airway responsiveness to intravenous 5-hydroxytryptamine (5-HT) was significantly increased. The provocative dose causing a 200% increase in RL (PD200) was significantly decreased from 10.0 +/- 1.2 to 6.5 +/- 0.8 microgram/kg (p < 0.001). Forty-five minutes after the end of HNE inhalation, total cells in bronchoalveolar lavage fluid (BALF) were significantly increased (p < 0.05). Histologic study of intrapulmonary bronchi demonstrated an acute inflammatory response characterized by damage to the epithelium, airway obstruction by mucus plugs, and recruitment of mononuclear and polymorphonuclear cells to the bronchial epithelium. r1/2SLPI (30 mg/kg) injected 5 min before the initiation of HNE inhalation significantly inhibited the airway constriction (p < 0.05), the airway hyperresponsiveness (p < 0.01), and the increase of cells in BALF (p < 0.05). The present data suggest that HNE plays a role in the induction of airway constriction and airway hyperresponsiveness in various inflammatory lung diseases with pulmonary neutrophil infiltration, such as chronic obstructive pulmonary diseases (COPD) and possibly bronchial asthma. r1/2SLPI may be useful as an antiprotease treatment.
Female sex offenders: Clinical and demographic features (2002)

Abstract This paper provides clinical and demographic data on 12 female child sex offenders in the correctional system in Victoria. Information was obtained through clinical assessments completed whilst women were incarcerated or in the community setting and from sentencing comments. An analysis of this information revealed that the characteristics of these women and their offences generally fitted the profile of female sex offenders described in the current literature. However, the findings also revealed that the women differed in some respects to the typical portrayal of female sex offenders. Although the majority of women were co-offenders with males, only a few females appeared coerced and motivated by fear. In the group of male accompanied offences, women were also motivated by rejection and revenge, leading to the development and extension of a new category - the male accompanied: rejected/revengeful.
αvβ6integrin promotes invasion of squamous carcinoma cells through up-regulation of matrix metalloproteinase-9 (2001)

The integrin alphaVbeta6 is a fibronectin receptor, which is not detectable on normal epithelium but is neo-expressed in oral epithelial dysplasia and oral squamous-cell carcinoma (SCC), suggesting a role in promoting malignant behaviour and tumour progression. We used transfection and retroviral infection to create a panel of SCC cell lines expressing various levels of alphaVbeta6 to examine this possibility. We found that increased expression of alphaVbeta6 in malignant keratinocytes up-regulates MMP-9 and MMP-2 expression and promotes invasion in an MMP-9-dependent manner. Our results suggest a possible mechanism for the involvement of alphaVbeta6 in squamous carcinoma in vivo.
Mannose-Binding Lectin-Associated Serine Protease-1 Is a Significant Contributor to Coagulation in a Murine Model of Occlusive Thrombosis (2011)

Bleeding disorders and thrombotic complications constitute a major cause of death and disability worldwide. Although it is known that the complement and coagulation systems interact, no studies have investigated the specific role or mechanisms of lectin-mediated coagulation in vivo. FeCl(3) treatment resulted in intra-arterial occlusive thrombogenesis within 10 min in wild-type (WT) and C2/factor B-null mice. In contrast, mannose-binding lectin (MBL)-null and MBL-associated serine protease (MASP)-1/-3 knockout (KO) mice had significantly decreased FeCl(3)-induced thrombogenesis. Reconstitution with recombinant human (rh) MBL restored FeCl(3)-induced thrombogenesis in MBL-null mice to levels comparable to WT mice, suggesting a significant role of the MBL/MASP complex for in vivo coagulation. Additionally, whole blood aggregation demonstrated increased MBL/MASP complex-dependent platelet aggregation. In vitro, MBL/MASP complexes were captured on mannan-coated plates, and cleavage of a chromogenic thrombin substrate (S2238) was measured. We observed no significant differences in S2238 cleavage between WT, C2/factor B-null, MBL-A(-/-), or MBL-C(-/-) sera; however, MBL-null or MASP-1/-3 KO mouse sera demonstrated significantly decreased S2238 cleavage. rhMBL alone failed to cleave S2238, but cleavage was restored when rMASP-1 was added to either MASP-1/-3 KO sera or rhMBL. Taken together, these findings indicate that MBL/MASP complexes, and specifically MASP-1, play a key role in thrombus formation in vitro and in vivo.
Double-stranded deoxyribonucleic acid binds to HLA class II molecules and inhibits HLA class II-mediated antigen presentation (1998)

CD4+ T cells proliferating in response to purified double-stranded deoxyribonucleic acid (dsDNA) have been recently demonstrated in peripheral blood mononuclear cells of patients with systemic lupus erythematosus. Their activation was inhibited by anti-HLA class II (HLA-II) monoclonal antibodies; thus, the existence of a molecular interaction between dsDNA and HLA-II is conceivable. In this report we show that dsDNA specifically bind to HLA-II. After preincubating cells with purified dsDNA or synthetic oligonucleotides, dsDNA was detected on the cell membrane and in the lysates of HLA-II+ but not of isogenic HLA-II- cell lines. We demonstrate that dsDNA binding inhibits that of a specific peptide to HLA-II. Mixed lymphocyte reaction and antigen-specific T cell proliferation were inhibited by the preincubation of stimulator cells or antigen-presenting cells with dsDNA. These results suggest the existence of a novel mechanism of down-modulation of the CD4+ T cell function generated by lack of stimulation due to the HLA-II presenting molecules being "occupied" by dsDNA.
Parvovirus H1 selectively induces cytotoxic effects on human neuroblastoma cells (2010)

Despite multimodal therapeutic concepts, advanced localized and high-risk neuroblastoma remains a therapeutic challenge with a long-term survival rate below 50%. Consequently, new modalities for the treatment of neuroblastoma, e.g., oncolytic virotherapy are urgently required. H-1PV is a rodent parvovirus devoid of relevant pathogenic effects in infected adult animals. In contrast, the virus has oncolytic properties and is particularly cytotoxic for transformed or tumor-derived cells of various species including cells of human origin. Here, a preclinical in vitro assessment of the application of oncolytic H-1PV for the treatment of neuroblastoma cells was performed. Infection efficiency, viral replication and lytic activity of H-1PV were analyzed in 11 neuroblastoma cell lines with different MYCN status. Oncoselectivity of the virus was confirmed by the infection of short term cultures of nonmalignant infant cells of different origin. In these nontransformed cells, no effect of H-1PV on viability or morphology of the cells was observed. In contrast, a lytic infection was induced in all neuroblastoma cell lines examined at MOIs between 0.001 and 10 pfu/cell. H-1PV actively replicated with virus titres increasing up to 5,000-fold within 48-96 hr after infection. The lytic effect of H-1PV was observed independent of MYCN oncogene amplification or differentiation status. Moreover, a significant G2-arrest and induction of apoptosis could be demonstrated. Infection efficiency, rapid virus replication and exhaustive lytic effects on neuroblastoma cells together with the low toxicity of H-1PV for nontransformed cells, render this parvovirus a promising candidate for oncolytic virotherapy of neuroblastoma.
Incomplete primer extension duringin vitroDNA amplification catalyzed byTaqpolymerase; exploitation for DNA sequencing (1989)

Polyacrylamide gel electrophoresis of DNA fragments obtained by the polymerase chain reaction using Taq polymerase revealed the presence of multiple fragments shorter than the expected product. These abortive extension products were observed even when analysis by agarose gel electrophoresis showed only a single band. The production of prematurely terminated fragments can be exploited for the sequencing of PCR products if phosphorothioate groups are incorporated base specifically during the reaction in the presence of two oligonucleotide primers, one of which is 5'-32P-labeled. The addition of snake venom phosphodiesterase to the reaction mixture after completion of the amplification cycles digests each fragment from the 3'-end to a phosphorothioate group so that the sequence can be read by polyacrylamide gel electrophoresis.