bluuebunny/crossref_metadata_2025_split huggingface dataset:
RVSDG
Authors: Reissmann Nico , Meyer Jan Christian , Bahmann Helge , Själander Magnus 
Published: July 2020

Intermediate Representations (IRs) are central to optimizing compilers as the way the program is represented may enhance or limit analyses and transformations. Suitable IRs focus on exposing the most relevant information and establish invariants that different compiler passes can rely on. While control-flow centric IRs appear to be a natural fit for imperative programming languages, analyses required by compilers have increasingly shifted to understand data dependencies and work at multiple abstraction layers at the same time. This is partially evidenced in recent developments such as the Multi-Level Intermediate Representation (MLIR) proposed by Google. However, rigorous use of data flow centric IRs in general purpose compilers has not been evaluated for feasibility and usability as previous works provide no practical implementations.
We present the Regionalized Value State Dependence Graph (RVSDG) IR for optimizing compilers. The RVSDG is a data flow centric IR where nodes represent computations, edges represent computational dependencies, and regions capture the hierarchical structure of programs. It represents programs in demand-dependence form, implicitly supports structured control flow, and models entire programs within a single IR. We provide a complete specification of the RVSDG, construction and destruction methods, as well as exemplify its utility by presenting Dead Node and Common Node Elimination optimizations. We implemented a prototype compiler and evaluate it in terms of performance, code size, compilation time, and representational overhead. Our results indicate that the RVSDG can serve as a competitive IR in optimizing compilers while reducing complexity.
Creating Hardware Component Knowledge Bases with Training Data Generation and Multi-task Learning
Authors: Hsiao Luke , Wu Sen , Chiang Nicholas , Ré Christopher , Levis Philip 
Published: July 2020

Hardware component databases are vital resources in designing embedded systems. Since creating these databases requires hundreds of thousands of hours of manual data entry, they are proprietary, limited in the data they provide, and have random data entry errors.
We present a machine learning based approach for creating hardware component databases directly from datasheets. Extracting data directly from datasheets is challenging because: (1) the data is relational in nature and relies on non-local context, (2) the documents are filled with technical jargon, and (3) the datasheets are PDFs, a format that decouples visual locality from locality in the document. Addressing this complexity has traditionally relied on human input, making it costly to scale. Our approach uses a rich data model, weak supervision, data augmentation, and multi-task learning to create these knowledge bases in a matter of days.
We evaluate the approach on datasheets of three types of components and achieve an average quality of 77 F1 points—quality comparable to existing human-curated knowledge bases. We perform application studies that demonstrate the extraction of multiple data modalities including numerical properties and images. We show how different sources of supervision such as heuristics and human labels have distinct advantages that can be utilized together to improve knowledge base quality. Finally, we present a case study to show how this approach changes the way practitioners create hardware component knowledge bases.
Study on Automated Approach to Recognize Characters for Handwritten and Historical Document
Authors: S Dhivya , G Usha Devi 
Published: July 2020

Script recognition is the mechanism of automatic script analysis and recognition whereby intensive study has been carried out and a significant amount of papers on this problem have been released over the past. But there are still a few issues to be solved, particularly in Indian historical manuscripts. This literature examines the Script recognition with reference to multi-script document and different historical scripts such as Kurdish-Latin, Devanagari, Grantha, Arabic handwritten characters, Bangladesh, Devanagari and Gurumukhi, ancient Chinese, Arabic, Nam Character, Greek, Nastalique Urdu, Georgian handwritten, Nandinagari, and Hebrew, which provide the course of study that focuses on the framework for script recognition. This review concentrates on scope of prediction, dataset type, the methods used for data preprocessing, and measures of performance used for analysis. On the basis of this survey, Current research constraints have been recognized and future study specifications are emphasized in the area of modeling historical manuscripts.
CCS Concepts:
Cache What You Need to Cache
Authors: Wang Hua , Zhang Jiawei , Huang Ping , Yi Xinbo , Cheng Bin , Zhou Ke 
Published: July 2020

The SSD has been playing a significantly important role in caching systems due to its high performance-to-cost ratio. Since the cache space is typically much smaller than that of the backend storage by one order of magnitude or even more, write density (defined as writes per unit time and space) of the SSD cache is therefore much more intensive than that of HDD storage, which brings about tremendous challenges to the SSD’s lifetime. Meanwhile, under social network workloads, quite a lot writes to the SSD cache are unnecessary. For example, our study on Tencent’s photo caching shows that about 61% of total photos are accessed only once, whereas they are still swapped in and out of the cache. Therefore, if we can predict these kinds of photos proactively and prevent them from entering the cache, we can eliminate unnecessary SSD cache writes and improve cache space utilization.
To cope with the challenge, we put forward a “one-time-access criteria” that is applied to the cache space and further propose a “one-time-access-exclusion” policy. Based on these two techniques, we design a prediction-based classifier to facilitate the policy. Unlike the state-of-the-art history-based predictions, our prediction is non-history oriented, which is challenging to achieve good prediction accuracy. To address this issue, we integrate a decision tree into the classifier, extract social-related information as classifying features, and apply cost-sensitive learning to improve classification precision. Due to these techniques, we attain a prediction accuracy greater than 80%. Experimental results show that the one-time-access-exclusion approach results in outstanding cache performance in most aspects. Take LRU, for instance: applying our approach improves the hit rate by 4.4%, decreases the cache writes by 56.8%, and cuts the average access latency by 5.5%.
Plasma Gelsolin Inhibits CD8+ T-cell Function and Regulates Glutathione Production to Confer Chemoresistance in Ovarian Cancer
Authors: Asare-Werehene Meshach , Communal Laudine , Carmona Euridice , Han Youngjin , Song Yong Sang , Burger Dylan , Mes-Masson Anne-Marie , Tsang Benjamin K. 
Published: July 2020

Abstract

Although initial treatment of ovarian cancer is successful, tumors typically relapse and become resistant to treatment. Because of poor infiltration of effector T cells, patients are mostly unresponsive to immunotherapy. Plasma gelsolin (pGSN) is transported by exosomes (small extracellular vesicle, sEV) and plays a key role in ovarian cancer chemoresistance, yet little is known about its role in immunosurveillance. Here, we report the immunomodulatory roles of sEV-pGSN in ovarian cancer chemoresistance. In chemosensitive conditions, secretion of sEV-pGSN was low, allowing for optimal CD8+ T-cell function. This resulted in increased T-cell secretion of IFNγ, which reduced intracellular glutathione (GSH) production and sensitized chemosensitive cells to cis-diaminedichloroplatinum (CDDP)-induced apoptosis. In chemoresistant conditions, increased secretion of sEV-pGSN by ovarian cancer cells induced apoptosis in CD8+ T cells. IFNγ secretion was therefore reduced, resulting in high GSH production and resistance to CDDP-induced death in ovarian cancer cells. These findings support our hypothesis that sEV-pGSN attenuates immunosurveillance and regulates GSH biosynthesis, a phenomenon that contributes to chemoresistance in ovarian cancer.

Significance:
These findings provide new insight into pGSN-mediated immune cell dysfunction in ovarian cancer chemoresistance and demonstrate how this dysfunction can be exploited to enhance immunotherapy.
Calibration of Pathogenicity Due to Variant-Induced Leaky Splicing Defects by Using BRCA2 Exon 3 as a Model System
Authors: Tubeuf Hélène , Caputo Sandrine M. , Sullivan Teresa , Rondeaux Julie , Krieger Sophie , Caux-Moncoutier Virginie , Hauchard Julie , Castelain Gaia , Fiévet Alice , Meulemans Laëtitia , Révillion Françoise , Léoné Mélanie , Boutry-Kryza Nadia , Delnatte Capucine , Guillaud-Bataille Marine , Cleveland Linda , Reid Susan , Southon Eileen , Soukarieh Omar , Drouet Aurélie , Di Giacomo Daniela , Vezain Myriam , Bonnet-Dorion Françoise , Bourdon Violaine , Larbre Hélène , Muller Danièle , Pujol Pascal , Vaz Fátima , Audebert-Bellanger Séverine , Colas Chrystelle , Venat-Bouvet Laurence , Solano Angela R. , Stoppa-Lyonnet Dominique , Houdayer Claude , Frebourg Thierry , Gaildrat Pascaline , Sharan Shyam K. , Martins Alexandra 
Published: July 2020

Abstract

BRCA2 is a clinically actionable gene implicated in breast and ovarian cancer predisposition that has become a high priority target for improving the classification of variants of unknown significance (VUS). Among all BRCA2 VUS, those causing partial/leaky splicing defects are the most challenging to classify because the minimal level of full-length (FL) transcripts required for normal function remains to be established. Here, we explored BRCA2 exon 3 (BRCA2e3) as a model for calibrating variant-induced spliceogenicity and estimating thresholds for BRCA2 haploinsufficiency. In silico predictions, minigene splicing assays, patients' RNA analyses, a mouse embryonic stem cell (mESC) complementation assay and retrieval of patient-related information were combined to determine the minimal requirement of FL BRCA2 transcripts. Of 100 BRCA2e3 variants tested in the minigene assay, 64 were found to be spliceogenic, causing mild to severe RNA defects. Splicing defects were also confirmed in patients' RNA when available. Analysis of a neutral leaky variant (c.231T&gt;G) showed that a reduction of approximately 60% of FL BRCA2 transcripts from a mutant allele does not cause any increase in cancer risk. Moreover, data obtained from mESCs suggest that variants causing a decline in FL BRCA2 with approximately 30% of wild-type are not pathogenic, given that mESCs are fully viable and resistant to DNA-damaging agents in those conditions. In contrast, mESCs producing lower relative amounts of FL BRCA2 exhibited either null or hypomorphic phenotypes. Overall, our findings are likely to have broader implications on the interpretation of BRCA2 variants affecting the splicing pattern of other essential exons.

Significance:
These findings demonstrate that BRCA2 tumor suppressor function tolerates substantial reduction in full-length transcripts, helping to determine the pathogenicity of BRCA2 leaky splicing variants, some of which may not increase cancer risk.
Role of inflammatory markers in corona virus disease (COVID-19) patients: A review
Authors: Upadhyay Jyoti , Tiwari Nidhi , Ansari Mohd N 
Published: July 2020

The whole world is locked down due to the outbreak of novel Coronavirus Disease 2019 (nCOVID-19). A novel virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus pandemic 2019. Investigating the role of inflammatory mediators and understanding the virology of nCOVID-19 virus help in designing a rational and effective therapy for this infection. This review provides an overview of the inflammatory mediators activated during nCOVID-19 infection and the pathophysiology of this viral infection. In this review, the authors have a detailed discussion about the types of viral strains of nCOVID-19, its mechanism of action, host immune response, and the dysregulation caused by the viruses in the host immune system causing disease progression. Understanding the role of inflammatory cytokines, chemokines, and clinical immunology will be the approach to find out the possible novel therapeutic interventions. Therapies involving regulation of immune responses help in inhibiting the various steps in the pathologies of infection. Also, updated knowledge regarding the dysregulation of immune system and disease outcome in critically ill patients serves as a precautionary measure in the development and evaluation of vaccine. Impact statement In late 2019, a novel virus called SARS-CoV-2, expanded globally from Wuhan, China and was declared a pandemic on 11 March 2020 by the WHO. The mechanism of virus entry inside the host cell depends upon the cellular proteases including cathepsins, HAT, and TMPRSS2, which splits up the spike protein and causes further penetration. MERS coronavirus uses DPP4, while coronavirus HCoV-NL63 and SARS-CoV and SARS-CoV-2 employ ACE-2 as the key receptor. Cytokine storm syndrome was analyzed in critically ill nCOVID-19 patients and it is presented with high inflammatory mediators, systemic inflammation, and multiple organ failure. Among various inflammatory mediators, the level of interleukins (IL-2, IL-7, IL-10), G-CSF, MIP1A, MCP1, and TNF-α was reported to be higher in critically ill patients. Understanding this molecular mechanism of ILs, T cells, and dendritic cells will be helpful to design immunotherapy and novel drugs for the treatment of nCOVID-19 infection.
Long‐term outcomes of patients with ulcerative proctitis: Analysis from a large referral centre cohort
Authors: Dubois Evelyne , Moens Annick , Geelen Rob , Sabino João , Ferrante Marc , Vermeire Séverine 
Published: July 2020

IntroductionLong‐term outcomes of patients with ulcerative proctitis (UP) have been poorly investigated, since these patients are excluded from participation in randomized controlled clinical trials.ObjectiveThe aim of this study was to investigate the prognostic and therapeutic long‐term outcomes of patients with UP.MethodsA retrospective study of patients with UP followed at our referral centre between 1 January 1998 and 1 January 2019 was performed. Treatment success was defined as clinical response (significant improvement in UP‐related symptoms) and endoscopic response (mayo endoscopic sub‐score of 0 or 1) if available at last follow‐up.ResultsFrom a total of 1561 patients with ulcerative colitis, 118 patients with UP were identified. A total of 36 (31%) patients were refractory to rectal and oral therapy with 5‐ASA and corticosteroids, necessitating azathioprine as monotherapy in 19 (16%) patients and/or biological therapies in 33 (28%) patients. After a median follow‐up of 71 months (interquartile range 29–149 months), treatment success was observed in 103/118 (87%) UP patients and in 25/36 (69%) patients with refractory UP. Clinical response rates were significantly higher for refractory UP patients treated with biologicals (23/33; 70%) compared to ones treated with azathioprine (2/19; 11%; p   =  0.001).ConclusionGood clinical outcomes were recorded in UP, with treatment success in 87% of patients. Nevertheless, 28% needed escalation to biologicals. Long‐term outcome in patients on biologicals was superior to azathioprine.
A risk-stratified therapy for infants with acute lymphoblastic leukemia: a report from the JPLSG MLL-10 trial
Authors: Tomizawa Daisuke , Miyamura Takako , Imamura Toshihiko , Watanabe Tomoyuki , Moriya Saito Akiko , Ogawa Atsushi , Takahashi Yoshihiro , Hirayama Masahiro , Taki Tomohiko , Deguchi Takao , Hori Toshinori , Sanada Masashi , Ohmori Shigeru , Haba Masami , Iguchi Akihiro , Arakawa Yuki , Koga Yuhki , Manabe Atsushi , Horibe Keizo , Ishii Eiichi , Koh Katsuyoshi 
Published: July 2020

Abstract
The prognosis for infants with acute lymphoblastic leukemia (ALL), particularly those with KMT2A gene rearrangement (KMT2A-r), is dismal. Continuous efforts have been made in Japan to investigate the role of hematopoietic stem cell transplantation (HSCT) for infants with KMT2A-r ALL, but improvement in outcome was modest. In the Japanese Pediatric Leukemia/Lymphoma Study Group MLL-10 trial, infants with ALL were stratified into 3 risk groups (low risk [LR], intermediate risk [IR], and high risk [HR]) according to KMT2A status, age, and presence of central nervous system leukemia. Children’s Oncology Group AALL0631 modified chemotherapy with the addition of high-dose cytarabine in early intensification was introduced to KMT2A-r patients, and the option of HSCT was restricted to HR patients only. The role of minimal residual disease (MRD) was also evaluated. Ninety eligible infants were stratified into LR (n = 15), IR (n = 19), or HR (n = 56) risk groups. The 3-year event-free survival (EFS) rate for patients with KMT2A-r ALL (IR + HR) was 66.2% (standard error [SE], 5.6%), and for those with germline KMT2A (KMT2A-g) ALL (LR), the 3-year EFS rate was 93.3% (SE, 6.4%). The 3-year EFS rate was 94.4% (SE, 5.4%) for IR patients and 56.6% (SE, 6.8%) for HR patients. In multivariable analysis, female sex and MRD ≥0.01% at the end of early consolidation were significant factors for poor prognosis. Risk stratification and introduction of intensive chemotherapy in this study were effective and were able to eliminate HSCT for a subset of infants with KMT2A-r ALL. Early clearance of MRD seems to have translated into favorable outcomes and should be incorporated into risk stratifications in future trials. This trial was registered at the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) as #UMIN000004801.
The dual PI3Kδ/CK1ε inhibitor umbralisib exhibits unique immunomodulatory effects on CLL T cells
Authors: Maharaj Kamira , Powers John J. , Achille Alex , Mediavilla-Varela Melanie , Gamal Wael , Burger Karen L. , Fonseca Renee , Jiang Kun , Miskin Hari P. , Maryanski Dave , Monastyrskyi Andrii , Duckett Derek R. , Roush William R. , Cleveland John L. , Sahakian Eva , Pinilla-Ibarz Javier 
Published: July 2020

AbstractThe in-clinic phosphatidylinositol 3-kinase (PI3K) inhibitors idelalisib (CAL-101) and duvelisib (IPI-145) have demonstrated high rates of response and progression-free survival in clinical trials of B-cell malignancies, such as chronic lymphocytic leukemia (CLL). However, a high incidence of adverse events has led to frequent discontinuations, limiting the clinical development of these inhibitors. By contrast, the dual PI3Kδ/casein kinase-1-ε (CK1ε) inhibitor umbralisib (TGR-1202) also shows high rates of response in clinical trials but has an improved safety profile with fewer severe adverse events. Toxicities typical of this class of PI3K inhibitors are largely thought to be immune mediated, but they are poorly characterized. Here, we report the effects of idelalisib, duvelisib, and umbralisib on regulatory T cells (Tregs) on normal human T cells, T cells from CLL patients, and T cells in an Eμ-TCL1 adoptive transfer mouse CLL model. Ex vivo studies revealed differential effects of these PI3K inhibitors; only umbralisib treatment sustained normal and CLL-associated FoxP3+ human Tregs. Further, although all 3 inhibitors exhibit antitumor efficacy in the Eμ-TCL1 CLL model, idelalisib- or duvelisib-treated mice displayed increased immune-mediated toxicities, impaired function, and reduced numbers of Tregs, whereas Treg number and function were preserved in umbralisib-treated CLL-bearing mice. Finally, our studies demonstrate that inhibition of CK1ε can improve CLL Treg number and function. Interestingly, CK1ε inhibition mitigated impairment of CLL Tregs by PI3K inhibitors in combination treatment. These results suggest that the improved safety profile of umbralisib is due to its role as a dual PI3Kδ/CK1ε inhibitor that preserves Treg number and function.
Glasdegib as maintenance therapy for patients with AML and MDS patients at high risk for postallogeneic stem cell transplant relapse
Authors: Kent Andrew , Vasu Sumithira , Schatz Derek , Monson Natalie , Devine Steven , Smith Clayton , Gutman Jonathan A. , Pollyea Daniel A. 
Published: July 2020

Key Points
Posttransplantation, glasdegib maintenance therapy in patients at high risk for relapse did not meaningfully reduce relapse incidence. Use of glasdegib in the posttransplantation setting was complicated by adverse events requiring drug holds and occasional discontinuation.
Comparative Study of Selenides and Tellurides of Transition Metals (Nb and Ta) with Respect to its Catalytic, Antimicrobial, and Molecular Docking Performance
Authors: Altaf S. , Haider A. , Naz S. , Ul-Hamid A. , Haider J. , Imran M. , Shahzadi A. , Naz M. , Ajaz H. , Ikram M. 
Published: July 2020

AbstractThe present research is a comparative study that reports an economical and accessible method to synthesize niobium (Nb) and Tantalum (Ta) selenides and tellurides with useful application in the removal of pollutants in textile, paper, and dyeing industries as well as in medical field. In this study, solid-state process was used to generate nanocomposites and various characterization techniques were employed to compare two groups of materials under investigation. Structure, morphology, elemental constitution, and functional groups of synthesized materials were analyzed with XRD, FESEM coupled with EDS, FTIR, and Raman spectroscopy, respectively. HR-TEM images displayed nanoscale particles with tetragonal and monoclinic crystal structures. The optical properties were evaluated in terms of cut-off wavelength and optical band gap using UV-visible spectroscopy. A comparative behavior of both groups of compounds was assessed with regards to their catalytic and microcidal properties. Extracted nanocomposites when used as catalysts, though isomorphs of each other, showed markedly different behavior in catalytic degradation of MB dye in the presence of NaBH4 that was employed as a reducing agent. This peculiar deviation might be attributed to slight structural differences between them. Escherichia coli and Staphylococcus aureus (G –ve and + ve bacteria, respectively) were designated as model strains for in vitro antibacterial tests of both clusters by employing disk diffusion method. Superior antibacterial efficacy was observed for telluride system (significant inhibition zones of 26-35 mm) compared with selenide system (diameter of inhibition zone ranged from 0.8 mm to 1.9 mm). In addition, molecular docking study was undertaken to ascertain the binding interaction pattern between NPs and active sites in targeted cell protein. The findings were in agreement with antimicrobial test results suggesting NbTe4 to be the best inhibitor against FabH and FabI enzymes.