Rapid Total Synthesis of DARPin pE59 and Barnase

We report the convergent total synthesis of two proteins: DARPin pE59 and Bacillus amyloliquefaciens RNase (Barnase). Leveraging our recently developed fast-flow peptide-synthesis platform, we rapidly explored numerous conditions for the assembly of long polypeptides, and were able to mitigate common side reactions, including deletion and aspartimide products. We report general strategies for improving the synthetic quality of difficult peptide sequences with our system. High-quality protein fragments produced under optimal synthetic conditions were subjected to convergent native chemical ligation, which afforded native full-length proteins after a final desulfurization step. Both DARPin and Barnase were folded and found to be as active as their recombinant analogues.MIT Faculty Start-up FundMassachusetts Institute of Technology (Charles E. Reed Faculty Initiative Fund)Deshpande Center for Technological InnovationDamon Runyon-Rachleff (Innovation Award)Sontag Foundation (Distinguished Scientist Award)AstraZeneca (Firm) (Distinguished Graduate Student Fellowship)Daniel S. Kemp Summer FellowshipNational Institutes of Health (U.S.). Biotechnology Training Program (5T32GM008334-25

Prevalence and associated factors of Schistosomiasis among children in Yemen: implications for an effective control programme

BACKGROUND Schistosomiasis, one of the most prevalent neglected tropical diseases, is a life-threatening public health problem in Yemen especially in rural communities. This cross-sectional study aims to determine the prevalence and associated risk factors of schistosomiasis among children in rural Yemen. METHODS/FINDINGS Urine and faecal samples were collected from 400 children. Urine samples were examined using filtration technique for the presence of Schistosoma haematobium eggs while faecal samples were examined using formalin-ether concentration and Kato Katz techniques for the presence of S. mansoni. Demographic, socioeconomic and environmental information were collected via a validated questionnaire. Overall, 31.8% of the participants were found to be positive for schistosomiasis; 23.8% were infected with S. haematobium and 9.3% were infected with S. mansoni. Moreover, 39.5% of the participants were anaemic whereas 9.5% had hepatosplenomegaly. The prevalence of schistosomiasis was significantly higher among children aged >10 years compared to those aged ≤ 10 years (P<0.05). Multivariate analysis confirmed that presence of other infected family member (P<0.001), low household monthly income (P = 0.003), using unsafe sources for drinking water (P = 0.003), living nearby stream/spring (P = 0.006) and living nearby pool/pond (P = 0.002) were the key factors significantly associated with schistosomiasis among these children. CONCLUSIONS/SIGNIFICANCE This study reveals that schistosomiasis is still highly prevalent in Yemen. These findings support an urgent need to start an integrated, targeted and effective schistosomiasis control programme with a mission to move towards the elimination phase. Besides periodic drug distribution, health education and community mobilisation, provision of clean and safe drinking water, introduction of proper sanitation are imperative among these communities in order to curtail the transmission and morbidity caused by schistosomiasis. Screening and treating other infected family members should also be adopted by the public health authorities in combating this infection in these communities

Excited state dynamics and exciton diffusion in triphenylamine/dicyanovinyl push-pull small molecule for organic optoelectronics

Triphenylamine-based small push-pull molecules have recently attracted substantial research attention due to their unique optoelectronic properties. Here, we investigate the excited state de-excitation dynamics and exciton diffusion in TPA-T-DCV-Ph-F small molecule, having simple chemical structure with asymmetrical architecture and end-capped with electron-withdrawing p-fluorodicyanovinyl group. The excited state lifetime in diluted solutions (0.04 ns in toluene and 0.4 ns in chloroform) are found to be surprisingly shorter compared to the solid state (3 ns in PMMA matrix). Time-dependent density functional theory indicates that this behavior originates from non-radiative relaxation of the excited state through a conical intersection between the ground and singlet excited state potential energy surfaces. Exciton diffusion length of similar to 16 nm in solution processed films was retrieved by employing time-resolved photoluminescence volume quenching measurements with Monte Carlo simulations. As means of investigating the device performance of TPA-T-DCV-Ph-F, we manufactured solution and vacuum processed bulk heterojunction solar cells that yielded efficiencies of similar to 1.5% and similar to 3.7%, respectively. Our findings demonstrate that the short lifetime in solutions does not hinder per se long exciton diffusion length in films thereby granting applications of TPA-T-DCV-Ph-F and similar push-pull molecules in vacuum and solution processable devices

Application of multi-criteria in the selection of running systems for regional use of tractors in agriculture

The basis of the modern machine and tractor fleet of industrial and agricultural tractors are power vehicles with tracked and wheeled operating systems of various design designs. Both of these and other energy products have both their advantages and quite significant disadvantages. The article discusses the summary parametric and factorial characteristics of wheeled and tracked power vehicles used in field and transport work in the Amur region. The criteria for the formation of their traction properties, ways to reduce slipping, reduce the load of the machine-tractor unit on the soil, and the use of agricultural machinery during waterlogging are analysed. The results of a study on the use of mobile energy means in waterlogged conditions during the cultivation of agricultural crops, where their main advantages and disadvantages are reflected, the directions of choosing an energy means for use in agricultural production technologies are substantiated. It has been established that the use of tracked power vehicles with high traction properties, when aggregated with wide-reach machines in the fields of the region, will be more effective during periods of work when there is a large precipitation. At the same time, wheel energy means will also be in demand in the natural and climatic conditions of the Amur region as the most versatile structurally suitable means for performing most agricultural field operations as part of a tractor-transport unit. In this connection, the expediency of equipping the production and industrial complex and means of mechanisation of farms and agricultural enterprises of the region with energy means with various running systems in accordance with the used and scientifically based regional system of machines and technologies is justified

Theodicy and End-of-Life Care

Acknowledgments The section on Islamic perspective is contributed by information provided by Imranali Panjwani, Tutor in Theology & Religious Studies, King's College London.Peer reviewedPublisher PD

Rapid Flow-Based Peptide Synthesis

A flow-based solid-phase peptide synthesis methodology that enables the incorporation of an amino acid residue every 1.8 min under automatic control or every 3 min under manual control is described. This is accomplished by passing a stream of reagent through a heat exchanger into a low volume, low backpressure reaction vessel, and through a UV detector. These features enable continuous delivery of heated solvents and reagents to the solid support at high flow rate, thereby maintaining maximal concentration of reagents in the reaction vessel, quickly exchanging reagents, and eliminating the need to rapidly heat reagents after they have been added to the vessel. The UV detector enables continuous monitoring of the process. To demonstrate the broad applicability and reliability of this method, it was employed in the total synthesis of a small protein, as well as dozens of peptides. The quality of the material obtained with this method is comparable to that for traditional batch methods, and, in all cases, the desired material was readily purifiable by RP-HPLC. The application of this method to the synthesis of the 113-residue Bacillus amyloliquefaciens RNase and the 130-residue DARPin pE59 is described in the accompanying manuscript.MIT Faculty Start-up FundMassachusetts Institute of Technology (Charles E. Reed Faculty Initiative Fund)Deshpande Center for Technological InnovationDamon Runyon-Rachleff (Innovation Award)Sontag Foundation (Distinguished Scientist Award)C. P. Chu and Y. Lai FellowshipDaniel S. Kemp Summer FellowshipNational Institute of General Medical Sciences (U.S.). Biotechnology Training Program (Grant 5T32GM008334-25)National Institutes of Health (U.S.) (Fellowship F32GM101762

Search for corannulene (C20H10) in the Red Rectangle

Polycyclic Aromatic Hydrocarbons (PAHs) are widely accepted as the carriers of the Aromatic Infrared Bands (AIBs), but an unambiguous identification of any specific interstellar PAH is still missing. For polar PAHs, pure rotational transitions can be used as spectral fingerprints for identification. Combining dedicated experiments, detailed simulations and observations, we explore d the mm wavelength domain to search for specific rotational transitions of corannulene (C20H10). We performed high-resolution spectroscopic measurements and a simulation of the emission spectrum of ultraviolet-excited C20H10 in the environment of the Red Rectangle (RR), calculating its synthetic rotational spectrum. Based on these results, we conducted a first observational campaign at the IRAM 30-m telescope towards this source to search for several high-J rotational transitions of C20H10. The laboratory detection of the J = 112 ← 111 transition of corannulene showed that no centrifugal splitting is present up to this line. Observations with the IRAM 30-m telescope towards the RR do not show any corannulene emission at any of the observed frequencies, down to a rms noise level of Tmb= 8 mK for the J =135 → 134 transition at 137.615 GHz. Comparing the noise level with the synthetic spectrum, we are able to estimate an upper limit to the fraction of carbon locked in corannulene of about 1.0 × 10−5 relative to the total abundance of carbon in PAHs. The sensitivity achieved in this work shows that radio spectroscopy can be a powerful tool to search for polar PAHs. We compare this upper limit with models for the PAH size distribution, emphasizing that small PAHs are much less abundant than predicted. We show that this cannot be explained by destruction but is more likely related to the chemistry of their formation in the environment of the R

Measurement of hadron cross sections with the SND detector

New results on exclusive hadron production in $e^+e^-$ annihilation obtained in experiments with the SND detector at the VEPP-2M and VEPP-2000 $e^+e^-$ colliders are presented.Comment: 4 pages, 4 figures, presented at the 14th International Workshop on Meson Production, Properties and Interaction (MESON 2016), Cracow, Poland, 2nd - 7th June 201