gebhart/patrepeval huggingface dataset:
Analysis of the Binding of Pro-urokinase and Urokinase-Plasminogen Activator Inhibitor-1 Complex to the Low Density Lipoprotein Receptor-related Protein Using a Fab Fragment Selected from a Phage-displayed Fab Library (1995)

The low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor (LRP) mediates endocytosis of a number of structurally unrelated ligands, including complexes of plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (t-PA) or urokinase plasminogen activator (u-PA), free t-PA, single-chain urokinase (pro-u-PA), alpha 2-macroglobulin-protease complexes, and lipoprotein lipase. So far, all ligands have in common the fact that they bind to the receptor in a Ca(2+)-dependent way and the fact that binding to the receptor can be inhibited by a 39-40-kDa protein, termed the receptor-associated protein. To obtain inhibitory antibodies for the analysis of the structure and function of the receptor we applied the combinatorial immunoglobulin repertoire cloning technique in order to specifically select monoclonal Fab fragments directed against Ca(2+)-dependent epitopes. In this report we describe the isolation of a Fab fragment (Fab A8) showing a high relative affinity for the receptor (0.5 nM). The binding of this Fab fragment to purified LRP is inhibited in the presence of 5 mM EDTA, receptor-associated protein, and lipoprotein lipase (IC50 values of 1.4 and 31 nM, respectively). By immunoblotting of CNBr-digested LRP it is shown that Fab A8 binds to a fragment that harbors the second cluster of cysteine-rich complement-type repeats flanked by epidermal growth factor repeats. Binding studies using 125I-labeled ligands and immobilized receptor show that Fab A8 partially inhibits the binding of [125I]u-PA.PAI-1 complexes (IC50 = 1.1 nM) and completely inhibits the binding of [125I]pro-u-PA to the receptor (IC50 = 2.2 nM). No inhibition was observed for the binding of 125I-labeled methylamine-activated alpha 2-macroglobulin or [125I]t-PA.PAI-1 to LRP. Degradation of [125I]u-PA.PAI-1 complexes by COS-1 cells was also partially (43%) inhibited by Fab A8. Our results provide evidence for the presence of an interaction site for pro-u-PA localized in the second cluster of cysteine-rich repeats that is unrelated to the t-PA.PAI-1 or methylamine-activated alpha 2-macroglobulin interaction sites.
The “oral” history of COVID‐19: Primary infection, salivary transmission, and post‐acute implications (2021)

Severe acute respiratorysyndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, has led to more than 3.25 million recorded deaths worldwide as of May 2021. COVID-19 is known to be clinically heterogeneous, and whether the reported oral signs and symptoms in COVID-19 are related to the direct infection of oral tissues has remained unknown. Here, we review and summarize the evidence for the primary infection of the glands, oral mucosae, and saliva by SARS-CoV-2. Not only were the entry factors for SARS-CoV-2 found in all oral tissues, but these were also sites of SARS-CoV-2 infection and replication. Furthermore, saliva from asymptomatic individuals contained free virus and SARS-CoV-2-infected oral epithelial cells, both of which were found to transmit the virus. Collectively, these studies support an active role of the oral cavity in the spread and transmission of SARS-CoV-2 infection. In addition to maintaining the appropriate use of personal protective equipment and regimens to limit microbial spread via aerosol or droplet generation, the dental community will also be involved in co-managing COVID-19 "long haulers"-now termed Post-Acute COVID-19 Syndrome. Consequently, we propose that, as SARS-CoV-2 continues to spread and as new clinical challenges related to COVID-19 are documented, oral symptoms should be included in diagnostic and prognostic classifications as well as plans for multidisciplinary care.
The Design and Implementation of a Full Field Inter-Well Tracer Program on a Giant UAE Carbonate Oil Field (2015)

Abstract This paper reviews the design and implementation of a full field inter well tracer program of a giant onshore oil field in Abu Dhabi. The field is under peripheral waterflooding in order to maintain reservoir pressure and provide a mechanism to sweep the oil. However, the existence of the strike-slip fault planes juxtaposed across the reservoirs added a variable to the complexity of the waterflood management. In order to improve the understanding towards the reservoir heterogeneity and reduce the uncertainties associated with major faults, a full field water tracer program which is possibly the largest in the Middle East has been designed. Based on streamline model, unique chemical tracers have been injected in twenty three water injectors covering all the peripheral areas and dozens of associated offset producers across the field were selected to monitor the tracer movement. The program have been designed carefully in terms of tracer selection &amp; compatibility test, chemical volume calculation, injection well and monitoring well selection, as well as the devise of the comprehensive monitoring plan. Ultimately the results of this tracer program will be used in combination with other reservoir surveillance tools to facilitate a better management of the reservoir. Interwell tracers technology is a valuable tool for reservoir management, however, reliable tracer data can only be obtained through judicious design, implementation and monitoring. The preliminary results from designing the tracer program include: 1) Twenty three water injectors were identified based on streamline modeling for tracer injection and dozens of producers for monitoring. 2) Injected tracers were selected based on the uniqueness, stability, detection limit and environmental friendliness, and compatibility tests were done in advance between tracers and reservoir fluids. 3) Total dilution method was used to calculate the quantity of tracers injected in each of the well. 4) A comprehensive monitoring program was scheduled to capture the arriving of the tracer as well as to depict the entire tracer wave. The presented full field water tracer program of a giant onshore oil field is possibly the largest in Middle East, and the described designing of the program, encountered problems and best practice could be of some use to those intended planning a tracer project.
Role of spinal GABAAreceptors in pudendal inhibition of nociceptive and nonnociceptive bladder reflexes in cats (2014)

Picrotoxin, an antagonist for γ-aminobutyric acid receptor subtype A (GABAA), was used to investigate the role of GABAA receptors in nociceptive and nonnociceptive reflex bladder activities and pudendal inhibition of these activities in cats under α-chloralose anesthesia. Acetic acid (AA; 0.25%) was used to irritate the bladder and induce nociceptive bladder overactivity, while saline was used to distend the bladder and induce nonnociceptive bladder activity. To modulate the bladder reflex, pudendal nerve stimulation (PNS) was applied at multiple threshold (T) intensities for inducing anal sphincter twitching. AA irritation significantly (P < 0.01) reduced bladder capacity to 34.3 ± 7.1% of the saline control capacity, while PNS at 2T and 4T significantly (P < 0.01) increased AA bladder capacity to 84.0 ± 7.8 and 93.2 ± 15.0%, respectively, of the saline control. Picrotoxin (0.4 mg it) did not change AA bladder capacity but completely removed PNS inhibition of AA-induced bladder overactivity. Picrotoxin (iv) only increased AA bladder capacity at a high dose (0.3 mg/kg) but significantly (P < 0.05) reduced 2T PNS inhibition at low doses (0.01-0.1 mg/kg). During saline cystometry, PNS significantly (P < 0.01) increased bladder capacity to 147.0 ± 7.6% at 2T and 172.7 ± 8.9% at 4T of control capacity, and picrotoxin (0.4 mg it or 0.03-0.3 mg/kg iv) also significantly (P < 0.05) increased bladder capacity. However, picrotoxin treatment did not alter PNS inhibition during saline infusion. These results indicate that spinal GABAA receptors have different roles in controlling nociceptive and nonnociceptive reflex bladder activities and in PNS inhibition of these activities.
Two in situ labeling techniques reveal different patterns of DNA fragmentation during spontaneous apoptosis in vivo and induced apoptosis in vitro. (1996)

Thus our data show that the DNA fragments formed during spontaneous apoptosis in breast tissues and preferentially during VP16 induced apoptosis in HL60 cells are either 5' recessed or blunt ended, being distinctly different from 3' recessed fragments seen in NHL and HNSCC or with a lesser frequency in VP 16 treated HL60 cells. Specific fragmentation patterns could be a result of activation of different endonucleases which as indicated by our data could be tissue specific and may be differentially activated by different chemotherapeutic agents. Therefore, screening for the presence of specific endonucleases in different tissues and for agents specifically activating them would have major clinical implications.
The Effect of Treatment on Mortality in Mild Hypertension (1982)

In the Hypertension Detection and Follow-up Program, 7825 (71.5 per cent) of the 10,940 participants had diastolic blood pressures averaging between 90 and 104 mm Hg on entry into the study and were designated Stratum 1. Half were referred to their usual source of care in the community (the referred-care group), and half were treated intensively in special clinics (the stepped-care group). Five-year mortality in the Stratum 1 patients given stepped care was 20.3 per cent lower than in those given referred care (P less than 0.01). Particularly noteworthy was the beneficial effect of stepped-care treatment on persons with diastolic pressures of 90 to 104 mm Hg who had no evidence of end-organ damage and were not receiving antihypertensive medication when they entered the study. This subgroup had 28.6 per cent fewer deaths at five years among those treated with stepped care than among those treated with referred care (P less than 0.01). These findings support a recommendation that in patients with mild hypertension, treatment should be considered early, before damage to end organs occurs.
Identification of a Selective RORγ Ligand That Suppresses TH17 Cells and Stimulates T Regulatory Cells (2012)

Nuclear receptors (NRs) are ligand-regulated transcription factors, many of which are validated targets for clinical purposes. The retinoic acid receptor-related orphan nuclear receptors alpha and gamma t (RORα and RORγt) are considered to be the master regulators of development of T(H)17 cells, a subset of T cells that have been implicated in the pathology of several autoimmune diseases, including multiple sclerosis (MS) and rheumatoid arthritis (RA). We report here the identification of a novel RORγ-specific synthetic ligand, SR1555, that not only inhibits T(H)17 cell development and function but also increases the frequency of T regulatory cells. Our data suggests synthetic RORγ ligands can be developed that target both suppression of T(H)17 and stimulation of T regulatory cells, offering key advantages in development of therapeutics targeting autoimmune diseases.
MicroRNA-21 promotes the ovarian teratocarcinoma PA1 cell line by sustaining cancer stem/progenitor populations in vitro (2013)

MicroRNA-21 plays a significant role in cancer growth by regulating stemness in cancer cells.
Surgical Robotics: The Early Chronicles (2002)

The use of robotics has been emerging for approximately 75 years, but only during the past 5 years has the potential of robotics been recognized by the surgical community as a whole. This personal perspective chronicles the development of robotics for the general surgical community, the role of the military medical research effort, and many of the major programs that contributed to the current success of robotics.
Differential inhibitory effects of lovastatin on protein isoprenylation and sterol synthesis. (1990)

It has been reported that when 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors are utilized for treatment of hypercholesterolemia, as much as 50% inhibition of whole body cholesterol biosynthesis is observed. As general inhibitors of isoprenoid biosynthesis, these compounds can also inhibit the synthesis of the substituents of isoprenylated proteins. For two mammalian proteins (p21ras and lamin A), it has been demonstrated that such inhibition of biosynthesis of the isoprenoid substituent blocks proteolytic maturation of these proteins. It has been argued that advantage may be taken of this phenomenon to block the synthesis of p21ras in malignancies. It is also possible that treatment of hypercholesterolemia with lovastatin might produce problematic inhibition of protein processing dependent upon isoprenylation. In this report, we compare the concentration dependence of inhibition of isoprenylation dependent protein processing and sterol biosynthesis. Effects of partial inhibition of isoprenylated protein processing on whole cells can be sensitively assessed by visualization of lamina structure through indirect immunofluorescence. Our results indicate that the degree of inhibition of p21ras and prelamin A maturation by lovastatin is identical. Thus, 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors are unlikely to be useful as anti-malignancy drugs. However, the conditions of lovastatin treatment which produce 50% inhibition of sterol biosynthesis analogous to pharmacological conditions, produce no observable effects on isoprenylated protein maturation.
Wavelet-based image indexing techniques with partial sketch retrieval capability (2002)

This paper describes WBIIS (Wavelet-Based Image Indexing and Searching), a new image indexing and retrieval algorithm with partial sketch image searching capability for large image databases. The algorithm characterizes the color variations over the spatial extent of the image in a manner that provides semantically-meaningful image comparisons. The indexing algorithm applies a Daubechies' wavelet transform for each of the three opponent color components. The wavelet coefficients in the lowest few frequency bands, and their variances, are stored as feature vectors. To speed up retrieval: a two-step procedure is used that first does a crude selection based on the variances, and then refines the search by performing a feature vector match between the selected images and the query. For better accuracy in searching, two level multiresolution matching may also be used. Masks are used for partial-sketch queries. This technique performs much better in capturing coherence of image, object granularity, local color/texture, and bias avoidance than traditional color layout algorithms. When tested on a database of more than 10,000 general-purpose images, WBIIS is much faster and more accurate than traditional algorithms.
Identification of mutations in the gene encoding lamins A/C in autosomal dominant limb girdle muscular dystrophy with atrioventricular conduction disturbances (LGMD1B) (2000)

LGMD1B is an autosomal dominantly inherited, slowly progressive limb girdle muscular dystrophy, with age-related atrioventricular cardiac conduction disturbances and the absence of early contractures. The disease has been linked to chromosome 1q11-q21. Within this locus another muscular dystrophy, the autosomal dominant form of Emery-Dreifuss muscular dystrophy (AD-EDMD) has recently been mapped and the corresponding gene identified. AD-ADMD is characterized by early contractures of elbows and Achilles tendons and a humero-peroneal distribution of weakness combined with a cardiomyopathy with conduction defects. The disease gene of AD-EDMD is LMNA which encodes lamins A/C, two proteins of the nuclear envelope. In order to identify whether or not LGMD1B and AD-EDMD are allelic disorders, we carried out a search for mutations in the LMNA gene in patients with LGMD1B. For this, PCR/SSCP/sequencing screening was carried out for the 12 exons of LMNA on DNA samples of individuals from three LGMD1B families that were linked to chromo-some 1q11-q21. Mutations were identified in all three LGMD1B families: a missense mutation, a deletion of a codon and a splice donor site mutation, respectively. The three mutations were identified in all affected members of the corresponding families and were absent in 100 unrelated control subjects. The present identification of mutations in the LMNA gene in LGMD1B demonstrates that LGMD1B and AD-EDMD are allelic disorders. Further analysis of phenotype-genotype relationship will help to clarify the variability of the phenotype observed in these two muscular dystrophies.
A Novel Viral Transcript with Homology to Human Interleukin-10 Is Expressed during Latent Human Cytomegalovirus Infection (2004)

Human cytomegalovirus (CMV) establishes latent infections in hematopoietic cells such as granulocyte-macrophage progenitors (GM-Ps). During latency the virus is sequestered in a nonreplicating state, although limited transcriptional activity has been previously reported. In this study we sought to further examine viral gene expression during the latent phase of infection. Using an experimental model of latency, primary human GM-Ps were latently infected with CMV strain Toledo and extracted RNA subjected to reverse transcription-PCR by using CMV gene-specific primers. Using this approach, we detected transcription from the UL111.5A region of the viral genome. This transcription was also detected in GM-Ps latently infected with AD169 and Towne strains, indicating that expression was CMV strain independent. Significantly, we detected UL111.5A-region transcripts in mononuclear cells from healthy bone marrow and mobilized peripheral blood allograft donors, demonstrating expression during natural latent infection. Mapping experiments with RNA extracted from latently infected GM-Ps revealed the expression of a novel UL111.5A region transcript with a splicing pattern that differed from that reported during productive infection of permissive cells. This UL111.5A region transcript expressed during latent infection is predicted to encode a 139-amino-acid protein with homology to the potent immunosuppressor interleukin-10 (IL-10) and to the viral IL-10 homolog that is expressed during productive CMV infection. Expression of a latency-associated cmvIL-10 may confer upon the virus an ability to avoid immune recognition and clearance during the latent phase of infection.
Amplified-Fragment Length Polymorphism Analysis: the State of an Art (1999)

In the past decade, various methods have been developed for the identification and typing of prokaryotic and eukaryotic organisms at the DNA level. These methods differ in their taxonomic range, discriminatory power, reproducibility, and ease of interpretation and standardization ([62][1], [67][2
Enhanced in vitro potency and in vivo immunogenicity of a CTL epitope from hepatitis C virus core protein following amino acid replacement at secondary HLA-A2.1 binding positions. (1998)

Since the natural immune response to hepatitis C virus (HCV) is often unable to clear the infection, to enhance immunogenicity we studied substituted peptides from an HCV cytotoxic T lymphocyte (CTL) epitope (C7A2) from a conserved region of the HCV core protein (DLMGYIPLV) recognized by CTL lines from HLA-A2.1(+) HCV-infected patients and HLA-A2.1 transgenic mice. HLA-A2.1 binding, human and murine CTL recognition, and in vivo immunogenicity (using mice transgenic for human HLA-A2 in lieu of immunizing humans) were analyzed to define peptides with enhanced immunogenicity. Peptides substituted at position 1 showed enhanced HLA-A2 binding affinity, but paradoxically poorer immunogenicity. A peptide with Ala substituted at position 8 (8A) showed higher HLA-A2 binding affinity and CTL recognition and was a more potent in vivo immunogen in HLA-A2-transgenic mice, inducing higher CTL responses with higher avidity against native C7A2 than induced by C7A2 itself. These results suggest that peptide 8A is a more potent in vitro antigen and in vivo immunogen than C7A2 and may be useful as a vaccine component. They provide proof of principle that the strategy of epitope enhancement can enhance immunogenicity of a CTL epitope recognized by human CTL.
Prolyl hydroxylase inhibitors increase neoangiogenesis and callus formation following femur fracture in mice (2009)

Skeletal trauma and impaired skeletal healing is commonly associated with diminished vascularity. Hypoxia inducible factor alpha (HIF-1) is a key transcription factor responsible for activating angiogenic factors during development and tissue repair. Small molecule inhibitors of the prolyl hydroxylase enzyme (PHD), the key enzyme responsible for degrading HIF-1, have been shown to activate HIF-1, and are effective in inducing angiogenesis. Here we examined the effects of several commercially available PHD inhibitors on bone marrow mesenchymal stromal cells (MSCs) in vitro and in a stabilized fracture model in vivo. Three PHD inhibitors [Desferrioxamine (DFO), L-mimosine (L-mim), and Dimethyloxalylglycine (DMOG)] effectively activated a HIF-1 target reporter, induced expression of vascular endothelial growth factor (VEGF) mRNA in vitro, and increased capillary sprouting in a functional angiogenesis assay. DFO and DMOG were applied by direct injection at the fracture site in a stabilized murine femur fracture model. PHD inhibition increased the vascularity at 14 days and increased callus size as assessed by microCT at 28 days. These results suggest that HIF activation is a viable approach to increase vascularity and bone formation following skeletal trauma.
Type I interferon is selectively required by dendritic cells for immune rejection of tumors (2011)

Cancer immunoediting is the process whereby the immune system suppresses neoplastic growth and shapes tumor immunogenicity. We previously reported that type I interferon (IFN-α/β) plays a central role in this process and that hematopoietic cells represent critical targets of type I IFN's actions. However, the specific cells affected by IFN-α/β and the functional processes that type I IFN induces remain undefined. Herein, we show that type I IFN is required to initiate the antitumor response and that its actions are temporally distinct from IFN-γ during cancer immunoediting. Using mixed bone marrow chimeric mice, we demonstrate that type I IFN sensitivity selectively within the innate immune compartment is essential for tumor-specific T cell priming and tumor elimination. We further show that mice lacking IFNAR1 (IFN-α/β receptor 1) in dendritic cells (DCs; Itgax-Cre(+)Ifnar1(f/f) mice) cannot reject highly immunogenic tumor cells and that CD8α(+) DCs from these mice display defects in antigen cross-presentation to CD8(+) T cells. In contrast, mice depleted of NK cells or mice that lack IFNAR1 in granulocytes and macrophage populations reject these tumors normally. Thus, DCs and specifically CD8α(+) DCs are functionally relevant targets of endogenous type I IFN during lymphocyte-mediated tumor rejection.