D2P: Automatically Creating Distributed Dynamic Programming Codes

Dynamic Programming (DP) algorithms are common targets for parallelization, and, as these algorithms are applied to larger inputs, distributed implementations become necessary. However, creating distributed-memory solutions involves the challenges of task creation, program and data partitioning, communication optimization, and task scheduling. In this paper we present D2P, an end-to-end system for automatically transforming a specification of any recursive DP algorithm into distributed-memory implementation of the algorithm. When given a pseudo-code of a recursive DP algorithm, D2P automatically generates the corresponding MPI-based implementation. Our evaluation of the generated distributed implementations shows that they are efficient and scalable. Moreover, D2P-generated implementations are faster than implementations generated by recent general distributed DP frameworks, and are competitive with (and often faster than) hand-written implementations

An adenovirus-derived protein: A novel candidate for anti-diabetic drug development

© 2015 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). Aims Exposure to human adenovirus Ad36 is causatively and correlatively linked with better glycemic control in animals and humans, respectively. Although the anti-hyperglycemic property of Ad36 may offer some therapeutic potential, it is impractical to use an infectious agent for therapeutic benefit. Cell-based studies identified that Ad36 enhances cellular glucose disposal via its E4orf1 protein. Ability to improve glycemic control in vivo is a critical prerequisite for further investigating the therapeutic potential of E4orf1. Therefore, the aim of this study was to determine the ability of E4orf1 to improve glycemic control independent of insulin despite high fat diet. Materials & Methods 8-9wk old male C57BL/6J mice fed a high-fat diet (60% kcal) were injected with a retrovirus plasmid expressing E4orf1, or a null vector (Control). Glycemic control was determined by glucose and insulin tolerance test. Islet cell size, amount of insulin and glucagon were determined in formalin-fixed pancreas. Rat insulinoma cell line (832/13) was infected with E4orf1 or control to determine changes in glucose stimulated insulin secretion. Protein from flash frozen adipose tissue depots, liver and muscle was used to determine molecular signaling by western blotting. Results In multiple experiments, retrovirus-mediated E4orf1 expression in C57BL/6J mice significantly and reproducibly improved glucose excursion following a glucose load despite a high fat diet (60% energy). Importantly, E4orf1 improved glucose clearance without increasing insulin sensitivity, production or secretion, underscoring its insulin-independent effect. E4orf1 modulated molecular signaling in mice tissue, which included greater protein abundance of adiponectin, p-AKT and Glucose transporter Glu4. Conclusions This study provides the proof of concept for translational development of E4orf1 as a potential anti-diabetic agent. High fat intake and impaired insulin signaling are often associated with obesity, diabetes and insulin resistance. Hence, the ability of E4orf1 to improve glycemic control despite high fat diet and independent of insulin, is particularly attractive

Proposal of RT-PCReBased Mass Population Screening for Severe Acute Respiratory Syndrome Coronavirus 2 (Coronavirus Disease 2019)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing has lagged in many countries because of test kit shortages and analytical process bottlenecks. This study investigated the feasibility and accuracy of a sample pooling approach for wide-scale population screening for coronavirus disease 2019. A total of 940 nasopharyngeal swab samples (934 negative and 6 positive) previously tested for SARS-CoV-2 were deidentified and assigned random numbers for analysis, and 94 pools of 10 samples each were generated. Automated RNA extraction, followed by RT-PCR, was performed in a 96-well plate. Positive pools were identified, and the individual samples were reanalyzed. Of the 94 pools/wells, four were positive [Ct values: N (22.7 to 28.3), ORF1ab (23.3 to 27.2), and internal control (34.4 to 35.4)]. The 40 samples comprising the four pools were identified and reanalyzed individually; six samples were positive, with Ct values of N gene, ORF1ab, and internal control comparable to their respective wells. Additional experiments were performed on samples with high Ct values, and overall results showed 91.6% positive and 100% negative agreement compared with individual testing approach. Thus, 940 samples were tested in 148 reactions compared with 940 reactions in routine screening. The sample pooling strategy may help catch up with testing needs and minimal turnaround times and facilitate enormous savings on laboratory supplies, extraction, and PCR kits currently in short supply

E4orf1: A Novel Ligand That Improves Glucose Disposal in Cell Culture

Reducing dietary fat intake and excess adiposity, the cornerstones of behavioral treatment of insulin resistance(IR), are marginally successful over the long term. Ad36, a human adenovirus, offers a template to improve IR, independent of dietary fat intake or adiposity. Ad36 increases cellular glucose uptake via a Ras-mediated activation of phosphatidyl inositol 3-kinase(PI3K), and improves hyperglycemia in mice, despite a high-fat diet and without reducing adiposity. Ex-vivo studies suggest that Ad36 improves hyperglycemia in mice by increasing glucose uptake by adipose tissue and skeletal muscle, and by reducing hepatic glucose output. It is impractical to use Ad36 for therapeutic action. Instead, we investigated if the E4orf1 protein of Ad36, mediates its anti-hyperglycemic action. Such a candidate protein may offer an attractive template for therapeutic development. Experiment-1 determined that Ad36 ‘requires’ E4orf1 protein to up-regulate cellular glucose uptake. Ad36 significantly increased glucose uptake in 3T3-L1 preadipocytes, which was abrogated by knocking down E4orf1 with siRNA. Experiment-2 identified E4orf1 as ‘sufficient’ to up-regulate glucose uptake. 3T3-L1 cells that inducibly express E4orf1, increased glucose uptake in an induction-dependent manner, compared to null vector control cells. E4orf1 up-regulated PI3K pathway and increased abundance of Ras–the obligatory molecule in Ad36-induced glucose uptake. Experiment-3: Signaling studies of cells transiently transfected with E4orf1 or a null vector, revealed that E4orf1 may activate Ras/PI3K pathway by binding to Drosophila discs-large(Dlg1) protein. E4orf1 activated total Ras and, particularly the H-Ras isoform. By mutating the PDZ domain binding motif(PBM) of E4orf1, Experiment-4 showed that E4orf1 requires its PBM to increase Ras activation or glucose uptake. Experiment-5: In-vitro, a transient transfection by E4orf1 significantly increased glucose uptake in preadipocytes, adipocytes, or myoblasts, and reduced glucose output by hepatocytes. Thus, the highly attractive anti-hyperglycemic effect of Ad36 is mirrored by E4orf1 protein, which may offer a novel ligand to develop anti-hyperglycemic drugs

Distributed Execution of Recursive Irregular Applications

Massive computing power and applications running on this power, primarily confined to expensive supercomputers a decade ago, have now become mainstream through the availability of clusters with commodity computers and high-speed interconnects running big-data era applications. The challenges associated with programming such systems, for effectively utilizing the computing power, have led to the creation of intuitive abstractions and implementations targeting average users, domain experts, and savvy (parallel) programmers. There is often a trade-off between the ease of programming and performance when using these abstractions. This thesis develops tools to bridge the gap between ease of programming and performance of irregular programs—programs that involve one or more of irregular- data structures, control structures, and communication patterns—on distributed-memory systems. Irregular programs are focused heavily in domains ranging from data mining to bioinformatics to scientific computing. In contrast to regular applications such as stencil codes and dense matrix-matrix multiplications, which have a predictable pattern of data access and control flow, typical irregular applications operate over graphs, trees, and sparse matrices and involve input-dependent data access pattern and control flow. This makes it difficult to apply optimizations such as those targeting locality and parallelism to programs implementing irregular applications. Moreover, irregular programs are often used with large data sets that prohibit single-node execution due to memory limitations on the node. Hence, distributed solutions are necessary in order to process all the data. In this thesis, we introduce SPIRIT, a framework consisting of an abstraction and a space-adaptive runtime system for simplifying the creation of distributed implementations of recursive irregular programs based on spatial acceleration structures. SPIRIT addresses the insufficiency of traditional data-parallel approaches and existing systems in effectively parallelizing computations involving repeated tree traversals. SPIRIT employs locality optimizations applied in a shared-memory context, introduces a novel pipeline-parallel approach to execute distributed traversals, and trades-off performance with memory usage to create a space-adaptive system that achieves a scalable performance, and outperforms implementations done in contemporary distributed graph processing frameworks. We next introduce Treelogy to understand the connection between optimizations and tree-algorithms. Treelogy provides an ontology and a benchmark suite of a broader class of tree algorithms to help answer: (i) is there any existing optimization that is applicable or effective for a new tree algorithm? (ii) can a new optimization developed for a tree algorithm be applied to existing tree algorithms from other domains? We show that a categorization (ontology) based on structural properties of tree-algorithms is useful for both developers of new optimizations and new tree algorithm creators. With the help of a suite of tree traversal kernels spanning the ontology, we show that GPU, shared-, and distributed-memory implementations are scalable and the two-point correlation algorithm with vptree performs better than the standard kdtree implementation. In the final part of the thesis, we explore the possibility of automatically generating efficient distributed-memory implementations of irregular programs. As manually creating distributed-memory implementations is challenging due to the explicit need for managing tasks, parallelism, communication, and load-balancing, we introduce a framework, D2P, to automatically generate efficient distributed implementations of recursive divide-conquer algorithms. D2P automatically generates a distributed implementation of a recursive divide-conquer algorithm from its specification, which is a high-level outline of a recursive formulation. We evaluate D2P with recursive Dynamic programming (DP) algorithms

E4orf1 Prevents Progression of Fatty Liver Disease in Mice on High Fat Diet

Non-alcoholic fatty liver disease (NAFLD) covers a broad spectrum of liver diseases ranging from steatosis to cirrhosis. There are limited data on prevention of hepatic steatosis or its progression to liver disease. Here, we tested if either transgenic (Tg) doxycycline-induced expression in adipose tissue of E4orf1 (E4), an adenoviral protein, or dietary fat restriction attenuated hepatic steatosis or its progression in mice. Twelve to fourteen-week-old TgE4 mice (E4 group) and control mice were exposed to a 60% (Kcal) high fat diet (HFD) for 20 weeks, while another group of mice on HFD for 10 weeks were switched to a chow diet (chow group) for another 10 weeks. Glycemic control was determined at weeks 10 and 20. Tissues were collected for gene and protein analysis at sacrifice. Compared to control, diet reversal significantly reduced body weight in the chow group, whereas E4 expression attenuated weight gain, despite HFD. E4 mice evinced significantly improved glucose clearance, lower endogenous insulin secretion, reduced serum triglycerides, attenuated hepatic steatosis and inflammation. Interestingly, in spite of weight loss and lower liver fat, chow mice showed significant upregulation of hepatic genes involved in lipid metabolism. Despite HFD, E4 prevents hepatic lipid accumulation and progression of hepatic steatosis, while diet reversal maintains hepatic health, but is unable to improve molecular changes

A cephalometric study to ascertain the use of nasion as a guide in locating the position of orbitale as an anterior reference point among a population of South Coastal Karnataka

Context: To ascertain the use of nasion as a guide in locating the position of orbitale as an anterior reference point in the face-bow transfer records in individuals having different facial types. Aims: This study evaluated the distance from the nasion to the orbitale using cephalometric measurements to ascertain the use of nasion as a guide in locating the position of orbitale as an anterior reference point in individuals having different facial types among a population of South Coastal Karnataka. Subjects and Methods: Anthropometric measurements were made on 61 subjects and they were classified into mesoprosopic, euryprosopic and leptoprosopic facial type groups based upon the prosopic index. Lateral cephalometric radiographs were taken and nasion to orbitale distance was measured. The collected data was tabulated and statistically analyzed. Statistical Analysis Used: The statistical test carried out was the analysis of variance test and correlations were checked for using Pearson′s correlation test. Results: The study found the mean distance from nasion to orbitale was 24.25 mm with a standard deviation 4.26 mm. A good correlation was found between prosopic index and nasion to orbitale distance. No statistically significant variation in nasion to orbitale distance in individuals of different facial types was found. Conclusions: Although, variation exists it was not statistically significant. However, since a large range of measurements were found, prior evaluation using cephalometric radiographs may be necessary in certain individuals

DDMIA: Distributed Dynamic Mutual Identity Authentication for Referrals in Blockchain-Based Health Care Networks

Patients go to multiple healthcare providers for treatment, and their health data is generally distributed among providers. The distributed health data and the decentralized health care system structure make it ideal for blockchain-based health information systems. The authors consider the referral use case; for instance, a patient goes to his primary health Centre (PHC) for treatment and is referred to a hospital. Authentication is usually done using certificates or key cryptography, which could become cumbersome when multiple parties are involved in a healthcare interaction. The security requirements were defined, and a novel multi-party, mutual patient identity authentication scheme called “Distributed Dynamic Mutual Identity Authentication (DDMIA)” was proposed for the referral use case in a blockchain-based e-health network. The DDMIA enables the PHC to authenticate the patient to the referred hospital. The DDMIA scheme was designed using Elliptic Curve Cryptography. It was proven to be secure by assuming the hardness of the elliptic curve discrete log problem (ECDLP) and Elliptic curve computational Diffie–Hellman problem (ECDH) using CK-Model. The formal security analysis using BAN logic proved that the sessions are secure after authentication. The DDMIA scheme was simulated in the AVISPA tool and proven safe against all active attacks. The scheme allows a patient to be authenticated by multiple parties without registering with all parties. It eliminates the need for multiple registration centers as well as digital certificates. Hence, the DDMIA scheme can be implemented for similar multiparty authentication requirements in blockchain-based networks

Improvization of conventional cytology by centrifuged liquid-based cytology in oral exfoliative cytology specimen

Background: Exfoliative cytology is the microscopic examination of shed or desquamated cells from the epithelial surface. Centrifuged liquid-based cytology (CLBC) is a modified technique that was used in the current study. Aims: To compare the efficacy of CLBC with conventional cytology in apparently normal mucosa after staining with Papanicolaou (PAP) stain. Materials and Methods: Fifty cases of apparently normal mucosa from healthy subjects were selected for the study. The first sample was taken and spread on the slide by the conventional technique. The second sample was flushed out in a suspending solution, centrifuged, and the cell pellet obtained was used to make the smear. The stained smears were compared for seven parameters such as adequate cellularity, clear background, uniform distribution, cellular overlapping, cellular elongation, mucus, and inflammatory cells. Chi-square test was used for statistical analysis and P ≤ 0.05 was considered to be statistically significant. Results: There was a statistically significant difference between CLBC and conventional cytology with parameters such as adequate cellularity (P = 0.001), clear background (P = 0.001), uniform distribution (0.005), cellular overlapping, and cellular elongation (P = 0). The presence of mucus and inflammatory cells was minimal as the samples were collected from healthy subjects. Conclusion: CLBC has better efficacy over the conventional method in all the parameters analyzed