gebhart/patrepeval huggingface dataset:
High- and low-infectivity phenotypes of clonal populations of in vitro-cultured Borrelia burgdorferi (1995)

Borrelias that cause Lyme disease lose the ability to infect and cause disease in laboratory animals following 10 to 16 passages of in vitro culture. In this study, clonal populations of the Sh-2-82 (Sh2) and B31 strains of Borrelia burgdorferi were isolated by subsurface plating on BSK-II agar plates and examined for infectivity in the C3H/HeN mouse model. Mice were injected intradermally with 10(5) B. burgdorferi organisms, and the tibiotarsal joint, heart, and bladder were cultured 2 to 4 weeks postinfection to determine whether viable organisms were present. Clones exhibited either a high-infectivity phenotype, in which cultures were consistently positive at all organ sites, or a low-infectivity phenotype, in which a low proportion of cultures were positive (5 of 40 in a representative experiment). In an Sh2 population that had undergone five in vitro passages, 7 of 10 clones were of the high-infectivity phenotype, and the remaining clones were of the low-infectivity phenotype. The proportion of high-infectivity clones decreased with continued in vitro passage, with only 1 of 10 clones exhibiting the high-infectivity phenotype after 10 passages and 0 of 10 clones yielding positive cultures after 20 passages. Representative high- and low-infectivity clones from passage 5 Sh2 cultures had 50% infectious doses of 1.8 x 10(2) and 1 x 10(5), respectively. Subclones consistently reflected the same infectivity phenotypes as those of the parent clones. The protein profiles and plasmid contents of the high- and low-infectivity clones were compared and exhibited few discernible differences. On the basis of these results, the loss of infectivity during in vitro culture results from the outgrowth of low-infectivity clones and begins to occur within the first five in vitro passages. Further examination of clonal populations may lead to the identification of genetic and protein factors important in the virulence and pathogenicity of Lyme disease borrelias.
The JNK pathway as a therapeutic target for diabetes (2005)

The hallmark of Type 2 diabetes is insulin resistance and pancreatic beta-cell dysfunction. Under diabetic conditions, the c-jun N-terminal kinase (JNK) pathway is activated in various tissues, which is involved in both insulin resistance and beta-cell dysfunction. Activation of the JNK pathway interferes with insulin action and reduces insulin biosynthesis, and suppression of the JNK pathway in diabetic mice improves insulin resistance and beta-cell function, leading to amelioration of glucose tolerance. Taken together, the JNK pathway is likely to play a central role in the progression of insulin resistance and beta-cell dysfunction and, thus, could be a potential therapeutic target for diabetes.
Detection of intrahepatic replication of hepatitis C virus RNA by in situ hybridization and comparison with histopathology. (1992)

A nonisotopic in situ hybridization (NISH) assay was used to detect hepatitis C virus (HCV) RNA. A synthetic oligonucleotide complementary to bases 252-301 of the highly conserved 5' noncoding region of the HCV genome was end-labeled by terminal deoxynucleotidyltransferase using digoxigenin-conjugated dUTP. The hybridized oligomer was revealed by an immunohistochemical reaction after incubation with an alkaline phosphatase-conjugated anti-digoxigenin antibody and subsequent amplification with a complex of alkaline phosphatase and anti-alkaline phosphatase antibodies. The intracellular distribution of HCV RNA was monitored in the livers of two chimpanzees experimentally infected with the H strain of HCV and compared with the serum alanine aminotransferase activity, serum HCV RNA, and liver histopathology. Most cells were stained in the cytoplasm as early as 2 days after inoculation, 1 and 2 days, respectively, before the appearance of viral RNA in the serum. The time course of HCV RNA replication was correlated with increases in serum alanine aminotransferase. However, neither one paralleled the appearance of liver cell necrosis nor showed any correlation with the inflammatory response. The NISH signal was not found in liver biopsy specimens taken from these two animals before inoculation with HCV, from chimpanzees with acute hepatitis type A, B, or delta, or from two animals never experimentally infected with any hepatitis agent; moreover, it disappeared when the positive specimens were predigested with RNase and it was not observed after hybridization of positive controls with a labeled oligomer unrelated to HCV RNA. Thus, detection of liver HCV RNA by NISH is a sensitive and specific method for studying HCV replication at the cellular level. Intracellular replication of HCV did not appear to be associated with histopathologic changes in the liver, although the correlation with increases of liver enzyme activity in the serum suggested possible damage to the liver cell membrane.
Asymmetric Block Copolymers with Homopolymers: Routes to Multiple Length Scale Nanostructures (2002)

Thin polymer films with cylindrical microdomains of controlled size (see Figure for an AFM image) have been produced from diblock copolymer/homopolymer mixtures. It is demonstrated that not only do the spatial order and orientation of the domains remain unperturbed but also that two distinct sizes of pores can be accessed from the same film.
Evolution of the c-kit-Positive Cell Response to Pathological Challenge in the Myocardium (2008)

Cumulative evidence indicates that myocardium responds to growth or injury by recruitment of stem and/or progenitor cells that participate in repair and regenerative processes. Unequivocal identification of this population has been hampered by lack of reagents or markers specific to the recruited population, leading to controversies regarding the nature of these cells. Use of a transgenic mouse expressing green fluorescent protein driven by the c-kit promoter allows for unambiguous identification of this cell population. Green fluorescent protein (GFP) driven by the c-kit promoter labels a fraction of the c-kit+ cells recognized by antibody labeling for c-kit protein. Expression of GFP by the c-kit promoter and accumulation of GFP-positive cells in the myocardium is relatively high at birth compared with adult and declines between postnatal weeks 1 and 2, which tracks in parallel with expression of c-kit protein and c-kit-positive cells. Acute cardiomyopathic injury by infarction prompts increased expression of both GFP protein and GFP-labeled cells in the region of infarction relative to remote myocardium. Similar increases were observed for c-kit protein and cells with a slightly earlier onset and decline relative to the GFP signal. Cells coexpressing GFP, c-kit, and cardiogenic markers were apparent at 1-2 weeks postinfarction. Cardiac-resident c-kit+ cell cultures derived from the transgenic line express GFP that is diminished in parallel with c-kit by induction of differentiation. The use of genetically engineered mice validates and extends the concept of c-kit+ cells participating in the response to myocardial injury.
Liposome: classification, preparation, and applications (2013)

Liposomes, sphere-shaped vesicles consisting of one or more phospholipid bilayers, were first described in the mid-60s. Today, they are a very useful reproduction, reagent, and tool in various scientific disciplines, including mathematics and theoretical physics, biophysics, chemistry, colloid science, biochemistry, and biology. Since then, liposomes have made their way to the market. Among several talented new drug delivery systems, liposomes characterize an advanced technology to deliver active molecules to the site of action, and at present, several formulations are in clinical use. Research on liposome technology has progressed from conventional vesicles to 'second-generation liposomes', in which long-circulating liposomes are obtained by modulating the lipid composition, size, and charge of the vesicle. Liposomes with modified surfaces have also been developed using several molecules, such as glycolipids or sialic acid. This paper summarizes exclusively scalable techniques and focuses on strengths, respectively, limitations in respect to industrial applicability and regulatory requirements concerning liposomal drug formulations based on FDA and EMEA documents.
A mutation of the glucocorticoid receptor in primary cortisol resistance. (1993)

The precise molecular abnormalities that cause primary cortisol resistance have not been completely described. In a subject with primary cortisol resistance we have observed glucocorticoid receptors (hGR) with a decreased affinity for dexamethasone. We hypothesize that a mutation of the hGR glucocorticoid-binding domain is the cause of cortisol resistance. Total RNA isolated from the index subject's mononuclear leukocytes was used to produce first strand hGR cDNAs, and the entire hGR cDNA was amplified in segments and sequenced. At nucleotide 2,317 we identified a homozygous A for G point mutation that predicts an isoleucine (ATT) for valine (GTT) substitution at amino acid 729. When the wild-type hGR and hGR-Ile 729 were expressed in COS-1 cells and assayed for [3H]-Dexamethasone binding, the dissociation constants were 0.799 +/- 0.068 and 1.54 +/- 0.06 nM (mean +/- SEM) (P < 0.01), respectively. When the wild-type hGR and hGR-Ile 729 were expressed in CV-1 cells that were cotransfected with the mouse mammary tumor virus long terminal repeat fused to the chloramphenicol acetyl transferase (CAT) gene, the hGR-Ile 729 conferred a fourfold decrease in apparent potency on dexamethasone stimulation of CAT activity. The isoleucine for valine substitution at amino acid 729 impairs the function of the hGR and is the likely cause of primary cortisol resistance in this subject.
Detection of Peptidoglycan and Endotoxin in Dialysate, Using Silkworm Larvae Plasma and Limulus Amebocyte Lysate Methods (1997)

Silkworm larvae plasma (SLP) reagent is activated by peptidoglycan (PG), a fragment of both the gram-positive and gram-negative bacterial cell wall, as well as beta-glucan (BG), a component of fungi. It is possible to measure contamination of gram-positive bacteria quantitatively by combining the conventional limulus amebocyte lysate (LAL) and PG measurement methods. Therefore, a more highly accurate analysis of dialysate can be made using both SLP and LAL methods to detect endotoxin (ET) and/or PG contamination. We studied the effects of contaminated dialysate on human peripheral blood mononuclear cells (PBMC) by producing various cytokines in vitro. Muramyl dipeptide (MDP) was used as the biologically active minimum constituent of PG. A total of 54 dialysate samples were obtained under sterile conditions from 4 sites: (1) reverse osmosis water unit; (2) proportioning unit; (3) multiple dialysate preparation console, and (4) personal dialysate preparation console, at 9 dialysis facilities. To detect bacterial contamination, the samples were measured with LAL(C), LAL(G) and SLP methods. PBMC were collected from 10 healthy controls and from 10 hemodialysis patients and cultured for 24 h with ET, MDP, ET + MDP and contaminated dialysate. IL-1 receptor antagonist (IL-1Ra), IL-1 beta and TNF-alpha in the culture medium supernatants were measured using the ELISA method. PG was not detected in dialysate from sites 1 or 2. However, dialysate from the inlet of the dialyzer at the bedside monitor of the central supply and personal console showed 4.1 +/- 6.1 ng/ml for site 3 (in 7 of 18 samples) and 3.3 +/- 4.6 ng/ml for site 4 (in 3 of 18 samples). Contamination by PG alone and complex contamination by PG and ET were also detected. Furthermore, IL-1Ra, IL-1 beta and TNF-alpha production by PBMC increased in accordance with the concentrations of MDP. Cytokine production was enhanced 5-10 times more where MDP and ET coexisted than where either MDP or ET existed alone, showing the synergic effects of MDP and ET. Based on these results, there is a high possibility that PG may also be a pyrogen in the dialysate prior to this study. ET had been considered the only pyrogen in dialysate. Therefore, it is essential to recognize the existence of both ET and PG in investigating dialysate contamination.
Enumeration of Waterborne Escherichia coli with Petrifilm Plates (2003)

Escherichia coli is often monitored in environmental waters as an indicator of the possible presence of human pathogens associated with feces. Petrifilm E. coli/coliform count plates (3M, Minneapolis, MN), previously validated for enumerating E. coli in food, were tested for monitoring E. coli in environmental water. Escherichia coli counts in environmental water samples enumerated with Petrifilm were significantly correlated (R > 0.9; slope = 0.9-1.0; p < 0.001) with counts obtained with three commonly used methods, mTEC (Becton Dickinson, Sparks, MD), m-ColiBlue (Hach, Loveland, CO), and Colilert-18/IDEXX Quanti-Tray 2000 (IDEXX, Westbrook, ME). Blue colonies on Petrifilm plates were most reliably identified as E. coli when accompanied by gas formation, as determined by characterization of the colonies on MacConkey agar plates (PML Microbiologicals, Mississauga, ON, Canada) and by polymerase chair reaction (PCR) with E. coli-specific primers. The main disadvantage of Petrifilm plates for environmental water testing is the small volume (1 mL per sample) that can be tested; however, the plates appear to be suitable for screening and locating sites that exceed criteria for total body and partial body contact. Simplicity of use and storage, reliability, and relatively low cost make Petrifilm plates suitable for volunteer-based and educational water quality monitoring applications, particularly when used as a preliminary screening method to identify problem sites.
Stereoselective Synthesis of over Two Million Compounds Having Structural Features Both Reminiscent of Natural Products and Compatible with Miniaturized Cell-Based Assays (1998)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTStereoselective Synthesis of over Two Million Compounds Having Structural Features Both Reminiscent of Natural Products and Compatible with Miniaturized Cell-Based AssaysDerek S. Tan, Michael A. Foley, Matthew D. Shair, and Stuart L. SchreiberView Author Information Department of Chemistry & Chemical Biology Harvard Institute of Chemistry & Cell Biology Howard Hughes Medical Institute Harvard University, 12 Oxford St. Cambridge, Massachusetts 02138 Cite this: J. Am. Chem. Soc. 1998, 120, 33, 8565–8566Publication Date (Web):August 8, 1998Publication History Received19 May 1998Published online8 August 1998Published inissue 1 August 1998https://pubs.acs.org/doi/10.1021/ja981746ohttps://doi.org/10.1021/ja981746orapid-communicationACS PublicationsCopyright © 1998 American Chemical SocietyRequest reuse permissionsArticle Views2642Altmetric-Citations163LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (4)»Supporting Information Supporting Information SUBJECTS:Assays,Genetics,Ligands,Organic acids,Pharmaceuticals Get e-Alerts
The Dependence of the Ultrasound-Induced Blood-Brain Barrier Opening Characteristics on Microbubble Size In Vivo (2009)

Recent neuropharmaceutical developments have led to potent disease‐modifying drugs. In spite of these advancements, most agents cannot traverse the blood‐brain barrier (BBB) and deposit in the brain. Focused ultrasound (FUS) with microbubbles has been shown to induce noninvasive, localized, and transient BBB opening. Although promising, safety and efficacy concerns still remain. Previously reported experiments used conventional imaging contrast agents that have a wide size distribution. In this study, we hypothesize that BBB opening characteristics are dependent on bubble diameter. A 25 μl bolus of in‐house manufactured, lipid‐shelled bubbles with either 1–2 or 4–5 μm diameter ranges was injected intravenously. Pulsed FUS (frequency: 1.5 MHz, peak‐negative pressure: 146–607 kPa, duty cycle: 20%, duration: 1‐min) was then applied to the left hippocampus of mice (n = 16) in vivo through the intact skin and skull. MRI or fluorescence microscopy was used to determine BBB opening. Contrast‐enhanced (Omniscan™; 0.75 mL; molecular weight: 574 Da) MRI (9.4‐T) was acquired on multiple days after sonication to determine BBB opening and closing. Fluorescence microscopy was also used to determine the feasibility of delivering large, 3 kDa dextran compounds through the BBB. The BBB opening acoustic pressure threshold for the 4–5μm bubbles was in the 146–304 kPa range while the threshold for the 1–2μm bubbles was higher. In conclusion, FUS‐induced BBB opening and closing was shown to be dependent on the bubble diameter indicating the possibility of specifically designing bubbles to enhance this therapeutic application.
Unified Separation Science (1991)

Equilibrium: Driving Force for Separative Displacement Separative Transport Flow Transport and Viscous Phenomena Zone Formation and Resolution Steady-State, Two-Dimensional, and Overlapping Zones Classification and Comparison of Methods Separation by External Fields (Sc Methods): Electrophoresis and Sedimentation Separation Using Perpendicular Flow, F(+): Field-Flow Fractionation, Chromatography, and Related Methods Chromatography: A Deeper Look Chromatography from a Molecular Viewpoint Plate Height and Optimization in Chromatography Appendices Author Index Subject Index.
Associating Groups of People (2009)

In a crowded public space, people often walk in groups, either with people they know or strangers. Associating a group of people over space and time can assist understanding individual’s behaviours as it provides vital visual context for matching individuals within the group. Seemingly an ‘easier’ task compared with person matching given more and richer visual content, this problem is in fact very challenging because a group of people can be highly non-rigid with changing relative position of people within the group and severe self-occlusions. In this paper, for the first time, the problem of matching/associating groups of people over large space and time captured in multiple non-overlapping camera views is addressed. Specifically, a novel people group representation and a group matching algorithm are proposed. The former addresses changes in the relative positions of people in a group and the latter deals with variations in illumination and viewpoint across camera views. In addition, we demonstrate a notable enhancement on individual person matching by utilising the group description as visual context. Our methods are validated using the 2008 i-LIDS Multiple-Camera Tracking Scenario (MCTS) dataset on multiple camera views from a busy airport arrival hall.
Subchondral bone drilling: a treatment for cartilage defects. (1991)

Clearly, no one surgical procedure is ideal for the treatment of degenerative joint disease. Many factors are involved in planning for the proper approach, such as age and activity of the patient, etiology, and stage of the disease. Arthroplasty, implant arthroplasty, cheilectomy, enclavement, various osteotomies, and joint fusions have been advocated as procedures for choice of degenerative joint disease of the first metatarsophalangeal joint (24-26). Similar procedures have been used to treat arthroses of the lesser metatarsophalangeal joints as well. Some of these procedures are designed to address the etiology of the degenerative process. This is the case with the enclavement and metatarsal osteotomies such as the Watermann procedure (25, 26). Most of these procedures are primarily effective in the early stages of the disease (26). Other procedures attempt to alleviate symptomatology as with the Keller arthroplasty, implant arthroplasties, cheilectomy, and joint fusions (24, 26). With the exception of the cheilectomy, these generally are reserved for late stage arthroses. Subchondral drilling has been used to treat cartilage defects in conjunction with other procedures that address the etiology and symptomatology of the disease process. It has been shown that small drill holes may be effective in producing fibrocartilage to replace full- and partial-thickness cartilage defects (14, 18). Such drilling has been useful in the treatment of osteochondral lesions of the ankle and promises to be equally effective in treatment of osteochondral lesions of the metatarsophalangeal joints. As with any procedure, applications are limited. Subchondral drilling addresses only the cartilage defect and the pain attributed to that defect. It does nothing to address the etiology of a biomechanical problem. (ABSTRACT TRUNCATED AT 250 WORDS)
Identification and characterization of the Egr-1 gene product, a DNA-binding zinc finger protein induced by differentiation and growth signals. (1990)

Egr-1 is an immediate-early response gene induced by diverse signals that initiate growth and differentiation. Its cDNA sequence predicts a protein with zinc fingers. We have generated an antiserum to the Egr-1 gene product and identified it as an 80-kilodalton short-lived protein in serum-stimulated mouse fibroblasts. The rat Egr-1 product has also been identified in nerve growth factor-induced PC12 cells. In addition, we show by cell fractionation and immunocytochemistry that the Egr-1 protein is located in the nucleus. We also demonstrate that it is phosphorylated. In vitro-generated Egr-1 protein binds with high affinity to the sequence CGCCCCCGC in a zinc-dependent manner.
Cu(II)-Catalyzed ortho-Selective Aminomethylation of Phenols (2017)

A Cu(II)-catalyzed ortho-selective functionalization of free phenols with trifluoroborates to afford C<sub>sp2</sub>-C<sub>sp3</sub> coupling products under mild conditions has been developed. A variety of functional groups on the phenol and the potassium aminomethyltrifluoroborate substrates were found compatible, furnishing the corresponding products in moderate to excellent yields. A single-electron transfer radical coupling mechanism involving a six-membered transition state is proposed to rationalize the high levels of ortho-selectivity in the reaction. This protocol provides straightforward access to ortho-aminomethyl-substituted phenols, unnatural amino acids and other bioactive small molecules.