gebhart/patrepeval huggingface dataset:
Genetic therapy for the nervous system (2011)

Genetic therapy is undergoing a renaissance with expansion of viral and synthetic vectors, use of oligonucleotides (RNA and DNA) and sequence-targeted regulatory molecules, as well as genetically modified cells, including induced pluripotent stem cells from the patients themselves. Several clinical trials for neurologic syndromes appear quite promising. This review covers genetic strategies to ameliorate neurologic syndromes of different etiologies, including lysosomal storage diseases, Alzheimer's disease and other amyloidopathies, Parkinson's disease, spinal muscular atrophy, amyotrophic lateral sclerosis and brain tumors. This field has been propelled by genetic technologies, including identifying disease genes and disruptive mutations, design of genomic interacting elements to regulate transcription and splicing of specific precursor mRNAs and use of novel non-coding regulatory RNAs. These versatile new tools for manipulation of genetic elements provide the ability to tailor the mode of genetic intervention to specific aspects of a disease state.
Enhancing the visual realism of hysteroscopy simulation. (2006)

Visualization is a very important part of a high fidelity surgical simulator. Due to modern computer graphics hardware, which offers more and more features and processing power, it is possible to extend the standard OpenGL rendering methods with advanced visualization techniques to achieve highly realistic rendering in real-time. For an easy and efficient use of these new capabilities, a stand-alone graphics engine has been implemented, which exploits these advanced rendering techniques and provides an interface in order to ensure the interoperability with a software framework for surgical simulators.
Automated detection of bolus arrival and initiation of data acquisition in fast, three-dimensional, gadolinium-enhanced MR angiography. (1997)

Automatic triggering of magnetic resonance (MR) angiography with detection of a contrast material bolus was evaluated. Signal intensity changes with time were tracked in a prescribed tracking or monitoring volume by a parallel signal processing unit that automatically started data acquisition once user-defined thresholds were exceeded. This technique, referred to as MR Smartprep, was reliable and avoided the inconsistencies of manual timing.
Investigation of the Molecular Mechanism of ICAN, a Novel Gene Amplification Method (2007)

Isothermal and Chimeric primer-initiated Amplification of Nucleic acids (ICAN) allows the amplification of target DNA under isothermal conditions at around 55 degrees C using only a pair of 5'-DNA-RNA-3' chimeric primers, thermostable RNaseH and a DNA polymerase with strand-displacing activity (H. Mukai et al. J. Biochemistry, in the preceding paper in this issue). Here we elucidated the mechanism of ICAN by analysing the nicking site of RNaseH, behaviour of chimeric primers and extension products. We found that the ICAN reaction was composed of two unique mechanisms, multi-priming and template-switching, that were responsible for the highly efficient amplifying capability of ICAN. The simultaneous occurrence of two types of reactions, one based on multi-priming and the other based on template-switching, is likely to drive the DNA amplification in ICAN.
A phase 2, multicenter study to evaluate the efficacy and safety using autologous tumor infiltrating lymphocytes (LN-145) in patients with recurrent, metastatic, or persistent cervical carcinoma. (2018)

TPS5604 Background: Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TIL) has demonstrated efficacy in the treatment of immunogenic tumors with high mutation loads, such as melanoma, and virally-associated tumors, such as HPV-mediated cervical cancer. As outcomes for patients with recurrent, metastatic or persistent cervical cancer remain extremely poor, there is an enormous need for the development of novel immunotherapeutic approaches with curative potential such as ACT with TIL. Methods: Clinical trial C-145-04 (NCT03108495) is a prospective, phase 2 multicenter, open-label study evaluating the efficacy of a single autologous TIL infusion (LN-145) followed by IL-2 after a non-myeloablative lymphodepletion (NMA-LD) regimen in patients with recurrent, metastatic, or persistent cervical cancer who have failed at least one prior systemic therapy. Patients undergo surgical resection of a tumor from which TIL are extracted and expanded at a central GMP manufacturing facility that prepares a cryo-preserved TIL (LN-145) product for infusion. One week prior to LN-145 infusion, patients undergo NMA-LD consisting of cyclophosphamide (60 mg/kg) daily x 2 days followed by fludarabine (25 mg/m2) daily x 5 days. LN-145 is infused 24 hours after NMA-LD and followed by up to 6 doses of IL-2 (600,000 IU/kg) every 8-12 hours. The primary endpoint is the objective response rate (ORR) per RECIST v1.1. Secondary endpoints include safety and efficacy parameters such as complete response, duration of response, disease control rate, progression free- and overall survival. In addition to the tumor resected, patients must have an additional measurable lesion for response assessment. Other major eligibility criteria include adequate bone marrow, liver, pulmonary, cardiac and renal function; ECOG performance status of 0 or 1. Clinical trial information: NCT03108495.
Nucleoside Oxazaphospholidines as Novel Synthons in Oligonucleotide Synthesis (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNucleoside Oxazaphospholidines as Novel Synthons in Oligonucleotide SynthesisRadhakrishnan P. Iyer, Dong Yu, Theresa Devlin, Nan-Hui Ho, and Sudhir AgrawalCite this: J. Org. Chem. 1995, 60, 17, 5388–5389Publication Date (Print):September 1, 1995Publication History Published online1 May 2002Published inissue 1 September 1995https://pubs.acs.org/doi/10.1021/jo00122a012https://doi.org/10.1021/jo00122a012research-articleACS PublicationsRequest reuse permissionsArticle Views168Altmetric-Citations14LEARN 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
CECAL LIGATION AND PUNCTURE (2005)

The model of cecal ligation and puncture (CLP) in rodents has been used extensively to investigate the clinical settings of sepsis and septic shock. This model produces a hyperdynamic, hypermetabolic state that can lead to a hypodynamic, hypometabolic stage, and eventual death. Blood cultures are positive for enteric organisms very early after CLP. The model has been widely used over the past 26 years and is highly versatile in adapting to a range of severity and testing objectives. It is inexpensive to prepare and technically straightforward. Aspects of sepsis research investigated using CLP include energetics, metabolism, resuscitation, antibiotic therapy, microbial factors, cardiovascular responses, immune function, mediator release, and cytokine expression patterns. The challenge of the small circulating blood volume in rodents can be overcome by using micromethods that enable analysis of small volumes, or alternatively, by using a large number of animals to obtain serial samples.
A Clockwork RNN (2014)

Sequence prediction and classification are ubiquitous and challenging problems in machine learning that can require identifying complex dependencies between temporally distant inputs. Recurrent Neural Networks (RNNs) have the ability, in theory, to cope with these temporal dependencies by virtue of the short-term memory implemented by their recurrent (feedback) connections. However, in practice they are difficult to train successfully when long-term memory is required. This paper introduces a simple, yet powerful modification to the simple RNN (SRN) architecture, the Clockwork RNN (CW-RNN), in which the hidden layer is partitioned into separate modules, each processing inputs at its own temporal granularity, making computations only at its prescribed clock rate. Rather than making the standard RNN models more complex, CW-RNN reduces the number of SRN parameters, improves the performance significantly in the tasks tested, and speeds up the network evaluation. The network is demonstrated in preliminary experiments involving three tasks: audio signal generation, TIMIT spoken word classification, where it outperforms both SRN and LSTM networks, and online handwriting recognition, where it outperforms SRNs.
Prototypal Diarrheagenic Strains of Hafnia alvei Are Actually Members of the Genus Escherichia (1999)

We analyzed five bacterial strains, designated 19982, 9194, 10457, 10790, and 12502, that were isolated from stool specimens of individuals with diarrheal illness by the International Centre for Diarrhoeal Disease Research in Dhaka, Bangladesh (M. J. Albert, S. M. Faruque, M. Ansaruzzaman, M. M. Islam, K. Haider, K. Alam, I. Kabir, and R. Robins-Browne, J. Med. Microbiol. 37:310-314, 1992). The strains were initially identified as Hafnia alvei with a commercial identification system and were reported to contain the eae gene of enteropathogenic Escherichia coli. Results of conventional biochemical analyses, testing of susceptibility to cephalothin, lysis by a Hafnia-specific phage, and amplification of the outer membrane protein gene phoE with species-specific primers support the identification of these strains as members of the genus Escherichia rather than Hafnia alvei. These strains varied from typical E. coli strains by their inability to produce acid from lactose or D-sorbitol and failure to elaborate the enzyme beta-D-glucuronidase. PCR analysis confirmed previous findings that the strains were positive for the eae gene and negative for other virulence markers present among recognized categories of diarrheagenic E. coli. Our findings support the hypothesis that these strains are a new category of diarrheagenic isolates belonging to the genus Escherichia and illustrate the importance of using multiple methodologies when identifying new bacterial agents of diarrheal disease.
Theory of diblock-copolymer segregation to the interface and free surface of a homopolymer layer (1992)

Equilibrium and dynamics of block-copolymer chains in a homopolymer layer (between the interface with another homopolymer and the free surface) are considered. An analytical mean-field theory for equilibrium copolymer segregation to the interface is presented, the results being in good agreement with those of another theoretical approach and with experimental data. The dynamics of an interface copolymer excess is also considered. The situation above the critical micelle concentration (cmc) is also analyzed. It is shown that (i) copolymer micelles usually strongly attract each other, tending to form a separate micellar macrophase; (ii) primings of the copolymer phase are attracted to the free surface and (somewhat weaker) to the interface; the superwetting of the free surface by t he micellar phase is expected for copolymer molecular weights exceeding some critical value; (iii) the formation of micelles is an activation process usually with a high energy of activation; so, the apparent cmc might be appreciably greater than the equilibrium cmc; (iv) for high enough copolymer molecular weights the micellar geometry should be dynamically controlled; in that case the formation of spherical micelles dominates over other geometries in a wide range of copolymer compositions including symmetric copolymers (provided that the copolymer volume fraction is small); (v) the micellar contribution to the free surface and interface excesses is due to higher rate of the micelle's formation at the surfaces.
Species differences in the metabolism of norephedrine in man, rabbit and rat (1973)

1. (+/-)-2-Amino-1-phenyl[1-(14)C]propan-1-ol ([(14)C]norephedrine) was administered orally to man, rat and rabbit and the metabolites excreted in the urine were identified and measured. Pronounced species differences in the metabolism of the drug were found. 2. Three male human subjects, receiving 25mg each of [(14)C]norephedrine hydrochloride, excreted over 90% of the (14)C in the first day. The main metabolite was the unchanged drug (86% of the dose) and minor metabolites were hippuric acid and 4-hydroxynorephedrine. 3. In rats given 12mg of the drug/kg almost 80% of the (14)C administered was excreted in the first day. The major metabolites in the urine were the unchanged drug (48% of the dose), 4-hydroxynorephedrine (28%) and trace amounts of side-chain degradation products. 4. Rabbits given 12mg of the drug/kg excreted 85-95% of the dose of (14)C in the urine in the first 24h after dosing. The major metabolites in the urine were conjugates of 1,2-dihydroxy-1-phenylpropane (31% of the dose) and of 1-hydroxy-1-phenylpropan-2-one (27%) and hippuric acid (20%). The unchanged drug was excreted in relatively small amounts (8%).
Formation of a Ruthenium(IV)-Oxo Complex by Electron-Transfer Oxidation of a Coordinatively Saturated Ruthenium(II) Complex and Detection of Oxygen-Rebound Intermediates in C–H Bond Oxygenation (2011)

A coordinatively saturated ruthenium(II) complex having tetradentate tris(2-pyridylmethyl)amine (TPA) and bidentate 2,2'-bipyridine (bpy), [Ru(TPA)(bpy)](2+) (1), was oxidized by a Ce(IV) ion in H(2)O to afford a Ru(IV)-oxo complex, [Ru(O)(H(+)TPA)(bpy)](3+) (2). The crystal structure of the Ru(IV)-oxo complex 2 was determined by X-ray crystallography. In 2, the TPA ligand partially dissociates to be in a facial tridentate fashion and the uncoordinated pyridine moiety is protonated. The spin state of 2, which showed paramagnetically shifted NMR signals in the range of 60 to -20 ppm, was determined to be an intermediate spin (S = 1) by the Evans' method with (1)H NMR spectroscopy in acetone-d(6). The reaction of 2 with various oraganic substrates in acetonitrile at room temperature afforded oxidized and oxygenated products and a solvent-bound complex, [Ru(H(+)TPA)(bpy)(CH(3)CN)], which is intact in the presence of alcohols. The oxygenation reaction of saturated C-H bonds with 2 proceeds by two-step processes: the hydrogen abstraction with 2, followed by the dissociation of the alcohol products from the oxygen-rebound complexes, Ru(III)-alkoxo complexes, which were successfully detected by ESI-MS spectrometry. The kinetic isotope effects in the first step for the reaction of dihydroanthrathene (DHA) and cumene with 2 were determined to be 49 and 12, respectively. The second-order rate constants of C-H oxygenation in the first step exhibited a linear correlation with bond dissociation energies of the C-H bond cleavage.
Abrogation of Fv-1 restriction by genome-deficient virions produced by a retrovirus packaging cell line (1990)

The Fv-1b-mediated restriction of N-tropic retrovirus vector infection of BALB/3T3 cells was partially abrogated by prior infection with N-tropic murine leukemia virus. Likewise, abrogation of the Fv-1b restriction of N-tropic murine leukemia virus replication was accomplished by prior infection with genome-deficient virions produced by an N-tropic murine leukemia virus packaging cell line. The latter observation suggests that the Fv-1 target in genome-deficient virions abrogates Fv-1 restriction in the absence of any viral genome-directed processes.
Head-Mounted Display Systems (2005)

Real-time three-dimensional (3D) interactive displays refer to display devices servo to the line of sight of a user, allowing not only free head motion, but also potentially and importantly full body mobility. Ideally,
Current State of Tolerance: The Holy Grail (2017)

Research in Tolerance and Chimerism by Transplant immunologists for over half a century is akin to the pursuit of the Holy Grail. Animal experiments for inducing tolerance may not have been successful initially but in that process, our knowledge of the fascinating immune system has been greatly enriched. Understanding of innate and adaptive immune systems has paved the way for development of potent immunosuppression. However, achieving clinical or operational tolerance long term in renal transplant recipients in the absence of immunosuppression is the ultimate goal for clinicians. Reduction in immunosuppression will lower morbidity and mortality associated with heavy burden of immunosuppression. This review article will be of particular interest to clinicians involved in delivering care to renal transplant recipients. We have elucidated mechanisms of self-tolerance through central and peripheral tolerance, evolution of tolerogenic strategies, difference between macro and micro-chimerism, overview of successful protocols for inducing tolerance and recent work in the development of expanding regulatory cell lines. It is most encouraging to note progress using cellular therapies as reported by Immune Tolerance Network and by Transplant Research & Immunology group at Oxford. We may not be far from achieving clinical tolerance albeit with minimal if not completely immunosuppression free regimens in the longer term.
Stereotactic Techniques in the Management of Brain Tumors (1997)

Contemporary Neurosurgery is a newsletter offering a continuing medical education program to neurosurgeons looking for AMA PRA Category 1 Credits™. An annual series of 18 lessons keeps readers aware of new developments and techniques in neurosurgery and offers up to 36 credits/year. Each issue contains an original article written by a leading specialist who provides an in-depth review of one specific topic. All articles are authoritative, concise, and supplemented by illustrations as well as a CME exam.​
Diagnosis and management of Graves' disease. (2003)

Graves' disease is characterized by hyperthyroidism, diffuse goitre, ophthalmopathy and, rarely, dermopathy. Although diagnostic testing is straightforward once Graves' disease is suspected, physicians need to be aware of heterogeneous and even atypical presentations of the disease, particularly in elderly patients. Because morbidity may be associated with even subtle forms of hyperthyroidism, treatment promoting long-term euthyroidism is necessary. Although all of the available treatments are effective, compliance is best assured by a full discussion of the risks and benefits of each approach. This review focuses on issues of diagnosis and management that will allow the primary care physician to identify patients with Graves' disease and guide them to recovery.
Leptin can induce proliferation, differentiation, and functional activation of hemopoietic cells (1996)

Many cytokines exert their biological effect through members of the hemopoietin receptor family. Using degenerate oligonucleotides to the common WSXWS motif, we have cloned from human hemopoietic cell cDNA libraries various forms of the receptor that was recently shown to bind the obesity hormone, leptin. mRNAs encoding long and short forms of the human leptin receptor were found to be coexpressed in a range of human and murine hemopoietic organs, and a subset of cells from these tissues bound leptin at the cell surface. Ectopic expression in murine Ba/F3 and M1 cell lines revealed that the long, but not the short, form of the leptin receptor can signal proliferation and differentiation, respectively. In cultures of murine or human marrow cells, human leptin exhibited no capacity to stimulate cell survival or proliferation, but it enhanced cytokine production and phagocytosis of Leishmania parasites by murine peritoneal macrophages. Our data provide evidence that, in addition to its role in fat regulation, leptin may also be able to regulate aspects of hemopoiesis and macrophage function.
Functional evidence for a monoclonal antibody that binds to the human IL-4 receptor. (1988)

The complex pleiotropic effects of the T-cell derived lymphokine interleukin-4 (IL-4) are becoming increasingly well documented; however, functional studies have been hampered by the lack of reagents directed against the receptor for this factor. In this report, we present data which suggest that the monoclonal antibody MR6 binds to the human interleukin-4 receptor (IL-4R). Addition of MR6 to cultures of T cells proliferating in response to IL-4 inhibited this response in a dose-dependent fashion, giving total inhibition at 10 micrograms/ml. Similarly, the IL-4-dependent production of specific antigen-induced IgE by B-cell populations was completely abrogated by MR6. Flow cytometric studies of the modulation of cell surface molecules after T-cell activation suggest that expression of the molecule detected by MR6 (p145-MR6) correlates inversely with that of the interleukin-2 receptor (IL-2R). These data, together with the previously determined molecular weight and tissue distribution of this molecule, strongly indicate that MR6 binds to the human IL-4R.
Controlling molecular transport in minimal emulsions (2016)

Emulsions are metastable dispersions in which molecular transport is a major mechanism driving the system towards its state of minimal energy. Determining the underlying mechanisms of molecular transport between droplets is challenging due to the complexity of a typical emulsion system. Here we introduce the concept of 'minimal emulsions', which are controlled emulsions produced using microfluidic tools, simplifying an emulsion down to its minimal set of relevant parameters. We use these minimal emulsions to unravel the fundamentals of transport of small organic molecules in water-in-fluorinated-oil emulsions, a system of great interest for biotechnological applications. Our results are of practical relevance to guarantee a sustainable compartmentalization of compounds in droplet microreactors and to design new strategies for the dynamic control of droplet compositions.
PHASE I TRIAL OF MURINE ANTI-GANGLIOSIDE (GD2) MONOCLONAL ANTIBODY (Mab) 14G2A IN CANCER PATIENTS (1992)

Murray, J. L.; Cunningham, J. E.; Brewer, H. M.; Janus, M. H.; Podoloff, D. A.; Bhad- kamakar, V. P.; Kasi, L. P.; Shah, R. S.; Benjamin, R. S.; Legha, S. S.; Plager, C.; Papadopoulos, N. E.; Jaffee, N.; Ater, J. L.; Mujoo, K.; Itoh, K.; Ross, M.; Bucana, C. D.; Rosenblum, M. G.
Pathways of Sexual Desire (2009)

Drugs that stimulate the activation of hypothalamic dopamine or that blunt endocannabinoid or serotonin release and/or postsynaptic binding may be effective in stimulating sexual desire in animals and humans. The characterization of how those drugs work will help generate a rational approach to drug development in the treatment of HSDD.
Treatment of Motor and Sensory Detrusor Instability by Electrical Stimulation (1983)

A new application of electrical stimulation to inhibit detrusor activity has been used in 15 patients with a variety of neural lesions. The results were astonishingly good and the device was well tolerated. In patients treated successfully for detrusor instability an absence of urgency occurred as a by-product of electrical stimulation. Therefore, stimulation was used to treat uncomfortable bladder urgency without detrusor instability and was successful in the majority of patients.