gebhart/patrepeval huggingface dataset:
Phylogenetic conservation of arylsulfatases. cDNA cloning and expression of human arylsulfatase B. (1990)

A 2.2-kilobase cDNA clone for human arylsulfatase B (ASB) and several genomic clones were isolated and sequenced. The deduced amino acid sequence of 533 amino acids contains a 41-amino acid N-terminal signal peptide and a mature polypeptide of 492 amino acid residues. Overexpression of ASB in transfected baby hamster kidney (BHK) cells resulted in up to 68-fold higher ASB activity than in untransfected BHK cells. Pulse-chase labeling showed that ASB was synthesized and secreted as a 64-kDa precursor and processed to a 47-kDa mature form in BHK cells. The 47-kDa ASB form was located in dense lysosomes. Transport of ASB to the lysosomes was accomplished in a mannose 6-phosphate receptor-dependent manner. The ASB cDNA clone hybridizes to 4.8-, 2.5-, and 1.8-kilobase species of RNA from human fibroblasts. The same pattern was observed in RNA from fibroblasts of three Maroteaux-Lamy patients who were deficient in ASB activity, as well as in RNA from fibroblasts of three patients with multiple sulfatase deficiency, in which all known sulfatases were markedly diminished. Deduced amino acid sequences of human arylsulfatase A, human ASB, human steroid sulfatase, human glucosamine-6-sulfatase, and an arylsulfatase from sea urchin showed a substantial degree of similarity suggesting that they arose from a common ancestral gene and are members of an arylsulfatase gene family.
The geometrical properties of irregular two-dimensional Voronoi tessellations (2001)

Abstract We describe a parameter used to quantify the regularity of two-dimensional Voronoi tessellations based upon assemblies of ‘hard-core’ discs. The value of this parameter may vary continuously from zero, for a completely random Poisson Voronoi tessellation, to one, for a fully ordered regular hexagonal honeycomb. For various values of this parameter, 105 Voronoi cells are simulated and the statistical distributions of the number of sides per cell, the cell vertex angles, the cell edge lengths, the cell perimeters and the cell areas are each derived. The mean perimeters, areas and numbers of sides in the neighbouring cells are also investigated for n-sided cells in these tessellations. We find that, for all except the cell vertex angle distributions, the data can be adequately described by fitting either to existing models or, in the cases of the mean perimeters and mean areas of n-sided cells, to models which we propose.
Enhanced fermentation of mannitol and release of cytotoxin by Clostridium difficile in alkaline culture media (1995)

Clostridium difficile ATCC 43255 fermented less than 10% of the mannitol in a medium at pH 7; however, when the initial pH of the medium was adjusted to 8.5 or 9, about 80% of the mannitol was fermented. Cell extracts of C. difficile phosphorylated mannitol with phosphoenolpyruvate, not ATP, indicating a phosphoenolpyruvate phosphotransferase system transport phosphorylation of mannitol. The phosphorylation product was dehydrogenated by D-mannitol-1-phosphate:NAD oxidoreductase. Growth at an initial pH of 8.5 yielded cytotoxin titers of 10(7) to 10(8) in Trypticase-yeast extract-mannitol medium, wit a titer of 10(8) as early as 13 h.
Novel human-derived cell-penetrating peptides for specific subcellular delivery of therapeutic biomolecules (2005)

Short peptide sequences that are able to transport molecules across the cell membrane have been developed as tools for intracellular delivery of therapeutic molecules. This work describes a novel family of cell-penetrating peptides named Vectocell peptides [also termed DPVs (Diatos peptide vectors)]. These peptides, originating from human heparin binding proteins and/or anti-DNA antibodies, once conjugated to a therapeutic molecule, can deliver the molecule to either the cytoplasm or the nucleus of mammalian cells. Vectocell peptides can drive intracellular delivery of molecules of varying molecular mass, including full-length active immunoglobulins, with efficiency often greater than that of the well-characterized cell-penetrating peptide Tat. The internalization of Vectocell peptides has been demonstrated to occur in both adherent and suspension cell lines as well as in primary cells through an energy-dependent endocytosis process, involving cell-membrane lipid rafts. This endocytosis occurs after binding of the cell-penetrating peptides to extracellular heparan sulphate proteoglycans, except for one particular peptide (DPV1047) that partially originates from an anti-DNA antibody and is internalized in a caveolar independent manner. These new therapeutic tools are currently being developed for intracellular delivery of a number of active molecules and their potentiality for in vivo transduction investigated.
The pathogenesis of adoptive murine autoimmune diabetes requires an interaction between alpha 4-integrins and vascular cell adhesion molecule-1. (1994)

An adoptive transfer model of insulin-dependent diabetes mellitus (IDDM) in the nonobese diabetic mouse was used to examine the roles of alpha 4-integrin, vascular cell adhesion molecule 1 (VCAM-1); and intercellular adhesion molecule 1 (ICAM-1) in the pathogenesis of autoimmune diabetes. Antibodies specific for both alpha 4-integrin and one of its ligands, VCAM-1, were able to delay onset of diabetes and decrease the incidence of the disease in adoptive transfer studies. This blocking of disease was accompanied by a marked decrease in lymphocytic infiltration of the islets of Langerhans. Furthermore, these antibodies preferentially block entrance of CD4 T cells into the tissue. Antibodies specific for ICAM-1 had little effect on the onset or incidence of IDDM. Thus, we conclude that an alpha 4-integrin-VCAM-1 interaction is important in T cell entry into the islets of Langerhans and in the pathogenesis of IDDM. In addition, the cascade of events leading to T cell transit across endothelium may be different for CD4 and CD8 cells, and may differ depending on the endothelium involved. Our results support the more general conclusion that an alpha 4-integrin-VCAM-1 interaction may be crucial in allowing activated effector CD4T cells to leave the blood and enter tissue to clear infection.
Immunogenicity Testing of a Novel Engineered HIV-1 Envelope Gp140 DNA Vaccine Construct (2006)

DNA vaccines expressing the envelope (env) of the human immunodeficiency virus type 1 (HIV-1) have been relatively ineffective at generating strong immune responses. In this study, we described the development of a recombinant plasmid DNA (pEK2P-B) expressing an engineered codon-optimized envelope gp140 gene of primary (nonrecombinant) HIV-1 subtype B isolate 6101. Codon usage and RNA optimization of HIV-1 structural genes has been shown to increase protein expression in vitro as well as in the context of DNA vaccines in vivo. To further increase the expression, a synthetic IgE leader with kozak sequences were fused into the env gene. The cytoplasmic tail of the gene was also truncated to prevent recycling. The expression of env by the recombinant pEK2P-B was evaluated using T7 coupled transcription/translation. The construct demonstrated high expression of the HIV-1 env gene in eukaryotic cells as demonstrated in transfected 293-T and RD cells. Immunogenicity of pEK2P-B was evaluated in mice using IFN-gamma ELISpot assay, and the construct was found to be highly immunogenic and crossreactive with HIV-1 clade C env peptides. Three immunodominant peptides were also mapped out. Furthermore, by performing a CFSE flow cytometry-based proliferation assay, 2.4 and 1.5% proliferation was observed in CD4+, CD8+, and CCR+ memory T cells, respectively. Therefore, this engineered synthetic optimized env DNA vaccine may be useful in DNA vaccine and other studies of HIV-1 immunogenicity.
Cell Therapy for Cardiovascular Disease: A Comparison of Methods of Delivery (2010)

The field of myocardial regeneration utilizing novel cell-based therapies, gene transfer, and growth factors may prove to play an important role in the future management of ischemic heart disease and cardiomyopathy. Phases I and II clinical trials have been published for a variety of biologics utilizing four methods of delivery: systemic infusion, intracoronary infusion, transvenous coronary sinus, and intramyocardial. This review discusses the advantages and disadvantages of the delivery approaches above.
Contrast Radiology, Computed Tomography and Ultrasonography in Detecting Internal Fistulas and Intra-Abdominal Abscesses in Crohn's Disease: A Prospective Comparative Study (2003)

Despite the fact that barium radiology is widely considered the method of choice in detection of internal fistulae, accuracy is not entirely satisfactory. Comparable accuracy was found for US and CT. The combination of barium and US studies, or the sole use of US in more CD patients with more severe disease, can reliably detect most internal fistulae and abscesses.
A review of time-delay estimation techniques (2004)

This paper reviews and evaluates suggested methods for estimating the time-delay of linear systems in automatic control applications. A classification of the methods according to the underlying principles is suggested. The evaluation, done by analyzing the estimates of the methods from extensive simulated data in open loop, shows that different classes of methods have different properties and are suitable in different cases. Some method are clearly inferior to others. Recommendations are given on how to choose estimation method and input signal.
Hypertext Markup Language - 2.0 (1995)

This document specifies an Internet standards track protocol for the Internet community, and requests discussion and suggestions for improvements.
Automatic diagnosis and response to memory corruption vulnerabilities (2005)

Cyber attacks against networked computers have become relentless in recent years. The most common attack method is to exploit memory corruption vulnerabilities such as buffer overflow and format string bugs. This paper presents a technique to automatically identify both known and unknown memory corruption vulnerabilities. Based on the observation that a randomized program usually crashes upon a memory corruption attack, this technique uses the crash as a trigger to initiate an automatic diagnosis algorithm. The output of the diagnosis includes the instruction that is tricked to corrupt data, the call stack at the time of corruption, and the propagation history of corrupted data. These results provide useful information in fixing the vulnerabilities. Moreover, the diagnosis process also generates a signature of the attack using data/address values embedded in the malicious input message, and is used to block future attacks. Such a signature is further associated with the program execution state to reduce false positives without decreasing the detection rate. The proposed techniques enable the development of a decentralized self-diagnosing and self-protecting defense mechanism for networked computers. We report the implementation experience and experimental evaluation of a prototype system on Linux.
Synthesis of a β-Estradiol-Biotin Chimera that Potently Heterodimerizes Estrogen Receptor and Streptavidin Proteins in a Yeast Three-Hybrid System (2003)

Small molecules that dimerize proteins in living cells provide powerful probes of biological processes and have potential as tools for the identification of protein targets of natural products. We synthesized 7-alpha-substituted derivatives of beta-estradiol tethered to the natural product biotin to regulate heterodimerization of estrogen receptor (ER) and streptavidin (SA) proteins expressed as components of a yeast three-hybrid system. Addition of an estradiol-biotin chimera bearing a 19-atom linker to yeast expressing DNA-bound ER-alpha or ER-beta LexA fusion proteins and wild-type SA protein fused to the B42 activation domain activated reporter gene expression by as much as 450-fold in vivo (10 muM ligand). Comparative analysis of lower affinity Y43A (biotin Kd approximately 100 pM) and W120A (biotin Kd approximately 100 nM) mutants of SA indicated that moderate affinity interactions can be readily detected with this system. Comparison of a 7-alpha-substituted estradiol-biotin chimera with a structurally similar dexamethasone-biotin chimera revealed that yeast expressing ER proteins can detect cognate ligands with up to 5-fold greater potency and 70-fold higher activity than yeast expressing analogous glucocorticoid receptor (GR) proteins. This approach may facilitate the identification of protein targets of biologically active small molecules screened against genetically encoded libraries of proteins expressed in yeast three-hybrid systems.
Eye gaze tracking using an active stereo head (2003)

In the eye gaze tracking problem, the goal is to determine where on a monitor screen a computer user is looking, ie., the gaze point. Existing systems generally have one of two limitations: either the head must remain fixed in front of a stationary camera, or, to allow for head motion, the user must wear an obstructive device. We introduce a 3D eye tracking system where the head motion is allowed without the need for markers or worn devices. We use a pair of stereo systems: a wide angle stereo system detects the face and steers an active narrow FOV stereo system to track the eye at high resolution. For high resolution tracking, the eye is modeled in 3D, including the corneal ball, pupil and fovea. We discuss the calibration of the stereo systems, the eye model, eye detection and tracking, and we close with an evaluation of the accuracy of the estimated gaze point on the monitor.
Increased concentrations of interleukin 1 beta, interleukin-2, and soluble interleukin-2 receptors in endoscopical mucosal biopsy specimens with active inflammatory bowel disease. (1992)

Concentrations of interleukin-1 beta (IL-1 beta), interleukin-2 (IL-2), and soluble IL-2 receptors (sIL-2R) were determined by enzyme linked immunosorbent assays (ELISA) in supernatants of sonicated endoscopical mucosal biopsy specimens from 31 patients with inflammatory bowel disease and 19 controls. IL-1 beta was detected in 53% of the patient supernatants (p = 0.0001), IL-2 in 35% (p = 0.0031), compared with none of the controls. Soluble IL-2R was present in 55% and 26% of the specimens, respectively (p = 0.07). The concentrations of IL-1 beta (p = 0.00015), IL-2 (p = 0.0019), and sIL-2R (p = 0.0073) were highest in the most inflamed biopsy specimens, compared with less inflamed specimens and controls. There were no significant differences in IL-1 beta, IL-2, and sIL-2R concentrations between ulcerative colitis (16) and Crohn's disease patients (15). The results suggest that enhanced cellular immunity operates in vivo at the mucosal level in active inflammatory bowel disease.
Antitumorigenic effects of HIV protease inhibitor ritonavir: inhibition of Kaposi sarcoma (2002)

Treatment of patients with human immunodeficiency virus (HIV) protease inhibitors such as ritonavir can result in increases in CD4(+) T-cell counts that are independent of a reduction in HIV-1 viral load. This lack of correlation between the 2 has led to the identification of additional effects of ritonavir that potentially alter HIV disease pathogenesis. Our previous studies indicated that ritonavir directly affects immune cell activation, proliferation, and susceptibility to apoptosis. We show here that ritonavir inhibited the activation and proliferation of primary endothelial cells and decreased the production of tumor necrosis factor alpha (TNF-alpha) interleukin 6 (IL-6), IL-8, and vascular endothelial growth factor, factors that all contribute to tumor neovascularization and to the development of Kaposi sarcoma (KS) lesions. Ritonavir also suppressed the expression of vascular cell adhesion molecule 1, intercellular adhesion molecule 1, and E-selectin, which correlated with a functional decrease in leukocyte adhesion. Transcriptional activation of nuclear factor-kappaB, as induced by the KS-promoting factor TNF-alpha, the HIV-1 Tat protein, or the human herpesvirus 8 protein ORF74, was inhibited by ritonavir. KS-derived cell lines underwent apoptosis in vitro after treatment with ritonavir at concentrations that are obtained in clinical therapy (3-15 microM). In a KS mouse xenotransplantation model, ritonavir inhibited tumor formation and progression by KS-derived cells. Taken together, these data suggest that ritonavir has antineoplastic effects that are independent from its ability to inhibit the HIV protease.
Fusing mobile, sensor, and social data to fully enable context-aware computing (2010)

In this paper, we identify mobile social networks as an important new direction of research in mobile computing, and show how an expanded definition of mobile social networks that includes sensor networks can enable exciting new context-aware applications, such as context-aware video screens, music jukeboxes, and mobile health applications. We offer SocialFusion as a system capable of systematically integrating such diverse mobile, social, and sensing input streams and effectuating the appropriate context-aware output action. We explain some of the major challenges that SocialFusion must overcome. We describe some preliminary results that we have obtained in implementing the SocialFusion vision.
Neurologic Abnormalities of Lyme Disease: Successful Treatment with High-Dose Intravenous Penicillin (1983)

Twelve patients were treated with high-dose intravenous penicillin for neurologic abnormalities of Lyme disease. Headache, stiff neck, and radicular pain usually began to subside by the second day of therapy and were often gone by 7 to 10 days. Five of the 12 patients continued to have intermittent mild headache for several more weeks, but no patient relapsed after therapy was stopped. Compared to 15 previous patients treated with prednisone alone, the duration of meningitic syndrome was significantly shorter in those given penicillin (mean duration, 1 versus 29 weeks, p less than 0.000001). However, in both groups, a mean of 7 to 8 weeks was required for complete recovery of motor deficits. Despite antibiotic therapy, 3 of the 12 patients treated with penicillin continued to have frequent arthralgias, musculoskeletal pain, and fatigue. We conclude that high-dose intravenous penicillin is effective therapy for neurologic abnormalities of Lyme disease.
Prevention of smooth muscle cell outgrowth from human atherosclerotic plaque by a recombinant cytotoxin specific for the epidermal growth factor receptor. (1993)

Smooth muscle cell proliferation in the intima of arteries is a principal event associated with vascular narrowing after balloon angioplasty and bypass surgery. Techniques for limiting smooth muscle cell proliferation, however, have not as yet yielded any therapeutic benefit for these conditions. This may reflect the present lack of sufficiently potent and specific inhibitors of smooth muscle cell proliferation. DAB389 EGF is a genetically engineered fusion protein in which the receptor-binding domain of diphtheria toxin has been replaced by human epidermal growth factor. We evaluated the effect of this fusion toxin on human vascular smooth muscle cells in culture. Incubation of proliferating cells with DAB389 EGF yielded a dose-dependent inhibition of protein synthesis, as assessed by uptake of [3H]leucine, with an IC50 of 40 pM. The cytotoxic effect was inhibited in the presence of excess EGF or with monoclonal antibody to the EGF receptor. We further studied the effect of the fusion toxin on smooth muscle cell outgrowth from human atherosclerotic plaque. Outgrowth was markedly inhibited after as little as 1 h of exposure to the fusion protein. Furthermore, complete inhibition of proliferation of cells within the plaque could be attained. These results demonstrate that DAB389 EGF is highly cytotoxic to human smooth muscle cells proliferating in culture and can prevent smooth muscle cell outgrowth from "growth-stimulated" human atherosclerotic plaque. DAB389 EGF may therefore be of therapeutic value in vascular diseases characterized by smooth muscle cell accumulation.
MALDI Imaging Mass Spectrometry – Painting Molecular Pictures (2010)

MALDI Imaging Mass Spectrometry is a molecular analytical technology capable of simultaneously measuring multiple analytes directly from intact tissue sections. Histological features within the sample can be correlated with molecular species without the need for target-specific reagents such as antibodies. Several studies have demonstrated the strength of the technology for uncovering new markers that correlate with disease severity as well as prognosis and therapeutic response. This review describes technological aspects of imaging mass spectrometry together with applications in cancer research.
Long-term treatment with vagus nerve stimulation in patients with refractory epilepsy (1999)

Long-term, open-label vagus nerve stimulation (VNS) provided seizure reduction similar to or greater than acute studies, for median reductions and for those reaching a > or =50% seizure reduction. VNS remained safe and well tolerated, with nearly three-quarters of the patients choosing to continue therapy.
Idiopathic Pulmonary Alveolar Proteinosis as an Autoimmune Disease with Neutralizing Antibody against Granulocyte/Macrophage Colony-Stimulating Factor (1999)

Idiopathic pulmonary alveolar proteinosis (I-PAP) is a rare disease of unknown etiology in which the alveoli fill with lipoproteinaceous material. We report here that I-PAP is an autoimmune disease with neutralizing antibody of immunoglobulin G isotype against granulocyte/macrophage colony-stimulating factor (GM-CSF). The antibody was found to be present in all specimens of bronchoalveolar lavage fluid obtained from 11 I-PAP patients but not in samples from 2 secondary PAP patients, 53 normal subjects, and 14 patients with other lung diseases. It specifically bound GM-CSF and neutralized bioactivity of the cytokine in vitro. The antibody was also found in sera from all I-PAP patients examined but not in sera from a secondary PAP patient or normal subjects, indicating that it exists systemically in I-PAP patients. As lack of GM-CSF signaling causes PAP in congenital cases and PAP-like disease in murine models, our findings strongly suggest that neutralization of GM-CSF bioactivity by the antibody causes dysfunction of alveolar macrophages, which results in reduced surfactant clearance.
Helios, CD73 and CD39 Induction in Regulatory T Cells Exposed to Adipose Derived Mesenchymal Stem Cells. (2020)

The results further confirm the immunosuppressive impacts of ASCs on T lymphocytes and direct them to specific regulatory phenotypes which may support immune evasion and tumor growth.