gebhart/patrepeval huggingface dataset:
P2‐497: Mechanism of action of app translation blockers: From model to human (2011)

It is possible to repress amyloid precursor protein (APP) mRNA translation as a novel anti-amyloid pharmacotherapy for Alzheimer's Disease (AD). This therapeutic model is consistent with well-documented cases where AD pathology can be the genetic consequence of duplications of the APP gene. This genetic duplication caused increased brain APP dose leading to over-expression of Ab amyloid and then disease onset. These findings support our pharmacological goal to reduce APP expression. As due diligence, we showed that FDA drugs (i.e., paroxetine & N-acetyl cysteine) selectively reduced APP translation in neural and epithelial cells while maintaining compensatory APLP-1/-2 levels, but then these drugs also limited Aß production in vivo. Paroxetineis a well-known selective serotonin reuptake inhibitor (SSRI) and a clinical anti-depressant that was identified to inhibit APP 5'untranslated region (5'UTR)-luciferase reporter expression. We showed proof-of-concept that unlike other SSRIs, paroxetine exhibits a planar tricyclic aromatic benzodioxole structure and provided anti-amyloid activity in the brains of APP(Swe) transgenic mice. Additionally, posiphen, a + enantiomer of the well-tested anti-cholinesterase phenserine, passed phase I clinical trials for AD as an APP 5'UTR inhibitor. Encouraged by this, we screened the 110,000 compound molecular library at Harvard's Laboratory for Drug Discovery in Neurodegenerative Diseases that had been optimized to obtain pharmacologically favorable activity agents; for example small molecules that inhibit mesangial cell proliferation following three-dimensional pharmacophore modeling. From our screen, thirteen top leads shared chemical features pertinent to their potently blocking APP 5'UTR directed translation (IC-50: 1nM to ∼100nM). This correlated well with their selective suppression of APP expression in several neural cell lines. The top compounds of these APP 5'UTR inhibitors were 50-fold more potent blockers of Aß precursor translation than either paroxetineor posiphen. The most active lead was the ninth compound in the series, APP blocker-9 (“JTR-009”). Critically, JTR-009 effectively reduced APP levels in primary mouse E-18 cortical neurons at single nanomolar concentrations similar to that for the serum concentrations of effective clinical drugs. Our top APP translation blocker, JTR-009, is a planar tricyclic benzimidazole that could potentially intercalate into the single 146 base APP 5'UTR specific RNA stem loop. Confirming specificity, we are checking how JTR-009 blocks ribosome scanning of the APP 5'UTR to impede translation (Aß output) but not to interact with the 5'UTRs of APP-like protein (APLP-1/-2) mRNAs. We are currently determining the in vivo pharmacokinetics and tolerance of JTR-009, and we are completing a structure activity relationship (SAR) study of ten close analogs using primary cortical neurons from the B6-R1.40 genomic mouse model of AD.
Digital Watermarking (2002)

The <i>Journal of Electronic Imaging</i> (JEI), copublished bimonthly with the Society for Imaging Science and Technology, publishes peer-reviewed papers that cover research and applications in all areas of electronic imaging science and technology.
WHATʼS NEW IN ORTHOPAEDIC REHABILITATION (2002)

Orthopaedic rehabilitation is a unique subspecialty of orthopaedic surgery that incorporates surgeons and allied health professionals from several disciplines and regional subspecialties. The subspecialty deals with problems associated with neuromuscular disorders (stroke, brain injury, cerebral palsy, and ­poliomyelitis), spinal injury and deformity, total joint reconstruction, sports injury, pediatric orthopaedic surgery, hand surgery, and foot and ankle surgery. The diversity of orthopaedic rehabilitation is reflected by the many diverse subspecialists found in the membership of the Orthopaedic Rehabilitation Association (ORA). Because of the diverse nature of this orthopaedic subspecialty, a discussion on advances in orthopaedic ­rehabilitation can be accomplished by coverage or separate discussions of several topics. The following report highlights some of the advancements in orthopaedic rehabilitation within the last year. It reviews several of the topics presented at the most recent Annual Meetings of the ORA as well as topics covered on ORA Specialty Day during the American Academy of Orthopaedic Surgeons (AAOS) Annual Meeting. In addition, recent information from published abstracts and manuscripts pertinent to orthopaedic rehabilitation is included. This information covers diverse topics, such as neuromuscular disorders (stroke and brain injury as well as poliomyelitis), spine surgery (vertebroplasty and kypho­plasty), adult reconstruction (total knee arthroplasty and ­associated rehabilitation), and several aspects of hand re­habilitation after surgery. We conclude the discussion with “What’s New in the Orthopaedic Rehabilitation Association,” including a brief background and an update on the society.

### Stroke and Traumatic Brain Injury

Several new operative procedures for the management of patients with acquired spasticity and paralysis have been recently discussed1-3. The shoulder, which has traditionally received r­elatively little attention in patients with stroke or traumatic brain injury, was among the main topics covered at the recent ORA Specialty Day held in San Francisco on March 3, 20011-3. There were discussions on evaluation, management …
Female mice lacking Pald1 exhibit endothelial cell apoptosis and emphysema (2017)

Paladin (Pald1, mKIAA1274 or x99384) was identified in screens for vascular-specific genes and is a putative phosphatase. Paladin has also been proposed to be involved in various biological processes such as insulin signaling, innate immunity and neural crest migration. To determine the role of paladin we have now characterized the Pald1 knock-out mouse in a broad array of behavioral, physiological and biochemical tests. Here, we show that female, but not male, Pald1 heterozygous and homozygous knock-out mice display an emphysema-like histology with increased alveolar air spaces and impaired lung function with an obstructive phenotype. In contrast to many other tissues where Pald1 is restricted to the vascular compartment, Pald1 is expressed in both the epithelial and mesenchymal compartments of the postnatal lung. However, in Pald1 knock-out females, there is a specific increase in apoptosis and proliferation of endothelial cells, but not in non-endothelial cells. This results in a transient reduction of endothelial cells in the maturing lung. Our data suggests that Pald1 is required during lung vascular development and for normal function of the developing and adult lung in a sex-specific manner. To our knowledge, this is the first report of a sex-specific effect on endothelial cell apoptosis.
Ralstonia mannitolilytica infections in an oncologic day ward: description of a cluster among high-risk patients (2017)

Although the source of <i>R. mannitolilytica</i> remains unidentified, CVC flushing with contaminated saline solution seems to be the most likely origin of <i>R. mannitolilytica</i> CVC colonization and subsequent infections. In order to prevent similar outbreaks we recommend removal of any CVC that is no longer necessary and the use of single-dose solutions for any parenteral treatment of oncology patients.
Iterative solutions of multimodels for incompressible flows (2000)

Summary: For the simulation of two-dimensional incompressible flows, the Navier-Stokes equations can be coupled with models of reduced complexity, such as Oseen and Stokes models. This approach is briefly reviewed here. Then we propose a numerical solution of the coupled problem by subdomain splitting. We give numerical results obtained by finite element and spectral element approximations on a couple of test problems of physical interest.
Implementation of experimental equipment with Wideband Non-Contiguous OFDM (2014)

Mobile data traffic continues to rapidly increase. Even though more frequency resources are needed to handle such mobile data traffic, acquiring new wide and continuous frequency bandwidth is difficult in lower frequency bands under 1 GHz. To handle additional mobile data traffic, we are studying the technology of Wideband Non-Contiguous Orthogonal Frequency Division Multiplexing (WNC-OFDM), whose main characteristic is gathering the unused frequency resources that are generally found in extremely wide bands and dispersed in frequency domains by activating OFDM subcarriers in the fragmented frequency bands that are not used by other wireless systems. In this paper, we describe the technical issues and the key technologies to implement WNC-OFDM equipment, the structure of our implemented experimental equipment, and its basic performance.
Modelling climate change impacts on marine fish populations: process‐based integration of ocean warming, acidification and other environmental drivers (2016)

Abstract Global climate change affects marine fish through drivers such as ocean warming, acidification and oxygen depletion, causing changes in marine ecosystems and socioeconomic impacts. While experimental and observational results can inform about anticipated effects of different drivers, linking between these results and ecosystem‐level changes requires quantitative integration of physiological and ecological processes into models to advance research and inform management. We give an overview of important physiological and ecological processes affected by environmental drivers. We then provide a review of available modelling approaches for marine fish, analysing their capacities for process‐based integration of environmental drivers. Building on this, we propose approaches to advance important research questions. Examples of integration of environmental drivers exist for each model class. Recent extensions of modelling frameworks increase the potential for including detailed mechanisms and improving model projections. Experimental results on energy allocation, behaviour and physiological limitations will advance the understanding of organism‐level trade‐offs and thresholds in response to multiple drivers. More explicit representation of life cycles and biological traits can improve description of population dynamics and adaptation, and data on food web topology and feeding interactions help to detail the conditions for possible regime shifts. Identification of relevant processes will also benefit the coupling of different models to investigate spatial–temporal changes in stock productivity and integrated responses of social–ecological systems. Thus, a more process‐informed foundation for models will promote the integration of experimental and observational results and increase the potential for model‐based extrapolations into a future under changing environmental conditions.
The syntax of case and agreement : its relationship to morphology and argument structure (2005)

OF DISSERTATION The Syntax of Case and Agreement: its Relationship to Morphology and Argument Structure
TwistMouse for simultaneous translation and rotation (2007)

A common task in many computer applications is positioning objects on the screen. In real life one would simply move the object on the two dimensional plane in one seamless motion translating and rotating simultaneously. These actions must be performed separately with a standard computer mouse when positioning two dimensional (2D) objects.&#13;\n&#13;\nIn the forty years since the first computer mouse was invented several alternative input devices have been produced and evaluated. Most have been developed for a specific domain and studies have consistently shown a standard mouse is still preferred for pointing performance.&#13;\n&#13;\nThis study proposes a mouse input device, the TwistMouse, with three degrees of freedom: horizontal (x), vertical (y) and rotational (z) on a two dimensional plane which can be used to simultaneously translate and rotate for improved efficiency, effectiveness and user satisfaction in object positioning tasks on screen. In all other respects it acts like a standard contemporary computer mouse. This report presents a methodology for evaluating such a device with a task adapted from real world business applications. The positioning mode of the TwistMouse, a standard mouse and a mouse which is set up to use the wheel for rotation are assessed using a single prototype device.&#13;\n&#13;\nOne mode performed significantly better than the others in this study; but it was the wheel mouse mode and not the TwistMouse mode as hypothesised.
The importance of forensic soil science and geology being connected to mainstream forensic science (2019)

Abstract Soil science and geology are specialist disciplines that can make a valuable contribution to forensic science investigations. Despite a resurgence in earth material examination associated with criminal investigations, its full potential has probably not been realized. This paper discusses some of the issues that impact on the effective participation of soil science and geology in a broad forensic science context and why it is important for meaningful partnerships between forensic science service providers and specialist soil science and geology institutions to be established.
Mathematic proof of Schachar's hypothesis of accommodation. (1993)

To evaluate whether there is increased or decreased zonular tension during accommodation, we developed a qualitative small displacement model using Rayleigh's method to determine the characteristics of the human lens changes that occur during accommodation. We found that the optical power of the human lens increased linearly with zonular tension. Our results definitely prove Schachar's hypothesis of accommodation.
Femtosecond Dynamics of Excited-State Evolution in [Ru(bpy) 3 ] 2+ (1997)

Time-resolved absorption spectroscopy on the femtosecond time scale has been used to monitor the earliest events associated with excited-state relaxation in tris-(2,2'-bipyridine)ruthenium(II). The data reveal dynamics associated with the temporal evolution of the Franck-Condon state to the lowest energy excited state of this molecule. The process is essentially complete in approximately 300 femtoseconds after the initial excitation. This result is discussed with regard to reformulating long-held notions about excited-state relaxation, as well as its implication for the importance of non-equilibrium excited-state processes in understanding and designing molecular-based electron transfer, artificial photosynthetic, and photovoltaic assemblies in which compounds of this class are currently playing a key role.
Salt—More Adverse Effects (1997)

Salt intake has been shown to be the most important determinant of blood pressure differences both between populations and within populations, as well as the main determinant of the rise in blood pressure with increasing age. In spite of this overwhelming evidence, the food industry for commercial reasons has sustained an artificial debate about the importance of salt intake. This has distracted attention from the other serious effects that a high salt intake may have. A high salt intake (a) exacerbates conditions where there is already sodium and water retention; (b) is the rate limiting factor for carcinoma of the stomach; (c) contributes to left ventricular hypertrophy; (d) is likely to hasten deterioration of renal function and renal disease; (e) is an exacerbating factor in asthma; and (f) increasingly is suggested as a major aggravating factor in osteoporosis.
Influencia de la temperatura y del tiempo de escaldado sobre la actividad de peroxidasa en guisantes almacenados a diferentes temperaturas: utilizando la integración de tiempos y temperaturas (1984)

La actividad de peroxidasa se determino tanto en guisantes frescos como escaldados a diferentes temperaturas y tiempos despues de su conservacion frigorifica a 20oC, 0oC y
-20oC, variando el tiempo de almacenamiento. En el estudio de este experimento, se ha intentado medir los grados de inactivacion y regeneracion de la actividad peroxidasica durante los almacenamientos frigorificos.
Al tener en cuenta diversas variables independientes dos clases de tiempos y dos clases de temperaturas, la interpretacion matematica de los resultados fue algo compleja, hasta dar con modelos exponenciales en cinco dimensiones para la determinacion de la actividad de la peroxidasa. La integracion cuadruple de estos modelos obtuvo un valor medio de peroxidasa, que rige como parametro a lo largo y a lo ancho de todo el proceso experimental. Finalmente, para estimar la eficacia de los resultados conseguidos, asi como los efectos combinados termicos y frigorificos, hubo necesidad de aplicar una doble integracion para obtener un criterio sencillo, que diese en forma numerica la informacion pertinente, sin ninguna ambiguedad a la hora de calificar los tratamientos aplicados. En ambos procesos matematicos se ha supuesto que la funcion principal no esta modificada por ninguna otra funcion perturbadora, ni en el tiempo, ni en el espacio, ni en la temperatura, por lo que se trata simplemente de una distribucion homogenea, sin densidad espectral ni efectos secundarios.
Estimating Likelihood of Dementia in the Absence of Diagnostic Data: A Latent Dementia Index in 10 Genetically Informed Studies (2022)

This latent dementia indicator approach may serve as a model for other research consortia confronted with similar data integration challenges.
Gating and habituation deficits in the schizophrenia disorders. (1995)

Gating and habituation deficits have been identified as major features of the schizophrenias. When gating and habituation functions are impaired, the schizophrenia patient can neither efficiently screen out trivial, distracting stimuli nor effectively attend to and process salient stimuli in the environment. Along with the clinical significance and symptom correlates of gating and habituation deficits in schizophrenia, studies of these functions have produced much important data. Specifically, such studies have demonstrated the involvement of structures in the cortico-striato-pallido-pontine (CSPP) neural circuitry in both schizophrenia and the normal processing of information. Thus, neurobiological manipulations along various axes of the CSPP can allow investigators to understand the neural basis of impaired gating and habituation in the schizophrenias.
IP-oriented QoS in next generation networks: application to wireless networks (2005)

The challenge of new communication architectures is to offer QoS in Internet networks. This paper investigates the QoS aspects in the NGN (Next Generation Networks), and especially in the wireless networks. Voice and video multimedia applications will be developed and used when QoS mechanisms will exist. Therefore new functions must be developed to guarantee performance, offer security, avoid jitter and to allow the respect of real-time constraints.
Topological Phases in AB-Stacked MoTe2/WSe2: Z2 Topological Insulators, Chern Insulators, and Topological Charge Density Waves (2022)

We present a theory on the quantum phase diagram of AB-stacked MoTe_{2}/WSe_{2} using a self-consistent Hartree-Fock calculation performed in the plane-wave basis, motivated by the observation of topological states in this system. At filling factor ν=2 (two holes per moiré unit cell), Coulomb interaction can stabilize a Z_{2} topological insulator by opening a charge gap. At ν=1, the interaction induces three classes of competing states, spin density wave states, an in-plane ferromagnetic state, and a valley polarized state, which undergo first-order phase transitions tuned by an out-of-plane displacement field. The valley polarized state becomes a Chern insulator for certain displacement fields. Moreover, we predict a topological charge density wave forming a honeycomb lattice with ferromagnetism at ν=2/3. Future directions on this versatile system hosting a rich set of quantum phases are discussed.
ASLT: An Extension of Hybrid Miniaturization Techniques (1967)

The hybrid miniaturization technique of applying active and passive components separately to a packaging substrate enables independent customization of components and minimizes stray capacitance between components. Manufacturing advantages result because all components can be pretested, and the critical component joining operation can be performed as a continuous operation. This paper describes IBM's Advanced Solid Logic Technology (ASLT) wherein the capabilities of hybrid circuit technology have been extended to produce a high-speed, high-density digital logic module compatible with automated production. Design considerations and assembly processes are detailed. A development of the power handling capability reviews the various thermal paths within the module.
Third-order nonlinear optical property of platinum group metal complexes with square planar configurations (1997)

The developments of novel materials having large third-order nonlinear optical susceptibility χ (3) and fast response give a considerable interest as the key subjects for future optoelectronic technology. It was proved in former researches that the large low dimensional delocalization field for optically excited electron is effective for large χ (3) value. Third-order optical nonlinearities of many materials, mainly inorganic semiconductors or organic conjugated polymers, have been investigated. Many inorganic materials have studied for their large χ (3) and thermal stability. On the other hands, organic nonlinear optical materials also have been noted, because they have advantages of fast optical response, architectural flexibility and ease of fabrication.
Automated Electrophysiology: High Throughput of Art (2003)

Electrophysiological measurements, in particular, patch clamping, have long been regarded as the "gold standard" for assaying ion channels. Despite its high information content, the technique suffers from laborious, manual processing by highly skilled workers and extremely low throughput. Recently, a number of researchers have started to automate patch clamping by either automating conventional micropipette-based patch clamping or developing planar microelectrode arrays. This article reviews the brief history of these emerging technologies and discusses the technical details, advantages, and disadvantages of each approach and technique. As will be evident from the discussion, two types of automated patch-clamping technologies are emerging. The first places emphasis on data quality, comparable to conventional patch clamping, and the second has much higher throughput. Future developments will include sophisticated patch-clamping devices with both high-quality data and high throughput capabilities and further integration of patch clamping with other cell-based assays.
An Iterative Frequency-Domain Decision-Feedback Receiver for MC-CDMA Schemes (2005)

The MC-CDMA techniques (multicarrier code division multiple access) combine a CDMA scheme with OFDM modulation (orthogonal frequency division multiplexing), so as to allow high transmission rates over severely time-dispersive channels without the need of a complex receiver implementation. We propose an iterative frequency-domain decision-feedback receiver for MC-CDMA signals. The proposed receiver has excellent performance, close to the single-code MFB (matched filter bound), even for severe time-dispersive scenarios and/or in the presence of strong interfering channels.