Application of a stochastic weather generator to assess climate change impacts in a semi-arid climate: The Upper Indus Basin

Assessing local climate change impacts requires downscaling from Global Climate Model simulations. Here, a stochastic rainfall model (RainSim) combined with a rainfall conditioned weather generator (CRU WG) have been successfully applied in a semi-arid mountain climate, for part of the Upper Indus Basin (UIB), for point stations at a daily time-step to explore climate change impacts. Validation of the simulated time-series against observations (1961–1990) demonstrated the models’ skill in reproducing climatological means of core variables with monthly RMSE of <2.0 mm for precipitation and ⩽0.4 °C for mean temperature and daily temperature range. This level of performance is impressive given complexity of climate processes operating in this mountainous context at the boundary between monsoonal and mid-latitude (westerly) weather systems. Of equal importance the model captures well the observed interannual variability as quantified by the first and last decile of 30-year climatic periods. Differences between a control (1961–1990) and future (2071–2100) regional climate model (RCM) time-slice experiment were then used to provide change factors which could be applied within the rainfall and weather models to produce perturbed ‘future’ weather time-series. These project year-round increases in precipitation (maximum seasonal mean change:+27%, annual mean change: +18%) with increased intensity in the wettest months (February, March, April) and year-round increases in mean temperature (annual mean +4.8 °C). Climatic constraints on the productivity of natural resource-dependent systems were also assessed using relevant indices from the European Climate Assessment (ECA) and indicate potential future risk to water resources and local agriculture. However, the uniformity of projected temperature increases is in stark contrast to recent seasonally asymmetrical trends in observations, so an alternative scenario of extrapolated trends was also explored. We conclude that interannual variability in climate will continue to have the dominant impact on water resources management whichever trajectory is followed. This demonstrates the need for sophisticated downscaling methods which can evaluate changes in variability and sequencing of events to explore climate change impacts in this region

The Use of Bone Morphogenetic Protein in the Intervertebral Disk Space in Minimally Invasive Transforaminal Lumbar Interbody Fusion

Study Design: Retrospective Cohort. Objective: The objective of this study was to characterize one surgeon’s experience over a 10-year period using rhBMP-2 in the disk space for minimally invasive transforaminal lumbar interbody fusion (MIS TLIF). Summary of Background Data: MIS TLIF has been utilized as a technique for decreasing patients’ immediate postoperative pain, decreasing blood loss, and shortened hospital stays. Effectiveness and complications of rhBMP-2’s use in the disk space is limited because of its off-label status. Methods: Retrospective analysis of consecutive MIS TLIFs performed by senior author between 2004 and 2014. rhBMP-2 was used in the disk space in all cases. Patients were stratified based on the dose of rhBMP-2 utilized. Patients had 9 to 12 month computerized tomography scan to evaluate for bony fusion and continued follow-up for 18 months. Results: A total of 688 patients underwent a MIS TLIF. A medium kit of rhBMP-2 was utilized in 97 patients, and small kit was used in 591 patients. Fusion rate was 97.9% and this was not different between the 2 groups with 96/97 patients fusing in the medium kit group and 577/591 patients fusing in the small kit group. Five patients taken back to the operating room for symptomatic pseudoarthrosis, 4 reoperated for bony hyperostosis, and 10 radiographic pseudoarthroses that did not require reoperation. A statistically significant difference in the rate of foraminal hyperostosis was found when using a medium sized kit of rhBMP-2 was 4.12% (4/97 patients), compared with a small kit (0/591 patients, P=0.0004). Conclusions: Utilization of rhBMP-2 in an MIS TLIF leads to high fusion rate (97.9%), with an acceptable complication profile. The development of foraminal hyperostosis is a rare complication that only affected 0.6% of patients, and seems to be a dose related complication, as this complication was eliminated when a lower dose of rhBMP-2 was utilized

Gaming in the library

Paper completed for Emerging Technologies, 9410 Seminar in Information Science and Learning Technology, Fall 2015, School of Information Science & Technologies, University of Missouri.Libraries are vital public spaces which benefit from a variety of collections. While video games may be a relative newcomer, board games have had a place in libraries since at least 1933 (“Broadening our definition,” 2008, p. 7) and promote “collaboration, inquiry, and critical thinking” (Crews, 2011, p. 10). For a new generation intent on having fun while learning, games can be a vital resource to improve social skills, problem solving, and leadership development (“Broadening the audience,” 2008, p. 28). Here are ten online resources to help librarians build a game collection, collaborate with other librarians, start a game night, or just learn more about how games can contribute to the mission of the library.Includes bibliographical references (page 4)

Generation of defects and disorder from deeply quenching a liquid to form a solid

We show how deeply quenching a liquid to temperatures where it is linearly unstable and the crystal is the equilibrium phase often produces crystalline structures with defects and disorder. As the solid phase advances into the liquid phase, the modulations in the density distribution created behind the advancing solidification front do not necessarily have a wavelength that is the same as the equilibrium crystal lattice spacing. This is because in a deep enough quench the front propagation is governed by linear processes, but the crystal lattice spacing is determined by nonlinear terms. The wavelength mismatch can result in significant disorder behind the front that may or may not persist in the latter stage dynamics. We support these observations by presenting results from dynamical density functional theory calculations for simple one- and two-component two-dimensional systems of soft core particles.Comment: 25 pages, 11 figure

HIV-1 Conserved Mosaics Delivered by Regimens with Integration-deficient, DC-targeting Lentivirus Induce Robust T Cells

Background: To be effective against HIV-1, vaccine-induced T cells must selectively target functionally conserved and, at the same time, protective epitopes present on the majority of currently circulating and reactivated HIV-1 strains, and rapidly reach protective frequencies upon exposure to the virus. Heterologous prime-boost regimens using virally vectored vaccines are currently the most promising strategy towards achieving this goal, nevertheless, induction of robust longterm memory remains challenging. To this end, lentiviral vectors induce high frequencies of memory cells due to their low-inflammatory nature, while typically inducing only low antivector immune responses. Methods: We describe construction of novel candidate vaccines ZVex.tHIVconsv1 and ZVex.tHIVconsv2, which are based on an integration-deficient lentiviral vector platform with preferential transduction of human dendritic cells and express bivalent mosaic of conserved-region T-cell immunogens with a high global HIV-1 match. Results: Each of the two mosaics was individually immunogenic and together in heterologous prime-boost regimens with nonreplicating simian (chimpanzee) adenovirus or non-replicating poxvirus MVA vaccines induced very high frequencies of plurifunctional and broadly cross-reactive T cells in BALB/c and outbred CD1-SWISS mice. Conclusions: These data support further development of this vaccine concept

Metabolite-dependent regulation of gene expression in trypanosoma brucei

Mechanisms regulating gene expression in trypanosomatid protozoa differ significantly from those in other eukaryotes. Transcription of the genome appears to be more or less constitutive with the polyadenylation and trans-splicing of large polycistronic RNAs producing monocistronic RNAs whose translation may then depend upon information within their 3′ untranslated regions (3′UTRs). Various 3′UTR sequences involved in life-cycle stage-dependent differential gene expression have been described. Moreover, several RNA-binding proteins have been implicated in regulating expression of these transcripts through altering either their stability or their ability to interact with ribosomes. In this issue of Molecular Microbiology Xiao et al. report on a regulatory element within the 3′UTR of the transcript that encodes the polyamine pathway regulatory protein called prozyme. It appears that the RNA element controls translation of the prozyme RNA causing expression to be upregulated when levels of decarboxylated S-adenosylmethionine (dcAdoMet) are depleted. Since prozyme activates the enzyme S-adenosylmethionine decarboxylase (AdoMetDC), which is responsible for the production of dcAdoMet, losing this metabolite leads to upregulation of prozyme, activation of AdoMetDC and restoration of optimal levels of dcAdomet. The system thus represents a novel metabolite-sensing regulatory circuit that maintains polyamine homeostasis in these cells

HIV-1 Conserved Mosaics Delivered by Regimens with Integration-Deficient DC-Targeting Lentiviral Vector Induce Robust T Cells

To be effective against HIV type 1 (HIV-1), vaccine-induced T cells must selectively target epitopes, which are functionally conserved (present in the majority of currently circulating and reactivated HIV-1 strains) and, at the same time, beneficial (responses to which are associated with better clinical status and control of HIV-1 replication), and rapidly reach protective frequencies upon exposure to the virus. Heterologous prime-boost regimens using virally vectored vaccines are currently the most promising vaccine strategies; nevertheless, induction of robust long-term memory remains challenging. To this end, lentiviral vectors induce high frequencies of memory cells due to their low-inflammatory nature, while typically inducing only low anti-vector immune responses. Here, we describe construction of novel candidate vaccines ZVex.tHIVconsv1 and ZVex.tHIVconsv2, which are based on an integration-deficient lentiviral vector platform with preferential transduction of human dendritic cells and express a bivalent mosaic of conserved-region T cell immunogens with a high global HIV-1 match. Each of the two mosaic vaccines was individually immunogenic. When administered together in heterologous prime-boost regimens with chimpanzee adenovirus and/or poxvirus modified vaccinia virus Ankara (MVA) vaccines to BALB/c and outbred CD1-Swiss mice, they induced a median frequency of over 6,000 T cells/10^6splenocytes, which were plurifunctional, broadly specific, and cross-reactive. These results support further development of this vaccine concept

Management of Intracranial Meningiomas Using Keyhole Techniques

BACKGROUND: Keyhole craniotomies are increasingly being used for lesions of the skull base. Here we review our recent experience with these approaches for resection of intracranial meningiomas. METHODS: Clinical and operative data were gathered on all patients treated with keyhole approaches by the senior author from January 2012 to June 2013. Thirty-one meningiomas were resected in 27 patients, including 9 supratentorial, 5 anterior fossa, 7 middle fossa, 6 posterior fossa, and 4 complex skull base tumors. Twenty-nine tumors were WHO Grade I, and 2 were Grade II. RESULTS: The mean operative time was 8 hours, 22 minutes (range, 2:55-16:14) for skull-base tumors, and 4 hours, 27 minutes (range, 1:45-7:13) for supratentorial tumors. Simpson Resection grades were as follows: Grade I = 8, II = 8, III = 1, IV = 15, V = 0. The median postoperative hospital stay was 4 days (range, 1-20 days). In the 9 patients presenting with some degree of visual loss, 7 saw improvement or complete resolution. In the 6 patients presenting with cranial nerve palsies, 4 experienced improvement or resolution of the deficit postoperatively. Four patients experienced new neurologic deficits, all of which were improved or resolved at the time of the last follow-up. Technical aspects and surgical nuances of these approaches for management of intracranial meningiomas are discussed. CONCLUSIONS: With careful preoperative evaluation, keyhole approaches can be utilized singly or in combination to manage meningiomas in a wide variety of locations with satisfactory results

HIV-1 Conserved Mosaics Delivered by Regimens with Integration-deficient, DC-targeting Lentivirus Induce Robust T Cells

Background: To be effective against HIV-1, vaccine-induced T cells must selectively target functionally conserved and, at the same time, protective epitopes present on the majority of currently circulating and reactivated HIV-1 strains, and rapidly reach protective frequencies upon exposure to the virus. Heterologous prime-boost regimens using virally vectored vaccines are currently the most promising strategy towards achieving this goal, nevertheless, induction of robust longterm memory remains challenging. To this end, lentiviral vectors induce high frequencies of memory cells due to their low-inflammatory nature, while typically inducing only low antivector immune responses. Methods: We describe construction of novel candidate vaccines ZVex.tHIVconsv1 and ZVex.tHIVconsv2, which are based on an integration-deficient lentiviral vector platform with preferential transduction of human dendritic cells and express bivalent mosaic of conserved-region T-cell immunogens with a high global HIV-1 match. Results: Each of the two mosaics was individually immunogenic and together in heterologous prime-boost regimens with nonreplicating simian (chimpanzee) adenovirus or non-replicating poxvirus MVA vaccines induced very high frequencies of plurifunctional and broadly cross-reactive T cells in BALB/c and outbred CD1-SWISS mice. Conclusions: These data support further development of this vaccine concept

HIV-1 Conserved Mosaics Delivered by Regimens with Integration-Deficient DC-Targeting Lentiviral Vector Induce Robust T Cells

To be effective against HIV type 1 (HIV-1), vaccine-induced T cells must selectively target epitopes, which are functionally conserved (present in the majority of currently circulating and reactivated HIV-1 strains) and, at the same time, beneficial (responses to which are associated with better clinical status and control of HIV-1 replication), and rapidly reach protective frequencies upon exposure to the virus. Heterologous prime-boost regimens using virally vectored vaccines are currently the most promising vaccine strategies; nevertheless, induction of robust long-term memory remains challenging. To this end, lentiviral vectors induce high frequencies of memory cells due to their low-inflammatory nature, while typically inducing only low anti-vector immune responses. Here, we describe construction of novel candidate vaccines ZVex.tHIVconsv1 and ZVex.tHIVconsv2, which are based on an integration-deficient lentiviral vector platform with preferential transduction of human dendritic cells and express a bivalent mosaic of conserved-region T cell immunogens with a high global HIV-1 match. Each of the two mosaic vaccines was individually immunogenic. When administered together in heterologous prime-boost regimens with chimpanzee adenovirus and/or poxvirus modified vaccinia virus Ankara (MVA) vaccines to BALB/c and outbred CD1-Swiss mice, they induced a median frequency of over 6,000 T cells/10^6splenocytes, which were plurifunctional, broadly specific, and cross-reactive. These results support further development of this vaccine concept