The origins of specificity in the microcin-processing protease TldD/E

TldD and TldE proteins are involved in the biosynthesis of microcin B17 (MccB17), an Escherichia coli thiazole/oxazole-modified peptide toxin targeting DNA gyrase. Using a combination of biochemical and crystallographic methods we show that E. coli TldD and TldE interact to form a heterodimeric metalloprotease. TldD/E cleaves the N-terminal leader sequence from the modified MccB17 precursor peptide, to yield mature antibiotic, while it has no effect on the unmodified peptide. Both proteins are essential for the activity; however, only the TldD subunit forms a novel metal-containing active site within the hollow core of the heterodimer. Peptide substrates are bound in a sequence-independent manner through beta sheet interactions with TldD and are likely cleaved via a thermolysin-type mechanism. We suggest that TldD/E acts as a "molecularpencil sharpener'': unfoldedpoly-peptides are fed through a narrow channel into the active site and processively truncated through the cleavage of short peptides from the N-terminal end

Supersymmetry Reach of the Tevatron via Trilepton, Like-Sign Dilepton and Dilepton plus Tau Jet Signatures

We determine the Tevatron's reach in supersymmetric parameter space in trilepton, like-sign dilepton, and two lepton one tau-jet channels. We critically study the standard model background processes. We find larger backgrounds and, hence, significantly smaller reach regions than recent analyses. We identify the major cause of the background discrepancy. We improve signal-to-noise by introducing an invariant mass cut which takes advantage of a sharp edge in the signal dilepton invariant mass distribution. Also, we independently vary the cuts at each point in SUSY parameter space to determine the set which yields the maximal reach. We find that this cut optimization can significantly enhance the Tevatron reach.Comment: 30 pages, 10 figure

Exploring van der Waals materials with high anisotropy: geometrical and optical approaches

The emergence of van der Waals (vdW) materials resulted in the discovery of their giant optical, mechanical, and electronic anisotropic properties, immediately enabling countless novel phenomena and applications. Such success inspired an intensive search for the highest possible anisotropic properties among vdW materials. Furthermore, the identification of the most promising among the huge family of vdW materials is a challenging quest requiring innovative approaches. Here, we suggest an easy-to-use method for such a survey based on the crystallographic geometrical perspective of vdW materials followed by their optical characterization. Using our approach, we found As2S3 as a highly anisotropic vdW material. It demonstrates rare giant in-plane optical anisotropy, high refractive index and transparency in the visible range, overcoming the century-long record set by rutile. Given these benefits, As2S3 opens a pathway towards next-generation nanophotonics as demonstrated by an ultrathin true zero-order quarter-waveplate that combines classical and the Fabry-Perot optical phase accumulations. Hence, our approach provides an effective and easy-to-use method to find vdW materials with the utmost anisotropic properties.Comment: 11 pages, 5 figure

New Preparative Approach to Purer Technetium-99 Samples—Tetramethylammonium Pertechnetate: Deep Understanding and Application of Crystal Structure, Solubility, and Its Conversion to Technetium Zero Valent Matrix

99Tc is one of the predominant fission products of 235U and an important component of nuclear industry wastes. The long half-life and specific activity of 99Tc (212,000 y, 0.63 GBq g−1) makes Tc a hazardous material. Two principal ways were proposed for its disposal, namely, long-term storage and transmutation. Conversion to metal-like technetium matrices is highly desirable for both cases and for the second one the reasonably high Tc purity was important too. Tetramethylammonium pertechnetate (TMAP) was proposed here as a prospective precursor for matrix manufacture. It provided with very high decontamination factors from actinides (that is imperative for transmutation) by means of recrystallisation and it was based on the precise data on TMAP solubility and thermodynamics accomplished in the temperature range of 3–68 °C. The structure of solid pertechnetates were re-estimated with precise X-ray structure solution and compared to its Re and Cl analogues and tetrabutylammonium analogue as well. Differential thermal and evolved gas analysis in a flow of Ar–5% H2 gas mixture showed that the major products of thermolysis were pure metallic technetium in solid matrix, trimethylammonium, carbon dioxide, and water in gas phase. High decontamination factors have been achieved when TMAP was used as an intermediate precursor for Tc

Современные возможности терапии хронической крапивницы у детей

Chronic urticaria in children is one of the diseases that are underestimated in their severity and impact on the quality of life. The world academic literature data gives very little information on epidemiology, etiology of chronic urticaria, and researches on application of various therapies in children with the studied disease. Second-generation antihistamines are the leading medications in the therapy of chronic urticarial; however, there are not enough studies on the use of other treatment options in children with this pathology. Resistance to standard therapy and to high doses of antihistamines is one of the problems of managing both adult patients and children. Omalizumab is the first generation of biologicals drug for treating chronic urticaria resistant to standard therapy; the pharmaceutical can be administered in children over 12 years. Further research on the drug efficacy in chronic urticaria is required including safety rate evaluation in the pediatric group of patients.Хроническая крапивница у детей — одно из недооцененных по своей тяжести и влиянию на качество жизни заболеваний. В мировой научной литературе крайне мало информации об эпидемиологии, и этиологии хронической крапивницы. Антигистаминные препараты 2-го поколения являются ведущими в терапии хронической крапивницы, однако исследований по применению других видов лечения у детей при данной патологии недостаточно. Резистентность к стандартной терапии и высоким дозам антигистаминных препаратов — одна из проблем ведения как взрослых пациентов, так и детей. Омализумаб — первый генно-инженерный биологический препарат для лечения резистентной к стандартной терапии хронической крапивницы, разрешен к применению у детей с 12 лет. Необходимы дальнейшие исследования по эффективности его применения при хронической крапивнице, в том числе с оценкой безопасности у педиатрической группы пациентов.КОНФЛИКТ ИНТЕРЕСОВЛ.С. Намазова-Баранова — получение исследовательских грантов от фармацевтических компаний Пьер Фабр, Genzyme Europe B. V., ООО «Астра зенека Фармасьютикалз», Gilead / PRA «Фармасьютикал Рисерч Ассошиэйтс СиАйЭс», «Bionorica», Teva Branded Pharmaceutical products R&D, Inc / ООО «ППД Девелопмент (Смоленск)», «Сталлержен С. А.» / «Квинтайлс ГезмбХ» (Австрия).Остальные авторы данной статьи подтверждают отсутствие конфликта интересов, о котором необходимо сообщить

Study of the production of charged pions, kaons, and protons in pPb collisions at √SNN=5.02 TeV

Peer reviewe

Design, Performance and Calibration of the CMS Forward Calorimeter Wedges

We report on the test beam results and calibration methods using charged particles of the CMS Forward Calorimeter (HF). The HF calorimeter covers a large pseudorapidity region (3\l |\eta| \le 5), and is essential for large number of physics channels with missing transverse energy. It is also expected to play a prominent role in the measurement of forward tagging jets in weak boson fusion channels. The HF calorimeter is based on steel absorber with embedded fused-silica-core optical fibers where Cherenkov radiation forms the basis of signal generation. Thus, the detector is essentially sensitive only to the electromagnetic shower core and is highly non-compensating (e/h \approx 5). This feature is also manifest in narrow and relatively short showers compared to similar calorimeters based on ionization. The choice of fused-silica optical fibers as active material is dictated by its exceptional radiation hardness. The electromagnetic energy resolution is dominated by photoelectron statistics and can be expressed in the customary form as a/\sqrt{E} + b. The stochastic term a is 198% and the constant term b is 9%. The hadronic energy resolution is largely determined by the fluctuations in the neutral pion production in showers, and when it is expressed as in the electromagnetic case, a = 280% and b = 11%

Alignment of the CMS silicon tracker during commissioning with cosmic rays

This is the Pre-print version of the Article. The official published version of the Paper can be accessed from the link below - Copyright @ 2010 IOPThe CMS silicon tracker, consisting of 1440 silicon pixel and 15 148 silicon strip detector modules, has been aligned using more than three million cosmic ray charged particles, with additional information from optical surveys. The positions of the modules were determined with respect to cosmic ray trajectories to an average precision of 3–4 microns RMS in the barrel and 3–14 microns RMS in the endcap in the most sensitive coordinate. The results have been validated by several studies, including laser beam cross-checks, track fit self-consistency, track residuals in overlapping module regions, and track parameter resolution, and are compared with predictions obtained from simulation. Correlated systematic effects have been investigated. The track parameter resolutions obtained with this alignment are close to the design performance.This work is supported by FMSR (Austria); FNRS and FWO (Belgium); CNPq, CAPES, FAPERJ, and FAPESP (Brazil); MES (Bulgaria); CERN; CAS, MoST, and NSFC (China); COLCIENCIAS (Colombia); MSES (Croatia); RPF (Cyprus); Academy of Sciences and NICPB (Estonia); Academy of Finland, ME, and HIP (Finland); CEA and CNRS/IN2P3 (France); BMBF, DFG, and HGF (Germany); GSRT (Greece); OTKA and NKTH (Hungary); DAE and DST (India); IPM (Iran); SFI (Ireland); INFN (Italy); NRF (Korea); LAS (Lithuania); CINVESTAV, CONACYT, SEP, and UASLP-FAI (Mexico); PAEC (Pakistan); SCSR (Poland); FCT (Portugal); JINR (Armenia, Belarus, Georgia, Ukraine, Uzbekistan); MST and MAE (Russia); MSTDS (Serbia); MICINN and CPAN (Spain); Swiss Funding Agencies (Switzerland); NSC (Taipei); TUBITAK and TAEK (Turkey); STFC (United Kingdom); DOE and NSF (USA)