gebhart/patrepeval huggingface dataset:
Expanding the Number of ‘Druggable’ Targets: Non‐Enzymes and Protein–Protein Interactions (2012)

Following sequencing and assembly of the human genome, the preferred methods for identification of new drug targets have changed dramatically. Modern tactics such as genome-wide association studies (GWAS) and deep sequencing are fundamentally different from the pharmacology-guided approaches used previously, in which knowledge of small molecule ligands acting at their cellular targets was the primary discovery engine. A consequence of the 'target-first, pharmacology-second' strategy is that many predicted drug targets are non-enzymes, such as scaffolding, regulatory or structural proteins, and their activities are often dependent on protein-protein interactions (PPIs). These types of targets create unique challenges to drug discovery efforts because enzymatic turnover cannot be used as a convenient surrogate for compound potency. Moreover, it is often challenging to predict how ligand binding to non-enzymes might affect changes in protein function and/or pathobiology. Thus, in the postgenomic era, targets might be strongly implicated by molecular biology-based methods, yet they often later earn the designation of 'undruggable'. Can the scope of available targets be widened to include these promising, but challenging, non-enzymes? In this review, we discuss advances in high-throughput screening (HTS) technology and chemical library design that are emerging to deal with these challenges.
M J B Management of Lumbar Spinal Stenosis with Lumbar Epidural Steroid Injections (2011)

Degenerative lumbar stenosis is a common source of pain and disability in middle age and elderly. It presents clinically with a variety of symptoms, though neurogenic claudication is the hallmark. There is a multifactorial pathogenesis to lumbar spinal stenosis and its symptoms. Epidural steroid injections are commonly utilized to help reduce radicular pain in lumbar spinal stenosis. It can be accomplished by one of three methods: caudal (C), interlaminar (IL), or transforaminal (TF). In this study we sought to determine the efficacy of fluoroscopically guided caudal and transforaminal epidural steroid injections for the management of radicular pain associated with lumbar spinal stenosis. The outcome measures of this study are patient satisfaction, pain relief, improved function and walking tolerance. Of 42 patients included in this study 71.4% of the patients had partial to complete pain relief at 1 month compared to 57.1% at 6 months and 45.2% at 12 months. 64.2% had full or improved function at 1 month compared to 50% at 6 months and 33.3% at 12 months. 66.6% of the patients were completely or somewhat satisfied at 1 month compared to 59.5% at 6 months and 38% at 12 months. When weighing the surgical alternatives and associated risk, cost, and outcomes, lumbar epidural steroid injections are a reasonable nonsurgical option in select patients especially in those patients who are unwilling to do surgery or in whom surgery is contraindicated.
Mobile Advertising : A Case study of Mobile advertising Solutions (2009)

This report has been produced as a result of a Thesis assignment conducted at Ericsson. Itspurpose is to give an overview of the Mobile Advertising industry. In this report an overviewof mobile advertising is presented and thru which channels advertising could be used. Thenthree mobile advertising campaigns are shown and described with background, strategy andresults. The different global markets, the different actors in the value chain and how the onlinebehavior has changed are analyzed. The problem area in this report is about profitability andefficiency of the solutions within mobile advertising and the inertia of mobile advertising andthis is discussed in the conclusion.
Switching transistors used as a substitute for mechanical low-level choppers (1955)

ONE of the interesting possibilities of using transistors as switches would be to replace mechanical vibrators or choppers in the input of d-c amplifiers. The ability of transistor switches to function with emitter-collector voltages of the order of 1 millivolt or less led to a further investigation of transistor-switching behavior at these very low levels. Peculiarities of circuits utilizing transistors as switches at these low levels are discussed and possible methods of compensating for these peculiarities are presented. Effects of temperature on behavior were also investigated and it was found that, by suitably matching pairs of transistors, the effects of temperature from -50 to +90 degrees centigrade (C) were practically negligible for germanium transistors.
Neonatal Tolerization With Glutamic Acid Decarboxylase But Not With Bovine Serum Albumin Delays the Onset of Diabetes in NOD Mice (1994)

To test the role of glutamic acid decarboxylase (GAD65) or bovine serum albumin (BSA) autoimmunity in the pathogenesis of diabetes, GAD65 or BSA was injected intraperitoneally into neonatal female NOD mice (100 micrograms/mouse of each protein). Treatment with GAD65, but not with BSA, significantly delayed the onset of diabetes compared with control mice (P < 0.05). At 18 weeks, 6 of 10 control mice compared with 0 of 10 GAD65-treated mice (P = 0.005) and 7 of 14 BSA-treated mice had developed diabetes. However, after 79 weeks, 6 of 10 of the GAD65-treated mice were diabetic compared with 9 of 10 of the control mice and 12 of 14 of the BSA-treated mice. In GAD65-treated mice without diabetes, insulitis was markedly reduced compared with control or BSA-treated mice (P < 10(-4)). To further elucidate why GAD becomes an autoantigen, the expression in NOD mice islets was studied. Quantitative immunohistochemistry revealed that islet cell expression of GAD was increased in 5-week-old NOD mice compared with BALB/c mice (P = 0.02). With the occurrence of insulitis (9-15 weeks), the GAD expression was further increased relative to 5-week-old NOD mice (P < 0.02). In conclusion, GAD, but not BSA, autoimmunity is important for the development of diabetes in NOD mice. Furthermore, concordant with the appearance of insulitis, the GAD expression increased in NOD mouse islets, which could possibly potentiate the beta-cell-directed autoimmunity.
Retinoic Acid and Arsenic Synergize to Eradicate Leukemic Cells in a Mouse Model of Acute Promyelocytic Leukemia (1999)

In acute promyelocytic leukemia (APL) patients, retinoic acid (RA) triggers differentiation while arsenic trioxide (arsenic) induces both a partial differentiation and apoptosis. Although their mechanisms of action are believed to be distinct, these two drugs both induce the catabolism of the oncogenic promyelocytic leukemia (PML)/RARalpha fusion protein. While APL cell lines resistant to one agent are sensitive to the other, the benefit of combining RA and arsenic in cell culture is controversial, and thus far, no data are available in patients. Using syngenic grafts of leukemic blasts from PML/RARalpha transgenic mice as a model for APL, we demonstrate that arsenic induces apoptosis and modest differentiation, and prolongs mouse survival. Furthermore, combining arsenic with RA accelerates tumor regression through enhanced differentiation and apoptosis. Although RA or arsenic alone only prolongs survival two- to threefold, associating the two drugs leads to tumor clearance after a 9-mo relapse-free period. These studies establishing RA/arsenic synergy in vivo prompt the use of combined arsenic/RA treatments in APL patients and exemplify how mouse models of human leukemia can be used to design or optimize therapies.
Complex Human Activity Recognition Using Smartphone and Wrist-Worn Motion Sensors (2016)

The position of on-body motion sensors plays an important role in human activity recognition. Most often, mobile phone sensors at the trouser pocket or an equivalent position are used for this purpose. However, this position is not suitable for recognizing activities that involve hand gestures, such as smoking, eating, drinking coffee and giving a talk. To recognize such activities, wrist-worn motion sensors are used. However, these two positions are mainly used in isolation. To use richer context information, we evaluate three motion sensors (accelerometer, gyroscope and linear acceleration sensor) at both wrist and pocket positions. Using three classifiers, we show that the combination of these two positions outperforms the wrist position alone, mainly at smaller segmentation windows. Another problem is that less-repetitive activities, such as smoking, eating, giving a talk and drinking coffee, cannot be recognized easily at smaller segmentation windows unlike repetitive activities, like walking, jogging and biking. For this purpose, we evaluate the effect of seven window sizes (2–30 s) on thirteen activities and show how increasing window size affects these various activities in different ways. We also propose various optimizations to further improve the recognition of these activities. For reproducibility, we make our dataset publicly available.
Self-Adjusting Fuzzy Logic Control for Vehicle Lateral Control (2007)

This paper deals with the lateral control of vehicles in Automated Highway Systems with the main emphasis on the lane change maneuvers. The desired trajectory for the lane change maneuvers, called the Virtual Desired Trajectory (VDT), is designed considering passenger's comfort and required transition time for the maneuver. The Self-Adjusting Fuzzy Logic controller is proposed as the tracking controller to make the vehicle to follow the VDT. Simulations have been conducted to evaluate the performance of the closed loop system under various driving conditions, and the results is presented to show the feasibility of using the designed Self-Adjusting Fuzzy Logic control for the lane change maneuver.
Fiber Optics, from Sensing to Non Invasive High Resolution Medical Imaging (2009)

Many concepts in optical imaging have initially been developed for Fiber Optic Sensing, Optics Communications or in Laser Physics Many concepts in optical imaging have initially been developed for Fiber Optic Sensing, Optics Communications or in Laser Physics The presentation will review several such concepts, the way they have been modified and implemented to achieve high resolution non-invasive optical imaging
Performance analysis of a kinematic human motion model (2003)

We describe a thorough quantitative analysis of a novel, kinematic model of the human body used for the tracking and extraction of gait variables. The model includes multiple levels of structural complexity coupled with absolute and probabilistic kinematic constraints; while the relevant variables include velocity, stride length, stance width, and stance times. The analysis is based on the accuracy of extracted gait variables for various permutations of the proposed kinematic body model. Using patterns of complex human motion collected from a multi-camera video monitoring system, we demonstrate the precise costs and benefits associated with various model components and kinematic constraints.
An active circuit for cancellation of common-mode voltage generated by a PWM inverter (1998)

This paper proposes an active common-noise canceler (ACC) that is capable of eliminating the common-mode voltage produced by a pulsewidth modulation (PWM) inverter. An emitter follower using complementary transistors and a common-mode transformer are incorporated into the ACC, the design method of which is also presented in detail. Experiments using a prototype ACC, whose design and construction are discussed in this paper, verify its viability and effectiveness in eliminating common-mode voltage in a 3.7 kW induction motor drive using an insulated gate bipolar transistor (IGBT) inverter. Some experimental results show that the ACC makes significant contributions to reducing a ground current and a conducted electromagnetic interference (EMI). In addition, the ACC can prevent an electric shock on a nongrounded motor frame and can suppress motor shaft voltage.
Activity-dependent Regulation of h Channel Distribution in Hippocampal CA1 Pyramidal Neurons (2007)

The hyperpolarization-activated cation current, I(h), plays an important role in regulating intrinsic neuronal excitability in the brain. In hippocampal pyramidal neurons, I(h) is mediated by h channels comprised primarily of the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel subunits, HCN1 and HCN2. Pyramidal neuron h channels within hippocampal area CA1 are remarkably enriched in distal apical dendrites, and this unique distribution pattern is critical for regulating dendritic excitability. We utilized biochemical and immunohistochemical approaches in organotypic slice cultures to explore factors that control h channel localization in dendrites. We found that distal dendritic enrichment of HCN1 is first detectable at postnatal day 13, reaching maximal enrichment by the 3rd postnatal week. Interestingly we found that an intact entorhinal cortex, which projects to distal dendrites of CA1 but not area CA3, is critical for the establishment and maintenance of distal dendritic enrichment of HCN1. Moreover blockade of excitatory neurotransmission using tetrodotoxin, 6-cyano-7-nitroquinoxaline-2,3-dione, or 2-aminophosphonovalerate redistributed HCN1 evenly throughout the dendrite without significant changes in protein expression levels. Inhibition of calcium/calmodulin-dependent protein kinase II activity, but not p38 MAPK, also redistributed HCN1 in CA1 pyramidal neurons. We conclude that activation of ionotropic glutamate receptors by excitatory temporoammonic pathway projections from the entorhinal cortex establishes and maintains the distribution pattern of HCN1 in CA1 pyramidal neuron dendrites by activating calcium/calmodulin-dependent protein kinase II-mediated downstream signals.
Initial Membrane Reaction in Peptidoglycan Synthesis (1973)

Abstract The initial membrane reaction in the biosynthesis of peptidoglycan is catalyzed by phospho-N-acetylmuramyl-pentapeptide translocase (UDP-MurNAc - l - Ala - d - γ-Glu - l - Lys - d - Ala - d - Ala:undecaprenyl - phosphate phospho - MurNAc-pentapeptide transferase). In addition to the transfer reaction, the enzyme catalyzes the exchange of [3H]uridine monophosphate with the uridine monophosphate moiety of UDP - MurNAc - pentapeptide. Lipid-dependent translocase was obtained in an inactive form by gel filtration of membranes from Staphylococcus aureus Copenhagen on agarose A-50m in the presence of 1% Triton X-100. The excluded fraction was depleted of undecaprenyl-diphosphate-MurNAc-pentapeptide (g95%) and partially depleted of undecaprenyl-phosphate (g75%). After removal of Triton X-100, the translocase was reactivated with a lipid extract from membranes of S. aureus Copenhagen. The translocase was partially reactivated (10 to 30%) by the addition of dioleoyl phosphatidylcholine, phosphatidylcholine (plant), phosphatidylglycerol, and, to a lesser extent, by phosphatidylinositol and phosphatidylethanolamine when added in the presence of 1 x 10-3 m sodium lauroyl sarcosinate. The optimal concentration of dioleoyl phosphatidylcholine was 1.2 x 10-4 m. Maximal reactivation of the exchange reaction required the addition of either 5 x 10-7 m undecaprenyl-diphosphate - MurNAc - pentapeptide or 1 x 10-6 m undecaprenyl-phosphate to lipid-dependent translocase in the presence of dioleoyl phosphatidylcholine and sodium lauroyl sarcosinate. Thus, for activity in the exchange reaction, the translocase requires a phosphatide and is markedly stimulated by the addition of either undecaprenyl-phosphate or undecaprenyl-diphosphate-MurNAc-pentapeptide. The implications of the results with the undecaprenyl derivatives are discussed in relation to proposed reaction mechanisms.
A MEMS DC Current Sensor Utilizing Neodymium Rare Earth Magnets (2014)

A silicon MEMS DC current sensor has been developed that utilizes a miniature NdFeB rare earth magnet attached to a silicon platform that is suspended by a dual torsional suspension system. An externally applied out-of-plane magnetic field, such as that produced by a DC current flowing through a nearby current trace, will cause a magnetic torque to be produced between the external field and the NdFeB magnet, causing a deflection of the suspended silicon platform which can be sensed capacitively. The device measures 5.6 mm X 5.6 mm, with the silicon components being manufactured using bulk micromachining processes. The variable capacitive structure is realized by metalizing the bottom side of the suspended silicon platform to allow the silicon platform to serve as the top electrode. The bottom electrode is provided by a bare pad on a printed circuit board (PCB) to which the frame of the silicon device is attached. This results in a variable capacitance with a nominal value of approximately 3–6 pF, depending on the exact width of the gap. The variable capacitance is large enough to be converted into a variable frequency square wave using just a simple CMOS relaxation oscillator circuit. To realize a practical device, multiple silicon components were manufactured. First, a silicon component had to be manufactured that included the anchor/frame, torsion springs, and suspended platform. To provide protection against destructive over-ranging of the mechanical components during very high accelerations or external magnetic fields, another silicon component was manufactured that provided mechanical stops at the limits of the useful displacement range. Two other components were also manufactured on the same die to provide for a cap over the device to seal it from the outside environment. Epoxy was used to bond the NdFeB magnet and the various silicon components together. The devices fabricated proved to behave similarly to their performance as predicted by mathematical modeling, with a test current of +/− 5 A causing a variation in the oscillation frequency of the CMOS oscillator circuit of +/− 8 kHz, from a nominal frequency of 26 kHz. Several fabrication and assembly issues had to be solved in order to realize the device. The gap width of the capacitive structure is dependent on the thickness of the agent used to electrically connect the silicon anchor to a pad on a PCB. As it is desirable to minimize this gap width, some experimentation was required to find a suitable agent and assembly method. Additionally, the bonding agent used to attach the silicon anchor to the PCB must be applied at a temperature near the expected operating temperature of the device to prevent large stresses from being applied to the silicon frame through the difference in the coefficients of thermal expansion between silicon and FR4. Also, during fabrication it was found that large, flat areas where a very uniform etch is critical required wet KOH etching, while deep reactive ion etching could be used for areas where depth and high aspect ratio were important.
Electric Field Directed Construction of Diodes Using Free-standing Three-dimensional Component (1999)

Spatially coupled bipolar electrochemistry(SCBE) is a novel technique for the formation of electrical connections between isolated metal components. When a voltage difference is applied across the platinum electrodes, the components become polarized, and copper electrodissolves from the right copper ring (see Figure), and the ions migrate to the silicon chip, where the copper electroplates in the form of a wire (see Cover).
Inside the Virtual Robotics Challenge: Simulating Real-Time Robotic Disaster Response (2015)

This paper presents the software framework established to facilitate cloud-hosted robot simulation. The framework addresses the challenges associated with conducting a task-oriented and real-time robot competition, the Defense Advanced Research Projects Agency (DARPA) Virtual Robotics Challenge (VRC), designed to mimic reality. The core of the framework is the Gazebo simulator, a platform to simulate robots, objects, and environments, as well as the enhancements made for the VRC to maintain a high fidelity simulation using a high degree of freedom and multisensor robot. The other major component used is the CloudSim tool, designed to enhance the automation of robotics simulation using existing cloud technologies. The results from the VRC and a discussion are also detailed in this work.
Rethinking the Welfare Cost of Inflation (2005)

New models of monetary economies, developed in the last 15 years, suggest that traditional measures of the welfare cost of inflation may underestimate the true loss that inflation inflicts on society. According to these models, the cost of 10 percent inflation ranges from 1 to 5 percent of real income.
A conserved mechanism for extracellular signaling in eukaryotes and prokaryotes (2002)

Epidermal growth factor receptor (EGFr) is a key mediator of cell communication during animal development and homeostasis. In Drosophila, the signaling event is commonly regulated by the polytopic membrane protein Rhomboid (RHO), which mediates the proteolytic activation of EGFr ligands, allowing the secretion of the active signal. Until very recently, the biochemical function of RHO had remained elusive. It is now believed that Drosophila RHO is the founder member of a previously undescribed family of serine proteases, and that it could be directly responsible for the unusual, intramembranous cleavage of EGFr ligands. Here we show that the function of RHO is conserved in Gram-negative bacteria. AarA, a Providencia stuartii RHO-related protein, is active in Drosophila on the fly EGFr ligands. Vice versa, Drosophila RHO-1 can effectively rescue the bacterium's ability to produce or release the signal that activates density-dependent gene regulation (or quorum sensing). This study provides the first evidence that prokaryotic and eukaryotic RHOs could have a conserved role in cell communication and that their biochemical properties could be more similar than previously anticipated.
Incremental extraction of domain-specific terms from online text resources (2001)

Incremental extraction of domain-specific terms from online text resources is necessary in many information retrieval (IR) and natural language processing (NLP) applications. The purpose of this paper is to present an efficient approach which can classify online text collections from the Internet dynamically and extract domain-specific terms incrementally. This approach is developed through a successful integration of PAT-tree indexing, term extraction and document classification techniques.
The Aromatization and Rearrangement of Cyclic Ketones. III. 2,3,5- and 3,4,5- Trimethylphenol from Isophorone<sup>1</sup> (1953)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Aromatization and Rearrangement of Cyclic Ketones. III. 2,3,5- and 3,4,5- Trimethylphenol from Isophorone1F. Marshall Beringer and Emil J. GeeringCite this: J. Am. Chem. Soc. 1953, 75, 11, 2633–2635Publication Date (Print):June 1, 1953Publication History Published online1 May 2002Published inissue 1 June 1953https://pubs.acs.org/doi/10.1021/ja01107a023https://doi.org/10.1021/ja01107a023research-articleACS PublicationsRequest reuse permissionsArticle Views356Altmetric-Citations1LEARN 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