gebhart/patrepeval huggingface dataset:
Human endothelial cells suppress prothrombin activation in nonanticoagulated whole blood in vitro. (1994)

Human endothelial cells cultivated on polystyrene microcarrier beads were used to study endothelial anticoagulant activity in vitro. Spontaneous whole blood coagulation was inhibited by endothelial cells on microcarriers at a surface to volume ratio of 16 cm2/ml blood. Thrombin activity generated in nonanticoagulated whole blood during 1 hour and assessed by its fibrinogen clotting effect was reduced by 87% in the presence of endothelial cells. Consistent with this observation, prothrombin fragment1+2, fibrinopeptide A, and thrombin-antithrombin III-complex release during the same period of time were inhibited by 81%, 47%, and 88%, respectively. Immunoblotting analysis of cell-free supernatants derived from the same samples demonstrated that prothrombin activation was strongly suppressed in the presence of endothelial cells. Furthermore, the incubation of nonanticoagulated whole blood with endothelialized beads for only 5 minutes after venipuncture was sufficient to prevent subsequent prothrombin activation in the cell-free supernatants of the same whole blood sample after centrifugation. These findings suggest that interruption of the coagulation cascade is probably one major mechanism of endothelial anticoagulant activity in vivo.
Characterization of membrane-associated and soluble states of SecA protein from wild-type and SecA51(TS) mutant strains of Escherichia coli. (1991)

The subcellular localization of SecA, a protein essential for the catalysis of general protein export, was studied to better understand its state(s) and function(s) within Escherichia coli cells. In a wild-type strain approximately half of the cellular SecA content was found to be associated with the inner membrane, while the remainder was soluble. Association of SecA protein with the inner membrane required the presence of anionic phospholipids and was modulated by ATP. A fraction of the membrane-bound SecA was found to be integrally associated with the membrane. In the secA51(Ts) mutant 75-95% of SecA protein was found to be membrane associated, independent of the protein export status of the cell, implying that the partitioning of this protein between the cell membrane and cytoplasm may play an important role in its function. secA-lacZ fusions were used to map a membrane association determinant to the amino-terminal quarter of SecA protein sequence. When this portion of SecA protein was expressed within cells, it was found solely in membrane fractions and complemented the growth and protein secretion defect of the secA51(Ts) mutant. This indicates that the membrane is the site of the limiting defect in this mutant and suggests that either SecA functions can be divided into at least two separable activities or that productive interaction between SecA and the amino-terminal fragment can occur in vivo.
Osteoclastogenesis-Related Antigen, a Novel Molecule on Mouse Stromal Cells, Regulates Osteoclastogenesis (2003)

Osteoclastogenesis is regulated by RANKL expressed on stromal cells. In this study, we sought to isolate a new surface molecule regulating osteoclastogenesis on stromal cells by generating monoclonal antibodies. A rat was immunized with the mouse stromal cell line, TSB13, which can support osteoclastogenesis, and a monoclonal antibody, A15-1, was obtained. A15-1 bound to a surface antigen on TSB13 cells, termed osteoclastogenesis-related antigen (OCRA), and immunoprecipitation with this antibody revealed that OCRA was a 220-kDa molecule. By means of flow cytometry, the A15-1 antigen (OCRA) was found to be expressed on various mesenchymal cell lines but not on hematopoietic cell lines, and the expression level of OCRA on the TSB13 cells was slightly increased by treatment with 1alpha,25(OH)2D3. When osteoclast progenitors and TSB13 cells were co-cultured in the presence of 1alpha,25(OH)2D3, the addition of A15-1 inhibited osteoclast differentiation in a dose-dependent manner; however, no significant inhibition of soluble RANKL-induced osteoclastogenesis was observed, suggesting that A15-1 inhibited only stromal cell-dependent osteoclastogenesis. The same inhibitory effect of A15-1 was also observed when primary bone marrow-derived stromal cells were used. The osteoclastogenesis-promoting effects of other osteotropic factors, such as parathyroid hormone (PTH) and interleukin (IL)-1beta, were also inhibited by A15-1. Time-course analysis of osteoclast differentiation in vitro indicated that the initial 2 days of treatment with A15-1 was sufficient for inhibition, suggesting that A15-1 inhibits the early stages of osteoclast differentiation. Finally, we investigated the in vivo effects of A15-1 on PTH-induced hypercalcemia in mice. Treatment with A15-1 significantly decreased the osteoclast surface in the PTH-administered mice. Taken together, our data indicate that OCRA, a novel A15-1-detected antigen, regulates stromal cell-dependent osteoclastogenesis.
Bardoxolone Methyl Decreases Megalin and Activates Nrf2 in the Kidney (2012)

Inflammation and oxidative stress are hallmarks and mediators of the progression of CKD. Bardoxolone methyl, a potent activator of the nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated antioxidant and anti-inflammatory response, increases estimated GFR and decreases BUN, serum phosphorus, and uric acid concentrations in patients with moderate to severe CKD. However, it also increases albuminuria, which is associated with inflammation and disease progression. Therefore, we investigated whether this bardoxolone methyl-induced albuminuria may result from the downregulation of megalin, a protein involved in the tubular reabsorption of albumin and lipid-bound proteins. Administration of bardoxolone methyl to cynomolgus monkeys significantly decreased the protein expression of renal tubular megalin, which inversely correlated with the urine albumin-to-creatinine ratio. Moreover, daily oral administration of bardoxolone methyl to monkeys for 1 year did not lead to any adverse effects on renal histopathologic findings but did reduce serum creatinine and BUN, as observed in patients with CKD. Finally, the bardoxolone methyl-induced decrease in megalin corresponded with pharmacologic induction of renal Nrf2 targets, including NAD(P)H:quinone oxidoreductase 1 enzyme activity and glutathione content. This result indicates that Nrf2 may have a role in megalin regulation. In conclusion, these data suggest that the increase in albuminuria that accompanies bardoxolone methyl administration may result, at least in part, from reduced expression of megalin, which seems to occur without adverse effects and with strong induction of Nrf2 targets.
Spectroscopic investigation on gel‐forming β‐sheet assemblage of peptide derivatives (2003)

The conformational studies of peptide derivatives A and B in a gel state were studied by using circular dichroism (CD), Fourier transformed infrared (FTIR), and fluorescence spectroscopic techniques. Birefringence and electron microscopic studies were carried out to characterize the morphological aspects of the fibrils in the gel. The FTIR spectra of the peptides show the absence of free NH in the gel state, implying that the intermolecular hydrogen-bond formation is the driving force for the aggregation. The CD spectrum of the peptide gels shows the presence of antiparallel and parallel beta-sheet conformation for peptide derivatives A and B, respectively. Electron microscopic studies (EM) of the peptide derivatives A and B reveal that peptide A formed rigid, rod-like structures without cross-linking and peptide B formed loose fibrils organized into highly noncovalently cross-linked mesh-like structural aggregates. Peptide A was much more soluble in alcoholic solvents than peptide B, and no birefringence was observed with Congo red (CR) staining in the temperature range of 0-80 degrees C. The spectroscopic studies indicate that peptide B consists of domains having a significant amount of beta-sheet structure and exhibiting golden yellow birefringence between 53 and 56 degrees C when stained with Congo red. On the other hand, peptide A gives no evidence of birefringence under polarized light. Fluorescence probe binding studies with pyrene in gel state with peptides A and B indicates the polarity in the interior of the aggregates. The data presented in the present work indicate that peptide B forms fibrils, which is similar to amyloid aggregates that are present in biological systems.
Adherence patterns in patients with type 2 diabetes on basal insulin analogues: missed, mistimed and reduced doses (2012)

Basal insulin dosing irregularities including missed, mistimed and reduced doses are common. A significant proportion of patients also report undertaking these irregular dosing behaviours at a frequency that would be considered by prescribers to negatively impact diabetes management. This is despite the potential under-reporting due to recall or social bias that may be a limitation of a self-reported survey around these behaviours.
Mechanism of mda-5 Inhibition by Paramyxovirus V Proteins (2008)

The RNA helicases encoded by melanoma differentiation-associated gene 5 (mda-5) and retinoic acid-inducible gene I (RIG-I) detect foreign cytoplasmic RNA molecules generated during the course of a virus infection, and their activation leads to induction of type I interferon synthesis. Paramyxoviruses limit the amount of interferon produced by infected cells through the action of their V protein, which binds to and inhibits mda-5. Here we show that activation of both mda-5 and RIG-I by double-stranded RNA (dsRNA) leads to the formation of homo-oligomers through self-association of the helicase domains. We identify a region within the helicase domain of mda-5 that is targeted by all paramyxovirus V proteins and demonstrate that they inhibit activation of mda-5 by blocking dsRNA binding and consequent self-association. In addition to this commonly targeted domain, some paramyxovirus V proteins target additional regions of mda-5. In contrast, V proteins cannot bind to RIG-I and consequently have no effect on the ability of RIG-I to bind dsRNA or to form oligomers.
The Role of OX40 Ligand Interactions in the Development of the Th2 Response to the Gastrointestinal Nematode Parasite Heligmosomoides polygyrus (2003)

In these studies, we examined the effects of OX40 ligand (OX40L) deficiency on the development of Th2 cells during the Th2 immune response to the intestinal nematode parasite Heligmosomoides polygyrus. Elevations in IL-4 production and total and Ag-specific serum IgE levels were partially inhibited during both the primary and memory immune responses to H. polygyrus in OX40L(-/-) mice. The host-protective memory response was compromised in OX40L(-/-) mice, as decreased worm expulsion and increased egg production were observed compared with H. polygyrus-inoculated OX40L(+/+) mice. To further examine the nature of the IL-4 defect during priming, adoptively transferred DO11.10 T cells were analyzed in the context of the H. polygyrus response. Although Ag-specific T cell IL-4 production was reduced in the OX40L(-/-) mice following immunization with OVA peptide plus H. polygyrus, Ag-specific T cell expansion, cell cycle progression, CXCR5 expression, and migration were comparable between OX40L(+/+) and OX40L(-/-) mice inoculated with OVA and H. polygyrus. These studies suggest an important role for OX40/OX40L interactions in specifically promoting IL-4 production, as well as associated IgE elevations, in Th2 responses to H. polygyrus. However, OX40L interactions were not required for serum IgG1 elevations, increases in germinal center formation, and Ag-specific Th2 cell expansion and migration to the B cell zone.
Nerve-Highlighting Fluorescent Contrast Agents for Image-Guided Surgery (2011)

Nerve damage is the major morbidity of many surgeries, resulting in chronic pain, loss of function, or both. The sparing of nerves during surgical procedures is a vexing problem because surrounding tissue often obscures them. To date, systemically administered nerve-highlighting contrast agents that can be used for nerve-sparing image-guided surgery have not been reported. In the current study, physicochemical and optical properties of 4,4'-[(2-methoxy-1,4-phenylene)di-(1E)-2,1-ethenediyl]bis-benzenamine (BMB) and a newly synthesized, red-shifted derivative 4-[(1E)-2-[4-[(1E)-2-[4-aminophenyl]ethenyl]-3-methoxyphenyl]ethenyl]-benzonitrile (GE3082) were characterized in vitro and in vivo. Both agents crossed the blood-nerve barrier and blood-brain barrier and rendered myelinated nerves fluorescent after a single systemic injection. Although both BMB and GE3082 also exhibited significant uptake in white adipose tissue, GE3082 underwent a hypsochromic shift in adipose tissue that provided a means to eliminate the unwanted signal using hyperspectral deconvolution. Dose and kinetic studies were performed in mice to determine the optimal dose and drug-imaging interval. The results were confirmed in rat and pig, with the latter used to demonstrate, for the first time, simultaneous fluorescence imaging of blood vessels and nerves during surgery using the FLARE™ (Fluorescence-Assisted Resection and Exploration) imaging system. These results lay the foundation for the development of ideal nerve-highlighting fluorophores for image-guided surgery.
Epidermal growth factor stimulates vascular endothelial growth factor production by human malignant glioma cells: a model of glioblastoma multiforme pathophysiology. (1993)

Hypervascularity, focal necrosis, persistent cerebral edema, and rapid cellular proliferation are key histopathologic features of glioblastoma multiforme (GBM), the most common and malignant of human brain tumors. By immunoperoxidase and immunofluorescence, we definitively have demonstrated the presence of vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFr) in five out of five human glioma cell lines (U-251MG, U-105MG, D-65MG, D-54MG, and CH-235MG) and in eight human GBM tumor surgical specimens. In vitro experiments with glioma cell lines revealed a consistent and reliable relation between EGFr activation and VEGF production; namely, EGF (1-20 ng/ml) stimulation of glioma cells resulted in a 25-125% increase in secretion of bioactive VEGF. Conditioned media (CM) prepared from EGF-stimulated glioma cell lines produced significant increases in cytosolic free intracellular concentrations of Ca2+ ([Ca2+]i) in human umbilical vein endothelial cells (HUVECs). Neither EGF alone or CM from glioma cultures prepared in the absence of EGF induced [Ca2+]i increases in HUVECs. Preincubation of glioma CM with A4.6.1, a monoclonal antibody to VEGF, completely abolished VEGF-mediated [Ca2+]i transients in HUVECs. Likewise, induction by glioma-derived CM of von Willebrand factor release from HUVECs was completely blocked by A4.6.1 pretreatment. These observations provide a key link in understanding the basic cellular pathophysiology of GBM tumor angiogenesis, increased vascular permeability, and cellular proliferation. Specifically, EGF activation of EGFr expressed on glioma cells leads to enhanced secretion of VEGF by glioma cells. VEGF released by glioma cells in situ most likely accounts for pathognomonic histopathologic and clinical features of GBM tumors in patients, including striking tumor angiogenesis, increased cerebral edema and hypercoagulability manifesting as focal tumor necrosis, deep vein thrombosis, or pulmonary embolism.
Dioxaphosphorinane-Constrained Nucleic Acid Dinucleotides as Tools for Structural Tuning of Nucleic Acids (2012)

We describe a rational approach devoted to modulate the sugar-phosphate backbone geometry of nucleic acids. Constraints were generated by connecting one oxygen of the phosphate group to a carbon of the sugar moiety. The so-called dioxaphosphorinane rings were introduced at key positions along the sugar-phosphate backbone allowing the control of the six-torsion angles α to ζ defining the polymer structure. The syntheses of all the members of the D-CNA family are described, and we emphasize the effect on secondary structure stabilization of a couple of diastereoisomers of α,β-D-CNA exhibiting wether B-type canonical values or not.
Virus distribution of the attenuated MVA and NYVAC poxvirus strains in mice (2007)

Recombinant vaccinia viruses based on the attenuated NYVAC and MVA strains are promising vaccine candidates against a broad spectrum of diseases. Whilst these vectors are safe and immunogenic in animals and humans, little is known about their comparative behaviour in vivo. In this investigation, a head-to-head analysis was carried out of virus dissemination in mice inoculated by the mucosal or systemic route with replication-competent (WRluc) and attenuated recombinant (MVAluc and NYVACluc) viruses expressing the luciferase gene. Bioluminescence imaging showed that, in contrast to WRluc, the attenuated recombinants expressed the reporter gene transiently, with MVAluc expression limited to the first 24 h and NYVACluc giving a longer signal, up to 72 h post-infection, for most of the routes assayed. Moreover, luciferase levels in MVAluc-infected tissues peaked earlier than those in tissues infected by NYVACluc. These findings may be of immunological relevance when these vectors are used as recombinant vaccines.
Neutrophil CD11b Expression and Circulating Interleukin-8 as Diagnostic Markers for Early-Onset Neonatal Sepsis (2001)

Measuring neutrophil CD11b expression and circulating IL-8 provides a means to identify early-onset neonatal sepsis. The findings may be helpful in planning strategies to safely reduce the use of antimicrobials in neonates.
Sequences of mRNAs derived from genome RNA segment 7 of influenza virus: colinear and interrupted mRNAs code for overlapping proteins. (1981)

RNA segment 7 of the influenza A virus genome codes for at least two proteins, M1 and M2, which are synthesized from separate mRNA species. Sequence analysis of the M2 mRNA has shown that it contains an interrupted sequence of 689 nucleotides. The approximately 51 virus-specific nucleotides comprising the 5'-end leader sequence of the M2 mRNA are the same as those found at the 5' end of the colinear M1 mRNA. Following the leader sequence of the M2 mRNA, where is a 271-nucleotide body region that is 3' coterminal with the M1 mRNA. Another small potential mRNA (mRNA3) related to RNA segment 7 has been found. mRNA3 has a leader sequence of approximately 11 virus-specific nucleotides that are the same as the 5' end of the M1 and M2 mRNAs, followed by an interrupted sequence of 729 nucleotides, and then a body region of approximately 271 nucleotides that is the same as that of the M2 mRNA. The nucleotide sequences found at the junctions of the interrupted sequences in M2 mRNA and mRNA3 are similar to those found at the splicing points of intervening sequences in eukaryotic mRNAs. In addition, both mRNAs contain 10-15 heterogeneous nonviral nucleotides at their 5' ends that appear to be derived from cellular RNAs used for priming the transcription of viral RNAs. Because the 5'-end sequences of the M1 mRNA and the M2 mRNA are the same and share the 5'-proximal initiation codon for protein synthesis, the first nine amino acids would be the same in the M1 and M2 protein and then the sequences would diverge. The approximately 271-nucleotide body region of the M2 mRNA can be translated in the +1 reading frame, and the sequence indicates that M1 and M2 overlap by 14 amino acids. The coding potential of the mRNA3 is for only nine amino acids, and these would be identical to the COOH-terminal region of the membrane protein (M1).
Recognition of Fusobacterium nucleatum subgroups Fn-1, Fn-2 and Fn-3 by ribosomal RNA gene restriction patterns (1989)

DNA from representative strains of Fusobacterium nucleatum subgroups Fn-1, Fn-2 and Fn-3 was digested with restriction enzymes EcoRI and TaqI and the electrophoretically separated fragmetns hybridized with a 32P-16S rRNA gene probe from E. coli. The rRNA gene restriction patterns from DNA digested with either enzyme allowed the clustering of strains into the three subgroups. However, TaqI digested DNA yielded a wider distribution of taxonomically useful bands (ca 0.65 ± 14.3 kbp) and the pattern produced was characteristic of each subgroup. The present method is a simple and reliable means of identifying the three subgroups of F. nucleatum and provides a useful method for further studies of the heterogeneity of F. nucleatum.
Increasing Burden of Invasive Group B Streptococcal Disease in Nonpregnant Adults, 1990–2007 (2009)

Invasive GBS disease in nonpregnant adults represents a substantial and increasing burden, particularly among older persons, black persons, and adults with diabetes. Prevention strategies are needed.
III–nitrides: Growth, characterization, and properties (2000)

During the last few years the developments in the field of III–nitrides have been spectacular. High quality epitaxial layers can now be grown by MOVPE. Recently good quality epilayers have also been grown by MBE. Considerable work has been done on dislocations, strain, and critical thickness of GaN grown on different substrates. Splitting of valence band by crystal field and by spin-orbit interaction has been calculated and measured. The measured values agree with the calculated values. Effects of strain on the splitting of the valence band and on the optical properties have been studied in detail. Values of band offsets at the heterointerface between several pairs of different nitrides have been determined. Extensive work has been done on the optical and electrical properties. Near band-edge spectra have been measured over a wide range of temperatures. Free and bound exciton peaks have been resolved. Valence band structure has been determined using the PL spectra and compared with the theoretically calculated spectra. Strain and its effect on the optical properties of the III–nitride layers have been studied both theoretically and experimentally. Both n and p conductivity have been achieved. InGaN quantum wells with GaN and AlGaN barriers and cladding layers have been investigated. PL of the quantum wells is affected by confinement effects, band filling, quantum confined Stark effect, and strain. This work has led to the fabrication of advanced optoelectronic and electronic devices. The light-emitting decodes emitting in the blue and green regions of the spectrum have been commercialized. The work leading to these developments is reviewed in this article. The device processing methods and actual devices are not discussed.