gebhart/patrepeval huggingface dataset:
Laminar distribution of GABAA- and glycine-receptor mediated tonic inhibition in the dorsal horn of the rat lumbar spinal cord: effects of picrotoxin and strychnine on expression of Fos-like immunoreactivity (2004)

Inhibitory mechanisms are essential in suppressing the development of allodynia and hyperalgesia in the normal animal and there is evidence that loss of inhibition can lead to the development of neuropathic pain. We used Fos expression to map the distribution of tonically inhibited cells in the healthy rat lumbar spinal cord. In a control group, Fos-like immunoreactive (Fos-LI) cells were rare, averaging 7.5+/-2.2 cells (mean+/-SEM; N=13 sections) per 20 microm thick section of dorsal horn. This rose to 103+/-11 (mean+/-SEM; N=20) in picrotoxin-treated rats and to 88+/-11 (mean+/-SEM; N=18) in strychnine-treated rats. These changes were significant (ANOVA; P<0.001). There were marked regional variations in the distribution of Fos-LI cells between picrotoxin- and strychnine-treated animals. Picrotoxin induced a significant increase in the number of Fos-LI cells throughout the dorsal horn (lamina I-VI) while strychnine significantly elevated Fos-like immunoreactivity only in deep laminae (III-VI). For both picrotoxin and strychnine, the increase in Fos-like immunoreactivity peaked in lamina V (at 3579+/-319 and 3649+/-375% of control, respectively; mean+/-SEM) but for picrotoxin an additional peak was observed in the outer part of lamina II (1959+/-196%). Intrathecal administration of both GABAA and glycine receptor antagonists has been shown elsewhere to induce tactile allodynia. The present data suggest that this allodynia could arise due to blockade of tonic GABAA and glycine-receptor mediated inhibition in the deep dorsal horn. GABAA antagonists also induce hypersensitivity to noxious inputs. The blockade of tonic inhibition in the superficial dorsal horn shown here may underlie this hyperalgesia.
Cytosolic phospholipase A2 and its mode of activation in human neutrophils by opsonized zymosan: Correlation between 42/44 kDa mitogen-activated protein kinase, cytosolic phospholipase A2 and NADPH oxidase (1997)

The role of cytosolic phospholipase A2 (cPLA2) and its mode of activation by opsonized zymosan (OZ) was studied in human neutrophils in comparison with activation by PMA. The activation of cPLA2 by 1 mg/ml OZ or 50 ng/ml PMA is evidenced by its translocation to the membrane fractions on stimulation. This translocation is consistent with dithiothreitol (DTT)-resistant phospholipase A2 (PLA2) activity detected in the membranes of activated cells. Neutrophils stimulated by either OZ or PMA exhibited an immediate stimulation of extracellular-signal-regulated kinases (ERKs). The inhibition of ERKs, DTT-resistant PLA2 and NADPH oxidase activities by the MAP kinase kinase inhibitor PD-98059 indicates that ERKs mediate the activation of cPLA2 and NADPH oxidase stimulated by either OZ or PMA. The protein kinase C (PKC) inhibitor GF-109203X inhibited epidermal growth factor receptor peptide kinase activity, the release of [3H]arachidonic acid, DTT-resistant PLA2 activity and superoxide generation induced by PMA, but did not inhibit any of these activities induced by OZ. PKC activity was similarly inhibited by GF-109203X in membrane fractions separated from neutrophils stimulated by either PMA or OZ. In the presence of the tyrosine kinase inhibit orgenistein, ERKs, PLA2 and NADPH oxidase activities were inhibited in cells stimulated by OZ, whereas they were hardly affected in cells stimulated by PMA. The results suggest that the activation of cPLA2 by PMA or OZ is mediated by ERKs. Whereas PMA stimulates ERKs activity through a PKC-dependent pathway, signal transduction stimulated by OZ involves tyrosine kinase activity leading to activation of ERKs via a PKC-independent pathway.
Administration of Live Varicella Vaccine to HIV‐Infected Children with Current or Past Significant Depression of CD4+T Cells (2006)

HIV-infected children with a CD4(+) T cell percentage of > or =15% and a CD4(+) T cell count of > or =200 cells/ microL are likely to benefit from receiving varicella vaccine.
Randomized phase 2 trial of plinabulin (NPI-2358) plus docetaxel in patients with advanced non-small cell lung cancer (NSCLC). (2014)

8054 Background: Plinabulin (N) inhibits tumor growth by targeting both angiogenesis and tumor vasculature as well as directly by inducing apoptosis via the Ras-JNK pathway. This trial compared the combination of N and docetaxel (DN) to docetaxel alone (D). Methods: Patients (pts) with advanced NSCLC previously treated with standard chemotherapy (ChRx) were randomized between D (75 mg/m2 IV) on Day 1 plus N 30 mg/m2 IV on Days 1 and 8 in 21-day cycles (DN) vs D (75 mg/m2 ) (30 Cohort). Pts with Stage IIIB/IV NSCLC and 1 or 2 prior ChRx were eligible. Prior D or vascular disrupting agent (VDA) were not allowed. A 2nd dose cohort (DN 20 mg/m2) of pts with 1 prior ChRx (20 Cohort) was enrolled. The primary end point was overall survival (OS). Results: 172 pts were randomized into 2 dosing cohorts with 163 treated: 30 Cohort (50 DN; 55 D) and 20 Cohort (40 DN; 18 D). For 30 Cohort, OS (months (M)), 90% confidence interval [90% CI]) was 8.7 (6.6, 12.6) for DN and 7.5 (6.3, 10.5) for D; response rate was 14.0% for DN and 14.5% for D; and duration of response (M, 90% CI) for DN was 12.7 (4.0, 13.9) and 1.5 (1.1, 3.1) for D (p=0.049). Results appeared better for the DN 30 Cohort vs 20 Cohort. Post hoc subset analysis identified pts with large, lung tumors (>3 cm) and 1 prior ChRx as having better survival with DN. OS (M, 95% CI) for this subset was 11.5 (7.1, 15.1) DN vs 7.8 (4.1, 17.4) D. The most common adverse events were nausea, fatigue, diarrhea, constipation, and anorexia. There were fewer dose reductions of D among DN pts (10%) vs D pts (18.2%). There was a lower incidence of neutropenia in patients in the DN 30 Cohort compared to D (8.0% vs 36.4%, p<0.001) and the DN 20 Cohort compared with its companion D (7.5% vs 22.2%). A post hoc analysis showed that the DN 30 Cohort (n=50) had a significantly lower incidence of ≥ Grade 3 neutropenia vs the pooled D (n=73) at 8.0% vs 27.4%, respectively (p=0.010). Conclusions: Pts with large, lung tumors (>3 cm) and 1 prior ChRx may be more likely to have an increased survival with DN as compared to D. This finding is consistent with the mechanism of action of a VDA with anti-angiogenesis and apoptotic properties. A Phase 3 trial in pts with large, lung tumors is planned. Clinical trial information: NCT00630110.
Simultaneous local and global state estimation for robotic navigation (2009)

Recent applications of robotics often demand two types of spatial awareness: 1) A fine-grained description of the robot's immediate surroundings for obstacle avoidance and planning, and 2) Knowledge of the robot's position in a large-scale global coordinate frame such as that provided by GPS. Although managing information at both of these scales is often essential to the robot's purpose, each scale has different requirements in terms of state representation and handling of uncertainty. In such a scenario, it can be tempting to pick either a body-centric coordinate frame or a globally fixed coordinate frame for all state representation. Although both choices have advantages, we show that neither is ideal for a system that must handle both global and local data. This paper describes an alternative design: a third coordinate frame that stays fixed to the local environment over short time-scales, but can vary with respect to the global frame. Careful management of uncertainty in this local coordinate frame makes it well-suited for simultaneously representing both locally and globally derived data, greatly simplifying system design and improving robustness. We describe the implementation of this coordinate frame and its properties when measuring uncertainty, and show the results of applying this approach to our 2007 DARPA Urban Challenge vehicle.
Monodisperse Cell-Encapsulating Peptide Microgel Beads for 3D Cell Culture (2009)

This paper describes a method to produce monodisperse cell-encapsulating microgel beads composed of a self-assembling peptide gel for three-dimensional (3D) cell culture. We used a 3D microfluidic axisymmetric flow-focusing device with an external gelation method. The finely powdered salts were dispersed into a continuous phase, and the salts induced the gelation when in contact with the peptide solution. Over 93% of the cells survived after the encapsulation, and the cells migrated and grew within the gels. Applications of our cell-encapsulating beads include bead-based cell assays in drug testing and engineering tissue constructs.
The modulated oral fluoropyrimidine prodrug S-1, and its use in gastrointestinal cancer and other solid tumors (2004)

The fluoropyrimidine anticancer agent 5-fluorouracil (5-FU) is active in a wide range of solid tumors, particularly gastric, colorectal, and head and neck cancers. Whilst infusional 5-FU is associated with higher response rates and a favorable safety profile as compared to the classical i.v. bolus administration, prolonged infusions can be inconvenient for the patients and catheter-related problems are common complications. An oral 5-FU formulation would allow for sustained 5-FU plasma concentrations, mimicking the pharmacokinetics (PK) of a continuous infusion with the addition of convenience of administration. The oral administration of 5-FU itself is not feasible due to the high activity of dihydropyrimidine dehydrogenase in the gut wall, which causes rapid metabolism of the drug, and results in decreased and erratic absorption of 5-FU and non-linear PK. To bypass this problem, oral fluoropyrimidine derivatives were developed either in the form of 5-FU prodrugs (i.e. tegafur, doxifluridine or capecitabine), or as enzyme inhibitors (i.e. eniluracil) administered with 5-FU, or as both prodrugs and enzyme inhibitors (i.e. S-1, UFT or BOF-A2). This review will focus on the oral fluoropyrimidine S-1, which consists of the 5-FU prodrug tegafur (ftorafur, FT) and two enzyme inhibitors, i.e. CDHP (5-chloro-2,4-dihydroxypyridine) and OXO (potassium oxonate), in a molar ratio of 1(FT):0.4 (CDHP):1(OXO). Phase II trials have demonstrated that S-1, as a single agent, is active for the treatment of gastric, colorectal, head and neck, breast, non-small cell lung, and pancreatic cancers. Phase III trials are currently underway in gastric cancer and these results are awaited to confirm the phase II findings. Furthermore, the combination of S-1 with cisplatin (CDDP), irinotecan or docetaxel for the treatment of gastric cancer and with CDDP for non-small cell and pancreatic cancer is feasible and active. The activity observed with S-1 in the phase II studies is at least equivalent, if not better, than continuous i.v. and bolus 5-FU and the other oral fluoropyrimidines. Thus, we may finally be seeing the realization of oral treatments for the management of various solid tumors and could be on the brink of a new approach to treatment strategies.
Giant magnetocaloric effect of MnAs1−xSbx (2001)

A giant magnetocaloric effect was found in MnAs, which undergoes a first-order ferromagnetic to paramagnetic transition at 318 K. The magnetic entropy change caused by a magnetic field of 5 T is as large as 30 J/K kg at the maximum value, which exceeds that of conventional magnetic refrigerant materials by a factor of 2–4. The adiabatic temperature change reaches 13 K in a field change of 5 T. The substitution of 10% Sb for As reduces the thermal hysteresis and lowers the Curie temperature to 280 K, while the giant magnetocaloric properties are retained.
High Performance Electrolyte Gated Carbon Nanotube Transistors (2002)

We have fabricated high performance field-effect transistors made from semiconducting single-walled carbon nanotubes (SWNTs). Using chemical vapor deposition to grow the tubes, annealing to improve the contacts, and an electrolyte as a gate, we obtain very high device mobilities and transconductances. These measurements demonstrate that SWNTs are attractive for both electronic applications and for chemical and biological sensing.
A new sandwich-type assay of estrogen using piezoelectric biosensor immobilized with estrogen response element (1999)

A new methodology, sandwich-type monitoring assay system using an estrogen response element (ERE)-immobilized piezoelectric biosensor in combination with flow injection technique, has been developed for analysis of estrogen (E). The principle of the assay is that the estrogen receptor (ER) captures estrogen and then the complex is bound with ERE immobilized on the sensor. It was confirmed that initial binding of the ERE with ER is significantly accelerated by the formation of an E–ER complex. This kinetic difference was monitored by real-time measurement of the resonance frequency of the ERE piezoelectric biosensor and applied to detect 17β-estradiol. The calibration graph was linear in the range 10–100 nmol l–1 with a detection limit of 7.8 nmol l–1, an RSD of 5.9% for 50 nmol l–1 (6 replicates), and one run time of 4 min. Gradient flow injection on-line connection to an array of ERE piezoelectric biosensors is in progress for the simultaneous determination of endogenous and synthetic estrogens in drinking water and urine. In comparison with present chromatographic methods coupled with MS, the proposed technique is simple, flexible and cheap and has great potential in applications such as field and on-site monitoring and screen testing of endocrine disruptors.
Magic is relevant (1990)

We define the magic-sets transformation for traditional relational systems (with duplicates, aggregation and grouping), as well as for relational systems extended with recursion. We compare the magic-sets rewriting to traditional optimization techniques for nonrecursive queries, and use performance experiments to argue that the magic-sets transformation is often a better optimization technique.
SinGAN: Learning a Generative Model From a Single Natural Image (2019)

We introduce SinGAN, an unconditional generative model that can be learned from a single natural image. Our model is trained to capture the internal distribution of patches within the image, and is then able to generate high quality, diverse samples that carry the same visual content as the image. SinGAN contains a pyramid of fully convolutional GANs, each responsible for learning the patch distribution at a different scale of the image. This allows generating new samples of arbitrary size and aspect ratio, that have significant variability, yet maintain both the global structure and the fine textures of the training image. In contrast to previous single image GAN schemes, our approach is not limited to texture images, and is not conditional (i.e. it generates samples from noise). User studies confirm that the generated samples are commonly confused to be real images. We illustrate the utility of SinGAN in a wide range of image manipulation tasks.
Dose-Response Relationships for Alendronate Treatment in Osteoporotic Elderly Women1 (1997)

Alendronate (ALN) is an aminobisphosphonate employed as an antiresorptive agent in the treatment of osteoporosis. The present study was carried out to determine dose-response relationships, particularly the effects of relatively low doses of ALN, on bone mineral density (BMD), biochemical indexes of bone and mineral metabolism, and bone histology, with particular attention to effects in elderly women. This prospective, randomized, double blind, 2-yr multicenter study compared the effects of placebo with those of 1.0, 2.5, or 5.0 mg ALN daily. All subjects received supplemental calcium (500 mg daily) as the carbonate. We studied 359 women with lumbar spine BMD at least 2.0 SD below the peak young adult mean. Subjects were stratified by age, with 135 aged 60-69 yr and 224 aged 70-85 yr. Histomorphometry was performed on transiliac bone biopsies obtained from 104 subjects after 1 yr and from 83 subjects after 2 yr. This study elucidated the previously uninvestigated lower region of the dose-response curve for ALN in osteoporosis. Over 2 yr, treatment with 1.0, 2.5, or 5.0 mg/day increased lumbar spine BMD, on the average, by 0.65%, 3.54%, and 5.67%, respectively, compared with that in the placebo group (P < 0.001 vs. placebo for the 2.5 and 5 mg groups). Significant dose-related increases were also seen in BMD at appendicular sites and in total body BMD. Dose-dependent reductions in bone turnover to new steady states were indicated by serum and urine biochemical markers as well as by histomorphometry. There was also a dose-related reduction in the proportion of subjects suffering nonvertebral fractures (P < 0.05). Safety profiles were similar for the ALN and placebo groups and for both age strata. Efficacy was similar for both age strata. There was no evidence of impaired mineralization or other histological abnormalities due to ALN treatment. We conclude that treatment with ALN over a period of 2 yr was well tolerated and produced dose-dependent increases in BMD without evidence of a plateau over the dose range of 1.0-5.0 mg daily. One milligram daily did not result in a significant effect on BMD, and 5.0 mg daily produced favorable effects at all sites measured. Other studies have demonstrated somewhat greater effects on 10 mg daily. ALN, was equally effective and well tolerated in osteoporotic women over 70 yr old as in younger women with the same condition.
StrongE×BFlow Shear and Reduced Fluctuations in a Reversed-Field Pinch (1998)

Large radial electric field gradients, leading to sheared $\mathbf{E}\ifmmode\times\else\texttimes\fi{}\mathbf{B}$ flow, are observed in enhanced confinement discharges in the Madison Symmetric Torus reversed-field pinch. The flow shear develops in a narrow region in the plasma edge. Electrostatic fluctuations are reduced over the entire plasma edge with an extra reduction in the shear region. Magnetic fluctuations, resonant in the plasma core but global in extent, are also reduced. The reduction of fluctuations in the shear region is presumably due to the strong shear, but the causes of the reductions outside this region have not been established.
Blockade of p38α MAPK Ameliorates Acute Inflammatory Renal Injury in Rat Anti-GBM Glomerulonephritis (2003)

The p38 mitogen-activated protein kinase (MAPK) pathway is a pro-inflammatory signal transduction pathway. The aim of this study was to examine the role of this pathway in acute renal inflammation. Immunostaining localized components of the p38 MAPK pathway (p38alpha, p-p38, p-ATF-2) in normal glomeruli, to podocytes, and occasional endothelial cells. This study identified an eightfold increase in glomerular activation of p38 MAPK (phosphorylated p38, p-p38) within 3 h of the induction of rat anti-glomerular basement membrane (GBM) glomerulonephritis and localized p-p38 and p-ATF-2 to infiltrating neutrophils, with increased staining of podocytes and endothelial cells. The relevance of these findings to human acute inflammatory renal disease was determined by examination of biopsy specimens. In patients with post-infectious glomerulonephritis, there was an increased number of positive p-p38 glomerular cells, including p-p38 staining of infiltrating neutrophils, compared with normal human kidney. In rats, administration of a specific p38 MAPK inhibitor, NPC 31145, before induction of anti-GBM disease prevented a loss of renal function and substantially reduced proteinuria. The reduction in renal injury was attributed to a 55% reduction in glomerular neutrophil infiltration and a 68% reduction in platelet accumulation. This was associated with an abrogation of glomerular P-selectin immunostaining and inhibition of glomerular P-selectin gene expression. In summary, this study has localized the components of the p38 MAPK pathway to cells in normal and diseased rat and human kidney and identified a number of important mechanisms by which signaling through the p38 MAPK pathway induces inflammatory renal disease. Blockade of the p38 pathway may be a novel therapeutic strategy for the treatment of acute renal inflammation.
Incompletely Condensed Fluoroalkyl Silsesquioxanes and Derivatives: Precursors for Low Surface Energy Materials (2011)

A novel synthetic method was developed for the controlled functionalization of fluorinated polyhedral oligomeric silsesquioxanes (F-POSS), which are useful as low surface energy materials for superhydrophobic and superoleophobic materials. Utilizing triflic acid, open-cage compounds were created and then reacted with a variety of dichlorosilanes to produce functional F-POSS structures possessing alkyl-, aryl-, and acrylate-based moieties. The crystal structure for an endo,endo-disilanol F-POSS compound was determined by single-crystal X-ray diffraction. The chemical structures were confirmed using multinuclear NMR spectroscopy ((1)H, (13)C, (19)F, and (29)Si), FT-IR, and combustion analysis. Dynamic contact angle measurements of these compounds were taken with water and hexadecane. These novel structures were found to possess excellent wetting-resistant behavior, similar to that of the parent F-POSS compound. They are the first well-defined fluorinated nano-building blocks with a controlled level of reactive functionality for the development of new superhydrophobic and superoleophobic materials.
Generation and Characterization of DNA Vaccines Targeting the Nucleocapsid Protein of Severe Acute Respiratory Syndrome Coronavirus (2004)

Severe acute respiratory syndrome (SARS) is a serious threat to public health and the economy on a global scale. The SARS coronavirus (SARS-CoV) has been identified as the etiological agent for SARS. Thus, vaccination against SARS-CoV may represent an effective approach to controlling SARS. DNA vaccines are an attractive approach for SARS vaccine development, as they offer many advantages over conventional vaccines, including stability, simplicity, and safety. Our investigators have previously shown that DNA vaccination with antigen linked to calreticulin (CRT) dramatically enhances major histocompatibility complex class I presentation of linked antigen to CD8(+) T cells. In this study, we have employed this CRT-based enhancement strategy to create effective DNA vaccines using SARS-CoV nucleocapsid (N) protein as a target antigen. Vaccination with naked CRT/N DNA generated the most potent N-specific humoral and T-cell-mediated immune responses in vaccinated C57BL/6 mice among all of the DNA constructs tested. Furthermore, mice vaccinated with CRT/N DNA were capable of significantly reducing the titer of challenging vaccinia virus expressing the N protein of the SARS virus. These results show that a DNA vaccine encoding CRT linked to a SARS-CoV antigen is capable of generating strong N-specific humoral and cellular immunity and may potentially be useful for control of infection with SARS-CoV.
Hepatitis vaccines. (1995)

The 1980s represented a decade of breakthroughs for the development of hepatitis vaccines. Plasma-derived and then recombinant hepatitis B vaccines were developed and introduced, killed hepatitis A vaccine was developed, and the virologic tools were discovered with which to lay the groundwork for a vaccine against hepatitis C. Even as the focus of the 1990s shifts toward antiviral therapy of chronic viral hepatitis, we cannot afford to neglect the importance of prevention by vaccination. Better vaccines and improved vaccination strategies for preventing hepatitis A and B will continue to demand research investment, and the most meager toehold will have to be exploited and pursued aggressively if a practical, effective hepatitis C vaccine is to be developed.
Community-acquired pneumonia in Christchurch and Waikato 1999-2000: microbiology and epidemiology. (2001)

Although S pneumoniae was the most commonly isolated organism in this study there have been significant changes in the prevalence of atypical organisms since previous surveys. Ongoing surveillance of antibiotic resistance and variations in the prevalence of organisms causing community-acquired pneumonia is required to guide clinicians' empiric antibiotic use.
Chandra Localization and Detection of a Burst and Pulsations from GRO J1744-28 (2014)

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