gebhart/patrepeval huggingface dataset:
Does the anesthetic 2,2,2‐trifluoroethanol interact with bovine serum albumin by direct binding or by solvent‐mediated effects? A calorimetric and spectroscopic investigation (2005)

Thermal unfolding of bovine serum albumin (BSA) has been studied in the presence of 2,2,2-trifluoroethanol (TFE) using high-sensitivity microdifferential scanning calorimetry. Quantitative thermodynamic parameters accompanying the thermal transitions have been evaluated. TFE is observed to be a stabilizer or a destabilizer of the folded state of BSA depending on the pH. CD spectroscopy revealed an increase in the alpha-helical content of BSA and a decrease in the tertiary structure in the presence of increasing molalities of TFE. Isothermal titration calorimetric results do not indicate appreciable binding of the TFE molecules to BSA. TFE quenches the steady-state tryptophan fluorescence of BSA only at higher molalities and there is no effect on the tryptophan fluorescence at lower molalities. The calorimetric and spectroscopic results obtained in this work suggest that solvent-mediated effects dominate the interaction of TFE with BSA and the binding component may be very weak. Since the binding component is very weak, one of the possibilities of anesthetic action of TFE molecules on the actual targets may be through perturbation of the structural and dynamic properties of the lipid bilayer so that the function of crucial but unspecified membrane proteins is affected.
Silicon and III-V nanoelectronics (2005)

Sustaining Moore's Law of doubling CMOS transistor density every twenty four months will require not only shrinking the transistor dimensions, but also introduction of new materials and new device architectures. We discuss in this talk the recent innovations that are being researched and pursued to enable high performance Si-based CMOS nanoelectronics such as the use of highly strained Si channel for enhanced carrier transport, high-K dielectric and metal gate stack for low gate leakage, and non-planar multiple gate transistors for reduced short channel effects. In the future, further power-performance benefit may even potentially be achieved by incorporating III-V compound semiconductor nanoelectronics as ultra-high channel mobility materials. Some novel benchmarking results comparing III-V transistors to state-of-the-art advanced Si transistors will be presented.
The AF-1 and AF-2 Activating Domains of Retinoic Acid Receptor-α (RARα) and Their Phosphorylation Are Differentially Involved in Parietal Endodermal Differentiation of F9 Cells and Retinoid-Induced Expression of Target Genes (2000)

Retinoic acid (RA) induces the differentiation of F9 cells cultured as monolayers into primitive endodermal-like cells, whereas a combination of RA and cAMP leads to parietal endodermal differentiation. In RA receptor alpha-null F9 cells (RARalpha-/- cells), RA still efficiently triggers RARgamma-mediated primitive endodermal differentiation, but parietal endodermal differentiation is markedly delayed. To investigate the role of RARalpha1 activation functions AF-1 and AF-2 and of their phosphorylation sites during RA- and cAMP-induced parietal differentiation, cell lines reexpressing WT or mutated RARalpha1 were established in RARalpha-/- cells. We have found that the protein kinase A (PKA) phosphorylation site and the AF-2AD core (helix 12) of RARalpha1 are required for efficient parietal endodermal differentiation, whereas the AF-1 proline-directed kinase phosphorylation site is dispensible. Interestingly, deletion of the AF-1 activating domain (the A/B region), but not of the AF-2AD core, generates a dominant negative mutant that abrogates primitive endodermal differentiation when expressed in RARalpha-/- cells. We also show that the RARalpha AF-1 and AF-2 activation functions, but not their phosphorylation sites, are involved in the induction of RA-responsive genes in a differential promoter context-dependent manner.
Consequence of Aβ immunization on the vasculature of human Alzheimer's disease brain (2008)

A major feature of Alzheimer's disease is the accumulation of amyloid-beta peptide (Abeta) in the brain both in the form of plaques in the cerebral cortex and in blood vessel as cerebral amyloid angiopathy (CAA). Experimental models and human clinical trials have shown that accumulation of Abeta plaques can be reversed by immunotherapy. In this study, we hypothesized that Abeta in plaques is solubilized by antibodies generated by immunization and drains via the perivascular pathway, detectable as an increase in cerebrovascular Abeta. We have performed a follow up study of Alzheimer's disease patients immunized against Abeta42. Neuropathological examination was performed on nine patients who died between four months and five years after their first immunization. Immunostaining for Abeta40 and Abeta42 was quantified and compared with that in unimmunized Alzheimer's disease controls (n = 11). Overall, compared with these controls, the group of immunized patients had approximately 14 times as many blood vessels containing Abeta42 in the cerebral cortex (P<0.001) and seven times more in the leptomeninges (P = 0.013); among the affected blood vessels in the immunized cases, most of them had full thickness and full circumference involvement of the vessel wall in the cortex (P = 0.001), and in the leptomeninges (P = 0.015). There was also a significantly higher level of cerebrovascular Abeta40 in the immunized cases than in the unimmunized cases (cortex: P = 0.009 and leptomeninges: P = 0.002). In addition, the immunized patients showed a higher density of cortical microhaemorrhages and microvascular lesions than the unimmunized controls, though none had major CAA-related intracerebral haemorrhages. The changes in cerebral vascular Abeta load did not appear to substantially influence the structural proteins of the blood vessels. Unlike most of the immunized patients, two of the longest survivors, four to five years after first immunization, had virtually complete absence of both plaques and CAA, raising the possibility that, given time, Abeta is eventually cleared from the cerebral vasculature. The findings are consistent with the hypothesis that Abeta immunization results in solubilization of plaque Abeta42 which, at least in part, exits the brain via the perivascular pathway, causing a transient increase in the severity of CAA. The extent to which these vascular alterations following Abeta immunization in Alzheimer's disease are reflected in changes in cognitive function remains to be determined.
Identification of Orally Active, Potent, and Selective 4-Piperazinylquinazolines as Antagonists of the Platelet-Derived Growth Factor Receptor Tyrosine Kinase Family (2002)

We have previously found that the 4-[4-(N-substituted carbamoyl)-1-piperazinyl]-6,7-dimethoxyquinazolines can function as potent and selective inhibitors of platelet-derived growth factor receptor (PDGFR) phosphorylation. A series of highly potent, specific, orally active, small molecule kinase inhibitors directed against members of PDGFR receptor have been developed through modifications of the novel quinazoline template I. Systematic modifications in the A-bicyclic ring and D-rings of protype I were carried out to afford potent analogues, which display IC(50) values of <250 nM in cellular betaPDGFR phosphorylation assays. An optimized analogue in this series, 75 (CT53518), inhibits Flt-3, betaPDGFR, and c-Kit receptor phosphorylation with IC(50) values of 50-200 nM, whereas 15-20-fold less potent activity against CSF-1R was observed. This analogue also inhibits autophosphorylation of Flt-3 ligand-stimulated wild-type Flt-3 and a constitutively activated Flt-3/internal tandem duplication (ITD) with IC(50) values of 30-100 nM. Through this optimization process, 75 was found to be metabolically stable and has desirable pharmacokinetic properties in all animal species studied (F% > 50%, T(1/2) > 8 h). Oral administration of 75 promotes mice survival and significantly delayed disease progression in a Flt-3/ITD-mediated leukemia mouse model and shows efficacy in a nude mouse model of chronic myelomonocytic leukemia.
Neuroprotection of γ‐aminobutyric acid receptor agonists via enhancing neuronal nitric oxide synthase (Ser847) phosphorylation through increased neuronal nitric oxide synthase and PSD95 interaction and inhibited protein phosphatase activity in cerebral ischemia (2008)

It is well documented that exitotoxicity induced by N-methyl-D-aspartate (NMDA) receptor activation plays a pivotal role in delayed neuronal death in the hippocampal CA1 region after transient global ischemia. However, the effect of gamma-aminobutyric acid (GABA) receptor activation is uncertain in ischemia brain injury. The aim of this study was to investigate whether the enhancement of GABA receptor activity could inhibit NMDA receptor-mediated nitric oxide (NO) production by neuronal NO synthase (nNOS) in brain ischemic injury. The results showed that both the GABA(A) receptor agonist muscimol and the GABA(B) receptor agonist baclofen had neuroprotective effect, and the combination of two agonists could significantly protect neurons against death induced by ischemia/reperfusion. Coapplication of muscimol with baclofen not only enhanced nNOS (Ser847) phosphorylation but also increased the interaction of nNOS with PSD95 at 6 hr and 1 day of reperfusion. Interestingly, the inhibitors of calcineurin and PP1/PP2A could enhance nNOS phosphorylation at Ser847 site at 1 day of reperfusion after ischemia but not at 6 hr of reperfusion. From these data, we conclude that GABA receptor activation could exert its neuroprotective effect through increasing nNOS (Ser847) phosphorylation by different mechanisms at 6 hr and 1 day of reperfusion. The increased interaction of nNOS and postsynaptic density-95 induced by GABA agonists is responsible for nNOS (Ser847) phosphorylation at both time points, but at 1 day of reperfusion the inhibition of protein phosphatase activity by GABA agonists also contributes to the neuroprotection. Our results suggest that GABA receptor agonists may serve as a potential and important neuroprotectant in therapy for ischemic stroke.
Shape from projecting a stripe pattern (2005)

This paper presents a simple method which determines the surface properties of an object by projecting a stripe pattern on to it. Assuming orthographical projection as a camera model and parallel light projection of the stripe pattern, the method obtains a 2(1/2)D representation of objects by estimating surface normals from the slopes and intervals of the stripes in the image. The 2(1/2)D image is further divided into planar or singly curved surfaces by examining the distribution of the surface normals in gradient space. Evaluation of the error in surface orientation is also described.
A speedy solution for balance and gait analysis: angular velocity measured at the centre of body mass (2005)

Angular velocity sensors can provide balance-relevant information directly to the clinician, and provide an important improvement on the complicated and time/cost-intensive techniques of traditional balance measurement systems.
Mutant FLT3 signaling contributes to a block in myeloid differentiation (2005)

FLT3 is a member of the class III receptor tyrosine kinase family and is primarily expressed on hematopoietic stem/progenitor cells. Somatic mutations of FLT3 involving internal tandem duplication (ITD) of the juxtamembrane domain or point mutations in the activation loop have been identified in approximately 17 - 34% and 7 - 9% of acute myeloid leukemia (AML) patients, respectively. The ITD mutations appear to activate the tyrosine kinase domain through receptor dimerization in a FLT3 ligand-independent manner. Constitutively activated FLT3 provides cells with proliferative and anti-apoptotic advantages and portends an especially poor prognosis for patients with this mutation. FLT3/ITD mutations also contribute to a block of myeloid differentiation. FLT3 tyrosine kinase inhibitors suppress the growth and induce apoptosis and differentiation of leukemia cells expressing FLT3/ITD mutants. Therefore, FLT3 is a therapeutic target and inhibition of FLT3 tyrosine kinase activity may provide a new approach in the treatment of leukemia carrying these mutations.
<title>Space-frequency quantization for wavelet image coding</title> (1996)

A novel wavelet packet image coder is introduced in this paper. It is based on our previous work on wavelet image coding using space-frequency quantization (SFQ), in which zerotree quantization and scalar quantization are jointly optimized in a rate-distortion sense. In this paper, we extend the powerful SFQ coding paradigm from the wavelet transform to the more general wavelet packet transformation. The resulting wavelet packet coder offers a universal transform coding framework within the constraints of filter bank structures by allowing joint transform and quantizer design without assuming a priori statistics of the input image. In other words, the new coder adaptively chooses the representation to suit the image and the quantization to suit the representation. Experimental results show that, for some image classes, our new coder is capable of achieving the best coding performances among those in the published literature.
News (1997)

beginning a research project, tentatively titled Prayer and Power, that will examine three Bridgettine convents in relationship with the new ideas that
Evaluation of macular holes by optical coherence tomography in Chinese patients (2001)

Aim: To evaluate the diagnostic significance of optical coherence tomography for macular holes. Materials and methods: From October 1999 to February 2000, forty six eyes of 40 patients with clinically diagnosed or suspected macular holes had optical coherence tomography performed via dilated pupils in both eyes. All images were measured and analyzed. Results: The optical coherence tomography technique showed lamellar macular holes in 11 eyes of 9 patients with partial neural epithelium defect. The average remaining retinal thickness of the macular area was 108 mm (standard deviation, 42.5 mm). Thirty eyes of 27 patients had full-thickness macular holes. The average diameter of the holes was 611 mm (standard deviation,  185.1 mm). The optical coherence tomography technique showed that the neural epithelium disappeared completely in full-thickness macular holes and the average thickness of the retina around the holes increased to 388.4 ± 109.8 mm with the presence of non-reflective cavities. The macular holes closed in 5 eyes after vitrectomy and gas tamponade. The normal foveal curve reappeared after surgery. Pseudoholes were present in the remaining 5 eyes of 4 patients. Conclusion: Optical coherence tomography is a non- contact, non-invasive, and high-resolution technique that is helpful in the diagnosis and monitoring of macular holes.
A level set approach for shape-driven segmentation and tracking of the left ventricle (2003)

Knowledge-based segmentation has been explored significantly in medical imaging. Prior anatomical knowledge can be used to define constraints that can improve performance of segmentation algorithms to physically corrupted and incomplete data. In this paper, the objective is to introduce such knowledge-based constraints while preserving the ability of dealing with local deformations. Toward this end, we propose a variational level set framework that can account for global shape consistency as well as for local deformations. In order to improve performance, the problems of segmentation and tracking of the structure of interest are dealt with simultaneously by introducing the notion of time in the process and looking for a solution that satisfies that prior constraints while being consistent along consecutive frames. Promising experimental results in magnetic resonance and ultrasonic cardiac images demonstrate the potentials of our approach.
Measles Virus as An Oncolytic Vector Platform (2008)

Viral vector systems are widely being used in the development of new genetic approaches for a variety of human diseases. Oncolytic viruses have shown great potential as cancer therapeutics. The ideal viral vector for cancer gene therapy eradicates a clinically significant fraction of malignant cells and leaves normal tissues unharmed. The Edmonston vaccine strain of measles virus is a replicating RNA virus which is characterized by its tumor selectivity and oncolysis. Its strong tumor suppressive potential combined with its excellent safety record as a viral vaccine makes it an optimal platform for oncolytic virotherapy of cancer. Recent advances in genetic engineering of measles virus allow insertion of therapeutic and diagnostic transgenes as well as complete retargeting of measles virus. These strategies resulted in the generation of recombinant measles viruses allowing non-invasive monitoring of viral replication and viral spread. The immune defense is a significant barrier for efficient viral gene therapy. Immune-evasive strategies have successfully been developed for measles virus enhancing its efficacy. This review gives an overview of measles virus as an anticancer agent; in particular, its use in oncologic virotherapy as well as new developments in targeting and immune evasive strategies.
Enantiodivergent Preparation of Chiral 2,5-Cyclohexadienone Synthons (1993)

Expedient enantiodivergent synthesis of synthons of two 2,5-cyclohexadienone derivatives has been developed using the common chiral building block obtained by lipase-mediated asymmetrization of the meso-symmetric starting material.
Apparent Failure of Current Intravesical Chemotherapy Prophylaxis to Influence the Long-Term Course of Superficial Transitional Cell Carcinoma of the Bladder (1995)

During the 4 decades since the first introduction of intravesical chemotherapy, 3,899 patients were enrolled in 22 randomized prospective controlled studies. Of these 22 studies 13 reported a statistically significant benefit of intravesical chemotherapy. With varying followup, the reported decrease in the incidence of patients with tumor recurrence averaged only 14% (range -3 to +43%). Unfortunately, long-term (5-year) studies show no decrease in the incidence of recurrent tumor. Maintenance chemotherapy has failed to improve these results and data suggest that a single early postoperative instillation may, in fact, be most effective. Among 10 studies that include progression data none showed decreased tumor progression, and overall among 2,011 randomized patients progression occurred in 7.5% of those receiving intravesical chemotherapy and 6.9% of those treated by surgery alone. Since intravesical chemotherapy has been demonstrated in animal models to be carcinogenic, these data raise the concern that intravesical chemotherapy might possibly be carcinogenic in humans. In the absence of demonstrated long-term benefit we question the advisability of routine prophylactic intravesical chemotherapy.
Semiquantitative Evaluation of Secondary Carbonates via Portable X-ray Fluorescence Spectrometry (2017)

Core Ideas PXRF found differences in Ca content related to secondary carbonate development stage. Strong correlation was found between intact aggregates and ground soil for Ca content. Support vector classification successfully classified carbonate development stage. Secondary CaCO3 is commonly found in soils of arid and semiarid regions in variable states of development as Bk, Bkk, Bkkm, Ck, or, more rarely, Ak horizons. Historically, a qualitative scale featuring various stages of development has been applied when evaluating carbonate-laden soils. By contrast, this study used portable X-ray fluorescence spectrometry to determine the soil Ca concentration of 75 soil samples from four US states in relation to developmental stage, as determined independently by five pedologists from the USDA–NRCS Soil Survey Staff. Although they were experienced, the evaluators unanimously agreed on the carbonate development stage on only 22.6% of the samples while evaluating the samples ex situ. Portable X-ray fluorescence-determined Ca content generally increased from Development Stage I through VI for intact aggregates as well as ground soil samples. The widest variation in Ca content was found in Stage III for both conditions. No substantive differences in Ca content were observed between Stages V and VI. A strong positive correlation was observed between the Ca content of intact aggregates vs. ground soil samples (r = 0.89). Both support vector machine classification and interpretable rules were used to classify secondary carbonate development stages using total Ca concentrations for intact aggregates and ground soil. Using scans of both conditions offers stronger predictive ability than either condition independently. Portable X-ray fluorescence provides an important analytical tool available to field soil scientists for evaluation of soils containing Ca as part of CaCO3.
The Chemistry and Pharmacology of a Series of Cycloalkanespiro-5'-hydantoins (1965)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Chemistry and Pharmacology of a Series of Cycloalkanespiro-5'-hydantoinsW. Oldfield and C. H. CashinCite this: J. Med. Chem. 1965, 8, 2, 239–249Publication Date (Print):March 1, 1965Publication History Published online1 May 2002Published inissue 1 March 1965https://doi.org/10.1021/jm00326a021RIGHTS & PERMISSIONSArticle Views193Altmetric-Citations17LEARN 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 InReddit PDF (796 KB) Get e-Alertsclose Get e-Alerts
Early Onset Photoreceptor Abnormalities Induced by Targeted Disruption of the Interphotoreceptor Retinoid-Binding Protein Gene (1998)

Vision in all vertebrates is dependent on an exchange of retinoids between the retinal pigment epithelium and the visual photoreceptors. It has been proposed that the interphotoreceptor retinoid-binding protein (IRBP) is essential for this intercellular exchange, and that it serves to prevent the potentially cytotoxic effects of retinoids. Although its precise function in vivo has yet to be defined, the early expression of IRBP suggests that it may also be required for normal photoreceptor development. To further assess the biological role of IRBP, we generated transgenic mice with targeted disruption of the IRBP gene (IRBP-/- mice). Specifically, homologous recombination was used to replace the first exon and promoter region of the IRBP gene with a phosphoglycerate kinase-promoted neomycin-resistant gene. Immunocytochemical and Western blot analyses demonstrated the absence of IRBP expression in the IRBP-/- mice. As early as postnatal day 11, histological examination of the retinas of IRBP-/- mice revealed a loss of photoreceptor nuclei and changes in the structural integrity of the receptor outer segments. At 30 d of age, the photoreceptor abnormalities in IRBP-/- mice were more severe, and electroretinographic recordings revealed a marked loss in photic sensitivity. In contrast, no morphological or electrophysiological changes were detected in age-matched heterozygotes. These observations indicate that normal photoreceptor development and function are highly dependent on the early expression of IRBP, and that in the absence of IRBP there is a slowly progressive degeneration of retinal photoreceptors.