One-loop quantum cosmological correction to the gravitational constant using the kink solution in de Sitter universe

In this paper, we show the equivalence between a classical static scalar field theory and the (closed) de Sitter cosmological model whose potential represents shape invariance property. Based on this equivalence, we calculate the one-loop quantum cosmological correction to the ground state energy of the kink-like solution in the (closed) de Sitter cosmological model in which the fluctuation potential $V^{\prime\prime}$ has a shape invariance property. It is shown that this type of correction, which yields a renormalized mass in the case of scalar field theory, may be {\it interpreted} as a renormalized gravitational constant in the case of (closed) de Sitter cosmological model. Keywords: One-loop correction; kink energy; shape invariance; zeta function regularization; de Sitter universe.Comment: 18 page

Restrained Th17 response and myeloid cell infiltration into the central nervous system by human decidua-derived mesenchymal stem cells during experimental autoimmune encephalomyelitis

Background: Multiple sclerosis is a widespread inflammatory demyelinating disease. Several immunomodulatory therapies are available, including interferon-β, glatiramer acetate, natalizumab, fingolimod, and mitoxantrone. Although useful to delay disease progression, they do not provide a definitive cure and are associated with some undesirable side-effects. Accordingly, the search for new therapeutic methods constitutes an active investigation field. The use of mesenchymal stem cells (MSCs) to modify the disease course is currently the subject of intense interest. Decidua-derived MSCs (DMSCs) are a cell population obtained from human placental extraembryonic membranes able to differentiate into the three germ layers. This study explores the therapeutic potential of DMSCs. Methods: We used the experimental autoimmune encephalomyelitis (EAE) animal model to evaluate the effect of DMSCs on clinical signs of the disease and on the presence of inflammatory infiltrates in the central nervous system. We also compared the inflammatory profile of spleen T cells from DMSC-treated mice with that of EAE control animals, and the influence of DMSCs on the in vitro definition of the Th17 phenotype. Furthermore, we analyzed the effects on the presence of some critical cell types in central nervous system infiltrates. Results: Preventive intraperitoneal injection of DMSCs resulted in a significant delay of external signs of EAE. In addition, treatment of animals already presenting with moderate symptoms resulted in mild EAE with reduced disease scores. Besides decreased inflammatory infiltration, diminished percentages of CD4+IL17+, CD11b+Ly6G+ and CD11b+Ly6C+ cells were found in infiltrates of treated animals. Early immune response was mitigated, with spleen cells of DMSC-treated mice displaying low proliferative response to antigen, decreased production of interleukin (IL)-17, and increased production of the anti-inflammatory cytokines IL-4 and IL-10. Moreover, lower RORγT and higher GATA-3 expression levels were detected in DMSC-treated mice. DMSCs also showed a detrimental influence on the in vitro definition of the Th17 phenotype. Conclusions: DMSCs modulated the clinical course of EAE, modified the frequency and cell composition of the central nervous system infiltrates during the disease, and mediated an impairment of Th17 phenotype establishment in favor of the Th2 subtype. These results suggest that DMSCs might provide a new cell-based therapy for the control of multiple sclerosis.This work was sponsored by grants from Acción Estratégica en Salud (PI13/00297 and PI11/00581), the Neurosciences and Aging Foundation, the Francisco Soria Melguizo Foundation, Octopharma, and Parkinson Madrid (PI2012/0032).S

Teleclinical Microbiology: An Innovative Approach to Providing Web-Enabled Diagnostic Laboratory Services in Syria

Objectives: Telemedicine can compensate for the lack of health care specialists in response to protracted humanitarian crises. We sought to assess the usability of a teleclinical microbiology (TCM) program to provide diagnostic services in a hard-to-reach region of Syria. Methods: A semimobile station was equipped with conventional micrograph and macrograph digital imaging systems. An electronic platform (Telemicrobiology in Humanitarian Crises, TmHC) was created to facilitate sharing, interpreting, and storing the results. A pilot study was conducted to identify the bacterial species and antimicrobial susceptibility pattern of 74 urinary clinical isolates. An experience survey was conducted to capture the feedback of 8 participants in the program. Results: The TmHC platform (https://sdh.ngo/tmhc/) enabled systematic transmission of the laboratory records and co-interpretation of the results. The isolates were identified as Escherichia coli (n = 61), Klebsiella pneumoniae (n = 12), and Proteus mirabilis(n = 1). All the isolates were multidrug resistant. The performance of our TCM module was rated 4 (satisfying) and 5 (very satisfying) by 6 and 2 users, respectively. Data security of and cost-effectiveness were the main perceived concerns. Conclusions: Although we encountered several context-related obstacles, our TCM program managed to reach a highly vulnerable population of 4 million people confined in the northwest region of Syria.publishedVersio

An improved CMOS-based inductor simulator with simplified structure for low-frequency applications

In this paper, an improved inductor simulator structure is presented, which can be configured as either grounded or floating inductor simulator with low component count. To achieve simplified structure, inductor simulator circuits are designed using a minimal number of transistors and small capacitance, rather than the complex components/modules such as current convey and operational trans-conductance amplifier which are traditionally used. The simulation results based on 0.5μm CMOS process parameters show that the proposed structure is able to produce a broad range of inductance values and compared to other similar structures, it provides wider operational frequency bandwidth for the same or comparable inductance value. Furthermore, the structure can be implemented with much smaller chip area using a small capacitance in the circuit, but at the price that it has a higher minimum operational frequency compared to other structures

Phosphoinositide acyl chain saturation drives CD8⁺ effector T cell signaling and function

How lipidome changes support CD8+ effector T (Teff) cell differentiation is not well understood. Here we show that, although naive T cells are rich in polyunsaturated phosphoinositides (PIPn with 3-4 double bonds), Teff cells have unique PIPn marked by saturated fatty acyl chains (0-2 double bonds). PIPn are precursors for second messengers. Polyunsaturated phosphatidylinositol bisphosphate (PIP2) exclusively supported signaling immediately upon T cell antigen receptor activation. In late Teff cells, activity of phospholipase C-γ1, the enzyme that cleaves PIP2 into downstream mediators, waned, and saturated PIPn became essential for sustained signaling. Saturated PIP was more rapidly converted to PIP2 with subsequent recruitment of phospholipase C-γ1, and loss of saturated PIPn impaired Teff cell fitness and function, even in cells with abundant polyunsaturated PIPn. Glucose was the substrate for de novo PIPn synthesis, and was rapidly utilized for saturated PIP2 generation. Thus, separate PIPn pools with distinct acyl chain compositions and metabolic dependencies drive important signaling events to initiate and then sustain effector function during CD8+ T cell differentiation

Randomised controlled trial of food elimination diet based on IgG antibodies for the prevention of migraine like headaches

<p>Abstract</p> <p>Background</p> <p>Research suggests that food intolerance may be a precipitating factor for migraine like headaches.</p> <p>Aim</p> <p>To evaluate the effectiveness of the ELISA (Enzyme Linked Immuno-Sorbent Assay) Test and subsequent dietary elimination advice for the prevention of migraine like headaches.</p> <p>Design</p> <p>Randomised controlled trial.</p> <p>Setting</p> <p>Community based volunteers in the UK.</p> <p>Participants</p> <p>Volunteers who met the inclusion criteria for migraine like headaches and had one or more food intolerance were included in the study. Participants received either a true diet (n = 84) or a sham diet (n = 83) sheet. Participants were advised to remove the intolerant foods from their diet for 12 weeks.</p> <p>Main outcome measures</p> <p>Number of headache days over a 12 week period (item A MIDAS questionnaire). Other measures includes the total MIDAS score and total HIT-6 score.</p> <p>Results</p> <p>The results indicated a small decrease in the number of migraine like headaches over 12 weeks, although this difference was not statistically significant (IRR 1.15 95% CI 0.94 to 1.41, p = 0.18). At the 4 week assessment, use of the ELISA test with subsequent diet elimination advice significantly reduced the number of migraine like headaches (IRR 1.23 95%CI 1.01 to 1.50, p = 0.04). The disability and impact on daily life of migraines were not significantly different between the true and sham diet groups.</p> <p>Conclusions</p> <p>Use of the ELISA test with subsequent diet elimination advice did not reduce the disability or impact on daily life of migraine like headaches or the number of migraine like headaches at 12 weeks but it did significantly reduce the number of migraine like headaches at 4 weeks.</p> <p>Trial registration number</p> <p>ISRCTN: <a href="http://www.controlled-trials.com/ISRTCN89559672">ISRTCN89559672</a></p

Comparative Study on the Therapeutic Potential of Neurally Differentiated Stem Cells in a Mouse Model of Multiple Sclerosis

Background: Transplantation of neural stem cells (NSCs) is a promising novel approach to the treatment of neuroinflammatory diseases such as multiple sclerosis (MS). NSCs can be derived from primary central nervous system (CNS) tissue or obtained by neural differentiation of embryonic stem (ES) cells, the latter having the advantage of readily providing an unlimited number of cells for therapeutic purposes. Using a mouse model of MS, we evaluated the therapeutic potential of NSCs derived from ES cells by two different neural differentiation protocols that utilized adherent culture conditions and compared their effect to primary NSCs derived from the subventricular zone (SVZ). Methodology/Principal Findings: The proliferation and secretion of pro-inflammatory cytokines by antigen-stimulated splenocytes was reduced in the presence of SVZ-NSCs, while ES cell-derived NSCs exerted differential immunosuppressive effects. Surprisingly, intravenously injected NSCs displayed no significant therapeutic impact on clinical and pathological disease outcomes in mice with experimental autoimmune encephalomyelitis (EAE) induced by recombinant myelin oligodendrocyte glycoprotein, independent of the cell source. Studies tracking the biodistribution of transplanted ES cellderived NSCs revealed that these cells were unable to traffic to the CNS or peripheral lymphoid tissues, consistent with the lack of cell surface homing molecules. Attenuation of peripheral immune responses could only be achieved through multiple high doses of NSCs administered intraperitoneally, which led to some neuroprotective effects within the CNS

CD28 Costimulation Augments CAR Signaling in NK Cells via the LCK/CD3ζ/ZAP70 Signaling Axis

Multiple factors in the design of a chimeric antigen receptor (CAR) influence CAR T-cell activity, with costimulatory signals being a key component. Yet, the impact of costimulatory domains on the downstream signaling and subsequent functionality of CAR-engineered natural killer (NK) cells remains largely unexplored. Here, we evaluated the impact of various costimulatory domains on CAR-NK cell activity, using a CD70-targeting CAR. We found that CD28, a costimulatory molecule not inherently present in mature NK cells, significantly enhanced the antitumor efficacy and long-term cytotoxicity of CAR-NK cells both in vitro and in multiple xenograft models of hematologic and solid tumors. Mechanistically, we showed that CD28 linked to CD3ζ creates a platform that recruits critical kinases, such as lymphocyte-specific protein tyrosine kinase (LCK) and zeta-chain-associated protein kinase 70 (ZAP70), initiating a signaling cascade that enhances CAR-NK cell function. Our study provides insights into how CD28 costimulation enhances CAR-NK cell function and supports its incorporation in NK-based CARs for cancer immunotherapy. Significance: We demonstrated that incorporation of the T-cell-centric costimulatory molecule CD28, which is normally absent in mature natural killer (NK) cells, into the chimeric antigen receptor (CAR) construct recruits key kinases including lymphocyte-specific protein tyrosine kinase and zeta-chain-associated protein kinase 70 and results in enhanced CAR-NK cell persistence and sustained antitumor cytotoxicity