gebhart/patrepeval huggingface dataset:
Mouse Model for Shwachman-Diamond Syndrome with the R126T Disease Mutation Leads to Severe Growth and Developmental Deficiencies with Impairment of Hematopoiesis. (2006)

Abstract Shwachman-Diamond syndrome (SDS) is a bone marrow failure syndrome characterized by exocrine pancreatic insufficiency and skeletal abnormalities, as well as hematological dysfunction. SDS is caused by mutations in SBDS, a highly conserved gene that has been suggested to be involved in RNA metabolism and/or ribosome biogenesis. It is essential, based on our mouse knock-out model studies and the absence of observed patients with the combination of two null alleles. We have generated an allele with the disease mutation, R126T, in the murine ortholog in order to develop new models of SDS. This mutation has been interpreted to be hypomorphic in nature, as it occurs in combination with the common null disease allele in two patients. Interestingly, these patients also have severe hematological disease phenotypes. SbdsR126T/+mice develop normally and show no disease phenotypes, in accordance with the recessive inheritance of SDS. However, the SbdsR126T/R126T and SbdsR126T/- mice did not survive birth, and exhibited marked size reduction. The growth difference became apparent in embryos during the mid-fetal period, at E12.5–14.5; there were also noted disturbances of major organs including the skeleton, brain and lung. Comparable deficiencies were noted overall, but the SbdsR126T/- embryos were consistently more severely affected than were SbdsR126T/R126T embryos. Examination of hematopoietic progenitors from the fetal livers of SbdsR126T/R126T and SbdsR126T/- mutant mice also showed marked reductions in BFU-E, CFU-G, CFU-M, CFU-GM and CFU-GEMM numbers, as revealed by standard colony formation assays, when compared to wild type and heterozygote littermates. In additional studies, primary fibroblast cultures from E16.5 day mutant embryos were found to exhibit slower growth and an extended G1 phase of the cell cycle compared to fibroblasts from wild type embryos. Further, total protein synthesis was measured by incorporation of radio-labeled amino acids and found to be notably reduced in the mutant fibroblasts. The small size, organ deficiencies and early death of the mutant mice together with the cellular deficiencies, which indicate severe autologous growth problems, emphasize the severe consequences of loss of Sbds. These animal disease models provide new avenues for investigation to elucidate basic functions of SBDS and the pathobiology of SDS.
Activity of NTDs Drug-discovery Research Consortium (2016)

Neglected tropical diseases (NTDs) are an extremely important issue facing global health care. To improve "access to health" where people are unable to access adequate medical care due to poverty and weak healthcare systems, we have established two consortiums: the NTD drug discovery research consortium, and the pediatric praziquantel consortium. The NTD drug discovery research consortium, which involves six institutions from industry, government, and academia, as well as an international non-profit organization, is committed to developing anti-protozoan active compounds for three NTDs (Leishmaniasis, Chagas disease, and African sleeping sickness). Each participating institute will contribute their efforts to accomplish the following: selection of drug targets based on information technology, and drug discovery by three different approaches (in silico drug discovery, "fragment evolution" which is a unique drug designing method of Astellas Pharma, and phenotypic screening with Astellas' compound library). The consortium has established a brand new database (Integrated Neglected Tropical Disease Database; iNTRODB), and has selected target proteins for the in silico and fragment evolution drug discovery approaches. Thus far, we have identified a number of promising compounds that inhibit the target protein, and we are currently trying to improve the anti-protozoan activity of these compounds. The pediatric praziquantel consortium was founded in July 2012 to develop and register a new praziquantel pediatric formulation for the treatment of schistosomiasis. Astellas Pharma has been a core member in this consortium since its establishment, and has provided expertise and technology in the area of pediatric formulation development and clinical development.
Multi-Die Polylithic Integration Enabled by Heterogeneous Interconnect Stitching Technology (HIST) (2018)

In this paper, a multi-die polylithic integration approach using Heterogeneous Interconnect Stitching Technology (HIST) is explored for low-loss, high-density, and low-energy electronic systems. In the HIST approach, stitch-chips, which are either active or passive, are used for such signal pathways between assembled `anchor chips,' while surface-embedded chips utilize 3D face-to-face electrical interconnections. Fine-pitch and multi-height Compressible MicroInterconnects (CMIs) are used to provide low-loss and mechanically robust interfaces between the anchor chips and the stitch-chips as well as the surface-embedded chips. Electrical measurements of the assembled chips are reported and demonstrate robust interconnection. EM simulations show that low-loss signal interconnection (<; -0.4 dB) can be achieved by using 90 μm tall CMIs and 500 μm long channels on quartz stitch-chips.
The antimalarial ferroquine is an inhibitor of hepatitis C virus (2013)

FQ is a novel, interesting anti-HCV molecule that could be used in combination with other direct-acting antivirals.
Comparing Python, Go, and C++ on the N-Queens Problem (2020)

Python currently is the dominant language in the field of Machine Learning but is often criticized for being slow to perform certain tasks. In this report, we use the well-known $N$-queens puzzle as a benchmark to show that once compiled using the Numba compiler it becomes competitive with C++ and Go in terms of execution speed while still allowing for very fast prototyping. This is true of both sequential and parallel programs. In most cases that arise in an academic environment, it therefore makes sense to develop in ordinary Python, identify computational bottlenecks, and use Numba to remove them.
Genetic Analysis of Punt, a Type II Dpp Receptor That Functions Throughout the Drosophila melanogaster Life Cycle (1998)

TGF-beta (transforming growth factor-beta-) mediated signal transduction affects growth and patterning in a variety of organisms. Here we report a genetic characterization of the Drosophila punt gene that encodes a type II serine/threonine kinase TGF-beta/Dpp (Decapentaplegic) receptor. Although the punt gene was originally identified based on its requirement for embryonic dorsal closure, we have documented multiple periods of punt activity throughout the Drosophila life cycle. We demonstrate that potentially related embryonic punt phenotypes, defects in dorsoventral patterning and dorsal closure, correspond to distinct maternal and zygotic requirements for punt. In addition, we document postembryonic requirements for punt activity. The tight correspondence between both embryonic and postembryonic loss-of-function punt and dpp phenotypes implicates a role for Punt in mediating virtually all Dpp signaling events in Drosophila. Finally, our comparison of punt homoallelic and heteroallelic phenotypes provides direct evidence for interallelic complementation. Taken together, these results suggest that the Punt protein functions as a dimer or higher order multimer throughout the Drosophila life cycle.
Linear-time inference for Gaussian Processes on one dimension (2020)

Gaussian Processes (GPs) provide powerful probabilistic frameworks for interpolation, forecasting, and smoothing, but have been hampered by computational scaling issues. Here we investigate data sampled on one dimension (e.g., a scalar or vector time series sampled at arbitrarily-spaced intervals), for which state-space models are popular due to their linearly-scaling computational costs. It has long been conjectured that state-space models are general, able to approximate any one-dimensional GP. We provide the first general proof of this conjecture, showing that any stationary GP on one dimension with vector-valued observations governed by a Lebesgue-integrable continuous kernel can be approximated to any desired precision using a specifically-chosen state-space model: the Latent Exponentially Generated (LEG) family. This new family offers several advantages compared to the general state-space model: it is always stable (no unbounded growth), the covariance can be computed in closed form, and its parameter space is unconstrained (allowing straightforward estimation via gradient descent). The theorem's proof also draws connections to Spectral Mixture Kernels, providing insight about this popular family of kernels. We develop parallelized algorithms for performing inference and learning in the LEG model, test the algorithm on real and synthetic data, and demonstrate scaling to datasets with billions of samples.
High speed and low power consumption modulator based on electro-optic polymer infiltrated subwavelength grating waveguide ring resonator (Conference Presentation) (2017)

Silicon-based high-speed optical modulators, fabricated using CMOS compatible nanofabrication technology, are the key components for integrated photonics, especially the high-speed intra- and inter-chip optical interconnects. In this paper, we propose a high speed, low power consumption electro-optic (EO) modulator based on the EO polymer/silicon hybrid subwavelength grating (SWG) waveguide ring resonator. The core of the SWG waveguide consists periodically arranged silicon pillars along the light propagation direction. EO polymer (SEO125) is used as the top cladding. An intriguing advantage that the SWG waveguide has over the conventional silicon strip waveguide is its large mode volume overlap with EO polymer. Besides, compared with the plasma dispersion effect, electro-optic polymers have a large electro-optic coefficient and ultrafast response speed. Furthermore, among the different modulator structures, ring resonator is one of the most promising structures as it has a small footprint which is the key for VLSI (Very Large Scale Integration), and it allows complex optical functionalities monolithically integrated with advanced electronics at a competitive cost. Thus, the proposed EO polymer infiltrated SWG waveguide ring resonator based modulator is a very promising candidate for low cost, small size, light weight, and low power consumption (CSWaP) optical interconnect.
A simple procedure for the isolation of bilirubin monoglucuronide and diglucuronide from bile. (1982)

Isolation of bilirubin monoglucuronide and diglucuronide from rat and human bile has been accomplished by affinity chromatography over albumin agarose, followed by reverse-phase adsorption chromatography over siliconized kieselguhr. The glucuronide nature of the conjugating saccharide was confirmed by TLC, employing two different solvent systems, of the sugar released by either alkaline hydrolysis or ammonolysis. The bilirubin diglucuronide preparation migrated as a single polar band on direct silica gel TLC, yielded exclusively the delta ethyl anthranilate azopigment, and had a sugar:bile pigment molar ratio of 2.01 +/- 0.03 (S.E.M.). The monoglucuronide migrated as a single, less polar band on TLC, yielded equimolar quantities of alpha and delta azopigments, and had a sugar:bile pigment ratio of 1.02 +/0- 0.04. Both conjugates were preparable in milligram quantities, free of phospholipid, bile acid, and cholesterol, at yields averaging 40% to 60%, and could be isolated with high specific activity by injection of pheonbarbital-penetrated rats with delta-aminolevulinic acid-4- 14C or -2,3-3H. Preparations of pure bilirubin conjugates should greatly facilitate studies of bilirubin metabolism.
Supplemental figure legends from Loss of <i>ARID1A</i> Activates <i>ANXA1</i>, which Serves as a Predictive Biomarker for Trastuzumab Resistance (2023)

&lt;p&gt;Supplemental Legends for figures S1-S5&lt;/p&gt;
Secure Channel, Key Distribution, and Certificates (2018)

In the previous chapter, we were considering how Bob can determine whether he's really communicating with Alice. Although Alice initiated the communication by sending a message to Bob, she has the mirror-image problem: she doesn't (yet) know that she's really talking with Bob. She knows that she's sending messages to Bob's address, but let's be paranoid for a minute. What if an attacker is intercepting those messages and sending back the attacker's version of the replies? Is there a way to rule out that possibility?
Frontispiece: Building a Bridge from Papermaking to Solar Fuels (2019)

Solar Fuels The preparation of graphene quantum dots from black liquor is reported by W. Sun, J. Chen, G. A. Ozin et al. in their Communication on page 14850 ff. The obtained GQDs were exploited to improve the photocatalytic H2O and CO2 reduction activities of TiO2.
CAR-T Engager proteins optimize anti-CD19 CAR-T cell therapies for lymphoma (2022)

B cell lymphoma therapy has been transformed by CD19-targeting cellular therapeutics that induce high clinical response rates and impressive remissions in relapsed and refractory patients. However, approximately half of all patients who respond to CD19-directed cell therapy relapse, the majority within 6 months. One characteristic of relapse is loss or reduction of CD19 expression on malignant B cells. We designed a unique therapeutic to prevent and reverse relapses due to lost or reduced CD19 expression. This novel biologic, a CAR T Engager, binds CD20 and displays the CD19 extracellular domain. This approach increases the apparent CD19 antigen density on CD19-positive/CD20-positive lymphoma cells, and prevents antigen-loss induced relapse, as CD19 bound to CD20 remains present on the cell surface. We demonstrate that this novel therapeutic prevents and reverses lymphoma relapse <i>in vitro</i> and prevents CD19-negative lymphoma growth and relapse <i>in vivo</i>.
ChemInform Abstract: SYNTH. CYCLISCHER PEPTIDE AN TRAEGERN MIT ZWEIFACHER FUNKTION (1970)

Abstract 4‐Methylthio‐phenol (I) liefert mit Formaldehyd das Polymere (II); p‐Mercaptophenol (III) liefert mit einem chlormethylierten Poly‐styrol‐divinylbenzol (IV) das Polymere (V).
Synthesis and properties of a series of β-cyclodextrin/nitrone spin traps for improved superoxide detection (2017)

Three new DEPMPO-based spin traps have been designed and synthesized for improved superoxide detection, each carrying a cyclodextrin (CD) moiety but with a different alkyl chain on the phosphorus atom or with a long spacer arm. EPR spectroscopy allowed us to estimate the half-life of the superoxide spin adducts which is close to the value previously reported for CD-DEPMPO (t<sub>1/2</sub> ≈ 50-55 min under the conditions investigated). The spectra are typical of superoxide adducts (almost no features of the HO˙ adduct that usually forms with time for other nitrone spin traps such as DMPO) and we show that at 250 μM, the new spin trap enables the reliable detection of superoxide by 1 scan at the position opposite to the corresponding spin trap without the CD moiety. The resistance of the spin adducts to a reduction process has been evaluated, and the superoxide spin adducts are sensitive to ascorbate and glutathione (GSH), but not to glutathione peroxidase/GSH, reflecting the exposed nature of the nitroxide moiety to the bulk solvent. To understand these results, 2D-ROESY NMR studies and molecular dynamics pointed to a shallow or surface self-inclusion of the nitrone spin traps and of nitroxide spin adducts presumably due to the high flexibility of the permethyl-β-CD rim.
Do Amorphous Troglitazones Prepared from Two Diastereomer-Pairs Have the Same Molecular Mobility and Crystallization Rate at the Surface? (2011)

The surface of amorphous compounds crystallizes faster compared to the bulk. This suggests that molecules at the surface have high molecular mobility. Crystallization behavior is affected by various factors including molecular weight and glass transition temperature (T(g)). In this study, we focus on troglitazone which is composed of diastereomers, RR/SS and RS/SR, as model compound, because each diastereomer has the same molecular weight and similar chemical structure. Troglitazone is isolated into each diastereomer, and both amorphous prepared from RR/SS and RS/SR showed similar T(g) (around 60°C). The surface relaxation of each amorphous troglitazone prepared from two diastereomers, RR/SS and RS/SR, was determined to compare surface molecular mobility, using inverse gas chromatography under dry conditions. As a result, amorphous prepared from RS/SR, showed the shorter surface relaxation time at 40°C (temperature below T(g)), which means it has higher molecular mobility than that from RR/SS at the surface although both have the same molecular weight and similar T(g). Microscopy analysis was conducted to observe the crstallization behavior at the surface of amorphous troglitazone in conditions of high temperature and humidity. Micrographs showed that crystallization area at the surface of amorphous prepared from RS/SR, which showed the shorter surface relaxation time, increased faster than that of the amorphous prepared from RR/SS. Although the reason for the difference in the surface relaxation time of each amorphous troglitazone could not be determined, factors such as the difference of configuration might affect the difference.
Angle-etched free-standing photonic crystal nanobeam cavities in single-crystal diamond (2012)

A bulk nanomachining technique to realize suspended photonic structures in diamond is presented. The developed fabrication methodology, employs oxygen plasma etching and yields free-standing nanobeam waveguides and photonic crystal cavities.
Shear band formation and fracture behavior of nanocrystalline (Co,Fe)-based alloys (2010)

The crystal structure, crystallization, fracture behavior and mechanical properties of (Co1 − x Fe x )89Zr7B4 (x = 0–0.7) nanocrystalline ribbons were investigated. The crystallization peaks of the amorphous ribbons tend to shift to higher temperatures with increasing Fe content. After annealing at 475°C for 3600 s, the main crystallization product is hcp-(Co,Fe) for the Co-rich composition (x = 0), bcc-(Co,Fe) for high Fe contents (x ≥ 0.3) and a mix of bcc, and fcc for intermediate compositions (0.025 ≤ x ≤ 0.15). The relative strain at fracture decreases dramatically (εf < 0.01) for x ≥ 0.15, whereas for lower Fe content it has a maximum (εf > 0.037) at x = 0.025 and 0.050 resulting in excellent resistance against fracture. The brittle ribbons (x ≥ 0.15) showed smooth fracture surface with dimples less than 230 nm in diameter, small localized or absent shear bands and large Vickers hardness (>1200 kg mm−2). On the other hand, the Co-rich ribbons with greater ductility (x = 0.025, 0.05) exhibit a vein pattern filled with voids (features ∼2–11 µm), extensive shear banding and lower Vickers hardness (<1050 kg mm−2).
Pickering emulsions with ethiodized oil and nanoparticles for slow release of intratumoral anti-CTLA4 immune checkpoint antibodies (2020)

Pickering emulsions of ethiodized oil and PLGA is an innovative radiopaque delivery platform that does not alter the functionality of anti-CTLA4 immune checkpoint antibodies. Beyond local anti-CTLA4 applications, these emulsions might be used with other therapeutic molecules for optimal intratumorous or intra-arterial delivery of novel cancer immunotherapies.
Optically-addressable spins in hexagonal boron nitride at room temperature (2022)

Optically addressable spins in materials are important platforms for quantum technologies, such as repeaters and sensors. Identification of such systems in two-dimensional (2d) layered materials offers advantages over their bulk counterparts, as their reduced dimensionality enables more feasible on-chip integration into devices. Here, we report room-temperature optically detected magnetic resonance (ODMR) from previously identified carbon-related single defects in 2d hexagonal boron nitride (hBN). We show that single-defect ODMR contrast is up to 100x stronger than that of ensembles and displays a magnetic-field dependence with both positive or negative sign per defect. Further, the ODMR lineshape comprises a doublet resonance, indicating a S=1 state with low but finite zero-field splitting. Our results offer a promising route towards realising a room-temperature spin-photon quantum interface in hexagonal boron nitride.
Auctioning Many Divisible Goods (2004)

We study the theory and practical implementation of auctioning many divisible goods.With multiple related goods, price discovery is important not only to reduce the winner's curse, but more importantly, to simplify the bidder's decision problem and to facilitate the revelation of preferences in the bids.Simultaneous clock auctions are especially desirable formats for auctioning many divisible goods.We examine the properties of these auctions and discuss important practical considerations in applying them.
Powertrain Integration and Controls Development Process for a Parallel Through the Road Plug-in Hybrid Electric Vehicle (2014)

&lt;div class="section abstract"&gt;&lt;div class="htmlview paragraph"&gt;The University of Washington Advanced Vehicle Works team has spent the last two years designing and integrating a Parallel Through The Road (PTTR) PHEV drive system into a stock Chevy Malibu as part of the EcoCAR 2 Advanced Vehicle Technology Competition. This paper presents the integration efforts performed throughout year 2 in an effort to produce a 65% “buyoff ready” prototype vehicle.&lt;/div&gt;&lt;div class="htmlview paragraph"&gt;EcoCAR2 challenges 16 universities across North America to reduce the environmental impact of a 2013 Chevrolet Malibu without compromising consumer acceptability. The architecture chosen by the team to address these goals is a PTTR PHEV which provides all-electric operation to displace petroleum usage, four wheel drive mode to improve utility performance for consumers, and an efficient charge-sustaining mode using 20% biodiesel (B20). The PTTR architecture is the lowest cost architecture to provide all of these benefits, and it does so without compromising the safety or performance of the platform.&lt;/div&gt;&lt;/div&gt;
DNA methylome combined with chromosome cluster-oriented analysis provides an early signature for cutaneous melanoma aggressiveness (2022)

Aberrant DNA methylation is a well-known feature of tumours and has been associated with metastatic melanoma. However, since melanoma cells are highly heterogeneous, it has been challenging to use affected genes to predict tumour aggressiveness, metastatic evolution, and patients' outcomes. We hypothesized that common aggressive hypermethylation signatures should emerge early in tumorigenesis and should be shared in aggressive cells, independent of the physiological context under which this trait arises. We compared paired melanoma cell lines with the following properties: (i) each pair comprises one aggressive counterpart and its parental cell line and (ii) the aggressive cell lines were each obtained from different host and their environment (human, rat, and mouse), though starting from the same parent cell line. Next, we developed a multi-step genomic pipeline that combines the DNA methylome profile with a chromosome cluster-oriented analysis. A total of 229 differentially hypermethylated genes was commonly found in the aggressive cell lines. Genome localization analysis revealed hypermethylation peaks and clusters, identifying eight hypermethylated gene promoters for validation in tissues from melanoma patients. Five Cytosine-phosphate-Guanine (CpGs) identified in primary melanoma tissues were transformed into a DNA methylation score that can predict survival (log-rank test, p=0.0008). This strategy is potentially universally applicable to other diseases involving DNA methylation alterations.