Can carbon emissions from tropical deforestation drop by 50% in 5 years?

Halving carbon emissions from tropical deforestation by 2020 could help bring the international community closer to the agreed goal of <2 degree increase in global average temperature change and is consistent with a target set last year by the governments, corporations, indigenous peoples' organizations and non‐governmental organizations that signed the New York Declaration on Forests (NYDF). We assemble and refine a robust dataset to establish a 2001–2013 benchmark for average annual carbon emissions from gross tropical deforestation at 2.270 Gt CO₂ yr^?1. Brazil did not sign the NYDF, yet from 2001 to 2013, Brazil ranks first for both carbon emissions from gross tropical deforestation and reductions in those emissions – its share of the total declined from a peak of 69% in 2003 to a low of 20% in 2012. Indonesia, an NYDF signatory, is the second highest emitter, peaking in 2012 at 0.362 Gt CO₂ yr^?1 before declining to 0.205 Gt CO₂ yr^?1 in 2013. The other 14 NYDF tropical country signatories were responsible for a combined average of 0.317 Gt CO₂ yr^?1, while the other 86 tropical country non‐signatories were responsible for a combined average of 0.688 Gt CO₂ yr^?1. We outline two scenarios for achieving the 50% emission reduction target by 2020, both emphasizing the critical role of Brazil and the need to reverse the trends of increasing carbon emissions from gross tropical deforestation in many other tropical countries that, from 2001 to 2013, have largely offset Brazil's reductions. Achieving the target will therefore be challenging, even though it is in the self‐interest of the international community. Conserving rather than cutting down tropical forests requires shifting economic development away from a dependence on natural resource depletion toward recognition of the dependence of human societies on the natural capital that tropical forests represent and the goods and services they provide.     

Force-field parameters for beryllium complexes in amorphous layers

Unknown force-field parameters for metal organic beryllium complexes used in emitting and electron transporting layers of OLED structures are determined. These parameters can be used for the predictive atomistic simulations of the structure and properties of amorphous organic layers containing beryllium complexes. The parameters are found for the AMBER force field using a relaxed scan procedure and quantum-mechanical DFT calculations of potential energy curves for specific internal (angular) coordinates in a series of three Be complexes (Bebq2; Be(4-mpp)2; Bepp2). The obtained parameters are verified in calculations of some molecular and crystal structures available from either quantum-mechanical DFT calculations or experimental data.

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Graphical Abstract Beryllium complexes in amorphous layers?

     

Frequent variations in cancer-related genes may play prognostic role in treatment of patients with chronic myeloid leukemia

Genome variability of host genome and cancer cells play critical role in diversity of response to existing therapies and overall success in treating oncological diseases. In chronic myeloid leukemia targeted therapy with tyrosine kinase inhibitors demonstrates high efficacy in most of the patients. However about 15 % of patients demonstrate primary resistance to standard therapy. Whole exome sequencing is a good tool for unbiased search of genetic variations important for prognosis of survival and therapy efficacy in many cancers. We apply this approach to CML patients with optimal response and failure of tyrosine kinase therapy. We analyzed exome variations between optimal responders and failures and found 7 variants in cancer-related genes with different genotypes in two groups of patients. Five of them were found in optimal responders: rs11579366, rs1990236, rs176037, rs10653661, rs3803264 and two in failures: rs3099950, rs9471966. These variants were found in genes associated with cancers (ANKRD35, DNAH9, MAGEC1, TOX3) or participating in cancer-related signaling pathways (THSD1, MORN2, PTCRA). We found gene variants which may become early predictors of the therapy outcome and allow development of new early prognostic tests for estimation of therapy efficacy in CML patients. Normal genetic variation may influence therapy efficacy during targeted treatment of cancers.     

Copper and Zinc Interactions with Cellular Prion Proteins Change Solubility of Full-Length Glycosylated Isoforms and Induce the Occurrence of Heterogeneous Phenotypes

Prion diseases are characterized biochemically by protein aggregation of infectious prion isoforms (PrP^Sc), which result from the conformational conversion of physiological prion proteins (PrP^C). PrP^C are variable post-translationally modified glycoproteins, which exist as full length and as aminoterminally truncated glycosylated proteins and which exhibit differential detergent solubility. This implicates the presence of heterogeneous phenotypes, which overlap as protein complexes at the same molecular masses. Although the biological function of PrP^C is still enigmatic, evidence reveals that PrP^C exhibits metal-binding properties, which result in structural changes and decreased solubility. In this study, we analyzed the yield of PrP^C metal binding affiliated with low solubility and changes in protein banding patterns. By implementing a high-speed centrifugation step, the interaction of zinc ions with PrP^C was shown to generate large quantities of proteins with low solubility, consisting mainly of full-length glycosylated PrP^C; whereas unglycosylated PrP^C remained in the supernatants as well as truncated glycosylated proteins which lack of octarepeat sequence necessary for metal binding. This effect was considerably lower when PrP^C interacted with copper ions; the presence of other metals tested exhibited no effect under these conditions. The binding of zinc and copper to PrP^C demonstrated differentially soluble protein yields within distinct PrP^C subtypes. PrP^C–Zn²⁺-interaction may provide a means to differentiate glycosylated and unglycosylated subtypes and offers detailed analysis of metal-bound and metal-free protein conversion assays.     

High-Purity Preparation of HSV-2 Vaccine Candidate ACAM529 Is Immunogenic and Efficacious In Vivo

Genital herpes is a sexually transmitted infection (STI) caused by herpes simplex virus 2 (HSV-2) and to a lesser extent herpes simplex virus 1 (HSV-1). Infection by HSV-2 is life-long and is associated with significant cost to healthcare systems and social stigma despite the highly prevalent nature of the disease. For instance, the proportion of HSV-2 seropositive to seronegative adults is approximately 1 in 5 in the US and greater than 4 in 5 in some areas of sub-Saharan Africa. The replication-defective vaccine strain virus dl5-29 was re-derived using cells appropriate for GMP manufacturing and renamed ACAM529. Immunization with dl5-29 was previously reported to be protective both in mice and in guinea pigs, however these studies were performed with vaccine that was purified using methods that cannot be scaled for manufacturing of clinical material. Here we describe methods which serve as a major step towards preparation of ACAM529 which may be suitable for testing in humans. ACAM529 can be harvested from infected cell culture of the trans-complementing cell line AV529 clone 19 (AV529-19) without mechanical cell disruption. ACAM529 may then be purified with respect to host cell DNA and proteins by a novel purification scheme, which includes a combination of endonuclease treatment, depth filtration, anion-exchange chromatography and ultrafiltration/diafiltration (UF/DF). The resultant virus retains infectivity and is ∼ 200-fold more pure with respect to host cell DNA and proteins than is ACAM529 purified by ultracentrifugation. Additionally, we describe a side-by-side comparison of chromatography-purified ACAM529 with sucrose cushion-purified ACAM529, which shows that both preparations are equally immunogenic and protective when tested in vivo.     

A Two One-Sided Parametric Tolerance Interval Test for Control of Delivered Dose Uniformity. Part 1—Characterization of FDA Proposed Test

The FDA proposed a parametric tolerance interval (PTI) test at the October 2005 Advisory Committee meeting as a replacement of the attribute (counting) test for delivered dose uniformity (DDU), published in the 1998 draft guidance for metered dose inhalers (MDIs) and dry powder inhalers (DPIs) and the 2002 final guidance for inhalation sprays and intranasal products. This article (first in a series of three) focuses on the test named by the FDA “87.5% coverage.” Unlike a typical two-sided PTI test, which controls the proportion of the DDU distribution within a target interval (coverage), this test is comprised of two one-sided tests (TOST) designed to control the maximum amount of DDU values in either tail of the distribution above and below the target interval. Through simulations, this article characterizes the properties and performance of the proposed PTI-TOST under different scenarios. The results show that coverages of 99% or greater are needed for a batch to have acceptance probability 98% or greater with the test named by the FDA “87.5% coverage” (95% confidence level), while batches with 87.5% coverage have less than 1% probability of being accepted. The results also illustrate that with this PTI-TOST, the coverage requirement for a given acceptance probability increases as the batch mean deviates from target. The accompanying articles study the effects of changing test parameters and the test robustness to deviations from normality.