gebhart/patrepeval huggingface dataset:
Restriction Landmark Genomic Scanning: Analysis of CpG Islands in Genomes by 2D Gel Electrophoresis (2008)

Restriction landmark genomic scanning (RLGS) is a method that provides a quantitative genetic and epigenetic (cytosine methylation) assessment of thousands of CpG islands in a single gel without prior knowledge of gene sequence. The method is based on two-dimensional separation of radiolabeled genomic DNA into nearly 2,000 discrete fragments that have a high probability of containing gene sequences. Genomic DNA is digested with an infrequently cutting restriction enzyme, such as NotI or AscI, radiolabeled at the cleaved ends, digested with a second restriction enzyme, and then electrophoresed through a narrow, 60-cm-long agarose tube-shaped gel. The DNA in the tube gel is then digested by a third, more frequently cutting restriction enzyme and electrophoresed, in a direction perpendicular to the first separation, through a 5% nondenaturing polyacrylamide gel, and the gel is autoradiographed. Radiolabeled NotI or AscI sites are frequently used as "landmarks" because NotI or AscI cannot cleave methylated sites and since an estimated 89% and 83% of the recognition sites, respectively, are found within CpG islands. Using a methylation-sensitive enzyme, the technique has been termed RLGS-M. The resulting RLGS profile displays both the copy number and methylation status of the CpG islands. Integrated with high-resolution gene copy-number analyses, RLGS enables one to define genetic or epigenetic alteration in cells. These profiles are highly reproducible and are therefore amenable to inter- and intraindividual DNA sample comparisons. RLGS was the first of many technologies to allow large-scale DNA methylation analysis of CpG islands.
Direct Calcium Binding Results in Activation of Brain Serine Racemase (2002)

Serine racemase (SR) is a brain enzyme present in glial cells, where it isomerizes L-serine into D-serine that, in turn, diffuses and coactivates the N-methyl-D-aspartate receptor through the binding to the so-called "glycine site." We have developed a method for the slow expression of SR in a eukaryotic vector that permits the correct insertion of the prosthetic group into the active site, rendering functional SR with a K(m) toward L-serine of 4.8 mm. Divalent cations such as calcium or manganese were necessary for complete enzyme activity, whereas the presence of chelators such as EDTA completely inhibited the enzyme. Moreover, direct binding of calcium to SR was evidenced using (45)Ca(2+). Gel filtration of the recombinant SR revealed the protein to be in a dimer-tetramer equilibrium. The addition of EDTA to a calcium-saturated serine racemase evokes a profound conformational change, as monitored by both fluorescence and circular dichroism techniques. Fluorescence titration allowed us to calculate a binding constant for calcium of 6.2 microm. Reagents that react with sulfhydryl groups, such as cystamine, were potent inhibitors of SR, in a clear reflection that one or more cysteine residues are important for enzyme activity. Additionally, 16 serine analogues were tested as a putative SR substrate or inhibitors. Significant inhibition was only observed for L-Ser-O-sulfate, L-cycloserine, and L-cysteine. Finally, activation of brain SR as a result of the changes in calcium concentration was studied in primary astrocytes. Treatment of astrocytes with the calcium ionophore, as well as with compounds that augment the intracellular calcium levels such as glutamate or kainate led to an increase in the amount of d-serine present in the extracellular medium. These results suggest that there might be a glutamatergic-mediated regulation of SR activity by intracellular calcium concentration.
Design of Gram-Negative Selective Antimicrobial Peptides (2001)

Lipopolysaccharide (LPS), a major component of Gram-negative bacteria, signals bacterial invasion and triggers defensive host responses. However, excessive responses also lead to the serious pathophysiological consequence of septic shock. To develop Gram-negative selective compounds that can inhibit the effects of LPS-induced sepsis, we have designed constrained cyclic antimicrobial peptides based on a cystine-stabilized beta-stranded framework mimicking the putative LPS-binding sites of the LPS-binding protein family. Our prototype termed R4A, c(PACRCRAG-PARCRCAG), consists of an eight amino acid degenerated repeat constrained by a head-to-tail cyclic peptide backbone and two cross-bracing disulfides. NMR study of K4A, an R4A analogue with four Arg --> Lys replacements, confirmed the amphipathic design elements with four Lys on one face of the antiparallel beta-strand and two hydrophobic cystine pairs plus two Ala on the opposite face. K4A and R4A displayed moderate microbicidal potency and Gram-negative selectivity. However, R4A analogues with single or multiple replacements of Ala and Gly with Arg or bulky hydrophobic amino acids displayed increased potency and selectivity in both low- and high-salt conditions. Analogues R5L and R6Y containing additional cationic and bulky hydrophobic amino acids proved the best mimics of the amphipathic topology of the "active-site" beta-strands of LPS-binding proteins. They displayed potent activity against Gram-negative E. coli with a minimal inhibitory concentration of 20 nM and a >200-fold selectivity over Gram-positive S. aureus. Our results suggest that an LPS-targeted design may present an effective approach for preparing selective peptide antibiotics.
Kinematics and Electromyography of Landing Preparation in Vertical Stop-Jump (2007)

Lower extremity motion patterns during landing of the stop-jump task are preprogrammed before landing. Female subjects prepared for landing with decreased hip and knee flexion at landing, increased quadriceps activation, and decreased hamstring activation, which may result in increased anterior cruciate ligament loading during the landing of the stop-jump task and the risk for noncontact ACL injury.
Human immunodeficiency virus type 1 gp120 mimics a hidden monomorphic epitope borne by class I major histocompatibility complex heavy chains. (1991)

Murine monoclonal antibodies (mAbs) M38 and L31 define two epitopes of a surface protein of activated lymphocytes and monocytes. It has been shown that M38 also defines a crossreactive epitope of human immunodeficiency virus type 1 (HIV-1) gp120 (Beretta et al., 1987. Eur. J. Immunol. 17: 1793). The mAb inhibits syncytia formation driven by HIV-1-infected cells. The surface protein was demonstrated to be a class I MHC alpha chain, by sequence analysis of the corresponding cDNA and by immunological means. The epitopes defined by mAbs M38 and L31 are monomorphic and hidden (i.e., inaccessible to antibodies) on native HLA molecules expressed by resting cells, but can be evidenced on denatured proteins by Western blot analysis. The two epitopes become accessible after activation processes have been implemented, likely reflecting a conformational alteration of alpha chains (such as that described by Schnabl et al. 1990. J. Exp. Med. 171:1431). Consistent with molecular data are the results of functional analysis, which indicate that the molecule recognized by M38 and L31 is a gate for pleiotropic negative signals, since the two mAbs were shown to inhibit monocyte antigen presentation and lymphocyte mitogenic proliferation, respectively.
Reversal of Inflammatory Bowel Disease (IBD) with Recurrent Faecal Microbiota Transplants (FMT) (2011)

Purpose: Faecal Microbiota Transplantation (FMT)effectively eradicates relapsing Clostridium difficile infection1. Benefit of FMT in active Ulcerative Colitis (UC) and/or Crohn's Disease (CD) is yet to be investigated. UC and CD are treated using long term immune-suppression or colectomy. A significant portion of inflammatory bowel disease (IBD) patients still fail to respond even to therapies such as anti-TNFα. Safer, effective treatments are needed. Methods: We report successful treatment of three UC/CD cases using recurrent FMT. Results: Case 1: Female (19 yrs) with an 11 year history of severe UC/CD colitis presented with worsening symptoms including diarrhea, marked urgency, blood and mucus. Colonoscopy showed markedly inflamed, ulcerated, oedamatous mucosa with extensive pseudopolyps rectum to hepatic flexure despite combined anti-IBD therapies. Prior to considering colectomy, the patient underwent FMT initially via colonoscopy in July 09 then by 7 daily rectal FMT and 26 weekly FMT's. She experienced symptom improvement within several days of FMT with 2 formed stool/day, no blood, mucus or urgency. Follow-up colonoscopy revealed no gross inflammation or oedema, with patient remaining clinically well. Case 2: Male (23 yrs) with 5 year history of steroid and anti-TNFα refractory UC/CD colitis presented with bloody diarrhea (>20/day), anal fissures, severe abdominal pain and joint pain. Pre-FMT colonoscopy - severe disease of the left colon with marked caecal inflammation. He underwent daily rectal FMT for the first month, followed by infusions of lessening frequency until he reached 1 FMT/6 weeks. He reported resolution of bleeding 1-2 weeks post-FMT, and formed stool at 1 month post-FMT, resumed work, study activities and regained weight. Colonoscopy at one year showed no histological inflammation but occasional pseudopolyps in the caecum and ascending colon, patient being asymptomatic. Case 3: Female (57 yrs) with 9 year history of 5-ASA antibiotics, probiotics and immunosuppressant refractory ulcerative proctitis in spite of treatment. After training in our clinic, she performed 69, initially daily then weekly rectal FMT with virtually immediate resolution of diarrhea, PR bleeding and mucus. Follow-up colonoscopy showed no visible or histological inflammation and she has remained off all therapy last 4 years. Conclusion: We report successful reversal of severe mixed IBD using recurrent FMT. FMT may act as an antagonist to etiological infective agent/s and aid in reestablishing depleted bacterial species, thereby reversing IBD. The rapid response of FMT and lack of adverse effects make FMT a viable option for treatmentrefractory patients and is certainly an added option for those facing colectomy.
Effect of selenium supplementation on dairy cattle (1992)

The adequacy of current supplemental dietary selenium allowances for dairy cattle has been reviewed from the literature and by monitoring responses of dairy herds in a veterinary practice specializing in nutritional consultation. Both information sources tend to agree that a reference range of 70 to 100 ng of Se/mL of serum is an acceptable target concentration. This range can be attained most often by providing > 6 mg of supplemental Se.animal-1.d-1, but several factors affect the serum Se responses of different cows to specific Se intakes. These factors may include forage types and sources, ruminal environment, supplemental fat, dietary calcium, trace metals, and genetics. The major benefits, observed experimentally, of maintaining optimal Se intakes include minimizing the incidence of mastitis and preventing calf losses associated with myopathy and(or) respiratory disease.
Combination CTLA-4 Blockade and 4-1BB Activation Enhances Tumor Rejection by Increasing T-Cell Infiltration, Proliferation, and Cytokine Production (2011)

This study shows that combining T-cell co-inhibitory blockade with αCTLA-4 and active co-stimulation with α4-1BB promotes rejection of B16 melanoma in the context of a suitable vaccine. In addition, we identify KLRG1 as a useful marker for monitoring the anti-tumor immune response elicited by this therapy. These findings should aid in the design of future trials for the immunotherapy of melanoma.
Fiber strain sensor based on a π-phase-shifted Bragg grating and the Pound-Drever-Hall technique (2008)

A fiber strain sensor based on a p-phase-shifted Bragg grating and an extended cavity diode laser is proposed. Locking the laser frequency to grating resonance by the Pound-Drever-Hall technique results in a strain power spectral density S(epsilon) (f) = (3 x 10(-19) f(-1) +2.6 x 10(-23)) epsilon(2)/Hz in the Fourier frequency range from 1 kHz to 10 MHz (epsilon being the applied strain), corresponding to a minimum sensitivity of 5 pepsilon Hz(-1/2) for frequencies larger than 100 kHz.
Crosslink architectures for a multiple satellite system (1987)

Several candidate crosslink communications architectures are described for a packet-switched, low-altitude, multiple satellite system (MSS). One architecture represents a frequency-division approach, in which a cellular concept is combined with dynamic time-domain allocation within a cell. A second architecture uses an unsynchronized space-time division approach consisting of directional antennas and random accessing. A third architecture uses toroiclal antennas with unsynchronized random accessing. The recommended architecture uses a synchronized space-time division approach, consisting of directional antennas and contention-based pair-wise scheduling. This architecture, called PRS (Pseudo-random Scheduling) is found to have significantly reduced power and bandwidth requirements relative to the other approaches.
Role of the c‐myc and the N‐myc proto‐oncogenes in the immortalization of neural precursors (1989)

To study the role of c-myc and N-myc in the immortalization of neural precursors, we infected neuroepithelial cells isolated from 10-day-old mouse embryos with a new retrovirus vector, pzen, harboring either the c-myc or the N-myc oncogene. The immortalized cell lines contain high levels of the virally expressed myc protein. The amount of myc proteins correlated with the capacity of the cells to differentiate spontaneously in vitro into neurons and glia; cell lines expressing high levels of myc protein can differentiate spontaneously while cell lines expressing low levels of the myc protein resemble epithelial cells. Addition of acidic or basic fibroblast growth factor enhanced differentiation of most cell lines. Some of the cell lines produced neurotrophic growth factors capable of supporting the growth of other cell lines at low density. There was no significant difference between cell lines immortalized with c-myc or with N-myc. Most of the immortalized cells lines generated from bipotential precursors are capable of differentiating into neurons and glia.
Electrophysiologic Endocardial Mapping from a Noncontact Nonexpandable Catheter: A Validation Study of a Geometry‐Based Concept (2000)

The study demonstrates that simultaneous endocardial mapping can be accomplished during a single beat from a spiral-shaped noncontact catheter with good accuracy.
The rice bZIP transcriptional activator RITA-1 is highly expressed during seed development. (1994)

Systematic protein-DNA binding studies have shown that plant basic leucine zipper (bZIP) proteins exhibit a differential binding specificity for ACGT motifs. Here, we show that the rice transcription activator-1 (RITA-1) displays a broad binding specificity for palindromic ACGT elements, being able to bind A-, C-, and G-box but not T-box elements. By using gel mobility shift assays with probes differing in sequences flanking the hexameric core, we identified high-affinity A-, C-, and G-box binding sites. Quantitative and competition DNA binding studies confirmed RITA-1 specificity for these sites. Using rice protoplasts as a transient expression system, we demonstrated that RITA-1 can transactivate reporter genes possessing high-affinity but not low-affinity RITA-1 binding sites. Our results established a direct relationship between in vivo transactivation and in vitro binding activity. Transient expression assays that demonstrated the ability of RITA-1 to transactivate a construct containing rita-1 5' flanking sequences suggest that the factor may be autoregulated. Histochemical analysis of transgenic rice plants showed that a rita-1-beta-glucuronidase transgene is expressed in aleurone and endosperm cells of developing rice seeds. We propose that RITA-1 plays a role in the regulation of rice genes expressed in developing rice seeds.
Exposure to Influenza Epidemics During Gestation and Adult Schizophrenia (1990)

We attempted to replicate earlier findings of an association between exposure to influenza in the second trimester of gestation and adult schizophrenia. The number of live births, of births of future schizophrenics, and of cases of influenza reported to the Ministry of Health in Denmark was ascertained by month from 1911 to 1950. The relationship between fetal exposure to influenza and adult schizophrenia was examined. It is possible that unknown factors produce excesses of both influenza and schizophrenia in the winter, creating an artifactual association. To control for this coincidence, the effects of season were removed from the monthly influenza and schizophrenic birth-rates by several methods. Using the residual scores, it was found that influenza rates higher than seasonally expected, occurring in the sixth month of gestation, were associated with rates of births of schizophrenics greater than seasonally expected. This association was not attributable to some winter-related, third factor or to climatic variables.
Rectification by a Monolayer of Hexadecylquinolinium Tricyanoquinodimethanide between Gold Electrodes (2001)

45 000 electrons per molecule per second: such currents and a rectification ratio of 5.38 at 2.2 V were detected between oxide-free Au electrodes for a Langmuir–Blodgett monolayer of the D+–π–A− molecule 1.
Network (1998)

This dual registered nursing/ residential home is in the process of devising care plans incorporating evaluation sheets. We would appreciate information from colleagues in a similar field.
Sequence Analyses of G-Protein-Coupled Receptors:  Similarities to Rhodopsin (2003)

G-protein-coupled receptors (GPCRs)() constitute a large superfamily of receptor proteins responsible for signal transduction (see http://www.gpcr.org/7tm). Throughout all higher organisms, these receptors mediate recognition of environmental stimuli like light, odor, and taste, but also hormonal and other types of communications across plasma membranes (1). They are also important targets for pharmacological intervention via activating or blocking their action (2). Three families of GPCRs were identified, with family A being by far the largest (reviewed in refs 3-5). Its members are more closely related to each other within a few functional domains than those of the other families. In addition, numerous diseases have been linked to specific mutations within the genes encoding GPCRs, also making these receptors targets for specific therapeutic interventions including gene transfer (6-9).
Phase I/II trial of nemorubicin hydrochloride in combination with cisplatin is supported by new preclinical evidences of its mechanism of action (2006)

14116 Background: Nemorubicin hydrochloride (nemorubicin) is a non-conventional anthracycline in Phase II evaluation in hepatocellular carcinoma (HCC). Its mechanism of action is not fully elucidated. Although structurally related to doxorubicin, nemorubicin is a topoisomerase I inhibitor, overcomes anthracyclines resistance, is minimally cardiotoxic and is biotransformed by hepatic CYP3A4 into hundred times more cytotoxic metabolite. Phase I and II trials were conducted in Europe and China to test nemorubicin by hepatic intra-arterial (IHA) infusion in HCC patients (pts). The drug was well tolerated up to 600 mcg/m 2 q4–6w; DLT was transient liver transaminase elevations. Overall, 57 HCC pts were evaluable for efficacy, with 11/57 confirmed liver CR/PRs (RR = 19.3%; 95% ci 10–31.9%) lasting 1–54+ months. Stable disease ≥ 3 months was observed in 17/57 (29.8%) pts, most with AJCC Stage III, IIIA and IVA. These data supported new trials of nemorubicin in HCC. Methods: To further characterize the mechanism of action of the drug, we generated cells (L1210) resistant to nemorubicin. Since resistant cells were more sensitive than the parental ones to UV irradiation, we reasoned that the nucleotide excision repair (NER) system might be involved in mediating the activity of nemorubicin. To test this hypothesis we used isogenic CHO cells proficient or deficient in excision repair cross-complementing (ERCC) genes, namely ERCC1 and ERCC6 genes. Results: In contrast with what is observed for most DNA damaging drugs that show resistance in the presence of high NER activity, nemorubicin is more cytotoxic in NER proficient than in deficient cells. This suggests that NER pathway plays a role in the cytotoxic effect of nemorubicin. Also, cells resistant to nemorubicin are NER-deficient and are highly sensitive to platinum derivatives and alkylating agents and synergism was found combining cisplatin with nemorubicin. Conclusions: Nemorubicin has a peculiar mechanism of action through the NER system providing the rationale for clinical combination studies with platinum derivatives. A Phase I/II trial of nemorubicin with cisplatin in HCC patients started in Italy at the end of 2005. No significant financial relationships to disclose.
Impact of Adipose Tissue on Plasma Plasminogen Activator Inhibitor-1 in Dieting Obese Women (1999)

The increased incidence of cardiovascular diseases in obese subjects could be partially attributed to impaired fibrinolysis due to elevated plasma levels of tissue plasminogen activator inhibitor 1 (PAI-1). The associations between changes in plasma PAI-1, metabolic variables, and adipose tissue during weight loss and regain were studied in 52 healthy, premenopausal, obese women participating in a weight reduction program with a hypocaloric diet. PAI-1, insulin, triglyceride, leptin, and adipsin levels were determined at entry, after the first week, after completion of the program, and after 5 months of follow-up. In the 33 obese women who completed the program, decreases in PAI-1 antigen (-54%), PAI activity (-74%), and leptin (-51%), but not of adipsin, were observed. Changes in PAI-1 were associated with changes in body mass index (BMI), body fat, leptin, and insulin. The decreased level of PAI-1 remained low after follow-up in the 14 women who maintained their reduced weight but increased in the 16 women who regained weight. This increase in PAI-1 was correlated with an increase in body fat and leptin. On multivariate analysis, BMI was the major determinant of PAI-1 level. In conclusion, during weight reduction with a hypocaloric diet, the decrease in PAI-1 is more closely related to changes in adipose tissue than to changes in metabolic variables, suggesting a significant role for adipose tissue in regulating plasma levels of PAI-1.
Word N-Gram Based Classification for Data Leakage Prevention (2013)

Revealing sensitive data to unauthorised personal is a serious problem to many organizations that can lead to devastating consequences. Traditionally, prevention of data leak was achieved through firewalls, VPNs and IDS, but without much consideration to sensitivity of the data. In recent years, new technologies such as data leakage prevention systems (DLPs) are developed, especially to either identify and protect sensitive data or monitor and detect sensitive data leakage. One of the most popular approaches used in DLPs is content analysis, where the content of exchanged documents, stored data or even network traffic is monitored for sensitive data. Contents of documents are examined using mainly text analysis and text clustering methods. Moreover, text analysis can be performed using methods such as pattern recognition, style variation and N-gram frequency. In this paper, we investigate the use of N-grams for data classification purposes. Our method is based on using the N-grams frequency to classify documents in order to detect and prevent leakage of sensitive data. We have studied the effectiveness of N-grams to measure the similarity between regular documents and existing classified documents.