Capillarity Theory for the Fly-Casting Mechanism

Biomolecular folding and function are often coupled. During molecular recognition events, one of the binding partners may transiently or partially unfold, allowing more rapid access to a binding site. We describe a simple model for this flycasting mechanism based on the capillarity approximation and polymer chain statistics. The model shows that flycasting is most effective when the protein unfolding barrier is small and the part of the chain which extends towards the target is relatively rigid. These features are often seen in known examples of flycasting in protein-DNA binding. Simulations of protein-DNA binding based on well-funneled native-topology models with electrostatic forces confirm the trends of the analytical theory

Lyophilisation of influenza, rabies and Marburg lentiviral pseudotype viruses for the development and distribution of a neutralisation-assay based diagnostic kit

Pseudotype viruses (PVs) are chimeric, replication-deficient virions that mimic wild-type virus entry mechanisms and can be safely employed in neutralisation assays, bypassing the need for high biosafety requirements and performing comparably to established serological assays. However, PV supernatant necessitates -80°C long-term storage and cold-chain maintenance during transport, which limits the scope of dissemination and application throughout resource-limited laboratories. We therefore investigated the effects of lyophilisation on influenza, rabies and Marburg PV stability, with a view to developing a pseudotype virus neutralisation assay (PVNA) based kit suitable for affordable global distribution. Infectivity of each PV was calculated after lyophilisation and immediate reconstitution, as well as subsequent to incubation of freeze-dried pellets at varying temperatures, humidities and timepoints. Integrity of glycoprotein structure following treatment was also assessed by employing lyophilised PVs in downstream PVNAs. In the presence of 0.5M sucrose-PBS cryoprotectant, each freeze-dried pseudotype was stably stored for 4 weeks at up to 37°C and could be neutralised to the same potency as unlyophilised PVs when employed in PVNAs. These results confirm the viability of a freeze-dried PVNA-based kit, which could significantly facilitate low-cost serology for a wide portfolio of emerging infectious viruses

Audio Cartography: Visual Encoding of Acoustic Parameters

Our sonic environment is the matter of subject in multiple domains which developed individual means of its description. As a result, it lacks an established visual language through which knowledge can be connected and insights shared. We provide a visual communication framework for the systematic and coherent documentation of sound in large-scale environments. This consists of visual encodings and mappings of acoustic parameters into distinct graphic variables that present plausible solutions for the visualization of sound. These candidate encodings are assembled into an application-independent, multifunctional, and extensible design guide. We apply the guidelines and show example maps that acts as a basis for the exploration of audio cartography

Are bisphosphonates effective in the treatment of osteoarthritis pain? A meta-analysis and systematic review.

Osteoarthritis (OA) is the most common form of arthritis worldwide. Pain and reduced function are the main symptoms in this prevalent disease. There are currently no treatments for OA that modify disease progression; therefore analgesic drugs and joint replacement for larger joints are the standard of care. In light of several recent studies reporting the use of bisphosphonates for OA treatment, our work aimed to evaluate published literature to assess the effectiveness of bisphosphonates in OA treatment

Scientific opinion on the evaluation of authorised ferric sodium EDTA as an ingredient in the context of Regulation (EC) 258/97 on novel foods and Regulation (EU) 609/2013 on food intended for infants and young children, food for special medical purposes and total diet replacement for weight control

The present opinion deals with the evaluation of the proposed increase of the currently authorised maximum amounts of ferric sodium ethylenediaminetetraacetic acid (EDTA) as a novel food ingredient used as a source of iron, and its extension of use in processed cereal‐based foods and baby foods. The applicant also provided information on two forms of ferric sodium EDTA, one previously assessed by EFSA and a new one of finer consistency. To support the proposed changes to the uses of ferric sodium EDTA, the applicant proposed a revision of the current acceptable daily intake (ADI) for EDTA, derived from that set for the food additive calcium disodium EDTA (E 385). The Panel confirmed that ferric sodium EDTA is a source from which iron is bioavailable. In assessing the safety of the proposed revision to the existing specifications for the novel food ingredient ferric sodium EDTA, the Panel noted that this would not discriminate between the previously evaluated substance and the one of finer consistency. In particular, the Panel noted that particle size was not one of the proposed parameters for the revised specifications. The Panel noted that it was not possible to determine whether particles of ferric sodium EDTA in the nano range were present in the product with finer consistency in the solid form. The toxicological data submitted did not add any new relevant information to the database on which the current ADI for EDTA is based. Consequently, the Panel concluded that there was no sound scientific justification to increase the ADI for EDTA and hence increase the use levels of ferric sodium EDTA or introduce additional uses as proposed by the applicant. The Panel recommended that additional toxicological data should be provided to address the shortcomings in the available toxicity database prior to the re‐evaluation of calcium disodium EDTA (E 385)

Refined exposure assessment of extracts of rosemary (E 392) from its use as food additive

The EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS) provides a scientific opinion on the refined exposure assessment of extracts of rosemary (E 392) when used as a food additive. Extracts of rosemary (E 392) was evaluated by the AFC Panel in 2008. Following this EFSA evaluation, extracts of rosemary (E 392) was authorised for use as a food additive in the EU in several food categories with maximum levels. In 2015, the ANS Panel provided a scientific opinion on the safety of the proposed extensions of use for extracts of rosemary (E 392) in fat-based spreads. In 2016, the Joint FAO/WHO Expert Committee on Food Additives (JECFA) has evaluated this food additive and established a temporary acceptable daily intake (ADI) of 0–0.3 mg/kg body weight (bw) for rosemary extract, expressed as carnosic acid plus carnosol. Based on the data provided by food industry, the Panel was able to refine the exposure estimates of extracts of rosemary (E 392). The highest mean refined exposure estimate (non-brand loyal scenario) was 0.09 mg/kg bw per day in children (3–9 years) and the highest 95th percentile of exposure was 0.20 mg/kg bw per day in children. Taking uncertainties into account, the Panel concluded that these exposure estimates very likely overestimate the real exposure to extracts of rosemary (E 392) from its use as a food additive according to Annex II. Margins of safety were estimated for children and adults using the refined exposure estimate; these are higher than the ones calculated in 2015. Intake of carnosic acid and carnosol from natural diet (herbs) was estimated. It was maximally 1.66 mg/kg bw per day (p95)

Search for the standard model Higgs boson in the H to ZZ to 2l 2nu channel in pp collisions at sqrt(s) = 7 TeV

A search for the standard model Higgs boson in the H to ZZ to 2l 2nu decay channel, where l = e or mu, in pp collisions at a center-of-mass energy of 7 TeV is presented. The data were collected at the LHC, with the CMS detector, and correspond to an integrated luminosity of 4.6 inverse femtobarns. No significant excess is observed above the background expectation, and upper limits are set on the Higgs boson production cross section. The presence of the standard model Higgs boson with a mass in the 270-440 GeV range is excluded at 95% confidence level.Comment: Submitted to JHE

Combined search for the quarks of a sequential fourth generation

Results are presented from a search for a fourth generation of quarks produced singly or in pairs in a data set corresponding to an integrated luminosity of 5 inverse femtobarns recorded by the CMS experiment at the LHC in 2011. A novel strategy has been developed for a combined search for quarks of the up and down type in decay channels with at least one isolated muon or electron. Limits on the mass of the fourth-generation quarks and the relevant Cabibbo-Kobayashi-Maskawa matrix elements are derived in the context of a simple extension of the standard model with a sequential fourth generation of fermions. The existence of mass-degenerate fourth-generation quarks with masses below 685 GeV is excluded at 95% confidence level for minimal off-diagonal mixing between the third- and the fourth-generation quarks. With a mass difference of 25 GeV between the quark masses, the obtained limit on the masses of the fourth-generation quarks shifts by about +/- 20 GeV. These results significantly reduce the allowed parameter space for a fourth generation of fermions.Comment: Replaced with published version. Added journal reference and DO