Origins of the Isospin Violation of Dark Matter Interactions

Light dark matter (DM) with a large DM-nucleon spin-independent cross section and furthermore proper isospin violation (ISV) $f_n/f_p\approx-0.7$ may provide a way to understand the confusing DM direct detection results. Combing with the stringent astrophysical and collider constraints, we systematically investigate the origin of ISV first via general operator analyses and further via specifying three kinds of (single) mediators: A light $Z'$ from chiral $U(1)_X$, an approximate spectator Higgs doublet (It can explain the $W+jj$ anomaly simultaneously) and color triplets. In addition, although $Z'$ from an exotic $U(1)_X$ mixing with $U(1)_Y$ generating $f_n=0$, we can combine it with the conventional Higgs to achieve proper ISV. As a concrete example, we propose the $U(1)_X$ model where the $U(1)_X$ charged light sneutrino is the inelastic DM, which dominantly annihilates to light dark states such as $Z'$ with sub-GeV mass. This model can address the recent GoGeNT annual modulation consistent with other DM direct detection results and free of exclusions.Comment: References added and English greatly improve

Intraseasonal Variability in the Makassar Strait Thermocline

Intraseasonal variability [ISV] in the Makassar Strait thermocline is examined through the analysis of along-channel flow, regional sea level anomaly and wind fields from January 2004 through November 2006. The dominant variability of 45-90 day in the Makassar Strait along-channel flow is horizontally and vertically coherent and exhibits vertical energy propagation. The majority of the Makassar ISV is uncoupled to the energy exerted by the local atmospheric ISV: instead the Makassar ISV is due to the combination of a remotely forced baroclinic wave radiating from Lombok Strait and deep reaching ISV originating in the Sulawesi Sea. Thermocline depth changes associated with ENSO influence the ISV characteristics in the Makassar Strait lower thermocline, with intensified ISV during El Nin˜o when the thermocline shallows and weakened ISV during La Nin˜a

The interindividual variability of multimodal brain connectivity maintains spatial heterogeneity and relates to tissue microstructure

Humans differ from each other in a wide range of biometrics, but to what extent brain connectivity varies between individuals remains largely unknown. By combining diffusion-weighted imaging (DWI) and magnetoencephalography (MEG), this study characterizes the inter-subject variability (ISV) of multimodal brain connectivity. Structural connectivity is characterized by higher ISV in association cortices including the core multiple-demand network and lower ISV in the sensorimotor cortex. MEG ISV exhibits frequency-dependent signatures, and the extent of MEG ISV is consistent with that of structural connectivity ISV in selective macroscopic cortical clusters. Across the cortex, the ISVs of structural connectivity and beta-band MEG functional connectivity are negatively associated with cortical myelin content indexed by the quantitative T1 relaxation rate measured by high-resolution 7 T MRI. Furthermore, MEG ISV from alpha to gamma bands relates to the hindrance and restriction of the white-matter tissue estimated by DWI microstructural models. Our findings depict the inter-relationship between the ISV of brain connectivity from multiple modalities, and highlight the role of tissue microstructure underpinning the ISV

Motor neuron-derived Thsd7a is essential for zebrafish vascular development via the Notch-dll4 signaling pathway.

BackgroundDevelopment of neural and vascular systems displays astonishing similarities among vertebrates. This parallelism is under a precise control of complex guidance signals and neurovascular interactions. Previously, our group identified a highly conserved neural protein called thrombospondin type I domain containing 7A (THSD7A). Soluble THSD7A promoted and guided endothelial cell migration, tube formation and sprouting. In addition, we showed that thsd7a could be detected in the nervous system and was required for intersegmental vessels (ISV) patterning during zebrafish development. However, the exact origin of THSD7A and its effect on neurovascular interaction remains unclear.ResultsIn this study, we discovered that zebrafish thsd7a was expressed in the primary motor neurons. Knockdown of Thsd7a disrupted normal primary motor neuron formation and ISV sprouting in the Tg(kdr:EGFP/mnx1:TagRFP) double transgenic zebrafish. Interestingly, we found that Thsd7a morphants displayed distinct phenotypes that are very similar to the loss of Notch-delta like 4 (dll4) signaling. Transcript profiling further revealed that expression levels of notch1b and its downstream targets, vegfr2/3 and nrarpb, were down-regulated in the Thsd7a morphants. These data supported that zebrafish Thsd7a could regulate angiogenic sprouting via Notch-dll4 signaling during development.ConclusionsOur results suggested that motor neuron-derived Thsd7a plays a significant role in neurovascular interactions. Thsd7a could regulate ISV angiogenesis via Notch-dll4 signaling. Thus, Thsd7a is a potent angioneurin involved in the development of both neural and vascular systems

Examining the Overlap Between ADHD and Autism Spectrum Disorder (ASD) Using Candidate Endophenotypes of ADHD

Objective: Recent discussions of aetiological overlap between ADHD and Autism Spectrum Disorder (ASD) require comparative studying of these disorders. Method: We examined performance of ASD patients with (ASD+) and without (ASD-) comorbid ADHD, ADHD patients, and controls for selected putative endophenotypes of ADHD: Intrasubject Variability (ISV) of reaction times, working memory (WM), inhibition, and temporal processing. Results: We found that patients with ADHD or ASD+, but not ASD-, had elevated ISV across the entire task battery and temporal processing deficits, and that none of the groups were impaired in WM or inhibition. High levels of ISV and generally poor performance in ASD+ patients were only partially due to additive effects of the pure disorders. Conclusion: Overall, we conclude that, within our limited but heterogeneous task battery, ISV and temporal processing deficits are most sensitive to ADHD symptomatology and that controlling for ADHD comorbidity is mandatory when assessing ISV in autism

Simulation of the intraseasonal variability over the Eastern Pacific ITCZ in climate models

During boreal summer, convective activity over the eastern Pacific (EPAC) inter-tropical convergence zone (ITCZ) exhibits vigorous intraseasonal variability (ISV). Previous observational studies identified two dominant ISV modes over the EPAC, i.e., a 40-day mode and a quasi-biweekly mode (QBM). The 40-day ISV mode is generally considered a local expression of the Madden-Julian Oscillation. However, in addition to the eastward propagation, northward propagation of the 40-day mode is also evident. The QBM mode bears a smaller spatial scale than the 40-day mode, and is largely characterized by northward propagation. While the ISV over the EPAC exerts significant influences on regional climate/weather systems, investigation of contemporary model capabilities in representing these ISV modes over the EPAC is limited. In this study, the model fidelity in representing these two dominant ISV modes over the EPAC is assessed by analyzing six atmospheric and three coupled general circulation models (GCMs), including one super-parameterized GCM (SPCAM) and one recently developed high-resolution GCM (GFDL HIRAM) with horizontal resolution of about 50 km. While it remains challenging for GCMs to faithfully represent these two ISV modes including their amplitude, evolution patterns, and periodicities, encouraging simulations are also noted. In general, SPCAM and HIRAM exhibit relatively superior skill in representing the two ISV modes over the EPAC. While the advantage of SPCAM is achieved through explicit representation of the cumulus process by the embedded 2-D cloud resolving models, the improved representation in HIRAM could be ascribed to the employment of a strongly entraining plume cumulus scheme, which inhibits the deep convection, and thus effectively enhances the stratiform rainfall. The sensitivity tests based on HIRAM also suggest that fine horizontal resolution could also be conducive to realistically capture the ISV over the EPAC, particularly for the QBM mode. Further analysis illustrates that the observed 40-day ISV mode over the EPAC is closely linked to the eastward propagating ISV signals from the Indian Ocean/Western Pacific, which is in agreement with the general impression that the 40-day ISV mode over the EPAC could be a local expression of the global Madden-Julian Oscillation (MJO). In contrast, the convective signals associated with the 40-day mode over the EPAC in most of the GCM simulations tend to originate between 150°E and 150°W, suggesting the 40-day ISV mode over the EPAC might be sustained without the forcing by the eastward propagating MJO. Further investigation is warranted towards improved understanding of the origin of the ISV over the EPAC

In situ vaccination using unique TLR9 ligand K3-SPG induces long-lasting systemic immune response and synergizes with systemic and local immunotherapy

Although checkpoint inhibitors (CPIs) have changed the paradigm of cancer therapy, low response rates and serious systemic adverse events remain challenging. In situ vaccine (ISV), intratumoral injection of immunomodulators that stimulate innate immunity at the tumor site, allows for the development of vaccines in patients themselves. K3-SPG, a second-generation nanoparticulate Toll-like receptor 9 (TLR9) ligand consisting of K-type CpG oligodeoxynucleotide (ODN) wrapped with SPG (schizophyllan), integrates the best of conventional CpG ODNs, making it an ideal cancer immunotherapy adjuvant. Focusing on clinical feasibility for pancreaticobiliary and gastrointestinal cancers, we investigated the antitumor activity of K3-SPG-ISV in preclinical models of pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer (CRC). K3-SPG-ISV suppressed tumor growth more potently than K3-ISV or K3-SPG intravenous injections, prolonged survival, and enhanced the antitumor effect of CPIs. Notably, in PDAC model, K3-SPG-ISV alone induced systemic antitumor effect and immunological memory. ISV combination of K3-SPG and agonistic CD40 antibody further enhanced the antitumor effect. Our results imply that K3-SPG-based ISV can be applied as monotherapy or combined with CPIs to improve their response rate or, conversely, with CPI-free local immunotherapy to avoid CPI-related adverse events. In either strategy, the potency of K3-SPG-based ISV would provide the rationale for its clinical application to puncturable pancreaticobiliary and gastrointestinal malignancies

Libration-point staging concepts for Earth-Mars transportation

The use of libration points as transfer nodes for an Earth-Mars transportation system is briefly described. It is assumed that a reusable Interplanetary Shuttle Vehicle (ISV) operates between the libration point and Mars orbit. Propellant for the round-trip journey to Mars and other supplies would be carried from low Earth orbit (LEO) to the ISV by additional shuttle vehicles. Different types of trajectories between LEO and libration points are presented, and approximate delta-V estimates for these transfers are given. The possible use of lunar gravity-assist maneuvers is also discussed

Isosteviol Has Beneficial Effects on Palmitate-Induced α-Cell Dysfunction and Gene Expression

BACKGROUND: Long-term exposure to high levels of fatty acids impairs insulin secretion and exaggerates glucagon secretion. The aim of this study was to explore if the antihyperglycemic agent, Isosteviol (ISV), is able to counteract palmitate-induced α-cell dysfunction and to influence α-cell gene expression. METHODOLOGY/PRINCIPAL FINDINGS: Long-term incubation studies with clonal α-TC1-6 cells were performed in the presence of 0.5 mM palmitate with or without ISV. We investigated effects on glucagon secretion, glucagon content, cellular triglyceride (TG) content, cell proliferation, and expression of genes involved in controlling glucagon synthesis, fatty acid metabolism, and insulin signal transduction. Furthermore, we studied effects of ISV on palmitate-induced glucagon secretion from isolated mouse islets. Culturing α-cells for 72-h with 0.5 mM palmitate in the presence of 18 mM glucose resulted in a 56% (p<0.01) increase in glucagon secretion. Concomitantly, the TG content of α-cells increased by 78% (p<0.01) and cell proliferation decreased by 19% (p<0.05). At 18 mM glucose, ISV (10(-8) and 10(-6) M) reduced palmitate-stimulated glucagon release by 27% (p<0.05) and 27% (p<0.05), respectively. ISV (10(-6) M) also counteracted the palmitate-induced hypersecretion of glucagon in mouse islets. ISV (10(-6) M) reduced α-TC1-6 cell proliferation rate by 25% (p<0.05), but ISV (10(-8) and 10(-6) M) had no effect on TG content in the presence of palmitate. Palmitate (0.5 mM) increased Pcsk2 (p<0.001), Irs2 (p<0.001), Fasn (p<0.001), Srebf2 (p<0.001), Acaca (p<0.01), Pax6 (p<0.05) and Gcg mRNA expression (p<0.05). ISV significantly (p<0.05) up-regulated Insr, Irs1, Irs2, Pik3r1 and Akt1 gene expression in the presence of palmitate. CONCLUSIONS/SIGNIFICANCE: ISV counteracts α-cell hypersecretion and apparently contributes to changes in expression of key genes resulting from long-term exposure to palmitate. ISV apparently acts as a glucagonostatic drug with potential as a new anti-diabetic drug for the treatment of type 2 diabetes