Nonadiabatic extension of the Heisenberg model

The localized states within the Heisenberg model of magnetism should be represented by best localized Wannier functions forming a unitary transformation of the Bloch functions of the narrowest partly filled energy bands in the metals. However, as a consequence of degeneracies between the energy bands near the Fermi level, in any metal these Wannier functions cannot be chosen symmetry-adapted to the complete paramagnetic group M^P. Therefore, it is proposed to use Wannier functions with the reduced symmetry of a magnetic subgroup M of M^P [case (a)] or spin dependent Wannier functions [case (b)]. The original Heisenberg model is reinterpreted in order to understand the pronounced symmetry of these Wannier functions. While the original model assumes that there is exactly one electron at each atom, the extended model postulates that in narrow bands there are as many as possible atoms occupied by exactly one electron. However, this state with the highest possible atomiclike character cannot be described within the adiabatic (or Born-Oppenheimer) approximation because in the (true) nonadiabatic system the electrons move on localized orbitals that are still symmetric on the average of time, but not at any moment. The nonadiabatic states have the same symmetry as the adiabatic states and determine the commutation properties of the nonadiabatic Hamiltonian H^n. The nonadiabatic Heisenberg model is a purely group- theoretical model which interprets the commutation properties of H^n that are explicitly given in this paper for the two important cases (a) and (b). There is evidence that the occurrence of these two types of Wannier functions in the band structure of a metal is connected with the occurrence of magnetism and superconductivity, respectively

Two-stage coarsening mechanism in a kinetically constrained model of an attractive colloid

We study an attractive version of the East model using the real-space renormalization group (RG) introduced by Stella et al. The former is a kinetically constrained model with an Ising-like interaction between excitations, and shows striking agreement with the phenomonology of attractive colloidal systems. We find that the RG predicts two nonuniversal dynamic exponents, which suggests that in the out-of-equilibrium regime the model coarsens via a two-stage mechanism. We explain this mechanism physically, and verify this prediction numerically. In addition, we find that the characteristic relaxation time of the model is a non-monotonic function of attraction strength, again in agreement with numerical results.Comment: 10 page

Sunset haematology: improving the end-of-life journey for patients and caregivers, in patients with haematologic malignancies

BACKGROUND AND AIM Haematologic Malignancies (HM) are diverse diseases with differing illness trajectories and therapeutic pathways. Unfortunately HM patients may rapidly and unexpectedly clinically deteriorate, resulting in suboptimal engagement of palliative and end-of-life (EOL) care.  Compared to patients with solid tumours, HM patients have many different factors affecting their end-of-life (EOL) journey. Uniquely, a subset of HM patients with bone marrow failure (BMF) can be supported for significant, but highly variable, periods of time with red blood cell transfusions (RBCT), platelet transfusions (PT) and prophylactic antibiotics.  Availability of chronic RBCTs and PTs make HM patients with BMF similar to elderly and poor prognosis patients with end stage kidney disease (ESKD). Multidisciplinary Palliative Supportive Care programs have been shown to be effective for these EKSD patients and may serve as supportive care models for EOL journey in HM patients. This project is  a pilot study aiming to provide a template for management of EOL for patients with HM with BMF, and their care-givers. METHODS Three components are being developed: 1) Survey of patient opinions around treatment decision-making. 2) Analyses of the impact of patient, disease and treatment factors on the probability of survival from start of PT, to inform patients. 3) Collaborative involvement between Haematology and Palliative Care staff involved in the local ESKD program, to develop a template for earlier EOL pathway planning in HM patients. CONCLUSION Progress of work to date will be presented including preliminary findings and next steps

Tolerance in TCR/Cognate Antigen Double-Transgenic Mice Mediated by Incomplete Thymic Deletion and Peripheral Receptor Downregulation

Influenza nucleoprotein (NP)-specific T-cell receptor transgenic mice (F5) were crossed with transgenic mice expressing the cognate antigenic protein under the control of the H- 2Kb promoter. Double-transgenic mice show negative selection of thymocytes at the CD4+8+TCR10 to CD4+8+TCRhi transition stage. A few CD8 T cells, however, escape clonal deletion, and in the peripheral lymphoid organs of these mice, they exhibit low levels of the transgenic receptor and upregulated levels of the CD44 memory marker. Such cells do not proliferate upon exposure to antigen stimulation in vivo or ex vivo, however, they can develop low but detectable levels of antigen-specific cytotoxic function after stimulation in vitro in the presence of IL-2

Positive and Negative Selection in Transgenic Mice Expressing a T-Cell Receptor Specific for Influenza Nucleoprotein and Endogenous Superantigen

A transgenic mouse was generated expressing on most (>80%) of thymocytes and peripheral T cells a T-cell receptor isolated from a cytotoxic T-cell clone (F5). This clone is CD8+ and recognizes αα366-374 of the nucleoprotein (NP 366-374) of influenza virus (A/NT/60/68), in the context of Class ,MHC Db (Townsend et al., 1986). The receptor utilizes the Vβ11 and Vα4 gene segments for the β chain and α chain, respectively (Palmer et al., 1989). The usage of Vβ11 makes this TcR reactive to Class II IE molecules and an endogenous ligand recently identified as a product of the endogenous mammary tumour viruses (Mtv) 8, 9, and 11 (Dyson et al., 1991). Here we report the development of F5 transgenic T cells and their function in mice of the appropriate MHC (C57BL/10 H-2b, IE-) or in mice expressing Class II MHC IE (e.g., CBA/Ca H-2k and BALB/c H-2d) and the endogenous Mtv ligands. Positive selection of CD8+ T cells expressing the Vβ11 is seen in C57BL/10 transgenic mice (H-2b). Peripheral T cells from these mice are capable of killing target cells in an antigen-dependent manner after a period of in vitro culture with IL-2. In the presence of Class II MHC IE molecules and the endogenous Mtv ligand, most of the single-positive cells carrying the transgenic T-cell receptor are absent in the thymus. Unexpectedly, CD8+ peripheral T-cells in these (H-2k or H-2d) F5 mice are predominantly Vβ11 positive and also have the capacity to kill targets in an antigen-dependent manner. This is true even following backcrossing of the F5 TcR transgene to H-2d scid/scid mice, in which functional rearrangement of endogenous TcR alpha- and beta-chain genes is impaired

Investigating the Relationships Between Three Important Functional Tasks Early After Stroke: Movement Characteristics of Sit-To-Stand, Sit-To-Walk, and Walking.

Background: Walking, sit-to-stand (STS) and sit-to-walk (STW) are all considered important functional tasks in achieving independence after stroke. Despite knowledge that sensitive measurement of movement patterns is crucial to understanding neuromuscular restitution, there is surprisingly little information available about the detailed biomechanical characteristics of, and relationships between, walking, sit-to-stand and sit-to-walk, particularly in the important time window early after stroke. Hence, here, the study aimed to: Identify the biomechanical characteristics of and determine any differences in both movement fluidity (hesitation, coordination and smoothness) and duration of movement phases, between sit-to-stand (STS) and sit-to-walk (STW) in people early after stroke.Determine whether measures of movement fluidity (hesitation, coordination, and smoothness) and movement phases during sit-to-stand (STS) and/or sit-to-walk (STW) are correlated strongly to commonly used measures of walking speed and/or step length ratio in people early after stroke. Methods: This study consisted of secondary data analysis from the SWIFT Cast Trial. Specifically, we investigated movement fluidity using established assessments of smoothness, hesitation and coordination and the time duration for specific movement phases in a group of 48 people after stroke. Comparisons were made between STS and STW and relationships to walking measures were explored. Results: Participants spent significantly more time in the initial movement phase, flexion momentum, during STS [mean time (SD) 1.74 ±1.45 s] than they did during STW [mean time (SD) 1.13 ± 1.03 s]. STS was also completed more smoothly but with more hesitation and greater coordination than the task of STW. No strong relationships were found between movement fluidity or duration with walking speed or step length symmetry. Conclusions: Assessment of movement after stroke requires a range of functional tasks and no one task should predominate over another. Seemingly similar or overlapping tasks such as STS and STW create distinct biomechanical characteristics which can be identified using sensitive, objective measures of fluidity and movement phases but there are no strong relationships between the functional tasks of STS and STW with walking speed or with step-length symmetry

No difference in clinical outcomes for African American and White patients hospitalized with SARS-CoV-2 pneumonia in Louisville, Kentucky

Introduction: Current literature indicates that African American individuals are at increased risk of becoming infected with the SARS-CoV-2 virus and suffer higher SARS-CoV-2-related mortality rates. However, there is a lack of consensus as to how the clinical outcomes of African American patients differ from those of other groups. The objective of this study was to define the clinical outcomes of African American and White hospitalized patients with SARS-CoV-2 community-acquired pneumonia (CAP) in Louisville, Kentucky. Methods: This was a retrospective cohort study of hospitalized patients with SARS-CoV-2 CAP at eight hospitals in Louisville, Kentucky. Severity of CAP at time of hospitalization was evaluated using the pneumonia severity index (PSI), CURB-65 score and SARS-CoV-2 viral load. The following thirteen clinical outcomes were compared: discharge alive to home, time to home discharge, admission to the ICU, length of ICU stay, need for invasive mechanical ventilation (IMV), duration of IMV, development of acute respiratory distress syndrome (ARDS), development of septic shock, need for vasopressors, development of cardiovascular events, time to cardiovascular events, in-hospital mortality, and time to death. Results: A total of 541 patients were eligible for this study, 343 White (63%) and 198 African American (37%). None of the thirteen clinical outcomes were statistically significantly different between the two groups. Conclusions: This study indicates that African American and White patients do not have different clinical outcomes after the point of hospitalization due to SARS-CoV-2 CAP

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

vitro synergy and enhanced murine brain penetration of saquinavir coadministered with mefloquine

ABSTRACT Highly active antiretroviral therapy has substantially improved prognosis in human immunodeficiency virus (HIV). However, the integration of proviral DNA, development of viral resistance, and lack of permeability of drugs into sanctuary sites (e.g., brain and lymphocyte) are major limitations to current regimens. Previous studies have indicated that the antimalarial drug chloroquine (CQ) has antiviral efficacy and a synergism with HIV protease inhibitors. We have screened a panel of antimalarial compounds for activity against HIV-1 in vitro. A limited efficacy was observed for CQ, mefloquine (MQ), and mepacrine (MC). However, marked synergy was observed between MQ and saquinavir (SQV), but not CQ in U937 cells. Furthermore, enhancement of the antiviral activity of SQV and four other protease inhibitors (PIs) by MQ was observed in MT4 cells, indicating a class specific rather than a drug-specific phenomenon. We demonstrate that these observations are a result of inhibition of multiple drug efflux proteins by MQ and that MQ also displaces SQV from orosomucoid in vitro. Finally, coadministration of MQ and SQV in CD-1 mice dramatically altered the tissue distribution of SQV, resulting in a Ͼ3-fold and Ͼ2-fold increase in the tissue/blood ratio for brain and testis, respectively. This pharmacological enhancement of in vitro antiviral activity of PIs by MQ now warrants further examination in vivo