147 research outputs found
Risk assessment in global supply chains, witrh an application to the high-tech manufacturing industry
Towards deep generation of guided wave representations for composite materials
Laminated composite materials are widely used in most fields of engineering.
Wave propagation analysis plays an essential role in understanding the
short-duration transient response of composite structures. The forward
physics-based models are utilized to map from elastic properties space to wave
propagation behavior in a laminated composite material. Due to the
high-frequency, multi-modal, and dispersive nature of the guided waves, the
physics-based simulations are computationally demanding. It makes property
prediction, generation, and material design problems more challenging. In this
work, a forward physics-based simulator such as the stiffness matrix method is
utilized to collect group velocities of guided waves for a set of composite
materials. A variational autoencoder (VAE)-based deep generative model is
proposed for the generation of new and realistic polar group velocity
representations. It is observed that the deep generator is able to reconstruct
unseen representations with very low mean square reconstruction error. Global
Monte Carlo and directional equally-spaced samplers are used to sample the
continuous, complete and organized low-dimensional latent space of VAE. The
sampled point is fed into the trained decoder to generate new polar
representations. The network has shown exceptional generation capabilities. It
is also seen that the latent space forms a conceptual space where different
directions and regions show inherent patterns related to the generated
representations and their corresponding material properties
The Medical Research Council Myeloma IX trial: the impact on treatment paradigms*
Osteolytic bone disease is a hallmark of symptomatic multiple myeloma. Bisphosphonates have been the mainstay of treatment to preserve skeletal integrity and prevent skeletal-related events in patients with myeloma-related bone disease. Recently, the MRC Myeloma IX trial demonstrated for the first time improved survival and delayed disease progression with the use of an intravenous amino-bisphosphonate, zoledronic acid, vs. an oral agent, clodronate, with intensive and non-intensive anti-myeloma treatment regimens in patients with newly diagnosed multiple myeloma. These results validate a large body of preclinical, translational and other clinical data suggesting anti-myeloma effects of amino-bisphosphonates. In addition, this trial also provided the first head-to-head evidence for superiority of one bisphosphonate over another (zoledronic acid vs. clodronate) for reducing skeletal morbidity in patients with multiple myeloma, as well as a prospective comparison of toxicities. Despite the use of non-bortezomib containing anti-myeloma treatment regimens in the MRC Myeloma IX trial, these results are encouraging and provide an impetus to continue to evaluate current treatment guidelines for myeloma-associated bone disease
Partially responsive celiac disease resulting from small intestinal bacterial overgrowth and lactose intolerance
BACKGROUND: Celiac disease is a common cause of chronic diarrhea and malabsorption syndrome all over the world. Though it was considered uncommon in India in past, it is being described frequently recently. Some patients with celiac disease do not improve despite gluten free diet (GFD). A study described 15 cases of celiac disease unresponsive to GFD in whom small intestinal bacterial overgrowth (SIBO) or lactose intolerance was the cause for unresponsiveness. CASE PRESENTATION: During a three-year period, 12 adult patients with celiac disease were seen in the Luminal Gastroenterology Clinic in a tertiary referral center in northern India. Two of these 12 patients (16.6%), who did not fully respond to GFD initially, are presented here. Unresponsiveness resulted from SIBO in one and lactose intolerance in the other. The former patient responded to antibiotics and the latter to lactose withdrawal in addition to standard GFD. CONCLUSION: In patients with celiac disease partially responsive or unresponsive to GFD, SIBO and lactose intolerance should be suspected; appropriate investigations and treatment for these may result in complete recovery
Heat shock factor 1 is a potent therapeutic target for enhancing the efficacy of treatments for multiple myeloma with adverse prognosis
Stapled ACE2 peptidomimetics designed to target the SARS-CoV-2 spike protein do not prevent virus internalisation
COVIDâ19 is caused by a novel coronavirus called severe acute respiratory syndromeâcoronavirus 2 (SARSâCoVâ2). Virus cell entry is mediated through a proteinâprotein interaction (PPI) between the SARSâCoVâ2 spike protein and angiotensinâconverting enzyme 2 (ACE2). A series of stapled peptide ACE2 peptidomimetics based on the ACE2 interaction motif were designed to bind the coronavirus Sâprotein RBD and inhibit binding to the human ACE2 receptor. The peptidomimetics were assessed for antiviral activity in an array of assays including a neutralization pseudovirus assay, immunofluorescence (IF) assay and inâvitro fluorescence polarization (FP) assay. However, none of the peptidomimetics showed activity in these assays, suggesting that an enhanced binding interface is required to outcompete ACE2 for Sâprotein RBD binding and prevent virus internalization
The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of hematologic malignancies: multiple myeloma, lymphoma, and acute leukemia
Increasing knowledge concerning the biology of hematologic malignancies as well as the role of the immune system in the control of these diseases has led to the development and approval of immunotherapies that are resulting in impressive clinical responses. Therefore, the Society for Immunotherapy of Cancer (SITC) convened a hematologic malignancy Cancer Immunotherapy Guidelines panel consisting of physicians, nurses, patient advocates, and patients to develop consensus recommendations for the clinical application of immunotherapy for patients with multiple myeloma, lymphoma, and acute leukemia. These recommendations were developed following the previously established process based on the Institute of Medicineâs clinical practice guidelines. In doing so, a systematic literature search was performed for high-impact studies from 2004 to 2014 and was supplemented with further literature as identified by the panel. The consensus panel met in December of 2014 with the goal to generate consensus recommendations for the clinical use of immunotherapy in patients with hematologic malignancies. During this meeting, consensus panel voting along with discussion were used to rate and review the strength of the supporting evidence from the literature search. These consensus recommendations focus on issues related to patient selection, toxicity management, clinical endpoints, and the sequencing or combination of therapies. Overall, immunotherapy is rapidly emerging as an effective therapeutic strategy for the management of hematologic malignances. Evidence-based consensus recommendations for its clinical application are provided and will be updated as the field evolves
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