Possible effects of tilt order on phase transitions of a fixed connectivity surface model

We study the phase structure of a phantom tethered surface model shedding light on the internal degrees of freedom (IDOF), which correspond to the three-dimensional rod like structure of the lipid molecules. The so-called tilt order is assumed as IDOF on the surface model. The model is defined by combining the conventional spherical surface model and the XY model, which describes not only the interaction between lipids but also the interaction between the lipids and the surface. The interaction strength between IDOF and the surface varies depending on the interaction strength between the variables of IDOF. We know that the model without IDOF undergoes a first-order transition of surface fluctuations and a first-order collapsing transition. We observe in this paper that the order of the surface fluctuation transition changes from first-order to second-order and to higher-order with increasing strength of the interaction between IDOF variables. On the contrary, the order of collapsing transition remains first-order and is not influenced by the presence of IDOF.Comment: 20 pages, 14 figure

Distributed functions of prefrontal and parietal cortices during sequential categorical decisions

Comparing sequential stimuli is crucial for guiding complex behaviors. To understand mechanisms underlying sequential decisions, we compared neuronal responses in the prefrontal cortex (PFC), the lateral intraparietal (LIP), and medial intraparietal (MIP) areas in monkeys trained to decide whether sequentially presented stimuli were from matching (M) or nonmatching (NM) categories. We found that PFC leads M/NM decisions, whereas LIP and MIP appear more involved in stimulus evaluation and motor planning, respectively. Compared to LIP, PFC showed greater nonlinear integration of currently visible and remembered stimuli, which correlated with the monkeys’ M/NM decisions. Furthermore, multi-module recurrent networks trained on the same task exhibited key features of PFC and LIP encoding, including nonlinear integration in the PFC-like module, which was causally involved in the networks’ decisions. Network analysis found that nonlinear units have stronger and more widespread connections with input, output, and within-area units, indicating putative circuit-level mechanisms for sequential decisions

Efficacy and Safety of a Brain-Penetrant Biologic TNF-α Inhibitor in Aged APP/PS1 Mice

Tumor necrosis factor alpha (TNF-α) plays a vital role in Alzheimer’s disease (AD) pathology, and TNF-α inhibitors (TNFIs) modulate AD pathology. We fused the TNF-α receptor (TNFR), a biologic TNFI that sequesters TNF-α, to a transferrin receptor antibody (TfRMAb) to deliver the TNFI into the brain across the blood–brain barrier (BBB). TfRMAb-TNFR was protective in 6-month-old transgenic APP/PS1 mice in our previous work. However, the effects and safety following delayed chronic TfRMAb-TNFR treatment are unknown. Herein, we initiated the treatment when the male APP/PS1 mice were 10.7 months old (delayed treatment). Mice were injected intraperitoneally with saline, TfRMAb-TNFR, etanercept (non-BBB-penetrating TNFI), or TfRMAb for ten weeks. Biologic TNFIs did not alter hematology indices or tissue iron homeostasis; however, TfRMAb altered hematology indices, increased splenic iron transporter expression, and increased spleen and liver iron. TfRMAb-TNFR and etanercept reduced brain insoluble-amyloid beta (Aβ) 1-42, soluble-oligomeric Aβ, and microgliosis; however, only TfRMAb-TNFR reduced Aβ peptides, Thioflavin-S-positive Aβ plaques, and insoluble-oligomeric Aβ and increased plaque-associated phagocytic microglia. Accordingly, TfRMAb-TNFR improved spatial reference memory and increased BBB-tight junction protein expression, whereas etanercept did not. Overall, despite delayed treatment, TfRMAb-TNFR resulted in a better therapeutic response than etanercept without any TfRMAb-related hematology- or iron-dysregulation in aged APP/PS1 mice

Biologic TNF-α Inhibitors Reduce Microgliosis, Neuronal Loss, and Tau Phosphorylation in a Transgenic Mouse Model of Tauopathy

Background Tumor necrosis factor-α (TNF-α) plays a central role in Alzheimer’s disease (AD) pathology, making biologic TNF-α inhibitors (TNFIs), including etanercept, viable therapeutics for AD. The protective effects of biologic TNFIs on AD hallmark pathology (Aβ deposition and tau pathology) have been demonstrated. However, the effects of biologic TNFIs on Aβ-independent tau pathology have not been reported. Existing biologic TNFIs do not cross the blood–brain barrier (BBB), therefore we engineered a BBB-penetrating biologic TNFI by fusing the extracellular domain of the type-II human TNF-α receptor (TNFR) to a transferrin receptor antibody (TfRMAb) that ferries the TNFR into the brain via receptor-mediated transcytosis. The present study aimed to investigate the effects of TfRMAb-TNFR (BBB-penetrating TNFI) and etanercept (non-BBB-penetrating TNFI) in the PS19 transgenic mouse model of tauopathy. Methods Six-month-old male and female PS19 mice were injected intraperitoneally with saline (n = 12), TfRMAb-TNFR (1.75 mg/kg, n = 10) or etanercept (0.875 mg/kg, equimolar dose of TNFR, n = 10) 3 days/week for 8 weeks. Age-matched littermate wild-type mice served as additional controls. Blood was collected at baseline and 8 weeks for a complete blood count. Locomotion hyperactivity was assessed by the open-field paradigm. Brains were examined for phosphorylated tau lesions (Ser202, Thr205), microgliosis, and neuronal health. The plasma pharmacokinetics were evaluated following a single intraperitoneal injection of 0.875 mg/kg etanercept or 1.75 mg/kg TfRMAb-TNFR or 1.75 mg/kg chronic TfRMAb-TNFR dosing for 4 weeks. Results Etanercept significantly reduced phosphorylated tau and microgliosis in the PS19 mouse brains of both sexes, while TfRMAb-TNFR significantly reduced these parameters in the female PS19 mice. Both TfRMAb-TNFR and etanercept treatment improved neuronal health by significantly increasing PSD95 expression and attenuating hippocampal neuron loss in the PS19 mice. The locomotion hyperactivity in the male PS19 mice was suppressed by chronic etanercept treatment. Equimolar dosing resulted in eightfold lower plasma exposure of the TfRMAb-TNFR compared with etanercept. The hematological profiles remained largely stable following chronic biologic TNFI dosing except for a significant increase in platelets with etanercept. Conclusion Both TfRMAb-TNFR (BBB-penetrating) and non-BBB-penetrating (etanercept) biologic TNFIs showed therapeutic effects in the PS19 mouse model of tauopathy

Trends and emissions of six perfluorocarbons in the Northern Hemisphere and Southern Hemisphere

Perfluorocarbons (PFCs) are potent greenhouse gases with global warming potentials up to several thousand times greater than CO2 on a 100-year time horizon. The lack of any significant sinks for PFCs means that they have long atmospheric lifetimes of the order of thousands of years. Anthropogenic production is thought to be the only source for most PFCs. Here we report an update on the global atmospheric abundances of the following PFCs, most of which have for the first time been analytically separated according to their isomers: c-octafluorobutane (c-C4F8), n-decafluorobutane (n-C4F10), n-dodecafluoropentane (n-C5F12), n-tetradecafluorohexane (n-C6F14), and n-hexadecafluoroheptane (n-C7F16). Additionally, we report the first data set on the atmospheric mixing ratios of perfluoro-2-methylpentane (i-C6F14). The existence and significance of PFC isomers have not been reported before, due to the analytical challenges of separating them. The time series spans a period from 1978 to the present. Several data sets are used to investigate temporal and spatial trends of these PFCs: time series of air samples collected at Cape Grim, Australia, from 1978 to the start of 2018; a time series of air samples collected between July 2015 and April 2017 at Tacolneston, UK; and intensive campaign-based sampling collections from Taiwan. Although the remote “background” Southern Hemispheric Cape Grim time series indicates that recent growth rates of most of these PFCs are lower than in the 1990s, we continue to see significantly increasing mixing ratios that are between 6 % and 27 % higher by the end of 2017 compared to abundances measured in 2010. Air samples from Tacolneston show a positive offset in PFC mixing ratios compared to the Southern Hemisphere baseline. The highest mixing ratios and variability are seen in air samples from Taiwan, which is therefore likely situated much closer to PFC sources, confirming predominantly Northern Hemispheric emissions for most PFCs. Even though these PFCs occur in the atmosphere at levels of parts per trillion molar or less, their total cumulative global emissions translate into 833 million metric tonnes of CO2 equivalent by the end of 2017, 23 % of which has been emitted since 2010. Almost two-thirds of the CO2 equivalent emissions within the last decade are attributable to c-C4F8, which currently also has the highest emission rates that continue to grow. Sources of all PFCs covered in this work remain poorly constrained and reported emissions in global databases do not account for the abundances found in the atmosphere

Rigid Chiral Membranes

Statistical ensembles of flexible two-dimensional fluid membranes arise naturally in the description of many physical systems. Typically one encounters such systems in a regime of low tension but high stiffness against bending, which is just the opposite of the regime described by the Polyakov string. We study a class of couplings between membrane shape and in-plane order which break 3-space parity invariance. Remarkably there is only {\it one} such allowed coupling (up to boundary terms); this term will be present for any lipid bilayer composed of tilted chiral molecules. We calculate the renormalization-group behavior of this relevant coupling in a simplified model and show how thermal fluctuations effectively reduce it in the infrared.Comment: 11 pages, UPR-518T (This replaced version has fonts not used removed.

Conformally parametrized surfaces associated with CP^(N-1) sigma models

Two-dimensional conformally parametrized surfaces immersed in the su(N) algebra are investigated. The focus is on surfaces parametrized by solutions of the equations for the CP^(N-1) sigma model. The Lie-point symmetries of the CP^(N-1) model are computed for arbitrary N. The Weierstrass formula for immersion is determined and an explicit formula for a moving frame on a surface is constructed. This allows us to determine the structural equations and geometrical properties of surfaces in R^(N^2-1). The fundamental forms, Gaussian and mean curvatures, Willmore functional and topological charge of surfaces are given explicitly in terms of any holomorphic solution of the CP^2 model. The approach is illustrated through several examples, including surfaces immersed in low-dimensional su(N) algebras.Comment: 32 page

Surfaces immersed in su(N+1) Lie algebras obtained from the CP^N sigma models

We study some geometrical aspects of two dimensional orientable surfaces arrising from the study of CP^N sigma models. To this aim we employ an identification of R^(N(N+2)) with the Lie algebra su(N+1) by means of which we construct a generalized Weierstrass formula for immersion of such surfaces. The structural elements of the surface like its moving frame, the Gauss-Weingarten and the Gauss-Codazzi-Ricci equations are expressed in terms of the solution of the CP^N model defining it. Further, the first and second fundamental forms, the Gaussian curvature, the mean curvature vector, the Willmore functional and the topological charge of surfaces are expressed in terms of this solution. We present detailed implementation of these results for surfaces immersed in su(2) and su(3) Lie algebras.Comment: 32 pages, 1 figure; changes: major revision of presentation, clarifications adde

Abrupt reversal in emissions and atmospheric abundance of HCFC-133a (CF3CH2Cl)

Hydrochlorofluorocarbon HCFC-133a (CF3CH2Cl) is an anthropogenic compound whose consumption for emissive use is restricted under the Montreal Protocol. A recent study showed rapidly increasing atmospheric abundances and emissions. We report that, following this rise, the at- mospheric abundance and emissions have declined sharply in the past three years. We find a Northern Hemisphere HCFC-133a increase from 0.13 ppt (dry air mole fraction in parts-per-trillion) in 2000 to 0.50 ppt in 2012–mid-2013 followed by an abrupt reversal to 0.44 ppt by early 2015. Global emissions derived from these observations peaked at 3.1 kt in 2011, followed by a rapid decline of 0.5 kt yr−2 to 1.5 kt yr−1 in 2014. Sporadic HCFC-133a pollution events are detected in Europe from our high-resolution HCFC-133a records at three European stations, and in Asia from sam- ples collected in Taiwan. European emissions are estimated to be <0.1 kt yr−1 although emission hotspots were identi- fied in France