Application of the group-theoretical method to physical problems

The concept of the theory of continuous groups of transformations has attracted the attention of applied mathematicians and engineers to solve many physical problems in the engineering sciences. Three applications are presented in this paper. The first one is the problem of time-dependent vertical temperature distribution in a stagnant lake. Two cases have been considered for the forms of the water parameters, namely water density and thermal conductivity. The second application is the unsteady free-convective boundary-layer flow on a non-isothermal vertical flat plate. The third application is the study of the dispersion of gaseous pollutants in the presence of a temperature inversion. The results are found in closed form and the effect of parameters are discussed

A discrete cluster of urinary biomarkers discriminates between active systemic lupus erythematosus patients with and without glomerulonephritis.

BackgroundManagement of lupus nephritis (LN) would be greatly aided by the discovery of biomarkers that accurately reflect changes in disease activity. Here, we used a proteomics approach to identify potential urinary biomarkers associated with LN.MethodsUrine was obtained from 60 LN patients with paired renal biopsies, 25 active non-LN SLE patients, and 24 healthy controls. Using Luminex, 128 analytes were quantified and normalized to urinary creatinine levels. Data were analyzed by linear modeling and non-parametric statistics, with corrections for multiple comparisons. A second cohort of 33 active LN, 16 active non-LN, and 30 remission LN SLE patients was used to validate the results.ResultsForty-four analytes were identified that were significantly increased in active LN as compared to active non-LN. This included a number of unique proteins (e.g., TIMP-1, PAI-1, PF4, vWF, and IL-15) as well as known candidate LN biomarkers (e.g., adiponectin, sVCAM-1, and IL-6), that differed markedly (>4-fold) between active LN and non-LN, all of which were confirmed in the validation cohort and normalized in remission LN patients. These proteins demonstrated an enhanced ability to discriminate between active LN and non-LN patients over several previously reported biomarkers. Ten proteins were found to significantly correlate with the activity score on renal biopsy, eight of which strongly discriminated between active proliferative and non-proliferative/chronic renal lesions.ConclusionsA number of promising urinary biomarkers that correlate with the presence of active renal disease and/or renal biopsy changes were identified and appear to outperform many of the existing proposed biomarkers

Repurposing Albendazole: new potential as a chemotherapeutic agent with preferential activity against HPV-negative head and neck squamous cell cancer.

Albendazole is an anti-helminthic drug that has been shown to exhibit anti-cancer properties, however its activity in head and neck squamous cell cancer (HNSCC) was unknown. Using a series of in vitro assays, we assessed the ability of albendazole to inhibit proliferation in 20 HNSCC cell lines across a range of albendazole doses (1 nM-10 μM). Cell lines that responded to treatment were further examined for cell death, inhibition of migration and cell cycle arrest. Thirteen of fourteen human papillomavirus-negative HNSCC cell lines responded to albendazole, with an average IC50 of 152 nM. In contrast, only 3 of 6 human papillomavirus-positive HNSCC cell lines responded. Albendazole treatment resulted in apoptosis, inhibition of cell migration, cell cycle arrest in the G2/M phase and altered tubulin distribution. Normal control cells were not measurably affected by any dose tested. This study indicates that albendazole acts to inhibit the proliferation of human papillomavirus-negative HNSCC cell lines and thus warrants further study as a potential chemotherapeutic agent for patients suffering from head and neck cancer

Wearable Positive End-Expiratory Pressure Valve Improves Exercise Performance

Positive end-expiratory pressure (PEEP) provides benefits to pulmonary patients, yet effects in healthy, exercising adults are unknown. PURPOSE: We designed two experiments (EXP) to test a novel PEEP (4.2 cmH2O PEEP) mouthpiece (PMP) on maximal cycling performance of physically active volunteers. METHODS: EXP-1 PMP vs. control (CON) mouthpiece (N=9, Age=30±2 yr, Weight=72.2±3.7 kg, BMI=24.4±1.2, 5♂); and EXP-2 PMP vs. no mouthpiece (NMP) (N=10, Age=27±1 yr, Weight=76.7±3.6 kg, BMI=23.9±0.8, ♂). Exercise test procedures for both experiments were identical. On Day 1, under the first mouthpiece condition assigned at random subjects performed graded exercise cycling testing (GXT) (Corival®) for VO2peak (ml*kg*min-1), oxygen pulse (mlO2*bt) (O2pulse), GXT endurance time (s) (GXT-T), and VO2(ml*kg*min-1)-at-ventilatory-threshold (VO2 @VT). Subjects returned 72 h later (Day 2), to complete an endurance ride timed (s)to exhaustion (VTER) at an intensity equivalent to their VO2 @VT power (W). One week later, subjects repeated exercise testing protocols (Days 3 & 4, time-of-day controlled) under the alternate mouthpiece condition. RESULTS: Selected outcomes were as follows (paired T-test, *PMP vs. CON, respectively: VO2peak=45.2±2.4* vs. 42.4±2.3; VO2@VT=33.7±2.0 vs. 32.3±1.6; GXT-T=521.7±73.4* vs. 495.3±72.8; VTER=846.2±166.0 vs. 743.1±124.7; O2pulse=24.5±1.4* vs. 23.1±1.3. PMP vs. NMP, respectively: VO2peak=43.3±1.6* vs. 41.7±1.6; VO2@AT=31.1±1.2* vs. 29.1±1.3; GXT-T=511.7*±49.6 vs. 486.4±49.6; VTER 872.4±134.0 vs. 792.9 ± 122.4; O2pulse=24.1±0.9* vs. 23.4±0.9. CONCLUSION: These results demonstrate that the novel PEEP mouthpiece we tested confers a significant performance benefit to cyclists completing high intensity exercise. By extension, it is likely to be an advantage in any physical activity having an aerobic component

Modeling the cognitive effects of diet discontinuation in adults with phenylketonuria (PKU) using pegvaliase therapy in PAH-deficient mice

Existing phenylalanine hydroxylase (PAH)-deficient mice strains are useful models of untreated or late-treated human phenylketonuria (PKU), as most contemporary therapies can only be initiated after weaning and the pups have already suffered irreversible consequences of chronic hyperphenylalaninemia (HPA) during early brain development. Therefore, we sought to evaluate whether enzyme substitution therapy with pegvaliase initiated near birth and administered repetitively to C57Bl/6-Pahenu2/enu2 mice would prevent HPA-related behavioral and cognitive deficits and form a model for early-treated PKU. The main results of three reported experiments are: 1) lifelong weekly pegvaliase treatment prevented the cognitive deficits associated with HPA in contrast to persisting deficits in mice treated with pegvaliase only as adults. 2) Cognitive deficits reappear in mice treated with weekly pegvaliase from birth but in which pegvaliase is discontinued at 3 months age. 3) Twice weekly pegvaliase injection also prevented cognitive deficits but again cognitive deficits emerged in early-treated animals following discontinuation of pegvaliase treatment during adulthood, particularly in females. In all studies, pegvaliase treatment was associated with complete correction of brain monoamine neurotransmitter content and with improved overall growth of the mice as measured by body weight. Mean total brain weight however remained low in all PAH deficient mice regardless of treatment. Application of enzyme substitution therapy with pegvaliase, initiated near birth and continued into adulthood, to PAH-deficient Pahenu2/enu2 mice models contemporary early-treated human PKU. This model will be useful for exploring the differential pathophysiologic effects of HPA at different developmental stages of the murine brain. Keywords: Behavior; Cognition; Dopamine; Hyperphenylalaninemia; Pegvaliase; Phenylalanine hydroxylase; Phenylketonuria; Serotonin; Tryptophan; Tryptophan hydroxylase; Tyrosine; Tyrosine hydroxylase

Generation of Bianchi type V cosmological models with varying Λ\Lambda-term

Bianchi type V perfect fluid cosmological models are investigated with cosmological term $\Lambda$ varying with time. Using a generation technique (Camci {\it et al.}, 2001), it is shown that the Einstein's field equations are solvable for any arbitrary cosmic scale function. Solutions for particular forms of cosmic scale functions are also obtained. The cosmological constant is found to be decreasing function of time, which is supported by results from recent type Ia supernovae observations. Some physical aspects of the models are also discussed.Comment: 16 pages, 3 figures, submitted to CJ