The Relativistic Generalization of the Gravitational Force for Arbitrary Spacetimes

It has been suggested that re-expressing relativity in terms of forces could provide fresh insights. The formalism developed for this purpose only applied to static, or conformally static, space-times. Here we extend it to arbitrary space-times. It is hoped that this formalism may lead to a workable definition of mass and energy in relativity.Comment: 16 page

Magnetic micro-swimmers propelling through bio-rheological liquid bounded within an active channel

The dynamics of a micro-organism swimming through a channel with undulating walls subject to constant transverse applied magnetic field is investigated. The micro-organism is modeled as self-propelling undulating sheet which is out of phase with the channel waves while the electrically conducting biofluid (through which micro-swimmers propel) is characterized by the non-Newtonian shear-rate dependent Carreau fluid model. Creeping flow is mobilized in the channel due to the self-propulsion of the micro-organism and the undulatory motion of narrow gapped walls. Under these conditions the conservation equations are formulated under the long wavelength and low Reynolds number assumptions. The speed of the self-propelling sheet and the rate of work done at higher values of rheological parameters are obtained by using a hybrid numerical technique (MATLAB routine bvp-4c combined with a modified Newton-Raphson method). The results are validated through an alternative hybrid numerical scheme (implicit finite difference method (FDM) in conjunction with a modified Newton-Raphson method). The assisting role of magnetic field and rheological effects of the surrounding biofluid on the swimming mode are shown graphically and interpreted at length. The global behavior of biofluid is also expounded via visualization of the streamlines in both regions (above and below the swimming sheet) for realistic micro-organism speeds. The computations reveal that optimal swimming conditions for the micro-organism (i.e., greater speed with lower energy losses) are achievable in magnetohydrodynamic (MHD) environments including magnetic field-assisted cervical treatments. Keywords: Micro-organism; peristaltic (active) channel; Carreau fluid; Swimming speed; biomagnetohydrodynamics (bioMHD); Rate of work done; Hybrid numerical method, Newton-Raphson method; Cervical magnetic therap

Unravelling the mechanism of TrkA-induced cell death by macropinocytosis in medulloblastoma Daoy cells

Macropinocytosis is a normal cellular process by which cells internalize extracellular fluids and nutrients from their environment and is one strategy that Ras-transformed pancreatic cancer cells use to increase uptake of amino acids to meet the needs of rapid growth. Paradoxically, in non-Ras transformed medulloblastoma brain tumors, we have shown that expression and activation of the receptor tyrosine kinase TrkA overactivates macropinocytosis, resulting in the catastrophic disintegration of the cell membrane and in tumor cell death. The molecular basis of this uncontrolled form of macropinocytosis has not been previously understood. Here, we demonstrate that the overactivation of macropinocytosis is caused by the simultaneous activation of two TrkA-mediated pathways: (i) inhibition of RhoB via phosphorylation at Ser185 by casein kinase 1, which relieves actin stress fibers, and (ii) FRS2-scaffolded Src and H-Ras activation of RhoA, which stimulate actin reorganization and the formation of lamellipodia. Since catastrophic macropinocytosis results in brain tumor cell death, improved understanding of the mechanisms involved will facilitate future efforts to reprogram tumors, even those resistant to apoptosis, to die

Multipliers for p-Bessel sequences in Banach spaces

Multipliers have been recently introduced as operators for Bessel sequences and frames in Hilbert spaces. These operators are defined by a fixed multiplication pattern (the symbol) which is inserted between the analysis and synthesis operators. In this paper, we will generalize the concept of Bessel multipliers for p-Bessel and p-Riesz sequences in Banach spaces. It will be shown that bounded symbols lead to bounded operators. Symbols converging to zero induce compact operators. Furthermore, we will give sufficient conditions for multipliers to be nuclear operators. Finally, we will show the continuous dependency of the multipliers on their parameters.Comment: 17 page

Automated Quantification of Neuropad Improves Its Diagnostic Ability in Patients with Diabetic Neuropathy.

PublishedResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov'tNeuropad is currently a categorical visual screening test that identifies diabetic patients at risk of foot ulceration. The diagnostic performance of Neuropad was compared between the categorical and continuous (image-analysis (Sudometrics)) outputs to diagnose diabetic peripheral neuropathy (DPN). 110 subjects with type 1 and 2 diabetes underwent assessment with Neuropad, Neuropathy Disability Score (NDS), peroneal motor nerve conduction velocity (PMNCV), sural nerve action potential (SNAP), Deep Breathing-Heart Rate Variability (DB-HRV), intraepidermal nerve fibre density (IENFD), and corneal confocal microscopy (CCM). 46/110 patients had DPN according to the Toronto consensus. The continuous output displayed high sensitivity and specificity for DB-HRV (91%, 83%), CNFD (88%, 78%), and SNAP (88%, 83%), whereas the categorical output showed high sensitivity but low specificity. The optimal cut-off points were 90% for the detection of autonomic dysfunction (DB-HRV) and 80% for small fibre neuropathy (CNFD). The diagnostic efficacy of the continuous Neuropad output for abnormal DB-HRV (AUC: 91%, P = 0.0003) and CNFD (AUC: 82%, P = 0.01) was better than for PMNCV (AUC: 60%). The categorical output showed no significant difference in diagnostic efficacy for these same measures. An image analysis algorithm generating a continuous output (Sudometrics) improved the diagnostic ability of Neuropad, particularly in detecting autonomic and small fibre neuropathy.National Institute of Health (NIH)Juvenile Diabetes Research Foundation (JDRF

Additive Value of Preprocedural Computed Tomography Planning Versus Stand-Alone Transesophageal Echocardiogram Guidance to Left Atrial Appendage Occlusion: Comparison of Real-World Practice

Background: Transesophageal echocardiogram is currently the standard preprocedural imaging for left atrial appendage occlusion. This study aimed to assess the additive value of preprocedural computed tomography (CT) planning versus stand-alone transesophageal echocardiogram imaging guidance to left atrial appendage occlusion. Methods and Results: We retrospectively reviewed 485 Watchman implantations at a single center to compare the outcomes of using additional CT preprocedural planning (n=328, 67.6%) versus stand-alone transesophageal echocardiogram guidance (n=157, 32.4%) for left atrial appendage occlusion. The primary end point was the rate of successful device implantation without major peri-device leak (\u3e5 mm). Secondary end points included major adverse events, total procedural time, delivery sheath and devices used, risk of major peri-device leak and device-related thrombus at follow-up imaging. A single/anterior-curve delivery sheath was used more commonly in those who underwent CT imaging (35.9% versus 18.8%; P\u3c0.001). Additional preprocedural CT planning was associated with a significantly higher successful device implantation rate (98.5% versus 94.9%; P=0.02), a shorter procedural time (median, 45.5 minutes versus 51.0 minutes; P=0.03) and a less frequent change of device size (5.6% versus 12.1%; P=0.01), particularly device upsize (4% versus 9.4%; P=0.02). However, there was no significant difference in the risk of major adverse events (2.1% versus 1.9%; P=0.87). Only 1 significant peri-device leak (0.2%) and 5 device-related thrombi were detected in follow-up (1.2%) with no intergroup difference. Conclusions: Additional preprocedural planning using CT in Watchman implantation was associated with a higher successful device implantation rate, a shorter total procedural time, and a less frequent change of device sizes

Small nerve fiber damage and Langerhans cells in type 1 and type 2 diabetes and LADA measured by corneal confocal microscopy

Purpose: Increased corneal and epidermal Langerhans cells (LCs) have been reported in patients with diabetic neuropathy. The aim of this study was to quantify the density of LCs in relation to corneal nerve morphology and the presence of diabetic neuropathy and to determine if this differed in patients with type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), and latent autoimmune diabetes of adults (LADA). Methods: Patients with T1DM (n = 25), T2DM (n = 36), or LADA (n = 23) and control subjects (n = 23) underwent detailed assessment of peripheral neuropathy and corneal confocal microscopy. Corneal nerve fiber density (CNFD), branch density (CNBD), length (CNFL) and total, immature and mature LC densities were quantified. Results: Lower CNFD (P < 0.001), CNBD (P < 0.0001), and CNFL (P < 0.0001) and higher LC density (P = 0.03) were detected in patients with T1DM, T2DM, and LADA compared to controls. CNBD was inversely correlated with mature (r = -0.5; P = 0.008), immature (r = -0.4; P = 0.02) and total (r = -0.5; P = 0.01) LC density, and CNFL was inversely correlated with immature LC density (r = -0.4; P = 0.03) in patients with T1DM but not in patients with T2DM and LADA. Conclusions: This study shows significant corneal nerve loss and an increase in LC density in patients with T1DM, T2DM, and LADA. Furthermore, increased LC density correlated with corneal nerve loss in patients with T1DM

Keratins Are Altered in Intestinal Disease-Related Stress Responses

Keratin (K) intermediate filaments can be divided into type I/type II proteins, which form obligate heteropolymers. Epithelial cells express type I-type II keratin pairs, and K7, K8 (type II) and K18, K19 and K20 (type I) are the primary keratins found in the single-layered intestinal epithelium. Keratins are upregulated during stress in liver, pancreas, lung, kidney and skin, however, little is known about their dynamics in the intestinal stress response. Here, keratin mRNA, protein and phosphorylation levels were studied in response to murine colonic stresses modeling human conditions, and in colorectal cancer HT29 cells. Dextran sulphate sodium (DSS)-colitis was used as a model for intestinal inflammatory stress, which elicited a strong upregulation and widened crypt distribution of K7 and K20. K8 levels were slightly downregulated in acute DSS, while stress-responsive K8 serine-74 phosphorylation (K8 pS74) was increased. By eliminating colonic microflora using antibiotics, K8 pS74 in proliferating cells was significantly increased, together with an upregulation of K8 and K19. In the aging mouse colon, most colonic keratins were upregulated. In vitro, K8, K19 and K8 pS74 levels were increased in response to lipopolysaccharide (LPS)-induced inflammation in HT29 cells. In conclusion, intestinal keratins are differentially and dynamically upregulated and post-translationally modified during stress and recovery.</p