MATLAB*P 2.0: A unified parallel MATLAB

MATLAB is one of the most widely used mathematical computing environments in technical computing. It is an interactive environment that provides high performance computational routines and an easy-to-use, C-like scripting language. Mathworks, the company that develops MATLAB, currently does not provide a version of MATLAB that can utilize parallel computing. This has led to academic and commercial efforts outside Mathworks to build a parallel MATLAB, using a variety of approaches. In a survey, 26 parallel MATLAB projects utilizing four different approaches have been identified. MATLAB*P is one of the 26 projects. It makes use of the backend support approach. This approach provides parallelism to MATLAB programs by relaying MATLAB commands to a parallel backend. The main difference between MATLAB*P and other projects that make use of the same approach is in its focus. MATLAB*P aims to provide a user-friendly supercomputing environment in which parallelism is achieved transparently through the use of objected oriented programming features in MATLAB. One advantage of this approach is that existing scripts can be run in parallel with no or minimal modifications. This paper describes MATLAB*P 2.0, which is a complete rewrite of MATLAB*P. This new version brings together the backend support approach with embarrassingly parallel and MPI approaches to provide the first complete parallel MATLAB framework.Singapore-MIT Alliance (SMA

Solving Multiple Classes of Problems in Parallel with MATLAB*P

MATLAB [7] is one of the most widely used mathematical computing environments in technical computing. It is an interactive environment that provides high performance computational routines and an easy-to-use, C-like scripting language. Mathworks, the company that develops MATLAB, currently does not provide a version of MATLAB that can utilize parallel computing [9]. This has led to academic and commercial efforts outside Mathworks to build a parallel MATLAB, using a variety of approaches. MATLAB*P is a parallel MATLAB that focus on enhancing productivity by providing an easy to use parallel computing tool. Using syntaxes identical to regular MATLAB, it can be used to solve large scale algebraic problems as well as multiple small problems in parallel. This paper describes how the innovative combination of ’*p mode’ and ’MultiMATLAB/MultiOctave mode’ in MATLAB*P can be used to solve a large range of real world problems.Singapore-MIT Alliance (SMA

Cervical radiograph of a patient with cervicogenic dizziness

Clinical image. This is a cervical X-ray of a patient suffering from long term dizziness and associated neck pain and stiffness.The X-ray showed that the C1 cervical vertebrae were in a rotated position.In some cases of dizziness, one of the causes can be attributed to pathology or dysfunction of upper cervical spine

Anosmin-1 contributes to brain tumor malignancy through integrin signal pathways

Anosmin-1, encoded by the KAL1 gene, is an extracellular matrix (ECM)-associated protein which plays essential roles in the establishment of olfactory and GNRH neurons during early brain development. Loss-of-function mutations of KAL1 results in Kallmann syndrome with delayed puberty and anosmia. There is, however, little comprehension of its role in the developed brain. As reactivation of developmental signal pathways often takes part in tumorigenesis, we investigated if anosmin-1-mediated cellular mechanisms associated with brain tumors. Our meta-analysis of gene expression profiles of patients' samples and public microarray datasets indicated that KAL1 mRNA was significantly upregulated in high-grade primary brain tumors compared with the normal brain and low-grade tumors. The tumor-promoting capacity of anosmin-1 was demonstrated in the glioblastoma cell lines, where anosmin-1 enhanced cell motility and proliferation. Notably, anosmin-1 formed a part of active β1 integrin complex, inducing downstream signaling pathways. ShRNA-mediated knockdown of anosmin-1 attenuated motility and growth of tumor cells and induced apoptosis. Anosmin-1 may also enhance the invasion of tumor cells within the ECM by modulating cell adhesion and activating extracellular proteases. In a mouse xenograft model, anosmin-1-expressing tumors grew faster, indicating the role of anosmin-1 in tumor microenvironment in vivo. Combined, these data suggest that anosmin-1 can facilitate tumor cell proliferation, migration, invasion, and survival. Therefore, although the normal function of anosmin-1 is required in the proper development of GNRH neurons, overexpression of anosmin-1 in the developed brain may be an underlying mechanism for some brain tumors

Modelo prolab: El Amauta, una propuesta que revolucionará la forma de aprender

En la actualidad, existe una problemática educativa respecto al desarrollo de competencias de los estudiantes en edad escolar, lo que limita su desempeño académico y se evidencia en indicadores tales como la prueba PISA. Esto se ha visto agravado por el COVID 19, lo que ocasionó el cierre de escuelas, aumento de la deserción escolar, etc., y trajo consigo una nueva forma de impartir la educación adaptándose al entorno digital. El presente proyecto tiene como fin demostrar que los padres y madres de familia están dispuestos a contratar servicios de reforzamiento académico que incentiven el interés de sus hijos, los cuales pueden contribuir en su aprendizaje y desarrollo de sus habilidades personales. Para ello, se utilizaron herramientas como el design thinking, business model canvas, lean startup, entre otras, lo que permitió tener un mejor entendimiento del usuario y su necesidad, dando como resultado una plataforma que ofrece contenidos virtuales alineados a la malla educativa oficial que integran recursos tecnológicos adaptados a un mercado carente de ofertas educativas digitales. Es así como nace El Amauta, una solución enfocada al acompañamiento de los estudiantes de hoy y líderes del mañana, potenciando su aprendizaje y competencias que contribuya a su desarrollo integral. Por su parte, los resultados económicos que acompañan la decisión de implementación demuestran la rentabilidad del proyecto en un periodo de cinco años, expresada en un valor actual neto económico (VANE) que asciende a S/2’524,189. Finalmente, la solución es sostenible porque además de su viabilidad financiera, impacta positivamente en la ODS 4 (Educación de calidad) y estima un valor actual neto social (VANS) de S/695,686, contribuyendo a la reducción del índice de la repitencia escolar.At the Present, there is an educational problem regarding the development of competences of students at school age students, which limits their academic performance and is evidenced in international indicators, such as the PISA test. This has been aggravated by COVID-19, which led to school closures, increased dropout rates, etc. Being a new way of imparting education adapting to the digital environment. The purpose of this project is to demonstrate that parents are willing to hire academic reinforcement services in a digital environment that adopts methodologies valued by their children, which contribute to their learning and the development of their personal skills. To do this, tools such as design thinking, business model canvas, lean startup, among others, were used, which allowed a better understanding of the user and their needs, resulting in a platform that offers virtual content through the integration of various technological resources and learning methodologies adapted to a market lacking digital educational offers. This is how El Amauta was born, a solution focused on the accompaniment of today's students and tomorrow's leaders, enhancing their learning and skills that guarantee their integral development. On the other hand, the economic results that accompany the implementation decision demonstrate the profitability of the project in a period of 5 years. On the other hand, the economic results that accompany the implementation decision demonstrate the profitability of the project in a period of 5 years, expressed in an economic net present value (ENPV) amounting to S/2’524,189. Finally, the solution is sustainable because in addition to its financial viability, it has a positive impact on SDG 4 (Quality education) and estimates a social net present value (SNPV) of S/695,686, contributing to the reduction of the school repetition index

Efficacy and safety of the biosimilar ABP 501 compared with adalimumab in patients with moderate to severe rheumatoid arthritis: a randomised, double-blind, phase III equivalence study

Objectives ABP 501 is a Food and Drug Administration-approved biosimilar to adalimumab; structural, functional and pharmacokinetic evaluations have shown that the two are highly similar. We report results from a phase III study comparing efficacy, safety and immunogenicity between ABP 501 and adalimumab. Methods In this randomised, double-blind, active comparator-controlled, 26-week equivalence study, patients with moderate to severe active rheumatoid arthritis (RA) despite methotrexate were randomised (1:1) to ABP 501 or adalimumab (40 mg) every 2 weeks. Primary endpoint was risk ratio (RR) of ACR20 between groups at week 24. Primary hypothesis that the treatments were equivalent would be confirmed if the 90% CI for RR of ACR20 at week 24 fell between 0.738 and 1.355, demonstrating that ABP 501 is similar to adalimumab. Secondary endpoints included Disease Activity Score 28-joint count-C reactive protein (DAS28-CRP). Safety was assessed via adverse events (AEs) and laboratory evaluations. Antidrug antibodies were assessed to determine immunogenicity. Results A total of 526 patients were randomised (n=264, ABP 501; n=262 adalimumab) and 494 completed the study. ACR20 response at week 24 was 74.6% (ABP 501) and 72.4% (adalimumab). At week 24, the RR of ACR20 (90% CI) between groups was 1.039 (0.954, 1.133), confirming the primary hypothesis. Changes from baseline in DAS28-CRP, ACR50 and ACR70 were similar. There were no clinically meaningful differences in AEs and laboratory abnormalities. A total of 38.3% (ABP 501) and 38.2% (adalimumab) of patients tested positive for binding antidrug antibodies. Conclusions Results from this study demonstrate that ABP 501 is similar to adalimumab in clinical efficacy, safety and immunogenicity in patients with moderate to severe RA

Low immunogenicity of tocilizumab in patients with rheumatoid arthritis

Objective Subcutaneous (SC) and intravenous formulations of tocilizumab (TCZ) are available for the treatment of patients with rheumatoid arthritis (RA), based on the efficacy and safety observed in clinical trials. Anti-TCZ antibody development and its impact on safety and efficacy were evaluated in adult patients with RA treated with intravenous TCZ (TCZ-IV) or TCZ-SC as monotherapy or in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Methods Data from 5 TCZ-SC and 8 TCZ-IV phase III clinical trials and 1 TCZ-IV clinical pharmacology safety study (>50 000 samples) were pooled to assess the immunogenicity profile of TCZ-SC and TCZ-IV (8974 total patients). The analysis included antidrug antibody (ADA) measurement following TCZ-SC or TCZ-IV treatment as monotherapy or in combination with csDMARDs, after dosing interruptions or in TCZ-washout samples, and the correlation of ADAs with clinical response, adverse events or pharmacokinetics (PK). Results The proportion of patients who developed ADAs following TCZ-SC or TCZ-IV treatment was 1.5% and 1.2%, respectively. ADA development was also comparable between patients who received TCZ monotherapy and those who received concomitant csDMARDs (0.7–2.0%). ADA development did not correlate with PK or safety events, including anaphylaxis, hypersensitivity or injection-site reactions, and no patients who developed ADAs had loss of efficacy. Conclusions The immunogenicity risk of TCZ-SC and TCZ-IV treatment was low, either as monotherapy or in combination with csDMARDs. Anti-TCZ antibodies developed among the small proportion of patients had no evident impact on PK, efficacy or safety

NSC23925, Identified in a High-Throughput Cell-Based Screen, Reverses Multidrug Resistance

Multidrug resistance (MDR) is a major factor which contributes to the failure of cancer chemotherapy, and numerous efforts have been attempted to overcome MDR. To date, none of these attempts have yielded a tolerable and effective therapy to reverse MDR; thus, identification of new agents would be useful both clinically and scientifically.To identify small molecule compounds that can reverse chemoresistance, we developed a 96-well plate high-throughput cell-based screening assay in a paclitaxel resistant ovarian cancer cell line. Coincubating cells with a sublethal concentration of paclitaxel in combination with each of 2,000 small molecule compounds from the National Cancer Institute Diversity Set Library, we identified a previously uncharacterized molecule, NSC23925, that inhibits Pgp1 and reverses MDR1 (Pgp1) but does not inhibit MRP or BCRP-mediated MDR. The cytotoxic activity of NSC23925 was further evaluated using a panel of cancer cell lines expressing Pgp1, MRP, and BCRP. We found that at a concentration of >10 microM NSC23925 moderately inhibits the proliferation of both sensitive and resistant cell lines with almost equal activity, but its inhibitory effect was not altered by co-incubation with the Pgp1 inhibitor, verapamil, suggesting that NSC23925 itself is not a substrate of Pgp1. Additionally, NSC23925 increases the intracellular accumulation of Pgp1 substrates: calcein AM, Rhodamine-123, paclitaxel, mitoxantrone, and doxorubicin. Interestingly, we further observed that, although NSC23925 directly inhibits the function of Pgp1 in a dose-dependent manner without altering the total expression level of Pgp1, NSC23925 actually stimulates ATPase activity of Pgp, a phenomenon seen in other Pgp inhibitors.The ability of NSC23925 to restore sensitivity to the cytotoxic effects of chemotherapy or to prevent resistance could significantly benefit cancer patients

Concurrent Oral 1 - Therapy of rheumatic disease: OP4. Effectiveness of Rituximab in Rheumatoid Arthritis: Results from the British Society for Rheumatology Biologics Register (BSRBR)

Background: Rituximab (RTX) in combination with methotrexate (MTX) has been licensed since 2006 for the management of severe active rheumatoid arthritis (RA) in patients who have failed at least one anti-tumour necrosis factor (anti-TNF) therapy. Published clinical trials have demonstrated the efficacy of RTX in improving both clinical symptoms and patients' physical function. This study aimed to assess the effectiveness of RTX in RA patients treated in routine clinical practice by examining clinical and patient reported outcomes six months after receiving a first course of RTX. Methods: The analysis involved 550 RA patients registered with the BSRBR, who were starting RTX and were followed up for at least 6 months. Change in Disease Activity Score (DAS28) and European League Against Rheumatism (EULAR) response were used to assess the clinical response while change in Health Assessment Questionnaire (HAQ) score was used to assess the physical function of the patients 6 months after starting RTX. The change in DAS28 and HAQ was compared between seronegative and seropositive patients and anti-TNF naïve patients versus anti-TNF failures. The response was also compared between patients receiving RTX in combination with MTX, other non-biologic disease modifying anti-rheumatic drugs (nbDMARDs) or no nbDMARDs. Results: The mean (s.d.) age of the cohort was 59 (12) years and 78% of the patients were females. The patients had a mean (s.d.) of 15 (10) years of disease duration. 16% were biologic naïve while 84% were anti-TNF failures. 32% of the patients were seronegative and 68% were seropositive. The mean (95% CI) DAS28 at baseline was 6.2 (6.1, 6.3) which decreased to 4.8 (4.7, 4.9) at 6 months of follow up. 16% were EULAR good responders, 43% were moderate responders and 41% were non responders. The mean (95% CI) change in HAQ was −0.1 (−0.2, −0.1) (Table 1). The mean change in DAS28 was similar in seropositive and seronegative patients (p = 0.18) while the anti-TNF naïve patients showed a greater reduction in DAS28 scores than anti-TNF failures (p = 0.05). Patients receiving RTX in combination with MTX showed similar changes in DAS28 and HAQ compared to patients receiving RTX alone or with other nbDMARDs. Conclusions: RTX has proven to be effective in the routine clinical practice. Anti-TNF naïve patients seem to benefit more from RTX treatment than anti-TNF failures. Disclosure statement: The authors have declared no conflicts of interes

An Epstein-Barr Virus Anti-Apoptotic Protein Constitutively Expressed in Transformed Cells and Implicated in Burkitt Lymphomagenesis: The Wp/BHRF1 Link

Two factors contribute to Burkitt lymphoma (BL) pathogenesis, a chromosomal translocation leading to c-myc oncogene deregulation and infection with Epstein-Barr virus (EBV). Although the virus has B cell growth–transforming ability, this may not relate to its role in BL since many of the transforming proteins are not expressed in the tumor. Mounting evidence supports an alternative role, whereby EBV counteracts the high apoptotic sensitivity inherent to the c-myc–driven growth program. In that regard, a subset of BLs carry virus mutants in a novel form of latent infection that provides unusually strong resistance to apoptosis. Uniquely, these virus mutants use Wp (a viral promoter normally activated early in B cell transformation) and express a broader-than-usual range of latent antigens. Here, using an inducible system to express the candidate antigens, we show that this marked apoptosis resistance is mediated not by one of the extended range of EBNAs seen in Wp-restricted latency but by Wp-driven expression of the viral bcl2 homologue, BHRF1, a protein usually associated with the virus lytic cycle. Interestingly, this Wp/BHRF1 connection is not confined to Wp-restricted BLs but appears integral to normal B cell transformation by EBV. We find that the BHRF1 gene expression recently reported in newly infected B cells is temporally linked to Wp activation and the presence of W/BHRF1-spliced transcripts. Furthermore, just as Wp activity is never completely eclipsed in in vitro–transformed lines, low-level BHRF1 transcripts remain detectable in these cells long-term. Most importantly, recognition by BHRF1-specific T cells confirms that such lines continue to express the protein independently of any lytic cycle entry. This work therefore provides the first evidence that BHRF1, the EBV bcl2 homologue, is constitutively expressed as a latent protein in growth-transformed cells in vitro and, in the context of Wp-restricted BL, may contribute to virus-associated lymphomagenesis in vivo