gebhart/patrepeval huggingface dataset:
Endocytosis of GPI-linked membrane folate receptor-alpha. (1996)

GPI-linked membrane folate receptors (MFRs) have been implicated in the receptor-mediated uptake of reduced folate cofactors and folate-based chemotherapeutic drugs. We have studied the biosynthetic transport to and internalization of MFR isoform alpha in KB-cells. MFR-alpha was synthesized as a 32-kD protein and converted in a maturely glycosylated 36-38-kD protein 1 h after synthesis. 32-kD MFR-alpha was completely soluble in Triton X-100 at 0 degree C. In contrast, only 33% of the 36-38-kD species could be solubilized at these conditions whereas complete solubilization was obtained in Triton X-100 at 37 degrees C or in the presence of saponin at 0 degree C. Similar solubilization characteristics were found when MFR-alpha at the plasma membrane was labeled with a crosslinkable 125I-labeled photoaffinity-analog of folic acid as a ligand. Triton X-100-insoluble membrane domains containing MFR-alpha could be separated from soluble MFR-alpha on sucrose flotation gradients. Only Triton X-100 soluble MFR-alpha was internalized from the plasma membrane. The reduced-folate-carrier, an integral membrane protein capable of translocating (anti-)folates across membranes, was completely excluded from the Triton X-100-resistant membrane domains. Internalized MFR-alpha recycled slowly to the cell surface during which it remained soluble in Triton X-100 at 0 degree C. Using immunoelectron microscopy, we found MFR-alpha along the entire endocytic pathway: in clathrin-coated buds and vesicles, and in small and large endosomal vacuoles. In conclusion, our data indicate that a large fraction, if not all, of internalizing MFR-alpha bypasses caveolae.
Biochemistry of Amyloid -Protein and Amyloid Deposits in Alzheimer Disease (2012)

Progressive cerebral deposition of the amyloid β-protein (Aβ) in brain regions serving memory and cognition is an invariant and defining feature of Alzheimer disease. A highly similar but less robust process accompanies brain aging in many nondemented humans, lower primates, and some other mammals. The discovery of Aβ as the subunit of the amyloid fibrils in meningocerebral blood vessels and parenchymal plaques has led to innumerable studies of its biochemistry and potential cytotoxic properties. Here we will review the discovery of Aβ, numerous aspects of its complex biochemistry, and current attempts to understand how a range of Aβ assemblies, including soluble oligomers and insoluble fibrils, may precipitate and promote neuronal and glial alterations that underlie the development of dementia. Although the role of Aβ as a key molecular factor in the etiology of Alzheimer disease remains controversial, clinical trials of amyloid-lowering agents, reviewed elsewhere in this book, are poised to resolve the question of its pathogenic primacy.
Doxycycline Hyclate Treatment of Experimental Canine Ehrlichiosis Followed by Challenge Inoculation with TwoEhrlichia canisStrains (1998)

Dogs were experimentally inoculated with Ehrlichia canis Florida to assess the efficacy of doxycycline hyclate for the treatment of acute ehrlichiosis. Treatment with doxycycline eliminated infection in eight of eight dogs. Untreated infected control dogs appeared to eliminate the infection or, alternatively, suppress the degree of ehrlichiemia to a level not detectable by tissue culture isolation or PCR or by transfusion of blood into recipient dogs. Prior infection did not infer protection against homologous (strain Florida) or heterologous (strain NCSU Jake) strains of E. canis. We conclude that doxycycline hyclate is an effective treatment for acute E. canis infection; however, these results may not be applicable to chronic infections in nature. Spontaneous resolution of infection, induced by the dog's innate immune response, provides evidence that an E. canis vaccine, once developed, might potentially confer protective immunity against the organism.
Effects of resting vagal tone on accessory atrioventricular connections. (1990)

The purpose of this study was to determine the effects of resting vagal tone on accessory atrioventricular (AV) connections. Atropine (0.04 mg/kg) was administered to 13 patients with the Wolff-Parkinson-White syndrome and was found to have the following effects on the accessory AV connection: the anterograde block cycle length shortened from 305 +/- 51 to 279 +/- 54 msec (mean +/- SD; p less than 0.001); the retrograde block cycle length shortened from 288 +/- 57 to 251 +/- 50 msec (p less than 0.001); and the effective refractory period measured at a basic drive cycle length of 400 msec shortened from 295 +/- 45 to 265 +/- 47 msec in the anterograde direction (p less than 0.001) and from 283 +/- 18 to 261 +/- 12 msec in the retrograde direction (p less than 0.01). During atrial fibrillation, the mean ventricular cycle length decreased from 434 +/- 88 to 352 +/- 56 msec (p less than 0.001), and the shortest preexcited RR interval decreased from 302 +/- 56 to 256 +/- 43 msec (p less than 0.01). In another seven patients, propranolol (0.2 mg/kg) was administered before atropine, and atropine lengthened the anterograde block cycle length and the effective refractory period of the accessory AV connection; the magnitude of these effects was similar to that in the patients who did not receive propranolol. In conclusion, these data demonstrate that resting vagal tone exerts a direct depressant effect on accessory AV connections that does not require background sympathetic activity to be manifest.
Practical, high-yield, regioselective, rhodium-catalyzed hydroformylation of functionalized .alpha.-olefins (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPractical, high-yield, regioselective, rhodium-catalyzed hydroformylation of functionalized .alpha.-olefinsGregory D. Cuny and Stephen L. BuchwaldCite this: J. Am. Chem. Soc. 1993, 115, 5, 2066–2068Publication Date (Print):March 1, 1993Publication History Published online1 May 2002Published inissue 1 March 1993https://pubs.acs.org/doi/10.1021/ja00058a079https://doi.org/10.1021/ja00058a079research-articleACS PublicationsRequest reuse permissionsArticle Views2277Altmetric-Citations235LEARN 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
Topical negative pressure and necrotising fasciitis (2003)

This article highlights the importance of using evidence-based practice to improve wound care and support clinical practice. It appraises the literature on the use of topical negative pressure therapy for the treatment of complex, acute and chronic wounds. In an effort to contribute to the substantial evidence already available in support of this therapy, a clinical example of how effective it was at managing necrotising fasciitis is described.
TcpP protein is a positive regulator of virulence gene expression in Vibrio cholerae (1998)

The production of several virulence factors in Vibrio cholerae O1, including cholera toxin and the pilus colonization factor TCP (toxin-coregulated pilus), is strongly influenced by environmental conditions. To specifically identify membrane proteins involved in these signal transduction events, we examined a transposon library of V. cholerae generated by Tnbla mutagenesis for cells that produce TCP when grown under various nonpermissive conditions. To select for TCP-producing cells we used the recently described bacteriophage CTX phi-Kan, which uses TCP as its receptor and carries a gene encoding resistance to kanamycin. Among the isolated mutants was a transposon insertion in a gene homologous to nqrB from Vibrio alginolyticus, which encodes a subunit of a Na(+)-translocating NADH:ubiquinone oxidoreductase, and tcpI, encoding a chemo-receptor previously implicated in the negative regulation of TCP production. A third transposon mutant had an insertion in tcpP, which is in an operon with tcpH, a known positive regulator of TCP production. However, TcpP was shown to be essential for TCP production in V. cholerae, as a tcpP-deletion strain was deficient in pili production. The amino-terminal region of TcpP shows sequence homology to the DNA-binding domains of several regulatory proteins, including ToxR from V. cholerae and PsaE from Yersinia pestis. Like ToxR, TcpP activates transcription of the toxT gene, an essential activator of tcp operon transcription. Furthermore, TcpH, with its large periplasmic domain and inner membrane anchor, has a structure similar to that of ToxS and was shown to enhance the activity of TcpP. We propose that TcpP/TcpH constitute a pair of regulatory proteins functionally similar to ToxR/ToxS and PsaE/PsaF that are required for toxT transcription in V. cholerae.
Synthesis of 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (BINAP), an atropisomeric chiral bis(triaryl)phosphine, and its use in the rhodium(I)-catalyzed asymmetric hydrogenation of .alpha.-(acylamino)acrylic acids (1980)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (BINAP), an atropisomeric chiral bis(triaryl)phosphine, and its use in the rhodium(I)-catalyzed asymmetric hydrogenation of .alpha.-(acylamino)acrylic acidsA. Miyashita, A. Yasuda, H. Takaya, K. Toriumi, T. Ito, T. Souchi, and R. NoyoriCite this: J. Am. Chem. Soc. 1980, 102, 27, 7932–7934Publication Date (Print):December 1, 1980Publication History Published online1 May 2002Published inissue 1 December 1980https://pubs.acs.org/doi/10.1021/ja00547a020https://doi.org/10.1021/ja00547a020research-articleACS PublicationsRequest reuse permissionsArticle Views10241Altmetric-Citations897LEARN 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-Alertsclose Get e-Alerts
Opportunities and challenges for quantum-assisted machine learning in near-term quantum computers (2018)

With quantum computing technologies nearing the era of commercialization and quantum supremacy, machine learning (ML) appears as one of the promising "killer" applications. Despite significant effort, there has been a disconnect between most quantum ML proposals, the needs of ML practitioners, and the capabilities of near-term quantum devices to demonstrate quantum enhancement in the near future. In this contribution to the focus collection on "What would you do with 1000 qubits?", we provide concrete examples of intractable ML tasks that could be enhanced with near-term devices. We argue that to reach this target, the focus should be on areas where ML researchers are struggling, such as generative models in unsupervised and semi-supervised learning, instead of the popular and more tractable supervised learning techniques. We also highlight the case of classical datasets with potential quantum-like statistical correlations where quantum models could be more suitable. We focus on hybrid quantum-classical approaches and illustrate some of the key challenges we foresee for near-term implementations. Finally, we introduce the quantum-assisted Helmholtz machine (QAHM), an attempt to use near-term quantum devices to tackle high-dimensional datasets of continuous variables. Instead of using quantum computers to assist deep learning, as previous approaches do, the QAHM uses deep learning to extract a low-dimensional binary representation of data, suitable for relatively small quantum processors which can assist the training of an unsupervised generative model. Although we illustrate this concept on a quantum annealer, other quantum platforms could benefit as well from this hybrid quantum-classical framework.
Pharmacological characterization of ATP‐ and LPS‐induced IL‐1β release in human monocytes (1999)

1. We have utilized the human monocytic cell line, THP-1, and freshly isolated adherent human monocytes with the compounds pyridoxalphosphate-6-azophenyl-2',4'-disuphonic acid (PPADS), oxidized ATP, and 1-(N, O-bis[5-isoquinolinesufonyll]-N-methyl-L-tyrosyl)-4-phenylpiper azi ne (KN-62) to pharmacologically characterize the P2 receptor involved in ATP-induced release of interleukin 1beta (IL-1beta). We have also investigated the involvement of P2 receptors in lipopolysaccharide (LPS)-induced IL-1beta release from both cell types. 2. ATP caused release of IL-1beta from LPS primed THP-1 cells in both a time- and concentration-dependent manner, with a minimal effective ATP concentration of 1 mM. Stimulation of cells with 5 mM ATP resulted in detectable concentrations of IL-1beta in cell supernatants within 30 min. 3. The ATP analogue benzoylbenzoyl ATP (DBATP), a P2X7 receptor agonist, was approximately 10 fold more potent than ATP at eliciting IL-1beta release. 4. KN-62 (1 micro M), PPADS (100 microM) or oxidized ATP (100 uM) significantly inhibited 5 mM ATP-induced IL-1beta release by 81, 90 and 66% respectively, but failed to significantly inhibit LPS-induced IL-1beta release in both THP-1 cells and in freshly isolated human monocytes. 5. In both THP-1 cells and freshly isolated human monocytes, addition of the ATP degrading enzyme apyrase (0.4 U ml(-1)) to cell supernatants prior to LPS activation failed to significantly inhibit the LPS-induced IL-1beta release. In addition there was no correlation between extracellular ATP concentrations and IL-1beta release in THP-1 cells when studied over a 6 h time period. 6. In conclusion our data confirm the involvement of P2X7 receptors in ATP-induced IL-1beta release in human monocytes. However no evidence was obtained which would support the involvement of either endogenous ATP release or P2X7 receptor activation as the mechanism by which LPS-induces IL-1beta release in either the THP-1 cell line or in freshly isolated human monocytes.
Digital Step Edges from Zero Crossing of Second Directional Derivatives (1984)

We use the facet model to accomplish step edge detection. The essence of the facet model is that any analysis made on the basis of the pixel values in some neighborhood has its final authoritative interpretation relative to the underlying gray tone intensity surface of which the neighborhood pixel values are observed noisy samples. With regard to edge detection, we define an edge to occur in a pixel if and only if there is some point in the pixel's area having a negatively sloped zero crossing of the second directional derivative taken in the direction of a nonzero gradient at the pixel's center. Thus, to determine whether or not a pixel should be marked as a step edge pixel, its underlying gray tone intensity surface must be estimated on the basis of the pixels in its neighborhood. For this, we use a functional form consisting of a linear combination of the tensor products of discrete orthogonal polynomials of up to degree three. The appropriate directional derivatives are easily computed from this kind of a function. Upon comparing the performance of this zero crossing of second directional derivative operator with the Prewitt gradient operator and the Marr-Hildreth zero crossing of the Laplacian operator, we find that it is the best performer; next is the Prewitt gradient operator. The Marr-Hildreth zero crossing of the Laplacian operator performs the worst.
The value of residual liver volume as a predictor of hepatic dysfunction and infection after major liver resection (2005)

The likelihood of severe hepatic dysfunction following liver resection can be predicted by a small %RLV and a high BMI whereas postoperative infection is more related to liver dysfunction than precise residual liver volume. Understanding the relationship between liver volume and synthetic and immune function is the key to improving the safety of major liver resection.
Disarmed by Time: The Second Amendment and the Failure of Originalism (2000)

Originalism provides the core arguments for an individual right "to keep and bear Arms." The appropriate role of original intent in constitutional law, however, has been debated for the past two decades. In this Article, Farber illustrates how the Second Amendment exemplifies the classic, well-known criticisms of originalism. This does not prove, of course, that the conventional understanding of the Second Amendment should be retained. But, Farber concludes, advocates for a drastic expansion of Second Amendment rights will need something beyond the ambiguous historical record if they wish to show why, in today's world, gun rights warrant constitutional protection.
Separation and Purification of Bacteria from Soil (1985)

Bacteria were released and separated from soil by a simple blending-centrifugation procedure. The percent yield of bacterial cells (microscopic counts) in the supernatants varied over a wide range depending on the soil type. The superantants contained large amounts of noncellular organic material and clay particles. Further purification of the bacterial cells was obtained by centrifugation in density gradients, whereby the clay particles and part of the organic materials sedimented. A large proportion of the bacteria also sedimented through the density gradient, showing that they had a buoyant density above 1.2 g/ml. Attachment to clay minerals and humic material may account for this apparently high buoyant density. The percent yield of cells was negatively correlated with the clay content of the soils, whereas the purity was positively correlated with it. The cell size distribution and the relative frequency of colony-forming cells were similar in the soil homogenate, the supernatants after blending-centrifugation, and the purified bacterial fraction. In purified bacterial fraction from a clay loam, the microscopically measured biomass could account for 20 to 25% of the total C and 30 to 40% of the total N as cellular C and N. The amount of cellular C and N may be higher, however, owing to an underestimation of the cell diameter during fluorescence. A part of the contamination could be ascribed to extracellular structures as well as partly decayed cells, which were not revealed by fluorescence microscopy.
Gene Therapy: Promises and Problems (2001)

Gene therapy can be broadly defined as the transfer of genetic material to cure a disease or at least to improve the clinical status of a patient. One of the basic concepts of gene therapy is to transform viruses into genetic shuttles, which will deliver the gene of interest into the target cells. Based on the nature of the viral genome, these gene therapy vectors can be divided into RNA and DNA viral vectors. The majority of RNA virus-based vectors have been derived from simple retroviruses like murine leukemia virus. A major shortcoming of these vectors is that they are not able to transduce nondividing cells. This problem may be overcome by the use of novel retroviral vectors derived from lentiviruses, such as human immunodeficiency virus (HIV). The most commonly used DNA virus vectors are based on adenoviruses and adeno-associated viruses. Although the available vector systems are able to deliver genes in vivo into cells, the ideal delivery vehicle has not been found. Thus, the present viral vectors should be used only with great caution in human beings and further progress in vector development is necessary.
How Do Small Water Clusters Bind an Excess Electron? (2004)

The arrangement of water molecules around a hydrated electron has eluded explanation for more than 40 years. Here we report sharp vibrational bands for small gas-phase water cluster anions, (H2O)(4-6)- and (D2O)(4-6)-. Analysis of these bands reveals a detailed picture of the diffuse electron-binding site. The electron is closely associated with a single water molecule attached to the supporting network through a double H-bond acceptor motif. The local OH stretching bands of this molecule are dramatically distorted in the pentamer and smaller clusters because the excited vibrational levels are strongly coupled to the electron continuum. The vibration-to-electronic energy transfer rates, as revealed by line shape analysis, are mode-specific and remarkably fast, with the symmetric stretching mode surviving for less than 10 vibrational periods [50 fs in (H2O)4-].
Effects of Body Position on the Upper Airway of Patients With Obstructive Sleep Apnea (1995)

Fast-CT scanning was used to study the effects of changes in body position on upper airway (UA) size and shape in 11 awake subjects with obstructive sleep apnea (OSA). Six patients with position (P)-dependent OSA were compared with five patients with nonposition (NP)-dependent OSA. Scans were repeated in the prone (PRN), right side (RS), and supine (SUP) body positions at both functional residual capacity and end-inspiratory tidal volume. Significant group, group by position, and borderline group by respiration effects were detected for minimum but not mean UA dimension data. Significant differences between groups were noted in minimum cross-sectional area and minimum lateral distance but not in minimum anteroposterior distance in the RS and SUP positions. Turning from the PRN to the RS or SUP position tended to decrease UA size in the NP group by decreasing the lateral distance, while the opposite effect was found in the P group. The results indicate that changes in body position during wakefulness affect the lateral but not the anteroposterior dimensions of the UA, and the UA behaves differently in patients with NP and P OSA in response to changes in body position.
Chicken neuronal acetylcholine receptor alpha 2-subunit gene exhibits neuron-specific expression in the brain and spinal cord of transgenic mice. (1993)

Transgenic mice carrying the complete structural gene of the alpha 2 subunit of the chicken neuronal nicotinic acetylcholine receptor (nAChR) and 7 kilobase pairs (kbp) of 5' upstream and 3 kbp of 3' downstream sequences have been generated. The transgene was stably integrated in transgenic lines and transmitted to their progeny. Avian transgene expression was predominant in the central nervous system as detected by specific alpha 2-subunit cDNA amplification. Moreover, in at least two independent mouse lines, its expression appeared to be neuron-specific and reproducibly restricted to subregions in the brain and spinal cord, as revealed by in situ hybridization histochemistry. Most cranial motor nuclei were positive, and several of the alpha 2-subunit transgene-expressing structures corresponded to cholinergic areas in rodents. This study reveals that regulatory mechanisms giving rise to neuronal-specific gene expression have been conserved at least in part between birds and mammals.