gebhart/patrepeval huggingface dataset:
Pipecolic esters as minimized templates for proteasome inhibition (2019)

Allosteric regulators of clinically important enzymes are gaining popularity as alternatives to competitive inhibitors. This is also the case for the proteasome, a major intracellular protease and a target of anti-cancer drugs. All clinically used proteasome inhibitors bind to the active sites in catalytic chamber and display a competitive mechanism. Unfortunately, inevitable resistance associated with this type of inhibition drives the search for non-competitive agents. The multisubunit and multicatalytic "proteolytic machine" such as the proteasome is occasionally found to be affected by agents with other primary targets. For example the immunosuppressive agent rapamycin has been shown to allosterically inhibit the proteasome albeit at levels far higher than its mTOR related efficacy. As part of an ongoing program to search for novel proteasome-targeting pharmacophores, we identified the binding domain of rapamycin as required for proteasome inhibition even without the macrocyclic context of the parent compound. By subsequent structure-activity relationship studies, we generated a pipecolic ester derivative compound 3 representing a new class of proteasome inhibitors. Compound 3 affects the core proteasome activities and proliferation of cancer cells with low micromolar/high nanomolar efficacy. Molecular modeling, atomic force microscopy imaging and biochemical data suggest that compound 3 binds into one of intersubunit pockets in the proteasomal α ring and destabilizes the α face and the gate. The α face is used as a docking area for proteasome-regulating protein modules and the gate is critical for controlling access to the catalytic chamber. Thus, the pipecolic ester template elicits a new and attractive mechanism for proteasome inhibition distinct from classical competitive drugs.
Developmental abnormalities and epimutations associated with DNA hypomethylation mutations. (1996)

A number of aberrant morphological phenotypes were noted during propagation of the Arabidopsis thaliana DNA hypomethylation mutant, ddm1, by repeated self-pollination. Onset of a spectrum of morphological abnormalities, including defects in leaf structure, flowering time, and flower structure, was strictly associated with the ddm1 mutations. The morphological phenotypes arose at a high frequency in selfed ddm1 mutant lines and some phenotypes became progressively more severe in advancing generations. The transmission of two common morphological trait syndromes in genetic crosses demonstrated that the phenotypes are caused by heritable lesions that develop in ddm1 mutant backgrounds. Loss of cytosine methylation in specific genomic sequences during the selfing regime was noted in the ddm1 mutants. Potential mechanisms for formation of the lesions underlying the morphological abnormalities are discussed.
Secukinumab for Long‐Term Treatment of Psoriatic Arthritis: A Two‐Year Followup From a Phase III, Randomized, Double‐Blind Placebo‐Controlled Study (2016)

Secukinumab provided sustained improvements in PsA at 2 years, with very little radiographic progression. Treatment was well tolerated over the long term.
Label-free assessment of mitochondrial organization in three-dimensional tissues (2014)

A Fourier-based method can be used to analyze endogenous NADH two-photon excited fluorescence images to characterize quantitatively mitochondrial organization. This optical biomarker is sensitive to metabolic changes that may occur at the onset of disease.
Results and Analysis of Using the MEDLL Receiver as a Multipath Meter (2000)

The Multipath Estimating Delay-Lock-Loop (MEDLL) is
a method for mitigating the effects due to multipath
within the receiver tracking loops. Recently the MEDLL
receiver was modified to output the multipath
parameters, hence the name ‘Multipath Meter’. These
parameters include the delay, relative amplitude, and
phase of the multipath signal along with the residual
values for each correlator. The multipath parameters are estimated by the MEDLL and the residuals indicate the quality estimation process. 
This paper investigates how the Multipath Meter can be used in real-time monitoring of the GPS signal. Using a GPS simulator the MEDLL receiver is tested to determine how accurately the multipath parameters can be measured. Also, data is collected from an antenna location on the roof of the NovAtel facility at Calgary, Alberta, Canada. Two specific situations are focused on: short delay and long delay multipath. Results show that the Multipath Meter is useful for signal quality monitoring and reference site surveys.
An optical multiple indicator dilution technique to measure lung permeability-surface area: calibration and baseline measurement (1995)

A device was designed to measure the change in optical density (/spl Delta/OD) of blood at selected wavelengths as a function of the concentration of optically absorbing multiple indicator dilution (MID) tracers. The optical MID (OMID) tracers selected for this measurement device and their corresponding wavelengths are the following: indocyanine green(ICG)-bound albumin measured at 820 nm, sulfhemoglobinated erythrocytes (Shb-RBC's) measured at 620 nm, and 1,2-propanediol measured at 9.55 /spl mu/m. Arterial blood from cannulated anesthetized dogs was circulated through an extracorporeal flow-through circuit which included this /spl Delta/OD measurement device. Calibration of the 820 nm and 620 nm channels produced r/sup 2/ of greater than 0.95 for the optical density-tracer mass regressions. The propanediol measurement channel (9.55 /spl mu/m) was also linearly calibrated. An in vivo optical MID study was performed and compared to a radioisotope MID study. Lung vascular permeability-surface area (PS) values calculated using the two methods were 5.76 and 5.73 mL/s. It is concluded that this OMID technique is an acceptable alternative to radioisotope MID studies.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Surface modification and biotribological behavior of <scp>UHMWPE</scp> nanocomposites with <scp>GO</scp> infiltrated by ultrasonic induction (2020)

In this study, we have innovatively proposed a method for surface modification of ultra-high molecular weight polyethylene (UHMWPE) artificial joint materials with graphene oxide (GO) infiltrated into UHMWPE substrate by ultrasonic induction. The mechanical properties of UHMWPE nanocomposites with GO infiltrated by ultrasonic induction were compared with that of GO mixed. The molecular structure, wettability, peak load, and bio-tribological behavior of GO/UHMWPE nanocomposites were studied using fourier transform infrared spectroscopy, contact angle measuring instrument, electronic universal material testing machine, tribometer, and profilometer, respectively. The results show that the ultrasonic-induction method can make GO adhere to UHMWPE surface well, and GO can significantly improve the wettability of UHMWPE substrate. When the ultrasound-inducted time is up to 12 hr, the wetting angle of the nanocomposites (12 h-GO/UHMWPE) is reduced to 65.24°, which is 20.51% lower than that of the pure UHMWPE. The peak load is 183 N, which is 20.22% higher than that of GO/UHMWPE prepared by the mixing method. The bio-tribological property of UHMWPE nanocomposites with GO infiltrated by ultrasonic induction for 12 hr (12 h-GO/UHMWPE) is the best, and its friction coefficient keeps more stable at a value of 0.0605 under the lubrication of calf serum, which is 11.81% lower than that of UHMWPE mixed with GO by a traditional method, and the wear rate is decreased to 3.25 × 10<sup>-5</sup> mm<sup>3</sup> N<sup>-1</sup> m<sup>-1</sup> .
2-Deoxystreptamine-containing aminoglycoside antibiotics: Recent advances in the characterization and manipulation of their biosynthetic pathways (2012)

The 2-deoxystreptamine-containing aminoglycosides, such as neomycin, kanamycin and gentamicin, are an important class of antibiotics. A detailed understanding of the complete biosynthetic pathway of aminoglycosides and their biosynthetic enzymes will allow us to not only generate more robust antibiotic agents or drugs with other altered biological activities, but also to produce clinically important semi-synthetic antibiotics by direct fermentation. This Highlight focuses on recent advances in the characterization of their biosynthetic enzymes and pathway as well as some chemo-enzymatic and metabolic engineering approaches for the biological production of natural, semi-synthetic, and novel aminoglycosides.
Improved Modulation Schemes for Lattice-Partition-Based Downlink Non-Orthogonal Multiple Access Systems (2020)

This letter proposes alternative modulation schemes for a two-user lattice-partition-based non-orthogonal multiple access (NOMA) system, where the NOMA transmission signal is composed of four elements from four amplitude-level groups, respectively, instead of two elements from two amplitude-level groups in the conventional method. Each user's message is split into most significant bits (MSBs) and least significant bits (LSBs), with the MSBs modulated at one of the higher-level groups and the LSBs modulated at one of the lower-level groups to meet the NOMA principle. Both analysis and simulation results show that the proposed schemes offer higher system capacity than the conventional method.
Identification ofPKD2L,a HumanPKD2-Related Gene: Tissue-Specific Expression and Mapping to Chromosome 10q25 (1998)

Mutations in PKD2 cause autosomal dominant kidney disease (ADPKD). Polycystin-2, the PKD2 gene product, is an integral membrane glycoprotein of unknown function. We have identified PKD2L, another member of the PKD2 gene family. PKD2L is expressed in adult heart and skeletal muscle, brain, spleen, testis, and retina, and alternative transcripts of 2.4, 2.7, and 3.0 kb are seen. PKD2L shows 56% identity and 76% similarity with polycystin-2 over a 581-amino-acid span; however, the COOH-terminal 65 residues of PKD2L are unrelated to PKD2. PKD2L is localized to chromosome 10q25 and is excluded as a candidate gene for autosomal recessive polycystic kidney disease, autosomal dominant polycystic liver disease, and the third form of ADPKD. Given the high degree of homology between PKD2L and PKD2, it is likely that the respective functions of these proteins are also closely related.
Deuterated L-arginine phosphate: a new efficient nonlinear crystal (1989)

Deuterated L-arginine phosphate (d-LAP) is a highly transparent monoclinic crystal with attractive properties for efficient frequency conversion. It is grown easily from aqueous solution, and it is phase-matchable for all nonlinear processes where KDP is phase-matchable. Over most of its usable frequency range, it is substantially more efficient than KDP. Crystals grown in large sizes (100 cm/sup 3/) have a high damage threshold, excellent optical quality, are less hygroscopic than KDP, and are easily fabricated into nonlinear devices. Deuterated LAP is attractive for harmonic generation of Nd lasers and for work in the ultraviolet down to about 250 nm.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
<scp>d</scp> -Serine is an endogenous ligand for the glycine site of the <i>N</i> -methyl- <scp>d</scp> -aspartate receptor (2000)

Functional activity of N-methyl-D-aspartate (NMDA) receptors requires both glutamate binding and the binding of an endogenous coagonist that has been presumed to be glycine, although D-serine is a more potent agonist. Localizations of D-serine and it biosynthetic enzyme serine racemase approximate the distribution of NMDA receptors more closely than glycine. We now show that selective degradation of d-serine with D-amino acid oxidase greatly attenuates NMDA receptor-mediated neurotransmission as assessed by using whole-cell patch-clamp recordings or indirectly by using biochemical assays of the sequelae of NMDA receptor-mediated calcium flux. The inhibitory effects of the enzyme are fully reversed by exogenously applied D-serine, which by itself did not potentiate NMDA receptor-mediated synaptic responses. Thus, D-serine is an endogenous modulator of the glycine site of NMDA receptors and fully occupies this site at some functional synapses.
Development of a Water Hydraulic Servovalve. (1998)

An electrohydraulic servovalve that uses fresh water as a pressure medium(water hydraulic servovalve)is developed. A conventional electrohydraulic servovalve cannot be operated with such a hostile fluid. In this paper, we explain the structure and functions of components, and the relationship between them, as well as the developmental procedure of the water hydraulic servovalve. The basic idea for the servovalve is to support the spool of the valve with hydrostatic bearings and to lead the water from the bearings to the flapper-nozzle system. The hydrostatic bearings constitute a laminar restriction that takes the place of the turbulent restriction in the conventional flapper-nozzle system. We also explain the design procedure of the hydrostatic bearing in the valve and the relationship between electromagnetic elements and fluidic elements. The water hydraulic servovalves fabricated show good characteristics of smooth motion, endurance and controllability, as well as good dynamic characteristics.
<title>B-Si masks for storage ring X-ray lithography</title> (1984)

The fabrication of masks used in storage ring X-ray lithography is described. These masks consist of a gold absorber electroplated over a substrate formed by a thin boron-doped silicon membrane covered by a layer of polyimide. Measurement of the properties of the materials which are of concern in this application is also described.
alpha-Amylase from the Hyperthermophilic Archaebacterium Pyrococcus furiosus (1993)

In this article, Anfinsen, et al, reported that while trying to study the factors that influenced protein thermostability, or the ability to remain stable at relatively high temperatures, they had cloned a gene from the hyperthermophilic bacterium Pyrococcus furiosus encoded with a highly thermostable alpha-amylase and expressed it in Escherichia Coli. The alpha-amylase expressed in E. Coli exhibited the temperature-dependent activation characteristic of the original enzyme from P. furiosus, but had a higher apparent molecular weight that was attributed to the improper formation of the native quaternary structure.
An efficient vaccine against bovine leukemia virus (2015)

Previous attempts to produce a vaccine against BLV faced problems of efficacy (i.e. only a fraction of animals were protected), persistence (i.e. rapid decrease of immune protection), cost (e.g. production of purified proteins) or safety (e.g. genetically modified hybrid viruses). We have designed a novel strategy based on the use of a live-attenuated BLV provirus. The rationale behind this strategy relies on the deletion of genes required to induce pathogenesis maintaining integrity of those involved in infectivity. We have identified a BLV deleted provirus that is infectious in cattle but replicates at reduced levels in cows as shown by real-time quantitative PCR. The deletant elicits a strong anti-BLV immune response as indicated by wild-type antibody titers. Vaccinated animals but not uninfected controls resist challenge by a wild type BLV virus. The deletant does not spread to uninfected sentinels maintained during 5 years in the same herd supporting biosafety of the vaccine. Passive immunity, but not viral infection, is transmitted to the newborn calves via the maternal colostrum. Assays regarding production, storage and delivery of the vaccine, as well as safety of the milk produced by vaccinated cows are currently being carried out with the aim to start a large scale trial that will be held in Argentina in real dairy conditions during this year.

# Poster award winner - 3rd place
Direct writing of fiber optic components in photonic crystal fibers and other specialty fibers (2016)

Femtosecond direct laser writing has recently shown great potential for the fabrication of complex integrated devices in the cladding of optical fibers. Such devices have the advantage of requiring no bulk optical components and no breaks in the fiber path, thus reducing the need for complicated alignment, eliminating contamination, and increasing stability. This technology has already found applications using combinations of Bragg gratings, interferometers, and couplers for the fabrication of optical filters, sensors, and power monitors. The femtosecond laser writing method produces a local modification of refractive index through non-linear absorption of the ultrafast laser pulses inside the dielectric material of both the core and cladding of the fiber. However, fiber geometries that incorporate air or hollow structures, such as photonic crystal fibers (PCFs), still present a challenge since the index modification regions created by the writing process cannot be generated in the hollow regions of the fiber. In this work, the femtosecond laser method is used together with a pre-modification method that consists of partially collapsing the hollow holes using an electrical arc discharge. The partial collapse of the photonic band gap structure provides a path for femtosecond laser written waveguides to couple light from the core to the edge of the fiber for in-line power monitoring. This novel approach is expected to have applications in other specialty fibers such as suspended core fibers and can open the way for the integration of complex devices and facilitate miniaturization of optical circuits to take advantage of the particular characteristics of the PCFs.
Anticancer activity of farnesyltransferase and geranylgeranyltransferase i inhibitors: prospects for drug development (1997)

Inhibition of farnesyltransferase (FTase) has been thoroughly investigated as a strategy to discover novel anticancer drugs because the oncoprotein Ras, requires farnesylation for its cancer-causing activity. Several highly potent and selective FTase inhibitors have been made and show excellent antitumour activity against human tumours in animal models without toxicity to normal cells. However, resistance of the most frequently mutated form of Ras, K-Ras, to FTase inhibitors and its alternative prenylation by geranylgeranyltransferase I (GGTase I), has cast doubts on whether K-Ras is the target for FTase inhibitors. This monthly update focuses on issues of critical importance to the further development of FTase inhibitors as anticancer agents. Alternative prenylation of K-Ras by GGTase I as a mechanism of resistance to FTase inhibitors, targets for FTase inhibitors other than K-Ras and the relevance of GGTase I inhibitors as antitumour agents will be discussed.
Economic benefits of optical transport layer reconfigurability and tighter coupling with the service layer (2004)

With the introduction of fast reconfigurable optical node elements and automatic configurability via signaling, the optical transport layer has become a very dynamic entity. This agility enables capital and operational savings, e.g., due to more efficient utilization of in-place resources, as well as new revenue generating service opportunities, like bandwidth on demand. Additionally, there can be substantial benefits in using the optical layer for restoration. We examine the benefits of optical layer dynamic reconfigurability, especially when there is greater coupling between a packet data service layer (taken here to be IP/MPLS for concreteness) and optical transport layer. We compare failure restoration using only the service layer to various alternatives involving the transport layer, with and without optical layer reconfigurability. We also consider orchestrated restoration between the data and optical transport layers, and propose a joint restoration mechanism. In single-layer restoration paradigms, we find that IP layer restoration is more cost-effective at lower aggregate traffic levels for link failures but, as traffic scales, optical layer restoration is more cost-effective. In multilayer protection paradigms, we find that overlaying joint router protection on transport layer link protection permits strong synergy of protection capacity reuse, thus leading to significant cost savings for operators.
300 Gb/s bidirectional fiber-coupled optical transceiver module based on 24 TX + 24 RX "holey" CMOS IC (2011)

A novel, compact 48-channel optical transceiver module has been designed and fabricated based on a "holey" Optochip - a single-chip CMOS transceiver IC with 24 receiver and 24 laser driver circuits each with a corresponding throughsubstrate optical via (hole). The holes enable 24-channel 850-nm VCSEL and photodiode arrays to be directly flip-chip soldered to the CMOS IC to maximize high-speed performance and facilitate direct fiber-coupling to a standard 4 x 12 MMF array. The Optochips were packaged into complete modules by flip-chip soldering to high-density, high-speed organic carriers. All 48-channels showed good performance up to 12.5 Gb/s/ch providing a 300 Gb/s bidirectional aggregate data rate.
Synthesis of color-tunable Cu–In–Ga–S solid solution quantum dots with high quantum yields for application to white light-emitting diodes (2012)

Synthesis and application of I–III–VI type Cu–In–Ga–S (CIGS) quantum dots (QDs) with varied In : Ga ratios to a white light-emitting diode (LED) are reported. The band gap and emission energies of CIGS QDs are found to be systematically higher with increasing Ga content as a result of an appropriate formation of CIS–CGS solid solution. ZnS shell-capped QDs of the CIGS/ZnS core–shell emit quite tunable wavelengths of 520–578 nm with exceptionally high photoluminescence quantum yield of 72–83%, depending on the composition. By combining highly fluorescent CIGS/ZnS QDs as color converters with a blue-emitting LED, efficient white QD-based LEDs with high luminous efficacies of 69.1–75.0 lm W−1 at a forward current of 20 mA are fabricated. A white QD-LED with an enhanced color rendering property is further developed by choosing and blending two kinds of CIGS/ZnS QDs, and its electroluminescent properties are characterized in detail as a function of applied current.
A framework for migrating production snapshots of composite applications to virtualized environments (2011)

Migrating production applications from physical datacenters to a virtualized environment is becoming essential to reduce operational costs. In order to avoid direct access to production systems, migration from disk snapshots is preferable. Model based migration approaches are not suitable for this purpose since they need to perform configuration discovery on production systems. Recent approaches that rely upon an isolated network require special setup and are limited to handling network configurations only. In this paper we present a framework for instantiating an application from disk snapshots in a virtualized environment. Our approach comprises of formally specifying the knowledge about product configurations and compiling the knowledge into a plan. The plan is capable of discovering application configurations in an inconsistent configuration setup. A key feature of our framework is that knowledge is specified once per product and re-used across applications that use the product. We have implemented a prototype of our approach and evaluated it on a real world application. The evaluation demonstrates the feasibility of our approach for migration using disk snapshots.