gebhart/patrepeval huggingface dataset:
Clostridium difficile--a spectrum of virulence and analysis of putative virulence determinants in the hamster model of antibiotic-associated colitis (1987)

Each of nine different toxigenic strains of Clostridium difficile was administered orally to groups of hamsters pre-treated with clindamycin and housed individually in sterile isolator boxes. Faecal pellets and caecal contents from well, diarrhoeic, moribund and freshly dead animals were analysed for C. difficile and toxins A (enterotoxin) and B (cytotoxin), and tissue obtained when animals were killed was examined histologically. Not all strains were equally virulent in this model. Four strains of C. difficile killed all animals within 48 h and are designated as highly virulent for hamsters. These strains were clinical isolates from three cases of disease in man and one case in a hamster. Five strains caused death of some animals but only after 5 and upt to 13 days and are designated as less virulent for hamsters. These strains were isolated from asymptomatic infants (2) and household pets (2), and from the environment (1). The surviving test hamsters were killed after 14 days and, in most cases, were colonised by C. difficile, though levels of toxins A and B in caecal contents were low. None of the cultures used for challenge was capsulate or hydrophobic. There was no correlation between virulence and production of toxins A and B in vitro in tryptic-nitrate broth. With two strains examined, there was a correlation between virulence and toxin A (but not toxin B) production in caecal emulsions derived from clindamycin pre-treated hamsters. Caecal contents from the majority of moribund and freshly dead animals had quantities of toxin A sufficient to cause disease or death if given orogastrically. Toxin B was not produced in a fixed ratio with toxin A. The data support the view that high virulence of C. difficile is determined by efficient disease-inducing colonisation of the gut and the ability to generate, rapidly, high levels of toxin A in vivo.
SEPARATION OF FELINE BONE MARROW CELLS BY COUNTERFLOW CENTRIFUGAL ELUTRIATION (1995)

Counterflow centrifugal elutriation (CCE) has been used to separate nucleated cells from mammalian bone marrow on the basis of size with the resultant isolation of hematopoietic cells in varying stages of lineage development. We examined the feasibility of identifying and isolating such cells from feline bone marrow. CCE was performed with a Beckman J6MI centrifuge and a Sanderson chamber, using a fixed rotor speed of 3000 rpm and collection of cells at (1) 16-, (2) 21-, (3) 25-, (4) 32 ml/min, and (5) a rotor off fraction. Recovery of the total input cells in four replicate experiments averaged 86%, with the maximum number of recovered cells in fraction 4. Analysis by flow cytometry and monoclonal antibodies revealed mononuclear cells in fractions 1 and 2 and early and late differentiating myeloid/erythroid cells in fractions 2 through 5. T lymphocytes and alloreactivity in a mixed lymphocyte reaction (MLR) were restricted to fractions 1 and 2; removal of T cells and MLR activity was accomplished by immunomagnetic depletion. In vitro cultures for clonogenic cells revealed CFU-GM and BFU-E colonies in fractions 2 through 5, with fraction 4 containing the greatest absolute number of myeloid colonies and fractions 3 and 4 the majority of the erythroid colonies. More important, in examining the plating efficiency for clonogenic cells in the different fractions it was found that this increased significantly in fractions 2 and 3 when the culture time was extended from 7 to 14 days; in contrast, fractions 4 and 5 reached their maximum plating efficiency within 7 days with no further increase on day 14. We interpret these findings to indicate the presence of late differentiating progenitors in the large-cell size fractions 4 and 5, while the smaller mononuclear cells in fractions 2 and 3 represent an earlier, more primitive population of hematopoietic cells requiring an extended time in culture for full colony development.
Amyloid-β Antibody Treatment Leads to Rapid Normalization of Plaque-Induced Neuritic Alterations (2003)

The accumulation of amyloid-beta into insoluble plaques is a characteristic feature of Alzheimer's disease. Neuronal morphology is distorted by plaques: rather than being essentially straight, they are substantially more curved than those in control tissue, their trajectories become altered, and they are frequently distended or swollen, presumably affecting synaptic transmission. Clearance of plaques by administration of antibodies to amyloid-beta is a promising therapeutic approach to the treatment of Alzheimer's disease, leading to stabilization of dementia by an unknown cellular mechanism. The effect of plaque clearance on plaque-induced neuronal alterations has not been studied previously. Here we show that both plaques and neuritic lesions are reversible in a strikingly short period of time after administration of a single dose of amyloid-beta antibody. Amyloid clearance and recovery of normal neuronal geometries were observed as early as 4 d and lasted at least 32 d after a single treatment. These results demonstrate that, once plaques are cleared, neuronal morphology is self-correcting and that passive antibody treatment has the potential to reverse neuronal damage caused by Alzheimer's disease and, hence, directly impact cognitive decline. Moreover, the rapid normalization of neuritic dystrophy suggests an unexpected degree of plasticity in the adult nervous system.
Oxidation of hydrocarbons. 9. The oxidation of alkynes by potassium permanganate (1979)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTOxidation of hydrocarbons. 9. The oxidation of alkynes by potassium permanganateDonald G. Lee and Victor S. ChangCite this: J. Org. Chem. 1979, 44, 15, 2726–2730Publication Date (Print):July 1, 1979Publication History Published online1 May 2002Published inissue 1 July 1979https://pubs.acs.org/doi/10.1021/jo01329a027https://doi.org/10.1021/jo01329a027research-articleACS PublicationsRequest reuse permissionsArticle Views1424Altmetric-Citations55LEARN 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-Alertsclose Get e-Alerts
Major phenylpropanoid‐derived metabolites in the human gut can arise from microbial fermentation of protein (2013)

This study demonstrates that certain microbial species have the ability to ferment all three AAAs and that protein fermentation is the likely source of major phenylpropanoid-derived metabolites in the colon.
Cell-Free Protein Synthesis for Structure Determination by X-ray Crystallography (2009)

Structure determination has been difficult for those proteins that are toxic to the cells and cannot be prepared in a large amount in vivo. These proteins, even when biologically very interesting, tend to be left uncharacterized in the structural genomics projects. Their cell-free synthesis can bypass the toxicity problem. Among the various cell-free systems, the wheat-germ-based system is of special interest due to the following points: (1) Because the gene is placed under a plant translational signal, its toxic expression in a bacterial host is reduced. (2) It has only little codon preference and, especially, little discrimination between methionine and selenomethionine (SeMet), which allows easy preparation of selenomethionylated proteins for crystal structure determination by SAD and MAD methods. (3) Translation is uncoupled from transcription, so that the toxicity of the translation product on DNA and its transcription, if any, can be bypassed. We have shown that the wheat-germ-based cell-free protein synthesis is useful for X-ray crystallography of one of the 4-bp cutter restriction enzymes, which are expected to be very toxic to all forms of cells retaining the genome. Our report on its structure represents the first report of structure determination by X-ray crystallography using protein overexpressed with the wheat-germ-based cell-free protein expression system. This will be a method of choice for cytotoxic proteins when its cost is not a problem. Its use will become popular when the crystal structure determination technology has evolved to require only a tiny amount of protein.
Sound-Based Analogue of Cavity Quantum Electrodynamics in Silicon (2011)

A quantum mechanical superposition of a long-lived, localized phonon and a matter excitation is described. We identify a realization in strained silicon: a low-lying donor transition (P or Li) driven solely by acoustic phonons at wavelengths where high-Q phonon cavities can be built. This phonon-matter resonance is shown to enter the strongly coupled regime where the "vacuum" Rabi frequency exceeds the spontaneous phonon emission into noncavity modes, phonon leakage from the cavity, and phonon anharmonicity and scattering. We introduce a micropillar distributed Bragg reflector Si/Ge cavity, where Q≃10(5)-10(6) and mode volumes V≲25λ(3) are reachable. These results indicate that single or many-body devices based on these systems are experimentally realizable.
Cytokine binding and clearance properties of proteinase-activated alpha 2-macroglobulins. (1991)

Multiple mechanisms are necessary to spatially and temporally restrict and direct the effects of potent mediators of inflammation, immune reactions and tissue repair. Recent studies implicate alpha 2-macroglobulin (alpha 2M) as a protein that regulates the distribution and activity of many cytokines, including transforming growth factors-beta (TGFs-beta), tumor necrosis factor-alpha (TNF-alpha), platelet derived growth factor (PDGF), interleukin-6 (IL-6), nerve growth factor (NGF), fibroblast growth factor (b-FGF), and interleukin-1 beta (IL-1 beta). Some cytokines, including PDGF, NGF, and IL-6 bind preferentially to the native secreted form of alpha 2M, whereas the TGF-beta s, TNF-alpha and IL-1 beta bind preferentially to forms of alpha 2M that have been modified by proteinases such as plasmin. Cytokines bound to native alpha 2M retain much of their biologic activity in various bioassays, whereas cytokines bound to "activated" alpha 2Ms have decreased activity in some cell systems. Because native alpha 2M in circulation can escape into extravascular fluid during tissue injury and inflammation, alpha 2M is a putative cytokine carrier, especially in the presence of heparin or specific cytokine receptors that can displace non-covalently bound cytokines from native alpha 2M. However, proteinase or chemically modified alpha 2Ms become activated for receptor-mediated endocytosis (RME) when they undergo conformational alterations that expose a latent alpha 2M receptor-recognition domain. Circulating activated alpha 2Ms, together with bound cytokines, are rapidly removed by hepatic alpha 2M-receptors (alpha 2M-R) but also bind to other cells expressing alpha 2M-R. This suggests that diseases resulting from an apparent change in the production of one or several different cytokines might represent changes in either the production of alpha 2M "cytokine scavengers" or their alpha 2M-receptor-mediated clearance/targeting mechanisms. The sequence identity between the LDL-receptor related protein and the alpha 2M receptor (115) provides a theoretical basis for interference with cytokine clearance by association of competing lipoprotein ligands with this cytokine clearance pathway. Furthermore, activated alpha 2Ms or augmentation of alpha 2M-receptor-dependent cytokine clearance might be novel strategies for preventing the harmful systemic or local effects of excess cytokines such as TGF-beta s and TNF-alpha in vivo.
Antimicrobial peptides: therapeutic potentials (2014)

The increasing appearance of multidrug-resistant pathogens has created an urgent need for suitable alternatives to current antibiotics. Antimicrobial peptides (AMPs), which act as defensive weapons against microbes, have received great attention because of broad-spectrum activities, unique action mechanisms and rare antibiotic-resistant variants. Despite desirable characteristics, they have shown limitations in pharmaceutical development due to toxicity, stability and manufacturing costs. Because of these drawbacks, only a few AMPs have been tested in Phase III clinical trials and no AMPs have been approved by the US FDA yet. However, these obstacles could be overcome by well-known methods such as changing physicochemical characteristics and introducing nonnatural amino acids, acetylation or amidation, as well as modern techniques like molecular targeted AMPs, liposomal formulations and drug delivery systems. Thus, the current challenge in this field is to develop therapeutic AMPs at a reasonable cost as well as to overcome the limitations.
Multilocus Sequence Typing System for Campylobacter jejuni (2001)

The gram-negative bacterium Campylobacter jejuni has extensive reservoirs in livestock and the environment and is a frequent cause of gastroenteritis in humans. To date, the lack of (i) methods suitable for population genetic analysis and (ii) a universally accepted nomenclature has hindered studies of the epidemiology and population biology of this organism. Here, a multilocus sequence typing (MLST) system for this organism is described, which exploits the genetic variation present in seven housekeeping loci to determine the genetic relationships among isolates. The MLST system was established using 194 C. jejuni isolates of diverse origins, from humans, animals, and the environment. The allelic profiles, or sequence types (STs), of these isolates were deposited on the Internet (http://mlst.zoo.ox.ac.uk), forming a virtual isolate collection which could be continually expanded. These data indicated that C. jejuni is genetically diverse, with a weakly clonal population structure, and that intra- and interspecies horizontal genetic exchange was common. Of the 155 STs observed, 51 (26% of the isolate collection) were unique, with the remainder of the collection being categorized into 11 lineages or clonal complexes of related STs with between 2 and 56 members. In some cases membership in a given lineage or ST correlated with the possession of a particular Penner HS serotype. Application of this approach to further isolate collections will enable an integrated global picture of C. jejuni epidemiology to be established and will permit more detailed studies of the population genetics of this organism.
Sickle Cell Disease, Vasculopathy, and Therapeutics (2012)

Sickle cell disease (SCD) is caused by a mutation in both beta globin genes, resulting in chronic hemolysis and multiorgan disease that ultimately leads to premature death. Although hemoglobin S (HbS) polymerization and vaso-occlusion are central to the pathogenesis of SCD, overlapping pathways implicated in SCD-related endothelial dysfunction include hemolysis, defects in nitric oxide metabolism, ischemia-reperfusion injury, oxidative stress, increased cell-to-cell adhesion, and proinflammatory and coagulation mediators. Progression of organ-specific vasculopathy often precedes organ dysfunction and may provide targets for therapeutic intervention. SCD-related vasculopathies include, but are not limited to, moyamoya that often precedes cerebral infarcts or hemorrhage, proliferative retinopathy prior to loss of eyesight, pulmonary vasculopathy associated with pulmonary hypertension, and renal vasculopathy prior to the onset of chronic renal disease. This review evaluates evidence that SCD vasculopathy is a harbinger for organ dysfunction and reviews the potential for targeted antivasculopathy therapies.
Efficient Image Dehazing with Boundary Constraint and Contextual Regularization (2013)

Images captured in foggy weather conditions often suffer from bad visibility. In this paper, we propose an efficient regularization method to remove hazes from a single input image. Our method benefits much from an exploration on the inherent boundary constraint on the transmission function. This constraint, combined with a weighted L_1-norm based contextual regularization, is modeled into an optimization problem to estimate the unknown scene transmission. A quite efficient algorithm based on variable splitting is also presented to solve the problem. The proposed method requires only a few general assumptions and can restore a high-quality haze-free image with faithful colors and fine image details. Experimental results on a variety of haze images demonstrate the effectiveness and efficiency of the proposed method.
Induction of immune tolerance to coagulation factor IX antigen by in vivo hepatic gene transfer (2003)

Gene replacement therapy is an attractive approach for treatment of genetic disease, but may be complicated by the risk of a neutralizing immune response to the therapeutic gene product. There are examples of humoral and cellular immune responses against the transgene product as well as absence of such responses, depending on vector design and the underlying mutation in the dysfunctional gene. It has been unclear, however, whether transgene expression can induce tolerance to the therapeutic antigen. Here, we demonstrate induction of immune tolerance to a secreted human coagulation factor IX (hF.IX) antigen by adeno-associated viral gene transfer to the liver. Tolerized mice showed absence of anti-hF.IX and substantially reduced in vitro T cell responses after immunization with hF.IX in adjuvant. Tolerance induction was antigen specific, affected a broad range of Th cell subsets, and was favored by higher levels of transgene expression as determined by promoter strength, vector dose, and mouse strain. Hepatocyte-derived hF.IX expression induced regulatory CD4 + T cells that can suppress anti-hF.IX formation after adoptive transfer. With a strain-dependent rate of success, tolerance to murine F.IX was induced in mice with a large F.IX gene deletion, supporting the relevance of these data for treatment of hemophilia B and other genetic diseases.
An Epidemiological Investigation of a Sustained High Rate of Pediatric Parapneumonic Empyema: Risk Factors and Microbiological Associations (2002)

We investigated the increasing incidence of pediatric empyema during the 1990s at Primary Children's Medical Center in Salt Lake City. Of 540 children hospitalized with community-acquired bacterial pneumonia (CAP) who were discharged from 1 July 1993 through 1 July 1999, 153 (28.3%) had empyema. The annual population incidence of empyema increased during the study period from 1 to 5 cases per 100,000 population aged <19 years. Streptococcus pneumoniae was identified as the most common cause of CAP with or without empyema; serotype 1 accounted for 50% of the cases of pneumococcal empyema. Patients with empyema were more likely to be >3 years old, to have > or =7 days of fever, to have varicella, and to have received antibiotics and ibuprofen before admission to the hospital, compared with patients without empyema (P<.0001 for each factor). The increasing incidence of empyema was associated with infection due to S. pneumoniae serotype 1, outpatient treatment with certain antibiotics, ibuprofen use, and varicella.
Treatment of bone and soft tissue defects in infected nonunion. (1992)

In the treatment of infected pseudarthroses the general principles of osteitis treatment are applied. This includes radical excision of pseudarthrotic and infected bone tissue, and of diseased surrounding soft tissue. External fixation devices are the preferred method of stabilization of the bone. Based on the data of a retrospective study of 31 Papineau procedures, 65 local flap transfers, and 46 free flap transfers we found that the Papineau procedure works in minor bone and soft tissue defects. Unstable scar formation is a major disadvantage of this method. Local muscular flaps are indicated in the treatment of soft tissue defects in the proximal and medial portions of the lower leg. A prerequisite for free flap transfers is the availability of trained personnel and suitable technical equipment. The option is limited by the patient's vascular situation. This kind of tissue transfer seems to be superior to other methods. For the substitution of bone defects corticocancellous bone transplantation may be used. A promising alternative method to deal with extensive bone defects is osteogenesis produced by callus distraction.
Chemical gating of In2O3 nanowires by organic and biomolecules (2003)

In 2 O 3 nanowire transistors were used to investigate the chemical gating effect of organic molecules and biomolecules with amino or nitro groups. The nanowire conductance changed dramatically after adsorption of these molecules. Specifically, amino groups in organic molecules such as butylamine, donated electrons to In2O3 nanowires and thus led to enhanced carrier concentrations and conductance, whereas molecules with nitro groups such as butyl nitrite made In2O3 nanowires less conductive by withdrawing electrons. In addition, intrananowire junctions created by partial exposure of the nanowire device to butyl nitrite were investigated, and pronounced rectifying current–voltage characteristics were obtained. Furthermore, chemical gating by low-density lipoprotein cholesterol, the offending agent in coronary heart diseases, was also observed and attributed to the amino groups carried by the bio species.
The potentiation of the antimicrobial activities of cutting fluid preservatives by EDTA (1978)

The potentiation of the antimicrobial activities of cutting fluid preservatives by EDTA was confirmed in experiments in which 500 ppm of the disodium salt of EDTA was used in combination with 12 different metalworking fluids containing 500 ppm of o-phenylphenol, tris(hydroxymethyl) nitromethane, hexahydro- 1,3,5-tris(2-hydroxyethyl)-s-triazine alone or complexed with iodine, hexahydro- 1,3,5-triethyl-s-triazine, 1-(3-chloroallyl)- 3,5,7-triaza- 1-azoniaadamantane hydrochloride, 1,2-benzisothiazolin-3-one, 4-(2-nitrobutyl) morpholine and 4,4-(2-ethyl-2-nitrotrimethylene) dimorpholine, or the sodium salt of 2-pyridinethiol- 1-oxide as a preservative. Based on a previous observation that the proper selection of the hydraulic fluid employed in the cutting machine is a major factor in controlling rancidity, the possibility of spoilage control by treating the fluid with EDTA alone was also demonstrated; the EDTA had a greater beneficial effect with a synthetic coolant than with an oil emulsion. Published data on the effects of EDTA indicate that it poses no significant water pollution problems upon disposal, exhibits a low order of animal toxicity, and rarely causes human allergies. Tables and 65 references.