Characterization of slow and fast phase nystagmus

A current literature review of the analog and digital process of vestibular and optical kinetic nystagmus reveals little agreement in the methods used by various labs. The strategies for detection of saccade (fast phase velocity component of nystagmus) vary between labs, and most of the process have not been evaluated and validated with a standard database. A survey was made of major vestibular labs in the U.S. that perform computer analyses of vestibular and optokinetic reflexes to stimuli, and a baseline was established from which to standardize data acquisition and analysis programs. The concept of an Error Index was employed as the criterium for evaluating the performance of the vestibular analysis software programs. The performance criterium is based on the detection of saccades and is the average of the percentages of missed detections and false detections. Evaluation of the programs produced results for lateral gaze with saccadic amplitude of one, two, three, five, and ten degrees with various signal-to-noise ratios. In addition, results were obtained for sinusoidal pursuit of 0.05, 0.10, and 0.50 Hz with saccades from one to ten degrees at various signal-to-noise ratios. Selection of the best program was made from the performance in the lateral gaze with three degrees of saccadic amplitude and in the 0.10 Hz sinusoid with three degrees of saccadic amplitude

The Equal Opportunities Commission and the Courts in Hong Kong: A Partnership Model?

Since the 1950s, the federal courts in the U.S. have developed a "new partnership" with public administrative agencies. The partnership enables the courts to play a large role in shaping public administrative decision making, implementation, other activity, and values. Severely criticized by scholars and practitioners as judicial meddling and interference with administration, the partnership model rests on the establishment of new constitutional rights for individuals in their encounters with public agencies, facilitation of suits against agencies, creation of remedial law, provision of qualified, rather than absolute, immunity in constitutional tort suits against public employees and officials, and adjustment of the level of judicial scrutiny of agencies on a continuum ranging from virtually "no look" to a "soft look" to a "hard look" depending on the administrative action involved. Our research demonstrates that some elements of the partnership model are present in Hong Kong, at least with respect to the courts and the Equal Opportunities Commission (EOC). Specifically, the courts have: 1) strengthened the statutory right to equal opportunity and the constitutional right to equality; 2) applied a hard look to administrative rationales for breaching these rights; 3) rejected "administrative difficulty" as a basis for using discriminatory gender classifications; and 4) mandated substantial institutional reform. In so doing, the courts have strengthened the EOC's ability to promote equal opportunity. This single case study adds to extant knowledge about courts and public administration and the adaptability of the partnership model to different political systems

Mirror Metrology Using Nano-Probe Supports

Thin, lightweight mirrors are needed for future x-ray space telescopes in order to increase x-ray collecting area while maintaining a reduced mass and volume capable of being launched on existing rockets. However, it is very difficult to determine the undistorted shape of such thin mirrors because the mounting of the mirror during measurement causes distortion. Traditional kinematic mounts have insufficient supports to control the distortion to measurable levels and prevent the mirror from vibrating during measurement. Over-constrained mounts (non-kinematic) result in an unknown force state causing mirror distortion that cannot be determined or analytically removed. In order to measure flexible mirrors, it is necessary to over-constrain the mirror. Over-constraint causes unknown distortions to be applied to the mirror. Even if a kinematic constraint system can be used, necessary imperfections in the kinematic assumption can lead to an unknown force state capable of distorting the mirror. Previously, thicker, stiffer, and heavier mirrors were used to achieve low optical figure distortion. These mirrors could be measured to an acceptable level of precision using traditional kinematic mounts. As lighter weight precision optics have developed, systems such as the whiffle tree or hydraulic supports have been used to provide additional mounting supports while maintaining the kinematic assumption. The purpose of this invention is to over-constrain a mirror for optical measurement without causing unacceptable or unknown distortions. The invention uses force gauges capable of measuring 1/10,000 of a Newton attached to nano-actuators to support a thin x-ray optic with known and controlled forces to allow for figure measurement and knowledge of the undeformed mirror figure. The mirror is hung from strings such that it is minimally distorted and in a known force state. However, the hanging mirror cannot be measured because it is both swinging and vibrating. In order to stabilize the mirror for measurement, nano-probes support the mirror, causing the mirror to be over-constrained

Mounting and Alignment of IXO Mirror Segments

A suspension-mounting scheme is developed for the IXO (International X-ray Observatory) mirror segments in which the figure of the mirror segment is preserved in each stage of mounting. The mirror, first fixed on a thermally compatible strongback, is subsequently transported, aligned and transferred onto its mirror housing. In this paper, we shall outline the requirement, approaches, and recent progress of the suspension mount processes

Withaferin A activates TRIM16 for its anti‐cancer activity in melanoma

Although selective BRAF inhibitors and novel immunotherapies have improved short-term treatment responses in metastatic melanoma patients, acquired resistance to these therapeutics still represent a major challenge in clinical practice. In this study, we evaluated the efficacy of Withaferin A (WFA), derived from the medicinal plant Withania Somnifera, as a novel therapeutic agent for the treatment of melanoma. WFA showed selective toxicity to melanoma cells compared to non-malignant cells. WFA induced apoptosis, significantly reduced cell proliferation and inhibited migration of melanoma cells. We identified that repression of the tumour suppressor TRIM16 diminished WFA cytotoxicity, suggesting that TRIM16 was in part responsible for the cytotoxic effects of WFA in melanoma cells. Together our data indicates that WFA has potent cytopathic effects on melanoma cells through TRIM16, suggesting a potential therapeutic application of WFA in the disease

Evaluation of the bulk mass flux formulation using large eddy simulations

In this study, bulk mass flux formulations for turbulent fluxes are evaluated for shallow and deep convection using large-eddy simulation data. The bulk mass flux approximation neglects two sources of variability: the inter-object variability due to differences between the average properties of different cloud objects, and the intra-object variability due to perturbations within each cloud object. Using a simple cloud-environment decomposition, the inter-object and intra-object contributions to the heat flux are comparable in magnitude with that from the bulk mass flux approximation, but do not share a similar vertical distribution, and so can not be parameterized with a rescaling method. A down-gradient assumption is also not appropriate to parameterize the neglected flux contributions because a non-negligible part is associated with non-local buoyant structures. A spectral analysis further suggests the presence of fine structures within the clouds. These points motivate investigations in which the vertical transports are decomposed based on the distribution of vertical velocity. As a result, a ``core-cloak" conceptual model is proposed to improve the representation of total vertical fluxes, comprised of a strong and a weak draft for both the updrafts and downdrafts. It is shown that the ``core-cloak" representation can well capture the magnitude and vertical distribution of heat and moisture fluxes for both shallow and deep convection

Sellafield Thermal Treatment Trials Using Advanced Joule Heated Ceramic Melter Technology -WM-10110

ABSTRACT The viability of thermal treatment using vitrification to immobilize two types of Sellafield intermediate level wastes (ILW) has been successfully demonstrated in proof-of-concept trials. The testing employed a type of Joule Heated Ceramic Melter (JHCM) technology that incorporates active mixing of the melt pool. Melt pool mixing improves heat and mass transport, increases waste processing rates, thereby reducing systems size and/or operating duration, and therefore overall treatment costs. Simulants for two Sellafield ILW streams-a Magnox sludge and a sand/clinoptilolite ion exchange waste slurry-were developed for testing in this work. Glass formulations were developed and tested for each of the two ILW streams. Acceptable glass formulations that met all processability and product quality constraints were selected for testing on a small-scale continuously-fed vitrification system. Two tests of nominally 50-hour duration were completed. Data were collected to characterize operating conditions, processing rates, and glass and off-gas compositions for mass balance. Key performance objectives included minimum nonactive additives; maximum volume reduction for the wastes; maximum retention of radionuclide and chemotoxic elements; minimal secondary wastes that require other processing; maximum passivation and stabilization of wastes; and meeting product compliance requirements. Test results demonstrate that vitrification using JHCM technology is well suited to immobilize the two Sellafield waste streams tested. The required system size and operating duration are well within the realm of prior experience of this technology. The technology offers the potential to significantly reduce lifecycle cost because the high volume reductions minimize the volume of treated wastes to be disposed, while the glass waste form offers superior waste form performance compared to almost all alternatives

Novel venom-derived inhibitors of the human EAG channel, a putative antiepileptic drug target

Recently, we and other groups revealed that gain-of-function mutations in the human ether à go-go voltage-gated potassium channel hEAG1 (K10.1) lead to developmental disorders with associated infantile-onset epilepsy. However, the physiological role of hEAG1 in the central nervous system remains elusive. Potent and selective antagonists of hEAG1 are therefore much sought after, both as pharmacological tools for studying the (patho)physiological functions of this enigmatic channel and as potential leads for development of anti-epileptic drugs. Since animal venoms are a rich source of potent ion channel modifiers that have been finely tuned by millions of year of evolution, we screened 108 arachnid venoms for hEAG1 inhibitors using electrophysiology. Two hit peptides (Aa1a and Ap1a) were isolated, sequenced, and chemically synthesised for structure-function studies. Both of these hEAG1 inhibitors are C-terminally amidated peptides containing an inhibitor cystine knot motif, which provides them with exceptional stability in both plasma and cerebrospinal fluid. Aa1a and Ap1a are the most potent peptidic inhibitors of hEAG1 reported to date, and they present a novel mode of action by targeting both the activation and inactivation gating of the channel. These peptides should be useful pharmacological tools for probing hEAG1 function as well as informative leads for the development of novel anti-epileptic drugs

Persistence of haemostatic response following gene therapy with valoctocogene roxaparvovec in severe haemophilia A.

INTRODUCTION: Valoctocogene roxaparvovec is an investigational AAV5-based factor VIII (FVIII) gene therapy that has demonstrated sustained clinical benefit in people with severe haemophilia A. AIM: To report safety, tolerability, efficacy, and quality of life (QOL) among participants who received valoctocogene roxaparvovec in a phase 1/2 clinical study (NCT02576795). METHODS: Men ≥18 years of age with severe haemophilia A (FVIII ≤1 IU/dl) without history of FVIII inhibitors or anti-AAV5 antibodies received a single infusion of valoctocogene roxaparvovec and were followed for 5 years (6 × 1013 vg/kg dose, n = 7) and 4 years (4 × 1013 vg/kg dose, n = 6). RESULTS: Over the past 2 years, few adverse events and no FVIII inhibitors were reported. Per chromogenic substrate (CSA) assay at years 5 and 4, four of seven and three of six participants in the 6 × 1013 and 4 × 1013 vg/kg cohorts, respectively, maintained median FVIII levels >5 IU/dl, corresponding to mild haemophilia. By regression analysis, rate of change in FVIII activity was -0.14 (95% confidence interval [CI]: -.32 to .03) IU/dl/wk in the 6 × 1013 vg/kg cohort in year 5 and -.06 (95% CI: -.14 to .01) IU/dl/wk in the 4 × 1013 vg/kg cohort in year 4. No participants resumed FVIII prophylaxis, and eight of 13 participants reported zero bleeds in the past 2 years. Improved QOL from baseline persisted in the 6 × 1013 vg/kg cohort; all six Haemo-QOL-A domain scores increased. For the 4 × 1013 vg/kg cohort, high baseline Haemo-QOL-A scores persisted. CONCLUSION: These results demonstrate transgene expression and haemostatic response for up to 5 years in individuals with haemophilia A