gebhart/patrepeval huggingface dataset:
Systemic delivery of therapeutic nucleic acids into skeletal muscle by means of lipid-based vectors (2005)

Introduction : Lipid-based vectors are considered a promising tool when a systemic delivery is desirable. Although not\nas efficient as viral vectors, lipoplexes present some major advantages, as they are non immunogenic, non mutagenic,\nas well as easy and cheap to prepare. We had previously shown that skeletal muscles are poorly accessible to\nlipoplexes via intra-venous administration, whereas local intra-arterial delivery yielded good preliminary results.\nObjectives : Optimization of a lipid-based, systemic gene delivery system capable of introducing therapeutic nucleic\nacids into skeletal muscle.\nMethods : We use lipid-based vehicles containing the cationic lipid DODAC, formulated either as conventional or\nencapsulated PEG-ylated lipoplexes.\nResults : We injected lipoplexes in the femoral artery of adult rats in which muscle regeneration was chemically induced\nin the TA muscles. Using an encapsulated formulation (SPLP, developed by Protiva Bioteherapeutics) we obtained up to\n10% of GFP+ve fibers after a single injection. High transfection levels were maintained for at least three weeks. At the\nsame time, we showed that SPLPs only induced a slight delay in the process of muscle regeneration and did not lead to\nany germ-line transmission of the transgene. More recently we began to apply our delivery protocol to the development\nof an exon-skipping approach for the correction of mutations in the dystrophin gene. In particular, we are using DODACbased\nlipoplexes to deliver an exon 23-specific morpholino AO into the muscles of mdx mice. Our initial data showed the\nproduction of a significant amount (i.e., as abundant as the wild type or higher) of the desired skipped mRNA in the leg\nmuscle groups of the injected limbs. The effect of the treatment on dystrophin production is presently being assessed.\nConclusions : Our data indicate that both encapsulated and conventional lipoplexes have the potential to be used for\nthe development of therapeutic protocols for muscle diseases.
Nidulal, a Novel Inducer of Differentiation of Human Promyelocytic Leukemia Cells from Nidula candida. (1996)

Nidulal (1), a novel inducer of differentiation of human HL-60 promyelocytic leukemia cells, was isolated from fermentations of the basidiomycete Nidula candida together with low amounts of niduloic acid (2). Both compounds are bisabolane sesquiterpenes. Their structures were elucidated by spectroscopic methods. In reporter gene assays nidulal (1) preferentially activated the transcription factor complex AP-1-mediated expression of secreted alkaline phosphatase in COS-7 cells. In addition nidulal (1) and niduloic acid (2) exhibited weak cytotoxic and antibiotic activities.
BYOC (2020)

Heterogeneous architectures and heterogeneous-ISA designs are growing areas of computer architecture and system software research. Unfortunately, this line of research is significantly hindered by the lack of experimental systems and modifiable hardware frameworks. This work proposes BYOC, a "Bring Your Own Core" framework that is specifically designed to enable heterogeneous-ISA and heterogeneous system research. BYOC is an open-source hardware framework that provides a scalable cache coherence system, that includes out-of-the-box support for four different ISAs (RISC-V 32-bit, RISC-V 64-bit, x86, and SPARCv9) and has been connected to ten different cores. The framework also supports multiple loosely coupled accelerators and is a fully working system supporting SMP Linux. The Transaction-Response Interface (TRI) introduced with BYOC has been specifically designed to make it easy to add in new cores with new ISAs and memory interfaces. This work demonstrates multiple multi-ISA designs running on FPGA and characterises the communication costs. This work describes many of the architectural design trade-offs for building such a flexible system. BYOC is well suited to be the premiere platform for heterogeneous-ISA architecture, system software, and compiler research.
Hydrogenation of dibenzyltoluene and the catalytic performance of Pt/ Al 2 O 3 with various Pt loadings for hydrogen production from perhydro‐dibenzyltoluene (2021)

The characteristics of the hydrogenation of dibenzyltoluene and dehydrogenation of perhydro-dibenzyltoluene (H18-DBT) are investigated. The hydrogenation experiments are conducted using Raney-Ni. It is found that 170°C and 7 MPa is the optimal reaction condition at which the hydrogen capacity of 6.2 wt% is achieved in 30 hours. The optimal temperature for the dehydrogenation of H18-DBT is found to be 290°C. Moreover, the dehydrogenation of H18-DBT is carried out over Pt/Al2O3 catalysts with different Pt metal loadings (1% ~ 5%). The results elucidate that 5% Pt/Al2O3 is the most active catalyst yielding 90.2% of the stored hydrogen in 7 hours. The catalytic activity of the catalysts is in the order 5% > 4% > 3% > 2% > 1% Pt/Al2O3. The increment in catalyst dosage increases the reaction rate and hydrogen yield%. Lastly, the cyclic experiments are conducted and DBT is found to be quite stable in all three cycles. HIGHLIGHTS The complete hydrogenation (6.2 wt%) of dibenzyltoluene is achieved at 170°C and 5 ~ 7 MPa. The dehydrogenation of perhydro-dibenzyltoluene is conducted over 1 ~ 5% Pt/Al2O3. The 90.2% of stored hydrogen is produced over the optimal catalyst, 5% Pt/Al2O3. The hydrogen production in all the three cycles is almost similar which makes dibenzyltoluene a stable liquid organic hydrogen carrier.
The first announcement about the 1918 "Spanish flu" pandemic in Greece through the writings of the pioneer newspaper "Thessalia" almost a century ago. (2015)

A local pioneer newspaper, "Thessalia", was the first to announce the arrival of "Spanish Flu" in Greece. It was July 19th 1918 when an epidemic outbreak occurred in the city of Patras. Until then, "Thessalia" had dealt in depth with the flu pandemic in the Greek district of Thessaly, informing the readers of the measures taken, as well as the social and economic aspects of the flu.
Discovery and Early Development of AVI-7537 and AVI-7288 for the Treatment of Ebola Virus and Marburg Virus Infections (2012)

There are no currently approved treatments for filovirus infections. In this study we report the discovery process which led to the development of antisense Phosphorodiamidate Morpholino Oligomers (PMOs) AVI-6002 (composed of AVI-7357 and AVI-7539) and AVI-6003 (composed of AVI-7287 and AVI-7288) targeting Ebola virus and Marburg virus respectively. The discovery process involved identification of optimal transcript binding sites for PMO based RNA-therapeutics followed by screening for effective viral gene target in mouse and guinea pig models utilizing adapted viral isolates. An evolution of chemical modifications were tested, beginning with simple Phosphorodiamidate Morpholino Oligomers (PMO) transitioning to cell penetrating peptide conjugated PMOs (PPMO) and ending with PMOplus containing a limited number of positively charged linkages in the PMO structure. The initial lead compounds were combinations of two agents targeting separate genes. In the final analysis, a single agent for treatment of each virus was selected, AVI-7537 targeting the VP24 gene of Ebola virus and AVI-7288 targeting NP of Marburg virus, and are now progressing into late stage clinical development as the optimal therapeutic candidates.
Efficient Synthesis of Nucleoside Diphosphate Glycopyranoses (2007)

Short and sweet: A new, short synthetic pathway for the synthesis of the enormously important class of nucleoside diphosphate sugars (NDP sugars) was developed using cyclo-saligenyl (cycloSal) nucleosyl phosphate triesters as active ester equivalents that form the target compounds in the presence of anomerically pure pyranose 1-phosphates in high yields (see scheme; T= thymine; X=OAc, H; Y=OH, H).
Photoactivated Localization Microscopy (PALM) of Adhesion Complexes (2013)

Abstract Key to understanding a protein's biological function is the accurate determination of its spatial distribution inside a cell. Although fluorescent protein markers allow the targeting of specific proteins with molecular precision, much of this information is lost when the resultant fusion proteins are imaged with conventional, diffraction‐limited optics. In response, several imaging modalities that are capable of resolution below the diffraction limit (∼200 nm) have emerged. Here, both single‐ and dual‐color superresolution imaging of biological structures using photoactivated localization microscopy (PALM) are described. The examples discussed focus on adhesion complexes: dense, protein‐filled assemblies that form at the interface between cells and their substrata. A particular emphasis is placed on the instrumentation and photoactivatable fluorescent protein (PA‐FP) tags necessary to achieve PALM images at ∼20 nm resolution in 5 to 30 min in fixed cells. Curr. Protoc. Cell Biol . 58:4.21.1‐4.21.28. © 2013 by John Wiley &amp; Sons, Inc.
Structure-Activity Relationships of Glutamate Carboxypeptidase II (GCPII) Inhibitors (2012)

Glutamate carboxypeptidase II (GCPII, EC 3.4.17.21) is a zinc metallopeptidase that hydrolyzes N-acetylaspartylglutamate (NAAG) into N-acetylaspartate (NAA) and glutamate in the nervous system. Inhibition of GCPII has the potential to reduce extracellular glutamate and represents an opportune target for treating neurological disorders in which excess glutamate is considered pathogenic. Furthermore, GCPII was found to be identical to a tumor marker, prostate-specific membrane antigen (PSMA), and has drawn significant interest as a diagnostic and/or therapeutic target in oncology. Over the past 15 years, tremendous efforts have been made in the discovery of potent GCPII inhibitors, particularly those with phosphorus-, urea- and thiol-based zinc binding groups. In addition, significant progress has been made in understanding the three-dimensional structural characteristics of GCPII in complex with various ligands. The purpose of this review article is to analyze the structure-activity relationships (SAR) of GCPII inhibitors reported to date, which are classified on the basis of their zinc-binding group. SAR and crystallographic data are evaluated in detail for each of these series to highlight the future challenges and opportunities to identify clinically viable GCPII inhibitors.
Temozolomide In Acute Myeloid Leukemia: A MGMT Promoter Methylation Status–Based Treatment Stratification (2010)

Abstract Abstract 3313 Introduction: Temozolomide sensitivity is determined by the methylation status of the MGMT promoter. As most AML patients have an unmethylated MGMT promoter, response rates to temozolomide have been very disappointing in the past. We designed this exploratory study to determine whether temozolomide therapy can be tailored according to the MGMT promoter status and to test the hypothesis that protracted, low-dose temozolomide can “prime” leukemia blasts to conventional doses of temozolomide in patients with unmethylated MGMT promoter. Patients and Methods: Elderly patients (&gt;60 years of age) with AML and high-risk features (relapsed/refractory, secondary AML or de novo with intermediate or unfavorable cytogenetics) were stratified according to MGMT promoter methylation status. Patients with methylated MGMT promoters received temozolomide 200mg/m2 orally for 7 days, while patients with unmethylated promoters received temozolomide 100mg/m2 orally for 14 days followed by temozolomide 200mg/m2 orally for 7 days. Results: 36 patients (median age, 75 years) were treated with temozolomide and 31 (86%) were found to have an unmethylated MGMT promoter. Overall response rate for the entire cohort was 36% (CR – 22%, CRp – 8%, LFS- 6%). The median duration of response and median overall survival among responding patients were 29 weeks and 35 weeks, respectively. No differences in outcomes (CR rate, OS rate and duration of remission) were noted among the 2 stratification groups (Table-1) Induction deaths (within 42 days of treatment initiation) occurred in 25% (9/36) of patients and were mostly caused by disease progression. Patients with low HCT-CI scores (≤ 2) had higher ORR 43% vs.0%, fewer induction deaths (17% vs. 67%, respectively) and longer median OS (94 days vs. 25.5 days). Hematological toxicities were the most commonly observed adverse events and difficult to distinguish from disease-related cytopenias. Conclusion: Temozolomide therapy, stratified according to MGMT promoter methylation status, demonstrated clinical activity in elderly patients with AML and high-risk features. Protracted low-dose temozolomide may reverse the temozolomide-resistant phenotype in patients with unmethylated MGMT promoters. Future studies in better-defined populations or in combination are warranted. This trial was registered at ClinicalTrials.gov as NCT00611247. Disclosures: Medeiros: Schering-Plough: Research Funding. Off Label Use: Temozolomide for elderly AML.
Formation and optimization of three-dimensional organoids generated from urine-derived stem cells for renal function in vitro (2020)

USC-organoids could be developed from USCs via an optimal procedure. Combining culture with kECM, USC-organoid properties including morphology, histology, and specific gene expression were identified to be similar with real renal organoids. Additionally, USC-organoids posed kECM in vitro showed the potential to be a drug screening tool which might take the place of renal organoids to some extent in the future.
Correction to “Formation of Vinyl-, Vinylhalide- or Acyl-Substituted Quaternary Carbon Stereogenic Centers through NHC–Cu-Catalyzed Enantioselective Conjugate Additions of Si-Containing Vinylaluminums to β-Substituted Cyclic Enones” (2014)

ADVERTISEMENT RETURN TO ISSUEPREVAddition/CorrectionNEXTORIGINAL ARTICLEThis notice is a correctionCorrection to "Formation of Vinyl-, Vinylhalide- or Acyl-Substituted Quaternary Carbon Stereogenic Centers through NHC–Cu-Catalyzed Enantioselective Conjugate Additions of Si-Containing Vinylaluminums to β-Substituted Cyclic Enones"Tricia L. May, Jennifer A. Dabrowski, and Amir H. Hoveyda*Cite this: J. Am. Chem. Soc. 2014, 136, 29, 10544Publication Date (Web):July 10, 2014Publication History Published online10 July 2014Published inissue 23 July 2014https://pubs.acs.org/doi/10.1021/ja506298xhttps://doi.org/10.1021/ja506298xcorrectionACS PublicationsCopyright © 2014 American Chemical Society. This publication is available under these Terms of Use. Request reuse permissions This publication is free to access through this site. Learn MoreArticle Views1949Altmetric-Citations9LEARN 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 PDF (483 KB) Get e-Alertsclose Get e-Alerts
Experimental Investigation on Lean Blow Out of a Piloted Aero-Engine Burner (2014)

One of the preferred ways to reduce NOX formation in an aero-engine is to operate lean throughout the whole operational range; however the lean combustion suffers from poor stability. To avoid the problem associated with stability, often a rich pilot flame is used along with a main flame to act as a source of heat and radicals to the main flame. The focus of the paper is to discuss the influence of the liquid fuel spray characteristics and effect of flow parameters on the lean blow out (LBO) limits of a piloted burner. In order to understand the observed remarkable LBO limits of the pilot flame with Jet A-1 (LBO = 145 kg-air to kg-fuel at 0.1 MPa of combustor pressure), velocity field measurements by laser Doppler Anemometry (LDA) technique have been performed. Furthermore, the flame structure has been analyzed with OH* chemiluminescence imaging. Experimental results show that the LBO limits of the burner running with liquid fuel further improves with an increase in combustor pressure. Such improvement in LBO limits is attributed to the change in the liquid fuel distribution caused by the change in the combustor pressure. For gaseous fuel measurements, results indicate that the equivalence ratio and the momentum ratio of the pilot jet to the co-annular flow are the dominating parameters that control the mixing process in the combustor and the ensuing effect on the flame structure and location of flame stabilization is substantial. The flame stabilizes either along the centreline or along the shear layer between two jets. Such information is useful in designing a lean partially premixed combustion system where a pilot flame is required to stabilize a main lean flame.
Sup Figure 2 from Interrogating Two Schedules of the AKT Inhibitor MK-2206 in Patients with Advanced Solid Tumors Incorporating Novel Pharmacodynamic and Functional Imaging Biomarkers (2023)

&lt;p&gt;Sup Figure 2. Box-and-whisker plots showing that the extent of multiparametric MRI (DCE-MRI (A), DWI (B), 1H-MRS (C) and ISW-MRI (D)) parameter changes in patients on MK-2206&lt;/p&gt;
Somatic Tissue Engineering in Mouse Models Reveals an Actionable Role for WNT Pathway Alterations in Prostate Cancer Metastasis (2020)

To study genetic factors influencing the progression and therapeutic responses of advanced prostate cancer, we developed a fast and flexible system that introduces genetic alterations relevant to human disease directly into the prostate glands of mice using tissue electroporation. These electroporation-based genetically engineered mouse models (EPO-GEMM) recapitulate features of traditional germline models and, by modeling genetic factors linked to late-stage human disease, can produce tumors that are metastatic and castration-resistant. A subset of tumors with <i>Trp53</i> alterations acquired spontaneous WNT pathway alterations, which are also associated with metastatic prostate cancer in humans. Using the EPO-GEMM approach and an orthogonal organoid-based model, we show that WNT pathway activation drives metastatic disease that is sensitive to pharmacologic WNT pathway inhibition. Thus, by leveraging EPO-GEMMs, we reveal a functional role for WNT signaling in driving prostate cancer metastasis and validate the WNT pathway as therapeutic target in metastatic prostate cancer. SIGNIFICANCE: Our understanding of the factors driving metastatic prostate cancer is limited by the paucity of models of late-stage disease. Here, we develop EPO-GEMMs of prostate cancer and use them to identify and validate the WNT pathway as an actionable driver of aggressive metastatic disease.<i>This article is highlighted in the In This Issue feature, p. 890</i>.
Proteomic analysis defines kinase taxonomies specific for subtypes of breast cancer (2018)

Multiplexed small molecule inhibitors covalently bound to Sepharose beads (MIBs) were used to capture functional kinases in luminal, HER2-enriched and triple negative (basal-like and claudin-low) breast cancer cell lines and tumors. Kinase MIB-binding profiles at baseline without perturbation proteomically distinguished the four breast cancer subtypes. Understudied kinases, whose disease associations and pharmacology are generally unexplored, were highly represented in MIB-binding taxonomies and are integrated into signaling subnetworks with kinases that have been previously well characterized in breast cancer. Computationally it was possible to define subtypes using profiles of less than 50 of the more than 300 kinases bound to MIBs that included understudied as well as metabolic and lipid kinases. Furthermore, analysis of MIB-binding profiles established potential functional annotations for these understudied kinases. Thus, comprehensive MIBs-based capture of kinases provides a unique proteomics-based method for integration of poorly characterized kinases of the understudied kinome into functional subnetworks in breast cancer cells and tumors that is not possible using genomic strategies. The MIB-binding profiles readily defined subtype-selective differential adaptive kinome reprogramming in response to targeted kinase inhibition, demonstrating how MIB profiles can be used in determining dynamic kinome changes that result in subtype selective phenotypic state changes.
P08.01: A novel deep learning based system for fetal cardiac screening (2019)

The ultrasonography of fetal heart is not easy because of fast heart beats and small organ. Some views were recommended to pick up congenital heart disease (CHD). But, it is difficult to take the correct image of views. Thus the rate of antenatal detection for CHD likely depends on skills of each sonographer. The aim of this study is to ascertain whether a novel artificial Intelligence (AI) technology systemwhich we have developed is helpful for segmental diagnosis of normal fetal heat. 2378 frames from 51 normal fetal cardiac screening movies at 18-20 weeks, were used as a training dataset for machine learning. 701 frames from 28 normal fetal cardiac screening movie used as test data. The movie included the hole images of fetal heart from stomach to base of heart. Correct positions of the heart and peripheral organs were annotated. The positions were following crux, ventricular septum, right atrium, tricuspid valve, right ventricle, left atrium, mitral valve, left ventricle, pulmonary artery, ascending aorta, superior vena cava, descending aorta, stomach spine, umbilical vein, inferior vena cava, pulmonary vein, ductus arteriosus. We calculated the accuracy of each parts of normal fetal heart ultrasound screening movie. The recall ratio of crux, ventricular septum, left ventricle and atrium, right ventricle and atrium, ascending aorta, pulmonary artery, stmach and spine were 97.1%, 69.3%, 96.6% and 90.6%, 84.8% and 96.9%, 61.9%, 100%, 100% and 100%, respectively. Supporting information can be found in the online version of this abstract Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Prevention and Therapy of Preterm Birth. Guideline of the DGGG, OEGGG and SGGG (S2k Level, AWMF Registry Number 015/025, February 2019) – Part 1 with Recommendations on the Epidemiology, Etiology, Prediction, Primary and Secondary Prevention of Preterm Birth (2019)

<b>Aims</b> This is an official guideline of the German Society for Gynecology and Obstetrics (DGGG), the Austrian Society for Gynecology and Obstetrics (ÖGGG) and the Swiss Society for Gynecology and Obstetrics (SGGG). The aim of this guideline is to improve the prediction, prevention and management of preterm birth based on evidence obtained from recent scientific literature, the experience of the members of the guideline commission and the views of self-help groups. <b>Methods</b> Based on the international literature, the members of the participating medical societies and organizations developed Recommendations and Statements. These were adopted following a formal process (structured consensus conference with neutral moderation, voting was done in writing using the Delphi method to achieve consensus). <b>Recommendations</b> Part I of this short version of the guideline lists Statements and Recommendations on the epidemiology, etiology, prediction and primary and secondary prevention of preterm birth.