gebhart/patrepeval huggingface dataset:
Droplet-based combinatorial indexing for massive scale single-cell epigenomics (2019)

Abstract While recent technical advancements have facilitated the mapping of epigenomes at single-cell resolution, the throughput and quality of these methods have limited the widespread adoption of these technologies. Here, we describe a droplet microfluidics platform for single-cell assay for transposase accessible chromatin (scATAC-seq) for high-throughput single-cell profiling of chromatin accessibility. We use this approach for the unbiased discovery of cell types and regulatory elements within the mouse brain. Further, we extend the throughput of this approach by pairing combinatorial indexing with droplet microfluidics, enabling single-cell studies at a massive scale. With this approach, we measure chromatin accessibility across resting and stimulated human bone marrow derived cells to reveal changes in the cis - and trans- regulatory landscape across cell types and upon stimulation conditions at single-cell resolution. Altogether, we describe a total of 502,207 single-cell profiles, demonstrating the scalability and flexibility of this droplet-based platform.
Multi-material topology optimization for maximizing structural stability under thermo-mechanical loading (2023)

Mechanical structures are often simultaneously subjected to thermal and mechanical loading, both of which can lead to buckling failure. Developing efficient structural forms with better capacity for stability is important to keep structures safe. This study aims to optimize structural buckling capacity by using a density-based topology optimization scheme. Instead of treating the mechanical and thermal loadings as a single coupled part in the linearized buckling analysis, the effects of mechanical and thermal loadings are decoupled, which allows to separately analyze and optimize buckling aspects induced by mechanical or thermal loading. Two optimization models based on the decoupled analysis models are developed to respectively maximize the critical load factor of buckling induced by mechanical loading under a specified thermal loading and buckling induced by thermal loading under a specified mechanical loading. Further, based on a three-phase material model, a multi-material topology optimization scheme is employed to optimize the buckling capacity of active structures made of structural and actuating materials and prestressed structures containing prestressed components. The actuation effects are mimicked by the thermal loading of active material. The sensitivities of the objective functions and constraints are derived through the adjoint technique, and the method of moving asymptotes (MMA) is employed to solve the topology optimization problems. Numerical examples are adopted to verify the effectiveness of the proposed approach.
The Complete Amino-Acid Sequence of the α and β Subunits of B-Phycoerythrin from the Rhodophytan AlgaPorphyridium Cruentum (1989)

Determination of the complete amino-acid sequence of the subunits of B-phycoerythrin from Porphyridium cruentum has shown that the alpha subunit contains 164 amino-acid residues and the beta subunit contains 177 residues. When the sequences of B- and C-phycoerythrins are aligned with those of other phycobiliproteins, it is obvious that B-phycoerythrin lacks a deletion at beta-21-22 present in C-phycoerythrin. However, relative to C-phycoerythrin from Fremyella diplosiphon (Calothrix) (Sidler, W., Kumpf, B., Rüdiger, W. and Zuber, H. (1986) Biol. Chem. Hoppe-Seyler 367, 627-642), B-phycoerythrin has deletions at beta-141k-o, beta-142, beta-143, beta-147 and beta-148. The four singly-linked phycoerythrobilins at positions alpha-84, alpha-143a, beta-84 and beta-155, and the doubly-linked phycoerythrobilin at position beta-50/61 are at sites homologous to the attachment sites in C-phycoerythrin. The aspartyl residues (alpha-87, beta-87, and beta-39), that interact with the bilins at alpha-84, beta-84, and beta-155 in C-phycocyanin, are found in the homologous positions in B-phycoerythrin. B-Phycoerythrin, in common with other phycobiliproteins, contains a N gamma-methylasparagine residue at position beta-72.
Pattern recognition using discriminative feature extraction (1997)

We propose a new design method, called discriminative feature extraction for practical modular pattern recognizers. A key concept of discriminative feature extraction is the design of an overall recognizer in a manner consistent with recognition error minimization. The utility of the method is demonstrated in a Japanese vowel recognition task.
Efficient synthesis of 5-(4'-methyl[1,1'-biphenyl]-2-yl)-1H-tetrazole (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleEfficient synthesis of 5-(4'-methyl[1,1'-biphenyl]-2-yl)-1H-tetrazoleRonald K. Russell and William V. MurrayCite this: J. Org. Chem. 1993, 58, 18, 5023–5024Publication Date (Print):August 1, 1993Publication History Published online1 May 2002Published inissue 1 August 1993https://pubs.acs.org/doi/10.1021/jo00070a051https://doi.org/10.1021/jo00070a051research-articleACS PublicationsRequest reuse permissionsArticle Views376Altmetric-Citations22LEARN 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-Alertsclose Get e-Alerts
On some QoS aspects of user profile in universal multimedia access (2004)

A UMA system adapts rich multimedia contents to provide a user with the best possible presentation under the constraints of various terminals and network connections. However, the quality of adapted contents may vary widely with respect to the points-of-view of different providers and different users. So, a user should have some control on the adaptation process. We present two user's description tools, the presentation priority preference and the modality conversion preference, which allow a user to have flexible choices on the quality and modality of output contents. We also propose a systematic approach to integrate these user preferences into the adaptation process. These description tools are developed in the process of MPEG-21 standardization.
Molecular Insights into the Role of Water in Early-stage Human Amylin Aggregation (2022)

Human islet amyloid polypeptide (hIAPP or human amylin) is known to aggregate into amyloid fibrils and is implicated in the development of type II diabetes. Prefibrillar species in particular have been linked to cell loss, prompting detailed investigation of early-stage hIAPP aggregation. Insights into the mechanisms underlying early-stage aggregation and the key intermediate structures formed during aggregation are valuable in understanding disease onset at the molecular level and guiding design of effective therapeutic strategies. Here, we use atomistic molecular dynamics simulations with the finite temperature string method to identify and compare multiple pathways for hIAPP trimer formation in water. We focus on the comparison between trimerization from three disordered hIAPP chains (which we call “3-chain assembly”) and trimerization from an hIAPP dimer approached by a single disordered chain (called “2+1 assembly”). We show that trimerization is a process uphill in free energy, regardless of the trimerization mechanism, and that a high free energy barrier of 40 k B T must be crossed in 2+1 assembly compared to a moderate barrier of 12 k B T for 3-chain assembly. We find this discrepancy to originate from differences in molecular-level water interactions involved in the two trimerization scenarios. Furthermore, we find that the more thermodynamically favorable 3-chain assembly begins from a previously identified dimer intermediate exhibiting transient β -sheet character, which is then incorporated into a similar trimer intermediate, suggesting stepwise aggregation dynamics.
Data from A Clinically Applicable Gene-Expression Classifier Reveals Intrinsic and Extrinsic Contributions to Consensus Molecular Subtypes in Primary and Metastatic Colon Cancer (2023)

&lt;div&gt;AbstractPurpose:&lt;p&gt;Four consensus molecular subtypes (CMS1–4) of colorectal cancer were identified in primary tumors and found to be associated with distinctive biological features and clinical outcomes. Given that distant metastasis largely accounts for colorectal cancer–related mortality, we examined the molecular and clinical attributes of CMS in metastatic colorectal cancer (mCRC).&lt;/p&gt;Experimental Design:&lt;p&gt;We developed a colorectal cancer–focused NanoString-based CMS classifier that is ideally suited to interrogate archival tissues. We successfully used this panel in the CMS classification of formalin-fixed paraffin-embedded (FFPE) tissues from mCRC cohorts, one of which is composed of paired primary tumors and metastases. Finally, we developed novel mouse implantation models to enable modeling of colorectal cancer &lt;i&gt;in vivo&lt;/i&gt; at relevant sites.&lt;/p&gt;Results:&lt;p&gt;Using our classifier, we find that the biological hallmarks of mCRC, including CMS, are in general highly similar to those observed in nonmetastatic early-stage disease. Importantly, our data demonstrate that CMS1 has the worst outcome in relapsed disease, compared with other CMS. Assigning CMS to primary tumors and their matched metastases reveals mostly concordant subtypes between primary and metastasis. Molecular analysis of matched discordant pairs reveals differences in stromal composition at each site. The development of two novel &lt;i&gt;in vivo&lt;/i&gt; orthotopic implantation models further reinforces the notion that extrinsic factors may impact on CMS identification in matched primary and metastatic colorectal cancer.&lt;/p&gt;Conclusions:&lt;p&gt;We describe the utility of a NanoString panel for CMS classification of FFPE clinical samples. Our work reveals the impact of intrinsic and extrinsic factors on colorectal cancer heterogeneity during disease progression.&lt;/p&gt;&lt;/div&gt;
HER2 testing in breast cancer by quantitative PCR: technical and clinical considerations. (2015)

e11619 Background: HER2 gene is amplified and/or overexpressed in approximate 15% to 20% of primary breast cancers. Knowing the HER2 status is therefore essential for making right decision. Quantitative PCR is originally designed for analyzing gene expression, and now is gaining wide use in molecular diagnostics. We made some key changes to the steps and streamlined the whole process to provide a convenient method for determining the HER2expression level in breast cancer patients. Methods: A total of 80 freshly-frozen or FFPE breast tumor samples, with a minimal of 30% tumor cell content, were collected from three different locations. Total RNA was extracted by a dual process and was adjusted to a concentration of 25 ng/ml. The same amount of RNA from each sample was analyzed by RT-PCR. Result was reported automatically as delta Ct (ΔCt) respect to a cutoff reference point (CRP), which was derived from a tumor HER2 mRNA population study and monitored in each assay with a traceable material, synthetic oligo. The ΔCtvalue then was used for determination of HER2 expression level. Results: We simplified quantitative PCR steps and optimized assay process by incorporating a self quality control mechanism. Our studies demonstrated that the improved method had a linear range up to 7-order magnitude with less than 8% intra- and inter-assay variance. We established criteria for using total RNA as assay normalizer; therefore, eliminated the needs for choosing a particular reference gene. We introduced a new scoring system based on a CRP, which produced consistent/comparable scoring results on different PCR machines and in different laboratories. A comparison study with FISH revealed an overall 90% agreement. Our method was also suitable for HER2 testing in blood samples, making it feasible to track patient HER2level after clinical intervention. Conclusions: HER2 testing by quantitative PCR method is accurate, consistent, and cost-effective. The whole process can be accomplished in less than 3 hours. The improved method also circumvents many drawbacks associated with testing by IHC and FISH. It is beyond doubt that adoption of quantitative PCR represents a new trend in HER2 testing and would improve clinical outcomes.
Nucleoside Optimization for RNAi: A High-Throughput Platform (2011)

The RNA induced silencing complex (RISC) contains at its core the endonuclease Argonaute (Ago) that allows for guide strand (GS)-mediated sequence-specific cleavage of the target mRNA. Functionalization of the sugar/phosphodiester backbone of the GS, which is in direct contact with Ago, presents a logical opportunity to affect RISC's activity. A systematic evaluation of modified nucleosides requires the synthesis of phosphoramidites corresponding to all four canonical bases (A, U, C, and G) and their sequential evaluation at each position along the 21-nucleotide-long GS. With the use of a platform approach, the sequential replacement of canonical bases with inosine greatly simplifies the problem and defines a new activity baseline toward which the corresponding sugar-modified inosines are compared. This approach was validated using 2'-O-benzyl modification, which demonstrated that positions 5, 8, 15, and 19 can accommodate this large group. Application of this high-throughput methodology now allows for hypothesis-driven rational design of highly potent, immunologically silent and stable siRNAs suitable for therapeutic applications.
The interaction specificity of peptides with DNA. Evidence of peptide β-sheet-DNA binding (1976)

Proton magnetic resonance studies (1H NMR) of the interaction of oligopeptide amides of defined sequence (and containing the amino acid, phenylalanine) with salmon sperm DNA are reported. The extent of upfield chemical shifts, deltasigma, and signal line broadening of the aromatic protons (in the presence of excess DNA) are found to depend on the primary sequence and stereochemistry of alpha carbons of the amino acids in the oligopeptide amides. The results obtained with 21 different di-, tri-, tetra-, penta- and hexapeptide amides are found to be consistent with a model whereby the peptide assumes a slightly modified single-stranded beta-sheet structure which is wrapped around the nucleic acid helix in a manner similar to that described by M. H. F. Wilkins (1956), Cold Spring Harbor Symp. Quant. Biol. 21, 75).
COOPERATIVE COMMUNICATIONS: Fundamental Limits and Practical Implementation (2006)

This chapter summarizes theoretically achievable gains and the construction of practical codes for user-cooperation.Most of these results relate to the relay channel, which is a three-terminal channel that captures the essence of usercooperation and serves as one of the primary building blocks for cooperation on a larger scale.In investigating the fundamental limits of relaying, we present information-theoretic results on the achievable throughput of relay channel in mutual-information terms.We also include results on Gaussian channels, and for the practically important case of half-duplex relaying.In the domain of relay coding, we specifically discuss pragmatic code constructions for half as well as full-duplex relaying, using LDPC codes as components.
Melanocortin Receptors, Melanotropic Peptides and Penile Erection (2007)

Penile erection is a complex physiologic event resulting from the interactions of the nervous system on a highly specialized vascular organ. Activation of central nervous system melanocortinergic (MC) receptors with either endogenous or synthetic melanotropic ligands may initiate and/or facilitate spontaneous penile erection. While the CNS contains principally the MC3 and MC4 receptor subtypes, there is conflicting data as to which receptor mediates erection. Although the MC4R is emerging as the principle effector of MC induced erection, the role of the MC3R is poorly understood. Manipulation of each receptor subtype with newly synthesized receptor specific agonists and antagonists, as well as knockout mice, has elucidated their individual contributions. Novel data from our laboratories suggests that antagonism of forebrain MC3R may enhance melanocortin-induced erections. Furthermore, melanocortin agents may interact with better-studied systems such as oxytocinergic pathways at the hypothalamic, brainstem or spinal level. Current therapies for erectile dysfunction target end organ vascular tissue. Manipulation of MC receptors may provide an alternative, centrally mediated therapeutic approach for erectile and other sexual dysfunctions. The non-specific “ superpotent ” MC agonist, PT-141, which is the carboxylate derivative of MT-II, has reached phase II human trials. Through their centrally mediated activity, melanocortin agonists have potential to treat erectile dysfunction as well as possible applications to the unmet medical needs of decreased sexual motivation and loss of libido.
Application of targeted maximum likelihood estimation technique to assess the impact of prenatal exposure to nitrogen dioxide and ozone on stillbirth in a California cohort study (2016)

Introduction: Prior work has established an association between ambient air pollution and stillbirth, but a causal relationship has not been demonstrated. Furthermore, prior studies have relied on parametric model assumptions that may not be justified. We addressed these limitations by applying modern causal inference and machine learning methods to quantify the causal effect of prenatal nitrogen dioxide (NO2) and ozone (O3) exposures on stillbirth. Method: We used data from the CA Dept. of Public Health and CA Air Resources Board to evaluate pollutant exposure during the 3rd trimester and subsequent birth outcomes among 2,581,211 women. Using inverse-probability-of censoring-weighted targeted maximum likelihood estimation (IPCW-TMLE), we estimated the causal attributable risk (CAR) of stillbirth for each exposure quartile and the marginal risk difference (RD) in stillbirth between exposures quartiles of the pollutants considered. An outcome regression and propensity score were estimated using Super Learner (a machine-learning algorithm based on cross-validation) and were incorporated in IPCW-TMLE to adjust for demographic, environmental and neighborhood-level confounders. Result: 0.28% of women experienced a stillbirth. Based on CAR estimates, if all pregnant women in our population were shifted to the highest NO2 or O3 exposure quartiles during the 3rd trimester, the proportion experiencing a stillbirth would increase by 0.19% (95% confidence interval (CI): 0.13, 0.24%) or 0.36% (0.32, 0.40%), respectively. Based on RD estimates, if all women moved from the lowest to the highest exposure quartiles of NO2 or O3 in the 3rd trimester, the probability of stillbirth would increase by 0.05% (-0.04, 0.13%) or 0.39% (0.35, 0.45%), respectively. Conclusion: Preliminary results support a causal impact of prenatal NO2 and O3 exposures on stillbirth, and demonstrate the utility of modern semi-parametric methods for assessing the impact of policies that target these pollutants.
Combining X-Ray Fluorescence Spectrometry and Vibrational Microscopy to Assess Highly Heterogeneous, Actinide-Contaminated Materials (1999)

Combining X-ray fluorescence (XRF) spectrometry with micro-Raman and infrared spectroscopies is shown to be a powerful experimental approach in providing information on components present in highly heterogeneous materials which contain or have been in contact with actinides. In this initial study, the quantitative XRF data demonstrate a correlation in the relative amounts of plutonium with other elements such as strontium and yttrium. The XRF mapping provides further evidence for correlation of these (and other) elements and identifies regions of interest within the sample to be further studied. These regions were then examined by vibrational microscopy to supply information on molecular species present and their spatial distribution. This experimental approach provides insight into very complex samples and provides a technique capable of exploring interactions of molecular components with actinides in complex media.
Supplementary Figure 4 from The Gut Microbiome Associates with Immune Checkpoint Inhibition Outcomes in Patients with Advanced Non–Small Cell Lung Cancer (2023)

&lt;p&gt;Supplementary Figure 4&lt;/p&gt;
D-Optimal Mixture Design: Optimization of Ternary Matrix Blends for Controlled Zero-Order Drug Release From Oral Dosage Forms (2006)

The objective of the present study was to develop a tablet formulation with a zero-order drug release profile based on a balanced blend of three matrix ingredients. To accomplish this goal, a 17-run, three-factor, two-level D-Optimal mixture design was employed to evaluate the effect of Polyox (X1), Carbopol (X2), and lactose (X3) concentrations on the release rate of theophylline from the matrices. Tablets were prepared by direct compression and were subjected to an in vitro dissolution study in phosphate buffer at pH 7.2. Polynomial models were generated for the responses Y4 (percent released in 8 h) and Y6 (similarity factor or f2). Fitted models were used to predict the composition of a formulation that would have a similar dissolution profile to an ideal zero-order release at a rate of 8.33% per hour. When tested, dissolution profile of the optimized formulation was comparable to the reference profile (f2 was 74.2, and n [release exponent] was 0.9). This study demonstrated that a balanced blend of matrix ingredients could be used to attain a zero-order release profile. Optimization was feasible by the application of response surface methodology, which proved efficient in designing controlled-release dosage forms.
Roles of Copper and Nickel in 13%Cr Stainless Steel for Improvement of Wet Carbon Dioxide Corrosion Resistance (2001)

Resistance to hydrogen sulfide (H2S) and carbon dioxide (CO2) corrosion in 13%Cr stainless steel (SS) has been studied to develop a new material in an application field of oil country tubular goods (OCTG). Recently, the combined addition of copper and nickel was found to increase the corrosion resistance of 13%Cr SS under wet, high-temperature, and CO2 environments. The purpose of the present work was to make clear the role of such copper and nickel elements as additive elements to the 13%Cr SS. With the increase in the addition of copper and nickel to the steel, a thickness of corrosion film growing in the immersion test decreased drastically, and the corrosion rate reached &amp;lt; 0.1 mm/y, even at 200°C. The transmission electron microscope analysis revealed that the thin corrosion film was an amorphous phase, and that the addition of copper caused the change of the corrosion film structure from a spinel crystalline to the amorphous one. Nano-ordered segregation of copper at the interface between the corrosion film and a steel was detected in the case of amorphous corrosion film; that is, the copper segregation was considered to be a dominant factor to form the amorphous corrosion film. Since the added nickel increased the solubility of copper in the steel, the role of nickel is discussed from the viewpoint of an assist effect of copper for the improvement of the corrosion resistance.