gebhart/patrepeval huggingface dataset:
Rational design and in vivo selection of SHIVs encoding transmitted/founder subtype C HIV-1 envelopes (2019)

Chimeric Simian-Human Immunodeficiency Viruses (SHIVs) are an important tool for evaluating anti-HIV Env interventions in nonhuman primate (NHP) models. However, most unadapted SHIVs do not replicate well in vivo limiting their utility. Furthermore, adaptation in vivo often negatively impacts fundamental properties of the Env, including neutralization profiles. Transmitted/founder (T/F) viruses are particularly important to study since they represent viruses that initiated primary HIV-1 infections and may have unique attributes. Here we combined in vivo competition and rational design to develop novel subtype C SHIVs containing T/F envelopes. We successfully generated 19 new, infectious subtype C SHIVs, which were tested in multiple combinatorial pools in Indian-origin rhesus macaques. Infected animals attained peak viremia within 5 weeks ranging from 103 to 107 vRNA copies/mL. Sequence analysis during primary infection revealed 7 different SHIVs replicating in 8 productively infected animals with certain clones prominent in each animal. We then generated 5 variants each of 6 SHIV clones (3 that predominated and 3 undetectable after pooled in vivo inoculations), converting a serine at Env375 to methionine, tyrosine, histidine, tryptophan or phenylalanine. Overall, most Env375 mutants replicated better in vitro and in vivo than wild type with both higher and earlier peak viremia. In 4 of these SHIV clones (with and without Env375 mutations) we also created mutations at position 281 to include serine, alanine, valine, or threonine. Some Env281 mutations imparted in vitro replication dynamics similar to mutations at 375; however, clones with both mutations did not exhibit incremental benefit. Therefore, we identified unique subtype C T/F SHIVs that replicate in rhesus macaques with improved acute phase replication kinetics without altering phenotype. In vivo competition and rational design can produce functional SHIVs with globally relevant HIV-1 Envs to add to the growing number of SHIV clones for HIV-1 research in NHPs.
CRISPR screens in physiologic medium reveal conditionally essential genes in human cells (2020)

SUMMARY Forward genetic screens across hundreds of diverse cancer cell lines have started to define the genetic dependencies of proliferating human cells and how these vary by genotype and lineage. Most screens, however, have been carried out in culture media that poorly resemble metabolite availability in human blood. To explore how medium composition influences gene essentiality, we performed CRISPR-based screens of human cancer cell lines cultured in traditional versus human plasma-like medium (HPLM). Sets of medium-dependent fitness genes span several cellular processes and can vary with both natural cell-intrinsic diversity and the specific combination of basal and serum components that comprise typical culture media. Notably, we traced the causes for each of three conditional growth phenotypes to the availability of metabolites uniquely defined in HPLM versus traditional media. Our findings reveal the profound impact of medium composition on gene essentiality in human cells, and also suggest general strategies for using genetic screens in HPLM to uncover new cancer vulnerabilities and gene-nutrient interactions.
Raman spectral characterization of pure and fluorine‐doped vitreous silica material (1982)

Abstract Fluorine doped silica samples have been investigated by Raman spectroscopy. The results obtained allow us to propose a model for dopant incorporation in the silica network, involving the formation of SiO 3 F tetrahedron. A relationship between the intensity of the ν(Si‐F) stretching vibration band and the refractive index is presented.
Onset of Material Alterations Due to Laser-Induced Plasma Exposure in Nanofilms Deposited on Photomasks (2009)

<para xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> Damage-free removal of sub-100 nm particles from photomasks with deposited nanofilms is a challenge in lithography. Laser-induced plasma (LIP) is an emerging noncontact, chemical-free, dry, and selective nanoparticle removal technique. Investigation of the onset of material alterations on bonded nanofilms for optimizing LIP particle removal process is the objective of this paper. Shockwave thermomechanical excitation and radiation heating from the plasma core are major potential sources of damage. Computational analyses reported here indicate radiation heating as the chief damage source. Damage thresholds for the critical nanofilm surface temperature rise and radial stress component have been identified for a given nanosecond pulsed laser. </para>
Targeted Maximum Likelihood Based Causal Inference (2010)

Given causal graph assumptions, intervention-specific counterfactual distributions of the data can be defined by the so called G-computation formula, which is obtained by carrying out these interventions on the likelihood of the data factorized according to the causal graph. The obtained G-computation formula represents the counterfactual distribution the data would have had if this intervention would have been enforced on the system generating the data. A causal effect of interest can now be defined as some difference between these counterfactual distributions indexed by different interventions. For example, the interventions can represent static treatment regimens or individualized treatment rules that assign treatment in response to time-dependent covariates, and the causal effects could be defined in terms of features of the mean of the treatment-regimen specific counterfactual outcome of interest as a function of the corresponding treatment regimens. Such features could be defined nonparametrically in terms of so called (nonparametric) marginal structural models for static or individualized treatment rules, whose parameters can be thought of as (smooth) summary measures of differences between the treatment regimen specific counterfactual distributions.\nIn this article, we provide templates for implementation of the targeted maximum likelihood estimator of causal effects of multiple time point interventions. This involves the use of loss-based super-learning to obtain an initial estimate of the unknown factors of the G-computation formula, and subsequently, applying a target-parameter specific optimal fluctuation function (least favorable parametric submodel) to each estimated factor, estimating the fluctuation parameter(s) with maximum likelihood estimation, and iterating this updating step till convergence. The targeted maximum likelihood step makes the resulting estimator of the causal effect double robust in the sense that it is consistent if either the initial estimator is consistent, or the estimator of the optimal fluctuation function is consistent. The optimal fluctuation function is correctly specified if the conditional distributions of the nodes in the causal graph one intervenes upon are correctly specified. The latter conditional distributions often comprise the so called treatment and censoring mechanism. Selection among different targeted maximum likelihood estimators (e.g., indexed by different initial estimators) can be based on loss-based cross-validation such as likelihood based cross-validation or cross-validation based on another appropriate loss function for the distribution of the data. Some specific loss functions are mentioned in this article.\nIn this article, a variety of interesting observations about targeted maximum likelihood estimation are made, and a concrete template for the practical implementation of targeted maximum likelihood estimation is presented as well. In addition, we demonstrate it for estimation of a causal effect of dynamic treatment rules defined in terms of a marginal structural working model, inspired by HIV applications.
Fusion-product bombardment of a tokamak first wall (1976)

A method of calculating the wall loading due to fusion products escaping from the plasma in a tokamak is described. For this purpose, the small-banana-width approximation is eliminated, yielding an analytic formulation for high-energy orbits and associated loss-cone limits. Wall-loading profiles (as a function of poloidal angle) are presented for various experimental devices (PLT, TFTR, and ORNL-EPR) and for a typical reactor (UWMAK-I). Peak-to-average alpha flux ratios of the order of 1.4 to 2.3 combined with average fluxes of ~ 1011 alphas per cm2 per second, suggest that localized blistering may be a serious source of impurity atoms as well as a wall erosion mechanism. Special wall panels in regions of high flux are suggested. Other implications include a unique suggestion for fuel injection along special orbits intercepted via a bundle divertor.
Parallel synthesis and biological evaluation of different sizes of bicyclo[2,3]‐Leu‐enkephalin analogues (2005)

Parallel synthesis of peptides and peptidomimetics has been an important approach to search for biologically active ligands. A novel systematic synthesis of different size bicyclic dipeptide mimetics was developed on solid-phase supports. By taking advantage of the enantioselective synthesis of omega-unsaturated amino acids and their N-methylated derivatives, the hemiaminal problem was prevented in the pathway to thiazolidine formation. The bicyclic dipeptide was generated on the solid-phase support in three steps by an unconventional method. By inserting this bicyclic scaffold into the synthesis of a larger bioactive peptide, 11 different sizes of bicyclo[2,3]-Leu-enkephalin analogues were synthesized in a fast and efficient way. Modeling studies show that a reversed turn structure at positions 2-3 was favored when an L- and L-bicyclic scaffold was used, and that an extended conformation at the N-terminal was favored when a D- and L-bicyclic scaffold was inserted. Binding affinities and bioassay studies show ligands with micromolar binding affinities and antagonist bioactivities for the [6,5]- and [7,5]-bicyclo-Leu-enkephalin analogues.
Microbial Profiling of Combat Wound Infection through Detection Microarray and Next-Generation Sequencing (2014)

Combat wound healing and resolution are highly affected by the resident microbial flora. We therefore sought to achieve comprehensive detection of microbial populations in wounds using novel genomic technologies and bioinformatics analyses. We employed a microarray capable of detecting all sequenced pathogens for interrogation of 124 wound samples from extremity injuries in combat-injured U.S. service members. A subset of samples was also processed via next-generation sequencing and metagenomic analysis. Array analysis detected microbial targets in 51% of all wound samples, with Acinetobacter baumannii being the most frequently detected species. Multiple Pseudomonas species were also detected in tissue biopsy specimens. Detection of the Acinetobacter plasmid pRAY correlated significantly with wound failure, while detection of enteric-associated bacteria was associated significantly with successful healing. Whole-genome sequencing revealed broad microbial biodiversity between samples. The total wound bioburden did not associate significantly with wound outcome, although temporal shifts were observed over the course of treatment. Given that standard microbiological methods do not detect the full range of microbes in each wound, these data emphasize the importance of supplementation with molecular techniques for thorough characterization of wound-associated microbes. Future application of genomic protocols for assessing microbial content could allow application of specialized care through early and rapid identification and management of critical patterns in wound bioburden.
Application and performance evaluation for the new material in the industrial SFF system using a SLS process (2008)

In the solid freeform fabrication (SFF) System using selective laser sintering (SLS), Polyamide-12 powder (below PA-I) is currently recognized as general materials. PA-I powder has properties as average particle size 58 ㎛, density is 0.59 g/cm3 and melting point is 184℃. So, it is most suitable for SFF system using SLS process in the powder base.However the PA-I powder has a problem with the highest cost. For the reason it is occurred a very low available rate of SFF system. It is only about 7days that there is the available rate for the year of about 400 systems introduced into domestic. This study was used raw materials instead of existing PA-I powder such as Polyamide-6 (PA-6) and Polyamide-12 (PA-12) that must have low cost and are applicable to SFF system. Here, the new materials have several properties such as shape, density, a melting point and sintering characteristics.Therefore, in this study, we propose new materials for the market competitiveness and performance guarantee. This study suggest that though development and evaluation of optimal sintering process applicable the use of laser sintering materials and materials of suitable characteristic of the industrial SFF system and for the laser sintering material with the excellent sintering characteristic.
Fabrication and Electrochemical Characterization of Boron-Doped Diamond Microdisc Array Electrodes (2002)

Abstract Microdisc array (MDA) electrodes of boron-doped diamond (BDD) were fabricated on structured silicon substrates. The BDD-MDA electrodes exhibited sigmoidal voltammetric curves, which show that they function as assemblies of single microelectrodes. The microelectrode behavior was also confirmed with biologically important species such as ascorbic acid and 3,4-dihydroxyphenylacetic acid, indicating its applicability in electroanalysis.
Cross-domain paraphrasing for improving language modelling using out-of-domain data (2013)

In natural languages the variability in the underlying linguistic generation rules significantly alters the observed surface word sequence they create, and thus introduces a mismatch against other data generated via alternative realizations associated with, for example, a different domain.Hence, direct modelling of out-of-domain data can result in poor generalization to the indomain data of interest.To handle this problem, this paper investigated using cross-domain paraphrastic language models to improve in-domain language modelling (LM) using out-ofdomain data.Phrase level paraphrase models learnt from each domain were used to generate paraphrase variants for the data of other domains.These were used to both improve the context coverage of in-domain data, and reduce the domain mismatch of the out-of-domain data.Significant error rate reduction of 0.6% absolute was obtained on a state-of-the-art conversational telephone speech recognition task using a cross-domain paraphrastic multi-level LM trained on a billion words of mixed conversational and broadcast news data.Consistent improvements on the in-domain data context coverage were also obtained.
Diffraction-based overlay for spacer patterning and double patterning technology (2011)

Overlay performance will be increasingly important for Spacer Patterning Technology (SPT) and Double Patterning Technology (DPT) as various Resolution Enhancement Techniques are employed to extend the resolution limits of lithography. Continuous shrinkage of devices makes overlay accuracy one of the most critical issues while overlay performance is completely dependent on exposure tool. Image Based Overlay (IBO) has been used as the mainstream metrology for overlay by the main memory IC companies, but IBO is not suitable for some critical layers due to the poor Tool Induced Shift (TIS) values. Hence new overlay metrology is required to improve the overlay measurement accuracy. Diffraction Based Overlay (DBO) is regarded to be an alternative metrology to IBO for more accurate measurements and reduction of reading errors. Good overlay performances of DBO have been reported in many articles. However applying DBO for SPT and DPT layers poses extra challenges for target design. New vernier designs are considered for different DPT and SPT schemes to meet overlay target in DBO system. In this paper, we optimize the design of the DBO target and the performance of DBO to meet the overlay specification of sub-3x nm devices which are using SPT and DPT processes. We show that the appropriate vernier design yields excellent overlay performance in residual and TIS. The paper also demonstrated the effects of vernier structure on overlay accuracy from SEM analysis.
Genetic factors and metastatic potential of prostatic cancer. (1991)

When a non-metastatic subline from the Dunning rat prostatic cancer was transfected with the v-Ha-ras oncogene, some transfectants acquired metastatic potential. Molecular analysis demonstrated that there was no simple dose-response relationship between v-Ha-ras expression and metastatic potential in this prostatic cancer system. Cytogenetic analysis on the same system demonstrated increased genetic instability following v-Ha-ras transfection. Progression of prostatic cancer from no metastatic to high metastatic potential may involve the loss of a metastasis suppressor gene. To test this possibility, non-metastatic and highly metastatic Dunning rat prostatic cancer cells were fused. Hybrid clones were isolated that conserved the chromosomes from their parental cells. When these hybrids were injected into animals, none developed distant metastases. When the non-metastatic primary tumours were passaged in vivo, distant metastases developed in occasional animals. Cytogenetic analysis of eight of these metastatic revertants demonstrated a consistent loss of normal chromosome 2. These studies show that metastasis is associated with the loss of a specific chromosome. These studies also suggest that a metastasis suppressor gene for rat prostatic cancer is located on chromosome 2. A more direct approach to identify a chromosome(s) carrying metastasis suppressor gene(s) by using microcell mediated chromosome transfer is currently progressing.
A 3D time reversal cavity for the focusing of high-intensity ultrasound pulses over a large volume (2017)

Shock wave ultrasound therapy techniques, increasingly used for non-invasive surgery, require extremely high pressure amplitudes in precise focal spots, and large high-power transducers arranged on a spherical shell are usually used to achieve that. This solution allows limited steering of the beam around the geometrical focus of the device at the cost of a large number of transducer elements, and the treatment of large and moving organs like the heart is challenging or impossible. This paper validates numerically and experimentally the possibility of using a time reversal cavity (TRC) for the same purpose. A 128-element, 1 MHz power transducer combined with different multiple scattering media in a TRC was used. We were able to focus high-power ultrasound pulses over a large volume in a controlled manner, with a limited number of transducer elements. We reached sufficiently high pressure amplitudes to erode an Ultracal<sup>®</sup> target over a 10 cm<sup>2</sup> area.
An application specific processor for a multi-system navigation receiver (2003)

An application-specific processor for use as the central component for both signal processing and general control tasks of a combined GPS/Loran-C/Omega/MIS navigation receiver is described. It is the first implementation of the transport-triggered Move architecture framework. Vector registers are included to enhance signal processing performance, resulting in a single-cycle multiply-accumulate operation, without compromising scalar performance. The projected clock frequency of this implementation is 125 MHz for a 180000-transistor, 1.6- mu m C MOS sea-of-gates chip.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Development of radiochromic dosimeters based on polyvinyl chloride films containing 2′-anilino-6′-di-n-pentylamino-3′-methylfluoran (Black305) (2021)

Abstract We fabricated polyvinyl chloride (PVC) films containing 2′-anilino-6′-di-n-pentylamino-3′-methylfluoran (Black305) to develop radiochromic materials with high sensitivity to radiation. The optical absorption spectra of these films before and after X-ray irradiation were measured, and for comparison, we also investigated the absorption spectra of polyvinyl butyral, poly(methyl methacrylate), and polystyrene films containing Black305. The absorbance at 460 and 600 nm increased with the X-ray dose, and the change in the absorbance of the PVC film integrated over wavelengths 350–800 nm was 3.2 × 10 2 –8.1 × 10 2 times those of other films at a radiation dose of 0.5 kGy. This suggests that the oxidation of Black305 proceeds efficiently by radicals generated from PVC. The sensitivity to radiation of the PVC film was 4.4–51 times greater than that of conventional plastics containing leuco dyes, and the lower limit of detection of 1 mm PVC film containing 1 wt% Black305 was 0.11 Gy, suitable for radiotherapy dosimetry.
Abstract 693: Oncogenic and osteolytic function of histone demethylase NO66 in castration resistant prostate cancer (2016)

Abstract Androgen ablation by pharmacological use or castration is a standard therapy for treating prostate cancer (PCa), however, at the later stage PCa becomes castration-resistant and is metastasized primarily to bones. Epigenetic changes that cause dysregulated gene expression during progression and metastasis of androgen-independent prostate cancer are not clearly understood. We previously reported that the jumonji C domain-containing NO66 is a histone demethylase specific for H3K4me3 and H3K36me3, which negatively regulates osteoblast differentiation and bone formation. By analyzing a multi-cancer tissue microarray, the serendipitous observation was made that NO66 is overexpressed in a variety of cancers. Our objective was to examine NO66's role in the pathogenesis of prostate cancer and bone metastasis. Our findings indicate that NO66 knockdown resulted in significant decreases in the proliferation and invasiveness of prostate cancer cells (PC3 and DU145) while overexpressing NO66 promoted their proliferation and invasion. Furthermore, NO66 depletion resulted in a two- to three fold decrease in colony formation and anchorage-independent growth of PCa cells suggesting an oncogenic function of NO66. RNAseq analysis comparing between control and NO66-depleted DU-145 cells revealed a repertoire of differentially expressed genes. NO66 up-regulates genes with proliferative activity such as chemokine CXCL5, growth factor IGFBP5, IL6, WNT and MAPK4 pathway, which are known to drive PCa proliferation. Furthermore, ChIP sequencing for NO66 and H3K9AC in NO66-overexpressing PC3 cells revealed that interaction sites of NO66 overlap with peaks of H3K9AC in majority of the genes. These data clearly indicate that NO66 activates a cohort of genes which are involved in tumor progression and metastasis. Strikingly, implanting NO66-overexpressing prostate cancer cells into the femur of SCID male mice caused massive femoral bone loss after three weeks, which suggests that NO66 causes osteolytic bone lesions similar to the clinico-pathological features of advanced PCa. Finally, analysis of tumor xenografts derived from patients by immunohistochemistry showed high expression of NO66 in high grade advanced PCa compared to low grade and hyperplasia suggesting that NO66 may be used as a biomarker to distinguish aggressive prostate cancer from indolent stage. Our data suggest that NO66 plays an important role in cell proliferation, cell invasion and bone metastasis of prostate cancer. Citation Format: Rozita Bagheri-Yarmand, Nora Navone, Xinhai Wan, Christopher Logothetis, Johnny Huard, Krishna Sinha. Oncogenic and osteolytic function of histone demethylase NO66 in castration resistant prostate cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 693.