gebhart/patrepeval huggingface dataset:
Pathlength reduction features in the PA-RISC architecture (2003)

A description is given of representative pathlength reduction features of PA-RISC (reduced instruction set computer) instructions in memory accessing, functional operations, and instruction sequencing. To illustrate the multi-op instructions in PA-RISC, comparison is made with the MIPS instruction set, rather than with some hypothetical single-op RISC instructions. It is noted that, while other RISC architectures strive to enable short cycle times and single cycle instruction execution, PA-RISC also supports pathlength reduction, without impacting either the cycle time or the CPI. Frequent operations are combined into a single multi-op instruction. Subword data are also operated on in parallel, making full use of the datapath width. Such instruction level parallelism gives PA-RISC some of the advantages of a very simple VLIW (very long instruction word) architecture (with short 32-b instructions), in addition to the inherent advantages of a streamlined RISC architecture.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Temporal expression and cellular localization of a gastrin-releasing peptide-related gene in ovine uterus during the oestrous cycle and pregnancy (1998)

Synthesis of both mRNA and peptide for gastrin-releasing peptide (GRP) has been demonstrated in the pregnant endometrium of sheep and women. However, it is not known whether GRP is synthesized in the sheep uterus during the oestrous cycle. Furthermore the cellular site of GRP mRNA synthesis in the uterus has not been determined. Therefore we examined the synthesis of GRP and determined the cellular location of GRP peptide and mRNA in sheep uterus taken at different times during the oestrous cycle (duration 17 days) and pregnancy (duration 145 days). Northern blot analysis of RNA isolated from ovine endometrium revealed low or no GRP mRNA at days 4, 10, 12 and 14 of the oestrous cycle and a 24-fold rise in GRP mRNA (normalized to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA) between days 14 and 16. A similar pattern was observed during early pregnancy, with a 12-fold rise in GRP mRNA:GAPDH mRNA between days 17 and 20 of pregnancy. Levels of GRP peptide were determined by RIA and found to be low in endometrium isolated at days 4, 10, 12 and 14 of the oestrous cycle (1.0-1.6 pmol/g) and 4 to 5-fold higher at day 16. In situ hybridization localized GRP synthesis to the epithelial cells of the uterine glands at day 16 of the oestrous cycle and at days 17, 20, 40 and 50 of pregnancy. At day 140 of pregnancy diffuse hybridization to cells of the myometrium was also observed. Immunohistochemistry localized GRP peptide to the apical cytoplasm of uterine glandular epithelial cells at day 16 of the oestrous cycle. For samples obtained at day 20 of pregnancy, the area surrounding the glands also showed moderately strong staining. Further staining in the glandular lumen and the stromal tissue surrounding the glands was apparent at day 140 of pregnancy. No GRP immunoreactivity could be detected in the peripheral plasma during the oestrous cycle or the first 20 days of pregnancy. Sizing chromatography of GRP immunoreactivity extracted from endometrial tissue taken at day 10 of the oestrous cycle revealed two peaks that co-eluted with GRP(1-27) and GRP(18-27). However, during luteolysis and oestrus the major peak of GRP immunoreactivity extracted from endometrial tissue was larger than GRP(1-27) and similar to that seen previously in the gravid ovine endometrium. These studies demonstrate that a peptide similar to, but larger than, GRP is a major product of the glandular epithelium of the ovine uterus during the luteal regression phase of the oestrous cycle and post-blastocyst implantation in pregnancy and provide further evidence that GRP-related peptides have important regulatory roles in uterine function.
Increasing Survival of Ischemic Tissue by Targeting CD47 (2007)

Thrombospondin-1 (TSP1) limits the angiogenic and vasodilator activities of NO. This activity of TSP1 can be beneficial in some disease states, but endogenous TSP1 limits recovery of tissue perfusion following fixed ischemic injury in dorsal skin flaps in mice. Using mice lacking the TSP1 receptors CD36 or CD47, we now show that CD47 is the necessary receptor for limiting NO-mediated vascular smooth muscle relaxation and tissue survival following ischemic injury in skin flaps and hindlimbs. We further show that blocking CD47 or TSP1 using monoclonal antibodies and decreasing CD47 expression using an antisense morpholino oligonucleotide are effective therapeutic approaches to dramatically increase survival of soft tissue subjected to fixed ischemia. These treatments facilitate rapid vascular remodeling to restore tissue perfusion and increase skin and muscle viability. Thus, limiting CD47-dependent antagonism of NO-mediated vasodilation and vascular remodeling is a promising therapeutic modality to preserve tissues subject to ischemic stress.
Depth of Presence in Virtual Environments (1994)

This paper describes a study to assess the influence of a variety of factors on reported level of presence in immersive virtual environments. It introduces the idea of “stacking depth,” that is, where a participant can simulate the process of entering the virtual environment while already in such an environment, which can be repeated to several levels of depth. An experimental study including 24 subjects was carried out. Half of the subjects were transported between environments by using virtual head-mounted displays, and the other half by going through doors. Three other binary factors were whether or not gravity operated, whether or not the subject experienced a virtual precipice, and whether or not the subject was followed around by a virtual actor. Visual, auditory, and kinesthetic representation systems and egocentric/exocentric perceptual positions were assessed by a preexperiment questionnaire. Presence was assessed by the subjects as their sense of “being there,” the extent to which they experienced the virtual environments as more the presenting reality than the real world in which the experiment was taking place, and the extent to which the subject experienced the virtual environments as places visited rather than images seen. A logistic regression analysis revealed that subjective reporting of presence was significantly positively associated with visual and kinesthetic representation systems, and negatively with the auditory system. This was not surprising since the virtual reality system used was primarily visual. The analysis also showed a significant and positive association with stacking level depth for those who were transported between environments by using the virtual HMD, and a negative association for those who were transported through doors. Finally, four of the subjects moved their real left arm to match movement of the left arm of the virtual body displayed by the system. These four scored significantly higher on the kinesthetic representation system than the remainder of the subjects.
Eradication of small intestinal bacterial overgrowth and oro-cecal transit in diabetics. (2003)

Our results show that bacterial overgrowth may contribute to the delay of intestinal transit as confirmed by its significant improvement after eradication therapy.
Activation of NADPH oxidase and extracellular superoxide production in seizure‐induced hippocampal damage (2004)

We sought to determine whether the extracellular compartment contributed to seizure-induced superoxide (O2*-) production and to determine the role of the NADPH oxidase complex as a source of this O2*- production. The translocation of NADPH oxidase subunits (p47phox, p67phox and rac1) was assessed by immunoblot analysis and NADPH-driven O2*- production was measured using 2-(4-hydroxybenzyl)-6-(4-hydroxyphenyl)-8-benzyl-3,7-dihydroimidazo [1,2-alpha] pyrazin-3-one-enhanced chemiluminescence. Kainate-induced status epilepticus resulted in a time-dependent translocation of NADPH oxidase subunits (p47phox, p67phox and rac-1) from hippocampal cytosol to membrane fractions. Hippocampal membrane fractions from kainate-injected rats showed increased NADPH-driven and diphenylene iodonium-sensitive O2*- production in comparison to vehicle-treated rats. The time-course of kainate-induced NADPH oxidase activation coincided with microglial activation in the rat hippocampus. Finally, kainate-induced neuronal damage and membrane oxygen consumption were inhibited in mice overexpressing extracellular superoxide dismutase. These results suggest that seizure activity activates the membrane NADPH oxidase complex resulting in increased formation of O2*-.
Small-molecule modulators of Hedgehog signaling: identification and characterization of Smoothened agonists and antagonists (2002)

Smo can have its activity modulated directly by synthetic small molecules. These studies raise the possibility that Hh signaling may be regulated by endogenous small molecules in vivo and provide potent compounds with which to test the therapeutic value of activating the Hh-signaling pathway in the treatment of traumatic and chronic degenerative conditions.
Inhibition of protein kinase C, (sodium plus potassium)-activated adenosine triphosphatase, and sodium pump by synthetic phospholipid analogues. (1990)

The effects and modes of action of certain antineoplastic phospholipid analogues (racemic 1-O-octadecyl-2-O-methyl glycero-3-phosphocholine, BM 41.440, JH-1, CV-3988, and HePC) on (sodium plus potassium)-activated adenosine triphosphatase (Na,K-ATPase) and sodium pump activities were investigated. Inhibition of Na,K-ATPase in purified rat brain synaptosomal membranes by these lipids, in contrast to ouabain, was subject to membrane surface dilution and unaffected by whether the reaction was started with KCl, NaCl, or ATP. Kinetic analysis indicated that the analogues, again dissimilar to ouabain, were likely to interact directly or indirectly with sodium-binding sites of Na,K-ATPase located at the intracellular surface of the plasma membrane, a conclusion also supported by studies using the inside-out vesicles of human erythrocyte membranes. The studies also showed that ouabain (but not the lipids) increased the affinity constant of Na,K-ATPase for K+, whereas the lipids (but not ouabain) increased that for Na+. The lipids also inhibited 86Rb uptake by intact human leukemia HL60 cells at potencies quite comparable to those seen for inhibition of purified protein kinase C or Na,K-ATPase. It is suggested that Na,K-ATPase (sodium pump) might represent a hitherto unrecognized site of action for the lipid analogues, and that the antineoplastic effects of the agents might be due to, in part, inhibition of both protein kinase C and Na,K-ATPase and perhaps other membrane-associated enzymes.
Polymer Size and Concentration Effects on the Size of Gold Nanoparticles Capped by Polymeric Thiols (2004)

Gold nanoparticles stabilized by thiol-terminated poly(ethylene glycol) monomethyl ethers with molecular weights ranging from 350 to 2000 have been prepared at thiol-to-gold molar ratios ranging from 3:1 to 1:8. Particle size distributions have been constructed for these particles from transmission electron microscopy images of hundreds of particles for each variation in synthetic conditions. The mean diameters of these particles range from 1.5 to 3.2 nm, with a slight increase in particle size with decreasing thiol content; these particles are smaller than those prepared using alkanethiols at similar thiol-to-gold ratios. Particles prepared under thiol-poor conditions exhibit much greater polydispersity than those prepared under thiol-rich conditions and include numerically rare large-particle outliers that contain much of the gold in the sample. The mean diameters of the gold nanoparticles decrease slightly with increasing polymer weight, especially under thiol-rich conditions. A simple model is developed to predict the trends in nanoparticle diameter that would result were the polymer's steric bulk protecting the nanoparticles from additional growth the principal factor controlling nanoparticle size in this system. This model predicts a much stronger dependence on thiol concentration than has been experimentally observed and a dependence on polymer molecular weight opposite to that experimentally observed. This suggests that the polymers' steric bulk is not the principal reason that these polymers yield smaller nanoparticles than alkanethiols at similar thiol-to-gold ratios. It is instead proposed that polar polymers may yield small nanoparticles by accelerating particle nucleation via coordination between functional groups in the polymer and atomic gold.
A new class of antivirals: antisense oligonucleotides combined with a hydrophobic substituent effectively inhibit influenza virus reproduction and synthesis of virus‐specific proteins in MDCK cells (1990)

To enhance the penetration of oligonucleotide ('oligo') into cells, the oligo was combined with the hydrophobic undecyl residue. Using the 'DNA-synthesator', we synthesized oligo, complementary to the loop-forming site of the RNA, encoding polymerase 3 of the influenza virus (type A), and combined it with the undecyl residue added to the 5' terminal phosphate group. It was found that the modified oligo effectively suppresses the influenza A/PR8/34 (H1N1) virus reproduction and inhibits the synthesis of virus-specific proteins in MDCK cells. Under the same conditions, the non-modified antisense oligo and modified nonsense oligo did not affect the virus development.
In Vivo Gene Transfer To Salivary Glands (1999)

Considerable progress has occurred recently in transferring foreign genes to different tissues in vivo. Gene transfer to salivary glands has mirrored progress in the general field. Most salivary studies have utilized replication-deficient, recombinant adenoviruses as gene transfer vectors in rat models. These vectors are able to transduce almost all rat salivary epithelial cell types and lead to relatively high levels of transgene expression. Additionally, successful, though quite modest, gene transfer to salivary glands has been achieved with retroviral vectors and with different plasmid conjugates (liposomes; nonrecombinant adenoviruses). Salivary gland gene transfer has been used for two potential clinical goals: (i) the repair of hypofunctional gland parenchyma, and (ii) the production of secretory transgene products for either systemic or upper gastrointestinal tract pharmaceutical use. Gene transfer can also be used as a powerful tool to alter cellular phenotype in vivo and probe cell biological questions. The current spectrum of studies demonstrates the potential broad and profound influence gene transfer can make on salivary physiology and pathophysiology.
Phase II trial of sorafenib plus interferon-alpha 2b (IFN-α2b) as first- or second-line therapy in patients (pts) with metastatic renal cell cancer (RCC) (2006)

4538 Background: Sorafenib is a VEGFR/PDGFR-β/Raf inhibitor that improves PFS in metastatic RCC with a RR of 2%. IFN-α improves OS in RCC with a RR of ≈10%. Methods: Based on the activity of sorafenib and IFN-α in RCC, a phase II combination trial was undertaken. Pts with RCC of any histology were eligible if they had received ≤1 prior treatment (excluding IFN-α). Treatment consisted of 8-wk cycles of sorafenib 400 mg po bid + IFN-α2b 10 MU sc tiw. Cycles were repeated until disease progression with 2-wk breaks between cycles permitted. This single-stage trial has a planned n = 40; primary objectives are RR and tolerability. Results: From November 2004-December 2005, 31 pts were enrolled. Pt characteristics included: median age 47, M/F: 23/8, PS 0/1: 25/6, clear cell/papillary: 24/3, no prior Rx/prior high-dose IL-2: 17/12, prior Nx: 26. Toxicities (n = 27) were mostly grade 1/2: fatigue (78%), anorexia (74%), rash (70%; 11% grade 3), diarrhea (67%), weight loss (63%), hypophosphatemia (59%; 33% grade 3), nausea (56%), neutropenia (48%; 19% grade 3), alopecia (44%), and oral mucositis (26%). Dose reductions of both agents for toxicity occurred in 58% of pts. The most common reasons for dose reduction were grade 3 rash or neutropenia and grade 2 fatigue or anorexia. Among 24 pts evaluable for response, the RR by RECIST criteria was 42% (38% PR, 4% CR). An additional 46% had stable disease for at least 1 cycle, including 8% with ≥20% regression. Responses were seen in lungs, pleura, kidney, liver, pancreas, and nodes. Three of the 10 responses occurred in patients who had failed prior high-dose IL-2. Conclusions: Sorafenib + IFN-α2b is a well-tolerated outpatient regimen with substantial antitumor activity in both untreated and IL-2-resistant metastatic RCC. Further investigation of this regimen in RCC is warranted. [Table: see text]
Can patients with epilepsy predict their seizures? (2007)

A significant subgroup of our adult patients with epilepsy were able to self-predict their seizures, which may yield novel therapeutic opportunities.
Protein Identification and Characterization by Mass Spectrometry (1998)

This overview describes some of the new technologies that can be employed to facilitate rapid identification and characterization of proteins, including the use of correlative approaches for protein identification, rapid posttranslational modification analysis, identification of components in complex mixtures, and direct mass analysis of gel-separated proteins. The mass spectrometric methods referred to in this overview include matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) and electrospray ionization mass spectrometry (ESI-MS).
Commonly used mesenchymal stem cell markers and tracking labels: Limitations and challenges. (2013)

Early observations that cultured mesenchymal stem cells (MSCs) could be induced to exhibit certain characteristics of osteocytes and chondrocytes led to the proposal that they could be transplanted for tissue repair through cellular differentiation. Therefore, many subsequent preclinical studies with transplanted MSCs have strived to demonstrate that cellular differentiation was the underlying mechanism for the therapeutic effect. These studies generally followed the minimal criteria set by The International Society for Cellular Therapy in assuring MSC identity by using CD70, CD90, and CD105 as positive markers and CD34 as a negative marker. However, the three positive markers are co-expressed in a wide variety of cells, and therefore, even when used in combination, they are certainly incapable of identifying MSCs in vivo. Another frequently used MSC marker, Stro-1, has been shown to be an endothelial antigen and whether it can identify MSCs in vivo remains unknown. On the other hand, the proposed negative marker CD34 has increasingly been shown to be expressed in native MSCs, such as in the adipose tissue. It has also helped establish that MSCs are likely vascular stem cells (VSCs) that reside in the capillaries and in the adventitia of larger blood vessels. These cells do not express CD31, CD104b, or α-SMA, and therefore are designated as CD34+CD31-CD140b-SMA-. Many preclinical MSC transplantation studies have also attempted to demonstrate cellular differentiation by using labeled MSCs. However, all commonly used labels have shortcomings that often complicate data interpretation. The β-gal (LacZ) gene as a label is problematic because many mammalian tissues have endogenous β-gal activities. The GFP gene is similarly problematic because many mammalian tissues are endogenously fluorescent. The cell membrane label DiI can be adsorbed by host cells, and nuclear stains Hoechst dyes and DAPI can be transferred to host cells. Thymidine analog BrdU is associated with loss of cellular protein antigenicity due to harsh histological conditions. Newer thymidine analog EdU is easier to detect by chemical reaction to azide-conjugated Alexa fluors, but certain bone marrow cells are reactive to these fluors in the absence of EdU. These caveats need to be taken into consideration when designing or interpreting MSC transplantation experiments.
Facile synthesis of the DD3R zeolite: performance in the adsorptive separation of buta-1,3-diene and but-2-ene isomers (2011)

Small pore size and hydrophobic nature of DD3R make this material a unique zeolite with high potential in industrial separation applications. However, the reproducible rapid synthesis of this zeolite is still a problem. In this work, a thorough assessment of different synthetic methods revealed that synthesis reproducibility relies on two main pillars: the use of properly cleaned autoclave liners and the synthesis composition. High quality DD3R crystals are obtained when KOH is used as a cleaning agent, eliminating memory effects, and when KF is used in the synthesis as a mineralizing agent. The effect of fluoride addition is investigated by use of several characterization techniques (13C, 19F and 29Si MAS-NMR and (2D) 29Si–1H correlation spectra), while monitoring the temporal crystallization of DDR. 29Si–1H NMR reveals that template molecules accommodated within the cages are sticking to these 8-ring windows through their amine group. High quality DD3R crystals are applied in the adsorptive separation of buta-1,3-diene and but-2-ene isomers, one of the most energy intensive separations in chemical industry. Mixture separation experiments revealed that the 8-ring apertures of the DD3R cages are only accessible to trans-but-2-ene and buta-1,3-diene, while excluding but-1-ene and cis-but-2-ene molecules, resulting in shape-selective separation in the presence of C4 mixtures.
Evolution of HIV-1 coreceptor usage through interactions with distinct CCR5 and CXCR4 domains (1997)

The chemokine receptor CXCR4 functions as a fusion coreceptor for T cell tropic and dual-tropic HIV-1 strains. To identify regions of CXCR4 that are important for coreceptor function, CXCR4-CXCR2 receptor chimeras were tested for the ability to support HIV-1 envelope (env) protein-mediated membrane fusion. Receptor chimeras containing the first and second extracellular loops of CXCR4 supported fusion by T tropic and dual-tropic HIV-1 and HIV-2 strains and binding of a monoclonal antibody to CXCR4, 12G5, that blocks CXCR4-dependent infection by some virus strains. The second extracellular loop of CXCR4 was sufficient to confer coreceptor function to CXCR2 for most virus strains tested but did not support binding of 12G5. Truncation of the CXCR4 cytoplasmic tail or mutation of a conserved DRY motif in the second intracellular loop did not affect coreceptor function, indicating that phosphorylation of the cytoplasmic tail and the DRY motif are not required for coreceptor function. The results implicate the involvement of multiple CXCR4 domains in HIV-1 coreceptor function, especially the second extracellular loop, though the structural requirements for coreceptor function were somewhat variable for different env proteins. Finally, a hybrid receptor in which the amino terminus of CXCR4 was replaced by that of CCR5 was active as a coreceptor for M tropic, T tropic, and dual-tropic env proteins. We propose that dual tropism may evolve in CCR5-restricted HIV-1 strains through acquisition of the ability to utilize the first and second extracellular loops of CXCR4 while retaining the ability to interact with the CCR5 amino-terminal domain.