gebhart/patrepeval huggingface dataset:
Functional Characterization of Naturally Occurring Pathogenic Mutations in the Human Leptin Receptor (2008)

We have recently reported the first naturally occurring missense mutations in the leptin receptor (LR) in patients with severe obesity. We have examined the molecular mechanisms by which these extracellular domain mutations disrupt LR signaling. The Ala409Glu mutant receptor is expressed at the cell surface, binds leptin normally but fails to signal to downstream pathways. A409 is present on the surface-exposed region of the Ig-like domain that forms the binding site III for interaction with leptin. This binding site does not appear to contribute to the binding affinity of leptin to its receptor but is critical for receptor activation in response to ligand binding. The Trp664Arg and His684Pro mutations are predicted to impair receptor folding. Both mutants result in a complete inability to signal to downstream pathways despite evidence for some residual cell surface expression and ligand binding. The Arg612His mutant falls in the second subdomain of the high-affinity binding site for leptin, and results in a receptor that shows evidence for intracellular retention but retains some residual signaling. These studies, which represent the first detailed characterization of the functional properties of naturally occurring missense mutations in the human LR, indicate that most such mutations affect receptor folding and expression at the cell surface rather than primarily impairing ligand binding. The exception is Ala409Glu, which interferes with the coupling of ligand binding to receptor activation. Naturally occurring mutations associated with human obesity are valuable tools with which to explore structure/function relationships within the LR.
Optimum design of In0.53Ga0.47As and InP junction field-effect transistors for optoelectronic integrated circuits (1989)

Monolithic integration of photonic devices, such as lasers, modulators, and photodetectors, along with their associated electronic circuitry, are attractive for second-generation photonic systems including optical interconnects, optical computing, signal processing, and communications.1
Towards a global spectral-geomechanical database of volcanic rocks using VNIR-SWIR spectroscopy (2022)

&amp;lt;p&amp;gt;Volcanoes are subject to intense fluid circulation, altering primary rock properties. The rock alteration can be due to &amp;amp;#8220;cold&amp;amp;#8221; water-driven weathering or &amp;amp;#8220;hot&amp;amp;#8221; hydrothermal fluids. Such alteration is facilitated by the efficient circulation of fluids through fractures and the connected pore-network. Fluid-driven alteration can manifest as mineral dissolution and precipitation, ultimately changing the properties of the host rock, such as strength and elasticity. Alteration-induced geomechanical changes are complex due to the large range of protolith porosity (e.g. 0.01-0.8) and permeability (e.g. 10&amp;lt;sup&amp;gt;-10&amp;lt;/sup&amp;gt; to &amp;amp;#8804;10&amp;lt;sup&amp;gt;-18&amp;lt;/sup&amp;gt; m&amp;lt;sup&amp;gt;2&amp;lt;/sup&amp;gt;). For example, fresh pyroclastic rocks can initially have low strength, which can be &amp;amp;#8216;reinforced&amp;amp;#8217; by mineral precipitation. In contrast, dense lava rocks can decrease their strength due to pore space enlargement and development of secondary clays, oxides, sulfides and sulfates.&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;This study analysed lab-tested samples from Ruapehu, Merapi, Whakaari, Chaos Crags, Ohakuri, Styrian Basin and La Soufri&amp;amp;#232;re de Guadeloupe volcanoes to provide new insights into the controls on geomechanical properties due to weathering and hydrothermal alteration. The volcaniclastic and lava rocks range from basaltic to rhyolitic in composition and encompass surface weathering and intermediate and advanced argillic alteration styles. The physical, geomechanical, Visible-Near Infrared (VNIR; 350-1000 nm), and Shortwave Infrared (SWIR; 1000-2500 nm) properties of the rocks were measured on core samples. Porosity, P-wave velocity, and uniaxial compressive strength ranged from 0.02-0.67, 88-5800 m/s, and 0.1-312 MPa, respectively. Partial Least Squares Regression (PLSR) was employed to successfully predict physical and mechanical properties using VNIR-SWIR spectroscopy data. The PLSR-based prediction models highlighted a handful of spectral bands around 400-600 nm, 1400 nm and 2200-2300 nm, indicating that hydrated secondary minerals were responsible for the observed geomechanical changes. The proposed method using VNIR-SWIR spectroscopy can lead to a new way of mapping physical and geomechanical properties at outcrop-scale using field spectrometers, and at volcano-scale using airborne and satellite remote sensing.&amp;lt;/p&amp;gt;
Biomolecular condensates govern PARP inhibitor trapping and present mechanisms of resistance (2022)

ABSTRACT Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi) are a class of cancer drugs that enzymatically inhibit PARP activity at sites of DNA damage. In the context of BRCA mutations, PARPi can be synthetically lethal, presenting ideal genetic targeting. Yet, PARPi function primarily by trapping PARP1 onto sites of DNA damage. How PARPi trap and why some are better trappers remain unknown. Here, we show trapping occurs primarily through a kinetic phenomenon within biomolecular condensates that correlates with PARPi k off . Our results suggest PARP trapping is not the physical stalling of PARP1 on DNA, rather the high probability of PARP re-binding damaged DNA in the absence of other DNA binding protein recruitment. Furthermore, we found recruitment of the DNA binding protein RPA1 correlates to cell line PARPi sensitivity independent of RPA1 expression, demonstrating that condensate recruitment alone can impact efficacy. These results shed new light on how PARPi function, describe how PARPi properties correlate to trapping potency, and suggest previously unknown mechanisms of PARPi resistance.
Pulse thermal processing of functional materials using directed plasma arc (2023)

A method of thermally processing a material includes exposing the material to at least one pulse of infrared light emitted from a directed plasma arc to thermally process the material, the pulse having a duration of no more than 10 s.
SPA: Economical and Workload-Driven Indexing for Data Analytics in the Cloud (2023)

Selective queries are not uncommon in large-scale data analytics, for example, when drilling down into a specific customer in a dashboard. Traditionally, selective queries are accelerated by creating secondary indexes. However, because of their large size, expensive maintenance, and difficulty to tune and automate, indexes are typically not used in modern cloud data warehouses or data lakes. Instead, such systems rely mostly on full table scans and lightweight optimizations like min/max filtering, whose effectiveness depends heavily on the data layout and value distributions.We propose SPA as the vision for automatically optimizing selective queries for immutable copy-on-write data formats. SPA adaptively indexes subsets of the data in an incremental and workload-driven manner. It makes fine-grained decisions and continuously monitors their benefit, dynamically allocating an optimization budget in a way that bounds the additional cost of indexing. Furthermore, it guarantees a performance improvement in the cases where indexes—potentially partial ones—prove to be beneficial. When indexes lose their benefit due to a shifting workload, they are gradually deconstructed in favor of optimizations that accommodate recent trends. As SPA does not require information about updates performed on the data, it can also be employed as an accelerator for systems that do not control the data, e.g., in cloud data lakes.
ChemInform Abstract: The Synthesis of a Rotationally Restricted Phenolic Analog of 5‐Methoxy‐3‐(1,2,5,6‐tetrahydropyrid‐4‐yl)indole (RU‐24,969). (1990)

Abstract The 2‐alkoxy‐5‐nitropyridines (III) are converted into the 6‐cyanomethyl derivatives (V) which are reductively cyclized, forming the 5‐alkoxypyrrolo(3,2‐b)pyridines (VI).
Deregulated expression of p27(Kip1) in human breast cancers. (1997)

Protein complexes composed of cyclins and cyclin-dependent kinases control the orderly progression of mammalian cells through the cell cycle. The p27(Kip1) protein belongs to a family of cyclin-dependent kinase-inhibitory proteins that are negative regulators of cell cycle progression and have been proposed as candidate tumor suppressor genes. However, the p27(Kip1) gene is only rarely mutated in human primary breast carcinomas and breast cancer cell lines. To further address the role of p27(Kip1) in the development of human tumors, we determined by Western blot analysis the levels of expression of the p27(Kip1) protein in a series of human cancer cell lines and found that this protein is expressed at high levels in many of these cell lines, even during exponential growth. The levels of p27(Kip1) were significantly associated with the levels of cyclins D1 and E. In contrast to the high level of p27(Kip1) in breast cancer cell lines, three cell lines established from normal mammary epithelium expressed low levels of this protein. Cell synchronization studies demonstrated deregulation of the expression of p27(Kip1) throughout the cell cycle in two breast cancer cell lines but normal regulation in a normal mammary epithelial cell line. Immunohistochemical studies on p27(Kip1) expression in 52 primary human breast cancers indicated that this protein was also expressed at relatively high levels in 44% of the tumor samples, but it was barely detectable or undetectable in the remaining 56% of the samples. Additional studies are required to determine why some breast cancer cells express relatively high levels of p27(Kip1) despite its known role as an inhibitor of cell cycle progression.
Investigation of microstructural changes in polyetherether-ketone films at cryogenic temperatures by positron lifetime spectroscopy (1991)

Microstructural changes in Polyetherether-ketone (PEEK) films were investigated in the temperature ranges of 23 to -196 C, using Positron Lifetime Spectroscopy (PLS) technique. It was determined that the total free volume decreases by about 46 percent in amorphous PEEK samples and about 36 percent in semicrystalline PEEK samples when they are cooled down from room temperature to liquid nitrogen (LN2) temperature. If this trend in reduction in free volume with decreasing temperature continues, as expected, it is surmised that PEEK will be able to withstand cooling down to liquid hydrogen (LH2) temperature without any detrimental effect on its diffusivity for liquid hydrogen.
Investigation of Coulomb scattering on sSi/Si0.5Ge0.5/sSOI quantum-well p-MOSFETs (2016)

sSi/Si0.5Ge0.5/sSOI quantum-well (QW) p-MOSFETs with HfO2/TiN gate stack were fabricated and characterized. According to the low temperature experimental results, carrier mobility of the strained Si0.5Ge0.5 QW p-MOSFET was mainly governed by phonon scattering from 300 to 150 K and Coulomb scattering below 150 K, respectively. Coulomb scattering was intensified by the accumulated inversion charges in the Si cap layer of this Si/SiGe heterostructure, which led to a degradation of carrier mobility in the SiGe channel, especially at low temperature.
Theoretical analysis of the off-center aperture mirror external cavity laser array (1988)

We present a self-consistent analysis to model and explain the experimental results obtained from laser arrays in the off-center aperture mirror external cavity, which we reported earlier.1 Good agreement is obtained between the calculations and experimental data.
DNA Manipulation and Separation in Sublithographic-Scale Nanowire Array (2013)

Electrokinetic manipulations of biomolecules using artificial nanostructures within microchannels have proven capability for controlling the dynamics of biomolecules. Because there is an inherent spatial size limitation to lithographic technology, especially for nanostructures with a small diameter and high aspect ratio, manipulating a single small biomolecule such as in DNA elongation before nanopore sequencing is still troublesome. Here we show the feasibility for self-assembly of a nanowire array embedded in a microchannel on a fused silica substrate as a means to manipulate the dynamics of a single long T4-DNA molecule and also separate DNA molecules. High-resolution optical microscopy measurements are used to clarify the presence of fully elongated T4-DNA molecules in the nanowire array. The spatial controllability of sublithographic-scale nanowires within microchannels offers a flexible platform not only for manipulating and separating long DNA molecules but also for integrating with other nanostructures to detect biomolecules in methods such as nanopore sequencing.
Photoaffinity labeling of glucosyltransferase of the dolichol cycle from rat mammary gland. (1990)

UDP-Glc:dolichol phosphate glucosyltransferase from lactating rat mammary gland has been partially purified by a combination of (NH4)2SO4 fractionation, gel filtration, ion-exchange chromatography on DEAE-TSK, and affinity chromatography. The partially purified enzyme exhibited several protein bands when examined by 10% sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions; among these, a 35-kDa polypeptide was quite prominent and appeared to be enriched during purification. Photoaffinity labeling of the partially purified enzyme preparation with 5-azido-[beta-32P]UDP-Glc identified a 35-kDa polypeptide. Labeling of a solubilized enzyme preparation from crude and stripped microsomes also revealed a 35-kDa band on 10% sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Photoinsertion of the probe in this polypeptide is enhanced by the presence of dolichol phosphate and Mg2+. Competition studies with UDP-Glc, UDP-glucuronic acid, other sugar nucleotides, and Glc-1-phosphate provide evidence to validate the specificity of photoaffinity labeling. These studies indicate that this 35-kDa polypeptide is involved in the synthesis of dolichol-P-Glc in rat mammary tissue. The possibility that this polypeptide may represent glucosyltransferase has been discussed.
Figure S4 from Cathepsin B Is Dispensable for Cellular Processing of Cathepsin B-Cleavable Antibody–Drug Conjugates (2023)

&lt;p&gt;Supplementary Figure 4: Relative quantitation via mass spectrometry of cathepsin distribution in lysosomal fractions of various cell lines. Methods are detailed under "Isolation of lysosomes and proteomic analysis" in Supplementary Methods.&lt;/p&gt;
Control to Range for Diabetes: Functionality and Modular Architecture (2009)

We believe that the modular control-to-range system is the best approach to incremental development, regulatory approval, industrial deployment, and clinical acceptance of closed-loop control for diabetes.
Quality Characteristics of Southeast Asian Salt-Fermented fish Sauces (2000)

To investigate quality characteristics of southeast asian salt-fermented fish sauces, various chemical properties were examined against 13 kinds of southeast asian salt-fermented fish sauces. The range of chemical compositions were moisture, crude protein and VBN. The pH and salinity were , respectively. Total nitrogen, amino nitrogen, total free amino acid, and total ATP related compounds (sum of , HxR, Hx and uric acid) were in the ranges of , respectively. Southeast asian salt-fermented lish sauces were rich in tree amino acids, such as glutamic acid, Iysine, leucine, alanine, aspartic acid, valine and isoleucine in the order.
A CAVITY-LESS MICROMACHINED CAPACITIVE PRESSURE SENSOR FOR WIRELESS OPERATION IN LIQUID AMBIENT (2008)

This paper reports a micromachined capacitive pressure sensor that does not use the traditional cavity and diaphragm, and its use in aqueous environment.
Safety and performance analysis of acriflavine and methylene blue for in vivo imaging of precancerous lesions using fibered confocal fluorescence microscopy (FCFM): an experimental study (2015)

Methylene blue can be used safely to image precancerous lesions in vivo. This study does not support the use of acriflavine in humans.
Fiber Optic Intrusion Sensor using Coherent Optical Time Domain Reflectometer (2003)

The optical fiber intrusion sensor using coherent optical time domain reflectometer is studied. The configuration of the sensor is an optical time domain reflectometer using coherent interference of Rayleigh backscattering in a single-mode fiber. When a certain part of the fiber is subjected to a perturbation, the localized intensity variation is induced at a time corresponding to the location of perturbation and the signal-to-noise ratio is about 3.3.
Machine Learning-Enabled Joint Antenna Selection and Precoding Design: From Offline Complexity to Online Performance (2021)

We investigate the performance of multi-user multiple-antenna downlink systems in which a BS serves multiple users via a shared wireless medium. In order to fully exploit the spatial diversity while minimizing the passive energy consumed by radio frequency (RF) components, the BS is equipped with M RF chains and N antennas, where M &lt; N. Upon receiving pilot sequences to obtain the channel state information, the BS determines the best subset of M antennas for serving the users. We propose a joint antenna selection and precoding design (JASPD) algorithm to maximize the system sum rate subject to a transmit power constraint and QoS requirements. The JASPD overcomes the non-convexity of the formulated problem via a doubly iterative algorithm, in which an inner loop successively optimizes the precoding vectors, followed by an outer loop that tries all valid antenna subsets. Although approaching the (near) global optimality, the JASPD suffers from a combinatorial complexity, which may limit its application in real-time network operations. To overcome this limitation, we propose a learning-based antenna selection and precoding design algorithm (L-ASPA), which employs a DNN to establish underlaying relations between the key system parameters and the selected antennas. The proposed L-ASPD is robust against the number of users and their locations, BS's transmit power, as well as the small-scale channel fading. With a well-trained learning model, it is shown that the L-ASPD significantly outperforms baseline schemes based on the block diagonalization and a learning-assisted solution for broadcasting systems and achieves higher effective sum rate than that of the JASPA under limited processing time. In addition, we observed that the proposed L-ASPD can reduce the computation complexity by 95% while retaining more than 95% of the optimal performance.
Very-High Energy Electron (VHEE) Studies at CERN's CLEAR User Facility (2018)

Here we investigate how inserts of various densities (0.001-2.2 g/cm³) affect the dose distribution properties of VHEE beams at ~150 MeV. A range variation comparison was also made with clinical proton beams using TOPAS/GEANT4 Monte Carlo simulations. In addition, we assess the viability of scattering foils for optimizing the size of VHEE beams for radiotherapy purposes. The experiments were conducted at CERN's CLEAR user facility.
TwHIN-BERT: A Socially-Enriched Pre-trained Language Model for Multilingual Tweet Representations at Twitter (2022)

Pre-trained language models (PLMs) are fundamental for natural language processing applications. Most existing PLMs are not tailored to the noisy user-generated text on social media, and the pre-training does not factor in the valuable social engagement logs available in a social network. We present TwHIN-BERT, a multilingual language model productionized at Twitter, trained on in-domain data from the popular social network. TwHIN-BERT differs from prior pre-trained language models as it is trained with not only text-based self-supervision, but also with a social objective based on the rich social engagements within a Twitter heterogeneous information network (TwHIN). Our model is trained on 7 billion tweets covering over 100 distinct languages, providing a valuable representation to model short, noisy, user-generated text. We evaluate our model on various multilingual social recommendation and semantic understanding tasks and demonstrate significant metric improvement over established pre-trained language models. We open-source TwHIN-BERT and our curated hashtag prediction and social engagement benchmark datasets to the research community.
Multilevel system optimisation via nonlinearity management (2006)

Nonlinearity management is explored as a multilevel tool to obtain maximum transmission reach in a WDM system. A technique for the fast calculation of the optimal dispersion pre-compensation in systems with distributed amplification is proposed.
Terahertz radiation using log-spiral-based low-temperature-grown InGaAs photoconductive antenna pumped by mode-locked Yb-doped fiber laser (2016)

We demonstrate a terahertz (THz) radiation using log-spiral-based low-temperature-grown (LTG) InGaAs photoconductive antenna (PCA) modules and a passively mode-locked 1030 nm Yb-doped fiber laser. The passively mode-locked Yb-doped fiber laser is easily implemented with nonlinear polarization rotation in the normal dispersion using a 10-nm spectral filter. The laser generates over 250 mW of the average output power with positively chirped 1.58 ps pulses, which are dechirped to 127 fs pulses using a pulse compressor outside the laser cavity. In order to obtain THz radiation, a home-made emitter and receiver constructed from log-spiral-based LTG InGaAs PCA modules were used to generate and detect THz signals, respectively. We successfully achieved absorption lines over 1.5 THz for water vapor in free space. Therefore, we confirm that a mode-locked Yb-doped fiber laser has the potential to be used as an optical source to generate THZ waves.
The characterization of Mediator 12 and 13 as conditional positive gene regulators in Arabidopsis (2020)

Mediator 12 (MED12) and MED13 are components of the Mediator multi-protein complex, that facilitates the initial steps of gene transcription. Here, in an Arabidopsis mutant screen, we identify MED12 and MED13 as positive gene regulators, both of which contribute broadly to morc1 de-repressed gene expression. Both MED12 and MED13 are preferentially required for the expression of genes depleted in active chromatin marks, a chromatin signature shared with morc1 re-activated loci. We further discover that MED12 tends to interact with genes that are responsive to environmental stimuli, including light and radiation. We demonstrate that light-induced transient gene expression depends on MED12, and is accompanied by a concomitant increase in MED12 enrichment during induction. In contrast, the steady-state expression level of these genes show little dependence on MED12, suggesting that MED12 is primarily required to aid the expression of genes in transition from less-active to more active states.