gebhart/patrepeval huggingface dataset:
Botulinum toxin in the treatment of dystonic tics (1994)

Botulinum toxin (BTX) injections provide effective treatment for a variety of disorders manifested by inappropriate muscle contractions, but its efficacy in the treatment of tics has not been previously studied. Ten male patients 13-53 years of age who were diagnosed with Tourette's syndrome manifested by disabling focal tics were included in this pilot study. Five patients had frequent blinking and blepharospasm, rendering them "blind," and five patients had severe and painful dystonic tics involving their neck muscles. All 10 patients experienced moderate to marked improvement in the intensity and frequency of tics after BTX injections into the involved muscles. Patients in whom premonitory urges preceded their tics noted marked lessening of these sensory symptoms. The benefit lasted 2-20 weeks after injections. There were no serious complications, except for transient ptosis in two and neck pain, stiffness, or weakness in three patients. BTX injections appear to be safe and effective treatment for patients with focal dystonic tics. The treatment ameliorates not only involuntary movements but also the premonitory sensory component associated with some tics.
Cytoplasmic tail–dependent internalization of membrane-type 1 matrix metalloproteinase is important for its invasion-promoting activity (2001)

Membrane-type 1 matrix metalloproteinase (MT1-MMP) is an integral membrane proteinase that degrades the pericellular extracellular matrix (ECM) and is expressed in many migratory cells, including invasive cancer cells. MT1-MMP has been shown to localize at the migration edge and to promote cell migration; however, it is not clear how the enzyme is regulated during the migration process. Here, we report that MT1-MMP is internalized from the surface and that this event depends on the sequence of its cytoplasmic tail. Di-leucine (Leu571-572 and Leu578-579) and tyrosine573 residues are important for the internalization, and the mu2 subunit of adaptor protein 2, a component of clathrin-coated pits for membrane protein internalization, was found to bind to the LLY573 sequence. MT1-MMP was internalized predominantly at the adherent edge and was found to colocalize with clathrin-coated vesicles. The mutations that disturb internalization caused accumulation of the enzyme at the adherent edge, though the net proteolytic activity was not affected much. Interestingly, whereas expression of MT1-MMP enhances cell migration and invasion, the internalization-defective mutants failed to promote either activity. These data indicate that dynamic turnover of MT1-MMP at the migration edge by internalization is important for proper enzyme function during cell migration and invasion.
Long-Term Follow-Up of Didanosine Administered Orally Twice Daily to Patients with Advanced Human Immunodeficiency Virus Infection and Hematologic Intolerance of Zidovudine (1993)

This phase 1 trial was conducted to evaluate the safety and tolerance of didanosine (ddI) in subjects with AIDS or AIDS-related complex (ARC) who previously had demonstrated hematologic intolerance of zidovudine. Thirty subjects, 21 with AIDS and nine with ARC, were enrolled. Initially, didanosine was administered orally twice daily for a total daily dose of either 750 mg or 1,500 mg. Subsequently, the dosage for those receiving 1,500 mg/d was reduced to a maximum of 750 mg/d (375 mg twice daily) when data from this and other phase 1 studies showed that the dosage of 1,500 mg/d (750 mg twice daily) was associated with an unacceptable risk of developing neuropathy. The subjects were studied for 46 weeks (mean time; range, 7-122 weeks). The dose-limiting toxic effect observed was peripheral neuropathy, which occurred in eight patients. Other significant toxic effects included pancreatitis in three patients and xerostomia in eleven. In general, didanosine was well tolerated from a hematologic standpoint by the majority of patients during prolonged administration.
Polyphenol (-)-Epigallocatechin Gallate during Ischemia Limits Infarct Size Via Mitochondrial KATPChannel Activation in Isolated Rat Hearts (2010)

Polyphenol (-)-epigallocatechin gallate (EGCG), the most abundant catechin of green tea, appears to attenuate myocardial ischemia/reperfusion injury. We investigated the involvement of ATP-sensitive potassium (K(ATP)) channels in EGCG-induced cardioprotection. Isolated rat hearts were subjected to 30 min of regional ischemia and 2 hr of reperfusion. EGCG was perfused for 40 min, from 10 min before to the end of index ischemia. A nonselective K(ATP) channel blocker glibenclamide (GLI) and a selective mitochondrial K(ATP) (mK(ATP)) channel blocker 5-hydroxydecanoate (HD) were perfused in EGCG-treated hearts. There were no differences in coronary flow and cardiodynamics including heart rate, left ventricular developed pressure, rate-pressure product, +dP/dt(max), and -dP/dt(min) throughout the experiments among groups. EGCG-treatment significantly reduced myocardial infarction (14.5+/-2.5% in EGCG 1 microM and 4.0+/-1.7% in EGCG 10 microM, P<0.001 vs. control 27.2+/-1.4%). This anti-infarct effect was totally abrogated by 10 microM GLI (24.6+/-1.5%, P<0.001 vs. EGCG). Similarly, 100 microM HD also aborted the anti-infarct effect of EGCG (24.1+/-1.2%, P<0.001 vs. EGCG ). These data support a role for the K(ATP) channels in EGCG-induced cardioprotection. The mK(ATP) channels play a crucial role in the cardioprotection by EGCG.
Expanding the Scope of Biomass‐Derived Chemicals through Tandem Reactions Based on Oxorhenium‐Catalyzed Deoxydehydration (2013)

New modes of DODH: Oxorhenium compounds act as deoxydehydration(DODH)/acid dual-purpose catalysts to transform biomass-derived diol substrates into a variety of commodity chemical precursors. The power of this approach is highlighted by a tandem [1,3]-OH shift/DODH of 2-ene-1,4-diols and 2,4-diene-1,6-diols, and by a DODH/esterification sequence of sugar acids to unsaturated esters for the production of polymers and plasticizers.
Specificity grafting of human antibody frameworks selected from a phage display library: generation of a highly stable humanized anti-CD22 single-chain Fv fragment (2003)

A prerequisite for the enrichment of antibodies screened from phage display libraries is their stable expression on a phage during multiple selection rounds. Thus, if stringent panning procedures are employed, selection is simultaneously driven by antigen affinity, stability and solubility. To take advantage of robust pre-selected scaffolds of such molecules, we grafted single-chain Fv (scFv) antibodies, previously isolated from a human phage display library after multiple rounds of in vitro panning on tumor cells, with the specificity of the clinically established murine monoclonal anti-CD22 antibody RFB4. We show that a panel of grafted scFvs retained the specificity of the murine monoclonal antibody, bound to the target antigen with high affinity (6.4-9.6 nM), and exhibited exceptional biophysical stability with retention of 89-93% of the initial binding activity after 6 days of incubation in human serum at 37 degrees C. Selection of stable human scaffolds with high sequence identity to both the human germline and the rodent frameworks required only a small number of murine residues to be retained within the human frameworks in order to maintain the structural integrity of the antigen binding site. We expect this approach may be applicable for the rapid generation of highly stable humanized antibodies with low immunogenic potential.
Invest in occupational health for greater productivity, NHS told (2009)

NHS employers should take the health of their staff as seriously as the quality of patient care, according to a major independent review ordered by the Department of Health.
Additional Bioactive Acetogenins, Annomutacin and (2,4-trans and cis)-10R-Annonacin-A-ones, from the Leaves of Annona muricata (1995)

In a continuation of our research on bioactive components from the leaves of Annona muricata, three novel monotetrahydrofuran Annonaceous acetogenins, namely, annomutacin [1], (2,4-trans)-10R-annonacin-A-one [2], and (2,4-cis)-10R- annonacin-A-one [3], have been identified. Their structures were deduced by ms, nmr, ir, and uv spectral and chemical methods, and the absolute configurations were determined by Mosher ester methodology. A known bioactive amide, N-p-coumaroyl tyramine, was also found. Compound 1 and the mixture of compounds 2 and 3 showed selective cytotoxicities against the human A-549 lung tumor cell line.
Human Eukaryotic Translation Initiation Factor 4G (eIF4G) Possesses Two Separate and Independent Binding Sites for eIF4A (1997)

Mammalian translation initiation factor 4F (eIF4F) consists of three subunits, eIF4A, eIF4E, and eIF4G. eIF4G interacts directly with both eIF4A and eIF4E. The binding site for eIF4E is contained in the amino-terminal third of eIF4G, while the binding site for eIF4A was mapped to the carboxy-terminal third of the molecule. Here we show that human eIF4G possesses two separate eIF4A binding domains in the middle third (amino acids [aa] 478 to 883) and carboxy-terminal third (aa 884 to 1404) of the molecule. The amino acid sequence of the middle portion of eIF4G is well conserved between yeasts and humans. We show that mutations of conserved amino acid stretches in the middle domain abolish or reduce eIF4A binding as well as eIF3 binding. In addition, a separate and nonoverlapping eIF4A binding domain exists in the carboxy-terminal third (aa 1045 to 1404) of eIF4G, which is not present in yeast. The C-terminal two-thirds region (aa 457 to 1404) of eIF4G, containing both eIF4A binding sites, is required for stimulating translation. Neither one of the eIF4A binding domains alone activates translation. In contrast to eIF4G, human p97, a translation inhibitor with homology to eIF4G, binds eIF4A only through the amino-terminal proximal region, which is homologous to the middle domain of eIF4G.
Chemoradiotherapy in Malignant Glioma: Standard of Care and Future Directions (2007)

Glioma has been considered resistant to chemotherapy and radiation. Recently, concomitant and adjuvant chemoradiotherapy with temozolomide has become the standard treatment for newly diagnosed glioblastoma. Conversely (neo-)adjuvant PCV (procarbazine, lomustine, vincristine) failed to improve survival in the more chemoresponsive tumor entities of anaplastic oligoastrocytoma and oligodendroglioma. Preclinical investigations suggest synergism or additivity of radiotherapy and temozolomide in glioma cell lines. Although the relative contribution of the concomitant and the adjuvant chemotherapy, respectively, cannot be assessed, the early introduction of chemotherapy and the simultaneous administration with radiotherapy appear to be key for the improvement of outcome. Epigenetic inactivation of the DNA repair enzyme methylguanine methyltransferase (MGMT) seems to be the strongest predictive marker for outcome in patients treated with alkylating agent chemotherapy. Patients whose tumors do not have MGMT promoter methylation are less likely to benefit from the addition of temozolomide chemotherapy and require alternative treatment strategies. The predictive value of MGMT gene promoter methylation is being validated in ongoing trials aiming at overcoming this resistance by a dose-dense continuous temozolomide administration or in combination with MGMT inhibitors. Understanding of molecular mechanisms allows for rational targeting of specific pathways of repair, signaling, and angiogenesis. The addition of tyrosine kinase inhibitors vatalanib (PTK787) and vandetinib (ZD6474), the integrin inhibitor cilengitide, the monoclonal antibodies bevacizumab and cetuximab, the mammalian target of rapamycin inhibitors temsirolimus and everolimus, and the protein kinase C inhibitor enzastaurin, among other agents, are in clinical investigation, building on the established chemoradiotherapy regimen for newly diagnosed glioblastoma.
The LiftLT: fast-lapped transforms via lifting steps (2000)

This paper introduces a class of multiband linear phase-lapped biorthogonal transforms with fast, VLSI-friendly implementations via lifting steps called the LiftLT. The transform is based on a lattice structure that robustly enforces both linear phase and perfect reconstruction properties. The lattice coefficients are parameterized as a series of lifting steps, providing fast, efficient, in-place computation of the transform coefficients. The new transform is designed for applications in image and video coding. Compared to the popular 8/spl times/8 DCT, the 8/spl times/16 LiftLT only requires one more multiplication, 22 more additions, and six more shifting operations. However, image coding examples show that the LiftLT is far superior to the DCT in both objective and subjective coding performance. Thanks to properly designed overlapping basis functions, the LiftLT can completely eliminate annoying blocking artifacts. In fact, the novel LT's coding performance consistently surpasses that of the much more complex 9/7-tap biorthogonal wavelet with floating-point coefficients. More importantly, the transform's block-based nature facilitates one-pass sequential block coding, region-of-interest coding/decoding, and parallel processing.
Transcellular activation of the human immunodeficiency virus type 1 long terminal repeat in cocultured lymphocytes (1992)

One of the unexplained aspects of the progression of AIDS is that immunological abnormalities are detectable before CD4+ T-helper cell depletion occurs (A.R. Gruters, F.G. Terpstra, R. De Jong, C.J.M. Van Noesel, R.A.W. Van Lier, and F. Miedema, Eur. J. Immunol. 20:1039-1044, 1990; F. Miedema, A.J. Chantal-Petit, F.G. Terpstra, J.K.M.E. Schattenkerk, F. de Wolf, B.J.M. Al, M. Roos, J.M.A. Lang, S.A. Danner, J. Goudsmit, and P.T.A. Schellekens, J. Clin. Invest. 82:1908-1914, 1988; G.M. Shearer, D.C. Bernstein, K.S. Tung, C.S. Via, R. Redfield, S.Z. Salahuddin, and R.C. Gallo, J. Immunol. 137:2514-2521, 1986). In this report, we describe a mechanism by which human immunodeficiency virus type 1 (HIV-1)-infected cells can influence neighboring HIV-1-infected T lymphocytes and uninfected T cells as well. We have examined the interaction of T-cell and macrophage cell lines that are transfected with HIV-1 DNA by using cocultured lymphocytes. The HIV-1 constructs we used lack a functional pol gene and therefore do not produce infectious virus. Cocultivation results in the transcellular activation of the HIV long terminal repeat in the cocultured T cells. This transcellular activation is evident in as little as 3 h of cocultivation, at ratios of HIV-expressing cells to target cells as low as 1:1,000, and is dependent on the Tat-responsive element. The demonstration that a small number of HIV-expressing cells can affect a large number of uninfected bystander cells in a short period of time suggests a mechanism by which global immune dysfunction can precede the high prevalence of infected cells.
Antisense Expression and Overexpression of Biotin Carboxylase in Tobacco Leaves (1997)

The plastid acetyl-coenzyme A carboxylase (ACCase) catalyzes the first committed step of fatty acid synthesis and in most plants is present as a heteromeric complex of at least four different protein subunits: the biotin carboxylase (BC), the biotin carboxyl carrier protein, and the alpha and beta subunits of the carboxyltransferase. To gain insight into the subunit organization of this heteromeric enzyme complex and to further evaluate the role of ACCase in regulating fatty acid synthesis, BC expression was altered in transgenic plants. Tobacco (Nicotiana tabacum) was transformed with antisense-expression and overexpression tobacco BC constructs, which resulted in the generation of plants with BC levels ranging from 20 to 500% of wild-type levels. Tobacco plants containing elevated or moderate decreases in leaf BC were phenotypically indistinguishable from wild-type plants. However, plants with less than 25% of wild-type BC levels showed severely retarded growth when grown under low-light conditions and a 26% lower leaf fatty acid content than wild-type plants. A comparison of leaf BC and biotin carboxyl carrier protein levels in plants with elevated and decreased BC expression revealed that these two subunits of the plastid ACCase are not maintained in a strict stoichiometric ratio.
Removing photography artifacts using gradient projection and flash-exposure sampling (2005)

Flash images are known to suffer from several problems: saturation of nearby objects, poor illumination of distant objects, reflections of objects strongly lit by the flash and strong highlights due to the reflection of flash itself by glossy surfaces. We propose to use a flash and no-flash (ambient) image pair to produce better flash images. We present a novel gradient projection scheme based on a gradient coherence model that allows removal of reflections and highlights from flash images. We also present a brightness-ratio based algorithm that allows us to compensate for the falloff in the flash image brightness due to depth. In several practical scenarios, the quality of flash/no-flash images may be limited in terms of dynamic range. In such cases, we advocate using several images taken under different flash intensities and exposures. We analyze the flash intensity-exposure space and propose a method for adaptively sampling this space so as to minimize the number of captured images for any given scene. We present several experimental results that demonstrate the ability of our algorithms to produce improved flash images.
Fast synthesis employing a microwave assisted neat protocol of new monomers potentially useful for the preparation of PDLC films (2011)

Abstract It has been reported that the length of the molecular chain and the rigidity of molecules influence the structure of the polymer network in PDLC films and hence the electro-optical properties of the composites. Herein, a series of new aromatic monomeric monomethacrylates, bismethacrylates and monovinylbenzene derivatives with a mesogenic core were successfully synthesized under microwave irradiation. The microwave assisted synthesis resulted in decreased reaction times, reduced solvent requirement, increased operational simplicity, and in most cases, improved yields and selectivity.
A single platform image cytometer for resource‐poor settings to monitor disease progression in HIV infection (2007)

The image cytometer is affordable (component costs $3,000), compact (25 x 25 x 20 cm(3)), and uses disposable test materials, making it a good candidate to monitor progression of immunodeficiency disease in resource-poor settings.
Two Classes of Genes in Plants (2000)

Two classes of genes were identified in three Gramineae (maize, rice, barley) and six dicots (Arabidopsis, soybean, pea, tobacco, tomato, potato). One class, the GC-rich class, contained genes with no, or few, short introns. In contrast, the GC-poor class contained genes with numerous, long introns. The similarity of the properties of each class, as present in the genomes of maize and Arabidopsis, is particularly remarkable in view of the fact that these plants exhibit large differences in genome size, average intron size, and DNA base composition. The functional relevance of the two classes of genes is stressed by (1) the conservation in homologous genes from maize and Arabidopsis not only of the number of introns and of their positions, but also of the relative size of concatenated introns; and (2) the existence of two similar classes of genes in vertebrates; interestingly, the differences in intron sizes and numbers in genes from the GC-poor and GC-rich classes are much more striking in plants than in vertebrates.
Glucose-Regulated Proinsulin Gene Expression Is Required for Adequate Insulin Production during Chronic Glucose Exposure (2002)

Psammomys obesus, an animal model of type 2 diabetes, shows rapid and marked depletion of pancreatic insulin content as hyperglycemia develops when fed a high-calorie diet. P. obesus islets do not increase proinsulin gene expression when exposed to high glucose, which may be related to absence of the conserved form of the transcription factor insulin promoter factor 1/pancreatic-duodenal homeobox 1. The present study assesses the importance of regulation of proinsulin gene expression by glucose for insulin production. Islets of diabetes-prone P. obesus and diabetes-resistant Wistar rats, cultured at various glucose concentrations for up to 24 h, were analyzed for proinsulin mRNA by quantitative RT-PCR, proinsulin biosynthesis by leucine incorporation into proinsulin, and insulin content and secretion by RIA. No increase in proinsulin mRNA was observed in P. obesus islets during 24-h exposure to increasing concentrations of glucose. In contrast, rat islets exposed to high glucose responded with a 2- to 3-fold stimulation of proinsulin mRNA. The failure of P. obesus islets to increase proinsulin mRNA was accompanied by a reduced proinsulin biosynthetic response: after 24 h, maximal proinsulin biosynthesis was blunted, associated with depletion of islet insulin content. Inhibition of glucose-stimulated proinsulin gene transcription in rat islets by actinomycin D did not affect the early proinsulin biosynthetic response, which, however, was reduced to the level of P. obesus islets after 24 h in culture. We conclude that stimulation of proinsulin gene transcription by glucose is necessary for maintaining proinsulin biosynthesis and hence conserving pancreatic insulin stores, under conditions of sustained secretory drive, but not for short-term regulation of proinsulin biosynthesis Our findings support the hypothesis that inadequate regulation of proinsulin gene expression by glucose contributes to the failure of P. obesus to cope with the increased demand for insulin associated with caloric excess, leading to depletion of insulin stores and diabetes.
Dexamethasone and mifepristone increase retroviral infectivity through different mechanisms (2009)

Using adapted retroviruses for gene delivery is a modern and powerful tool in biological research as well as a promising approach for gene therapy. An important limitation for the extensive use of retroviral vectors is the low infection rate in target cells such as pulmonary vascular endothelial cells due to the insufficient infectivity of standard retrovirus supernatants that can only be overcome by complicated methods of virus concentration. This paper describes two easy methods to augment target cell infectivity, first by increasing the retroviral titer in the medium collected from packaging cells by stimulation of viral propagation with dexamethasone, and second, by increasing target cell sensitivity to retroviral infection by the glucocorticoid receptor antagonist, mifepristone. Using this method, we increased the infectivity of pulmonary microvascular endothelial cells from 16% to 85%. We demonstrate that mifepristone increased the susceptibility of target cells to retroviruses without increasing the viral titer of the supernatant. Dexamethasone, but not mifepristone, increased expression of delivered proteins such as GFP that are important for early identification of infected cells. Each, or both step(s), may be included in a standard protocol for retrovirus propagation and infection of target cells.