Cosmic ray isotope measurements with a new Cerenkov X total energy telescope

Measurements of the isotopic composition of cosmic nuclei with Z = 7-20 are reported. These measurements were made with a new version of a Cerenkov x total E telescope. Path length and uniformity corrections are made to all counters to a RMS level 1%. Since the Cerenkov counter is crucial to mass measurements using the C x E technique - special care was taken to optimize the resolution of the 2.4 cm thick Pilot 425 Cerenkov counter. This counter exhibited a beta = 1 muon equivalent LED resolution of 24%, corresponding to a total of 90 p.e. collected at the 1st dynodes of the photomultiplier tubes

Cosmic ray charge and energy spectrum measurements using a new large area Cerenkov x dE/dx telescope

In September, 1981, a new 0.5 square meter ster cosmic ray telescope was flown to study the charge composition and energy spectrum of cosmic ray nuclei between 0.3 and 4 GeV/nuc. A high resolution Cerenkov counter, and three dE/dx measuring scintillation counters, including two position scintillators were contained in the telescope used for the charge and energy spectrum measurements. The analysis procedures did not require any large charge or energy dependent corrections, and absolute fluxes could be obtained to an accuracy approximately 5%. The spectral measurements made in 1981, at a time of extreme solar modulation, could be compared with measurements with a similar telescope made by our group in 1977, at a time of minimum modulation and can be used to derive absolute intensity values for the HEAO measurements made in 1979 to 80. Using both data sets precise energy spectra and abundance ratios can be derived over the entire energy range from 0.3 to greater than 15 GeV/nuc

A new method for studying human polycystic kidney disease epithelia in culture

A new method for studying human polycystic kidney disease epithelia in culture. Human polycystic kidney disease (PKD) epithelia were successfully grown in culture and expressed abnormal characteristics. Cysts lining epithelia of superficial and deep cysts were microdissected and compared to individual normal human proximal straight tubules (PST) and cortical collecting tubules (CCT) grown in defined media. PKD cyst epithelia differed from normal renal tubular epithelia in growth patterns and structural and functional properties. PKD epithelia grew more rapidly and showed cyst–like areas in otherwise confluent monolayers. Polygonal and elongate cells contained an epithelial–specific cytokeratin antigen and had polarized morphology. An extremely abnormal basement membrane morphology was seen and consisted of some banded collagen and numerous unique blebs or spheroids. These blebs were apparently extruded from intracellular vacuoles and stained with ruthenium red, suggesting a proteoglycan component. Cytochemistry of marker enzymes demonstrated the presence of NaK-ATPase and alkaline phosphatase, but a lack of γ-glutamyl transpeptidase. The response of adenylate cyclase activity to vasopressin, parathyroid hormone, and forskolin was significantly diminished in PKD cells as compared to PST and CCT. These studies suggest a defect in cell growth and basement membrane synthesis in human PKD. Cultured PKD epithelia provide a new tool for the study of the pathogenesis of this disease

Characterization of designed, synthetically accessible bryostatin analog HIV latency reversing agents.

HIV latency in resting CD4+ T cell represents a key barrier preventing cure of the infection with antiretroviral drugs alone. Latency reversing agents (LRAs) can activate HIV expression in latently infected cells, potentially leading to their elimination through virus-mediated cytopathic effects, host immune responses, and/or therapeutic strategies targeting cells actively expressing virus. We have recently described several structurally simplified analogs of the PKC modulator LRA bryostatin (termed bryologs) designed to improve synthetic accessibility, tolerability in vivo, and efficacy in inducing HIV latency reversal. Here we report the comparative performance of lead bryologs, including their effects in reducing cell surface expression of HIV entry receptors, inducing proinflammatory cytokines, inhibiting short-term HIV replication, and synergizing with histone deacetylase inhibitors to reverse HIV latency. These data provide unique insights into structure-function relationships between A- and B-ring bryolog modifications and activities in primary cells, and suggest that bryologs represent promising leads for preclinical advancement

Role of chemokines and cytokines in a reactivation model of arthritis in rats induced by injection with streptococcal cell walls

Intraarticular injection of streptococcal cell wall (SCW) antigen followed by intravenous challenge results in a T cellâ mediated monoarticular arthritis in female Lewis rats. Initial studies showed that this reactivation response to intravenous SCW antigen is dependent on the presence of interleukinâ 1 (ILâ 1) and tumor necrosis factor α (TNFâ α) and that the early phase of swelling is neutrophilâ dependent. Neutrophil depletion or passive immunization with antibodies to Pâ selectin or macrophage inflammatory proteinâ 2 reduced the intensity of ankle edema and the influx of neutrophils. After the first few days, however, the arthritic response is mediated primarily by mononuclear cells. Joint tissues showed upâ regulation of mRNA for monocyte chemotactic proteinâ 1 (MCPâ 1), which could be inhibited in part by antiâ ILâ 4; treatment of rats with antibodies to ILâ 4 or MCPâ 1 significantly suppressed development of ankle edema and histopathological evidence of inflammation. Antibodies to interferonâ γ or ILâ 10 had no effect. Treatment with antiâ MCPâ 1 also suppressed influx of 111Inâ labeled T cells into the ankle joint. These data suggest that the late, mononuclearâ dependent phase of SCWâ induced arthritis in female Lewis rats requires cytokines that upâ regulate MCPâ 1, which in turn may facilitate recruitment and extravasation of mononuclear cells into the joint. J. Leukoc. Biol. 63: 359â 363; 1998.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/142294/1/jlb0359.pd

Evaluation of the EndoPAT as a Tool to Assess Endothelial Function

Endothelial dysfunction is a potential target for (pharmaceutical) intervention of several systemic pathological conditions. We investigated the feasibility of the EndoPAT to evaluate acute changes in endothelial function with repeated noninvasive measurements and assessed its discriminating power in different populations. Endothelial function was stable over a longer period of time in renally impaired patients (coefficient of variation 13%). Endothelial function in renally impaired and type 2 diabetic patients was not decreased compared to healthy volunteers (2.9 ± 1.4 and 1.8 ± 0.3, resp., versus 1.8 ± 0.5, P > 0.05). The EndoPAT did not detect an effect of robust interventions on endothelial function in healthy volunteers (glucose load: change from baseline 0.08 ± 0.50, 95% confidence interval −0.44 to 0.60; smoking: change from baseline 0.49 ± 0.92, 95% confidence interval −0.47 to 1.46). This suggests that at present the EndoPAT might not be suitable to assess (changes in) endothelial function in early-phase clinical pharmacology studies. Endothelial function as measured by the EndoPAT could be physiologically different from endothelial function as measured by conventional techniques. This should be investigated carefully before the EndoPAT can be considered a useful tool in drug development or clinical practice

Evaluation of onset, cessation and seasonal precipitation of the Southeast Asia rainy season in CMIP5 regional climate models and HighResMIP global climate models

Representing the rainy season of the maritime continent is a challenge for global and regional climate models. Here, we compare regional climate models (RCMs) based on the coupled model intercomparison project phase 5 (CMIP5) model generation with high-resolution global climate models with a comparable spatial resolution from the HighResMIP experiment. The onset and the total precipitation of the rainy season for both model experiments are compared against observational datasets for Southeast Asia. A realistic representation of the monsoon rainfall is essential for agriculture in Southeast Asia as a delayed onset jeopardizes the possibility of having three annual crops. In general, the coupled historical runs (Hist-1950) and the historical force atmosphere run (HighresSST) of the high-resolution model intercomparison project (HighResMIP) suite were consistently closer to the observations than the RCM of CMIP5 used in this study. We find that for the whole of Southeast Asia, the HighResMIP models simulate the onset date and the total precipitation of the rainy season over the region closer to the observations than the other model sets used in this study. High-resolution models in the HighresSST experiment showed a similar performance to their low-resolution equivalents in simulating the monsoon characteristics. The HighresSST experiment simulated the anomaly of the onset date and the total precipitation for different El Niño-southern oscillation conditions best, although the magnitude of the onset date anomaly was underestimated. © 2021 The Authors. International Journal of Climatology published by John Wiley Sons Ltd on behalf of Royal Meteorological Society

Molecular spintronics: Coherent spin transfer in coupled quantum dots

Time-resolved Faraday rotation has recently demonstrated coherent transfer of electron spin between quantum dots coupled by conjugated molecules. Using a transfer Hamiltonian ansatz for the coupled quantum dots, we calculate the Faraday rotation signal as a function of the probe frequency in a pump-probe setup using neutral quantum dots. Additionally, we study the signal of one spin-polarized excess electron in the coupled dots. We show that, in both cases, the Faraday rotation angle is determined by the spin transfer probabilities and the Heisenberg spin exchange energy. By comparison of our results with experimental data, we find that the transfer matrix element for electrons in the conduction band is of order 0.08 eV and the spin transfer probabilities are of order 10%.Comment: 13 pages, 6 figures; minor change

Renal structure and hypertension in autosomal dominant polycystic kidney disease

Renal structure and hypertension in autosomal dominant polycystic kidney disease. Hypertension has been reported to occur in 50 to 75 percent of subjects with autosomal dominant polycystic kidney disease (ADPKD) prior to the onset of marked renal insufficiency but concurrent with cystic deformation of the renal parenchyma. The present study was undertaken to examine whether the renal structural abnormalities are greater in hypertensive (HBP) versus normotensive (NBP) male and female patients with ADPKD who were matched within gender groups for age, body surface area, serum creatinine concentration (males HBP 1.2 ± 0.02 vs. NBP 1.1 ± 0.03 mg/dl, NS; females HBP 0.9 ± 0.03 vs. NBP 0.9 ± 0.02 mg/dl, NS) and creatinine clearance (males HBP 100 ± 3 vs. NBP 108 ± 3 ml/min/1.73 m2, NS; females HBP 97 ± 3 vs. NBP 96 ± 2 ml/min/1.73 m2, NS). Renal volume was significantly greater in the HBP compared to the NBP group (males HBP 624 ± 47 vs. NBP 390 ± 43 cm3, P < 0.0005; females HBP 466 ± 32 vs. NBP 338 ± 24 cm3, P < 0.002). Since increased renal volume is due to increased cysts, the results indicate that the early high incidence of hypertension in ADPKD correlates with the renal structural abnormalities in this disorder

Reduction of the ATPase inhibitory factor 1 (IF1) leads to visual impairment in vertebrates

In vertebrates, mitochondria are tightly preserved energy producing organelles, which sustain nervous system development and function. The understanding of proteins that regulate their homoeostasis in complex animals is therefore critical and doing so via means of systemic analysis pivotal to inform pathophysiological conditions associated with mitochondrial deficiency. With the goal to decipher the role of the ATPase inhibitory factor 1 (IF1) in brain development, we employed the zebrafish as elected model reporting that the Atpif1a−/− zebrafish mutant, pinotage (pnttq209), which lacks one of the two IF1 paralogous, exhibits visual impairment alongside increased apoptotic bodies and neuroinflammation in both brain and retina. This associates with increased processing of the dynamin-like GTPase optic atrophy 1 (OPA1), whose ablation is a direct cause of inherited optic atrophy. Defects in vision associated with the processing of OPA1 are specular in Atpif1−/− mice thus confirming a regulatory axis, which interlinks IF1 and OPA1 in the definition of mitochondrial fitness and specialised brain functions. This study unveils a functional relay between IF1 and OPA1 in central nervous system besides representing an example of how the zebrafish model could be harnessed to infer the activity of mitochondrial proteins during development