gebhart/patrepeval huggingface dataset:
In Vivo Verification of an Automatic Noninvasive System for Real Time Kt Evaluation (1993)

It is generally accepted that morbidity and mortality of hemodialysis patients is related to dialysis quantitation. Currently available methods for the quantitation of dialysis require blood sampling or a continuous measurement of changes in urea concentration during treatment. These maneuvers are time consuming and expensive, and are generally performed, at most, once per month. The authors introduce an on-line, automated method for measurement of dialyzer electrolyte clearance comparable to urea clearance by using dialysate conductivity sensors placed pre and post dialyzer, and measuring conductivity at three different pre dialyzer levels. Conditions that reduce clearance, such as recirculation or fiber clotting, are automatically taken into account so that the method measures effective clearance rather than dialyzer clearance. In vitro and in vivo studies validate the method. Results are immediately available and can be used to address problems such as improper needle placement and access recirculation. In addition, repetitive electrolyte clearance data can serve to enhance quality assurance programs with respect to verifying the function of reused or new dialyzers. Appropriate algorithms can be used to calculate delivered Kt/V.
Physician Outlook Toward Fecal Microbiota Transplantation in the Treatment of Clostridium difficile Infection (2013)

Sofi, Aijaz Ahmed MD; Georgescu, Claudiu MD; Sodeman, Thomas MD; Nawras, Ali MD, FACG Author Information
Dystonia associated with mutation of the neuronal sodium channel Scn8a and identification of the modifier locus Scnm1 on mouse chromosome 3 (1999)

The mouse mutant medJ contains a splice site mutation in the neuronal sodium channel Scn8a that results in a very low level of expression. On a C57BL/6J genetic background, medJ homozygotes exhibit progressive paralysis and juvenile lethality. The C3H genetic background has an ameliorating effect, producing viable adults with a novel dystonic phenotype. The dystonic mice exhibit movement-induced, sustained abnormal postures of the trunk and limbs. A dominant modifier locus responsible for the difference between strains was mapped to a 4.5 +/- 1.3 cM interval on mouse chromosome 3. Our findings establish a role for ion channels in dystonia and demonstrate the impact of genetic background on its severity and progression. This new model suggests that SCN8A on chromosome 12q13 and SCNM1 on chromosome 1p21-1q21 may contribute to human inherited dystonia.
Nkx2–5 transactivates the Ets-related protein 71 gene and specifies an endothelial/endocardial fate in the developing embryo (2009)

Recent studies support the existence of a common progenitor for the cardiac and endothelial cell lineages, but the underlying transcriptional networks responsible for specification of these cell fates remain unclear. Here we demonstrated that Ets-related protein 71 (Etsrp71), a newly discovered ETS family transcription factor, was a novel downstream target of the homeodomain protein, Nkx2-5. Using genetic mouse models and molecular biological techniques, we demonstrated that Nkx2-5 binds to an evolutionarily conserved Nkx2-5 response element in the Etsrp71 promoter and induces the Etsrp71 gene expression in vitro and in vivo. Etsrp71 was transiently expressed in the endocardium/endothelium of the developing embryo (E7.75-E9.5) and was extinguished during the latter stages of development. Using a gene disruption strategy, we found that Etsrp71 mutant embryos lacked endocardial/endothelial lineages and were nonviable. Moreover, using transgenic technologies and transcriptional and chromatin immunoprecipitation (ChIP) assays, we further established that Tie2 is a direct downstream target of Etsrp71. Collectively, our results uncover a novel functional role for Nkx2-5 and define a transcriptional network that specifies an endocardial/endothelial fate in the developing heart and embryo.
Viability, adhesion, and bone phenotype of osteoblast‐like cells on polyelectrolyte multilayer films (2002)

The aim of this study was to develop new biocompatible coatings for bone implants by the alternating deposition of oppositely charged polyelectrolytes. Polyelectrolyte films were built up with different terminating layers on which SaOS-2 osteoblast-like cells and human periodontal ligament (PDL) cells were grown. The terminating layer was made of one of the following polyelectrolytes: poly(ethylene imine) (PEI), poly(sodium 4-styrenesulfonate) (PSS), poly(allylamine hydrochloride) (PAH), poly(L-glutamic acid) (PGA), or poly(L-lysine) (PLL). Cell adherence, viability, stability of osteoblast phenotype, and inflammatory response were studied. Adherence and viability were good on all terminating layers except the PEI-terminating layer, which was cytotoxic. Maintenance of osteoblast phenotype marker expression was observed on PSS- and PGA-terminating films for both cell types, whereas downregulation, associated with the induction of Interleukin-8 (IL-8) secretion, was detected on PEI and PAH for both cell types and on PLL for PDL cells. These results suggested a good biocompatibility of PSS- and PGA-ending films for PDL cells and of PSS-, PGA-, and PLL-terminating films for SaOS-2 cells. As a result, polyelectrolyte multilayer films could emerge as new alternatives for implant coatings.
Glycosylation of CD44 is implicated in CD44-mediated cell adhesion to hyaluronan. (1996)

CD44-mediated cell adhesion to hyaluronate is controlled by mechanisms which are poorly understood. In the present work we examine the role of N-linked glycosylation and Ser-Gly motifs in regulating CD44-hyaluronate interaction. Our results show that treatment of a panel of human cell lines which constitutively express CD44 with the inhibitor of N-linked glycosylation tunicamycin results in the loss of attachment of these cells to hyaluronate-coated substrate. In contrast, treatment of the same cells with deoxymannojirimycin, which inhibits the conversion of high mannose oligosaccharides to complex N-linked carbohydrates, results in either no change or an increase in CD44-mediated adhesion to hyaluronate, suggesting that complex N-linked oligosaccharides may not be required for and may even inhibit CD44-HA interaction. Using human melanoma cells stably transfected with CD44 N-linked glycosylation site-specific mutants, we show that integrity of five potential N-linked glycosylation sites within the hyaluronate recognition domain of CD44 is critical for hyaluronate binding. Mutation of any one of these potential N-linked glycosylation sites abrogates CD44-mediated melanoma cell attachment to hyaluronate-coated surfaces, suggesting that all five sites are necessary to maintain the HA-recognition domain in the appropriate conformation. We also demonstrate that mutation of serine residues which constitute the four Ser-Gly motifs in the membrane proximal domain, and provide potential sites for glycosaminoglycan side chain attachment, impairs hyaluronate binding. Taken together, these observations indicate that changes in glycosylation of CD44 can have profound effects on its interaction with hyaluronic acid and suggest that glycosylation may provide an important regulatory mechanism of CD44 function.
10 minute guide to cc:Mail 6 (1996)

From the Publisher:
The 10 Minute Guide to cc:Mail 6 offers simple, practical help for busy people who need fast results. Through goal-oriented, 10-minute lessons, you'll learn all the essential tasks for using electronic mail. 10 minutes is all you need to learn how to send and receive messages, organize your incoming mail, customize cc:Mail to work the way you work, easily exchange information with cc:Mail's new built-in forms, post messages to company-wide electronic bulletin boards, and learn the basic of scheduling and planning online with Lotus Organizer.
The expression of slow myosin during mammalian somitogenesis and limb bud differentiation. (1988)

The developmental pattern of slow myosin expression has been studied in mouse embryos from the somitic stage to the period of secondary fiber formation and in myogenic cells, cultured from the same developmental stages. The results obtained, using a combination of different polyclonal and monoclonal antibodies, indicate that slow myosin is coexpressed in virtually all the cells that express embryonic (fast) myosin in somites and limb buds in vivo as well as in culture. On the contrary fetal or late myoblasts (from 15-d-old embryos) express in culture only embryonic (fast) myosin. At this stage, muscle cells in vivo, as already shown (Crow, M.T., and F.A. Stockdale. 1986. Dev. Biol. 113:238-254; Dhoot, G.K. 1986. Muscle & Nerve. 9:155-164; Draeger, A., A.G. Weeds, and R.B. Fitzsimons. 1987. J. Neurol. Sci. 81:19-43; Miller, J.B., and F.A. Stockdale. 1986. J. Cell Biol. 103:2197-2208), consist of primary myotubes, which express both myosins, and secondary myotubes, which express preferentially embryonic (fast) myosin. Under no circumstance neonatal or adult fast myosins were detected. Western blot analysis confirmed the immunocytochemical data. These results suggest that embryonic myoblasts in mammals are all committed to the mixed embryonic-(fast) slow lineage and, accordingly, all primary fibers express both myosins, whereas fetal myoblasts mostly belong to the embryonic (fast) lineage and likely generate fibers containing only embryonic (fast) myosin. The relationship with current models of avian myogenesis are discussed.
Abnormalities of Striatal Projection Neurons andN-Methyl-D-Aspartate Receptors in Presymptomatic Huntington's Disease (1990)

HUNTINGTON'S disease is an autosomal dominant disease characterized by slowly progressive personality changes, dementia, and movement disorders.1 , 2 The average age at onset is 30 to 40 years, and the disease lasts for an average of 15 to 20 years. Analysis with restriction-fragmentlength polymorphisms (RFLPs) has localized the Huntington's disease gene close to the telomere of the short arm of chromosome 4.1 2 3 Prominent striatal atrophy with loss of striatal neurons and relative sparing of fibers of passage and afferent axons is the pathological hallmark of Huntington's disease.4 Recent studies have demonstrated a distinct pattern of vulnerability of striatal neurons in Huntington's . . .
Cellular Delivery of Impermeable Effector Molecules in the Form of Conjugates with Peptides Capable of Mediating Membrane Translocation (2001)

Most molecules that are not actively imported by living cells are impermeable to cell membranes, including practically all macromolecules and even many small molecules whose physicochemical properties prevent passive membrane diffusion. The use of peptide vectors capable of transporting such molecules into cells in the form of covalent conjugates has become an increasingly attractive solution to this problem. Not only has this technology permitted the study of modulating intracellular target proteins, but it has also gained importance as an alternative to conventional cellular transfection with oligonucleotides. Peptide vectors derived from viral, bacterial, insect, and mammalian proteins endowed with membrane translocation properties have now been proposed as delivery vectors. These are discussed comprehensively and critically in terms of relative utility, applications to compound classes and specific molecules, and relevant conjugation chemistry. Although in most cases the mechanisms of membrane translocation are still unclear, physicochemical studies have been carried out with a number of peptide delivery vectors. Unifying and distinguishing mechanistic features of the various vectors are discussed. Until a few years ago speculations that it might be possible to deliver peptides, proteins, oligonucleotides, and impermeable small molecules with the aid of cellular delivery peptides not only to target cells in vitro, but in vivo, was received with scepticism. However, the first studies showing pharmacological applications of conjugates between macromolecules and peptide delivery vectors are now being reported, and therapies based on such conjugates are beginning to appear feasible.
Activated nitriles in heterocyclic synthesis: reaction of cyanogen bromide with some functionally substituted enamines (1985)

Z. E. Kandeel, F. M. Abdelrazek, N. E. M. S. Eldin and M. H. Elnagdi, J. Chem. Soc., Perkin Trans. 1, 1985, 1499 DOI: 10.1039/P19850001499
Synthesis of Peptide‐Oligonucleotide Conjugates Using a Heterobifunctional Crosslinker (2010)

Peptide-oligonucleotide conjugates (POCs) are molecular chimeras composed of a nucleic acid moiety covalently attached to a polypeptide moiety. POCs have been used in numerous applications from therapeutics to nanotechnology, and most recently as combinatorial agents in the assembly of bivalent protein affinity reagents. This unit describes the synthesis and purification of POC molecules using the heterobifunctional crosslinking reagent succinimidyl-4-(N-maleimidomethyl)cyclohexane-1-carboxylate (SMCC), which enables amine-modified oligonucleotides to become covalently linked to cysteine-modified polypeptides. This solution-based protocol consists of a two-step synthesis followed by a single purification step.
ABERRANT ERG EXPRESSION COOPERATES WITH PTEN LOSS TO PROMOTE PROSTATE TUMORIGENESIS (2008)

You have accessJournal of Urology1 Apr 2008ABERRANT ERG EXPRESSION COOPERATES WITH PTEN LOSS TO PROMOTE PROSTATE TUMORIGENESIS Brett S Carver, Jennifer Tran, Anuhadra Gopalan, Peter T Scardino, William Gerald, and Pier P Pandolfi Brett S CarverBrett S Carver More articles by this author , Jennifer TranJennifer Tran More articles by this author , Anuhadra GopalanAnuhadra Gopalan More articles by this author , Peter T ScardinoPeter T Scardino More articles by this author , William GeraldWilliam Gerald More articles by this author , and Pier P PandolfiPier P Pandolfi More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(08)61350-6AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "ABERRANT ERG EXPRESSION COOPERATES WITH PTEN LOSS TO PROMOTE PROSTATE TUMORIGENESIS." The Journal of Urology, 179(4S), p. 460 © 2008 by American Urological AssociationFiguresReferencesRelatedDetails Volume 179Issue 4SApril 2008Page: 460 Advertisement Copyright & Permissions© 2008 by American Urological AssociationMetricsAuthor Information Brett S Carver More articles by this author Jennifer Tran More articles by this author Anuhadra Gopalan More articles by this author Peter T Scardino More articles by this author William Gerald More articles by this author Pier P Pandolfi More articles by this author Expand All Advertisement PDF downloadLoading ...
Working memory, long-term memory, and medial temporal lobe function (2011)

Early studies of memory-impaired patients with medial temporal lobe (MTL) damage led to the view that the hippocampus and related MTL structures are involved in the formation of long-term memory and that immediate memory and working memory are independent of these structures. This traditional idea has recently been revisited. Impaired performance in patients with MTL lesions on tasks with short retention intervals, or no retention interval, and neuroimaging findings with similar tasks have been interpreted to mean that the MTL is sometimes needed for working memory and possibly even for visual perception itself. We present a reappraisal of this interpretation. Our main conclusion is that, if the material to be learned exceeds working memory capacity, if the material is difficult to rehearse, or if attention is diverted, performance depends on long-term memory even when the retention interval is brief. This fundamental notion is better captured by the terms subspan memory and supraspan memory than by the terms short-term memory and long-term memory. We propose methods for determining when performance on short-delay tasks must depend on long-term (supraspan) memory and suggest that MTL lesions impair performance only when immediate memory and working memory are insufficient to support performance. In neuroimaging studies, MTL activity during encoding is influenced by the memory load and correlates positively with long-term retention of the material that was presented. The most parsimonious and consistent interpretation of all the data is that subspan memoranda are supported by immediate memory and working memory and are independent of the MTL.
Fibrosis in heart disease: understanding the role of transforming growth factor‐β1 in cardiomyopathy, valvular disease and arrhythmia (2006)

The importance of fibrosis in organ pathology and dysfunction appears to be increasingly relevant to a variety of distinct diseases. In particular, a number of different cardiac pathologies seem to be caused by a common fibrotic process. Within the heart, this fibrosis is thought to be partially mediated by transforming growth factor-beta1 (TGF-beta1), a potent stimulator of collagen-producing cardiac fibroblasts. Previously, TGF-beta1 had been implicated solely as a modulator of the myocardial remodelling seen after infarction. However, recent studies indicate that dilated, ischaemic and hypertrophic cardiomyopathies are all associated with raised levels of TGF-beta1. In fact, the pathogenic effects of TGF-beta1 have now been suggested to play a major role in valvular disease and arrhythmia, particularly atrial fibrillation. Thus far, medical therapy targeting TGF-beta1 has shown promise in a multitude of heart diseases. These therapies provide great hope, not only for treatment of symptoms but also for prevention of cardiac pathology as well. As is stated in the introduction, most reviews have focused on the effects of cytokines in remodelling after myocardial infarction. This article attempts to underline the significance of TGF-beta1 not only in the post-ischaemic setting, but also in dilated and hypertrophic cardiomyopathies, valvular diseases and arrhythmias (focusing on atrial fibrillation). It also aims to show that TGF-beta1 is an appropriate target for therapy in a variety of cardiovascular diseases.
The affinity adsorptive recovery of an infectious Herpes Simplex Virus vaccine (1999)

The chromatographic purification of a recombinant Herpes Simplex Virus (type 2) from salt- and heparin-released harvests of infected complementing Vero (CR2) cells is addressed. Functionalized matrices and process operating conditions are identified that provide adequate virus titres in eluates that are significantly reduced in CR2 cell protein and DNA and possess a low level of HSV-2 protein. Virus from diluted salt-released harvests (0.14 M NaCl) was not appreciably adsorbed onto either heparin-Sepharose or Cellufine-heparin matrices but was virtually completely adsorbed onto Cellufine-sulfate and heparin-HP matrices. Virus was recovered by either a linear salt gradient elution (0.14-2 M NaCl) or by a single-step elution with 1.5 M NaCl in phosphate buffer. Recoveries of infectious virus with step elution were 21% and 89%, respectively, for these matrices. Virus from undiluted salt-released harvest (0.8 M NaCl) was substantially adsorbed onto Cellufine-sulfate gel (44% adsorption) and completely adsorbed onto heparin-HP matrices. This virus was recovered with high yield by either gradient or step elution with phosphate-buffered saline. Finally, heparin-harvested virus was fed directly to these matrices and quantitatively adsorbed. The virus could be completely recovered from the heparin-HP matrix with 1.5 M NaCl buffer to provide a purified preparation containing only 0.05 pg protein/pfu and 1.2 x 10(-4) pg DNA/pfu.
Molecular Interplay between Mammalian Target of Rapamycin (mTOR), Amyloid-β, and Tau (2010)

Accumulation of amyloid-beta (Abeta) and Tau is an invariant feature of Alzheimer disease (AD). The upstream role of Abeta accumulation in the disease pathogenesis is widely accepted, and there is strong evidence showing that Abeta accumulation causes cognitive impairments. However, the molecular mechanisms linking Abeta to cognitive decline remain to be elucidated. Here we show that the buildup of Abeta increases the mammalian target of rapamycin (mTOR) signaling, whereas decreasing mTOR signaling reduces Abeta levels, thereby highlighting an interrelation between mTOR signaling and Abeta. The mTOR pathway plays a central role in controlling protein homeostasis and hence, neuronal functions; indeed mTOR signaling regulates different forms of learning and memory. Using an animal model of AD, we show that pharmacologically restoring mTOR signaling with rapamycin rescues cognitive deficits and ameliorates Abeta and Tau pathology by increasing autophagy. Indeed, we further show that autophagy induction is necessary for the rapamycin-mediated reduction in Abeta levels. The results presented here provide a molecular basis for the Abeta-induced cognitive deficits and, moreover, show that rapamycin, an FDA approved drug, improves learning and memory and reduces Abeta and Tau pathology.
Phase I Study in Cancer Patients of a Replication-Defective Avipox Recombinant Vaccine That Expresses Human Carcinoembryonic Antigen (1999)

These studies constitute the first phase I trial of an avipox recombinant in cancer patients. The recombinant vaccine ALVAC-CEA seems to be safe and has been demonstrated to elicit CEA-specific CTL responses. These studies thus form the basis for the further clinical exploration of the ALVAC-CEA recombinant vaccine in phase I/II studies in protocols designed to enhance the generation of human T-cell responses to CEA.
Thermoelectric figure of merit of a one-dimensional conductor (1993)

We investigate the effect on the thermoelectric figure of merit of preparing materials in the form of one-dimensional conductors or quantum wires. Our calculations show that this approach has the potential to achieve a significant increase in the figure of merit over both the bulk value and the calculated superlattice values.
In vitro cytotoxicity and antibiotic activity of polymyxin B nonapeptide (1986)

Polymyxin B nonapeptide, prepared by enzymic removal of the fatty acyl diaminobutyric acid side chain from polymyxin B, was about 100-fold less toxic to K562 cells than polymyxin B. MICs of polymyxin B nonapeptide against a test panel of bacteria were 2- to 64-fold lower than those of polymyxin B.
Plasma MicroRNA-122 as a Biomarker for Viral-, Alcohol-, and Chemical-Related Hepatic Diseases (2010)

Our findings suggest that circulating miR-122 has potential as a novel, predictive, and reliable blood marker for viral-, alcohol-, and chemical-induced liver injury.
On the accuracy and effectiveness of dose reconstruction for tomotherapy (2001)

Dose reconstruction is a process that re-creates the treatment-time dose deposited in a patient provided there is knowledge of the delivered energy fluence and the patient's anatomy at the time of treatment. A method for reconstructing dose is presented. The process starts with delivery verification, in which the incident energy fluence from a treatment is computed using the exit detector signal and a transfer matrix to convert the detector signal to energy fluence. With the verified energy fluence and a CT image of the patient in the treatment position, the treatment-time dose distribution is computed using any model-based algorithm such as convolution/superposition or Monte Carlo. The accuracy of dose reconstruction and the ability of the process to reveal delivery errors are presented. Regarding accuracy, a reconstructed dose distribution was compared with a measured film distribution for a simulated breast treatment carried out on a thorax phantom. It was found that the reconstructed dose distribution agreed well with the dose distribution measured using film: the majority of the voxels were within the low and high dose-gradient tolerances of 3% and 3 mm respectively. Concerning delivery errors, it was found that errors associated with the accelerator, the multileaf collimator and patient positioning might be detected in the verified energy fluence and are readily apparent in the reconstructed dose. For the cases in which errors appear in the reconstructed dose, the possibility for adaptive radiotherapy is discussed.