gebhart/patrepeval huggingface dataset:
Virtual Reality Therapy: an Effective Treatment for the Fear of Public Speaking (1998)

The major goal of this research was to investigate the efficacy of virtual reality therapy (VRT) in the treatment of the fear of public speaking. After an extensive two-stage screening process, sixteen subjects were selected from the pool. They were assigned to two treatment conditions: VRT (N=8) and comparison group (N=8). Fourteen subjects completed the study. The VRT group was exposed to the virtual reality public speaking scene while the comparison group was exposed to a trivial virtual reality scene and guided by the experimenters to manage their phobia either by using visualization techniques or selfexposure to the situation they feared. The VRT and comparison group sessions were conducted on an individual basis over a five week period. Two assessment measures were used in this study. The first measure used was the Attitude Towards Public Speaking (ATPS) Questionnaire. The second measure used was the eleven-point Subjective Units of Disturbance (SUD) scale. These measurements assessed the anxiety, avoidance, attitudes and disturbance associated with their fear of public speaking before and after treatments. In addition, objective measures such as heart rate was collected in each stage of the treatment. Significant differences between the six subjects who completed the VRT sessions and comparison group were found on all measures. The VRT group showed significant improvement after five weeks of treatment. The comparison group did not show any meaningful changes. The authors concluded that VRT was successful in reducing the fear of the public speaking.
Studies on the Mechanism of Positive Inotropic Activity of Ro 13–6438, a Structurally Novel Cardiotonic Agent with Vasodilating Properties (1984)

We investigated the possible mechanisms involved in the positive inotropic activity of Ro 13-6438 (R-6-chloro-1,5-dihydro-3- methylimidazo -[2,1-b] quinazolin -2[ 3H]-one), a structurally novel cardiotonic agent with vasodilating properties. The positive inotropic response to Ro 13-6438 of the isolated guinea pig papillary muscle was accompanied by inhibition of myocardial phosphodiesterase (PDE) activity and elevation of intracellular cyclic AMP (cAMP) levels Ro 13-6438 had no effect on Na+,K+-stimulated or Ca2+-stimulated ATPase activity and did not influence the rate of 45Ca uptake in cardiac membrane vesicles. Ro 13-6438 caused a concentration-dependent increase in the upstroke velocity, overshoot, and duration of slow action potentials evoked in partially depolarized papillary muscles. Pretreatment of guinea pigs with reserpine did not prevent the effects of Ro 13-6438 on slow action potentials, but slightly decreased its positive inotropic activity. The muscarinic agonist carbachol reversed the Ro 13-6438-induced enhancement of contractility and changes in the slow action potential in an atropine-sensitive manner. These results indicate that the positive inotropic effects of Ro 13-6438 are correlated with PDE inhibition, increased cAMP levels, and an increase of the slow action potential in ventricular myocardium. It is suggested that the elevated cAMP levels resulting from the Ro 13-6438-induced inhibition of PDE enhance the slow inward Ca2+ current.
Effects of amniotic membrane suspension in human corneal wound healing in vitro. (2009)

These results demonstrate that the suspension form of AM maintains its beneficial effect on corneal epithelial wound healing in vitro, and that AM suspension leads to significant increases in corneal epithelial migration and proliferation with increasing AM concentrations.
Monocyte Chemotactic Protein 1 Regulates Oral Tolerance Induction by Inhibition of T Helper Cell 1–related Cytokines (1998)

Experimental autoimmune encephalomyelitis (EAE) is a T cell-mediated autoimmune demyelinating disease of the central nervous system that serves as an animal model for multiple sclerosis. Antigen-specific tolerance regimens, including oral tolerance, have been used prophylactically to prevent development of acute EAE as well as a number of other autoimmune diseases. Two mechanisms have been proposed to explain the immunologic basis for disease inhibition: bystander immune suppression and clonal anergy/deletion. This report demonstrates a novel mechanism for monocyte chemotactic protein (MCP)-1 as a regulatory factor of oral tolerance. Oral administration of proteolipid protein peptide (PLP139-151) increased MCP-1 expression in the intestinal mucosa, Peyer's patch, and mesenteric lymph nodes. Increase in MCP-1 expression resulted in downregulation of mucosal interleukin (IL)-12 expression with concomitant increase in mucosal IL-4 expression. Functionally, MCP-1 upregulation was shown to regulate oral tolerance induction by the ability of antibodies to MCP-1 to inhibit tolerance induction. The anti-MCP-1 abrogation of oral tolerance induction also resulted in restoration of mucosal IL-12 expression as well as peripheral antigen-specific T helper cell 1 responses. These results demonstrate a novel and important role for MCP-1 in the regulation or oral tolerance for the prevention and treatment of autoimmune disease.
Primary prophylaxis with warfarin prevents thrombosis in paroxysmal nocturnal hemoglobinuria (PNH) (2003)

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hemolytic anemia in which venous thrombosis is the most common cause of death. Here we address the risk factors for thrombosis and the role of warfarin prophylaxis in PNH. The median follow-up of 163 PNH patients was 6 years (range, 0.2-38 years). Of the patients, 29 suffered thromboses, with a 10-year incidence of 23%. There were 9 patients who presented with thrombosis, and in the remainder the median time to thrombosis was 4.75 years (range, 3 months-15 years). The 10-year risk of thrombosis in patients with large PNH clones (PNH granulocytes > 50%) was 44% compared with 5.8% with small clones (P <.01). Patients with large PNH clones and no contraindication to anticoagulation were offered warfarin. There were no thromboses in the 39 patients who received primary prophylaxis. In comparison, 56 patients with large clones and not taking warfarin had a 10-year thrombosis rate of 36.5% (P =.01). There were 2 serious hemorrhages in more than 100 patient-years of warfarin therapy. Large PNH granulocyte clones are predictive of venous thrombosis, although the exact cut-off for clone size is still to be determined. Primary prophylaxis with warfarin in PNH prevents thrombosis with acceptable risks.
Androgen Receptor Up-Regulates Insulin-Like Growth Factor Binding Protein-5 (IGFBP-5) Expression in a Human Prostate Cancer Xenograft (1999)

The insulin-like growth factor (IGF) binding proteins (IGFBPs) are important modulators of IGF action in many tissues including human prostate. IGFBPs and the androgen receptor (AR) are expressed in CWR22, an androgen-dependent epithelial cell human CaP xenograft that retains biological characteristics of human CaPs, including regression following androgen withdrawal and recurrent growth of AR-containing cells in the absence of testicular androgens beginning several months after castration. Northern blot and in situ hybridization analyses demonstrated that IGFBP-5 is androgen-regulated in CWR22. IGFBP-5 messenger RNA (mRNA) decreased by 90% following castration of tumor-bearing mice compared with noncastrate androgen-stimulated mice. Testosterone treatment of CWR22 tumor-bearing mice 6 or 12 days after castration increased IGFBP-5 mRNA 10- to 12-fold. Levels of other IGFBP mRNAs did not change following androgen withdrawal and replacement. IGFBP-5 protein in tumor extracts bound 125I-labeled IGF-I in ligand blot assays and the amounts of IGFBP-5 measured by immunoblotting paralleled the levels of IGFBP-5 mRNA. Androgen-induced expression of IGFBP5 was at a maximum level within 24 h after testosterone replacement, whereas the major increase in cell proliferation as measured by Ki-67 immunostaining occurred between 24–48 h. This time course suggested IGFBP-5 may be a mediator of androgen-induced growth of CWR22. In tumors that recurred several months following castration, IGFBP-5 mRNA and protein increased to levels that approached those in androgen-stimulated CWR22 tumors from noncastrate mice. IGFBP-5 immunohistochemical staining of prostate tissue specimens from patients was stronger in androgen-dependent and androgen-independent CaP than in areas of intraepithelial neoplasia (PIN) or benign prostatic hyperplasia (BPH). IGFBP-5 mRNA in these specimens was localized predominantly to stromal cells and IGFBP-5 protein to epithelial cell membranes.
A Food-Grade Enzyme Preparation with Modest Gluten Detoxification Properties (2009)

Clinical studies are warranted to evaluate whether a fixed dose ratio combination of ASP and DPPIV can provide near-term relief for celiac patients suffering from inadvertent gluten exposure. Due to its markedly greater hydrolytic activity against gluten than endogenous pepsin, food-grade ASP may also augment the activity of therapeutically relevant doses of glutenases such as EP-B2 and certain prolyl endopeptidases.
Evaluation of Induction of CYP3A mRNA Using the HepG2 Cell Line and Reverse Transcription-PCR. (1999)

Cytochrome P-450 3A (CYP3A) is a drug-metabolizing enzyme dominant in the human liver. We have designed a useful method for evaluation of induction of CYP3A mRNA by various drugs using HepG2 cells known to retain liver-cellular functions. Using semi-quantitative reverse transcription-PCR (RT-PCR), we demonstrated that cultured HepG2 cells constitutively expressed CYP3A mRNA. This mRNA was expressed at high levels in culture for several days and was further induced by several drugs (e.g. rifampicin (RFP), dexamethasone). Treatment of HepG2 cells with RFP induced CYP3A mRNA in a dose- and time-dependent manner. Cells in culture for 48 h with 1 and 50 micromol/l RFP increased 2.7- and 5.0-fold in CYP3A mRNA expression in comparison with untreated controls, respectively. In contrast, no change in the amount of CYP3A mRNA was observed when the cells were treated with cimetidine which has been shown to inhibit CYP3A activity. Our method using a combination of HepG2 cells and RT-PCR allowed evaluation of the degree of induction of CYP3A mRNA both easily and rapidly.
Application of corneal tomography before keratorefractive procedure for laser vision correction (2016)

Ectasia after refractive surgery represents a major concern among refractive surgeons. Corneal abnormalities and preexisting corneal ectasia are the most important risk factors. Corneal topography and central corneal thickness are the factors traditionally screening for in refractive surgery candidates. Study of the anterior surface by Placido topography allows for identification of keratoconus before biomicroscopy. However, this is insufficient for the evaluation of pre-operative refractive surgery. There are cases of ectasia after laser in situ keratomilusis (LASIK) without identifiable risk factors such that there is a need to go beyond the corneal surface. A key requirement is quantifying susceptibility to corneal biomechanical instability and progression to ectasia. Tomographic indices derived from elevation maps and pachymetry spatial variation produce a Belin Ambrosio display final D index (BAD-D index), which has shown better results compared to surface curvature indices for detecting very mild forms of ectasia. A logistic regression formula, integrating age, residual stromal bed, and BAD-D (Ectasia Susceptibility Score, ESS) resulted in a significant improvement in accuracy, leading to 100% sensitivity and 94% specificity for detecting susceptible cases. A comprehensive corneal structural analysis based on corneal segmental tomography can detect susceptible corneas, which increases safety for refractive surgery patients.
Proteasome inhibitor ameliorates severe acute pancreatitis and associated lung injury of rats (2008)

The proteasome inhibitor MG-132 shows a protective effect on severe acute pancreatitis and associated lung injury of rats.
A human Lactobacillus strain (Lactobacillus casei sp strain GG) promotes recovery from acute diarrhea in children. (1991)

To determine the effect of a human Lactobacillus strain (Lactobacillus casei sp strain GG, Gefilac) on recovery from acute diarrhea (82% rotavirus), 71 well-nourished children between 4 and 45 months of age were studied. After oral rehydration, the patients randomly received either Lactobacillus GG-fermented milk product, 125 g (10(10-11) colony-forming units) twice daily (group 1); Lactobacillus GG freeze-dried powder, one dose (10(10-11) colony-forming units) twice daily (group 2); or a placebo, a pasteurized yogurt (group 3) 125 g twice daily; each diet was given for 5 days, in addition to normal full diet otherwise free of fermented dairy products. The mean (SD) duration of diarrhea after commencing the therapy was significantly shorter in group 1 (1.4 [0.8] days) and in group 2 (1.4 [0.8] days) than in group 3 (2.4 [1.1] days); F = 8.70, P less than 0.001. After rehydration, each dietary group maintained a positive weight trend. The urinary lactulose-mannitol recovery ratios (means [95% confidence intervals]) on admission were 0.09 (0.03, 0.24) in group 1, 0.12 (0.07, 0.22) in group 2, and 0.08 (0.04, 0.18) in group 3; no significant alterations in intestinal permeability were observed at retesting after 2 days of realimentation. The result indicates that early nutritional repletion after rehydration causes no mucosal disruption and is beneficial for recovery from diarrhea. It is further suggested that Lactobacillus GG in the form of fermented milk or freeze-dried powder is effective in shortening the course of acute diarrhea.
Reply: Definitions of Pediatric Septic Shock (2005)

Pediatric Critical Care Medicine: July 2005 - Volume 6 - Issue 4 - p 501 doi: 10.1097/01.PCC.0000168164.08360.8C
Central Role for G Protein-Coupled Phosphoinositide 3-Kinase γ in Inflammation (2000)

Phosphoinositide 3-kinase (PI3K) activity is crucial for leukocyte function, but the roles of the four receptor-activated isoforms are unclear. Mice lacking heterotrimeric guanine nucleotide-binding protein (G protein)-coupled PI3Kgamma were viable and had fully differentiated neutrophils and macrophages. Chemoattractant-stimulated PI3Kgamma-/- neutrophils did not produce phosphatidylinositol 3,4,5-trisphosphate, did not activate protein kinase B, and displayed impaired respiratory burst and motility. Peritoneal PI3Kgamma-null macrophages showed a reduced migration toward a wide range of chemotactic stimuli and a severely defective accumulation in a septic peritonitis model. These results demonstrate that PI3Kgamma is a crucial signaling molecule required for macrophage accumulation in inflammation.
Processing and Translation Initiation of Non-long Terminal Repeat Retrotransposons by Hepatitis Delta Virus (HDV)-like Self-cleaving Ribozymes (2011)

Many non-long terminal repeat (non-LTR) retrotransposons lack internal promoters and are co-transcribed with their host genes. These transcripts need to be liberated before inserting into new loci. Using structure-based bioinformatics, we show that several classes of retrotransposons in phyla-spanning arthropods, nematodes, and chordates utilize self-cleaving ribozymes of the hepatitis delta virus (HDV) family for processing their 5' termini. Ribozyme-terminated retrotransposons include rDNA-specific R2, R4, and R6, telomere-specific SART, and Baggins and RTE. The self-scission of the R2 ribozyme is strongly modulated by the insertion site sequence in the rDNA, with the most common insertion sequences promoting faster processing. The ribozymes also promote translation initiation of downstream open reading frames in vitro and in vivo. In some organisms HDV-like and hammerhead ribozymes appear to be dedicated to processing long and short interspersed elements, respectively. HDV-like ribozymes serve several distinct functions in non-LTR retrotransposition, including 5' processing, translation initiation, and potentially trans-templating.
Engineering domain fusion chimeras from I-OnuI family LAGLIDADG homing endonucleases (2012)

Although engineered LAGLIDADG homing endonucleases (LHEs) are finding increasing applications in biotechnology, their generation remains a challenging, industrial-scale process. As new single-chain LAGLIDADG nuclease scaffolds are identified, however, an alternative paradigm is emerging: identification of an LHE scaffold whose native cleavage site is a close match to a desired target sequence, followed by small-scale engineering to modestly refine recognition specificity. The application of this paradigm could be accelerated if methods were available for fusing N- and C-terminal domains from newly identified LHEs into chimeric enzymes with hybrid cleavage sites. Here we have analyzed the structural requirements for fusion of domains extracted from six single-chain I-OnuI family LHEs, spanning 40-70% amino acid identity. Our analyses demonstrate that both the LAGLIDADG helical interface residues and the linker peptide composition have important effects on the stability and activity of chimeric enzymes. Using a simple domain fusion method in which linker peptide residues predicted to contact their respective domains are retained, and in which limited variation is introduced into the LAGLIDADG helix and nearby interface residues, catalytically active enzymes were recoverable for ≈ 70% of domain chimeras. This method will be useful for creating large numbers of chimeric LHEs for genome engineering applications.
New discoveries in diabetes- and thyroid-related eye disease (1997)

Although reports from Europe indicate a reduction in the incidence of diabetes-related visual loss, diabetic retinopathy continues to be the leading cause of blindness. One agent, vascular endothelial growth factor (VEGF), has been found to stimulate angiogenesis and may be the cause of diabetic neovascularization and visual loss. New research implies that the manipulation of the VEGF pathway may be able to prevent diabetic visual loss. Type I (insulin-dependent) and type II (non-insulin-dependent) diabetes mellitus are different disease processes. There have been few attempts in the past to differentiate the retinopathy associated with these two distinct disorders. Recent reports indicate that these disorders have different responses to ocular therapy. Thyroid orbitopathy combined with ocular hypertension can produce true glaucoma. Nevertheless, this requires a prolonged duration of orbitopathy and most patients who have this combination will improve and not develop permanent glaucomatous changes. Similarly, the majority of Graves' disease patients develop improved function over time; however, the psychologic sequelae continue after the disease process is in remission, which warrants further studies.
A comparative analysis of SARS-CoV-2 antivirals in human airway models characterizes 3CL(pro) inhibitor PF-00835231 as a potential new treatment for COVID-19 (2021)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiological agent of Coronavirus Disease 2019 (COVID-19). There is a dire need for novel effective antivirals to treat COVID-19, as the only approved direct-acting antiviral to date is remdesivir, targeting the viral polymerase complex. A potential alternate target in the viral life cycle is the main SARS-CoV-2 protease 3CL(pro) (M(pro)). The drug candidate PF-00835231 is the active compound of the first anti-3CL(pro) regimen in clinical trials. Here, we perform a comparative analysis of PF-00835231, the pre-clinical 3CL(pro) inhibitor GC-376, and the polymerase inhibitor remdesivir, in alveolar basal epithelial cells modified to express ACE2 (A549(+ACE2) cells). We find PF-00835231 with at least similar or higher potency than remdesivir or GC-376. A time-of-drug-addition approach delineates the timing of early SARS-CoV-2 life cycle steps in A549(+ACE2) cells and validates PF-00835231’s early time of action. In a model of the human polarized airway epithelium, both PF-00835231 and remdesivir potently inhibit SARS-CoV-2 at low micromolar concentrations. Finally, we show that the efflux transporter P-glycoprotein, which was previously suggested to diminish PF-00835231’s efficacy based on experiments in monkey kidney Vero E6 cells, does not negatively impact PF-00835231 efficacy in either A549(+ACE2) cells or human polarized airway epithelial cultures. Thus, our study provides in vitro evidence for the potential of PF-00835231 as an effective SARS-CoV-2 antiviral and addresses concerns that emerged based on prior studies in non-human in vitro models.
Development of a Multi-Material Mask-Image-Projection-Based Stereolithography for the Fabrication of Digital Materials (2011)

Digital materials such as the ones shown by Objet’s Connex family demonstrate that a new material with desired characteristics can be achieved by combining two different base materials with various concentrations and structures. We investigate the feasibility of using additive manufacturing processes based on digital mask projection in the fabrication of such digital materials. A multi-material mask-image-projection-based Stereolithography process has been developed. The related challenges on the development of such a process are identified. Our approaches to address such challenges are presented. A testbed has been developed to fabricate component with designed digital materials. Experimental results illustrate desired material properties can be achieved based on the developed process. Several multi-material designs have been produced to highlight the capability of this promising technology for fabricating three-dimensional, multi-material objects with spatial control over placement of both material and structure. The limitations and challenges for future development have also been identified.
Continuous liquid-phase piezoelectric biosensor for kinetic immunoassays (1989)

The reactions of immunoglobulins with protein A and, subsequently, of antibodies to these immunoglobulins were continuously monitored by a piezoelectric biosensor. AT-cut crystals, with a fundamental resonant frequency of 10 MHz, were mounted in a Plexiglas holder, and one side was directly coated with protein A. Upon exposure to solutions containing rabbit or human IgG the resonant frequency was followed continuously and its decrease due to the binding of IgG to protein A observed. Subsequent addition of sheep antihuman IgG to the now immobilized human IgG caused a specific 3-fold further decrease in resonant frequency. We observed a frequency change of approximately 1 Hz fore each 10 ng of added immunoglobulin. Decreasing the pH to 3 released the bound IgG but not the protein A and permitted reuse of the crystal for further IgG binding.
Fabrication of binary phase surface relief optical elements by selective deposition of dielectric layers (1999)

We propose and demonstrate a new scheme to fabricate surface relief binary phase elements by using selective deposition of dielectric layers through a contact mask. By using in situ optical thickness monitoring, accurate (∼1%), repeatable, and robust layer thicknesses are readily obtained, leading to accurate phases. We demonstrate our scheme by forming a circular π phase element that is used to form a dark optical trap for atoms.