gebhart/patrepeval huggingface dataset:
Training set optimization under population structure in genomic selection (2014)

Population structure must be evaluated before optimization of the training set population. Maximizing the phenotypic variance captured by the training set is important for optimal performance. The optimization of the training set (TRS) in genomic selection has received much interest in both animal and plant breeding, because it is critical to the accuracy of the prediction models. In this study, five different TRS sampling algorithms, stratified sampling, mean of the coefficient of determination (CDmean), mean of predictor error variance (PEVmean), stratified CDmean (StratCDmean) and random sampling, were evaluated for prediction accuracy in the presence of different levels of population structure. In the presence of population structure, the most phenotypic variation captured by a sampling method in the TRS is desirable. The wheat dataset showed mild population structure, and CDmean and stratified CDmean methods showed the highest accuracies for all the traits except for test weight and heading date. The rice dataset had strong population structure and the approach based on stratified sampling showed the highest accuracies for all traits. In general, CDmean minimized the relationship between genotypes in the TRS, maximizing the relationship between TRS and the test set. This makes it suitable as an optimization criterion for long-term selection. Our results indicated that the best selection criterion used to optimize the TRS seems to depend on the interaction of trait architecture and population structure.
Targeted Degradation of Oncogenic KRAS <sup>G12C</sup> by VHL-Recruiting PROTACs (2020)

KRAS is mutated in ∼20% of human cancers and is one of the most sought-after targets for pharmacological modulation, despite having historically been considered "undruggable." The discovery of potent covalent inhibitors of the KRAS<sup>G12C</sup> mutant in recent years has sparked a new wave of interest in small molecules targeting KRAS. While these inhibitors have shown promise in the clinic, we wanted to explore PROTAC-mediated degradation as a complementary strategy to modulate mutant KRAS. Herein, we report the development of LC-2, the first PROTAC capable of degrading endogenous KRAS<sup>G12C</sup>. LC-2 covalently binds KRAS<sup>G12C</sup> with a MRTX849 warhead and recruits the E3 ligase VHL, inducing rapid and sustained KRAS<sup>G12C</sup> degradation leading to suppression of MAPK signaling in both homozygous and heterozygous KRAS<sup>G12C</sup> cell lines. LC-2 demonstrates that PROTAC-mediated degradation is a viable option for attenuating oncogenic KRAS levels and downstream signaling in cancer cells.
Dehydroepiandrosterone-Induced Peroxisome Proliferation in the Rat: Evaluation of Sex Differences (1994)

Dehydroepiandrosterone (DHEA) is a newly identified peroxisome proliferator that causes hepatomegaly, peroxisome proliferation, and induction of peroxisome-associated enzymes in rats and mice, and hepatocellular carcinomas in rats. In the present study, we have systematically analyzed sex differences and the effect of castration on DHEA-induced peroxisome proliferation in male and female rats, since no information is available on this subject. DHEA was fed in diet at a concentration of 0.45% for 2 weeks and livers were analyzed for hepatomegaly, peroxisome volume density, peroxisome proliferator associated Mr 80,000 polypeptide (PPA-80), and enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase (PBE) mRNA. Both intact and castrated rats showed similar response to DHEA characterized by increased peroxisome volume density, PBE mRNA, and PPA-80. Significant difference was observed in the liver weights between castrated and intact animals in both the sexes. Castrated rats that received DHEA had 20%-30% more liver weight than DHEA-administered intact rats. These results clearly indicate that peroxisome proliferative effect of DHEA is not influenced by sex hormones and it is equally potent in both males and females.
Double heterostructure Pb1-<i>x</i>Sn<i>x</i> Te–PbTe lasers with cw operation at 77 K (1974)

Diode lasers that operate cw at 77 K have been made from a Pb0.88Sn0.12 Te–PbTe double heterostructure grown by liquid phase epitaxy. Junction diffusion during growth has been prevented by the use of Tl-doped PbTe substrates. The wavelength emitted in cw operation has been temperature tuned from 10.5 μm at 12 K to less than 8.2 μm at 80 K, a range of nearly 280 cm−1. The cw threshold current density increases from 1.6 × 103 A/cm2 at 12 K to 4.2 × 103 A/cm2 at 77 K. The measured cw power is 10 mW in four modes at 12 K (1.8 × 104 A/cm2) and 1.2 mW in a single mode at 77 K (7.5 × 103 A/cm2).
The use of radio-collars for monitoring wildlife diseases: a case study from Iberian ibex affected by Sarcoptes scabiei in Sierra Nevada, Spain (2013)

We report, for the first time, the successful use of radio collars for wildlife diseases monitoring using Iberian ibex/S. scabiei as a model. By using radio collars we documented that most of the Sarcoptes-infected Iberian ibex are resistant to this disease, and we estimated the average time for Iberian ibex recovering from mange infection and the average survival time of the non-resistant ones. We expect wider use of radio-collars for wild animals diseases monitoring, affected/not-affected animals interaction, and treatment efficacy, among others.
Discrete time techniques for time delay estimation (1993)

Basic aspects of time delay estimation (TDE) based on sampled signals are investigated. The direct cross-correlation method is analyzed and compared to the average square difference function (ASDF) and the (addition only based) average magnitude difference function (AMDF) estimators, Their relative accuracy is theoretically evaluated, and previous empirical results are explained. It is shown that both the ASDF- and the AMDF-based estimators outperform the direct cross-correlation based estimator for medium-high signal-to-noise ratios. Moreover, the AMDF-based estimator, which avoids any multiplications, significantly reduces the computational complexity of the estimation procedure while offering only a moderate performance loss with respect to the ASDF based estimator.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Antigen‐specific blocking of CD4‐Specific immunological synapse formation using BPI and current therapies for autoimmune diseases (2011)

In this review, we discuss T-cell activation, etiology, and the current therapies of autoimmune diseases (i.e., MS, T1D, and RA). T-cells are activated upon interaction with antigen-presenting cells (APC) followed by a "bull's eye"-like formation of the immunological synapse (IS) at the T-cell-APC interface. Although the various disease-modifying therapies developed so far have been shown to modulate the IS and thus help in the management of these diseases, they are also known to present some undesirable side effects. In this study, we describe a novel and selective way to suppress autoimmunity by using a bifunctional peptide inhibitor (BPI). BPI uses an intercellular adhesion molecule-1 (ICAM-1)-binding peptide to target antigenic peptides (e.g., proteolipid peptide, glutamic acid decarboxylase, and type II collagen) to the APC and therefore modulate the immune response. The central hypothesis is that BPI blocks the IS formation by simultaneously binding to major histocompatibility complex-II and ICAM-1 on the APC and selectively alters the activation of T cells from T(H)1 to T(reg) and/or T(H)2 phenotypes, leading to tolerance.
Repair synthesis by human cell extracts in cisplatin damaged DNA is preferentially determined by minor adducts (1992)

During reaction of cis-diamminedichloroplatinum(II) (cis-DDP) with DNA, a number of adducts are formed which may be discriminated by the excision-repair system. An in vitro excision-repair assay with human cell-free extracts has been used to assess the relative repair extent of monofunctional adducts, intrastrand and interstrand cross-links of cis-DDP on plasmid DNA. Preferential removal of cis-DDP 1,2-intrastrand diadducts occurred in the presence of cyanide ions. In conditions where cyanide treatment removed 85% of total platinum adducts while approximately 70% of interstrand cross-links remained in plasmid DNA, no significant variation in repair synthesis by human cell extracts was observed. Then, we constructed three types of plasmid DNA substrates containing mainly either monoadducts, 1,2-intrastrand cross-links or interstrand cross-links lesions. The three plasmid species were modified in order to obtain the same extent of total platinum DNA adducts per plasmid. No DNA repair synthesis was detected with monofunctional adducts during incubation with human whole cell extracts. However, a two-fold increase in repair synthesis was found when the proportion of interstrand cross-links in plasmid DNA was increased by 2-3 fold. These findings suggest that (i) cis-DDP 1,2-intrastrand diadducts are poorly repaired by human cell extracts in vitro, (ii) among other minor lesions potentially cyanide-resistant, cis-DDP interstrand cross-links represent a major lesion contributing to the repair synthesis signal in the in vitro assay. These results could account for the drug efficiency in vivo.
Phosphorylation of a Ras-related GTP-binding protein, Rap-1b, by a neuronal Ca2+/calmodulin-dependent protein kinase, CaM kinase Gr. (1991)

A neuron-specific Ca2+/calmodulin-dependent protein kinase, CaM kinase Gr, phosphorylates selectively a Ras-related GTP-binding protein (Rap-1b) that is enriched in brain tissue. The phosphorylation reaction achieves a stoichiometry of about 1 and involves a serine residue near the carboxyl terminus of the substrate. Both CaM kinase Gr and cAMP-dependent protein kinase, but not CaM kinase II, phosphorylate identical or contiguous serine residues in Rap-1b. The rate of phosphorylation of Rap-1b by CaM kinase Gr is enhanced following autophosphorylation of the protein kinase. Other low molecular weight GTP-binding proteins belonging to the Ras superfamily, including Rab-3A, Rap-2b, and c-Ha-ras p21, are not phosphorylated by CaM kinase Gr. The phosphorylation of Rap-1b itself can be reversed by an endogenous brain phosphoprotein phosphatase. These observations provide a potential connection between a neuronal Ca2(+)-signaling pathway and a specific low molecular weight GTP-binding protein that may regulate neuronal transmembrane signaling, vesicle transport, or neurotransmitter release.
A Microfluidic Biomaterial (2005)

We report on the incorporation of microfluidic structure within a high-water-content hydrogel [4% (w/v) calcium alginate]. We used the microfluidic network to control the chemical environment within the hydrogel and demonstrated higher rates of delivery and extraction of solutes than was achievable by diffusion alone.
The Modula--3 type system (1989)

This paper presents an overview of the programming language Modula-3, and a more detailed description of its type system.
A patient-specific visualization tool for comprehensive analysis of coronary CTA and perfusion MRI data (2011)

Cardiac magnetic resonance perfusion imaging (CMR) and computed tomography angiography (CTA) are widely used to assess heart disease. CMR is used to measure the global and regional myocardial function and to evaluate the presence of ischemia; CTA is used for diagnosing coronary artery disease, such as coronary stenoses. Nowadays, the hemodynamic significance of coronary artery stenoses is determined subjectively by combining information on myocardial function with assumptions on coronary artery territories. As the anatomy of coronary arteries varies greatly between individuals, we developed a patient-specific tool for relating CTA and perfusion CMR data. The anatomical and functional information extracted from CTA and CMR data are combined into a single frame of reference. Our graphical user interface provides various options for visualization. In addition to the standard perfusion Bull's Eye Plot (BEP), it is possible to overlay a 2D projection of the coronary tree on the BEP, to add a 3D coronary tree model and to add a 3D heart model. The perfusion BEP, the 3D-models and the CTA data are also interactively linked. Using the CMR and CTA data of 14 patients, our tool directly established a spatial correspondence between diseased coronary artery segments and myocardial regions with abnormal perfusion. The location of coronary stenoses and perfusion abnormalities were visualized jointly in 3D, thereby facilitating the study of the relationship between the anatomic causes of a blocked artery and the physiological effects on the myocardial perfusion. This tool is expected to improve diagnosis and therapy planning of early-stage coronary artery disease.
The Use of Blast Furnace Slag in North Sea Cementing Applications (1994)

ABSTRACT This paper discusses further the application of Blast Furnace Slag (BFS) in the cementing of oil and gas wells, with particular emphasis being placed on the suitability of BFS for offshore operations in the North Sea. The paper outlines the chemical reactions which occur during curing of BFS and discusses effects of different BFS sources and testing requirements. The application of BFS as a drilling fluid additive to improve cement bonding by solidification of the filter cake is discussed with respect to the effects of BFS on drilling fluid rheology and fluid loss. BFS is found suitable for low volume operations such as plug cementing, however wider use BFS is seen to be limited by logistics and occupational safety aspects for offshore North Sea applications. The environmental benefits to be gained by use of BFS is limited.
The iDEA DSP Block-Based Soft Processor for FPGAs (2014)

DSP blocks in modern FPGAs can be used for a wide range of arithmetic functions, offering increased performance while saving logic resources for other uses. They have evolved to better support a plethora of signal processing tasks, meaning that in other application domains they may be underutilised. The DSP48E1 primitives in new Xilinx devices support dynamic programmability that can help extend their usefulness; the specific function of a DSP block can be modified on a cycle-by-cycle basis. However, the standard synthesis flow does not leverage this flexibility in the vast majority of cases. The lean DSP Extension Architecture (iDEA) presented in this article builds around the dynamic programmability of a single DSP48E1 primitive, with minimal additional logic to create a general-purpose processor supporting a full instruction-set architecture. The result is a very compact, fast processor that can execute a full gamut of general machine instructions. We show a number of simple applications compiled using an MIPS compiler and translated to the iDEA instruction set, comparing with a Xilinx MicroBlaze to show estimated performance figures. Being based on the DSP48E1, this processor can be deployed across next-generation Xilinx Artix-7, Kintex-7, Virtex-7, and Zynq families.
Dynamic Stabilization in the Surgical Management of Painful Lumbar Spinal Disorders (2005)

Posterior dynamic stabilization systems may provide benefit comparable to fusion techniques, but without the elimination of movement. Further study is required to determine optimal design and clinical indications.
Diverse Pathways for the Palladium(II)-Mediated Oxidation of Olefins by <i>tert</i>-Butylhydroperoxide (2002)

[reaction: see text] New procedures are described for the palladium-catalyzed oxidation of olefins by tert-butylhydroperoxide under slightly basic conditions in CH(2)Cl(2) solution at 0-25 degrees C.
Mapping techniques and catheter ablation of ventricular tachycardia due to coronary artery disease. (1998)

In contrast to the high success rates for catheter ablation of focal ventricular tachycardia, radiofrequency ablation for ventricular tachycardia due to coronary artery disease has met with limited to variable success. In performing catheter ablation for ventricular tachycardia due to coronary disease, mapping techniques used to locate the isthmus of the reentrant circuit are crucial. Appropriate use of mapping techniques determines the success rate of the procedure. We classify different methods of mapping into indirect and direct. The indirect methods include analysis of the 12-lead electrocardiogram, endocardial pace-mapping, and analysis of electrograms recorded from different parts of the heart during sinus rhythm. The direct methods include activation sequence mapping and entrainment mapping. The direct methods are more important in evaluating ventricular tachycardia due to coronary disease. While using the technique of entrainment mapping, three criteria are important: a) entrainment with concealed fusion; b) post pacing interval within or less than 10 ms of tachycardia cycle length; c) stimulus-to-QRS interval should equal electrogram-to-QRS interval. A high success rate in terminating the tachycardia is seen if these criteria are met.
Agrobacterium-Mediated Transformation of Stem Disks from Oilseed Rape (Brassica napus L.) (2003)

The commercial importance of oilseed rape (Brassica nupus L.) makes it desirable to have an efficient transformation protocol for practical applications. With the exception of a few reports, transformation experiments with B. napus using Agrobacterium tumefaciens yielding transgenic plants have been performed principally with the spring variety B. napus L. ssp. oleifera cv. Westar (1–5). Transformation protocols are relatively specific for cv. Westar and cannot be extended to most of the other spring and none of the winter varieties tested (6). There are only isolated reports on transgenic winter oilseed rape plants (6–8).
Relationship between Growth Rate and ATP Concentration in Escherichia coli (2004)

Previous studies showed that adenosine triphosphate (ATP) concentrations in Escherichia coli changed during certain growth transitions and directly controlled the rate of rRNA transcription initiation at those times. The relationship between ATP concentration and rRNA transcription during steady-state growth is less clear, however. This is because two commonly employed methods for measuring ATP concentrations in bacteria, both of which rely on physical extraction followed by chromatographic separation of small molecules, resulted in dramatically different conclusions about whether ATP concentration changed with steady-state growth rate. Extraction with formic acid indicated that ATP concentration did not change with growth rate, whereas formaldehyde treatment followed by extraction with alkali indicated that ATP concentration increased proportionally to the growth rate. To resolve this discrepancy, we developed a bioassay for ATP based on the expression of a variant of the firefly luciferase enzyme in vivo and measurement of luminescence in cells growing in different conditions. We found that the available ATP concentration did not vary with growth rate, either in wild-type cells or in cells lacking guanosine 5'-diphosphate, 3'-diphosphate, providing insight into the regulation of rRNA transcription. More broadly, the luciferase bioassay described here provides a general method for evaluating the ATP concentration available for biochemical processes in E. coli and potentially in other organisms.
Mobile-end transport protocol: an alternative to TCP/IP over wireless links (2002)

Unlike wired links, wireless network bandwidth is highly limited and the channel usually suffers from frequent and bursty loss due to its vulnerability to various kinds of interference. At the same time, the traditional TCP with its congestion control is well known for its poor performance over wireless links. This paper proposes a new protocol that (1) replaces TCP/IP over the wireless link by a simpler protocol with smaller headers, if the link is the last hop along a data path, (2) shifts functions needed to communicate with an Internet host using TCP/IP from the mobile host to the base station, so that the distinct wireless link is hidden from the outside Internet, and (3) exploits link-layer acknowledgments and retransmissions to quickly recover losses over the wireless link. Our simulation results show a substantial performance improvement achieved by the new protocol.
A method of measuring marker position/orientation for VR interface by monocular image processing (1997)

The method of measuring position/orientation in the real world determines the construction of the VR interface. This paper proposes a method of measuring marker position/orientation by image processing. The marker is rectangular. The position/orientation is measured using a single camera. The orientation of the marker is estimated by optimization, utilizing the information of two vanishing points obtained from an image. Then, the position of the marker is determined by calculations. This is facilitated because we have only to attach a marker to a target of measurements. The expansion in the measurement of multiple objects is straightforward and the system can be constructed cheaply because no special circuitry is required. Also, the measurement range is easily modified by resetting the camera lens. The advantage of this method is shown by computer simulations and experimental results using a real image. The real-time measuring accuracy of the system, which was composed of ready-made devices and a highly distorted camera, was 0.5 degrees in directional deviations and 1 mm in depth deviation. © 1997 Scripta Technica, Inc. Electron Comm Jpn Pt 3, 80(3): 1–12, 1997
A20 Negatively Regulates T Cell Receptor Signaling to NF-κB by Cleaving Malt1 Ubiquitin Chains (2009)

The Carma1-Bcl10-Malt1 signaling module bridges TCR signaling to the canonical IkappaB kinase (IKK)/NF-kappaB pathway. Covalent attachment of regulatory ubiquitin chains to Malt1 paracaspase directs TCR signaling to IKK activation. Further, the ubiquitin-editing enzyme A20 was recently suggested to suppress T cell activation, but molecular targets for A20 remain elusive. In this paper, we show that A20 regulates the strength and duration of the IKK/NF-kappaB response upon TCR/CD28 costimulation. By catalyzing the removal of K63-linked ubiquitin chains from Malt1, A20 prevents sustained interaction between ubiquitinated Malt1 and the IKK complex and thus serves as a negative regulator of inducible IKK activity. Upon T cell stimulation, A20 is rapidly removed and paracaspase activity of Malt1 has been suggested to cleave A20. Using antagonistic peptides or reconstitution of Malt1(-/-) T cells, we show that Malt1 paracaspase activity is required for A20 cleavage and optimal IL-2 production, but dispensable for initial IKK/NF-kappaB signaling in CD4(+) T cells. However, proteasomal inhibition impairs A20 degradation and impedes TCR/CD28-induced IKK activation. Taken together, A20 functions as a Malt1 deubiquitinating enzyme and proteasomal degradation and de novo synthesis of A20 contributes to balance TCR/CD28-induced IKK/NF-kappaB signaling.
Modeling of local reduction in TiSi/sub 2/ and CoSi/sub 2/ growth near spacers in MOS technologies: influence of mechanical stress and main diffusing species (2002)

This paper presents an improved model for the simulation of silicide growth by either silicon or metal diffusion. For the first time, the shape of TiSi/sub 2/ and CoSi/sub 2/ layers, especially near spacer edges and on top of polysilicon lines, has been accurately simulated using mechanical stress effects. Furthermore, the importance of correctly simulating the silicidation to obtain accurate contact resistances is shown.