gebhart/patrepeval huggingface dataset:
The targeting pathway of <i>Escherichia coli</i> presecretory and integral membrane proteins is specified by the hydrophobicity of the targeting signal (2001)

Previous studies have demonstrated that presecretory proteins such as maltose binding protein (MBP) and outer membrane protein A (OmpA) are targeted to the Escherichia coli inner membrane by the molecular chaperone SecB, but that integral membrane proteins are targeted by the signal recognition particle (SRP). In vitro studies have suggested that trigger factor binds to a sequence near the N terminus of the mature region of OmpA and shunts the protein into the SecB pathway by blocking an interaction between SRP and the signal peptide. By contrast, we have found that the targeting pathway of a protein under physiological conditions is dictated by the composition of its targeting signal. Replacement of the MBP or OmpA signal peptide with the first transmembrane segment of AcrB abolished the dependence on SecB for transport and rerouted both proteins into the SRP targeting pathway. More modest alterations of the MBP signal peptide that simply increase its hydrophobicity also promoted SRP binding. Furthermore, we obtained evidence that SRP has a low affinity for typical signal peptides in vivo. These results imply that different classes of E. coli proteins are targeted by distinct pathways because bacterial SRP binds to a more restricted range of targeting signals than its eukaryotic counterpart.
Image registration using Fermat transforms (1988)

Binary boundary maps are obtained by edge detection, then their relative translation is determined by conventional crosscorrelation computed by Fermat transform. Use of boundary maps emphasises edges and sharp discontinuities, while rejecting disturbances related to nonuniform illumination, thus avoiding the costly normalisation step. Use of integer arithmetic allows significant savings in computatio
METHYLPHENIDATE (RITALIN) HYDROCHLORIDE PARENTERAL SOLUTION (1956)

• Methylphenidate hydrochloride was administered in 10-mg. doses by intravenous injection to 164 hospitalized mental patients who manifested sleepiness and other symptoms of overdosage with tranquilizing drugs. The conditions of only 4 of the 164 were refractory to the analeptic effects of the methyphenidate; the other 160 all responded to one, two, or at most three injections by increase in alertness and decrease in side-reactions. Safe and effective dosages were thus determined, and in addition it was found that the improved condition of 151 of the 160 patients could be maintained by giving the methylphenidate solution thrice daily by mouth. A group of 11 chronic, regressed, underactive patients were then treated with intravenous injections of the drug. Three injections of 10 mg. sufficed in every case to cause marked clinical improvement, with increased activity, sudden awareness of surroundings, and other marked changes of behavior. These changes were obtained repeatedly, appeared promptly, were of limited duration, and were not seen after injections of a placebo. They are exemplified in the case histories of two patients who, after 21 and 17 years of extreme inactivity in the hospital, showed dramatic improvement in behavior.
FELLOW CLINICAL GERONTOLOGISTS... (1991)

No abstract available for this article.
DETECT-dual energy transmission estimation CT-for improved attenuation correction in SPECT and PET (1998)

Accurate attenuation correction is a vital component of any quantitative emission CT (ECT) study, especially /sup 131/I-mIBG SPECT where accurate activity measurements are required for dosimetry calculations. Conventional CT is often used to obtain an attenuation map, which is then scaled to the /sup 131/I emission energy (364 keV). Scaling inaccuracies due to the increased photoelectric component of the attenuation coefficients of bone at CT energies lead to an overestimate of activity. Dual energy CT is more accurate but must be justified against increased cost scan time and dose to the patient. We propose a method (DETECT) of obtaining two attenuation maps from a single CT scan using a conventional CT scanner operating at 120 and 140 kVp for alternate slices. Each map's missing slices are reconstructed using weighted linear interpolation. The effect of the X-ray beam spectrum has been investigated by simulated scaling using the CT spectra and by a phantom study. Assuming a perfect emission detector, segmented abdominal CT data predicts a mean activity overestimate of 2/spl plusmn/3% for DETECT compared to 12/spl plusmn/5% for the standard single energy (120 kVp) CT method when scaled to 364 keV, suggesting that DETECT can offer reliable attenuation correction with no dose or user penalty.
Stochastic View of Photon Migration in Turbid Media (2004)

Light propagation in an infinite uniform turbid medium is treated as a Markov stochastic process of photons to provide an intuitive framework for photon migration. The macroscopic physical quantities of photon migration are shown to be completely determined by the microscopic statistics of the photon propagation direction in direction space and a generalized Poisson distribution of the number of scattering events that includes an exponential decay absorption factor. A proper diffusion solution is derived with an exact time-dependent central position and half width of photon migration in this framework. The diffusion coefficient is found to be absorption-independent.
Suppression of Tumor Growth by Designed Dimeric Epidithiodiketopiperazine Targeting Hypoxia-Inducible Transcription Factor Complex (2013)

Hypoxia is a hallmark of solid tumors, is associated with local invasion, metastatic spread, resistance to chemo- and radiotherapy, and is an independent, negative prognostic factor for a diverse range of malignant neoplasms. The cellular response to hypoxia is primarily mediated by a family of transcription factors, among which hypoxia-inducible factor 1 (HIF1) plays a major role. Under normoxia, the oxygen-sensitive α subunit of HIF1 is rapidly and constitutively degraded but is stabilized and accumulates under hypoxia. Upon nuclear translocation, HIF1 controls the expression of over 100 genes involved in angiogenesis, altered energy metabolism, antiapoptotic, and pro-proliferative mechanisms that promote tumor growth. A designed transcriptional antagonist, dimeric epidithiodiketopiperazine (ETP 2), selectively disrupts the interaction of HIF1α with p300/CBP coactivators and downregulates the expression of hypoxia-inducible genes. ETP 2 was synthesized via a novel homo-oxidative coupling of the aliphatic primary carbons of the dithioacetal precursor. It effectively inhibits HIF1-induced activation of VEGFA, LOX, Glut1, and c-Met genes in a panel of cell lines representing breast and lung cancers. We observed an outstanding antitumor efficacy of both (±)-ETP 2 and meso-ETP 2 in a fully established breast carcinoma model by intravital microscopy. Treatment with either form of ETP 2 (1 mg/kg) resulted in a rapid regression of tumor growth that lasted for up to 14 days. These results suggest that inhibition of HIF1 transcriptional activity by designed dimeric ETPs could offer an innovative approach to cancer therapy with the potential to overcome hypoxia-induced tumor growth and resistance.
Mode-adaptive neural networks for quadruped motion control (2018)

Quadruped motion includes a wide variation of gaits such as walk, pace, trot and canter, and actions such as jumping, sitting, turning and idling. Applying existing data-driven character control frameworks to such data requires a significant amount of data preprocessing such as motion labeling and alignment. In this paper, we propose a novel neural network architecture called Mode-Adaptive Neural Networks for controlling quadruped characters. The system is composed of the motion prediction network and the gating network. At each frame, the motion prediction network computes the character state in the current frame given the state in the previous frame and the user-provided control signals. The gating network dynamically updates the weights of the motion prediction network by selecting and blending what we call the expert weights, each of which specializes in a particular movement. Due to the increased flexibility, the system can learn consistent expert weights across a wide range of non-periodic/periodic actions, from unstructured motion capture data, in an end-to-end fashion. In addition, the users are released from performing complex labeling of phases in different gaits. We show that this architecture is suitable for encoding the multi-modality of quadruped locomotion and synthesizing responsive motion in real-time.
Decoding EEG and LFP signals using deep learning (2016)

Deep learning technology is uniquely suited to analyse neurophysiological signals such as the electroencephalogram (EEG) and local field potentials (LFP) and promises to outperform traditional machine-learning based classification and feature extraction algorithms. Furthermore, novel cognitive computing platforms such as IBM's recently introduced neuromorphic TrueNorth chip allow for deploying deep learning techniques in an ultra-low power environment with a minimum device footprint. Merging deep learning and TrueNorth technologies for real-time analysis of brain-activity data at the point of sensing will create the next generation of wearables at the intersection of neurobionics and artificial intelligence.
Europe and Azerbaijan: The End of Shame (2015)

The autocratic regime of President Ilham Aliyev in Azerbaijan has managed to steal the soul of Europe’s most important human rights institution, the Council of Europe. This article reveals Azerbaijan’s hidden agenda to neutralize the “naming and shaming” strategy of the international human-rights movement, build influence through “caviar diplomacy,” and unleash a wave of repression against human-rights defenders. For the Council of Europe, whose function is to defend the European Convention of Human Rights, to align itself with a regime jailing humanrights activists is unprecedented and deeply disturbing. As the space for human-rights organizations to operate is shrinking in many parts of the world today, the capture of the Council of Europe sends a warning to all supporters of human rights, and not only in Europe.
Time-domain Pade approximation and modal-Pade method for multivariable systems (1987)

This paper presents the time-domain Pade approximation and modal-Pade method for single and multivariable systems. In the first part of the paper, Pade equations are derived for SISO and MIMO systems by assuming a state-space description of the higher order system and its reduced order model. For a SISO system, it is shown that these Pade equations are the same as the Pade equations obtained by a frequency-domain procedure. However, for a multivariable system, it is shown that,. although a full Pade approximation exists in the frequency domain, the time-domain procedure leads only to a partial Pade approximation. In the next part, the time-domain modal-Pade method for SISO and MIMO systems is proposed. A relationship between the state vectors of the system and the model is derived for the modal-Pade reduction procedure and is referred to as an "exact aggregation matrix."
1,2-Didehydrophenothiazines: preparation of 1-alkyl and 1-aryl-substituted phenothiazines by lithium-directed alkylation (1985)

A general route to 1-alkyl substituted phenothiazines is described. Reactions of 2-chlorophenothiazine with an excess of methyl-, n-butyl-, s-butyl, t-butyl-or phenyl-lithiums give the corresponding 1-substituted phenothiazines via 10-lithio-1,2-dehydrophenothiazine. Attempts to trap the presumed 1,10-dilithio intermediate failed. The reaction of 1-chlorophenothiazine with s-butyl-lithium results in preferential metallation of the 9-position. 2-Chlorophenothiazine reacts with nitrogen nucleophiles (lithium dialkylamides) to give 2-substituted products.
Reducing power consumption for high-associativity data caches in embedded processors (2003)

Modern embedded processors use data caches with higher and higher degrees of associativity in order to increase performance. A set-associative data cache consumes a significant fraction of the total power budget in such embedded processors. This paper describes a technique for reducing the D-cache power consumption and shows its impact on power and performance of an embedded processor. The technique utilizes cache line address locality to determine (rather than predict) the cache way prior to the cache access. It thus allows only the desired way to be accessed for both tags and data. The proposed mechanism is shown to reduce the average L1 data cache power consumption when running the MiBench embedded benchmark suite for 8, 16 and 32-way set-associate caches by, respectively, an average of 66%, 72% and 76%. The absolute power savings from this technique increase significantly with associativity. The design has no impact on performance and, given that it does not have mis-prediction penalties, it does not introduce any new non-deterministic behavior in program execution.
Environmental Education in Western Australian Secondary Schools (1996)

This paper reports on research carried out to investigate the extent of environmental education in Western Australian secondary schools. The research found: a high level of support for environmental education amongst teachers, that environmental education was being pursued to some extent in all responding schools, that there existed areas of neglect which were often politically controversial and divisive contemporary issues, and that city schools were generally more involved in environmental education than country schools and public schools more than private schools. Barriers to the further implementation of environmental education in schools are identified and recommandations made to improve the availability and standard of environmental education in Western Australian secondary schools.
A Versatile Carbonic Anhydrase IX Targeting Ligand-Functionalized Porous Silicon Nanoplatform for Dual Hypoxia Cancer Therapy and Imaging (2017)

Hypoxia occurs in most solid tumors, and it has been shown to be an independent prognostic indicator of a poor clinical outcome for patients with various cancers. Therefore, constructing a nanosystem specifically targeting cancer cells under hypoxia conditions is a promising approach for cancer therapy. Herein, we develop a porous silicon (PSi)-based nanosystem for targeted cancer therapy. VD11-4-2, a novel inhibitor for carbonic anhydrase IX (CA IX), is anchored on PSi particles (VD-PSi). As CA IX is mainly expressed on the cancer cell membrane under hypoxia condition, this nanocomplex inherits a strong affinity toward hypoxic human breast adenocarcinoma (MCF-7) cells; thus, a better killing efficiency for the hypoxia-induced drug resistance cancer cell is observed. Furthermore, the release of doxorubicin (DOX) from VD-PSi showed pH dependence, which is possibly due to the hydrogen-bonding interaction between DOX and VD11-4-2. The fluorescence resonance energy transfer effect between DOX and VD11-4-2 is observed and applied for monitoring the DOX release intracellularly. Protein inhibition and binding assays showed that VD-PSi binds and inhibits CA IX. Overall, we developed a novel nanosystem inheriting several advantageous properties, which has great potential for targeted treatment of cancer cells under hypoxic conditions.
Reciprocal Role of ERK and Nf-κb Pathways in Survival and Activation of Osteoclasts (2000)

To examine the role of mitogen-activated protein kinase and nuclear factor kappa B (NF-kappaB) pathways on osteoclast survival and activation, we constructed adenovirus vectors carrying various mutants of signaling molecules: dominant negative Ras (Ras(DN)), constitutively active MEK1 (MEK(CA)), dominant negative IkappaB kinase 2 (IKK(DN)), and constitutively active IKK2 (IKK(CA)). Inhibiting ERK activity by Ras(DN) overexpression rapidly induced the apoptosis of osteoclast-like cells (OCLs) formed in vitro, whereas ERK activation after the introduction of MEK(CA) remarkably lengthened their survival by preventing spontaneous apoptosis. Neither inhibition nor activation of ERK affected the bone-resorbing activity of OCLs. Inhibition of NF-kappaB pathway with IKK(DN) virus suppressed the pit-forming activity of OCLs and NF-kappaB activation by IKK(CA) expression upregulated it without affecting their survival. Interleukin 1alpha (IL-1alpha) strongly induced ERK activation as well as NF-kappaB activation. Ras(DN) virus partially inhibited ERK activation, and OCL survival promoted by IL-1alpha. Inhibiting NF-kappaB activation by IKK(DN) virus significantly suppressed the pit-forming activity enhanced by IL-1alpha. These results indicate that ERK and NF-kappaB regulate different aspects of osteoclast activation: ERK is responsible for osteoclast survival, whereas NF-kappaB regulates osteoclast activation for bone resorption.
Study of Hexane Adsorption in Nanoporous MCM-41 Silica (2003)

We study here the adsorption of hexane on nanoporous MCM-41 silica at 303,313, and 323 K, for various pore diameters between 2.40 and 4.24 nm. Adsorption equilibria, measured thermogravimetrically, show that all the isotherms, that are somewhat akin to those of type V, exhibit remarkably sharp capillary adsorption phase transition steps and are reversible. The position of the phase transition step gradually shifts from low to high relative pressure with an increase in the temperature as well as the pore sizes. The isosteric heats of adsorption derived from the equilibrium information using the Clapeyron equation reveal a gradual decrease with increasing adsorbed amount because of the surface heterogeneity but approach a constant value near the phase transition. A decrease in the pore size results in an increase in the isosteric heat of adsorption because of the increased dispersion forces. A simple strategy, based on the Broekhoff and De Boer adsorption theory, successfully interprets the hexane adsorption isotherms for the different pore size MCM-41 samples. The parameters of an empirical expression, used to represent the potential of interaction between the adsorbate and adsorbent, are obtained by fitting the monolayer region prior to capillary condensation and the experimental phase transition simultaneously, for some pore sizes. Subsequently, the parameters are used to predict the adsorption isotherm on other pore size samples, which showed good agreement with experimental data.
Efflux of Iron from the Cerebrospinal Fluid to the Blood at the Blood-CSF Barrier: Effect of Manganese Exposure (2008)

The blood-cerebrospinal fluid (CSF) barrier (BCB) resides within the choroid plexus, with the apical side facing the CSF and the basolateral side towards the blood. Previous studies demonstrate that manganese (Mn) exposure in rats disrupts iron (Fe) homeostasis in the blood and CSF. The present study used a primary culture of rat choroidal epithelial cells grown in the two-chamber Transwell system to investigate the transepithelial transport of Fe across the BCB. Free, unbound Fe as [(59)Fe] was added to the donor chamber and the radioactivity in the acceptor chamber was quantified to determine the direction of Fe fluxes. Under the normal condition, the [(59)Fe] efflux (from the CSF to the blood) was 128% higher than that of the influx (P < 0.01). Mn exposure significantly increased the efflux rate of [(59)Fe] (P < 0.01) and the effect was inhibited when the cells were pre-incubated with the antibody against divalent metal transport 1 (DMT1). Moreover, when the siRNA knocked down the cellular DMT1 expression, the elevated Fe uptake caused by Mn exposure in the choroidal epithelial Z310 cells was completely abolished, indicating that Mn may facilitate Fe efflux via a DMT1-mediated transport mechanism. In vivo subchronic exposure to Mn in rats reduced Fe clearance from the CSF, as demonstrated by the ventriculo-cisternal brain perfusion, along with up-regulated mRNAs encoding DMT1 and transferrin receptor (TfR) in the same animals. Taken together, these data suggest that free Fe appears to be favorably transported from the CSF toward the blood by DMT1 and this process can be facilitated by Mn exposure. Enhanced TfR-mediated influx of Fe from the blood and ferroportin-mediated expelling Fe toward the CSF may compromise DMT1-mediated efflux, leading to an increased Fe concentration in the CSF as seen in Mn-exposed animals.
Stereo- and regio-control of electrophilic additions to cyclohexene systems by neighbouring groups: participation of allylic and homoallylic ester groups in hypobromous acid addition to some 5-unsaturated cholestane derivatives (1988)

Hypobromous acid addition to 3β,7β-, 3δ,7α-, 3β,7β-, and 3α,7α-diacetoxycholest-5-ene (8)–(11) and 3β,7β,19- and 3β,7α,19-triacetoxycholest-5-ene (12) and (13) involves intramolecular participation of the neighbouring acetoxy group(s). Competing reaction pathways responsible for the product distribution are discussed. The relative importance of steric, electronic (Markownikoff), and stereoelectronic effects has been elucidated. The findings may be used for prediction of the reaction outcome. They also demonstrate that the purposeful introduction of a neighbouring group can direct the addition along the desired route.
Rosiglitazone inhibits migration, proliferation, and phenotypic differentiation in cultured human lung fibroblasts (2010)

Recent studies have indicated that peroxisome proliferator-activated receptor gamma (PPARgamma) is capable of modulating inflammation, which prompted us to investigate the potential of PPARgamma ligands as lung protective agents in pulmonary fibrosis. The present study was undertaken to investigate the effects of rosiglitazone (RSG), a highly potent ligand of PPARgamma, on migration, proliferation, and phenotypic differentiation of human lung fibroblasts (MRC-5) and to explore its potential for therapy of pulmonary fibrosis. The cell migration potential was observed in a scratch wound model. Cell proliferation was determined by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) method, immunocytochemical staining, and flow cytometry, and protein expression by Western blot analysis. RSG slowed cell migration distance induced by fetal bovine serum (FBS), decreased cell proliferation initiated by FBS or platelet-derived growth factor-BB (PDGF-BB), and decreased alpha-smooth muscle actin (alpha-SMA) protein expression induced by transforming growth factor-beta1 (TGF-beta1). In addition, RSG incubation reduced the ratio of phospho-extracellular signal-regulated kinases 1/2 (p-ERK1/2) to ERK1/2 expression stimulated by FBS, PDGF-BB, and TGF-beta1. These findings show that RSG treatment inhibits lung fibroblast migration and proliferation and myofibroblast transdifferentiation stimulated by FBS and growth factors in vitro, which suggests that PPARgamma agonists could antagonize pulmonary fibrosis and have potential for therapeutic application in pulmonary fibrosis.