gebhart/patrepeval huggingface dataset:
Rapid and Efficient CRISPR/Cas9-Based Mating-Type Switching of Saccharomyces cerevisiae (2017)

Rapid and highly efficient mating-type switching of <i>Saccharomyces cerevisiae</i> enables a wide variety of genetic manipulations, such as the construction of strains, for instance, isogenic haploid pairs of both mating-types, diploids and polyploids. We used the CRISPR/Cas9 system to generate a double-strand break at the <i>MAT</i> locus and, in a single cotransformation, both haploid and diploid cells were switched to the specified mating-type at ∼80% efficiency. The mating-type of strains carrying either rod or ring chromosome III were switched, including those lacking <i>HML</i>α and <i>HMR</i> <b>a</b> cryptic mating loci. Furthermore, we transplanted the synthetic yeast chromosome V to build a haploid polysynthetic chromosome strain by using this method together with an endoreduplication intercross strategy. The CRISPR/Cas9 mating-type switching method will be useful in building the complete synthetic yeast (Sc2.0) genome. Importantly, it is a generally useful method to build polyploids of a defined genotype and generally expedites strain construction, for example, in the construction of fully <b>a/a</b>/α/α isogenic tetraploids.
Optimizing Resource Allocation in a Genomic Breeding Program for Perennial Ryegrass to Balance Genetic Gain, Cost, and Inbreeding (2016)

Genomic selection (GS) has been recognized as offering numerous potential benefits for ryegrass ( Lolium perenne L.) breeding. While the theoretical benefits of GS in ryegrass breeding are clear, the best way to apply GS in practical breeding programs remains to be determined. The present study aimed to investigate genomic breeding options that best balance genetic gain, breeding costs, and the level of inbreeding using stochastic simulation. Nine GS scenarios were tested, including different numbers of selection candidates (10,000, 5000, and 2000 F 1 seedlings) and three reference population sizes for GS composed of plots representing a sward‐based trial (500, 200, and 100 plots). Low to moderate prediction accuracy was achieved for productivity traits across cycles (i.e., 0.1–0.45 for yield [ h 2 = 0.3]). Scenarios with larger reference populations (i.e., 500 plots) achieved higher prediction accuracy but, when considering field trial costs, were more expensive per unit of genetic gain. All nine GS scenarios delivered significantly higher genetic gain (up to fourfold) than the conventional breeding scenario over a 20‐yr period. Scenarios with moderate selection intensity on F 1 seedlings with fewer plots tested in field gave the most genetic gain per dollar invested (i.e., 2000 or 5000 F 1 seedlings and 100 plots). However, all GS scenarios reduced genetic diversity in the breeding population more than phenotypic selection, highlighting the need to mitigate inbreeding when applying GS in perennial ryegrass.
Data from Homozygous Deletions and Chromosome Amplifications in Human Lung Carcinomas Revealed by Single Nucleotide Polymorphism Array Analysis (2023)

&lt;div&gt;Abstract&lt;p&gt;Genome-wide copy number changes were analyzed in 70 primary human lung carcinoma specimens and 31 cell lines derived from human lung carcinomas, with high-density arrays representing ∼115,000 single nucleotide polymorphism loci. In addition to previously characterized loci, two regions of homozygous deletion were found, one near the &lt;i&gt;PTPRD&lt;/i&gt; locus on chromosome segment 9p23 in four samples representing both small cell lung carcinoma (SCLC) and non–small cell lung carcinoma (NSCLC) and the second on chromosome segment 3q25 in one sample each of NSCLC and SCLC. High-level amplifications were identified within chromosome segment 8q12-13 in two SCLC specimens, 12p11 in two NSCLC specimens and 22q11 in four NSCLC specimens. Systematic copy number analysis of tyrosine kinase genes identified high-level amplification of &lt;i&gt;EGFR&lt;/i&gt; in three NSCLC specimens, &lt;i&gt;FGFR1&lt;/i&gt; in two specimens and &lt;i&gt;ERBB2&lt;/i&gt; and &lt;i&gt;MET&lt;/i&gt; in one specimen each. &lt;i&gt;EGFR&lt;/i&gt; amplification was shown to be independent of kinase domain mutational status.&lt;/p&gt;&lt;/div&gt;
Discrete multiscale Bayesian image reconstruction (2002)

Statistical and discrete-valued methods can substantially improve the reconstruction quality by incorporating prior information about both the imaging system and the object being imaged. A statistical method shown to perform well in the tomographic setting is Bayesian MAP estimation. However, computing the MAP estimate in the tomographic domain is a computationally involved optimization problem. Furthermore, discrete-valued MAP reconstruction requires accurate knowledge of the density or emission levels in the cross-section. In this paper we present an efficient multiscale algorithm for discrete-valued MAP reconstruction including estimation of the discrete levels. Experimental results indicate that the multiscale algorithm has improved convergence behaviour over fixed scale reconstruction and is more robust with respect to local minima.
LS channel estimation performance analysis for RoF channel environment in the OFDM system (2014)

Generally in real implementation of OFDM system, the simple and fast LS channel estimation method has been used for the wireless channel in the OFDM systems. If the wireless channel environment were mixed with RoF (Radio Over Fiber) channel, could we still use the conventional least square (LS) channel estimation method for proper communication? Therefore, in this paper, we analyzed that the performance of LS channel estimation where both wireless and RoF channel are coexisted in the OFDM based mobile communication system.
Intramolecular cyclization of an allyl cation. The formation of 11-membered carbocyclic rings via cationic processes (1989)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTIntramolecular cyclization of an allyl cation. The formation of 11-membered carbocyclic rings via cationic processesPaul G. Gassman and Richard J. RiehleCite this: J. Am. Chem. Soc. 1989, 111, 6, 2319–2320Publication Date (Print):March 1, 1989Publication History Published online1 May 2002Published inissue 1 March 1989https://pubs.acs.org/doi/10.1021/ja00188a065https://doi.org/10.1021/ja00188a065research-articleACS PublicationsRequest reuse permissionsArticle Views204Altmetric-Citations10LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Low immune infiltrate level is associated with worse overall survival and complete loss of TP53 and RB1 in pleomorphic rhabdomyosarcoma (2023)

Rhabdomyosarcoma accounts for roughly 1% of adult sarcomas, with pleomorphic rhabdomyosarcoma (PRMS) as the most common subtype. Survival outcomes remain poor for patients with PRMS and little is known about the molecular drivers of this disease. To better characterize PRMS, we performed a broad array of genomic and immunostaining analyses on 25 patient samples. In terms of gene expression and methylation, PRMS clustered more closely with other complex karyotype sarcomas than with pediatric alveolar and embryonal rhabdomyosarcoma. Immune infiltrate levels in PRMS were among the highest observed in multiple sarcoma types and contrasted with low levels in other rhabdomyosarcoma subtypes. Higher immune infiltrate levels were associated with improved overall survival while lower immune infiltrate was associated with complete loss of both TP53 and RB1. This comprehensive characterization of the genetic, epigenetic and immune landscape of PRMS provides a roadmap for improved prognostications and therapeutic exploration.
Effective Work Function Engineering for Aggressively Scaled Planar and Multi-Gate Fin Field-Effect Transistor-Based Devices with High-k Last Replacement Metal Gate Technology (2013)

This work reports on aggressively scaled replacement metal gate, high- k last devices (RMG-HKL), exploring several options for effective work function (EWF) engineering, and targeting logic high-performance and low-power applications. Tight low-threshold voltage ( V T ) distributions for scaled NMOS devices are obtained by controlled TiN/TiAl-alloying, either by using RF-physical vapor deposition (RF-PVD) or atomic layer deposition (ALD) for TiN growth. The first technique allows optimization of the TiAl/TiN thicknesses at the bottom of gate trenches while maximizing the space to be filled with a low-resistance metal; using ALD minimizes the occurrence of preferential paths, at gate sidewalls, for Al diffusion into the high- k dielectric, reducing gate leakage ( J G ). For multi-gate fin field-effect transistors (FinFETs) which require smaller EWF shifts from mid-gap for low- V T : 1) conformal, lower- J G ALD-TiN/TaSiAl; and 2) Al-rich ALD-TiN by controlled Al diffusion from the fill-metal are demonstrated to be promising candidates. Comparable bias temperature instability (BTI), improved noise behavior, and slightly reduced equivalent oxide thickness (EOT) are measured on Al-rich EWF-metal stacks.
Nutritional markers and proteome in patients undergoing treatment for pulmonary tuberculosis differ by geographic region (2021)

We have identified differentially expressed nutrition and lipid pathway proteins by geographic region in TB patients undergoing treatment for pulmonary tuberculosis, which appear to be associated with differential treatment responses. Future TB clinical trials should collect expanded measures of nutritional status and further evaluate the relationship between nutrition and microbiologic treatment response.
ChemInform Abstract: Synthesis of Taxoids. Part 1. Regioselective Lewis Acid Mediated Ring‐ Opening of Aryl Orthoacetates. (1997)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Amyloid-β-induced occludin down-regulation and increased permeability in human brain endothelial cells is mediated by MAPK activation (2009)

Vascular dysfunction is emerging as a key pathological hallmark in Alzheimer's disease (AD). A leaky blood-brain barrier (BBB) has been described in AD patient tissue and in vivo AD mouse models. Brain endothelial cells (BECs) are linked together by tight junctional (TJ) proteins, which are a key determinant in restricting the permeability of the BBB. The amyloid beta (Abeta) peptides of 1-40 and 1-42 amino acids are believed to be pivotal in AD pathogenesis. We therefore decided to investigate the effect of Abeta 1-40, the Abeta variant found at the highest concentration in human plasma, on the permeability of an immortalized human BEC line, hCMEC/D3. Abeta 1-40 induced a marked increase in hCMEC/D3 cell permeability to the paracellular tracer 70 kD FITC-dextran when compared with cells incubated with the scrambled Abeta 1-40 peptide. Increased permeability was associated with a specific decrease, both at the protein and mRNA level, in the TJ protein occludin, whereas claudin-5 and ZO-1 were unaffected. JNK and p38MAPK inhibition prevented both Abeta 1-40-mediated down-regulation of occludin and the increase in paracellular permeability in hCMEC/D3 cells. Our findings suggest that the JNK and p38MAPK pathways might represent attractive therapeutic targets for preventing BBB dysfunction in AD.
Expansion, persistence, and efficacy of donor memory-like NK cells infused for posttransplant relapse (2022)

Background Responses to conventional donor lymphocyte infusion for postallogeneic hematopoietic cell transplantation (HCT) relapse are typically poor. Natural killer (NK) cell–based therapy is a promising modality to treat post-HCT relapse.Methods We initiated this ongoing phase I trial of adoptively transferred cytokine-induced memory-like (CIML) NK cells in patients with myeloid malignancies who relapsed after haploidentical HCT. All patients received a donor-derived NK cell dose of 5 to 10 million cells/kg after lymphodepleting chemotherapy, followed by systemic IL-2 for 7 doses. High-resolution profiling with mass cytometry and single-cell RNA sequencing characterized the expanding and persistent NK cell subpopulations in a longitudinal manner after infusion.Results In the first 6 enrolled patients on the trial, infusion of CIML NK cells led to a rapid 10- to 50-fold in vivo expansion that was sustained over months. The infusion was well tolerated, with fever and pancytopenia as the most common adverse events. Expansion of NK cells was distinct from IL-2 effects on endogenous post-HCT NK cells, and not dependent on CMV viremia. Immunophenotypic and transcriptional profiling revealed a dynamic evolution of the activated CIML NK cell phenotype, superimposed on the natural variation in donor NK cell repertoires.Conclusion Given their rapid expansion and long-term persistence in an immune-compatible environment, CIML NK cells serve as a promising platform for the treatment of posttransplant relapse of myeloid disease. Further characterization of their unique in vivo biology and interaction with both T cells and tumor targets will lead to improvements in cell-based immunotherapies.Trial Registration ClinicalTrials.gov NCT04024761.Funding Dunkin’ Donuts, NIH/National Cancer Institute, and the Leukemia and Lymphoma Society.
Architecture and Applications of DADO: A Large-Scale Parallel Computer for Artificial Intelligence (1983)

As part of our research on very high performance parallel architectures, we have been investigating; machine architectures specially adapted to the highly efficient implementation of artificial intelligence (AI) software. In the course of our research we designed DADO, a highly parallel, VLSI-based, tree-structured machine, and implemented a high-speed algorithm for production systems on a simulator for DADO. Subsequent research has convinced us that DADO can support many other AI applications, including the very rapid execution of PROLOG programs, and a large share of the symbolic processing typical of contemporary knowledge-based systems. In this brief report, we outline the hardware design of a moderate size DADO prototype, comprising 1023 processing elements, which is currently under construction at Columbia University. We then sketch the software base being implemented on a small 15 processing element prototype system including several applications written in PPL/M, a high-level language designed for specifying parallel computations on DADO.
SEM contour based metrology for microlens process studies in CMOS image sensor technologies (2018)

International audience
Clinical impact of PTEN genomic deletions and TMPRSS2-ERG gene fusions in prostate cancer (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

5674 

The inactivation of tumor suppressor genes, and the disruption of transcription factor function play a central role in the initiation and progression of many human cancers. Supportive evidence for this model in prostate cancer (CaP) has been provided by the high frequency PTEN tumor suppressor gene losses in tumors, and the recent demonstration of activating genomic fusion rearrangements of ETS transcription factor genes, such as ERG with the TMPRSS2 locus in ~60% of CaP. The strong association between PTEN haploinsufficiency and CaP in both the knockout mouse and in sporadic human cancers, together with the high specificity and frequency of TMPRSS2-ETS fusions in human CaP, implies that both pathways are directly involved in the pathogenesis of CaP. To date there has been no large-scale systematic analysis of the influence of genomic PTEN deletion and TMPRSS2-ETS gene fusions on the clinical parameters of CaP progression, including incidence-free survival, biochemical response and other clinical-pathologic determinants of outcome. Moreover, no studies have been performed to determine the frequency with which PTEN and TMPRSS2-ETS rearrangements occur together in CaP, or to examine clinical phenotypes associated with genomic mutations affecting both pathways. This study was designed to retrospectively assess the overall frequency with which PTEN deletions and TMPRSS2-ERG fusion rearrangements occur simultaneously, and their clinical impact through FISH analysis using well-annotated high-throughput tissue microarrays (TMAs) derived from 107 CaP patients. In addition, four-color FISH analysis of the TMPRSS2-ERG fusion was used to precisely delineate the interstitial deletion of genomic content from this region of chromosome 21. Analysis of the TMAs by interphase FISH indicated that PTEN deletion was present in 47/107 (44%) of CaP, with a homozygous PTEN deletion present in 5 of the 47 tumors. Kaplan-Meier survival analysis of PTEN deleted (hemizygously or homozygously) vs. not deleted identified three subgroups with different prognosis with respect to time to biochemical relapse after surgery. Overall the analysis demonstrated a significant association (P=0.0003) between PTEN deletion and a shorter time interval to PSA recurrence. Significantly, homozygous PTEN deletion in five tumors was associated with a much earlier onset of biochemical recurrence based on PSA values. It was noteworthy that 35% of tumors had neither a PTEN deletion nor a TMPRSS2-ERG fusion event. While the ERG and PTEN pathways are distinct, these data suggest that PTEN loss and ETS activation by TMPRSS2-ERG fusions do not occur independently. Given the uncertainty regarding the biological impact of ETS fusion transcripts in CaP, alone or in combination with PTEN genomic losses, these new genotype-phenotype correlative studies will provide valuable prognostic information for future CaP treatment and long-term management.
Phosphonic Acid Adsorbates Tune the Surface Potential of TiO2 in Gas and Liquid Environments (2014)

Controlled attachment of molecules to the surface of a material can alter the band structure energies with respect to the surrounding environment via a combination of intrinsic and bonding-induced dipoles. Here, we demonstrate that the surface potential of an application-relevant material, anatase TiO2, can be tuned over a broad energy range of ∼1 eV using a family of dipolar phosphonic acid-based adsorbates. Using TiO2 as an example, we show with photoelectron spectroscopy that these adsorbates are stable in a liquid environment (propylene carbonate). More interestingly, the tunability is substantially retained and follows trends in the computed bound dipole. The electrochemical surface potential is shown to vary over 600 meV, the highest range in electrolytes to the best of our knowledge. Using density functional theory calculations, we rationalize the measured trends and show that the effective dipole upon molecular adsorption and not the intrinsic dipole of the isolated molecules correlates with observed changes in surface potential. Control of the effective dipole, through judicious choice of robust surface species, can allow in situ tuning of energy levels and functionality at active surfaces for energy conversion and storage, biosensing, and molecular electronics.
ATP-dependent transport of vinblastine in vesicles from human multidrug-resistant cells. (1988)

Resistance of human cancer cells to multiple cytotoxic hydrophobic agents (multidrug resistance) is due to overexpression of the "MDR1" gene, whose product is the plasma membrane P-glycoprotein. Plasma membrane vesicles partially purified from multidrug-resistant human KB carcinoma cells, but not from drug-sensitive cells, accumulate [3H]vinblastine in an ATP-dependent manner. This transport is osmotically sensitive, with an apparent Km of 38 microM for ATP and of approximately equal to 2 microM for vinblastine. The nonhydrolyzable analog adenosine 5'-[beta, gamma-imido]triphosphate does not substitute for ATP but is a competitive inhibitor of ATP for the transport process. Vanadate, an ATPase inhibitor, is a potent noncompetitive inhibitor of transport. These results indicate that hydrolysis of ATP is probably required for active transport of vinblastine. Several other drugs to which multidrug-resistant cell lines are resistant inhibit transport, with relative potencies as follows: vincristine greater than actinomycin D greater than daunomycin greater than colchicine = puromycin. Verapamil and quinidine, which reverse the multidrug-resistance phenotype, are good inhibitors of the transport process. These results confirm that multidrug-resistant cells express an energy-dependent plasma membrane transporter for hydrophobic drugs, and establish a system for the detailed biochemical analysis of this transport process.
Ex Vivo Perfusion-Simulation Measurements of Microbubbles as a Scattering Contrast Agent for Grating-Based X-Ray Dark-Field Imaging (2015)

The investigation of dedicated contrast agents for x-ray dark-field imaging, which exploits small-angle scattering at microstructures for contrast generation, is of strong interest in analogy to the common clinical use of high-atomic number contrast media in conventional attenuation-based imaging, since dark-field imaging has proven to provide complementary information. Therefore, agents consisting of gas bubbles, as used in ultrasound imaging for example, are of particular interest. In this work, we investigate an experimental contrast agent based on microbubbles consisting of a polyvinyl-alcohol shell with an iron oxide coating, which was originally developed for multimodal imaging and drug delivery. Its performance as a possible contrast medium for small-animal angiography was examined using a mouse carcass to realistically consider attenuating and scattering background signal. Subtraction images of dark field, phase contrast and attenuation were acquired for a concentration series of 100%, 10% and 1.3% to mimic different stages of dilution in the contrast agent in the blood vessel system. The images were compared to the gold-standard iodine-based contrast agent Solutrast, showing a good contrast improvement by microbubbles in dark-field imaging. This study proves the feasibility of microbubble-based dark-field contrast-enhancement in presence of scattering and attenuating mouse body structures like bone and fur. Therefore, it suggests a strong potential of the use of polymer-based microbubbles for small-animal dark-field angiography.