Aquaporin-4 Functionality and Virchow-Robin Space Water Dynamics: Physiological Model for Neurovascular Coupling and Glymphatic Flow.

The unique properties of brain capillary endothelium, critical in maintaining the blood-brain barrier (BBB) and restricting water permeability across the BBB, have important consequences on fluid hydrodynamics inside the BBB hereto inadequately recognized. Recent studies indicate that the mechanisms underlying brain water dynamics are distinct from systemic tissue water dynamics. Hydrostatic pressure created by the systolic force of the heart, essential for interstitial circulation and lymphatic flow in systemic circulation, is effectively impeded from propagating into the interstitial fluid inside the BBB by the tightly sealed endothelium of brain capillaries. Instead, fluid dynamics inside the BBB is realized by aquaporin-4 (AQP-4), the water channel that connects astrocyte cytoplasm and extracellular (interstitial) fluid. Brain interstitial fluid dynamics, and therefore AQP-4, are now recognized as essential for two unique functions, namely, neurovascular coupling and glymphatic flow, the brain equivalent of systemic lymphatics

Pion Form Factors in Holographic QCD

Using a holographic dual model of QCD, we compute the pion electromagnetic form factor F_pi(Q^2) in the spacelike momentum transfer region, as well as pion couplings to vector mesons g_rho^(n) pi pi. Spontaneous and explicit chiral symmetry breaking are intrinsic features of this particular holographic model. We consider variants with both ``hard-wall'' and ``soft-wall'' infrared cutoffs, and find that the F_pi(Q^2) data tend to lie closer to the hard-wall model predictions, although both are too shallow for large Q^2. By allowing the parameters of the soft-wall model (originally fixed by observables such as m_rho) to vary, one finds fits that tend to agree better with F_pi(Q^2). We also compute the pion charge radius for a variety of parameter choices, and use the values of f^(n)_rho, g_{rho^(n) pi pi} and m^(n)_rho to observe the saturation of F_pi(0) by rho poles.Comment: 17 pages, 2 figures, revised fits using consistent normalization of f_pi. References update

Stabilized high-power laser system for the gravitational wave detector advanced LIGO

An ultra-stable, high-power cw Nd:YAG laser system, developed for the ground-based gravitational wave detector Advanced LIGO (Laser Interferometer Gravitational-Wave Observatory), was comprehensively characterized. Laser power, frequency, beam pointing and beam quality were simultaneously stabilized using different active and passive schemes. The output beam, the performance of the stabilization, and the cross-coupling between different stabilization feedback control loops were characterized and found to fulfill most design requirements. The employed stabilization schemes and the achieved performance are of relevance to many high-precision optical experiments

Stabilized lasers for advanced gravitational wave detectors

Second generation gravitational wave detectors require high power lasers with more than 100 W of output power and with very low temporal and spatial fluctuations. To achieve the demanding stability levels required, low noise techniques and adequate control actuators have to be part of the high power laser design. In addition feedback control and passive noise filtering is used to reduce the fluctuations in the so-called prestabilized laser system (PSL). In this paper, we discuss the design of a 200 W PSL which is under development for the Advanced LIGO gravitational wave detector and will present the first results. The PSL noise requirements for advanced gravitational wave detectors will be discussed in general and the stabilization scheme proposed for the Advanced LIGO PSL will be described

Nanomolar Binding of Peptides Containing Noncanonical Amino Acids by a Synthetic Receptor

This paper describes the molecular recognition of phenylalanine derivatives and their peptides by the synthetic receptor cucurbit[7]uril (Q7). The 4-tert-butyl and 4-aminomethyl derivatives of phenylalanine (tBuPhe and AMPhe) were identified from a screen to have 20–30-fold higher affinity than phenylalanine for Q7. Placement of these residues at the N-terminus of model tripeptides (X-Gly-Gly), resulted in no change in affinity for tBuPhe-Gly-Gly, but a remarkable 500-fold increase in affinity for AMPhe-Gly-Gly, which bound to Q7 with an equilibrium dissociation constant (Kd) value of 0.95 nM in neutral phosphate buffer. Structure–activity studies revealed that three functional groups work in a positively cooperative manner to achieve this extraordinary stability (1) the N-terminal ammonium group, (2) the side chain ammonium group, and (3) the peptide backbone. Addition of the aminomethyl group to Phe substantially improved the selectivity for peptide versus amino acid and for an N-terminal vs nonterminal position. Importantly, Q7 binds to N-terminal AMPhe several orders of magnitude more tightly than any of the canonical amino acid residues. The high affinity, single-site selectivity, and small modification in this system make it attractive for the development of minimal affinity tags

Photometric Analysis of Recently Discovered Eclipsing Binary GSC 00008-00901

Photometric analysis of $BVR_C$ light curves of newly discovered eclipsing binary GSC 0008-00901 is presented. The orbital period is improved to 0.28948(11) days. Photometric parameters are determined, as well. The analysis yielded to conclusion that system is an over-contact binary of W UMa type with components not in thermal contact. The light curves from 2005 show the presence of a spot on the surface of one of the components, while light curves from 2006 are not affected by maculation.Comment: Accepted for publication in Astrophysics & Space Scienc

Guide to the Unification Process and Its Implementation: Progress Report on Extending the Grammar

There are two steps in generating an English sentence using a functional grammar: unification with the grammar and linearization of the resulting structure. This report is intended as an introduction and a guide to the unification process and its implementation. The program and grammar used are modified versions of those used in the TEXT system [McKeown 82]. We describe the major functions of the program, noting how we have made it more general and more efficient. We also describe the extensions and improvements made to the original functional grammar used in the TEXT system

Exercise prehabilitation for people with myeloma undergoing autologous stem cell transplantation: results from PERCEPT pilot randomised controlled trial

BACKGROUND: Autologous stem cell transplant (ASCT) is first line treatment for newly diagnosed patients with myeloma but often results in functional deficits and reduced quality of life (QOL). Physically active myeloma patients have better QOL, less fatigue and reduced morbidity. This trial aimed to investigate the feasibility of a physiotherapist-led exercise intervention delivered across the continuum of the myeloma ASCT pathway at a UK centre. Initially designed and delivered as a face-to-face trial, the study protocol was adapted to virtual delivery in response to the COVID-19 pandemic. MATERIAL AND METHODS: A pilot randomised controlled trial of a partly supervised exercise intervention with incorporated behaviour change techniques delivered before, during and for 3 months following ASCT compared to usual care. Face-to-face delivery of the pre-ASCT supervised intervention was adapted to virtually-supervised group classes via video conferencing. Primary outcomes related to feasibility; recruitment rate, attrition and adherence. Secondary outcomes included patient reported measures of QOL (EORTC C30, FACT-BMT, EQ5D), and fatigue (FACIT-F), measures of functional capacity (six-minute walk test (6MWT), timed sit-to-stand (TSTS), hand grip strength, self-reported and objective physical activity (PA). RESULTS: Over 11 months 50 participants were enrolled and randomised. Overall, uptake to the study was 46%. The attrition rate was 34%, mainly related to failure to undergo ASCT. Loss of follow-up for other reasons was low. Secondary outcomes demonstrate potential for the benefit of exercise prior to, during and after ASCT with improvements in QOL, fatigue, functional capacity and PA evident on admission for ASCT and 3 months post-ASCT. DISCUSSION: Results indicate acceptability and feasibility of delivering exercise prehabilitation, in person and virtually within the ASCT pathway in myeloma. The effects of prehabilitation and rehabilitation provision as a component of the ASCT pathway warrants further investigation

"What I wanted to do was build myself back up and prepare": qualitative findings from the PERCEPT trial of prehabilitation during autologous stem cell transplantation in myeloma

BACKGROUND: The addition of qualitative methodology to randomised controlled trials evaluating complex interventions allows better understanding of contextualised factors and their potential influence on trial delivery and outcomes, as well as opportunities for feedback on trial participation to improve future trial protocols. This study explored the experiences of participation in cancer rehabilitation research during active cancer treatment. Participants were people living with haematological cancer myeloma, undergoing autologous stem cell transplantation (ASCT) recruited to the PERCEPT myeloma pilot trial. METHODS: A qualitative semi-structured interview study, embedded within a pilot randomised controlled trial of a physiotherapist-led exercise intervention delivered before, during and after ASCT among people living with myeloma. Transcripts were analysed using reflexive thematic analysis. RESULTS: Interviews from 16 trial participants (n = 8 intervention group; n = 8 control group; mean age 61 years, 56% male) were analysed. Four main themes were identified: (1) "It's not just beneficial for me, it's for people after me as well"; (2) Disparities in experience of recovery - expectations, feeling prepared and support; (3) "What I wanted to do was build myself back up and prepare"; (4) Active ingredients - participants' experience of the trial intervention. Participants reported both altruistic and perceived personal gain as motivators for enrolling in the trial. Disappointment caused by allocation to control arm may have led to participants seeking exercise elsewhere, indicating possible contamination of control condition. Disparities in experience of recovery from transplant were evident with intervention participants reporting greater trajectory of recovery. CONCLUSIONS: The findings from this embedded qualitative study highlight numerous considerations required when designing pilot and efficacy trials of complex interventions. The addition of qualitative investigation offers greater understanding of motivations for participation, intervention mechanisms at play as well as effects of participation that may impact interpretation of quantitative outcomes. TRIAL REGISTRATION: Qualitative findings from a prospectively registered pilot trial (ISRCTN15875290), registered 13/02/2019