Emission Characteristics of the Projectile Fragments at Relativistic Energy

A projectile (84^Kr_36) having kinetic energy around 1 A GeV was used to expose NIKFI BR-2 emulsion target. A total of 700 inelastic events are used in the present studies on projectile fragments. The emission angle of the projectile fragments are strongly affected by charge of the other projectile fragments emitted at same time with different emission angle is observed. The angular distribution studies show symmetrical nature for lighter charge projectile fragments. The symmetrical nature decreased with the charge of projectile fragments. At ~4o of emission angle for double charge projectile fragments, the momentum transfer during interaction is similar for various target species of emulsion were observed. We also observed a small but significant amplitude peaks on both side of the big peak for almost all light charge projectile fragments having different delta angle values. It reflects that there are few percent of projectile fragments that are coming from the decay of heavy projectile fragments or any other process.Comment: 32 pages, 17 Figure

Opportunities and priorities for breast surgical research

The Breast Cancer Campaign Gap analysis (2013) established breast cancer research priorities without specific focus on surgical research nor the role of surgeons. The majority of breast cancer patients encounter a surgeon at diagnosis or during treatment, thus surgical involvement in design and delivery of high-quality research to improve patient care is critical. This review aims to identify opportunities and priorities for breast surgical research to complement the previous gap analysis

Presence of RD149 Deletions in M. tuberculosis Central Asian Strain1 Isolates Affect Growth and TNFα Induction in THP-1 Monocytes

Central Asian Strain 1 (CAS1) is the prevalent Mycobacterium tuberculosis genogroup in South Asia. CAS1 strains carry deletions in RD149 and RD152 regions. Significance of these deletions is as yet unknown. We compared CAS1 strains with RD149 and concurrent RD149-RD152 deletions with CAS1 strains without deletions and with the laboratory reference strain, M. tuberculosis H37Rv for growth and for induction of TNFα, IL6, CCL2 and IL10 in THP-1 cells. Growth of CAS1 strains with deletions was slower in broth (RD149; p = 0.024 and RD149-RD152; p = 0.025) than that of strains without deletions. CAS1 strains with RD149 deletion strains further showed reduced intracellular growth (p = 0.013) in THP-1 cells as compared with strains without deletions, and also as compared with H37Rv (p = 0.007) and with CAS1 RD149-RD152 deletion strains (p = 0.029). All CAS1 strains induced higher levels of TNFα and IL10 secretion in THP-1 cells than H37Rv. Additionally, CAS1 strains with RD149 deletions induced more TNFα secretion than those without deletions (p = 0.013). CAS1 RD149 deletion strains from extrapulmonary sources showed more rapid growth and induced lower levels of TNFα and IL6 secretion in THP-1 cells than isolates from pulmonary sources. This data suggests that presence of RD149 reduces growth and increases the induction of TNFα in host cells by CAS1 strains. Differences observed for extrapulmonary strains may indicate an adaptation which increases potential for dissemination and tropism outside the lung. Overall, we hypothesise that RD149 deletions generate genetic diversity within strains and impact interactions of CAS1 strains with host cells with important clinical consequences

Secure Multiparty RAM Computation in Constant Rounds

Securing computation of a random access machine (RAM) program typically entails that it be first converted into a circuit. This conversion is unimaginable in the context of big-data applications where the size of the circuit can be exponential in the running time of the original RAM program. Realizing these constructions, without relinquishing the efficiency of RAM programs, often poses considerable technical hurdles. Our understanding of these techniques in the multi-party setting is largely limited. Specifically, the round complexity of all known protocols grows linearly in the running time of the program being computed. In this work, we consider the multi-party case and obtain the following results: 1. Semi-honest model: We present a constant-round black-box secure computation protocol for RAM programs. This protocol is obtained by building on the new black-box garbled RAM construction by Garg, Lu, and Ostrovsky [FOCS 2015], and constant-round secure computation protocol for circuits of Beaver, Micali, and Rogaway [STOC 1990]. This construction allows execution of multiple programs on the same persistent database. 2. Malicious model: Next, we show how to extend our semi-honest results to the malicious setting, while ensuring that the new protocol is still constant-round and black-box in nature

Chromothripsis orchestrates leukemic transformation in blast phase MPN through targetable amplification of DYRK1A

Chromothripsis, the process of catastrophic shattering and haphazard repair of chromosomes, is a common event in cancer. Whether chromothripsis might constitute an actionable molecular event amenable to therapeutic targeting remains an open question. We describe recurrent chromothripsis of chromosome 21 in a subset of patients in blast phase of a myeloproliferative neoplasm (BP-MPN), which alongside other structural variants leads to amplification of a region of chromosome 21 in ∼25% of patients (‘chr21amp’). We report that chr21amp BP-MPN has a particularly aggressive and treatment-resistant phenotype. The chr21amp event is highly clonal and present throughout the hematopoietic hierarchy. DYRK1A, a serine threonine kinase and transcription factor, is the only gene in the 2.7Mb minimally amplified region which showed both increased expression and chromatin accessibility compared to non-chr21amp BP-MPN controls. We demonstrate that DYRK1A is a central node at the nexus of multiple cellular functions critical for BP-MPN development, including DNA repair, STAT signalling and BCL2 overexpression. DYRK1A is essential for BP-MPN cell proliferation in vitro and in vivo, and DYRK1A inhibition synergises with BCL2 targeting to induce BP-MPN cell apoptosis. Collectively, these findings define the chr21amp event as a prognostic biomarker in BP-MPN and link chromothripsis to a druggable target

Opportunities and priorities for breast surgical research

Background: The Breast Cancer Campaign Gap analysis (2013) established breast cancer research priorities without specific focus on surgical research nor the role of surgeons. The majority of breast cancer patients encounter a surgeon at diagnosis or during treatment, thus surgical involvement in design and delivery of high-quality research to improve patient care is critical. This review aims to identify opportunities and priorities for breast surgical research to complement the previous gap analysis. Methods: Research-active breast surgeons met and identified topic areas for breast surgical research which mapped to the patient pathway. These included diagnosis, neoadjuvant treatment, surgery, adjuvant therapy and special groups (e.g. risk-reducing surgery). Section leads were identified based on research interests with invited input from experts in specific areas, supported by consultation with the Association of Breast Surgery (ABS) membership and Independent Cancer Patients’ Voice (ICPV). The document was iteratively modified until participants were satisfied that key priorities for surgical research were clear. Results: Key research gaps were identified for each topic area including: (1) issues surrounding overdiagnosis and treatment; (2) optimising selection for neoadjuvant therapies and subsequent surgery; (3) reducing re-operation rates for breast conserving surgery; (4) generating evidence for the clinical and cost-effectiveness of breast reconstruction and mechanisms for evaluating novel interventions; (5) determining optimal axillary management, especially post-neoadjuvant treatment; (6) defining and standardising indications for risk-reducing surgery. Strategies for resolving these knowledge gaps are proposed. Conclusions: Surgeons are ideally placed for a central role in breast cancer research and should foster a culture of engagement and participation in research to benefit patients and the NHS. Development of infrastructure and surgical research capacity together with appropriate allocation of research funding will be needed to successfully address the key clinical and translational research gaps highlighted in this analysis within the next two decades