gebhart/patrepeval huggingface dataset:
Modelling selection response in plant breeding programs using crop models as mechanistic gene-to-phenotype (CGM-G2P) multi-trait link functions (2020)

Abstract Plant breeding programs are designed and operated over multiple cycles to systematically change the genetic makeup of plants to achieve improved trait performance for a Target Population of Environments (TPE). Within each cycle, selection applied to the standing genetic variation within a structured reference population of genotypes (RPG) is the primary mechanism by which breeding programs make the desired genetic changes. Selection operates to change the frequencies of the alleles of the genes controlling trait variation within the RPG. The structure of the RPG and the TPE has important implications for the design of optimal breeding strategies. The breeder’s equation, together with the quantitative genetic theory behind the equation, informs many of the principles for design of breeding programs. The breeder’s equation can take many forms depending on the details of the breeding strategy. Through the genetic changes achieved by selection, the cultivated varieties of crops (cultivars) are improved for use in agriculture. From a breeding perspective, selection for specific trait combinations requires a quantitative link between the effects of the alleles of the genes impacted by selection and the trait phenotypes of plants and their breeding value. This gene-to-phenotype link function provides the G2P map for one to many traits. For complex traits controlled by many genes, the infinitesimal model for trait genetic variation is the dominant G2P model of quantitative genetics. Here we consider motivations and potential benefits of using the hierarchical structure of crop models as CGM-G2P trait link functions in combination with the infinitesimal model for the design and optimisation of selection in breeding programs.
Dominant localization of prostaglandin D receptors on arachnoid trabecular cells in mouse basal forebrain and their involvement in the regulation of non-rapid eye movement sleep (2001)

Infusion of prostaglandin (PG) D(2) into the lateral ventricle of the brain induced an increase in the amount of non-rapid eye movement sleep in wild-type (WT) mice but not in mice deficient in the PGD receptor (DP). Immunofluorescence staining of WT mouse brain revealed that DP immunoreactivity was dominantly localized in the leptomeninges (LM) of the basal forebrain but that PGD synthase immunoreactivity was widely distributed in the LM of the entire brain. Electron microscopic observation indicated that DP-immunoreactive particles were predominantly located on the plasma membranes of arachnoid trabecular cells of the LM. The region with the highest DP immunoreactivity was clearly defined as bilateral wings in the LM of the basal forebrain located lateral to the optic chiasm in the proximity of the ventrolateral preoptic area, one of the putative sleep centers, and the tuberomammillary nucleus, one of the putative wake centers. The LM of this region contained DP mRNA 70-fold higher than that in the cortex as judged from the results of quantitative reverse transcription-PCR. PGD(2) infusion into the subarachnoid space of this region increased the extracellular adenosine level more than 2-fold in WT mice but not in the DP-deficient mice. These results indicate that DPs in the arachnoid trabecular cells of the basal forebrain mediate an increase in the extracellular adenosine level and sleep induction by PGD(2).
Foundry-processed optomechanical photonic integrated circuits (2021)

Photonic integrated circuits (PICs) are a maturing technology with foundries enabling wafer-scale PIC fabrication. At the same time, optomechanics, in which micro-/nano-optical and -mechanical structures are coupled, is well-established with many basic research and practical applications. However, optomechanical devices have so far required highly-customized fabrication that limits their inclusion in foundry-processed PICs. To address this need, we design optomechanical PICs using standard low-loss process design kit (PDK) components. Our approach ensures access to the foundry’s low-loss PDK components and enables process compatibility. As a demonstration, we design a foundry-processed optomechanical Mach-Zehnder interferometer (MZI). Measurements demonstrate that a π-phase shift can be accumulated over an optomechanical interaction length of only 60 µm and tunable phase shifting can be achieved using gradient electric force actuation. We further demonstrate all-optical excitation and readout of mechanical resonances for sensing applications. Our PDK-focused optomechanics design approach enables the co-integration of optomechanics, photonics, and electronics in a single PIC.
Development of a Virtual Human for Supporting Tobacco Cessation During the COVID-19 Pandemic (Preprint) (2022)

<sec> <title>UNSTRUCTURED</title> People who consume tobacco are at greater risk of developing severe COVID-19. Unfortunately, the COVID-19 pandemic reduced the accessibility of tobacco cessation services as a result of necessary social restrictions. Innovations were urgently needed to support tobacco cessation during the pandemic. Virtual humans are artificially intelligent computer agents with a realistic, humanlike appearance. Virtual humans could be a scalable and engaging way to deliver tobacco cessation information and support. Florence, a virtual human health worker, was developed in collaboration with the World Health Organization to remotely support people toward tobacco cessation during the COVID-19 pandemic. Florence delivers evidence-based information, assists with making quit plans, and directs people to World Health Organization–recommended cessation services in their country. In this viewpoint, we describe the process of developing Florence. The development was influenced by a formative evaluation of data from 115 early users of Florence from 49 countries. In general, Florence was positively perceived; however, changes were requested to aspects of her design and content. In addition, areas for new content were identified (eg, for nonsmoker support persons). Virtual health workers could expand the reach of evidence-based tobacco cessation information and personalized support. However, as they are a new innovation in tobacco cessation, their efficacy, feasibility, and acceptability in this application needs to be evaluated, including in diverse populations. </sec>
Hematopoietic stem cells, explicitly (2006)

gene expression and/or proteomic profiling, looking for similarities to nodal interfollicular B cells and to Reed-Sternberg cells.It might also be worth exploring the possibility that occasional cases of nodal diffuse large B-cell lymphomas arise from these cells (ie, are the peripheral equivalent of mediastinal B-cell lymphoma).
ChemInform Abstract: POLYFLUOROALKYL DERIVATIVES OF NITROGEN PART 40, REACTION OF TRIFLUORONITROSOMETHANE WITH NN‐BISTRIFLUOROMETHYLAMINO‐SUBSTITUTED ALLENES (1973)

Abstract Trifluornitrosomethan (II) reagiert mit den Allenen (Ia) bzw. (Ib) bei 70 bzw. 25°C überwiegend zu den Oxazetidinen (IIIa) bzw. (IIIb), deren Pyrolyse neben dem Formamid (IV) die Iminoäthylene (Va) bzw. (Vb) liefert.
Burkholderia pseudomallei Penetrates the Brain via Destruction of the Olfactory and Trigeminal Nerves: Implications for the Pathogenesis of Neurological Melioidosis (2014)

ABSTRACT Melioidosis is a potentially fatal disease that is endemic to tropical northern Australia and Southeast Asia, with a mortality rate of 14 to 50%. The bacterium Burkholderia pseudomallei is the causative agent which infects numerous parts of the human body, including the brain, which results in the neurological manifestation of melioidosis. The olfactory nerve constitutes a direct conduit from the nasal cavity into the brain, and we have previously reported that B. pseudomallei can colonize this nerve in mice. We have now investigated in detail the mechanism by which the bacteria penetrate the olfactory and trigeminal nerves within the nasal cavity and infect the brain. We found that the olfactory epithelium responded to intranasal B. pseudomallei infection by widespread crenellation followed by disintegration of the neuronal layer to expose the underlying basal layer, which the bacteria then colonized. With the loss of the neuronal cell bodies, olfactory axons also degenerated, and the bacteria then migrated through the now-open conduit of the olfactory nerves. Using immunohistochemistry, we demonstrated that B. pseudomallei migrated through the cribriform plate via the olfactory nerves to enter the outer layer of the olfactory bulb in the brain within 24 h. We also found that the bacteria colonized the thin respiratory epithelium in the nasal cavity and then rapidly migrated along the underlying trigeminal nerve to penetrate the cranial cavity. These results demonstrate that B. pseudomallei invasion of the nerves of the nasal cavity leads to direct infection of the brain and bypasses the blood-brain barrier. IMPORTANCE Melioidosis is a potentially fatal tropical disease that is endemic to northern Australia and Southeast Asia. It is caused by the bacterium Burkholderia pseudomallei, which can infect many organs of the body, including the brain, and results in neurological symptoms. The pathway by which the bacteria can penetrate the brain is unknown, and we have investigated the ability of the bacteria to migrate along nerves that innervate the nasal cavity and enter the frontal region of the brain by using a mouse model of infection. By generating a mutant strain of B. pseudomallei which is unable to survive in the blood, we show that the bacteria rapidly penetrate the cranial cavity using the olfactory (smell) nerve and the trigeminal (sensory) nerve that line the nasal cavity.
SM22α suppresses cytokine-induced inflammation and the transcription of NF-κB inducing kinase (Nik) by modulating SRF transcriptional activity in vascular smooth muscle cells (2017)

Vascular smooth muscle cell (VSMC) phenotypic modulation is characterized by the downregulation of SMC actin cytoskeleton proteins. Our published study shows that depletion of SM22α (aka SM22, Transgelin, an actin cytoskeleton binding protein) promotes inflammation in SMCs by activating NF-κB signal pathways both in cultured VSMCs and in response to vascular injury. The goal of this study is to investigate the underlying molecular mechanisms whereby SM22 suppresses NF-κB signaling pathways under inflammatory condition. NF-κB inducing kinase (Nik, aka MAP3K14, activated by the LTβR) is a key upstream regulator of NF-κB signal pathways. Here, we show that SM22 overexpression suppresses the expression of NIK and its downstream NF-κB canonical and noncanonical signal pathways in a VSMC line treated with a LTβR agonist. SM22 regulates NIK expression at both transcriptional and the proteasome-mediated post-translational levels in VSMCs depending on the culture condition. By qPCR, chromatin immunoprecipitation and luciferase assays, we found that Nik is a transcription target of serum response factor (SRF). Although SM22 is known to be expressed in the cytoplasm, we found that SM22 is also expressed in the nucleus where SM22 interacts with SRF to inhibit the transcription of Nik and prototypical SRF regulated genes including c-fos and Egr3. Moreover, carotid injury increases NIK expression in Sm22-/- mice, which is partially relieved by adenovirally transduced SM22. These findings reveal for the first time that SM22 is expressed in the nucleus in addition to the cytoplasm of VSMCs to regulate the transcription of Nik and its downstream proinflammatory NF-kB signal pathways as a modulator of SRF during vascular inflammation.
Modelling and Robustness Analysis of Model Predictive Control for Electrical Submersible Pump Lifted Heavy Oil Wells (2016)

In this paper we consider the problem of automatic control of oil production wells equipped with Electric Submersible Pumps (ESP). To facilitate robustness analysis of automatic control algorithms for such systems, a high fidelity simulator of ESP lifted well producing heavy viscous crude oil, has been developed. Model Predictive Control strategy proposed by the authors in an earlier publication has been tested on this simulator with the main focus on controller performance and robustness. The results demonstrated sufficient robustness of the controller with respect to system nonlinearities, variations in operating conditions, disturbances and measurement noise.
Sterol 14α-Demethylase Structure-Based Optimization of Drug Candidates for Human Infections with the Protozoan Trypanosomatidae (2018)

Sterol 14α-demethylases (CYP51) are cytochrome P450 enzymes essential for sterol biosynthesis in eukaryotes and therapeutic targets for antifungal azoles. Multiple attempts to repurpose antifungals for treatment of human infections with protozoa (Trypanosomatidae) have been undertaken, yet so far none of them have revealed sufficient efficacy. VNI and its derivative VFV are two potent experimental inhibitors of Trypanosomatidae CYP51, effective in vivo against Chagas disease, visceral leishmaniasis, and sleeping sickness and currently under consideration as antiprotozoal drug candidates. However, VNI is less potent against Leishmania and drug-resistant strains of Trypanosoma cruzi and VFV, while displaying a broader spectrum of antiprotozoal activity, and is metabolically less stable. In this work we have designed, synthesized, and characterized a set of close analogues and identified two new compounds (7 and 9) that exceed VNI/VFV in their spectra of antiprotozoal activity, microsomal stability, and pharmacokinetics (tissue distribution in particular) and, like VNI/VFV, reveal no acute toxicity.
Development of Mobile Module for High-Accuracy MEMS Rate Integrating Gyroscope and Demonstration of Position Tracking (2020)

This paper presents the first compact MEMS rate integrating gyroscope (RIG) module for direct angle measurement and its experimental demonstration of position estimation. The 5-cm prototype module vertically integrates a vacuum-sealed MEMS RIG device, an analog front-end PCB, and a digital microcontroller PCB. Continuous angle measurement is confirmed with an angular random walk of 0.6 deg/rt-h and a bias instability of 4.3 deg/h, proving comparable noise performances with previous FPGA-based large RIG systems. The RIG module provides direct information of rotation angle, which eliminates the integration error of offset and noise occurred in the conventional rate-gyroscope based systems. In position tracking experiments of model train running (560-cm distance) and indoor pedestrian walking (88-m distance), the maximum position errors are 3 cm (0.5%) and 1.6 m (1.8%), respectively.
Ipriflavone inhibits interleukin-I stimulated neutral metalloprotease synthesis in human chondrocytes cultivated in clusters (1994)

peer reviewed
An atomic resolution structure for human fibroblast growth factor 1 (2004)

A 1.10-A atomic resolution X-ray structure of human fibroblast growth factor 1 (FGF-1), a member of the beta-trefoil superfold, has been determined. The beta-trefoil is one of 10 fundamental protein superfolds and is the only superfold to exhibit 3-fold structural symmetry (comprising 3 "trefoil" units). The quality of the diffraction data permits unambiguous assignment of Asn, Gln, and His rotamers, Pro ring pucker, as well as refinement of atomic anisotropic displacement parameters (ADPs). The FGF-1 structure exhibits numerous core-packing defects, detectable using a 1.0-A probe radius. In addition to contributing to the relatively low thermal stability of FGF-1, these defects may also permit domain motions within the structure. The availability of refined ADPs allows a translation/libration/screw (TLS) analysis of putative rigid body domains. The TLS analysis shows that beta-strands 6-12 together form a rigid body, and there is a clear demarcation in TLS motions between the adjacent carboxyl- and amino-termini. Although separate from beta-strands 6-12, the individual beta-strands 1-5 do not exhibit correlated motions; thus, this region appears to be comparatively flexible. The heparin-binding contacts of FGF-1 are located within beta-strands 6-12; conversely, a significant portion of the receptor-binding contacts are located within beta-strands 1-5. Thus, the observed rigid body motion in FGF-1 appears related to the ligand-binding functionalities.
Evaluation of Reference Genes and Expression Level of Genes Potentially Involved in the Mode of Action of Cry1Ac and Cry1F in a Susceptible Reference Strain of Chrysodeixis includens (2021)

Soybean looper (SBL), <i>Chrysodeixis includens</i> (Walker), is one of the major lepidopteran pests of soybean in the American continent. SBL control relies mostly on the use of insecticides and genetically modified crops expressing <i>Bacillus thuringiensis</i> (Bt) insecticidal Cry proteins. Due to the high selection pressure exerted by these control measures, resistance has developed to different insecticides and Bt proteins. Nevertheless, studies on the mechanistic background are still scarce. Here, the susceptibility of the laboratory SBL-Benzon strain to the Bt proteins Cry1Ac and Cry1F was determined in diet overlay assays and revealed a greater activity of Cry1Ac than Cry1F, thus confirming results obtained for other sensitive SBL strains. A reference gene study across larval stages with four candidate genes revealed that <i>RPL10</i> and <i>EF1</i> were the most stable genes for normalization of gene expression data obtained by RT-qPCR. Finally, the basal expression levels of eight potential Bt protein receptor genes in six larval instars were analyzed, including ATP-binding cassette (<i>ABC</i>) transporters, alkaline phosphatase, aminopeptidases, and cadherin. The results presented here provide fundamental knowledge to support future SBL resistance studies.
Thalamic disequilibrium syndrome after thrombolytic therapy for acute myocardial infarction (2005)

Thalamic disequilibrium syndrome (TDS) refers to unsteady stance and gait resulting from unilateral thalamic lesion. Posterolateral thalamic involvement may result in disequilibrium with minimal motor or sensory deficit.1 However, this entity has received less attention in comparison with thalamic sensory, movement, and ataxic disorders. The transient nature of TDS underscores its importance for the prevention of falls in neurorehabilitation. The current report highlights development of TDS due to right thalamic hemorrhage after thrombolytic therapy for acute myocardial infarction.

A 65-year-old man underwent thrombolytic therapy for acute anterior wall myocardial infarction with streptokinase followed by heparin and oral antiplatelet agents. When he tried to move 3 days later, he could not stand or walk unassisted. On assisted standing, he had truncal instability with axial lateropulsion to the left. He also required assistance for sitting up in bed. Neurologically he had normal visual fields, cranial nerve function (especially ocular movements), muscle power, and …
Data consolidation solution for internal security needs (2012)

The threats of the 21st century are too complex, difficult and time consuming to discern with traditional intelligence practices that shun advances in information technology and rely heavily on human experts. Good information is fundamental to understand and respond to 21st century national security threats. Without comprehensive information, decision-makers operate with a limited understanding of the threat horizon or the best means to address it. Required information exists across a variety of proprietary and open sources, and the volume of data available that might potentially contain relevant facts is simply too large and the bandwidth of the trained analysts is limited. Such information must be available in time-critical situations to be able to quickly connect the dots across various related pieces of information. It is imperative that decision-makers are provided intelligent tools that can automatically extract new relevant information from data without being explicitly asked, leading to actionable intelligence. To overcome these challenges we propose an information collection, management and analysis framework to meet the ever-growing threats to national security. The proposed framework establishes a collaborative environment to semi-automatically generate actionable intelligence by ensuring that the right people have access to all inclusive information at the right time. The core of this framework is to create a single view of entity by correlating information from different sources, stored in different formats. These sources can be passport, immigration, driving license, FIR records, Telecom and Utility services. The correlation algorithm is able to handle varied amount of noise in the data such as syntactic and semantic variations, format changes, spelling error, incomplete data, regional and linguistics variation as well as addition or removal of fields. The framework can further exploit the consolidated view to discover relationships between entities thus expanding the reach for relevant information. The framework provides multiple avenues of interaction and the foresight needed to incorporate new sources of data as they arise in future.
Precise localization of theFHIT gene to the common fragile site at 3p14.2 (FRA3B) and characterization of homozygous deletions within FRA3B that affectFHIT transcription in tumor cell lines (1997)

Chromosomal or allelic losses at 3p14 are common in a variety of human tumors, including those of the lung, breast, kidney, and head and neck. This suggests the existence of a tumor suppressor gene in this band. A promising candidate is the recently cloned FHIT gene, which spans the common fragile site, FRA3B, at 3p14.2. We previously identified a region of fragility at 3p14.2 (FRA3B) of > 85 kb by cloning DNA flanking pSV2neo integrations and constructed a partial genomic contig of the region. Using probes from the contig, we tested for deletions within this region in DNA from 105 human tumor cell lines, predominantly derived from lung cancers. We identified one gastric and four lung cancer cell lines with homozygous interstitial deletions involving the FRA3B region. The deletion in one lung cancer cell line lies entirely within our contig and is < 65 kb. We have identified, cloned, and sequenced this breakpoint junction. We have also shown that our probes lie within intron S of the FHIT gene and, furthermore, that exon 5 is located approximately 1 kb from one of our probes and, thus, lies within the region of fragility. Two lines with entirely intronic deletions yield FHIT transcripts of normal size. In one of these, this was the sole transcript identified. In the other line, an FHIT transcript completely normal in sequence was accompanied by two larger abnormal transcripts. These results leave open the possibility that some homozygous deletions within the FHIT gene are without phenotypic effect and result from genetic instability of this region. However, taken together, our results provide evidence that breakage and rearrangement within the FRA3B fragile site sequences result in alterations of FHIT and are likely to be involved in carcinogenesis.
96 W AlGaN/GaN heterojunction FET with field-modulating plate (2003)

An AlGaN/GaN heterojunction FET with a field-modulating plate has been successfully fabricated. A maximum drain current of 900 mA/mm was obtained with a gate–drain breakdown voltage of over 150 V. A 24 mm-wide FET exhibited 96 W (4.0 W/mm) output power, 54% power-added efficiency and 8.5 dB linear gain at a drain bias of 32 V.