gebhart/patrepeval huggingface dataset:
Treatment of acute graft-versus-host disease with humanized anti-Tac: an antibody that binds to the interleukin-2 receptor (1994)

Humanized anti-Tac is a genetically engineered human IgG1 monoclonal antibody specific for Tac, the alpha subunit of the interleukin-2 (IL-2) receptor, and blocks IL-2-dependent activation of human T lymphocytes. The safety, pharmacokinetics, and immunosuppressive activity of humanized anti-Tac were evaluated in 20 patients who developed acute graft-versus-host disease (GVHD) after allogeneic marrow transplantation. Patients had developed acute GVHD at 5 to 26 (median, 14) days after transplantation and had failed to respond to primary therapy with glucocorticoids. Sequential groups of 4 patients each received a single 1-hour infusion of antibody in escalating doses of 0.5, 1.0, or 1.5 mg/kg; 8 additional patients were then treated with 1.5 mg/kg. A second infusion of antibody was administered after 11 to 48 (median, 16) days in 8 patients who had transient improvement of GVHD after the first infusion. Acute side effects, limited to chills in 1 patient and diaphoresis in another, were observed during or shortly after the antibody infusion. Overall improvement of acute GVHD occurred in 8 patients, 6 of whom were treated with a single antibody infusion and 2 with two infusions. Four responses were complete and 4 were partial. Three additional patients had improvement in one organ but progression in another. Responses occurred in 9 of 16 cases with skin disease, 3 of 15 with liver disease, and 6 of 12 with gastrointestinal disease. Two patients survive at 529 and 645 days after antibody treatment. Two patients died after relapse of leukemia. Sixteen patients died of infection or organ failure between 5 and 211 (median, 55) days. The terminal elimination half-life of the antibody was 44 to 363 hours, with a harmonic mean of 79, 88, and 94 hours, respectively, for the three doses studied. Absolute peripheral blood T-lymphocyte counts remained unchanged during the 56 days after infusion of the antibody. A fraction of circulating T cells expressed the alpha chain of the IL-2 receptor that, in some patients, was bound by antibody in vivo up to 28 days after treatment. No patient developed a measurable antibody response to humanized anti-Tac. Humanized anti-Tac has a long half-life after intravenous injection in humans, superior to any rodent monoclonal antibody specific for human T cells, and does not appear to induce antibody formation in recipients of marrow transplants. Improvement of steroid-refractory GVHD in 40% of patients after only one or two antibody infusions indicates that humanized anti-Tac is immunosuppressive.
Sensitive and Selective Photoinduced‐Electron‐Transfer‐Based Sensing of Alkylating Agents (2006)

Photoinduced-electron-transfer (PET)-based chemosensing is a very elegant way of reporting the presence of a guest species in solution. This method was successfully applied for the detection of different ionic species, such as cations, anions, and protons. Herein, we report on the application of the PET chemosensing concept for the efficient and selective detection of different alkylating agents. 2-(2-Dimethylaminoethyl)benzo[de]isoquinoline-1,3-dione (1) was found to be a highly selective and effective PET chemosensor that turns luminescent upon reacting with different alkylating agents. This PET-based system detected even rather weak alkylating agents, such as dichloromethane. A PET-based sensor that consists of 1 as the active component could detect rather low concentrations of alkylating agents in solution and in the gas phase.
Intrapericardial Delivery of Gelfoam Enables the Targeted Delivery of Periostin Peptide after Myocardial Infarction by Inducing Fibrin Clot Formation (2012)

The results of this study suggest that intrapericardial drug delivery of Gelfoam, enhanced by triggered clot formation, can be used to effectively deliver rPN to the myocardium in a clinically relevant model of myocardial infarction. The work presented here should enhance the translational potential of pharmaceutical-based strategies that must be targeted to the myocardium.
Decreased Expression of Toll-Like Receptor-4 and MD-2 Correlates with Intestinal Epithelial Cell Protection Against Dysregulated Proinflammatory Gene Expression in Response to Bacterial Lipopolysaccharide (2001)

The lumenal surface of the colonic epithelium is continually exposed to Gram-negative commensal bacteria and LPS. Recognition of LPS by Toll-like receptor (TLR)-4 results in proinflammatory gene expression in diverse cell types. Normally, however, commensal bacteria and their components do not elicit an inflammatory response from intestinal epithelial cells (IEC). The aim of this study is to understand the molecular mechanisms by which IEC limit chronic activation in the presence of LPS. Three IEC lines (Caco-2, T84, HT-29) were tested for their ability to activate an NF-kappaB reporter gene in response to purified, protein-free LPS. No IEC line responded to LPS, whereas human dermal microvessel endothelial cells (HMEC) did respond to LPS. IEC responded vigorously to IL-1beta in this assay, demonstrating that the IL-1 receptor signaling pathway shared by TLRs was intact. To determine the reason for LPS hyporesponsiveness in IEC, we examined the expression of TLR4 and MD-2, a critical coreceptor for TLR4 signaling. IEC expressed low levels of TLR4 compared with HMEC and none expressed MD-2. To determine whether the low level of TLR4 expression or absent MD-2 was responsible for the LPS signaling defect in IEC, the TLR4 or MD-2 gene was transiently expressed in IEC lines. Transient transfection of either gene individually was not sufficient to restore LPS signaling, but cotransfection of TLR4 and MD-2 in IEC led to synergistic activation of NF-kappaB and IL-8 reporter genes in response to LPS. We conclude that IEC limit dysregulated LPS signaling by down-regulating expression of MD-2 and TLR4. The remainder of the intracellular LPS signaling pathway is functionally intact.
Catalase Activity as a Predictor of Amniotic Fluid Culture Results in Preterm Labor or Premature Rupture of Membranes (1995)

Catalase activity is a simple, rapid test that is useful in identifying subclinical intra-amniotic infection in patients with preterm labor or PROM.
Surfactant replacement in the management of the neonatal respiratory distress syndrome. (1987)

Several recent reports have documented the efficacy of surfactants replacement therapy in the neonatal respiratory distress syndrome (RDS). The surfactants tested in these trials were obtained from animal lungs or human amniotic fluid. In general, such natural preparations seem to be superior to entirely synthetic surfactants, although promising results have recently been obtained in animal experiments with artificial surfactant based on isolated apoproteins and synthetic phospholipids. Furthermore, surfactant replacement therapy seems to be more effective when the exogenous material is administered at birth, before the first breath, than when surfactant is instilled into the airways after a period of ventilation. This discrepancy may be due to maldistribution of the exogenous material, or to the rapid development of epithelial lesions in the immature lung, with leakage of surfactant-inhibiting proteins into the airspaces. A transient beneficial response to surfactant replacement may also be due to circulatory problems, especially reversal of the shunt through a patent ductus arteriosus, with overloading of the lung circulation leading to pulmonary oedema and recurrent respiratory failure. Additional, properly randomized clinical trials are required to evaluate the benefits and potential hazards of surfactant replacement therapy in neonatal RDS.
Postoperative Ileus: A Review (2004)

Paralytic postoperative ileus continues to be a significant problem after abdominal and other types of surgery. The etiology is multifactorial and is best treated with a combination of different approaches. Currently, the important factors that could effect the duration and recovery from postoperative ileus include limitation of narcotic use by substituting alternative medications such as nonsteroidals and placing a thoracic epidural with local anesthetic when possible. The selective use of nasogastric decompression and correction of electrolyte imbalances also are important factors to consider.
Preparation of synthetic tandem-repetitive probes for DNA fingerprinting. (1990)

DNA fingerprints are generated using probes that hybridize to hypervariable minisatellites, also known as variable number tandem repeat loci. Cloned minisatellites have served as the predominant source of DNA fingerprinting probes. A short segment within the repeat units of minisatellites, called the "core" sequence, is highly conserved within a family of related minisatellites, thereby allowing a single-cloned minisatellite to cross-hybridize to 20 to 40 other minisatellites. In this article, we describe a method for the synthetic preparation of polymeric core sequence probes for DNA fingerprinting. Unlike "monomeric" oligonucleotide probes, the polymeric probes mimic the tandem-repetitive structure of minisatellites, and thus each probe molecule can potentially form many sites of hybridization with a target minisatellite. The synthetic probes are cloned into plasmid DNA to provide a perpetual source of probe material.
Activation of protein kinase C results in the displacement of its myristoylated, alanine-rich substrate from punctate structures in macrophage filopodia. (1990)

The myristoylated, alanine-rich C kinase substrate (MARCKS) is a prominent substrate for protein kinase C (PKC) in a variety of cells, and has been implicated in diverse cellular processes including neurosecretion, fibroblast mitogenesis, and macrophage activation. In macrophages that have spread on the substratum, MARCKS has a punctate distribution at the cell-substratum interface of pseudopodia and filopodia. At these points, MARCKS co-localizes with vinculin and talin. Activation of PKC with phorbol esters results in the rapid disappearance of punctate staining of MARCKS, but not vinculin or talin, and is accompanied by cell spreading and loss of filopodia. The morphological changes and disappearance of punctate staining follow a time-course that closely approximates both the PKC-dependent phosphorylation of MARCKS, and its phosphorylation-dependent release from the plasma membrane. Our results suggest a role for PKC-dependent phosphorylation of MARCKS in the regulation of the membrane cytoskeleton.
ASSOCIATION BETWEEN SERUM SELENIUM AND THE RISK OF CANCER (1984)

A matched-pair analysis was conducted with data based on a prospective six-year follow-up of a random population sample to study the association between serum selenium and the risk of cancer. Case-control pairs were from a population, after exclusions, of 8,113 persons examined in 1972 from two counties in eastern Finland. Cases were 31- to 59-year-old men and women initially free of cancer. One control was matched to each case according to age, gender, daily tobacco consumption, and serum cholesterol concentration. The mean serum selenium of the 128 cases was 50.5 micrograms/liter and that of the controls was 54.3 micrograms/liter (p = 0.012 for difference). When the residual variation in tobacco consumption and serum cholesterol as well as that in four other possible confounders was allowed for in a multiple logistic model, serum selenium of less than 45 micrograms/liter was associated with a relative risk of cancer of 3.1 (95% confidence interval, 1.5-6.7, p less than 0.01). These data support the hypothesis that selenium deficiency increases the risk of certain cancers in middle-aged persons.
Equation of state and electron transport effects in exploding wire evolution (2002)

Accurate MHD modeling of a single exploding Al wire is a prerequisite to being able to model a wire array. We have compared our simulation results to the high-quality laboratory measurements from exploding-wire experiments recently done at Cornell University. Exploding wire simulations have identified regions where our transport models must be most accurate. Improvements we have made in these regions (e.g., solid density, near melt, and the metal-insulator transition) have proven to be critical for achieving accurate simulations.
Differential cell surface expression of mannoprotein epitopes in yeast and mycelial forms of Candida albicans. (1993)

The ultrastructural localization of mannoprotein constituents (MP) of the cell wall of yeast and hyphal forms of Candida albicans was studied by immunoelectron microscopy. To this aim, two monoclonal antibodies (mAbs AF1 and 1D10), recognizing distinct oligomannoside epitopes of MP molecules, and a second antibody coupled to colloidal gold, were employed. Preembedding methods revealed the presence of both AF1- and, albeit to a lesser intensity, 1D10-epitopes within the fibrillar, capsular layer of yeast cells of the fungus, provided this capsule was preserved and stabilized by treatment of whole cells with Concanavalin A. These cell surface-associated MP were absent in hyphal cells, despite the presence in these cells of a capsular layer not different in form and thickness from that present in yeast cells. Postembedding methods showed that both yeast and hyphal forms of growth of C. albicans synthesized the relevant mannoproteins and similarly incorporated them into inner layers of the cell wall. Apparently, however, the "export" of these MP to the outermost, capsular layer occurred in yeast but not in hyphal cells. These ultrastructural data, coupled with previous biochemical ones, emphasize form-associated patterns of MP expression on Candida cell surface. Given the value of MP as main immunogenic components of Candida, this differential expression could be a means by which the fungus evades from, or attenuates host's response.
Shared tree wireless network multicast (2002)

In this paper we propose a multicast protocol for a multihop, mobile wireless network with cluster based routing and token access protocol within each cluster. The multicast protocol uses a shared tree which is dynamically updated to adjust to changes in topology and membership (i.e. dynamic joins and quits). Two options for tree maintenance have been simulated and evaluated: "hard state" (i.e. each connection must be explicitly cleared) and "soft state" (each connection is automatically timed out and must be refreshed). For the soft state policy, the performance of different choices of timeout and refresh timers is first analyzed for a range of node mobility values. Next, soft state and hard state policies are compared based on throughput, join delay, and control overhead criteria.
Immediate Occlusal Loading of Brånemark TiUnite™ Implants Placed Predominantly in Soft Bone: 1‐Year Results of a Prospective Clinical Study (2003)

The applied immediate loading protocol in combination with a slightly tapered implant and a modified implant surface texture was shown to be a successful treatment alternative even in regions exhibiting soft bone.
A Comparison of the Deposition Patterns of Different Nasal Spray Formulations Using a Nasal Cast (2014)

For nasally delivered medications, it is quite a challenge in the formulation development to characterize the deposition pattern in vivo. An in vitro nose model has been developed recently and adopted in our study to compare the deposition pattern of different nasal solution formulations. One low-viscosity nasal solution and five other solutions containing either Avicel or hydroxypropyl methylcellulose (HPMC) as the viscosity enhancers were examined in this study. The viscosity, spray pattern, plume geometry, and droplet size were characterized. The in vitro deposition patterns were assessed using an anatomically correct silicone nasal cast combined with a color-based image-analysis method. The correlations between the formulation variables, the spray characteristics, and the deposition pattern were investigated. The addition of each viscosity enhancer resulted in increasing viscosity, larger droplet size, narrower plume angle, and lesser anterior deposition. However, it appears that the changes in spray characteristics and deposition pattern are influenced heavily by the identity of the viscosity enhancer, rather than merely by the formulation viscosity itself. Although the Avicel additions led to larger increases in the formulation viscosity, the HPMC additions had far greater impact on the spray characteristics and deposition pattern. The formulations with suboptimal deposition patterns, i.e., the formulations with ‘forward’ or ‘backward’ dripping, were successfully identified in this study. This in vitro method was able to discriminate between formulations, revealing differences in regional deposition and the tendency of formulations to drip. As such, the nasal cast method is recommended as a valuable tool for the development of nasal spray formulations.
The Physics of Intensity-Modulated Radiation Therapy (2002)

By spatially varying the intensity of an x-ray beam, IMRT enables careful sculpting of radiation treatments around sensitive tissues.
Surface-Initiated Radical Polymerization on Porous Silica (1997)

A novel chemical reaction to minimize termination reactions in radical polymerization is applied for the first time to the growth of thin polymer films on silica. A living polyacrylamide thin film is grown from a self-assembled benzyl chloride monolayer on silica gel using Cu(bpy)2Cl to control the radical population. The polymerization is sufficiently well controlled that films grown on nanoporous silica leave the pores intact, as shown by its ability to separate proteins by size exclusion. The living polyacrylamide film covers the silica surface uniformly, as shown by the highly efficient elution of lysozme, a strongly basic protein, at pH 4.7. The new chemistry for film growth enables polymers to be used to make new stationary phases on porous silica gel.
Non-conservation of a catalytic residue in a dipeptidyl aminopeptidase IV-related protein encoded by a gene on human chromosome 7 (1993)

Noboru Yokotani, Katsuml Doi, Robert J.Wenthold, Kelji Wada; Non-conservation of a catalytic residue in a dipeptidyl aminopeptidase IV-related protein encoded
Glucocorticoids Selectively Inhibit Translation of Ribosomal Protein mRNAs in P1798 Lymphosarcoma Cells (1987)

When P1798 murine lymphosarcoma cells are exposed to 10(-7) M dexamethasone, there is a dramatic inhibition of rRNA synthesis, which is completely reversible when the hormone is withdrawn. In the present experiments we examined whether dexamethasone treatment causes any alteration in the accumulation or utilization of mRNAs that encode ribosomal proteins (rp mRNAs). No effect on the accumulation of six different rp mRNAs was detected. However, the translation of five of six rp mRNAs was selectively inhibited in the presence of the hormone, as judged by a substantial decrease in ribosomal loading. Normal translation of rp mRNA was resumed within a few hours after hormone withdrawal. In untreated or fully recovered cells, the distribution of rp mRNAs between polyribosomes and free ribonucleoprotein is distinctly bimodal, suggesting that rp mRNAs are subject to a particular form of translational control in which they are either translationally inactive or fully loaded with ribosomes. A possible relationship between this mode of translational control and the selective suppression of rp mRNA translation by glucocorticoids is discussed.
Chemical Synthesis and Expression of a Synthetic Gene for the Flavodoxin from Clostridium MP (1989)

A gene coding for the flavodoxin from Clostridium MP was designed, synthesized, and expressed in Escherichia coli. The sequence of the coding region was derived from the published amino acid sequence of the protein (Tanaka, M., Haniu, M., Yasunobu, K.T., and Mayhew, S. G. (1974) J. Biol. Chem. 249, 4393-4397) and was designed for optimal expression and for use of the cassette mutagenesis approach. The structural gene was subassembled in three sections, each of which was constructed by the enzymatic ligation of three complementary pairs of chemically synthesized oligodeoxyribonucleotides having short single-stranded ends complementary to that of the adjacent pair. Coligation of the three sections produced the final structural gene which consists of 420 nucleotides. The synthetic gene was cloned behind the hybrid tac promoter (Amman, E., Brosius, J., and Ptashne, M. (1983) Gene (Amst.) 25, 167-178) in the pKK223-3 vector or adjacent to the strong T7 RNA polymerase promoter in the pET-3a expression vector (Rosenberg, A.H., Lade, B. N., Chui, D-S., Lin, S-W., Dunn, J. J., and Studier, F. W. (1987) Gene (Amst.) 56, 125-135) for expression in E. coli. Upon induction with isopropyl-beta-D-thiogalactoside, the flavodoxin polypeptide was expressed from the artificial gene to levels approaching 20% of total extractable proteins using either expression system. The flavodoxin was purified from cellular extracts as the holoprotein containing bound flavin mononucleotide. The recombinant flavodoxin protein was found to have an ultraviolet/visible spectrum, amino-terminal sequence, and amino acid composition identical to the wild-type flavodoxin protein purified from Clostridium MP. This work represents the first chemical synthesis and expression in E. coli of an artificial gene coding for a bacterial flavodoxin.
Barriers to Glaucoma Drug Delivery (2008)

Topical medications remain the mainstay of glaucoma treatment. This review will aim to cover the pharmacokinetics of topically applied drops, the ocular barriers to drug delivery, and the role of ophthalmic drug formulation in enhancing drug delivery to the target tissue while minimizing side effects and increasing patient compliance. Recent advances in surgical techniques, therapeutic approaches, and material sciences have produced exciting new therapies for ocular diseases. The development of new vehicles and drug formulations that require less patient compliance is also discussed, as are the routes of drug delivery for neuroprotection.
Key Role of 5-HT1BReceptors in the Regulation of Paradoxical Sleep as Evidenced in 5-HT1BKnock-Out Mice (1999)

The involvement of 5-HT1B receptors in the regulation of vigilance states was assessed by investigating the spontaneous sleep-waking cycles and the effects of 5-HT receptor ligands on sleep in knock-out (5-HT1B-/-) mice that do not express this receptor type. Both 5-HT1B-/- and wild-type 129/Sv mice exhibited a clear-cut diurnal sleep-wakefulness rhythm, but knock-out animals were characterized by higher amounts of paradoxical sleep and lower amounts of slow-wave sleep during the light phase and by a lack of paradoxical sleep rebound after deprivation. In wild-type mice, the 5-HT1B agonists CP 94253 (1-10 mg/kg, i.p.) and RU 24969 (0.25-2.0 mg/kg, i.p.) induced a dose-dependent reduction of paradoxical sleep during the 2-6 hr after injection, whereas the 5-HT1B/1D antagonist GR 127935 (0.1-1.0 mg/kg, i.p.) enhanced paradoxical sleep. In addition, pretreatment with GR 127935, but not with the 5-HT1A antagonist WAY 100635, prevented the effects of both 5-HT1B agonists. In contrast, none of the 5-HT1B receptor ligands, at the same doses as those used in wild-type mice, had any effect on sleep in 5-HT1B-/- mutants. Finally, the 5-HT1A agonist 8-OH-DPAT (0.2-1.2 mg/kg, s.c.) induced in both strains a reduction in the amount of paradoxical sleep. Altogether, these data indicate that 5-HT1B receptors participate in the regulation of paradoxical sleep in the mouse.