gebhart/patrepeval huggingface dataset:
A PCA-like Autoencoder (2019)

An autoencoder is a neural network which data projects to and from a lower dimensional latent space, where this data is easier to understand and model. The autoencoder consists of two sub-networks, the encoder and the decoder, which carry out these transformations. The neural network is trained such that the output is as close to the input as possible, the data having gone through an information bottleneck : the latent space. This tool bears significant ressemblance to Principal Component Analysis (PCA), with two main differences. Firstly, the autoencoder is a non-linear transformation, contrary to PCA, which makes the autoencoder more flexible and powerful. Secondly, the axes found by a PCA are orthogonal, and are ordered in terms of the amount of variability which the data presents along these axes. This makes the interpretability of the PCA much greater than that of the autoencoder, which does not have these attributes. Ideally, then, we would like an autoencoder whose latent space consists of independent components, ordered by decreasing importance to the data. In this paper, we propose an algorithm to create such a network. We create an iterative algorithm which progressively increases the size of the latent space, learning a new dimension at each step. Secondly, we propose a covariance loss term to add to the standard autoencoder loss function, as well as a normalisation layer just before the latent space, which encourages the latent space components to be statistically independent. We demonstrate the results of this autoencoder on simple geometric shapes, and find that the algorithm indeed finds a meaningful representation in the latent space. This means that subsequent interpolation in the latent space has meaning with respect to the geometric properties of the images.
Host-guest complexation. 26. Cavitands composed of fluorobenzene units bonded in their 2,6-positions to form macrocycles (1984)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTHost-guest complexation. 26. Cavitands composed of fluorobenzene units bonded in their 2,6-positions to form macrocyclesDonald J. Cram, S. Bruce Brown, Takeo Taguchi, Martin Feigel, Emily Maverick, and Kenneth N. TruebloodCite this: J. Am. Chem. Soc. 1984, 106, 3, 695–701Publication Date (Print):February 1, 1984Publication History Published online1 May 2002Published inissue 1 February 1984https://pubs.acs.org/doi/10.1021/ja00315a039https://doi.org/10.1021/ja00315a039research-articleACS PublicationsRequest reuse permissionsArticle Views244Altmetric-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 InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
HIV‐1 Tat protein disrupts the blood–brain barrier through the oxidative and inflammatory mechanisms (2003)

Tat protein, which is released from HIV‐infected cells, may play a major role in HIV‐induced pathological processes in the CNS, including HIV‐associated dementia. Therefore, the aim of the present study was to examine the effects of Tat on vascular inflammatory responses as well as blood–brain barrier structure and function both in vitro and in vivo environments. Tat treatment induced cellular oxidative processes, activities of redox‐regulated transcription factors, and expression of inflammatory mediators. Most importantly, Tat disrupted the blood–brain barrier and stimulated monocyte infiltration of the CNS. Disruption tight junction protein integrity appeared to be the underlying mechanism of these effects. Among studied junctional proteins, claudin 5 expression was the most affected by Tat treatment. These data provide evidence that Tat can be involved in the blood–brain barrier breakdown and HIV entry into the brain. Acknowledgements: Supported by NIH; NS39254, MH63022, and AA013843.
Quantifying the Effect of Applying the NCEP ATP III Criteria in a Managed Care Population Treated With Statin Therapy (2004)

Taking into account the revised risk stratification of the ATP III guidelines and the lack of LDL-C goal attainment in patients currently taking statins, there will be an increase in the number of statin patients who require dose or agent adjustment, combination therapy, or compliance counseling to achieve their lower LDL-C goal.
Germ Cell Specification in Mice (2007)

Specification of germ cells in mice occurs relatively late in embryonic development. It is initiated by signals that induce expression of Blimp1, a key regulator of the germ cell, in a few epiblast cells of early postimplantation embryos. Blimp1 represses the incipient somatic program in these cells and promotes progression toward the germ cell fate. Blimp1 may also have a role in the maintenance of early germ cell characteristics by ensuring their escape from the somatic fate as well as possible reversion to pluripotent stem cells.
Rapid Polymer/Gas Solution Formation for Continuous Production of Microcellular Plastics (1996)

An extrusion system that can create a polymer/gas solution rapidly for continuous processing of microcellular plastics is presented. Microcellular plastics are characterized by cell densities greater than 109 cells/cm3 and fully grown cells smaller than 10 μm. Previously these microcellular structures have been produced in a batch process by saturating a polymeric material with an inert gas under high pressure followed by inducing a rapid drop in the gas solubility. The diffusion phenomena encountered in this batch processing is typically slow, resulting in long cycle times. In order to produce microcellular plastics at industrial production rates, a means for the rapid solution formation is developed. The processing time required for completing the solution formation in the system was estimated from experimental data and the dispersive mixing theory based on an order-of-magnitude analysis. A means for promoting high bubble nucleation rates in the gas-saturated polymer via rapid heating is also discussed. The feasibility of the continuous production of microcellular plastics by the rapid polymer/gas solution formation and rapid heating was demonstrated through experiments. The paper includes not only a brief treatment of the basic science of the polymer/gas systems, but also the development of an industrially viable technology that fully utilizes the unique properties of microcellular plastics.
Sequential chemical modification of tyrosyl residues in alkaline phosphatase of Escherichia coli (1971)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSequential chemical modification of tyrosyl residues in alkaline phosphatase of Escherichia coliBert L. Vallee, Philipp Christen, and Robert T. SimpsonCite this: Biochemistry 1971, 10, 8, 1377–1384Publication Date (Print):April 1, 1971Publication History Published online1 May 2002Published inissue 1 April 1971https://pubs.acs.org/doi/10.1021/bi00784a016https://doi.org/10.1021/bi00784a016research-articleACS PublicationsRequest reuse permissionsArticle Views44Altmetric-Citations18LEARN 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
Distinctive Roles for Prolactin and Growth Hormone in the Activation of Signal Transducer and Activator of Transcription 5 in Pancreatic Islets of Langerhans (2004)

Although the beta-cells of the pancreatic islets of Langerhans express both prolactin (PRL) and GH receptors, we have observed that PRL is considerably more effective than GH in the up-regulation of islet function in vitro. This study examined whether differences in the activation of the Janus kinase 2/signal transducer and activator of transcription (STAT) 5 signaling pathway by these closely related receptors may be involved in this disparity. The activation of STAT5B by PRL was biphasic, with an initial peak within 30 min, a nadir between 1 and 3 h, and prolonged activation after 4 h. In contrast, the response to GH was transient for 1 h. The importance of the long-term activation of STAT5B by PRL was supported by the similar dose response curves for STAT5B activation and the PRL-induced increases in insulin secretion and islet cell proliferation. Because the pulsatile secretion of GH affects its actions in other target tissues, the ability of pretreatment with either hormone to affect subsequent stimulation was also examined. Surprisingly, the response to PRL was inhibited by prior exposure for less than 3 h to either PRL or GH and disappeared with a longer pretreatment with either hormone. Similar to other tissues, the response to GH was inhibited by any length of prior exposure to GH. However, pretreatment with PRL had no effect. These experiments are the first demonstration of the transient desensitization of the PRL receptor by either PRL or GH pretreatment in any tissue and the desensitization of GH stimulation in islet cells. These observations provide insight into the mechanisms that regulate the desensitization of these receptors and, more importantly, allow the long-term activation of STAT5B by the PRL receptor. These results may apply to other members of the cytokine superfamily of receptors. We also demonstrate that the increase in islet cell proliferation required continuous stimulation with PRL, whereas the smaller effect with GH occurred with either continuous or pulsatile stimulation. In summary, this study demonstrates that islets are sensitive to the temporal pattern of stimulation by these hormones and provides a new basis for understanding their physiological roles in the regulation of islet function.
Inflammatory repertoire of Alzheimer's disease and nondemented elderly microglia in vitro (2001)

We have previously developed and characterized isolated microglia and astrocyte cultures from rapid (<4 h) brain autopsies of Alzheimer's disease (AD) and nondemented elderly control (ND) patients. In the present study, we evaluate the inflammatory repertoire of AD and ND microglia cultured from white matter (corpus callosum) and gray matter (superior frontal gyrus) with respect to three major proinflammatory cytokines, three chemokines, a classical pathway complement component, a scavenger cell growth factor, and a reactive nitrogen intermediate. Significant, dose-dependent increases in the production of pro-interleukin-1beta (pro-IL-1beta), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory peptide-1alpha (MIP-1alpha), IL-8, and macrophage colony-stimulating factor (M-CSF) were observed after exposure to pre-aggregated amyloid beta peptide (1-42) (Abeta1-42). Across constitutive and Abeta-stimulated conditions, secretion of complement component C1q, a reactive nitrogen intermediate, and M-CSF was significantly higher in AD compared with ND microglia. Taken together with previous in situ hybridization findings, these results demonstrate unequivocally that elderly human microglia provide a brain endogenous source for a wide range of inflammatory mediators.
Sustained increase in intracellular calcium promotes neuronal survival (1991)

Ciliary ganglion neurons, half of which normally suffer developmental death in the embryo, will survive in culture in medium supplemented with depolarizing concentrations of potassium. It is not known how elevated potassium acts inside the cell to promote survival. We report here that depolarizing concentrations of extracellular potassium promote neuronal survival by causing a sustained increase in intracellular calcium. Raising extracellular potassium from 5 to 40 mM, an optimal concentration for survival, caused a sustained increase in intracellular calcium from 250 nM to greater than 600 nM. By 26 hr, at which time greater than 90% of neurons in 5 mM potassium had died, the calcium concentration of neurons in 40 mM potassium was still above 400 nM. Reduction of extracellular potassium from 40 to 5 nM, which prevents the increase in survival, also reduced intracellular calcium back to rest levels. PN200-110, a dihydropyridine calcium channel blocker that inhibits the survival-promoting effect of elevated potassium, also prevented and reversed the potassium,-mediated increase in intracellular calcium. In addition, there was a strong, quantitative correlation between the percentage of neuronal survival and the intracellular calcium concentration over a wide range of extracellular potassium concentrations. These results suggest that elevated potassium opens dihydropyridine-sensitive calcium channels, causing a sustained increase in intracellular calcium that quantitatively determines the number of surviving neurons.
Moving beyond Rules: The Development of a Central Nervous System Multiparameter Optimization (CNS MPO) Approach To Enable Alignment of Druglike Properties (2010)

The interplay among commonly used physicochemical properties in drug design was examined and utilized to create a prospective design tool focused on the alignment of key druglike attributes. Using a set of six physicochemical parameters ((a) lipophilicity, calculated partition coefficient (ClogP); (b) calculated distribution coefficient at pH = 7.4 (ClogD); (c) molecular weight (MW); (d) topological polar surface area (TPSA); (e) number of hydrogen bond donors (HBD); (f) most basic center (pK(a))), a druglikeness central nervous system multiparameter optimization (CNS MPO) algorithm was built and applied to a set of marketed CNS drugs (N = 119) and Pfizer CNS candidates (N = 108), as well as to a large diversity set of Pfizer proprietary compounds (N = 11 303). The novel CNS MPO algorithm showed that 74% of marketed CNS drugs displayed a high CNS MPO score (MPO desirability score ≥ 4, using a scale of 0-6), in comparison to 60% of the Pfizer CNS candidates. This analysis suggests that this algorithm could potentially be used to identify compounds with a higher probability of successfully testing hypotheses in the clinic. In addition, a relationship between an increasing CNS MPO score and alignment of key in vitro attributes of drug discovery (favorable permeability, P-glycoprotein (P-gp) efflux, metabolic stability, and safety) was seen in the marketed CNS drug set, the Pfizer candidate set, and the Pfizer proprietary diversity set. The CNS MPO scoring function offers advantages over hard cutoffs or utilization of single parameters to optimize structure-activity relationships (SAR) by expanding medicinal chemistry design space through a holistic assessment approach. Based on six physicochemical properties commonly used by medicinal chemists, the CNS MPO function may be used prospectively at the design stage to accelerate the identification of compounds with increased probability of success.
Binding of Proprotein Convertase Subtilisin/Kexin Type 9 to Epidermal Growth Factor-like Repeat A of Low Density Lipoprotein Receptor Decreases Receptor Recycling and Increases Degradation (2007)

Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes degradation of hepatic low density lipoprotein receptors (LDLR), the major route of clearance of circulating cholesterol. Gain-of-function mutations in PCSK9 cause hypercholesterolemia and premature atherosclerosis, whereas loss-of-function mutations result in hypocholesterolemia and protection from heart disease. Recombinant human PCSK9 binds the LDLR on the surface of cultured hepatocytes and promotes degradation of the receptor after internalization. Here we localized the site of binding of PCSK9 within the extracellular domain of the LDLR and determined the fate of the receptor after PCSK9 binding. Recombinant human PCSK9 interacted in a sequence-specific manner with the first epidermal growth factor-like repeat (EGF-A) in the EGF homology domain of the human LDLR. Similar binding specificity was observed between PCSK9 and purified EGF-A. Binding to EGF-A was calcium-dependent and increased dramatically with reduction in pH from 7 to 5.2. The addition of PCSK9, but not heat-inactivated PCSK9, to the medium of cultured hepatocytes resulted in redistribution of the receptor from the plasma membrane to lysosomes. These data are consistent with a model in which PCSK9 binding to EGF-A interferes with an acid-dependent conformational change required for receptor recycling. As a consequence, the LDLR is rerouted from the endosome to the lysosome where it is degraded.
Mining unstructured data (1999)

Article Free Access Share on Mining unstructured data Author: Ronen Feldman Mathematics and Computer Science Department of Bar-Ilan University in Israel Mathematics and Computer Science Department of Bar-Ilan University in IsraelView Profile Authors Info & Claims KDD '99: Tutorial notes of the fifth ACM SIGKDD international conference on Knowledge discovery and data miningAugust 1999 Pages 182–236https://doi.org/10.1145/312179.312192Online:01 August 1999Publication History 5citation1,519DownloadsMetricsTotal Citations5Total Downloads1,519Last 12 Months85Last 6 weeks10 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
Robust remote gaze estimation method based on multiple geometric transforms (2015)

The remote gaze estimation (RGE) technique has been widely used as a natural interface in consumer electronic devices for decades. Although outstanding outcomes on RGE have been recently reported in the literature, tracking gaze under large head movements is still an unsolved problem. General RGE methods estimate a user’s point of gaze (POG) using a mapping function representing the relationship between several infrared light sources and their corresponding corneal reflections (CRs) in the eye image. However, the minimum number of available CRs required for a valid POG estimation cannot be satisfied in those methods because the CRs often tend to be distorted or disappeared inevitably under the unconstrained eye and head movements. To overcome this problem, a multiple-transform-based method is proposed. In the proposed method, through three different geometric transform-based normalization processes, several nonlinear mapping functions are simultaneously obtained in the calibration process and then used to estimate the POG. The geometric transforms and mapping functions can be alternatively employed according to the number of available CRs even under large head movement. Experimental results on six subjects demonstrate the effectiveness of the proposed method.
Testosterone Supplementation in Older Men: A Rational Idea Whose Time Has Not Yet Come (2001)

Forty years after the introduction of estrogens, the debate over the risks and benefits of estrogen replacement therapy in postmenopausal women is still not entirely settled.In contrast, the issues of testosterone replacement in older men are just beginning to be addressed.There is agreement that total, free, and bioavailable testosterone (ie, not bound by sex hormone-binding globulin) levels decline progressively with advancing age (Harman and Tsitouras,
Biosensor Technologies for Augmented Brain–Computer Interfaces in the Next Decades (2012)

The study of brain-computer interfaces (BCIs) has undergone 30 years of intense development and has grown into a rich and diverse field. BCIs are technologies that enable direct communication between the human brain and external devices. Conventionally, wet electrodes have been employed to obtain unprecedented sensitivity to high-temporal-resolution brain activity; recently, the growing availability of various sensors that can be used to detect high-quality brain signals in a wide range of clinical and everyday environments is being exploited. This development of biosensing neurotechnologies and the desire to implement them in real-world applications have led to the opportunity to develop augmented BCIs (ABCIs) in the upcoming decades. An ABCI is similar to a BCI in that it relies on biosensors that record signals from the brain in everyday environments; the signals are then processed in real time to monitor the behavior of the human. To use an ABCI as a mobile brain imaging technique for everyday, real-life applications, the sensors and the corresponding device must be lightweight and the equipment response time must be short. This study presents an overview of the wide range of biosensor approaches currently being applied to ABCIs, from their use in the laboratory to their application in clinical and everyday use. The basic principles of each technique are described along with examples of current applications of cutting-edge neuroscience research. In summary, we show that ABCI techniques continue to grow and evolve, incorporating new technologies and advances to address ever more complex and important neuroscience issues, with advancements that are envisioned to lead to a wide range of real-life applications.