gebhart/patrepeval huggingface dataset:
1509 Differences in chromatin architecture pre- and post-induction therapy in pediatric lupus patients (2021)

<h3>Background</h3> Systemic lupus erythematosus (SLE) may be triggered by gene-environment interactions. Data remain scarce on how epigenetic variance contributes to disease risk in pediatric SLE (pSLE). Our objectives were to identify differences in chromatin architecture in treatment-naïve pSLE compared to healthy children (HC) and pSLE patients after induction therapy. <h3>Methods</h3> We used assays for transposase-accessible chromatin-sequencing (ATACseq) in 8 pSLE patients pre- and post-induction therapy and 5 HC to investigate whether regions of open chromatin unique to pSLE patients demonstrate enrichment for transcriptional regulators, using standard computational approaches and a false discovery rate of &lt;0.05. <h3>Results</h3> The mean age of onset was 13.75 (range 7-17) years in pSLE, and mean SLEDAI was 12.8 (range 6-24). We identified 245 differentially accessible regions (DAR) around peaks unique to treatment-naïve pSLE patients, of which over 50% appear to be more accessible in pSLE than HC, and are located more than 100kb from the nearest transcription start site (nTSS), implying transcription factors (TF) may be acting on distal enhancers to regulate transcription. pSLE DAR were enriched for the enhancer H3K4me3. In DAR encompassing TF binding sites, pSLE samples, but not HC, were enriched for several disease-associated SNPs previously identified in lupus genome-wide association studies. Variant calling within DAR found 3864 genes belonging to 129 different biologic processes, including cellular activation in immune response and responses to external stimuli. In contrast, over 80% of peaks unique to pSLE patients post-induction therapy are located distal to nTSS. Induction therapy for pSLE patients included corticosteroids in all patients, cyclophosphamide in 5, and mycophenolate in 3. DAR from the pSLE patients post-induction therapy were not enriched for enhancers or disease-associated SNPs. <h3>Conclusion</h3> We demonstrate an epigenetically-distinct profile in pSLE B cells when compared to HC, indicating pSLE B cells are predisposed for disease development. Pathways of significance analyses identified immunologic pathways important in the pro-inflammatory response in treatment-naïve pSLE patients. These pathways were absent in analyses from the same pSLE patients post-induction therapy. Thus, increased chromatin accessibility in genomic regions controlling activation of inflammatory and immune responses suggest transcriptional dysregulation of key players in immune cell activation plays an important role in pathogenesis of SLE. Treatment with corticosteroids and immunosuppressive medication changes this epigenetic profile, making pathways responsible for inflammation and B cell activation less accessible. <h3>Acknowledgment</h3> This work would not have been possible without the expertise of Dr Frank Jenkins. This work was funded by the Rheumatology Research Foundation.
Biochemical and Functional Correlates of Myocardium-Like Transformed Skeletal Muscle as a Power Source for Cardiac Assist Devices (1989)

Skeletal muscles, such as the latissimus dorsi muscle, can be transformed to gain considerable fatigue resistance to be suitable either for cardiomyoplasty, or to power a cardiac assist device. Such transformation of the skeletal muscle can be achieved by low frequency electrical stimulation for several weeks. In this article, we reviewed the stimulation protocol, and subsequent histochemical, biochemical, and functional changes in the skeletal muscle, and compared them to those of the cardiac muscle. The parameters that should be useful for stimulating such a muscle to assist the heart are defined. The issues currently under study, including the optimal transformation parameters, the feasibility of working transformation, and the importance of device design to minimize vascular compromise of the muscle, are also discussed. It is concluded that there is a great potential to use the plasticity of skeletal muscle for clinical purposes, specifically by transforming the skeletal muscle to resemble the myocardium in order to use it either to replace or repair the myocardium, or as the endogenous power source for a cardiac assist device.
Chemotherapy-Free Targeted Anti-BCR-ABL+ Acute Lymphoblastic Leukemia Therapy May Benefit the Heart (2022)

Targeted therapies are currently considered the best cost-benefit anti-cancer treatment. In hematological malignancies, however, relapse rates and non-hematopoietic side effects including cardiotoxicity remain high. Here, we describe significant heart damage due to advanced acute lymphoblastic leukemia (ALL) with t(9;22) encoding the bcr-abl oncogene (BCR-ABL+ ALL) in murine xenotransplantation models. Echocardiography reveals severe cardiac dysfunction with impaired left ventricular function and reduced heart and cardiomyocyte dimensions associated with increased apoptosis. This cardiac damage is fully reversible, but cardiac recovery depends on the therapy used to induce ALL remission. Chemotherapy-free combination therapy with dasatinib (DAS), venetoclax (VEN) (targeting the BCR-ABL oncoprotein and mitochondrial B-cell CLL/Lymphoma 2 (BCL2), respectively), and dexamethasone (DEX) can fully revert cardiac defects, whereas the depletion of otherwise identical ALL in a genetic model using herpes simplex virus type 1 thymidine kinase (HSV-TK) cannot. Mechanistically, dexamethasone induces a pro-apoptotic BCL2-interacting mediator of cell death (BIM) expression and apoptosis in ALL cells but enhances pro-survival B-cell lymphoma extra-large (BCLXL) expression in cardiomyocytes and clinical recovery with the reversion of cardiac atrophy. These data demonstrate that therapies designed to optimize apoptosis induction in ALL may circumvent cardiac on-target side effects and may even activate cardiac recovery. In the future, combining the careful clinical monitoring of cardiotoxicity in leukemic patients with the further characterization of organ-specific side effects and signaling pathways activated by malignancy and/or anti-tumor therapies seems reasonable.
Development of on‐chip fully automated immunoassay system “μTASWako i30” to measure the changes in glycosylation profiles of alpha‐fetoprotein in patients with hepatocellular carcinoma (2016)

Glycosylation profiles significantly change during oncogenesis. Aberrant glycosylation can be used as a cancer biomarker in clinical settings. Different glycoforms can be separately detected using lectin affinity electrophoresis and lectin array-based methods. However, most methodologies and procedures need experienced technique to perform the assays and expertise to interpret the results. To apply glycomarkers for clinical practice, a robust assay system with an easy-to-use workflow is required. Wako's μTASWako i30, a fully automated immunoanalyzer, was developed for in vitro diagnostics based on microfluidic technology. It utilizes the principles of liquid-phase binding assay, where immunoreactions are performed in a liquid phase, and electrokinetic analyte transport assay. Capillary electrophoresis on microfluidic chip has enabled the detection of different glycoform types of alpha-fetoprotein (AFP), a serum biomarker for hepatocellular carcinoma. AFP with altered glycosylation can be separated based on the reactivity to Lens culinaris agglutinin on electrophoresis. The glycoform AFP-L3 was reportedly more specific in hepatocellular carcinoma. This assay system can provide a high sensitivity and rapid results in 9 min. The test results for ratio of AFP-L3 to total AFP using μTASWako i30 are correlated with those of conventional methodology. The μTASWako assay system and the technology can be utilized for glycosylation analysis in the postgenomic era.
Air Pump – Improvement of a ‘Skyscraper-type’ exercise for Mechanical Engineering Programs (2011)

The ‘Air Pump’ is a current criteria-based 'design-build-test' exercise in the MEC1110 first-year project module. Students work from a ‘functional requirement’ sheet where criteria are related to primary and complementary functions and constraints. Building materials are disposable coffee cups and stir-sticks, freezer bags, and the like. Flow, pressure, and volume are tested. A first reflection phase is individual, followed by a group discussion. Team organisation, time management, responsibilities are discussed as well as ethics (as all had chances to ‘pretend’ on their score-sheets or financial reporting). Some tuning is required to improve the percentage of working pumps, and the benefits of the reflection phase. The teachers of the module hope a collaborative freestyle hands-on exercise by CDIO colleagues will benefit all involved. (A short video 'AirPump(EPM)_iPod.mp4' 16MB can be made available.)
Something Old, Something New, Something Borrowed; How the Thermoacidophilic Archaeon Sulfolobus solfataricus Responds to Oxidative Stress (2009)

To avoid molecular damage of biomolecules due to oxidation, all cells have evolved constitutive and responsive systems to mitigate and repair chemical modifications. Archaea have adapted to some of the most extreme environments known to support life, including highly oxidizing conditions. However, in comparison to bacteria and eukaryotes, relatively little is known about the biology and biochemistry of archaea in response to changing conditions and repair of oxidative damage. In this study transcriptome, proteome, and chemical reactivity analyses of hydrogen peroxide (H(2)O(2)) induced oxidative stress in Sulfolobus solfataricus (P2) were conducted. Microarray analysis of mRNA expression showed that 102 transcripts were regulated by at least 1.5 fold, 30 minutes after exposure to 30 microM H(2)O(2). Parallel proteomic analyses using two-dimensional differential gel electrophoresis (2D-DIGE), monitored more than 800 proteins 30 and 105 minutes after exposure and found that 18 had significant changes in abundance. A recently characterized ferritin-like antioxidant protein, DPSL, was the most highly regulated species of mRNA and protein, in addition to being post-translationally modified. As expected, a number of antioxidant related mRNAs and proteins were differentially regulated. Three of these, DPSL, superoxide dismutase, and peroxiredoxin were shown to interact and likely form a novel supramolecular complex for mitigating oxidative damage. A scheme for the ability of this complex to perform multi-step reactions is presented. Despite the central role played by DPSL, cells maintained a lower level of protection after disruption of the dpsl gene, indicating a level of redundancy in the oxidative stress pathways of S. solfataricus. This work provides the first "omics" scale assessment of the oxidative stress response for an archeal organism and together with a network analysis using data from previous studies on bacteria and eukaryotes reveals evolutionarily conserved pathways where complex and overlapping defense mechanisms protect against oxygen toxicity.
Survivable network architecture for colorless WDM-PON against both feeder and distribution fiber failures (2008)

We experimentally d emonstrate a novel survivable WDM-PON architecture with colorless ONUs. It uses N × N arrayed waveguide grating to provide bidirectional protection capability against not only feeder fiber cut but also distribution fiber cuts.
Capturing viral diversity for in-vitro test reagents and HIV vaccine immunogen design (2007)

These recent findings and newly developed strategies that allow more comprehensive detection of HIV-specific T-cell responses provide the tools necessary to assess vaccine immunogenicity and breadth within genetically different host populations and relative to diverse local viral populations. They will ultimately inform design of vaccine immunogen sequences that can induce broadly protective cellular immunity.
UV-induced porosity using photogenerated acids to catalyze the decomposition of sacrificial polymers templated in dielectric films (2006)

A UV-initiated process for selective incorporation of porosity and tuning of refractive index in a dielectric film is presented. The formation of porosity via radiation offers the advantages of lower processing temperatures and shorter processing times than most processes that rely on thermally-induced porosity. The ability to pattern porosity via the use of a photomask allows structures such as porous direct-write waveguides to be made. The direct-write process presented here used UV-generated acids to catalyze the decomposition of sacrificial polymers templated in a crosslinked matrix, resulting in the formation of porosity and decrease of refractive index and dielectric constant after subsequent removal of the generated acid. In unexposed areas, no acid molecules were generated, thus these areas remained non-porous and their refractive index remained relatively high compared to porous regions. Base-catalyzed gelation was used to crosslink the matrix at temperatures well below the glass transition temperature of the matrix in order to avoid thermal activation of the photoacid generators (PAGs) in the direct-write formulation. After crosslinking the matrix, deep ultraviolet (DUV) radiation was used to initiate the direct-write reactions thus creating a refractive index profile within the film. Neutralization or volatilization of the photogenerated acid was used to deactivate the system. The lowest interline dielectric constant achieved by direct-written films was 2.36 after the volatilization step compared to a value of 2.29 for porous films formed via the traditional template process. At optimum conditions, the average amount of UV-induced porosity was estimated to be as high as 21%. Transmission electron microscopy (TEM) imaging showed that elongated mesopores (10 nm by about 20–30 nm) and elongated macropores (100 nm by about 200 nm in size) were produced within the internal structure of direct-written films. The porous films formed via the traditional template technique had internal structures with large collections of spherical mesopores (5–10 nm) located in close proximity to one another due to phase segregation of the polymer at high temperatures.
Reaction of carbonyl compounds with dimethyl 3‐ketoglutarate. Synthesis of bicyclic furan derivatives (1977)

Abstract Acid catalyzed reaction of cyelododecane‐1,2‐dione VI with dimethyl,3‐ketoglutarate II led to the formation of methyl ( E )‐6,7,8,9,10,11,12,13‐octahydro‐3‐(methoxycarbonyl)cyclododeca‐[ b ]furan‐2‐aeetate IX, presumably formed through the dihydrodihydroxy furan VIII. This dihydrofuran intermediate VIII was shown to be characteristic of the reaction of 2‐substituted carbonyl‐compounds with 11 for both α‐chlorocyclohexanone and α‐chlorocyclopentanone furnished furans XVIa and XX, respectively, when treated with 11. The effect of dihydrodihydroxy‐furan intermediates on the course of such reactions is discussed.
New natural anthraquinones from cochineal (Dactylopius coccus) (2010)

Cochineal is one of most well known organic red dyes. Dactylopius coccus Costa (Dactylopiidae) is a scale insect that is used as the source of the dye known as Mexican cochineal. Cochineal is today a natural food colorant (E120) and is also used in cosmetics and in pharmaceutical industry. Although cochineal has been used in art objects (textiles and paintings) for centuries, its exact chemical consistency is not well clarified [1] except for carminic acid which is the major component and kermesic and flavokermesic acids. Several minor components (typically less than 5% of the coloring material) remain unknown even though their presence is characteristic for the origin of cochineal. Chemical investigation of the methanol extract of the dried insects, after subsequent HPLC chromatographic separations, led to the isolation and structure elucidation of two new anthraquinones (1 and 2), along with the known compounds karminic acid, kermesic acid and flavokermesic acid. The structures of the new compounds were elucidated on the basis of their NMR and MS data. Interestingly, the new compounds were detected as minor constituents of historical art objects.
Progression Model of Prostate Cancer (2003)

Prostate cancer is the most common form of cancer diagnosed in men (other than skin cancer). In 1999, in the United States alone there were approximately 179,300 new cases and 37,000 deaths due to prostate cancer (1). In 1999, the prostate cancers diagnosed accounted for 29% of cancers in men and 14.7% of all cancers (other than skin) in both sexes, making it the most diagnosed cancer in the total population. In the prostate, the formation of histologically identifiable neoplastic lesions is a very frequent event, occurring in nearly one-third of the male population over 45 years of age (2). Fortunately, it has been estimated that only a small percentage of these men will actually die from prostate cancer (3–6). There is evidence to support environmental (including cell-cell interactions), epigenetic, and other factors playing a role in prostate tumorigenesis (7–17). However, that cancer in general is a genetic disease is currently the most widely accepted model of tumor etiology (18,19). A number of genetic changes have been documented in prostate cancer. Consistently, allelic losses of specific chromosomes are observed in prostate tumors, but this is not true for mutations on specific genes (20–22). Prostate cancers require many years to develop. It is believed that during these years they accumulate a number of genetic alterations. However, the molecular events that underlie the development of prostate neoplasia are not well defined (22). Thus, it has been difficult to establish a genetic model for the progression of prostate cancer.
Consideration of current resonant converter topology for bi-directional applications (2013)

This paper investigates the topology selection of the current resonant converter for bidirectional applications. The current resonant converter has several topologies which categorized switch network construction and resonant network construction. It is important that the topology is selected suitable for each application from several circuit topologies. In this paper, the operating characteristics are discussed in detailed in order to evaluate the appropriateness for each application. Moreover, the applicable topology is selected from detail operating characteristics.
The F12-Vif derivative Chim3 inhibits HIV-1 replication in CD4+ T lymphocytes and CD34+-derived macrophages by blocking HIV-1 DNA integration (2009)

The viral infectivity factor (Vif) is essential for HIV-1 infectivity and hence is an ideal target for promising anti-HIV-1/AIDS gene therapy. We previously demonstrated that F12-Vif mutant inhibits HIV-1 replication in CD4(+) T lymphocytes. Despite macrophage relevance to HIV-1 pathogenesis, most gene therapy studies do not investigate macrophages because of their natural resistance to genetic manipulation. Here, we confirm the F12-Vif antiviral activity also in macrophages differentiated in vitro from transduced CD34(+) human stem cells (HSCs). Moreover, we identified the 126- to 170-amino-acid region in the C-terminal half of F12-Vif as responsible for its antiviral function. Indeed, Chim3 protein, containing this 45-amino-acid region embedded in a WT-Vif backbone, is as lethal as F12-Vif against HIV-1. Of major relevance, we demonstrated a dual mechanism of action for Chim3. First, Chim3 functions as a transdominant factor that preserves the antiviral function of the natural restriction factor APOBEC3G (hA3G). Second, Chim3 blocks the early HIV-1 retrotranscript accumulation and thereby HIV-1 DNA integration regardless of the presence of WT-Vif and hA3G. In conclusion, by impairing the early steps of HIV-1 life cycle, Chim3 conceivably endows engineered cells with survival advantage, which is required for the efficient immune reconstitution of patients living with HIV/AIDS.
P3‐182: Identification of target engagement biomarkers for MARK inhibitor discovery using quantitative mass spectrometry (2010)

Neurofibrillary tangles, a major pathological hallmark of Alzheimer's disease, are composed mainly of hyper-phosphorylated tau. Microtubule affinity regulating kinase (MARK) is a major kinase that phosphorylates Ser262 of tau. Ser262 phosphorylation prevents the binding of tau to microtubule, thereby increasing the pool of monomeric tau to aggregate eventually into neurofibrillary tangles. Therefore, developing a MARK inhibitor to lower Ser262 tau phosphorylation may represent a novel disease-modifying treatment for AD. In the course to develop highly selective kinase inhibitors, it is critical to co-develop target engagement biomarkers as they are essential for the interpretation of in vivo PK/PD relationship. However, there exist few known specific kinase substrates for MARK that could be used as target engagement markers. Since the level of autophosphorylation of many kinases is known to correlate with the level of kinase activity, we developed a mass-spectrometry-based approach combined with SILAC (stable isotope labeling with amino acids in cell culture) to discover autophosphorylation sites on MARK as target engagement biomarkers. From human MARK3 protein purified from transiently transfected HEK293 cells, we mapped 22 Serine/Threonine phosphorylation sites on MARK3. Comparing the MARK3 protein purified from either vehicle or MARK inhibitor treated cells, the levels of three phospho-peptides (including five phosphorylated Serines) reduced in response to MARK inhibitor compounds from two distinct structural series and in a dose-dependent manner, correlating to inhibitor potency on reducing Ser262 tau phosphorylation. These results suggest that these sites are auto-phosphorylation sites of MARK3. We identified five potential auto-phosphorylation sites of MARK3 by quantitative mass spectrometry. Next, antibodies could be raised against these sites to confirm their regulation by MARK inhibitors via Western blot analysis. Once confirmed, these autophosphorylation sites may serve as target engagement biomarkers for MARK inhibition.
Advanced Free Radical Reactions for Organic Synthesis By Hideo Togo (Chiba University). Elsevier:  Amsterdam. 2004. xii + 258 pp. $178.00. ISBN 0-08-044374-5. (2004)

ADVERTISEMENT RETURN TO ISSUEPREVBook ReviewNEXTAdvanced Free Radical Reactions for Organic Synthesis By Hideo Togo (Chiba University). Elsevier: Amsterdam. 2004. xii + 258 pp. $178.00. ISBN 0-08-044374-5.Dennis P. CurranView Author Information University of PittsburghCite this: J. Am. Chem. Soc. 2004, 126, 34, 10795–10796Publication Date (Web):July 10, 2004Publication History Published online10 July 2004Published inissue 1 September 2004https://pubs.acs.org/doi/10.1021/ja0409255https://doi.org/10.1021/ja0409255book-reviewACS PublicationsCopyright © 2004 American Chemical SocietyRequest reuse permissionsArticle Views410Altmetric-Citations1LEARN 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 SUBJECTS:Chemical reactions,Cyclization,Organic reactions Get e-Alerts