Semiarid watershed response in central New Mexico and its sensitivity to climate variability and change

Hydrologic processes in the semiarid regions of the Southwest United States are considered to be highly susceptible to variations in temperature and precipitation characteristics due to the effects of climate change. Relatively little is known about the potential impacts of climate change on the basin hydrologic response, namely streamflow, evapotranspiration and recharge, in the region. In this study, we present the development and application of a continuous, semi-distributed watershed model for climate change studies in semiarid basins of the Southwest US. Our objective is to capture hydrologic processes in large watersheds, while accounting for the spatial and temporal variations of climate forcing and basin properties in a simple fashion. We apply the model to the Río Salado basin in central New Mexico since it exhibits both a winter and summer precipitation regime and has a historical streamflow record for model testing purposes. Subsequently, we use a sequence of climate change scenarios that capture observed trends for winter and summer precipitation, as well as their interaction with higher temperatures, to perform long-term ensemble simulations of the basin response. Results of the modeling exercise indicate that precipitation uncertainty is amplified in the hydrologic response, in particular for processes that depend on a soil saturation threshold. We obtained substantially different hydrologic sensitivities for winter and summer precipitation ensembles, indicating a greater sensitivity to more intense summer storms as compared to more frequent winter events. In addition, the impact of changes in precipitation characteristics overwhelmed the effects of increased temperature in the study basin. Nevertheless, combined trends in precipitation and temperature yield a more sensitive hydrologic response throughout the year

Pharmacology of DB844, an orally active aza analogue of pafuramidine, in a monkey model of second stage human African trypanosomiasis

Novel drugs to treat human African trypanosomiasis (HAT) are still urgently needed despite the recent addition of nifurtimox-eflornithine combination therapy (NECT) to WHO Model Lists of Essential Medicines against second stage HAT, where parasites have invaded the central nervous system (CNS). The pharmacology of a potential orally available lead compound, N-methoxy-6-{5-[4-(N-methoxyamidino) phenyl]-furan-2-yl}-nicotinamidine (DB844), was evaluated in a vervet monkey model of second stage HAT, following promising results in mice. DB844 was administered orally to vervet monkeys, beginning 28 days post infection (DPI) with Trypanosoma brucei rhodesiense KETRI 2537. DB844 was absorbed and converted to the active metabolite 6-[5-(4-phenylamidinophenyl)-furanyl-2-yl]-nicotinamide (DB820), exhibiting plasma C(max) values of 430 and 190 nM for DB844 and DB820, respectively, after the 14th dose at 6 mg/kg qd. A 100-fold reduction in blood trypanosome counts was observed within 24 h of the third dose and, at the end of treatment evaluation performed four days post the last drug dose, trypanosomes were not detected in the blood or cerebrospinal fluid of any monkey. However, some animals relapsed during the 300 days of post treatment monitoring, resulting in a cure rate of 3/8 (37.5%) and 3/7 (42.9%) for the 5 mg/kg×10 days and the 6 mg/kg×14 days dose regimens respectively. These DB844 efficacy data were an improvement compared with pentamidine and pafuramidine both of which were previously shown to be non-curative in this model of CNS stage HAT. These data show that synthesis of novel diamidines with improved activity against CNS-stage HAT was possible

Discrete Cylindrical Vector Beam Generation from an Array of Optical Fibers

A novel method is presented for the beam shaping of far field intensity distributions of coherently combined fiber arrays. The fibers are arranged uniformly on the perimeter of a circle, and the linearly polarized beams of equal shape are superimposed such that the far field pattern represents an effective radially polarized vector beam, or discrete cylindrical vector (DCV) beam. The DCV beam is produced by three or more beams that each individually have a varying polarization vector. The beams are appropriately distributed in the near field such that the far field intensity distribution has a central null. This result is in contrast to the situation of parallel linearly polarized beams, where the intensity peaks on axis

Generation of a wave packet tailored to efficient free space excitation of a single atom

We demonstrate the generation of an optical dipole wave suitable for the process of efficiently coupling single quanta of light and matter in free space. We employ a parabolic mirror for the conversion of a transverse beam mode to a focused dipole wave and show the required spatial and temporal shaping of the mode incident onto the mirror. The results include a proof of principle correction of the parabolic mirror's aberrations. For the application of exciting an atom with a single photon pulse we demonstrate the creation of a suitable temporal pulse envelope. We infer coupling strengths of 89% and success probabilities of up to 87% for the application of exciting a single atom for the current experimental parameters.Comment: to be published in Europ. Phys. J.

A History of the Men\u27s Physical Education Program at Utah State Agricultural College

This study will present a historical review of the men\u27s physical education program at Utah State Agricultural College from 1888 through 1954. Specifically, it will give special attention to: (1) philosophy, (2) organization and administration, (3) leadership, (4) equipment and facilities, and (5) program

3D in vitro cancer models for drug screening: A study of glucose metabolism and drug response in 2D and 3D culture models

Current drug screening protocols use in vitro cancer cell panels grown in 2D to evaluate drug response and select the most promising candidates for further in vivo testing. Most drug candidates fail at this stage, not showing the same efficacy in vivo as seen in vitro. An improved first screening that is more translatable to the in vivo tumor situation could aid in reducing both time and cost of cancer drug development. 3D cell cultures are an emerging standard for in vitro cancer cell models, being more representative of in vivo tumour conditions. To overcome the translational challenges with 2D cell cultures, 3D systems better model the more complex cell-to-cell contact and nutrient levels present in a tumour, improving our understanding of cancer complexity. Furthermore, cancer cells exhibit altered metabolism, a phenomenon described a century ago by Otto Warburg, and possibly related to changes in nutrient access. However, there are few reports on how 3D cultures differ metabolically from 2D cultures, especially when grown in physiological glucose conditions. Along with this, metabolic drug targeting is considered an underutilized and poorly understood area of cancer therapy. Therefore, the aim of this work was to investigate the effect of culture conditions on response to metabolic drugs and study the metabolism of 3D spheroid cultures in detail. To achieve this, multiple cancer cell lines were studied in high and low glucose concentrations and in 2D and 3D cultures. We found that glucose concentration is important at a basic level for growth properties of cell lines with different metabolic phenotypes and it affects sensitivity to metformin. Furthermore, metformin is able to shift metabolic phenotype away from OXPHOS dependency. There are significant differences in glucose metabolism of 3D cultures compared to 2D cultures, both related to glycolysis and oxidative phosphorylation. Spheroids have higher ATP-linked respiration in standard nutrient conditions and higher non-aerobic ATP production in the absence of supplemented glucose. Multi-round treatment of spheroids is able to show more robust response than standard 2D drug screening, including resistance to therapy. Results from 2D cultures both over and underestimate drug response at different concentrations of 5-fluorouracil (5-FU). A higher maximum effect of 5-FU is seen in models with lower OCR/ECAR ratios, an indication of a more glycolytic metabolic phenotype. In conclusion, both culture method and nutrient conditions are important consideration for in vitro cancer models. There is good reason to not maintain in vitro cultures in artificially high glucose conditions. It can have downstream affects on drug response and likely other important metrics. If possible, assays should also be implemented in 3D. If not in everyday assays, at least as a required increase in complexity to validate 2D results. Finally, metabolism even in the small scope presented here, is complex in terms of phenotypic variation. This shows the importance of metabolic screening in vitro to better understand the effects of these small changes and to model how a specific tumor may behave based on its complex metabolism

Burmese amber fossils bridge the gap in the Cretaceous record of polypod ferns

publisher: Elsevier articletitle: Burmese amber fossils bridge the gap in the Cretaceous record of polypod ferns journaltitle: Perspectives in Plant Ecology, Evolution and Systematics articlelink: http://dx.doi.org/10.1016/j.ppees.2016.01.003 content_type: article copyright: Copyright © 2016 Elsevier GmbH. All rights reserved.Copyright © 2016 Elsevier GmbH. All rights reserved. This document is the authors' final accepted version of the journal article. You are advised to consult the publisher's version if you wish to cite from it

Efficacy of DB289 in Thai Patients with Plasmodium vivax or Acute, Uncomplicated Plasmodium falciparum Infections

BackgroundDB289 is the orally active prodrug of the diamidine DB75, which was developed for the treatment of human African trypanosomiasis MethodsWe tested the safety and efficacy of DB289 for the treatment of Plasmodium vivax and acute, uncomplicated P. falciparum infections in an open-label pilot study at the Hospital for Tropical Diseases in Bangkok. Nine patients with P. vivax infections and 23 patients with P. falciparum infections were admitted and treated with 100 mg of DB289 given orally twice a day for 5 days and were followed for 28 days. Patients with P. vivax infections were also treated with primaquine on days 10-23 ResultsAll patients cleared parasites by day 7, with a mean±SD clearance time of 43±41 h. One patient with a P. vivax infection had a recurrence of parasitemia on day 9. Of the 23 patients with P. falciparum infections, 3 had recurrences of parasitemia caused by P. vivax and 2 had recurrences of parasitemia caused by P. falciparum. In only 1 of 2 recurrences of parasitemia caused by P. falciparum were the parasites genotypically distinct from the infecting parasites the patient had at enrollment, which means there was a 96% cure rate ConclusionsDB289 is a promising new antimalarial compound that could become an important component of new antimalarial combination

Efficacy, safety, and dose of Pafuramidine, a new oral drug for treatment of first stage sleeping sickness, in a phase 2a clinical study and phase 2b randomized clinical studies

Sleeping sickness (human African trypanosomiasis [HAT]) is caused by protozoan parasites and characterized by a chronic progressive course, which may last up to several years before death. We conducted two Phase 2 studies to determine the efficacy and safety of oral pafuramidine in African patients with first stage HAT.; The Phase 2a study was an open-label, non-controlled, proof-of-concept study where 32 patients were treated with 100 mg of pafuramidine orally twice a day (BID) for 5 days at two trypanosomiasis reference centers (Angola and the Democratic Republic of the Congo [DRC]) between August 2001 and November 2004. The Phase 2b study compared pafuramidine in 41 patients versus standard pentamidine therapy in 40 patients. The Phase 2b study was open-label, parallel-group, controlled, randomized, and conducted at two sites in the DRC between April 2003 and February 2007. The Phase 2b study was then amended to add an open-label sequence (Phase 2b-2), where 30 patients received pafuramidine for 10 days. The primary efficacy endpoint was parasitologic cure at 24 hours (Phase 2a) or 3 months (Phase 2b) after treatment completion. The primary safety outcome was the rate of occurrence of World Health Organization Toxicity Scale Grade 3 or higher adverse events. All subjects provided written informed consent.; Pafuramidine for the treatment of first stage HAT was comparable in efficacy to pentamidine after 10 days of dosing. The cure rates 3 months post-treatment were 79% in the 5-day pafuramidine, 100% in the 7-day pentamidine, and 93% in the 10-day pafuramidine groups. In Phase 2b, the percentage of patients with at least 1 treatment-emergent adverse event was notably higher after pentamidine treatment (93%) than pafuramidine treatment for 5 days (25%) and 10 days (57%). These results support continuation of the development program for pafuramidine into Phase 3

Performance evaluation of turbulence-accentuated interchannel crosstalk for hybrid fibre and free-space optical wavelength-division-multiplexing systems using digital pulse-position modulation

A hybrid fibre and free-space optical communication link using digital pulse-position modulation (DPPM) in a wavelength-division-multiplexing system is proposed. Such a system, which could provide a power efficient, robust and flexible solution to high-speed access networks, is a contender for a passive optical network solution and could readily be deployed in areas with restrictions in optical fibre installation, or alternatively as a disaster recovery network. Interchannel crosstalk and atmospheric turbulence are major impairments in such a system and could combine in some cases to degrade the system. Both impairments are investigated here and the results are presented in the form of bit error probability, required optical transmission power and power penalties. Depending on the position of the interferer relative to the desired user, power penalties of about 0.2–3.0 dB for weak turbulence and above 20 dB for strong turbulence regimes are reported for bit error rate of 10−6. DPPM scheme with a coding level of 2 show about 2 dB improvements over on–off-keying scheme