gebhart/patrepeval huggingface dataset:
The Biology of Hematopoietic Stem Cells (1995)

Hematopoietic stem cells (HSC) are the only cells in the blood-forming tissues that can give rise to all blood cell types and that can self-renew to produce more HSC. In mouse and human, HSC represent up to 0.05% of cells in the bone marrow. HSC are almost entirely responsible for the radioprotective and short- and long-term reconstituting effects observed after bone marrow transplantation. The subsets of HSC that give rise to short-term vs long-term multilineage reconstitution can be separated by phenotype, demonstrating that the fates of HSC are intrinsically determined. Here we review the ontogeny and biology of HSC, their expression of fate-determining genes, and the clinical importance of HSC for transplantation and gene therapy.
Synthesis, crystal structure, and olefin polymerization activity of a zwitterionic .eta.6-arene zirconium tris(hydrocarbyl) (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis, crystal structure, and olefin polymerization activity of a zwitterionic .eta.6-arene zirconium tris(hydrocarbyl)Claudio Pellecchia, Alfonso Grassi, and Attilio ImmirziCite this: J. Am. Chem. Soc. 1993, 115, 3, 1160–1162Publication Date (Print):February 1, 1993Publication History Published online1 May 2002Published inissue 1 February 1993https://pubs.acs.org/doi/10.1021/ja00056a057https://doi.org/10.1021/ja00056a057research-articleACS PublicationsRequest reuse permissionsArticle Views349Altmetric-Citations145LEARN 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 (2)»Supporting Information Supporting Information Get e-Alerts
25‐hydroxycholesterol provokes oligodendrocyte cell line apoptosis and stimulates the secreted phospholipase A2 type IIA via LXR beta and PXR (2009)

In several neurodegenerative diseases of the CNS, oligodendrocytes are implicated in an inflammatory process associated with altered levels of oxysterols and inflammatory enzymes such as secreted phospholipase A2 (sPLA2). In view of the scarce literature related to this topic, we investigated oxysterol effects on these myelinating glial cells. Natural oxysterol 25-hydroxycholesterol (25-OH; 1 and 10 microM) altered oligodendrocyte cell line (158N) morphology and triggered apoptosis (75% of apoptosis after 72 h). These effects were mimicked by 22(S)-OH (1 and 10 microM) which does not activate liver X receptor (LXR) but not by a synthetic LXR ligand (T0901317). Therefore, oxysterol-induced apoptosis appears to be independent of LXR. Interestingly, sPLA2 type IIA (sPLA2-IIA) over-expression partially rescued 158N cells from oxysterol-induced apoptosis. In fact, 25-OH, 24(S)-OH, and T0901317 stimulated sPLA2-IIA promoter and sPLA2 activity in oligodendrocyte cell line. Accordingly, administration of T0901317 to mice enhanced sPLA2 activity in brain extracts by twofold. Short interfering RNA strategy allowed to establish that stimulation of sPLA2-IIA is mediated by pregnane X receptor (PXR) at high oxysterol concentration (10 microM) and by LXR beta at basal oxysterol concentration. Finally, GC coupled to mass spectrometry established that oligodendrocytes contain oxysterols and express their biosynthetic enzymes, suggesting that they may act through autocrine/paracrine mechanism. Our results show the diversity of oxysterol signalling in the CNS and highlight the positive effects of the LXR/PXR pathway which may open new perspectives in the treatment of demyelinating and neurodegenerative diseases.
TRANSPERITONEAL APPROACH TO THE INTERVERTEBRAL DISC IN THE.LUMBAR AREA (1948)

LANE, JOHN D. JR. M.D., F.A.C.S., SENIOR SCRGEON AND; MOORE, EMORY S. JR. M.D., SENIOR ASSISTANT SURGEON Author Information
Modulation of amyloid β protein precursor processing as a means of retarding progression of Alzheimer’s disease (1999)

Alzheimer’s disease (AD), a chronic neurodegenerative disorder, is characterized neuropathologically by an abundance of extracellular neuritic plaques (NPs) containing large amounts of a predominantly fibrillar peptide termed amyloid β (Aβ). The brains of victims of AD also harbor excessive numbers of neurofibrillary tangles (NFTs). NFTs are intraneuronal accumulations of paired helical filaments composed primarily of hyperphosphorylated isoforms of the microtubule-associated protein tau. In the United States, a definitive diagnosis of AD is based, at autopsy, on histopathological evidence of high numbers of both NPs and NFTs in individuals having a previous clinical history of progressive dementia. Additional neuropathological changes typically accompanying AD include congophilic angiopathy (Aβ fibrils within the basement membrane of the cerebrovasculature) and selective neuronal cell loss.
Mitochondrial dysfunction, oxidative stress, regulation of exocytosis and their relevance to neurodegenerative diseases (2007)

A common feature in the early stages of many neurodegenerative diseases lies in mitochondrial dysfunction, oxidative stress, and reduced levels of synaptic transmission. Many genes associated with neurodegenerative diseases are now known to regulate either mitochondrial function, redox state, or the exocytosis of neurotransmitters. Mitochondria are the primary source of reactive oxygen species and ATP and control apoptosis. Mitochondria are concentrated in synapses and significant alterations to synaptic mitochondrial localization, number, morphology, or function can be detrimental to synaptic transmission. Mitochondrial by-products are capable of regulating various steps of neurotransmission and mitochondrial dysfunction and oxidative stress occur in the early stages of many neurodegenerative diseases. This mini-review will highlight the prospect that mitochondria regulates synaptic exocytosis by controlling synaptic ATP and reactive oxygen species levels and that dysfunctional exocytosis caused by mitochondrial abnormalities may be a common underlying phenomenon in the initial stages of some human neurodegenerative diseases.
Epithelial hypoxia-inducible factor-1 is protective in murine experimental colitis (2004)

Mucosal epithelial cells are uniquely equipped to maintain barrier function even under adverse conditions. Previous studies have implicated hypoxia in mucosal tissue damage resulting from both acute and chronic inflammation. Given the importance of the transcriptional regulator hypoxia-inducible factor-1 (HIF-1) for adaptive hypoxia responses, we hypothesized that HIF-1 may serve as a barrier-protective element during mucosal inflammation. Initial studies of hapten-based murine colitis revealed extensive mucosal hypoxia and concomitant HIF-1 activation during colitis. To study this in more detail, we generated 2 mouse lines with intestinal epithelium–targeted expression of either mutant Hif1a (inability to form HIF-1) or mutant von Hippel-Lindau gene (Vhlh; constitutively active HIF-1). Studies of colitis in these mice revealed that decreased HIF-1 expression correlated with more severe clinical symptoms (mortality, weight loss, colon length), while increased HIF levels were protective in these parameters. Furthermore, colons with constitutive activation of HIF displayed increased expression levels of HIF-1–regulated barrier-protective genes (multidrug resistance gene-1, intestinal trefoil factor, CD73), resulting in attenuated loss of barrier during colitis in vivo. Taken together, these studies provide insight into tissue microenvironmental changes during model inflammatory bowel disease and identify HIF-1 as a critical factor for barrier protection during mucosal insult.
Identification, Cloning, and Expression of the CAMP factor gene ( cfa ) of Group A Streptococci (1999)

The CAMP reaction is a synergistic lysis of erythrocytes by the interaction of an extracellular protein (CAMP factor) produced by some streptococcal species with the Staphylococcus aureus sphingomyelinase C (beta-toxin). Group A streptococci (GAS [Streptococcus pyogenes]) have been long considered CAMP negative, and this reaction commonly has been used to distinguish GAS from Streptococcus agalactiae. We here provide evidence that GAS possess this gene and produce an extracellular CAMP factor capable of participating in a positive CAMP reaction. The S. pyogenes CAMP factor is specified by a 774-bp open reading frame homologous to the CAMP factor genes from S. agalactiae and Streptococcus uberis. This gene, designated cfa, was isolated on a 1,256-bp fragment and cloned in Escherichia coli. Recombinant clones of E. coli expressing cfa secreted an active CAMP factor. The deduced 28.5-kDa protein encoded by cfa consists of 257 amino acids, with a predicted 28-amino-acid signal peptide. The cfa gene is widely spread among GAS: 82 of 100 clinical GAS isolates produced a positive CAMP reaction. Of the CAMP-negative strains, 17 of the 18 GAS strains contained the cfa gene. Additionally, CAMP activity was detected in streptococci from serogroups C, M, P, R, and U. The cfa gene was cloned and actively expressed in Escherichia coli and gene fusions were made, placing the beta-galactosidase gene (lacZ) under control of the cfa promoter. These cfa promoter-lacZ fusions were introduced into S. pyogenes via a bacteriophage-derived site-specific integration vector where they showed that the cfa gene has a strong promoter that may be subject to as-yet-unidentified regulatory factors. The results presented here, along with previous reports, indicate that the CAMP factor gene is fairly widespread among streptococci, being present at least in groups A, B, C, G, M, P, R, and U.
Complement regulation in innate immunity and the acute-phase response: inhibition of mannan-binding lectin-initiated complement cytolysis by C-reactive protein (CRP) (1998)

Mannan-binding lectin (MBL) is an acute-phase protein which activates complement at the level of C4 and C2. We recently reported that the alternative pathway also is required for haemolysis via this 'lectin pathway' in human serum. CRP is another acute-phase reactant which activates the classical pathway, but CRP also inhibits the alternative pathway on surfaces to which it binds. Since serum levels of both proteins generally increase with inflammation and tissue necrosis, it was of interest to determine the effect of CRP on cytolysis via the lectin pathway. We report here that although CRP increases binding of C4 to MBL-sensitized erythrocytes, which in turn enhances lectin pathway haemolysis, it inhibits MBL-initiated cytolysis by its ability to inhibit the alternative pathway. This inhibition is characterized by increased binding of complement control protein H and decreased binding of C3 and C5 to the indicator cells, which in turn is attributable to the presence of CRP. Immunodepletion of H leads to greatly enhanced cytolysis via the lectin pathway, and this cytolysis is no longer inhibited by CRP. These results indicate that CRP regulates MBL-initiated cytolysis on surfaces to which both proteins bind by modulating alternative pathway recruitment through H, pointing to CRP as a complement regulatory protein, and suggesting a co-ordinated role for these proteins in complement activation in innate immunity and the acute-phase response.
Reconfigurable photonic switch based on a binary system using the white cell and micromirror arrays (2003)

We describe an N×N optical switch for use in cross-connects. It is a free-space device, based on multiple bounces in a pair of White cells sharing a spatial light modulator at one end. In a companion paper, we described various polynomial cells, in which the number of outputs was proportional to the number of bounces raised to some power. In the binary device described here, the number of possible outputs is proportional to the number two raised to the power of the number of bounces. It allows a 1024 × 1024 switch using a single digital two-state tip/tilt micromirror array, four spherical mirrors, and a spot displacement device. It is highly scalable and insensitive to micromirror pointing accuracy.
Herpes simplex virus 1 mutant deleted in the alpha 22 gene: growth and gene expression in permissive and restrictive cells and establishment of latency in mice (1985)

R325-beta TK+, a herpes simplex virus 1 mutant carrying a 500-base-pair deletion in the alpha 22 gene and the wild-type (beta) thymidine kinase (TK) gene, was previously shown to grow efficiently in HEp-2 and Vero cell lines. We report that in rodent cell lines exemplified by the Rat-1 line, plating efficiency was reduced and growth was multiplicity dependent. A similar multiplicity dependence for growth and lack of virus spread at low multiplicity was seen in resting, confluent human embryonic lung (HEL) cells. The shutoff of synthesis of beta proteins was delayed and the duration of synthesis of gamma proteins was extended in R325-beta TK+-infected HEL cells relative to cells infected with the wild-type parent, but no significant differences were seen in the total accumulation of viral DNA. To quantify the effect on late (gamma 2) gene expression, a recombinant carrying the deletion in the alpha 22 gene and a gamma 2-TK gene (R325-gamma 2 TK) was constructed and compared with a wild-type virus (R3112) carrying a chimeric gamma 2-TK gene. In Vero cells, the gamma 2-TK gene of R325-gamma 2TK was expressed earlier than and at the same level as the gamma 2-TK gene of R3112. In the confluent resting HEL cells, the expression of the gamma 2-TK gene of the alpha 22- virus was grossly reduced relative to that of the alpha 22+ virus. Electron microscopic studies indicated that the number of intranuclear capsids of R325-beta TK+ virus was reduced relative to that of the parent virus in resting confluent HEL cells, but the number of DNA-containing capsids was higher. Notwithstanding the grossly reduced neurovirulence on intracerebral inoculation in mice, R325-beta TK+ virus was able to establish latency in mice. We conclude that (i) the alpha 22 gene affects late (gamma 2) gene expression, and (ii) a host cell factor complements that function of the alpha 22 gene to a greater extent in HEp-2 and Vero cells than in confluent, resting HEL cells.
ISOLATION AND CHARACTERIZATION OF POLYPHENOLIC COMPOUNDS IN CRANBERRIES (1978)

ABSTRACT Methanolic extracts of cranberries were evaporated and reextracted with ethyl acetate. Residues from the dried ethyl acetate extract were isolated by thin‐layer, column, and paper chromatography. A large diffuse area indicated the presence of high molecular weight polymeric polyphenols. In addition, seven discrete spots were identified as: (a) catechin; (b) epicatechin; (c) a dimeric epicatechin with a C 4 ‐C 8 linkage; (d) an unknown polymer which degraded on acid hydrolysis to three compounds, of which one was cyanidin; (e) an unknown polymer which degraded to at least four compounds of which one was cyanidin and one was the compound described above as (d). Compounds (f) and (g) were present in very small amounts. These compounds may contribute to the astringency of cranberries.
Hirschsprung disease: a developmental disorder of the enteric nervous system (2012)

Hirschsprung disease (HSCR), which is also called congenital megacolon or intestinal aganglionosis, is characterized by an absence of enteric (intrinsic) neurons from variable lengths of the most distal bowel. Because enteric neurons are essential for propulsive intestinal motility, infants with HSCR suffer from severe constipation and have a distended abdomen. Currently the only treatment is surgical removal of the affected bowel. HSCR has an incidence of around 1:5,000 live births, with a 4:1 male:female gender bias. Most enteric neurons arise from neural crest cells that emigrate from the caudal hindbrain and then migrate caudally along the entire gut. The absence of enteric neurons from variable lengths of the bowel in HSCR results from a failure of neural crest-derived cells to colonize the affected gut regions. HSCR is therefore regarded as a neurocristopathy. HSCR is a multigenic disorder and has become a paradigm for understanding complex factorial disorders. The major HSCR susceptibility gene is RET. The penetrance of several mutations in HSCR susceptibility genes is sex-dependent. HSCR can occur as an isolated disorder or as part of syndromes; for example, Type IV Waardenburg syndrome is characterized by deafness and pigmentation defects as well as intestinal aganglionosis. Studies using animal models have shown that HSCR genes regulate multiple processes including survival, proliferation, differentiation, and migration. Research into HSCR and the development of enteric neurons is an excellent example of the cross fertilization of ideas that can occur between human molecular geneticists and researchers using animal models. WIREs Dev Biol 2013, 2:113-129. doi: 10.1002/wdev.57 For further resources related to this article, please visit the WIREs website.
Mutagenesis of the NS2B-NS3-Mediated Cleavage Site in the Flavivirus Capsid Protein Demonstrates a Requirement for Coordinated Processing (1999)

Analysis of flavivirus polyprotein processing has revealed the presence of a substrate for the virus-encoded NS2B-NS3 protease at the carboxy-terminal end of the C (capsid or core) protein. Cleavage at this site has been implicated in the efficient generation of the amino terminus of prM via signal peptidase cleavage. Yellow fever virus has four basic residues (Arg-Lys-Arg-Arg) in the P1 through P4 positions of this cleavage site. Multiple alanine substitutions were made for these residues in order to investigate the substrate specificity and biological significance of this cleavage. Mutants were analyzed by several methods: (i) a cell-free trans processing assay for direct analysis of NS2B-NS3-mediated cleavage; (ii) a trans processing assay in BHK-21 cells, using a C-prM polyprotein, for analysis of prM production; (iii) an infectivity assay of full-length transcripts to determine plaque-forming ability; and (iv) analysis of proteins expressed from full-length transcripts to assess processing in the context of the complete genome. Mutants that exhibited severe defects in processing in vitro and in vivo were incapable of forming plaques. Mutants that contained two adjacent basic residues within the P1 through P4 region were processed more efficiently in vitro and in vivo, and transcripts bearing these mutations were fully infectious. Furthermore, two naturally occurring plaque-forming revertants were analyzed and shown to have restored protein processing phenotypes in vivo. Finally, the efficient production of prM was shown to be dependent on the proteolytic activity of NS3. These data support a model of two coordinated cleavages, one that generates the carboxy terminus of C and another that generates the amino terminus of prM. A block in the viral protease-mediated cleavage inhibits the production of prM by the signal peptidase, inhibits particle release, and eliminates plaque formation.
MEASUREMENT OF IMPOSED VOLTAGE GRADIENT ADEQUATE TO MODULATE NEURONAL FIRING (1956)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
In Vitro Antiviral Activity of V-073 against Polioviruses (2009)

V-073, an enterovirus capsid inhibitor, was evaluated for its spectrum of antipoliovirus activity. V-073 inhibited all 45 polioviruses tested in a virus-induced cytopathic effect protection assay, with 50% effective concentration (EC50) values ranging from 0.003 to 0.126 microM. Ninety percent of the polioviruses tested were inhibited at EC(50)s of < or = 0.076 microM (MIC90 = 32 ng/ml). V-073 is a promising antiviral candidate for the posteradication management of poliovirus incidents.
Microsurgery in Children (1995)

Advances in microsurgical techniques have permitted replantation and reconstructive procedures to restore amputated or injured parts with a high degree of success in children. Despite this progress, some technical concerns remain. During a 15-year period, replantations were done in 53 children with major limb (18), hand (10), or digit (25) amputations. Even in patients with crush or avulsion injuries, the results suggest that replantation procedures are justified considering the superior recuperative ability in children. Free tissue transfer was used for reconstructive procedures in 26 children, including free flaps, vascularized bone transfers, nerve grafts, and toe-to-thumb transfers. The microsurgical success rate was 86.8% for replantation procedures and 96% for reconstructive procedures. Although the technical aspects and outcome of replantation attempts still differ between adults and children, there appears to be little difference in free tissue transfer. Thus, most replantation and reconstructive procedures can be attempted with a high possibility of success in children.
Novel Sorption Materials for Solar Heating and Cooling (2012)

Heat transformation based on adsorption/desorption of water in microporous adsorbents has been considered for the application as adsorption chiller (ACS), adsorption heat pump (AHP) or thermochemical storage (TCS) since the 1980s. Unfortunately, most of the available adsorbents like zeolites were not optimized for the use in these processes as they originally had been developed for gas separation or catalysis processes. Within the last decade, intensive research on adsorbents yielded in improved and very promising new sorption materials with an enhanced adsorption capacity. This work gives a broad overview on current developments on materials including the new class of metal-organic frameworks for the use in adsorption processes for heat storage and transformation.