Effects of Process Variables and Size Scale on Solidification Microstructure in Laser-Based Solid Freeform Fabrication of Ti-6Al-4V

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Alterations in vascular function in primary aldosteronism - a cardiovascular magnetic resonance imaging study

Introduction: Excess aldosterone is associated with increased cardiovascular risk. Aldosterone has a permissive effect on vascular fibrosis. Cardiovascular magnetic resonance imaging (CMR) allows study of vascular function by measuring aortic distensibility. We compared aortic distensibility in primary aldosteronism (PA), essential hypertension (EH) and normal controls and explored the relationship between aortic distensibility and pulse wave velocity (PWV).<p></p> Methods: We studied PA (n=14) and EH (n=33) subjects and age-matched healthy controls (n=17) with CMR, including measurement of aortic distensibility, and measured PWV using applanation tonometry. At recruitment, PA and EH patients had similar blood pressure and left ventricular mass.<p></p> Results: Subjects with PA had significantly lower aortic distensibilty and higher PWV compared to EH and healthy controls. These changes were independent of other factors associated with reduced aortic distensibility, including aging. There was a significant relationship between increasing aortic stiffness and age in keeping with physical and vascular aging. As expected, aortic distensibility and PWV were closely correlated.<p></p> Conclusion: These results demonstrate that PA patients display increased arterial stiffness compared to EH, independent of vascular aging. The implication is that aldosterone invokes functional impairment of arterial function. The long-term implications of arterial stiffening in aldosterone excess require further study.<p></p&gt

Robotic ubiquitous cognitive ecology for smart homes

Robotic ecologies are networks of heterogeneous robotic devices pervasively embedded in everyday environments, where they cooperate to perform complex tasks. While their potential makes them increasingly popular, one fundamental problem is how to make them both autonomous and adaptive, so as to reduce the amount of preparation, pre-programming and human supervision that they require in real world applications. The project RUBICON develops learning solutions which yield cheaper, adaptive and efficient coordination of robotic ecologies. The approach we pursue builds upon a unique combination of methods from cognitive robotics, machine learning, planning and agent- based control, and wireless sensor networks. This paper illustrates the innovations advanced by RUBICON in each of these fronts before describing how the resulting techniques have been integrated and applied to a smart home scenario. The resulting system is able to provide useful services and pro-actively assist the users in their activities. RUBICON learns through an incremental and progressive approach driven by the feed- back received from its own activities and from the user, while also self-organizing the manner in which it uses available sensors, actuators and other functional components in the process. This paper summarises some of the lessons learned by adopting such an approach and outlines promising directions for future work

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer.

Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM -/- patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

Recognition of microbial viability via TLR8 drives TFH cell differentiation and vaccine responses

Live attenuated vaccines are generally highly efficacious and often superior to inactivated vaccines, yet the underlying mechanisms of this remain largely unclear. Here we identify recognition of microbial viability as a potent stimulus for follicular helper T cell (TFH cell) differentiation and vaccine responses. Antigen-presenting cells (APCs) distinguished viable bacteria from dead bacteria through Toll-like receptor 8 (TLR8)-dependent detection of bacterial RNA. In contrast to dead bacteria and other TLR ligands, live bacteria, bacterial RNA and synthetic TLR8 agonists induced a specific cytokine profile in human and porcine APCs, thereby promoting TFH cell differentiation. In domestic pigs, immunization with a live bacterial vaccine induced robust TFH cell and antibody responses, but immunization with its heat-killed counterpart did not. Finally, a hypermorphic TLR8 polymorphism was associated with protective immunity elicited by vaccination with bacillus Calmette-Guérin (BCG) in a human cohort. We have thus identified TLR8 as an important driver of TFH cell differentiation and a promising target for TFH cell–skewing vaccine adjuvants

SEROLOGICAL TESTS FOR DETECTION OF SUNFLOWER NECROSIS TOSPO VIRUS CAUSING NECROSIS DISEASE OF SUNFLOWER (HELIANTHUS ANNUS L.)

India occupies third place to produce oil seeds in the world. India has vast area of about 19 million hectares under oilseed crops In order to formulate management practices for the control of necrosis disease of sunflower; reliable tests are required for its detection. Such tests are lacking in India. Sunflower is widely cultivated in India. Sunflower crop is extensively cultivated in Rayalaseema region of Andhra Pradesh. Sunflower showed symptom of virus disease characterised by severe mosaic, necrosis of leaves, necrosis along the stems and floral parts, malformation of young leaves, markedly reduced leaves and stunting of plants. Hence, in this study, direct antigen coating-enzyme linked immunosorbent assay (DAC-ELISA), Double antibody sandwich-ELISA (DAS-ELISA) and Dot-ELISA tests were evaluated for the detection of sunflower necrosis a tospo virus (SfNV) causing necrosis disease of sunflower in Andhra Pradesh in India. In DAC-ELISA, Sunflower Necrosis Virus was detected up to 0.370μg/mL in purified virus preparation and up to 10-4 dilution in leaf sap extracted from virus infected sunflower leaves. In Dot-ELISA, Sunflower Necrosis Virus was detected up to 0.0370μg/mL in purified virus preparation and up to 10-5 dilution in leaf sap from infected sunflower leaves. Where as in DAS-ELISA the virus was detected up to 370μg/mL and 10-3 dilution in purified virus preparation and in leaf sap extracted from infected sunflower leaves, respectively. Hence, it is concluded that DAC-ELISA and Dot-ELISA were found to be the suitable tests for the detection of Sunflower necrosis virus

CITRUS YELLOW MOSAIC: A TRANSMISSIBLE VIRUS OF CITRUS SPIECES IN INDIA

The yellow mosaic disease of citrus is one of the important diseases causing heavy losses in citrus industry. In the present study, an attempt has been made to analyze certain studies on host range and transmission in citrus yellow mosaic virus infecting Rangapur lime, sweet orange and acid lime. The virus disease of citrus was recognized by mosaic symptoms were noticed in sweet orange, Rangapur lime and acid lime plants. Systemically infected Rangapur lime, sweet orange and acid lime leaves showing characteristic yellow mosaic were collected from AICRP on Tropical Fruits (Citrus), Tirupati. During the present investigations major efforts were made on characterization of CYMV and following information have been generated. The virus under study has a narrow host range. Mechanically sap transmissible from rangpur lime to rangpur lime, sweet orange and acid lime among the citrus hosts and to Canna indica, maize and sorghum in non-citrus hosts. Pure cultures of the virus were developed by sap transmission and there have been used in experiments. The virus culture was maintained on citrus plants. Studies on graft transmission indicated that T-budding (65.56%) and back patch (61.7%) were the best in per cent transmission than leaf patch (42.5%) grafting. The CYMV transmission from sweet orange to sweet orange and Rangapur lime; Rangapur lime to sweet orange and Rangapur lime; and acid lime to acid lime was found better. The transmission of CYMV was very low when it was from acid lime to sweet orange and rangpur lime and vice versa. The citrus mosaic virus was also transmitted by mealy bug, Planococcus citri after 48h acquisition feeding and 4 days inoculation feeding

c-FOS drives reversible basal to squamous cell carcinoma transition.

While squamous transdifferentiation within subpopulations of adenocarcinomas represents an important drug resistance problem, its underlying mechanism remains poorly understood. Here, using surface markers of resistant basal cell carcinomas (BCCs) and patient single-cell and bulk transcriptomic data, we uncover the dynamic roadmap of basal to squamous cell carcinoma transition (BST). Experimentally induced BST identifies activator protein 1 (AP-1) family members in regulating tumor plasticity, and we show that c-FOS plays a central role in BST by regulating the accessibility of distinct AP-1 regulatory elements. Remarkably, despite prominent changes in cell morphology and BST marker expression, we show using inducible model systems that c-FOS-mediated BST demonstrates reversibility. Blocking EGFR pathway activation after c-FOS induction partially reverts BST in vitro and prevents BST features in both mouse models and human tumors. Thus, by identifying the molecular basis of BST, our work reveals a therapeutic opportunity targeting plasticity as a mechanism of tumor resistance

Contraceptive Choices for Premenopausal Women and Breast Cancer Risk

This Viewpoint explores the injunction against taking hormonal contraceptives among premenopausal women at increased risk for breast cancer