Uncertainty of biomass contributions from agriculture and forestry to renewable energy resources under climate change

In the future, Germany's land-use policies and the impacts of climate change on yields will affect the amount of biomass available for energy production. We used recent published data on biomass potentials in the federal states of Germany to assess the uncertainty caused by climate change effects in the potential supply of biomass available for energy production. In this study we selected three climate scenarios representing the maximum, mean and minimum temperature increase for Germany out of 21 CMIP5-projections driven by the Representative Concentration Pathways (RCP) 8.5 scenario. Each of the three selected projections was downscaled using the regional statistical climate model STARS. We analysed the yield changes of four biomass feedstock crops (forest, short-rotation coppices (SRC), cereal straw (winter wheat) and energy maize) for the period 2031–2060 in comparison to 1981–2010. The mean annual yield changes of energy wood from forest and short-rotation coppices were modelled using the process-based forest growth model 4C. The yield changes of winter wheat and energy maize from agricultural production were simulated with the statistical yield model IRMA. Germany's annual biomass potential of 1500 PJ varies between minus 5 % and plus 8 % depending on the climate scenario realisation. Assuming that 1500 PJ of biomass utilisation can be achieved, climate change effects of minus 75 (5 %) PJ or plus 120 (8 %) PJ do not impede overall bioenergy targets of 1287 PJ in 2020 and 1534 PJ in 2050. In five federal states the climate scenarios lead to decreasing yields of energy maize and winter wheat. Impacts of climate scenarios on forest yields are mainly positive and show both positive and negative effects on yields of SRC

Field Safety Experience with an Autologous Cancer Vaccine in Tumor-Bearing Cats: A Retrospective Study of 117 Cases (2015-2020)

OBJECTIVES: The aim of this study was to determine the frequency and severity of adverse events (AEs) reported from use of an adjuvanted whole-cell autologous cancer vaccine in cats with solid tumors under field conditions. METHODS: The case accession database at Torigen Pharmaceuticals was searched to identify client-owned cats that underwent biopsy or surgical resection of their primary tumor, had histologic confirmation of neoplasia and received at least one subcutaneous dose of an adjuvanted whole-cell autologous cancer vaccine. Records were reviewed for any reported AEs. RESULTS: In total, 117 cats met the inclusion criteria and received 422 doses of autologous cancer vaccine. Six (5.1%) cats had seven reported AEs, with the majority of these (85.7%) being characterized as grade 1 or 2 (mild) and resolving without medical intervention. CONCLUSIONS AND RELEVANCE: AEs were infrequent in cats treated with an adjuvanted whole-cell autologous cancer vaccine under typical field use conditions. This form of active cancer immunotherapy appears to be well tolerated by cats and may represent a treatment option for owners who are concerned about AEs associated with chemotherapy or radiotherapy. Additional studies are warranted to determine the efficacy of this form of individualized immunotherapy in cats with solid tumors

River infiltration to a subtropical alluvial aquifer inferred using multiple environmental tracers

Chloride (Cl−), stable isotope ratios of water (δ18O and δ2H), sulfur hexafluoride (SF6), tritium (3H), carbon-14 (14C), noble gases (4He, Ne, and Ar), and hydrometry were used to characterize groundwater-surface water interactions, in particular infiltration rates, for the Lower Namoi River (New South Wales, Australia). The study period (four sampling campaigns between November 2009 and November 2011) represented the end of a decade-long drought followed by several high-flow events. The hydrometry showed that the river was generally losing to the alluvium, except when storm-derived floodwaves in the river channel generated bank recharge—discharge cycles. Using 3H/14C-derived estimates of groundwater mean residence time along the transect, infiltration rates ranged from 0.6 to 5 m yr−1. However, when using the peak transition age (a more realistic estimate of travel time in highly dispersive environments), the range in infiltration rate was larger (4–270 m yr−1). Both river water (highest δ2H, δ18O, SF6, 3H, and 14C) and an older groundwater source (lowest δ2H, δ18O, SF6, 3H, 14C, and highest 4He) were found in the riparian zone. This old groundwater end-member may represent leakage from an underlying confined aquifer (Great Artesian Basin). Environmental tracers may be used to estimate infiltration rates in this riparian environment but the presence of multiple sources of water and a high dispersion induced by frequent variations in the water table complicates their interpretation

ARHGEF9 disease: Phenotype clarification and genotype-phenotype correlation.

ObjectiveWe aimed to generate a review and description of the phenotypic and genotypic spectra of ARHGEF9 mutations.MethodsPatients with mutations or chromosomal disruptions affecting ARHGEF9 were identified through our clinics and review of the literature. Detailed medical history and examination findings were obtained via a standardized questionnaire, or if this was not possible by reviewing the published phenotypic features.ResultsA total of 18 patients (including 5 females) were identified. Six had de novo, 5 had maternally inherited mutations, and 7 had chromosomal disruptions. All females had strongly skewed X-inactivation in favor of the abnormal X-chromosome. Symptoms presented in early childhood with delayed motor development alone or in combination with seizures. Intellectual disability was severe in most and moderate in patients with milder mutations. Males with severe intellectual disability had severe, often intractable, epilepsy and exhibited a particular facial dysmorphism. Patients with mutations in exon 9 affecting the protein's PH domain did not develop epilepsy.ConclusionsARHGEF9 encodes a crucial neuronal synaptic protein; loss of function of which results in severe intellectual disability, epilepsy, and a particular facial dysmorphism. Loss of only the protein's PH domain function is associated with the absence of epilepsy

Airspace Diameter Map-A Quantitative Measurement of All Pulmonary Airspaces to Characterize Structural Lung Diseases.

(1) Background: Stereological estimations significantly contributed to our understanding of lung anatomy and physiology. Taking stereology fully 3-dimensional facilitates the estimation of novel parameters. (2) Methods: We developed a protocol for the analysis of all airspaces of an entire lung. It includes (i) high-resolution synchrotron radiation-based X-ray tomographic microscopy, (ii) image segmentation using the free machine-learning tool Ilastik and ImageJ, and (iii) calculation of the airspace diameter distribution using a diameter map function. To evaluate the new pipeline, lungs from adult mice with cystic fibrosis (CF)-like lung disease (βENaC-transgenic mice) or mice with elastase-induced emphysema were compared to healthy controls. (3) Results: We were able to show the distribution of airspace diameters throughout the entire lung, as well as separately for the conducting airways and the gas exchange area. In the pathobiological context, we observed an irregular widening of parenchymal airspaces in mice with CF-like lung disease and elastase-induced emphysema. Comparable results were obtained when analyzing lungs imaged with μCT, sugges-ting that our pipeline is applicable to different kinds of imaging modalities. (4) Conclusions: We conclude that the airspace diameter map is well suited for a detailed analysis of unevenly distri-buted structural alterations in chronic muco-obstructive lung diseases such as cystic fibrosis and COPD

Capillary Assembly of Anisotropic Particles at Cylindrical Fluid-Fluid Interfaces

The unique behavior of colloids at liquid interfaces provides exciting opportunities for engineering the assembly of colloidal particles into functional materials. The deformable nature of fluid-fluid interfaces means that we can use the interfacial curvature, in addition to particle properties, to direct self-assembly. To this end, we use a finite element method (Surface Evolver) to study the self-assembly of rod-shaped particles adsorbed at a simple curved fluid-fluid interface formed by a sessile liquid drop with cylindrical geometry. Specifically, we study the self-assembly of single and multiple rods as a function of drop curvature and particle properties such as shape (ellipsoid, cylinder, and spherocylinder), contact angle, aspect ratio, and chemical heterogeneity (homogeneous and triblock patchy). We find that the curved interface allows us to effectively control the orientation of the rods, allowing us to achieve parallel, perpendicular, or novel obliquely orientations with respect to the cylindrical drop. In addition, by tuning particle properties to achieve parallel alignment of the rods, we show that the cylindrical drop geometry favors tip-to-tip assembly of the rods, not just for cylinders, but also for ellipsoids and triblock patchy rods. Finally, for triblock patchy rods with larger contact line undulations, we can achieve strong spatial confinement of the rods transverse to the cylindrical drop due to the capillary repulsion between the contact line undulations of the particle and the pinned contact lines of the sessile drop. Our capillary assembly method allows us to manipulate the configuration of single and multiple rod-like particles and therefore offers a facile strategy for organizing such particles into useful functional materials

Discovery of antibiotic (E)-3-(3-carboxyphenyl)-2-(4-cyanostyryl)quinazolin-4(3 H)-one

© 2015 American Chemical Society. In the face of the clinical challenge posed by resistant bacteria, the present needs for novel classes of antibiotics are genuine. In silico docking and screening, followed by chemical synthesis of a library of quinazolinones, led to the discovery of (E)-3-(3-carboxyphenyl)-2-(4-cyanostyryl)quinazolin-4(3H)-one (compound 2) as an antibiotic effective in vivo against methicillin-resistant Staphylococcus aureus (MRSA). This antibiotic impairs cell-wall biosynthesis as documented by functional assays, showing binding of 2 to penicillin-binding protein (PBP) 2a. We document that the antibiotic also inhibits PBP1 of S. aureus, indicating a broad targeting of structurally similar PBPs by this antibiotic. This class of antibiotics holds promise in fighting MRSA infections.Peer Reviewe

Functional and clinical studies reveal pathophysiological complexity of CLCN4-related neurodevelopmental condition

Missense and truncating variants in the X-chromosome-linked CLCN4 gene, resulting in reduced or complete loss-of-function (LOF) of the encoded chloride/proton exchanger ClC-4, were recently demonstrated to cause a neurocognitive phenotype in both males and females. Through international clinical matchmaking and interrogation of public variant databases we assembled a database of 90 rare CLCN4 missense variants in 90 families: 41 unique and 18 recurrent variants in 49 families. For 43 families, including 22 males and 33 females, we collated detailed clinical and segregation data. To confirm causality of variants and to obtain insight into disease mechanisms, we investigated the effect on electrophysiological properties of 59 of the variants in Xenopus oocytes using extended voltage and pH ranges. Detailed analyses revealed new pathophysiological mechanisms: 25% (15/59) of variants demonstrated LOF, characterized by a “shift” of the voltage-dependent activation to more positive voltages, and nine variants resulted in a toxic gain-of-function, associated with a disrupted gate allowing inward transport at negative voltages. Functional results were not always in line with in silico pathogenicity scores, highlighting the complexity of pathogenicity assessment for accurate genetic counselling. The complex neurocognitive and psychiatric manifestations of this condition, and hitherto under-recognized impacts on growth, gastrointestinal function, and motor control are discussed. Including published cases, we summarize features in 122 individuals from 67 families with CLCN4-related neurodevelopmental condition and suggest future research directions with the aim of improving the integrated care for individuals with this diagnosis

Early Antiretroviral Therapy Reduces AIDS Progression/Death in Individuals with Acute Opportunistic Infections: A Multicenter Randomized Strategy Trial

Background: Optimal timing of ART initiation for individuals presenting with AIDS-related OIs has not been defined. Methods and Findings: A5164 was a randomized strategy trial of ‘‘early ART’’ - given within 14 days of starting acute OI treatment versus ‘‘deferred ART’’ - given after acute OI treatment is completed. Randomization was stratified by presenting OI and entry CD4 count. The primary week 48 endpoint was 3-level ordered categorical variable: 1. Death/AIDS progression; 2. No progression with incomplete viral suppression (ie HIV viral load (VL) [greater than or equal to] 50 copies/ml); 3. No progression with optimal viral suppression (ie HIV VL <50 copies/ml). Secondary endpoints included: AIDS progression/death; plasma HIV RNA and CD4 responses and safety parameters including IRIS. 282 subjects were evaluable; 141 per arm. Entry OIs included Pneumocytis jirovecii pneumonia 63%, cryptococcal meningitis 12%, and bacterial infections 12%. The early and deferred arms started ART a median of 12 and 45 days after start of OI treatment, respectively. The difference in the primary endpoint did not reach statistical significance: AIDS progression/death was seen in 20 (14%) vs. 34 (24%); whereas no progression but with incomplete viral suppression was seen in 54 (38%) vs. 44 (31%); and no progression with optimal viral suppression in 67 (48%) vs 63 (45%) in the early vs. deferred arm, respectively (p = 0.22). However, the early ART arm had fewer AIDS progression/deaths (OR = 0.51; 95% CI = 0.27–0.94) and a longer time to AIDS progression/death (stratified HR = 0.53; 95% CI = 0.30–0.92). The early ART had shorter time to achieving a CD4 count above 50 cells/mL (p<0.001) and no increase in adverse events. Conclusions: Early ART resulted in less AIDS progression/death with no increase in adverse events or loss of virologic response compared to deferred ART. These results support the early initiation of ART in patients presenting with acute AIDS-related OIs, absent major contraindications