gebhart/patrepeval huggingface dataset:
Abstract B094: Successful identification of neoantigen-specific T-cell responses in low mutation burden colorectal cancers for personalized cancer vaccine development (2019)

Abstract Innovative treatment options are required to improve cure rates in advanced colorectal cancer patients. Immune checkpoint blockade therapy (anti-PD-1) was shown to be effective in colorectal cancers with high mutation burden (e.g., mismatch repair deficient) as antitumor reactivity is largely explained by the recognition of somatically mutated antigens (neoantigens). No immunotherapeutic strategies are currently available for patients diagnosed with low mutation burden colorectal cancer. We hypothesized that if neoantigen-reactive T-cells are present in low mutation burden patients, the latter could benefit from immunotherapeutic interventions that stimulate neoantigen recognition and the onset of a robust antitumor immune response.In order to detect neoantigens, whole exome and RNA next-generation sequencing analyses were performed in cancer and healthy tissues from five colorectal cancer patients. Corresponding neoepitopes were synthesized and tested for their ability to induce immune cell activation in T-cells isolated from the tumor tissue (TIL) and from peripheral blood. Neoantigen-specific T-cell responses were identified in the majority of patients that presented with tumors carrying 25 to 36 transcribed, non-synonymous variants. Up to six different neoantigens were recognized per tumor, which resulted in a higher detection rate than anticipated based on published data. Moreover, we discovered the merits of isolating CD39+CD103+CD8+ T-cells for detection of a broad recognition of HLA class I-restricted neoantigens. This CD39+CD103+CD8+ T-cell subset comprises the majority and a broader repertoire of neoantigen-specific T-cells compared to bulk TIL populations or lymphocytes derived from peripheral blood. In conclusion, we developed a neoantigen screening pipeline to unlock the immunogenic potential of colorectal cancers with low mutation burden. We have detected a relatively high number of neoantigens that are recognized by tumor- and/or PBMC-derived T-cells in mismatch repair proficient, low mutation burden colorectal cancer patients, and show the importance of the CD39+CD103+CD8+ T-cell subset for neoantigen-based immunotherapies. These findings warrant the further exploration of the potential to employ neoantigen-targeted therapies to improve clinical outcomes of colorectal cancer patients. Citation Format: Jitske van den Bulk, Dina Ruano, Marieke E. Ijsselsteijn, Marten Visser, Ruud van der Breggen, Koen C.M.J. Peeters, Thomas Duhen, Rebekka Duhen, Andrew D Weinberg, Sjoerd S.H. van der Burg, Els M.E. Verdegaal, Noel F. de Miranda. Successful identification of neoantigen-specific T-cell responses in low mutation burden colorectal cancers for personalized cancer vaccine development [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B094.
The clinically used serine protease inhibitor nafamostat reduces influenza virus replication and cytokine production in human airway epithelial cells and viral replication in mice (2020)

The effects of the clinically used protease inhibitor nafamostat on influenza virus replication have not been well studied. Primary human tracheal (HTE) and nasal (HNE) epithelial cells were pretreated with nafamostat and infected with the 2009 pandemic [A/Sendai-H/108/2009/(H1N1) pdm09] or seasonal [A/New York/55/2004(H3N2)] influenza virus. Pretreatment with nafamostat reduced the titers of the pandemic and seasonal influenza viruses and the secretion of inflammatory cytokines, including interleukin-6 and tumor necrosis factor-α, in the supernatants of the cells infected with the pandemic influenza virus. HTE and HNE cells exhibited mRNA and/or protein expression of transmembrane protease serine 2 (TMPRSS2), TMPRSS4, and TMPRSS11D. Pretreatment with nafamostat reduced cleavage of the precursor protein HA0 of the pandemic influenza virus into subunit HA1 in HTE cells and reduced the number of acidic endosomes in HTE and HNE cells where influenza virus RNA enters the cytoplasm. Additionally, nafamostat (30 mg/kg/day, intraperitoneal administration) reduced the levels of the pandemic influenza virus [A/Hyogo/YS/2011 (H1N1) pdm09] in mouse lung washes. These findings suggest that nafamostat may inhibit influenza virus replication in human airway epithelial cells and mouse lungs and reduce infection-induced airway inflammation by modulating cytokine production.
Mobile interfaces to computational, data, and service grid systems (2002)

This article briefly describes the issues related to providing mobile access to computational, data, and service Grids. Then it describes our preliminary efforts to enhance computational and service Grids to handle mobile access. In particular, we focus on how the HARNESS mobile extensions project approaches the problem of enhancing Grid computers with mobile access and we describe how the InviNet project provides access to service Grids with consistent quality of service.
A novel galactolipase from a green microalga Chlorella kessleri: purification, characterization, molecular cloning, and heterologous expression (2018)

We have identified an enzyme, galactolipase (ckGL), which hydrolyzes the acyl ester bond of galactolipids such as digalactosyldiacylglycerol (DGDG), in the microalga Chlorella kessleri. Following purification of the enzyme to electrophoretic homogeneity from cell-free extract, the maximum activity toward DGDG was observed at pH 6.5 and 37 °C. ckGL was Ca<sup>2+</sup>-dependent enzyme and displayed an apparent molecular mass of approx. 53 kDa on SDS-PAGE. The substrate specificity was in the order: DGDG (100%) > monogalactosyldiacylglycerol ≈ phosphatidylglycerol (~ 40%) > sulfoquinovosyldiacylglycerol (~ 20%); the enzyme exhibited almost no activity toward glycerides and other phospholipids. Gas chromatography analysis demonstrated that ckGL preferably hydrolyzed the sn-1 acyl ester bond in the substrates. The genomic DNA sequence (5.6 kb) containing the ckGL gene (designated glp1) was determined and the cDNA was cloned. glp1 was composed of 10 introns and 11 exons, and the 1608-bp full-length cDNA encoded a mature ckGL containing 475 amino acids (aa), with a presequence (60 aa) containing a potential chloroplast transit peptide. Recombinant functional ckGL was produced in Escherichia coli. Although the deduced aa sequence of ckGL contained the typical GXSXG motif of serine hydrolases together with conserved histidine and aspartate residues which would form part of the catalytic triad of α/β-hydrolases, ckGL showed no significant overall similarity with known lipases including GLs from Chlamydomonas reinhardtii and Aspergillus japonicus, indicating that ckGL is a novel GL. ckGL, with high specificity for DGDG, could be applicable to food processing as an enzyme capable of improving material textures.
Cloud Computing: Distributed Internet Computing for IT and Scientific Research (2009)

Cloud computing is a disruptive technology with profound implications not only for Internet services but also for the IT sector as a whole. Its emergence promises to streamline the on-demand provisioning of software, hardware, and data as a service, achieving economies of scale in IT solutions' deployment and operation. This issue's articles tackle topics including architecture and management of cloud computing infrastructures, SaaS and IaaS applications, discovery of services and data in cloud computing infrastructures, and cross-platform interoperability. Still, several outstanding issues exist, particularly related to SLAs, security and privacy, and power efficiency. Other open issues include ownership, data transfer bottlenecks, performance unpredictability, reliability, and software licensing issues. Finally, hosted applications' business models must show a clear pathway to monetizing cloud computing. Several companies have already built Internet consumer services such as search, social networking, Web email, and online commerce that use cloud computing infrastructure. Above all, cloud computing's still unknown "killer application" will determine many of the challenges and the solutions we must develop to make this technology work in practice.
Sodium pyrophosphate inhibition of RNA.DNA hybrid degradation by reverse transcriptase. (1978)

Sodium pyrophosphate inhibits synthesis of anticomplementary DNA during a reverse transcriptase (RNA-directed DNA nucleotidyltransferase, EC 2.7.7.7) catalyzed reaction. In the presence of pyrophosphate, the complementary DNA remains stably complexed to the RNA template. In the absence of pyrophosphate, the DNA. RNA hybrid template is degraded and anticomplementary DNA is synthesized. High concentrations of additives containing phosphodiester bonds appear to inhibit the ribonuclease H activity (hybrid nuclease, EC 3.1.4.34) of the reverse transcriptase, therby preventing formation of RNA primers necessary for the synthesis of anticomplementary DNA.
Locating Parallelization Potential in Object-Oriented Data Structures (2014)

The free lunch of ever increasing single-processor performance is over. Software engineers have to parallelize software to gain performance improvements. But not every software engineer is a parallel expert and with millions of lines of code that have not been developed with multicore in mind, we have to find ways to assist in identifying parallelization potential. This paper makes three contributions: 1) An empirical study of more than 900,000 lines of code reveals five use cases in the runtime profile of object-oriented data structures that carry parallelization potential. 2) The study also points out frequently used data structures in realistic software in which these use cases can be found. 3) We developed DSspy, an automatic dynamic profiler that locates these use cases and makes recommendations on how to parallelize them. Our evaluation shows that DSspy reduces the search space for parallelization by up to 77% and engineers only need to consider 23% of all data structure instances for parallelization.
THE EPIDEMIOLOGY OF CRYPTOCOCCAL INFECTION IN SOLID ORGAN TRANSPLANTATION (1999)

357 Purpose: to investigate the incidence and mortality of cryptococcal disease in solid organ transplant recipients in our medical center. Methods: The diagnosis of cryptococcosis required a positive culture and/or positive cryptococcal antigen together with compatible clinical picture. Cases were electronically searched and identified from microbiology and pathology medical records. Results: During a 10 year period (1989-1998), 41 cases of cryptococcosis were identified, all secondary to Cryptococcus neoformans. The follow-up was for a median of 5 yrs after transplantation. The cases included: pneumonia (14), disseminated (14), meningitis (9), and other sites (4). The patients comprised liver (24), heart (10), kidney (6), and lung (1) recipients. The immunosuppression treatment included tacrolimus or Cyclosporine A together with steroids. The mean age was 52.8 yrs. (s.d. ± 10.4). There were 29 (70.7%) males. The diagnosis of cryptococcosis was made at a median of 11.8 months (range 16 days- 16 years) after organ transplantation. Cryptococcosis occurred more frequently among heart recipients compared to other organs (p=0.005). The average yearly incidence of cryptococcosis per 1000 transplants was: 5.3, 1.3, 0.6, 0.4 for heart, liver, kidney and lung recipients, respectively. The mortality associated with cryptococcosis was 22%, and was higher in patients with disseminated infection (p=0.04), and in heart recipients (p=0.18). Conclusions: Cryptococcosis is a late infection and is associated with high mortality after solid organ transplantation. The reason why it tends to occur more frequently among heart recipients compared to other solid organs remains unclear.
Enabling IC Traceability via Blockchain Pegged to Embedded PUF (2019)

Globalization of IC supply chain has increased the risk of counterfeit, tampered, and re-packaged chips in the market. Counterfeit electronics poses a security risk in safety critical applications like avionics, SCADA systems, and defense. It also affects the reputation of legitimate suppliers and causes financial losses. Hence, it becomes necessary to develop traceability solutions to ensure the integrity of supply chain, from the time of fabrication to the end of product-life, which allows a customer to verify the provenance of a device or a system. In this article, we present an IC traceability solution based on blockchain. A blockchain is a public immutable database that maintains a continuously growing list of data records secured from tampering and revision. Over the lifetime of an IC, all ownership transfer information is recorded and archived in a blockchain. This safe, verifiable method prevents any party from altering or challenging the legitimacy of the information being exchanged. However, a chain of sales record is not enough to ensure provenance of an IC. There is a need for clone-proof method for securely binding the identity of an IC to the blockchain information. In this article, we propose a method of IC supply chain traceability via blockchain pegged to embedded physically unclonable function (PUF). The blockchain provides ownership transfer record, while the PUF provides unique identification for an IC allowing it to be linked uniquely to a blockchain. Our proposed solution automates hardware and software protocols using blockchain-powered Smart Contract that allows supply chain participants to authenticate, track, trace, analyze, and provision chips throughout their entire life cycle.
Periodic selection in longterm continuous-flow cultures of the filamentous fungus Fusarium graminearum (1993)

By monitoring increases and decreases in the proportion of cycloheximide-resistant macroconidia, periodic selection was observed in populations of the filamentous fungus Fusarium graminearum, grown in glucose-limited chemostat cultures. The results indicated that periodic selection of advantageous mutants of F. graminearum occurred at intervals of about 124 h at both high (D = 0.19 h-1, approximately 34 generations) and low (D = 0.06 h-1, approximately 11 generations) dilution rates. Several 'adaptive' peaks (each indicating the appearance of an advantageous mutation) were observed before morphological (highly branched) mutants appeared in the populations; these mutants have previously been observed to have a selective advantage over the parental strain. At intervals, macroconidia harvested from the chemostat were used to inoculate plates of non-antibiotic-containing agar medium, and it was possible to monitor periodic selection in the original chemostat culture using second generation macroconidia harvested from these cultures. The proportion of cycloheximide-, potassium chlorate-, and p-fluoro-DL-phenylalanine-resistant macroconidia in these second generation macroconidia changed in a pattern similar to that observed when monitoring the proportion of cycloheximide-resistant macroconidia in the first generation population harvested directly from the chemostat. The experiments demonstrated that populations of filamentous fungi are heterogeneous and that much of this heterogeneity may already be present at the end of batch growth, i.e., before the onset of continuous cultivation.
Design and modeling of a novel single-actuator differentially driven robot (2014)

In this paper, we introduce a concept design for a single-actuator differentially driven robot. The design is based on connecting two variable-diameter wheels to the same drive shaft. The wheels are designed to have engineered stiffness so that the diameters of the wheels are varied by shifting the weight of the drive mechanism from side to side. We also develop the kinostatic and dynamic models of the mobile platform, which is used later to perform motion planning techniques.
Optimal condition of vitrification method for cryopreservation of human ovarian cortical tissues (2011)

The 10-min exposure group for vitrification showed better results compared with other conditions and the slow-freezing group.
Norwalk virus-associated gastroenteritis traced to ice consumption aboard a cruise ship in Hawaii: comparison and application of molecular method-based assays (1994)

Investigation of an outbreak of acute nonbacterial gastroenteritis on a cruise ship provided an opportunity to assess new molecular method-based diagnostic methods for Norwalk virus (NV) and the antibody response to NV infection. The outbreak began within 36 h of embarkation and affected 30% of 672 passengers and crew. No single meal, seating, or food item was implicated in the transmission of NV, but a passenger's risk of illness was associated with the amount of ice (but not water) consumed (chi-square for trend, P = 0.009). Of 19 fecal specimens examined, 7 were found to contain 27-nm NV-like particles by electron microscopy and 16 were positive by PCR with very sensitive NV-specific primers, but only 5 were positive by a new highly specific antigen enzyme immunoassay for NV. Ten of 12 serum specimen pairs demonstrated a fourfold or greater rise in antibody titer to recombinant baculovirus-expressed NV antigen. The amplified PCR band shared only 81% nucleotide sequence homology with the reference NV strain, which may explain the lack of utility of the fecal specimen enzyme immunoassay. This report, the first to document the use of these molecular method-based assays for investigation of an outbreak, demonstrates the importance of highly sensitive viral diagnostics such as PCR and serodiagnosis for the epidemiologic investigation of NV gastroenteritis.
Expression, purification and characteristic of thermostable alkaline phosphatase (TAPND27) (2000)

Through purification and characteristic determination, it was found that TAPND27 is a octamer with 65deg C as its optimal reaction temperature. It remains 49.4% enzymatic activity after incubation at 99deg C for 30 min while it remains above 70% enzymatic activity with 5% SDS or Tween20 in the reaction system. It is also stable in wide-range pH. The results implied that TAPND27 is suitable for the application on the condition of high temperature and concentration of detergent.
Centromere Protein B of African Green Monkey Cells: Gene Structure, Cellular Expression, and Centromeric Localization (1996)

Centromere protein B (CENP-B) is a centromeric DNA-binding protein which recognizes a 17-bp sequence (CENP-B box) in human and mouse centromeric satellite DNA. The African green monkey (AGM) is phylogenetically closer to humans than mice and is known to contain large amounts of alpha-satellite DNA, but there has been no report of CENP-B boxes or CENP-B in the centromere domains of its chromosomes. To elucidate the AGM CENP-B-CENP-B box interaction, we have analyzed the gene structure, expression, biochemical properties, and centromeric localization of its CENP-B. The amino acid sequence deduced from the cloned AGM CENP-B gene was established to be highly homologous to that of human and mouse CENP-B. In particular, the DNA binding and homodimer formation domains demonstrated 100% identity to their human and mouse counterparts. Immunoblotting and DNA mobility shift analyses revealed CENP-B to be expressed in AGM cell lines. As predicted from the gene structure, the AGM CENP-B in the cell extracts exhibited the same DNA binding specificity and homodimer forming activity as human CENP-B. By indirect immunofluorescent staining of AGM mitotic cells with anti-CENP-B antibodies, a centromere-specific localization of AGM CENP-B could be demonstrated. We also isolated AGM alpha-satellite DNA with a CENP-B box-like sequence with CENP-B affinity. These results not only prove that CENP-B functionally persists in AGM cells but also suggest that the AGM genome contains the recognition sequences for CENP-B (CENP-B boxes with the core recognition sequence or CENP-B box variants) in centromeric satellite DNA.
WEBDIFF: Automated identification of cross-browser issues in web applications (2010)

Cross-browser (and cross-platform) issues are prevalent in modern web based applications and range from minor cosmetic bugs to critical functional failures. In spite of the relevance of these issues, cross-browser testing of web applications is still a fairly immature field. Existing tools and techniques require a considerable manual effort to identify such issues and provide limited support to developers for fixing the underlying cause of the issues. To address these limitations, we propose a technique for automatically detecting cross-browser issues and assisting their diagnosis. Our approach is dynamic and is based on differential testing. It compares the behavior of a web application in different web browsers, identifies differences in behavior as potential issues, and reports them to the developers. Given a page to be analyzed, the comparison is performed by combining a structural analysis of the information in the page's DOM and a visual analysis of the page's appearance, obtained through screen captures. To evaluate the usefulness of our approach, we implemented our technique in a tool, called WEBDIFF, and used WEBDIFF to identify cross-browser issues in nine real web applications. The results of our evaluation are promising, in that WEBDIFF was able to automatically identify 121 issues in the applications, while generating only 21 false positives. Moreover, many of these false positives are due to limitations in the current implementation of WEBDIFF and could be eliminated with suitable engineering.
Defining high risk (2010)

The article “Proliferation of prenatal ultrasonography” [1][1] is commendable as an attempt to define current trends in prenatal ultrasonography. However, a population-based study has an inherent weakness, i.e. completeness of case ascertainment, potentially resulting in incorrect assignment of
Enhancing online personal connections through the synchronized sharing of online video (2008)

Going to movies in a group and inviting friends over to watch TV are common social activities. This social engagement both improves the viewing experience and helps us stay close with our friends and family. To bring this feeling of co-presence to the Internet, we developed a set of prototypes that enable people to feel more connected by watching web video together in sync. We present the preliminary results of a quantitative usage study and show initial evidence that simultaneous video sharing online can help people feel closer and more connected to their friends and family.
High mitochondrial DNA copy number is associated with longer survival in young patients with glioblastoma (2019)

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