gebhart/patrepeval huggingface dataset:
Differential mitogenic responses of human macrovascular and microvascular endothelial cells to cytokines underline their phenotypic heterogeneity (2001)

A variety of growth factors promote the complex multistep process of angiogenesis. The mitogenic activity of vascular endothelial growth factors (VEGFs) and placental growth factors (PlGFs), known as cytokines acting predominantly on endothelial cells, was tested on human umbilical vein endothelial cells (HUVEC) and microvascular endothelial cells (MIEC) and compared with the potency of the universally acting basic fibroblast growth factor (FGF-2). The cells were seeded at different cell numbers and incubated with various doses of growth factors for a period of 24-72 h in culture medium +/- serum. Proliferation was determined by measuring the optical density after staining the cells with the tetrazolium salt WST-1. VEGF121 and VEGF165 increased the number of HUVEC and MIEC at low and high seeding densities various doses and incubation times. The efficiency of FGF-2 was less pronounced at high seeding densities of the cells under serum-free conditions. PlGF-1 and PlGF-2 stimulated mitogenesis on HUVEC only at low cell numbers and after a short incubation time by 125 +/- 3% and 102 +/- 5% (P < 0.001), respectively. Longer incubation times with the lower seeding density in the absence of FCS did not induce a significant stimulatory effect of the PlGFs. MIEC responded stronger to all growth factors. In particular under serum free conditions, PlGF-1 and PlGF-2 effectively stimulated cell proliferation by 247 +/- 54% (P < 0.01) and 288 +/- 40% (P < 0.05) at low cell numbers, and by 81 +/- 13% (P < 0.05) and 49 +/- 13% (P < 0.01), respectively, at high cell numbers. The addition of fetal calf serum caused a reduced proliferative response of all growth factors on both cell types related to the controls. In conclusion, MIEC and HUVEC differ in their proliferative response to VEGFs, PlGFs and FGF-2.
Conformationally restricted analogs of somatostatin with high mu-opiate receptor specificity. (1985)

A series of cyclic, conformationally restricted analogs of somatostatin have been prepared and tested for their ability to inhibit the binding of [3H]naloxone and [D-Ala2, D-Leu5] [3H]enkephalin to rat brain membranes. The most potent analog, D-Phe-Cys-Tyr-D-Trp-Lys-Thr-Pen-Thr-NH2 where Pen is penicillamine in [D-Phe5, Cys6, Tyr7, D-Trp8, Pen11]somatostatin-(5-12)-octapeptide amide, exhibited high affinity for mu-opiate receptors (IC50 value of [3H]naloxone = 3.5 nM), being 7800 times more potent than somatostatin. The cyclic octapeptide also displayed high mu-opiate receptor selectivity with an IC50 [( D-Ala2,D-Leu5]enkephalin)/IC50 (naloxone) ratio of 271. The high affinity and selectivity of the somatostatin analog for mu-opiate receptors may be of use in examining the physiological role(s) of the mu-opiate receptor.
Efficacy of a genotype 2 Newcastle disease vaccine (Avinew®) against challenge with highly virulent genotypes 5d and 3d (2009)

Since 2002, following its introduction, the lineage 5d Newcastle disease virus (so-called Goose paramyxovirus - GPMV) strain has caused numerous disease outbreaks among commercial and backyard poultry in South Africa, raising questions about the ability of commercially available Newcastle disease vaccines to fully protect poultry against the strain. This study aimed to determine whether there are differences in the level of protection offered by Avinew Newcastle disease vaccine against GPMV virus as compared with a 3d Newcastle disease virus isolated in South Africa in 1993 (Rainbow challenge virus - RCV) strain. Six groups of 10-day-old, specific pathogen-free chickens were vaccinated with doses of 10(3.0), 10(4.5) and 10(6.0) EID50 of Avinew vaccine and challenged at 4 weeks of age intramuscularly at a dose of 10(5.3) EID50/0.2 ml/bird of GPMV and RCV. No statistically significant difference could be found in the protection offered by Avinew vaccine against GPMV as compared to RCV challenge. The protection offered against the ND challenge was found to be dose dependent. At the recommended field dose of 10(6.0) EID50 the vaccine gave 100% protection from mortality against both the challenge viruses, but not against infection and replication of the viruses, as gross lesions were evident even in apparently healthy birds that survived the challenge. The protective dose (PD90) of the Avinew vaccine against GPMV challenge was calculated at 10(4.38) and against that of RCV at 10(4.43).
Development of primary and secondary immune responses to mouse monoclonal antibodies used in the diagnosis and therapy of malignant neoplasms. (1986)

Human anti-mouse immunoglobulin immune responses were studied in ten patients, eight with ovarian cancer and two with grade IV gliomas, diagnosed and treated with radiolabeled (123I, 131I) murine monoclonal antibodies. It was found that serum from these patients before treatment and from 18 control healthy individuals contained detectable antibodies to antigenic determinants on the Fc but not the F(ab')2 portion of mouse immunoglobulin. No change in this reactivity occurred after the initial (imaging) dose of monoclonal antibodies. However, repeated administration of mouse immunoglobulins for therapy resulted in an elevated immune response directed against determinants on both Fc and F(ab')2 regions of mouse immunoglobulin. This response contained increased levels of immunoglobulin M as well as immunoglobulin G and showed a marked prozone effect in our enzyme linked immunosorbent assay system. None of the immunized patients developed a detectable antiidiotypic response.
Complete Genome Sequence of Lactobacillus buchneri NRRL B-30929, a Novel Strain from a Commercial Ethanol Plant (2011)

Lactobacillus buchneri strain NRRL B-30929 was a contaminant obtained from a commercial ethanol fermentation. This facultative anaerobe is unique because of its rapid growth on xylose and simultaneous fermentation of xylose and glucose. The strain utilizes a broad range of carbohydrate substrates and possesses a high tolerance to ethanol and other stresses, making it an attractive candidate for bioconversion of biomass substrates to various bioproducts. The genome sequence of NRRL B-30929 will provide insight into the unique properties of this lactic acid bacterium.
Enhanced vector space models for content-based recommender systems (2010)

The use of Vector Space Models (VSM) in the area of Information Retrieval is an established practice within the scientific community. The reason is twofold: first, its very clean and solid formalism allows us to represent objects in a vector space and to perform calculations on them. On the other hand, as proved by many contributions, its simplicity does not hurt the effectiveness of the model. Although Information Retrieval and Information Filtering undoubtedly represent two related research areas, the use of VSM in Information Filtering is much less analzyed.
Muscle development in mdx mutant mice (1984)

Mechanical and contractile properties of tibialis anterior (TA) muscles from X-linked muscular dystrophic (mdx) mutant mice at different stages of development are compared to those of muscles from normal control animals. There is no difference between the tension output, speeds of contraction and relaxation, and weight of TA muscles from mutant adults and normal control animals. However, it is found that in 3-4-week-old mutant animals, tension output and muscle weight are very much reduced, and half relaxation time is prolonged. Thus, during this stage of development, muscles from mdx mice do not function properly. Histological examination of these muscles provides further evidence that, in these animals, rapid muscle destruction occurs at a particular time of development and that it is followed by complete recovery. This new mutant therefore presents an interesting case of muscle destruction and rapid regeneration. However, it is not an adequate model for Duchenne muscular dystrophy.
Targeting Cytomegalovirus-Infected Cells Using T Cells Armed with Anti-CD3 × Anti-CMV Bispecific Antibody (2012)

Human cytomegalovirus (CMV) reactivation and infection can lead to poor outcomes after allogeneic stem cell transplantation. We hypothesized that anti-CD3 activated T cells (ATCs) armed with chemically heteroconjugated anti-CD3 × polyclonal anti-CMV bispecific antibody (CMVBi) will target and eliminate CMV-infected cells. Arming doses of CMVBi as low as 0.01 ng/10(6) ATCs was able to mediate specific cytotoxicity (SC) directed at CMV-infected target cells significant above unarmed ATCs at mutiplicities of infection (MOI) between 0.01 and 1. At effector-to-target ratios (E:T) of 25:1, 12.5:1, 6.25:1, and 3.125:1, armed ATCs significantly enhanced killing of CMV-infected targets compared with unarmed ATCs. At an MOI of 1.0, the mean % SC directed at CMV-infected targets cells for CMVBi-armed ATCs at E:T of 3.12, 6.25, and 12.5 were 79%, 81%, and 82%, respectively; whereas the mean % SC for unarmed ATCs at the same E:T were all <20%. ATCs, Cytogam(®), or CMVBi alone did not lyse uninfected or CMV-infected targets. Co-cultures of CMVBi-armed ATCs with CMV-infected targets induced cytokine and chemokine release from armed ATCs. This nonmajor histocompatibility complex restricted strategy for targeting CMV could be used to prevent or treat CMV infections after allogeneic stem cell transplantation or organ transplantation.
Tenascin‐R and C in multiple sclerosis lesions: relevance to extracellular matrix remodelling (1999)

In the present study the distribution of the inhibitory extracellular molecules tenascin‐R (TN‐R) and tenascin‐ C (TN‐C) was examined by immunocytochemistry during evolution of the multiple sclerosis (MS) lesion, in which astrogliosis is a prominent feature. Sections were cut from five control cases and from 22 blocks containing lesions representing different pathological stages in 18 cases of secondary progressive MS. Widespread expression of TN‐R was found in the normal human central nervous system (CNS), while that of TN‐C was in general restricted to white matter. In acute MS plaques however, there was a similar striking loss of both TN‐R and TN‐C up to the edge of the lesion, where the macrophage density is greatest, extending into the apparently normal white matter. In subacute lesions a TN‐C and/or TN‐R‐immunopositive reactive astrocyte subpopulation was prominent, reflecting synthesis of extracellular matrix molecules. Both tenascins were expressed throughout chronic MS plaques at levels similar to those seen in adjacent white matter. The loss of TN‐R and TN‐C in acute plaques is indicative of enzyme‐mediated breakdown of the matrix which may be a marker of blood–brain barrier breakdown and leucocyte extravasation. Subsequent production of tenascins by reactive astrocytes may result in glial scar formation impeding remyelination and axonal repair in MS lesions.
Engineering T cells for cancer: our synthetic future (2013)

Video podcast available Go to www.immunologicalreviews.com to watch an interview with Guest Editor Dr Carl June.
Contractile properties of skeletal muscles from young, adult and aged mice. (1988)

1. Comparisons were made in vitro at 25 degrees C among soleus and extensor digitorum longus (EDL) muscles from young (2-3 months), adult (9-10 months), and aged (26-27 months) male mice. We tested the hypotheses that, compared with soleus and EDL muscles of young and adult mice, those from aged mice develop decreased maximum tetanic force (P0, mN) and specific P0 (N/cm2), and that no significant differences occur for contraction time, half-relaxation time, or force-velocity relationship. 2. For the aged mice, the P0 of the soleus muscles and EDL muscles were 78 and 73% respectively of the values for adult mice. The specific P0 of EDL muscles of aged mice was 78% of the value of 23 N/cm2 obtained for young and adult mice. For soleus muscles, the specific P0 of 21 N/cm2 did not change with age. 3. Compared to values for young and adult mice, the contraction and half-relaxation times of soleus muscles from aged mice were increased, but the overall force-velocity relationships of soleus and EDL muscles did not change. The pooled values for the maximum velocity of unloaded shortening extrapolated from the force-velocity relationship of soleus and EDL muscles were 4.6 and 10.1 fibre lengths/s, respectively. 4. The decrease in the specific P0 of the EDL muscle with ageing must result from either a decrease in the number of cross-bridges in the driving stroke or a decrease in the force developed by each cross-bridge.
Antigenic and molecular analyses of different Chlamydia pneumoniae strains (1997)

Chlamydia pneumoniae is an important human respiratory pathogen. Classification of C. pneumoniae isolates into distinguishable serovars or genotypes has not yet been reported. To determine whether antigenic or molecular variants among C. pneumoniae isolates exist, six strains were studied via immunoblot analysis and DNA sequence determination of the entire major outer membrane protein (MOMP) gene omp1. The strains included four prototype strains and two clinical isolates from our laboratory. Immunoblot analysis of sera from patients infected with C. pneumoniae revealed antigenic differences between the C. pneumoniae strains. Strong reactivity of one serum sample with a 65-kDa protein in two C. pneumoniae strains which was not observed with the other strains was the most prominent finding. All sera reacted with the 40-kDa MOMP. Comparison of the omp1 DNA sequences revealed that the omp1 genes of all strains were identical and were 100% identical to the sequence of the omp1 gene of C. pneumoniae AR-39. The results of this study demonstrate that unlike C. trachomatis, the omp1 gene is conserved in C. pneumoniae. Furthermore, it was shown that C. pneumoniae strains are antigenically different. This finding indicates that more than one serovar of C. pneumoniae exist.
Structural analysis of the complex of Keap1 with a prothymosin α peptide (2008)

The Nrf2 transcription factor, which plays important roles in oxidative and xenobiotic stress, is negatively regulated by the cytoplasmic repressor Keap1. The beta-propeller/Kelch domain of Keap1, which is formed by the double-glycine repeat and C-terminal region domains (Keap1-DC), interacts directly with the Neh2 domain of Nrf2. The nuclear oncoprotein prothymosin alpha (ProTalpha) also interacts directly with Keap1 and may play a role in the dissociation of the Keap1-Nrf2 complex. The structure of Keap1-DC complexed with a ProTalpha peptide (amino acids 39-54) has been determined at 1.9 A resolution. The Keap1-bound ProTalpha peptide possesses a hairpin conformation and binds to the Keap1 protein at the bottom region of the beta-propeller domain. Complex formation occurs as a consequence of their complementary electrostatic interactions. A comparison of the present structure with recently reported Keap1-DC complex structures revealed that the DLG and ETGE motifs of the Neh2 domain of Nrf2 and the ProTalpha peptide bind to Keap1 in a similar manner but with different binding potencies.
Evidence for a Granule Targeting Sequence within Platelet Factor 4 (2005)

Platelets achieve bleeding arrest at sites of vascular injury via secretion of secretory proteins from their storage granules, termed alpha-granules. We have recently analyzed granule targeting of platelet factor 4 (PF4), a secretory alpha-granule chemokine, and demonstrated that PF4 alpha-granule storage relied upon determinants within PF4 mature sequence. To define these determinants, PF4 mutants fused to the fluorescent reporter protein green fluorescent protein were generated by progressive deletions and site-directed mutagenesis. They were then transfected in AtT20 cells and assessed for granule targeting by colocalization with ACTH-containing granules, using laser scanning confocal microscopy. This strategy identified the amino acid 41-50 (LIATLKNGRK) sequence as most critical for PF4 granule targeting and/or storage; its deletion from PF4 induced a marked decrease in granule storage (from 81 +/- 2% to 17 +/- 3%, p < or = 0.0001). Ala-scanning mutagenesis of LIATLKNGRK narrowed down the targeting motif to LKNG. A direct role for LKNG in alpha-granule targeting was confirmed in the thrombopoietin-induced human megakaryocytic Dami cells, in which the LKNG-green fluorescent protein chimera exhibited an 82.5 +/- 1.8% colocalization with the alpha-granule proteins von Willebrand factor and P-selectin. LKNG is poorly conserved within the chemokine family. However three-dimensional alignments of the human alpha-granule chemokines Nap-2 (neutrophil-activating peptide) and RANTES (Regulated upon Activation Normal T Cell Expressed and Secreted) with PF4 revealed that LKNG, a surface-exposed hydrophilic turn/loop, matched Nap-2 (LKDG) and RANTES (TRKN) peptides with similar features. Moreover Nap-2 and RANTES peptides exhibited the same alpha-granule targeting efficiency than LKNG. We therefore postulate that the three-dimensional and physicochemical characteristics of PF4 LKNG are of general relevance to alpha-granule targeting of chemokines and possibly of other alpha-granule proteins.
Regulated Ire1-dependent decay of messenger RNAs in mammalian cells (2009)

Maintenance of endoplasmic reticulum (ER) function is achieved in part through Ire1 (inositol-requiring enzyme 1), a transmembrane protein activated by protein misfolding in the ER. The cytoplasmic nuclease domain of Ire1 cleaves the messenger RNA (mRNA) encoding XBP-1 (X-box-binding protein 1), enabling splicing and production of this active transcription factor. We recently showed that Ire1 activation independently induces the rapid turnover of mRNAs encoding membrane and secreted proteins in Drosophila melanogaster cells through a pathway we call regulated Ire1-dependent decay (RIDD). In this study, we show that mouse fibroblasts expressing wild-type Ire1 but not an Ire1 variant lacking nuclease activity also degrade mRNAs in response to ER stress. Using a second variant of Ire1 that is activated by a small adenosine triphosphate analogue, we show that although XBP-1 splicing can be artificially induced in the absence of ER stress, RIDD appears to require both Ire1 activity and ER stress. Our data suggest that cells use a multitiered mechanism by which different conditions in the ER lead to distinct outputs from Ire1.
BRIDGE SYSTEMS MADE OF FRP COMPONENTS (1990)

High maintenance costs associated with the corrosion of steel in bridges have led researchers and contractors to investigate new unconventional materials such as fiber reinforced plastics (FRP) in lieu of steel. This paper discusses some innovative and efficient systems made of FRP that are built and being tested under static loads and their performance being experimentally monitored and theoretically investigated.
Psychiatric Illness in the Families of Hyperactive Children (1972)

A systematic psychiatric examination of the parents of 50 hyperactive children and 50 matched control children was carried out. Increased prevalence rates for alcoholism, sociopathy, and hysteria were found in the parents of the hyperactive children. Ten percent of the parents of the hyperactive children were thought to have been hyperactive children themselves, and, of this 10%, all were psychiatrically ill with alcoholism, sociopathy, or hysteria. The data support the notion that the hyperactive child syndrome is passed from generation to generation and may be a precursor of certain adult psychiatric illnesses.
Structure of C-phycocyanin fromSpirulina platensisat 2.2 Å resolution: a novel monoclinic crystal form for phycobiliproteins in phycobilisomes (2001)

The crystal structure of C-phycocyanin from the cyanobacterium S. platensis has been determined at 2.2 A resolution. The crystals belong to the monoclinic crystal form, which has not been previously reported for phycobiliprotein structures. The structure was solved using the molecular-replacement method with a final R value of 18.9% (R(free) = 23.7%) after model building and refinement. In the crystals used for the study, the C-phycocyanin hexamers formed by face-to-face association of two trimers are arranged in layers rather than in columns. Three different kinds of packing between adjacent hexamers in the layer were compared. The tight packing of two adjacent hexamers formed by four trimers in the asymmetric unit brings beta155 PCB chromophores close together, so it is possible that lateral energy transfer takes place through the beta155-beta155 route.
Effect of Moisture on the Stability of Solid Dosage Forms (1988)

It has long been known that moisture affects the stability of some drug substances. Aspirin is a classical example. Aspirin is not wet granulated. Even though the water is driven off in a wet granulation, there is still sufficient moisture stress in the process to induce excessive decomposition on subsequent storage. Dry methods (slugging, roller compaction) are therefore resorted to. In other instances, the moisture sensitivity of a drug may warrant using a hard shall capsule approach. This presumes that the drug substance is not particularly hygroscopic, since, otherwise, the capsule shell will provide an unwanted source of moisture.
Genetic requirement for Ras in the transformation of fibroblasts and hematopoietic cells by the Bcr-Abl oncogene. (1995)

To determine the functional importance of Ras in transformation by Abl oncogenes, we used a genetic approach to measure the effect of impaired Ras activity on the ability of Bcr-Abl or v-Abl to transform cells. Expression of the catalytic domain of the GTPase activating protein for Ras (Gap C terminus) impaired soft agar colony formation by fibroblasts expressing v-Abl or Bcr-Abl by 70-80%. To test Ras function in a model that more closely resembles clinical diseases involving Bcr-Abl, double gene retroviruses expressing Bcr-Abl paired with the Gap C terminus or dominant negative Ras were introduced into naive mouse bone marrow cells. Transformation by Bcr-Abl was completely blocked in both situations. Coexpression of normal c-H-Ras accelerated the transforming activity of Bcr-Abl. These findings show that Ras activation is essential for the leukemogenic activity of Abl oncogenes in two distinct model systems. The results genetically define a connection between the Bcr-Abl cytoplasmic tyrosine kinase and Ras and add to the accumulating evidence that deregulation of Ras is a central event in the genesis of a number of molecularly distinct forms of human myeloid leukemia.
Arabidopsis Tic40 Expression in Tobacco Chloroplasts Results in Massive Proliferation of the Inner Envelope Membrane and Upregulation of Associated Proteins (2008)

The chloroplast inner envelope membrane (IM) plays essential roles in lipid synthesis, metabolite transport, and cellular signaling in plants. We have targeted a model nucleus-encoded IM protein from Arabidopsis thaliana, pre-Tic40-His, by relocating its expression from the nucleus to the chloroplast genome. Pre-Tic40-His was properly targeted, processed, and inserted. It attained correct topology and was folded and assembled into a TIC complex, where it accounted for up to 15% of the total chloroplast protein. These results confirm the existence of a novel pathway for protein targeting to the IM. Tic40-His overexpression resulted in a massive proliferation of the IM (up to 19 layers in electron micrographs) without significant effects on plant growth or reproduction. Consistent with IM proliferation, the expression levels of other endogenous IM proteins (IEP37, PPT, Tic110) were significantly (10-fold) upregulated but those of outer envelope membrane (Toc159), stromal (hsp93, cpn60), or thylakoid (LHCP, OE23) proteins were not increased, suggesting retrograde signal transduction between chloroplast and nuclear genomes to increase lipid and protein components for accommodation of increased accumulation of Tic40. This study opens the door for understanding the regulation of membrane biogenesis within the organelle and the utilization of transgenic chloroplasts as bioreactors for hyperaccumulation of membrane proteins for biotechnological applications.