gebhart/patrepeval huggingface dataset:
A novel PU.1 inhibitor for the treatment of Alzheimer’s disease (2021)

Abstract Background In 2015, we identified the microglia‐specific transcription factor PU.1, encoded for by SPI1 , as a master regulator of neuroinflammation in a mouse model of Alzheimer’s Disease and in human brain tissue from deceased Alzheimer’s Disease patients 1 . In 2017, a GWAS SNP that delays onset of Alzheimer’s Disease, was shown to reduce PU.1 expression levels 2 . Here, we describe a high‐throughput screen for small molecules that inhibit PU.1 activity. Our goal is to develop novel agents that can rein in the abnormal neuroimmune response associated with Alzheimer’s dementia. Method We used a stable immortalized mouse microglia (BV2) reporter line that expresses luciferase in a PU.1‐dependent manner. We screened a total of 58’100 molecules from 3 separate chemical libraries and obtained 264 hits. We further validated these hits using multiple assays in human stem cell derived microglia. Finally, we administered our top hit (A11) to transgenic mouse models of Alzheimer’s Disease. Result A11 exhibits anti‐inflammatory effects at a concentration of 20 nM in activated microglia, as assessed by RTqPCR and ELISA for IL1β, morphological analyses and lipid accumulation quantification. In mice, A11 preferentially distributed to brain tissues after systemic (intraperitoneal) application and reached a peak concentration at 4 hours. When dosing mice that develop severe neurodegeneration (CK‐p25 transgenic mice), we found a reduction of microglial proliferation, astrogliosis and retention of p25‐positive neurons in the hippocampus. No abnormalities were seen in the treated control littermates. Conclusion Our novel PU.1 inhibitor (A11) shows nanomolar potency and efficacy in multiple assays and cell lines. Mouse experiments demonstrate suitability for systemic application. Administration of A11 in CK‐p25 transgenic mice show an amelioration of neurodegeneration‐associated hallmarks, such as microglial and astrocytic activation and loss of p25‐positive neurons. References: (1) Gjoneska,E, A R Pfenning, H Mathys, G Quon, A Kundaje, L H Tsai and M Kellis. 2015. Conserved epigenomic signals in mice and humans reveal immune basis of Alzheimer’s disease. Nat. 518(7539)365‐9. (2) Huang,K L, E Marcora, A A Pimenova, A F Di Narzo et al. 2017. A common haplotype lowers PU.1 expression in myeloid cells and delays onset of Alzheimer’s disease. Nat Neurosci. 20(8) 1052‐1061.
Bounds for Codes in Products of Spaces, Grassmann, and Stiefel Manifolds (2008)

Upper bounds are derived for codes in Stiefel and Grassmann manifolds with given minimum chordal distance. They stem from upper bounds for codes in the product of unit spheres and projective spaces. The new bounds are asymptotically better than the previously known ones.
Efficient Large-Scale Neural Domain Classification with Personalized Attention (2018)

In this paper, we explore the task of mapping spoken language utterances to one of thousands of natural language understanding domains in intelligent personal digital assistants (IPDAs). This scenario is observed in mainstream IPDAs in industry that allow third parties to develop thousands of new domains to augment builtin first party domains to rapidly increase domain coverage and overall IPDA capabilities. We propose a scalable neural model architecture with a shared encoder, a novel attention mechanism that incorporates personalization information and domain-specific classifiers that solves the problem efficiently. Our architecture is designed to efficiently accommodate incremental domain additions achieving two orders of magnitude speed up compared to full model retraining. We consider the practical constraints of real-time production systems, and design to minimize memory footprint and runtime latency. We demonstrate that incorporating personalization significantly improves domain classification accuracy in a setting with thousands of overlapping domains.
Pinch, Click, or Dwell: Comparing Different Selection Techniques for Eye-Gaze-Based Pointing in Virtual Reality (2021)

While a pinch action is gaining popularity for selection of virtual objects in eye-gaze-based systems, it is still unknown how well this method performs compared to other popular alternatives, e.g., a button click or a dwell action. To determine pinch’s performance in terms of execution time, error rate, and throughput, we implemented a Fitts’ law task in Virtual Reality (VR) where the subjects pointed with their (eye-)gaze and selected / activated the targets by pinch, clicking a button, or dwell. Results revealed that although pinch was slower, made more errors, and had less throughput compared to button clicks, none of these differences were significant. Dwell exhibited the least errors but was significantly slower and achieved less throughput compared to the other conditions. Based on these findings, we conclude that the pinch gesture is a reasonable alternative to button clicks for eye-gaze-based VR systems.
Tissue‐Specific Expression of Promoter Regions of the αr1(VI) Collagen Gene in Cell Cultures and Transgenic Mice (1997)

Cis-acting regions regulating transcription of the alpha1(VI) collagen chain have been investigated in vitro by transfection of promoter-CAT (where CAT is chloramphenicol acetyltransferase) constructs in different types of cultured cells and in vivo in transgenic mice carrying the same CAT constructs or minigenes derived from the fusion of genomic and cDNA sequences in which small deletions of the collagenous domain had been engineered. 215 bp of 5'-flanking sequence showed promoter activity in vitro, yet were not expressed in any tissue of six transgenic lines, indicating that this fragment contains the basal promoter, but not activator sequences. Constructs with 0.6 and 1.4 kb of the 5'-flanking region produced significantly higher CAT activity in transfected cells and were expressed in tissues of about 30% of transgenic lines. Although CAT activity was totally unrelated to the pattern of expression of the alpha1(VI) mRNA, these results suggest the presence of an activator(s) between -0.2 and -0.6 kb from the transcription start site. When the promoter size was increased to 5.4 or 6.5 kb, CAT activity was stimulated severalfold relative to the construct p1.4CAT and p4.0CAT in NIH3T3 fibroblasts and chick embryo chondroblasts. This stimulation was, however, not observed in C2C12 myoblasts. Transgenic mice generated with 6.5CAT construct or minigenes, containing 6.2 kb of promoter, exhibited very high levels of expression, which was similar to the relative amount alpha1(VI) mRNA in the majority of tissues, with the exception of lung, adrenal gland and uterus. CAT activity in tissues was 100-1000-fold higher than that measured in transgenic mice with shorter promoter (0.6 or 1.4 kb). Since expression of minigenes was determined by RNase protection assay, the levels of mRNA per transgene copy were compared to those of the chromosomal gene and found to be always less than one quarter. These data suggest that the region -4.0/-5.4 contains an important activator(s) sequence which induces transcription in several, but not all, type VI collagen-producing tissues. Finally, analysis with the longest promoter fragment (7.5 kb) revealed a complex effect of the region -6.5/-7.5 on alpha1(VI) chain transcription. The sequence was inhibitory in NIH3T3 cells, indifferent in myoblasts and activating in chondroblasts in vitro, whereas transgenic animals generated with 7.5CAT construct produced a pattern of expression comparable to that of 6.5CAT and minigenes. During postnatal development transcription from both the endogenous gene and the transgenes decreased. However, the ratio of transgene/chromosomal gene expression was not constant, but varied in a way dependent on the tissue. This observation suggests that the fragment studied contains key sequences for the age-dependent regulation of the alpha1(VI) gene. No phenotypic alterations were induced by the presence of mutations in the minigenes.
Toward the realization of six degrees-of-freedom with compressed light fields (2017)

360° video, supporting the ability to present views consistent with the rotation of the viewer's head along three axes (roll, pitch, yaw) is the current approach for creation of immersive video experiences. Nevertheless, a more fully natural, photorealistic experience - with support of visual cues that facilitate coherent psycho-visual sensory fusion without the side-effect of cyber-sickness - is desired. 360° video applications that additionally enable the user to translate in x, y, and z directions are clearly a subsequent frontier to be realized toward the goal of sensory fusion without cyber-sickness. Such support of full Six Degrees-of-Freedom (6 DoF) for next generation immersive video is a natural application for light fields. However, a significant obstacle to the adoption of light field technologies is the large data necessary to ensure that the light rays corresponding to the viewer's position relative to 6-DoF are properly delivered, either from captured light information or synthesized from available views. Experiments to improve known methods for view synthesis and depth estimation are therefore a fundamental next step to establish a reference framework within which compression technologies can be evaluated. This paper describes a testbed and experiments to enable smooth and artefact-free view transitions that can later be used in a framework to study how best to compress the data.
Low-noise microwave generation with optical microresonators (2017)

Optical frequency combs provide an equidistant grid of optical frequency components, enabling a wide array of diverse and new technologies [1]. One such application is photonic microwave generation where optical frequency combs provide unprecedented low-noise performance via optical frequency division [2]. Although providing excellent performance, it comes at the expense of size and complexity. In this work, we pursue a different route to provide both a compact and low-noise microwave source by direct microwave generation with microresonator based optical Kerr frequency combs (KFC) [3] that are formed via dissipative Kerr temporal solitons (DKS) in the microresonators [4]. A unique aspect of KFCs is their wide comb spacing (10 GHz-1THz) due to the small dimensions of the resonator. This enables a wide range of applications including optical communications, spectroscopy and direct generation of microwave signals. For this latter application, crystalline resonators are appealing over other microresonator platforms, as their low thermorefractive coefficient imply that the noise introduced by the resonator will be very low.
Spatial Division Selectivity for High Density Users with Millimeter-Wave Massive Collocated- and Distributed-MIMO (2023)

Massive multiple input and multiple output (MIMO) can enhance the cell capacity. Although massive MIMO using space division multiplexing has been developed, the cell capacity for densely populated users has had limited investigation. This paper describes experimental measurements and mathematical analysis of spatial division selectivity using collocated-MIMO (C-MIMO) and distributed-MIMO (D-MIMO) systems. We measure signal to noise ratio (SNR) of down link (DL) multi-user transmission using zero-forcing precoding in over the air environments at 28 GHz by changing user equipment (UE) density. Additionally, mathematical analysis reveals that the beam width causes the differences of spatial division selectivity between C-MIMO and D-MIMO. The experimental and mathematical results demonstrate that C-MIMO degrades the DL SNR as the UE density increases, whereas D-MIMO maintains the high SNR even in the high UE density. D-MIMO enables to enhance the cell capacity in densely populated user environments.
Micro-CT of small insects by projection x-ray microscopy (2006)

The projection X-ray microscope utilized a very small X-ray source emitted from a thin (0.1-3 &#956;m) target metal film excited by the focused electron beam of a scanning electron microscope (SEM). When an object is placed just below the target metal film, the diverging X-rays enlarge the shadow of the object. Because no X-ray optics such as a zone-plate is used, the focal depth is, in principle, infinitely large. We exploited this to apply projection X-ray microscopy to three-dimensional (3-D) structure analysis by means of cone-beam computed tomography (CT). A small arthropod (<i>Pseudocneorhinus bifasciatus</i>, 5 mm in length) was examined for CT study. The projection images were recorded at 3-degree increments over the whole range (360°) of a stepping-motor-controlled sample rotator. The 3-D reconstructed image was calculated to be 256 x 256 x 256 (5 &#956;m) voxel data. The reconstructed 3-D image showed in detail the internal structure of an opaque object. Trial for element mapping using projection X-ray microscope is also performed by developing a new target exchanger. This apparatus enables exchange of metal targets without leaking vacuum of SEM. By taking images using K&#945; line from nickel and cobalt targets, distribution of iron, which has absorption edge between two K&#945; lines, can be shown. Distribution of less than 10 &#956;m iron particles is distinguished from cobalt particles. This system would be applicable for 3-D element analysis.
Scaling wideband distributed transmit beamforming via aggregate feedback (2015)

We investigate distributed beamforming from a cluster of N cooperating transmitters to a distant destination over a wideband dispersive channel. Feedback from the destination is critical for enabling this. In order to develop protocols that scale to arbitrarily large numbers of cooperating nodes, we restrict attention to aggregate feedback broadcast from the destination to the entire transmit cluster, rather than per-transmitter channel feedback as in conventional feedback-based MIMO systems. We first show that naive application of a one-bit feedback algorithm developed for narrowband channels to each subcarrier in an OFDM system does achieve beamforming gain on each subcarrier, but results in an effective channel at the destination with severe phase discontinuities across frequency, which is not amenable to standard receive channel estimation algorithms. We then show that it is possible to enforce smoothness of phase across frequency by augmenting the feedback to 2 bits per subcarrier, which enables modeling and estimation of the effective channel as sparse in the time domain. Our preliminary results show that, even when the SNR per node is well below the threshold for reliable demodulation, it is possible to bootstrap using the N-fold power pooling gain obtained from incoherent combining of the signals from multiple transmitters, and to attain a significant fraction of the N2-fold beamforming gain using the proposed algorithm. We also discuss a number of open issues, recognizing that this is only a first step in developing scalable, wideband, distributed MIMO systems.
Formation of high quality screen-printed contacts to homogeneous high sheet resistance emitters (HHSE) (2011)

In this paper we report on the formation of high quality contacts to HHSE with a sheet resistance variation of ≥30 Ω/sq using a commercial front-side Ag paste, PV16A from DuPont. We fabricated and characterized solar cells with emitter sheet resistances of 65, 75, 85, 95 and 105 Ω/sq. We found that emitter sheet resistances in the range of 65-95 Ω/sq can be contacted with low average series resistance of 0.63-0.77 Ω-cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> and high fill factor (FF) of 77.4-78.8%. The 75 Ω/sq emitter gave the best average efficiency of 18.3%, followed by 18.2% for the 65 Ω/sq, 18.0% for the 85 Ω/sq, and finally 17.7% for the 95 Ω/sq. The 105 Ω/sq emitter gave a low FF due to high series resistance, but the shunt resistance and ideality factor were excellent, which suggests the paste was not encroaching the shallow emitter junction.
Control of power-shuttle motion-inverter (2005)

The topic of this paper is the design of the control system for the automatic motion-inverter in agricultural tractors. The objective of this system is to perform a fully-automated symmetric motion inversion. The device (reverser) used for the automatic motion inversion is an electro-hydraulic system, constituted by two clutches (one for the forward, and one for the reverse motion), driven by a proportional electrohydraulic valve (EVP) and by an on-off directional electrohydraulic valve (EVD). The measured variables are the input/output rotational speeds of the reverser. All the subtasks of the reverser control systems are considered: the design of an inner-loop for the EVP, the open-loop switching strategies, and the design and analysis of the outer control loop which regulates the vehicle speed during the motion-inversion.
The (gamma,pn) and (gamma,pp) reactions in 12C (1993)

The (gamma,NN) reactions at intermediate energies have long been suggested as a source of information on nucleon-nucleon correlations in nuclei. In particular, the (gamma,pp) reaction may hold particular promise because it is much less sensitive to medium range MEC effects. In the past limited intensity and resolution of the available photon beams has hindered progress. Using the Galsgow photon tagging spectrometers at the Mainz MAMI-A and MAMI-B electron microtrons, data on both (gamma,pn) and (gamma,pp) reactions in 12C have now been obtained with much improved energy resolution (~7 MeV in missing energy). The very recent MAMI-B data extends up to 750 MeV which permits shorter range effects to be sought.
AlGaAsOI Photonics and Low-Loss Links for High-Speed Entanglement-Based Quantum Key Distribution (2022)

We report a record-high detected entangled-photon pair coincidence rate from an AlGaAs-on-insulator microring resonator with raw coincidence rates &gt; 19 kHz that is capable of time-bin entanglement-based QKD with an estimated secure key rate of 1.4 kbits/second.
Correlations Among Electrogastrogram, Gastric Dysmotility, and Duodenal Dysmotility in Patients With Functional Dyspepsia (2009)

More than two-thirds of patients with functional dyspepsia have abnormalities in the EGG and antral/duodenal motility. The sensitivity of these 2 different methods is essentially the same. EGG and antroduodenal manometry can complement each other in demonstrating gastric motor dysfunction in patients with functional dyspepsia.
Electrochemistry in ionic liquids: Case study of a manganese corrole (2017)

Voltammetry of [5,10,15-tris(pentafluorophenylcorrole)]Mn(III) was investigated in four different ionic liquids (ILs): 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide (BMIm-TFSI); 1-ethyl-3-methylimidazolium ethylsulfate (EMIm-EtOSO3); 1-ethyl-3-methylimidazolium triflate (EMIm-OTf); and 1-ethyl-3-methylimidazolium tetracyanoborate (EMIm-TCB). We found that MnIV/III E 1/2 values depend on IL counter anion: OTf–< EtOSO3 − < TFSI− < TCB−. In EMIm-TCB and BMIm- TFSI, reversible, diffusion-controlled MnIV/III reactions occurred, as evidenced in each case by the ratio of anodic to cathodic diffusion coefficients over a range of scan rates. Axial coordination was evidenced by a cathodic to anodic diffusion coefficient ratio greater than one, an increasing cathodic to anodic peak current ratio with increasing scan rate, and a split Soret band in the UV-vis spectrum of the complex.
ChemInform Abstract: DECOMPOSITION RATES, SYNTHESIS, AND SPECTRAL PROPERTIES OF A SERIES OF ALKYL HYPONITRITES (1984)

Abstract Silberhyponitrit (I) liefert mit Halogenverbindungen die entsprechenden Alkylhyponitrite (II) in mäßigen Ausbeuten.
Annular Illumination and Collection in Solid Immersion (2009)

Abstract Tailoring the angular spectrum with annular illumination and collection can significantly improve integrated circuit analysis with an optical microscope, when combined with solid immersion. We present the development, testing, and optimization of a simple and compact apparatus to implement annular illumination and collection in a Hamamatsu iPHEMOS system. We demonstrated improved imaging of an IBM 45nm silicon-oninsulator circuit, with annular illumination and collection in confocal scanning optical microscopy and widefield microscopy with an InGaAs camera.
General Principles of Molecular Imaging (2021)

The field of molecular imaging continues to innovate advancing new strategies for detection of molecular and cellular events in intact living subjects. As the molecular underpinnings of biology and pathology are more fully delineated, additional opportunities to develop novel molecular imaging MI techniques continue to emerge. The next generation of innovations are anticipated to further advance unique capabilities for noninvasive interrogation of molecular events in intact subjects. Interdisciplinary contributions are required from diverse biomedical and scientific disciplines to fuel continued advances in molecular imaging. This chapter provides a foundational overview of molecular imaging concepts and strategies used to probe both simple and complex processes while cells reside in their native relevant biological context.
DSA and RSA Key and Signature Encoding for the KeyNote Trust Management System (2000)

This memo describes RSA and DSA key and signature encoding, and binary key encoding for version 2 of the KeyNote trust-management system.
ARE THE CRACKS STARTING TO APPEAR IN BISPHOSPHONATE THERAPY (2016)

Introduction:Osteoporosis is a global health issue with 200 million people suffering worldwide and it is a common condition in the elderly.Bisphosphonates including alendronate and risendronate are considered as the first line treatment for osteoporosis.However, there is increasing evidence that bisphosphonate (BP) therapy is associated with atypical fractures.Animal studies have reported a dose-dependent association between the duration of BP therapy and the accumulation of microdamage.We tested the hypothesis that hip fracture patients treated with BP exhibited greater micro-damage density than untreated fracture and 'healthy' aging nonfracture controls.Method: Trabecular bone cores from patients treated with BP were compared with patients who had not received any treatment for bone metabolic disease (ethics reference: R13004).Non-fractured cadaveric femora from individuals with no history of bone metabolic disease were used as controls.Cores were imaged in high spatial resolution (~1.3m) using Synchrotron X-ray tomography (Diamond Light Source Ltd.)A novel classification system was devised to characterise features of micro-damage in the Synchrotron images: micro-cracks, diffuse damage and perforations.Synchrotron micro-CT stacks were visualised and analysed using ImageJ, Avizo and VGStudio MAX.Results: Our findings show that the BP group had the highest micro-damage density across all groups.The BP group (7.7/mm 3 ) also exhibited greater micro-crack density than the fracture (4.3/mm 3 ) and non-fracture (4.1/mm 3 ) controls.Furthermore, the BP group (1.9/mm 3 ) demonstrated increased diffuse damage when compared to the fracture (0.3/mm 3 ) and non-fracture (0.8/mm 3 ) controls.In contrast, the BP group (1.9.mm 3 ) had fewer perforations than fracture (3.0/mm 3 ) and nonfracture controls (3.9/mm 3 ).Conclusion: BP inhibits bone remodelling, thereby reducing the number of perforated trabeculae, but over-suppression leads to micro-damage accumulation.Accumulated damage could weaken the trabecular bone in the femoral head and neck, increasing the risk of a fracture during a trip or fall.