gebhart/patrepeval huggingface dataset:
Regulation of Cell Cycle Progression by Calcium/Calmodulin-Dependent Pathways (2003)

Many hormones, growth factors, and cytokines regulate proliferation of their target cells. Perhaps the most universal signaling cascades required for proliferative responses are those initiated by transient rises in intracellular calcium (Ca(2+)). The major intracellular receptor for Ca(2+) is calmodulin (CaM). CaM is a small protein that contains four EF-hand Ca(2+) binding sites and is highly conserved among eukaryotes. In all organisms in which the CaM gene has been deleted, it is essential. Although Ca(2+)/CaM is required for proliferation in both unicellular and multicellular eukaryotes, the essential targets of Ca(2+)/CaM-dependent pathways required for cell proliferation remain elusive. Potential Ca(2+)/CaM-dependent targets include the serine/threonine phosphatase calcineurin and the family of multifunctional Ca(2+)/CaM-dependent protein kinases. Whereas these enzymes are essential in Aspergillus nidulans, they are not required under normal growth conditions in yeast. However, in mammalian cells, studies demonstrate that both types of enzymes contribute to the regulation of cell cycle progression. Unfortunately, the mechanism by which Ca(2+)/CaM and its downstream targets, particularly calcineurin and the Ca(2+)/CaM-dependent protein kinases, regulate key cell cycle-regulatory proteins, remains enigmatic. By understanding how Ca(2+)/CaM regulates cell cycle progression in normal mammalian cells, we may gain insight into how hormones control cell division and how cancer cells subvert the need for Ca(2+) and its downstream targets to proliferate.
On the use of decorrelation in scalar signal separation (2002)

In this paper we describe a method to separate a scalar mixture of two signals. The method is based on the use of decorrelation as a signal separation criterion. It is proven analytically that decorrelating the output signals at different time lags is sufficient provided that the normalised autocorrelation functions of the source signals are sufficiently distinct. The method involves an iterative least-squares solution of a set of nonlinear equations. Alternatively, a gradient search algorithm can also be used to find the minimum of the sum of squares of these equations. Both time- and frequency-domain formulations are given. Some convergence and stability issues are discussed and a small example is given at the end.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Discovery of 6-Phenylpyrimido[4,5-b][1,4]oxazines as Potent and Selective Acyl CoA:Diacylglycerol Acyltransferase 1 (DGAT1) Inhibitors with in Vivo Efficacy in Rodents (2014)

The discovery and optimization of a series of acyl CoA:diacylglycerol acyltransferase 1 (DGAT1) inhibitors based on a pyrimido[4,5-b][1,4]oxazine scaffold is described. The SAR of a moderately potent HTS hit was investigated resulting in the discovery of phenylcyclohexylacetic acid 1, which displayed good DGAT1 inhibitory activity, selectivity, and PK properties. During preclinical toxicity studies a metabolite of 1 was observed that was responsible for elevating the levels of liver enzymes ALT and AST. Subsequently, analogues were synthesized to preclude the formation of the toxic metabolite. This effort resulted in the discovery of spiroindane 42, which displayed significantly improved DGAT1 inhibition compared to 1. Spiroindane 42 was well tolerated in rodents in vivo, demonstrated efficacy in an oral triglyceride uptake study in mice, and had an acceptable safety profile in preclinical toxicity studies.
Intracerebroventricular Viral Injection of the Neonatal Mouse Brain for Persistent and Widespread Neuronal Transduction (2014)

With the pace of scientific advancement accelerating rapidly, new methods are needed for experimental neuroscience to quickly and easily manipulate gene expression in the mouse brain. Here we describe a technique first introduced by Passini and Wolfe for direct intracranial delivery of virally-encoded transgenes into the neonatal mouse brain. In its most basic form, the procedure requires only an ice bucket and a microliter syringe. However, the protocol can also be adapted for use with stereotaxic frames to improve consistency for researchers new to the technique. The method relies on the ability of adeno-associated virus (AAV) to move freely from the cerebral ventricles into the brain parenchyma while the ependymal lining is still immature during the first 12-24 hr after birth. Intraventricular injection of AAV at this age results in widespread transduction of neurons throughout the brain. Expression begins within days of injection and persists for the lifetime of the animal. Viral titer can be adjusted to control the density of transduced neurons, while co-expression of a fluorescent protein provides a vital label of transduced cells. With the rising availability of viral core facilities to provide both off-the-shelf, pre-packaged reagents and custom viral preparation, this approach offers a timely method for manipulating gene expression in the mouse brain that is fast, easy, and far less expensive than traditional germline engineering.
Coordinating distributed applets with Shade/Java (1998)

Article Coordinating distributed applets with Shade/Java Share on Authors: P. Ciancarini Dipartimento di Scienze dell'Informazione, University of Bologna, Italy and Mura Anteo Zamboni 7, 40127 Bologna, Italy Dipartimento di Scienze dell'Informazione, University of Bologna, Italy and Mura Anteo Zamboni 7, 40127 Bologna, ItalyView Profile , D. Rossi Dipartimento di Scienze dell'Informazione, University of Bologna, Italy and Mura Anteo Zamboni 7, 40127 Bologna, Italy Dipartimento di Scienze dell'Informazione, University of Bologna, Italy and Mura Anteo Zamboni 7, 40127 Bologna, ItalyView Profile Authors Info & Claims SAC '98: Proceedings of the 1998 ACM symposium on Applied ComputingFebruary 1998 Pages 130–138https://doi.org/10.1145/330560.330660Online:27 February 1998Publication History 2citation202DownloadsMetricsTotal Citations2Total Downloads202Last 12 Months1Last 6 weeks0 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 SiteGet Access
Amyotrophic lateral sclerosis (motor neuron disease): proposed mechanisms and pathways to treatment (2006)

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterised by loss of motor neurons. The cause of disease is unknown other than in the rare cases of familial disease arising from mutations in the superoxide dismutase 1 gene. Many theories for pathogenesis have been proposed - including oxidative stress, excitotoxicity, mitochondrial dysfunction and abnormal protein aggregation - based on studies of human post mortem tissue, research on animal models, and in vitro work. Here we review the evidence for the main pathogenic mechanisms and outline how they might interact to cause motor neuron death. Clinical trials have as yet failed to identify any truly effective therapies in ALS, with only riluzole providing a modest improvement in survival. Ongoing trials are exploring the value of antiglutamatergic agents, including the cephalosporin antibiotic ceftriaxone, as well as antioxidants, mitochondrial enhancers and anti-apoptotic drugs. It is likely that effective therapy will involve combinations of agents acting on different mechanisms. Gene therapy with neurotrophic factors will soon be in clinical trials, while work on stem cell therapy remains preclinical. In addition to finding effective therapies, research also needs to identify early disease markers because therapy is likely to be of most benefit when given early in the course of disease.
A chromatin insulator protects retrovirus vectors from chromosomal position effects (2000)

Recombinant murine retroviruses are widely used as delivery vectors for gene therapy. However, once integrated into a chromosome, these vectors often suffer from profound position effects, with vector silencing observed in vitro and in vivo. To overcome this problem, we investigated whether the HS4 chromatin insulator from the chicken beta-globin locus control region could protect a retrovirus vector from position effects. When used to flank a reporter vector, this element significantly increased the fraction of transduced cells that expressed the provirus in cultures and in mice transplanted with transduced marrow. These results demonstrate that a chromatin insulator can improve the expression performance of a widely used class of gene therapy vectors by protecting these vectors from chromosomal position effects.
Perisynaptic Location of Metabotropic Glutamate Receptors mGluR1 and mGluR5 on Dendrites and Dendritic Spines in the Rat Hippocampus (1996)

Ionotropic and metabotropic (mGluR1a) glutamate receptors were reported to be segregated from each other within the postsynaptic membrane at individual synapses. In order to establish whether this pattern of distribution applies to the hippocampal principal cells and to other postsynaptic metabotropic glutamate receptors, the mGluR1a/b/c and mGluR4 subtypes were localized by immunocytochemistry. Principal cells in all hippocampal fields were reactive for mGluR5, the strata oriens and radiatum of the CA1 area being most strongly immunolabelled. Labelling for mGluR1b/c was strongest on some pyramids in the CA3 area, weaker on granule cells and absent on CA1 pyramids. Subpopulations of non-principal cells showed strong mGluR1 or mGluR5 immunoreactivity. Electron microscopic pre-embedding immunoperoxidase and both pre- and postembedding immunogold methods consistently revealed the extrasynaptic location of both mGluRs in the somatic and dendritic membrane of pyramidal and granule cells. The density of immunolabelling was highest on dendritic spines. At synapses, immunoparticles for both mGluR1 and mGluR5 were found always outside the postsynaptic membrane specializations. Receptors were particularly concentrated in a perisynaptic annulus around type 1 synaptic junctions, including the invaginations at 'perforated' synapses. Measurements of immunolabelling on dendritic spines showed decreasing levels of receptor as a function of distance from the edge of the synaptic specialization. We propose that glutamergic synapses with an irregular edge develop in order to increase the circumference of synaptic junctions leading to an increase in the metabotropic to ionotropic glutamate receptor ratio at glutamate release sites. The perisynaptic position of postsynaptic metabotropic glutamate receptors appears to be a general feature of glutamatergic synaptic organization and may apply to other G-protein-coupled receptors.
Clinical pattern and risk factors for dyskinesias following fetal nigral transplantation in Parkinson's disease: A double blind video‐based analysis (2008)

The objective of this study is to assess dyskinesias in 34 Parkinson's disease patients randomized to receive bilateral fetal nigral transplantation with 4 donors per side (12), 1 donor per side (11), or placebo (11). Videotape recordings were performed at the baseline, 3, 6, 12, 18, and 24 month visits during the "practically defined off" (12 hours after last evening dopaminergic therapy) and "best on" (best response following morning dopaminergic therapy) states. Videotapes were analyzed in random order by a blinded investigator. Dyskinesias during "best on" (on-medication dyskinesia) were observed in all, but 1 patient at baseline, and in all patients at each subsequent visit. There were no differences between groups. No patient had dyskinesia at baseline in "practically-defined off" ("off-medication" dyskinesia). Following transplantation, off-medication dyskinesia was observed in 13 of 23 patients, but not in any patient in the placebo group (P = 0.019). There was no difference in dyskinesia score between patients in the 1 and 4 donor groups. On-medication dyskinesias were typically generalized and choreiform, whereas off-medication dyskinesias were usually repetitive, stereotypic movements in the lower extremities with residual Parkinsonism in other body regions. Off-medication dyskinesias are common following transplantation and may represent a prolonged form of diphasic dyskinesias.
The synthetic triterpenoid CDDO-imidazolide induces monocytic differentiation by activating the Smad and ERK signaling pathways in HL60 leukemia cells (2006)

Synthetic triterpenoids, CDDO (2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid) or CDDO-imidazolide [2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid imidazolide (CDDO-Im)], induce cell differentiation in myeloid leukemia cells but their mechanism of action is not known. CDDO-Im induces monocytic differentiation markers, CD14, and nonspecific esterase in HL60 leukemia cells. We show that CDDO-Im activates the extracellular signal-regulated kinase (ERK) signaling pathway and up-regulates CCAAT/enhancer-binding protein beta, a transcription factor critical for monocytic differentiation. The monocytic differentiation induced by CDDO-Im was partially blocked by the mitogen-activated protein kinase/ERK kinase 1 inhibitor PD98059, suggesting that the mitogen-activated protein kinase-ERK1/2 pathway plays a role in the differentiation induced by CDDO-Im. Furthermore, CDDO-Im activates the transforming growth factor beta (TGF-beta)/Smad signaling pathway. CDDO-Im enhanced the phosphorylation of the receptor-regulated Smads, phospho-Smad3, and phospho-Smad1/5, but not phospho-Smad2, and induced the expression of Smad4. Monocytic differentiation induced by CDDO-Im was blocked by both TGF-beta antibody and the bone morphogenetic protein (BMP) antagonist Noggin. This indicates that activation of the Smad signaling pathway by triterpenoids is an important mechanism of monocytic differentiation. CDDO-Im induced the synthesis of mRNA for TGF-beta2, BMP6, TGF-beta type II receptor, and BMP type II receptor. CDDO-Im synergized with members of the TGF-beta superfamily or with 1alpha,25(OH)2vitamin D3 (D3) in monocytic differentiation, and the synergistic effect was particularly striking in combination with D3. The combination of triterpenoids and D3 may have a practical use in differentiation therapy of myeloid leukemia as well as for promoting the formation of bone and cartilage.
Homography-based 2D visual servoing (2006)

The objective of this paper is to propose a new homography-based approach to image-based visual servoing. The visual servoing method does not need any measure of the 3D structure of the observed target. Only visual information measured from the reference and the current image are needed to compute the task function (isomorphic to the camera pose) and the control law to be applied to the robot. The control law is designed in order to make the task function converge to zero. We provide the theoretical proof of the existence of the isomorphism between the task function and the camera pose and the theoretical proof of the local stability of the control law. The experimental results, obtained with a 6 d.o.f. robot, show the advantages of the proposed method with respect to the existing approaches
Treatment Outcomes in Type A and B Alcohol Dependence 6 Months After Serotonergic Pharmacotherapy (2004)

These data support the importance of considering alcohol subtype when pharmacologically treating alcohol dependence.
Multimodal saliency-based bottom-up attention a framework for the humanoid robot iCub (2008)

This work presents a multimodal bottom-up attention system for the humanoid robot iCub where the robot's decisions to move eyes and neck are based on visual and acoustic saliency maps. We introduce a modular and distributed software architecture which is capable of fusing visual and acoustic saliency maps into one egocentric frame of reference. This system endows the iCub with an emergent exploratory behavior reacting to combined visual and auditory saliency. The developed software modules provide a flexible foundation for the open iCub platform and for further experiments and developments, including higher levels of attention and representation of the peripersonal space.
Deliberate Mild Hypothermia (1995)

Core body temperature is normally rigidly regulated by effective thermoregulatory responses that are triggered by small deviations in core and skin temperature. All general anesthetics so far tested markedly impair thermoregulatory control, increasing the range of temperatures not triggering protective responses by approximately 20-fold. Inhibition of thermoregulatory control--and reemergence of protective responses--are major factors influencing intraoperative temperature. Mild hypothermia provides dramatic protection against cerebral ischemia and therefore is frequently indicated during neurosurgery. Hypothermia to core temperatures near 34 degrees C can usually be instituted passively so long as thermoregulatory vasoconstriction is inhibited by sufficient anesthesia or neurosurgery per se. When core temperature must be rapidly reduced, or reduced to values approaching 32 degrees C, active cooling will usually be needed. Forced air appears to be the most effective clinically practical cooling method. Mild hypothermia is also associated with serious complications including myocardial ischemia, impaired resistance to surgical wound infections, coagulopathies, and postoperative shivering. Consequently, patients deliberately made hypothermic during neurosurgery should subsequently be actively rewarmed.
Cyclization Reactions through DDQ-Mediated Vinyl Oxazolidinone Oxidation (2009)

Vinyl oxazolidinones react with DDQ to form alpha,beta-unsaturated acyliminium ions in a new method for forming electrophiles under oxidative conditions. Appended nucleophiles undergo 1,4-addition reactions with these intermediates to form cyclic vinyl oxazolidinones with good levels of diastereocontrol, highlighting a new approach to utilizing oxidative carbon-hydrogen bond functionalization to increase molecular complexity.
Recipe recommendation using ingredient networks (2012)

The recording and sharing of cooking recipes, a human activity dating back thousands of years, naturally became an early and prominent social use of the web. The resulting online recipe collections are repositories of ingredient combinations and cooking methods whose large-scale and variety yield interesting insights about both the fundamentals of cooking and user preferences. At the level of an individual ingredient we measure whether it tends to be essential or can be dropped or added, and whether its quantity can be modified. We also construct two types of networks to capture the relationships between ingredients. The complement network captures which ingredients tend to co-occur frequently, and is composed of two large communities: one savory, the other sweet. The substitute network, derived from user-generated suggestions for modifications, can be decomposed into many communities of functionally equivalent ingredients, and captures users' preference for healthier variants of a recipe. Our experiments reveal that recipe ratings can be well predicted with features derived from combinations of ingredient networks and nutrition information.
A comparison of the performance of time-delay estimators in medical ultrasound (2003)

Time-delay estimation (TDE) is a common operation in ultrasound signal processing. In applications such as blood flow estimation, elastography, phase aberration correction, and many more, the quality of final results is heavily dependent upon the performance of the time-delay estimator implemented. In the past years, several algorithms have been developed and applied in medical ultrasound, sonar, radar, and other fields. In this paper we analyze the performances of the widely used normalized and non-normalized correlations, along with normalized covariance, sum absolute differences (SAD), sum squared differences (SSD), hybrid-sign correlation, polarity-coincidence correlation, and the Meyr-Spies method. These techniques have been applied to simulated ultrasound radio frequency (RF) data under a variety of conditions. We show how parameters, which include center frequency, fractional bandwidth, kernel window size, signal decorrelation, and signal-to-noise ratio (SNR) affect the quality of the delay estimate. Simulation results also are compared with a theoretical performance limit set by the Cramér-Rao lower bound (CRLB). Results show that, for high SNR, high signal correlation, and large kernel size, all of the algorithms closely match the theoretical bound, with relative performances that vary by as much as 20%. As conditions degrade, the performances of various algorithms differ more significantly. For signals with a correlation level of 0.98, SNR of 30 dB, center frequency of 5 MHz with a fractional bandwidth of 0.5, and kernel size of 2 micros, the standard deviation of the jitter error is on the order of few nanoseconds. Normalized correlation, normalized covariance, and SSD have an approximately equal jitter error of 2.23 ns (the value predicted by the CRLB is 2.073 ns), whereas the polarity-coincidence correlation performs less well with a jitter error of 2.74 ns.
Toll-Like Receptor 2-Dependent Inhibition of Macrophage Class II MHC Expression and Antigen Processing by 19-kDa Lipoprotein of Mycobacterium tuberculosis (2001)

Mycobacterium tuberculosis (MTB) induces vigorous immune responses, yet persists inside macrophages, evading host immunity. MTB bacilli or lysate was found to inhibit macrophage expression of class II MHC (MHC-II) molecules and MHC-II Ag processing. This report characterizes and identifies a specific component of MTB that mediates these inhibitory effects. The inhibitor was extracted from MTB lysate with Triton X-114, isolated by gel electroelution, and identified with Abs to be MTB 19-kDa lipoprotein. Electroelution- or immunoaffinity-purified MTB 19-kDa lipoprotein inhibited MHC-II expression and processing of both soluble Ags and Ag 85B from intact MTB bacilli. Inhibition of MHC-II Ag processing by either MTB bacilli or purified MTB 19-kDa lipoprotein was dependent on Toll-like receptor (TLR) 2 and independent of TLR 4. Synthetic analogs of lipopeptides from Treponema pallidum also inhibited Ag processing. Despite the ability of MTB 19-kDa lipoprotein to activate microbicidal and innate immune functions early in infection, TLR 2-dependent inhibition of MHC-II expression and Ag processing by MTB 19-kDa lipoprotein during later phases of macrophage infection may prevent presentation of MTB Ags and decrease recognition by T cells. This mechanism may allow intracellular MTB to evade immune surveillance and maintain chronic infection.
A Pilot‐Plant Study of Continuous Ultrasonic Extraction of Soybean Protein (1982)

ABSTRACT Methods were studied to extract soybean proteins from commercial defatted flakes with ultrasonic energy, continuously and efficiently, in a pilot plant. Studies also included batchwise sonication of aqueous soybean slurries in a tank. Parameters investigated included soybean‐to‐solvent ratios of 1:10, 1:20, and 1:30; solvents of tap water and 0.1N NaOH; and extraction with and without sonication. Protein yield and energy requirements for extraction were measured to correlate the operating condition with the extent of protein extraction. For a residence time of 0.7 sec in the continuous sonication process, the extracted protein yield was greatest at 1:30 soy‐to‐alkaline solvent ratio. Energy input to produce protein isolate is the least at 1:10 soy‐to‐alkaline solvent. Although the continuous sonication procedure is workable, the commercial operation remains to be tested.