Principles of genetic circuit design

Cells navigate environments, communicate and build complex patterns by initiating gene expression in response to specific signals. Engineers seek to harness this capability to program cells to perform tasks or create chemicals and materials that match the complexity seen in nature. This Review describes new tools that aid the construction of genetic circuits. Circuit dynamics can be influenced by the choice of regulators and changed with expression 'tuning knobs'. We collate the failure modes encountered when assembling circuits, quantify their impact on performance and review mitigation efforts. Finally, we discuss the constraints that arise from circuits having to operate within a living cell. Collectively, better tools, well-characterized parts and a comprehensive understanding of how to compose circuits are leading to a breakthrough in the ability to program living cells for advanced applications, from living therapeutics to the atomic manufacturing of functional materials.National Institute of General Medical Sciences (U.S.) (Grant P50 GM098792)National Institute of General Medical Sciences (U.S.) (Grant R01 GM095765)National Science Foundation (U.S.). Synthetic Biology Engineering Research Center (EEC0540879)Life Technologies, Inc. (A114510)National Science Foundation (U.S.). Graduate Research FellowshipUnited States. Office of Naval Research. Multidisciplinary University Research Initiative (Grant 4500000552

Use of Nafamostat Mesilate as an Anticoagulant during Extracorporeal Membrane Oxygenation

Although the incidence of bleeding complications during extracorporeal membrane oxygenator (ECMO) support has decreased in various trials, bleeding is still the most fatal complication. We investigated the ideal dosage and efficacy of nafamostat mesilate for use with ECMO in patients with acute cardiac or respiratory failure. We assessed 73 consecutive patients who received ECMO due to acute cardiac or respiratory failure between January 2006 and December 2009. To evaluate the efficacy of nafamostat mesilate, we divided the patients into 2 groups according to the anticoagulants used during ECMO support. All patients of nafamostat mesilate group were male with a mean age of 49.2 yr. Six, 3, 5, and 3 patients were diagnosed with acute myocardial infarction, cardiac arrest, septic shock, and acute respiratory distress syndrome, respectively. The mean dosage of nafamostat mesilate was 0.64 mg/kg/hr, and the mean duration of ECMO was 270.7 hr. The daily volume of transfused packed red blood cells, fresh frozen plasma, and cryoprecipitate and the number of complications related to hemorrhage and thrombosis was lower in the nafamostat mesilate group than in the heparin group. Nafamostat mesilate should be considered as an alternative anticoagulant to heparin to reduce bleeding complications during ECMO

Identification of α(1,6)fucosylated proteins differentially expressed in human colorectal cancer

<p>Summary</p> <p>Background</p> <p>A universal hallmark of cancer cells is the change in their glycosylation phenotype. One of the most frequent alterations in the normal glycosylation pattern observed during carcinogenesis is the enhancement of α(1,6)linked fucose residues of glycoproteins, due to the up-regulation of the α(1,6)fucosyltransferase activity. Our previous results demonstrated the specific alteration of this enzyme activity and expression in colorectal cancer, suggesting its implication in tumour development and progression.</p> <p>Methods</p> <p>In the current work we combined a LCA-affinity chromatography with SDS-PAGE and mass spectrometry in order to identify α(1,6)fucosylated proteins differentially expressed in colorectal cancer. This strategy allowed the identification of a group of α(1,6)fucosylated proteins candidates to be involved in CRC malignancy.</p> <p>Results</p> <p>The majority of the identified proteins take part in cell signaling and interaction processes as well as in modulation of the immunological response. Likewise, we confirmed the increased expression of GRP94 in colorectal cancer tissue and the significant down-regulation of the IgGFcBP expression in tumour cells.</p> <p>Conclusion</p> <p>All these results validate the importance of <it>core-</it>fucosylated proteins profile analysis to understand the mechanisms which promote cancer onset and progression and to discover new tumour markers or therapeutic targets.</p

The Thermal Infrared Visual Object Tracking VOT-TIR2015 challenge results

The Thermal Infrared Visual Object Tracking challenge 2015, VOT-TIR2015, aims at comparing short-term single-object visual trackers that work on thermal infrared (TIR) sequences and do not apply pre-learned models of object appearance. VOT-TIR2015 is the first benchmark on short-term tracking in TIR sequences. Results of 24 trackers are presented. For each participating tracker, a short description is provided in the appendix. The VOT-TIR2015 challenge is based on the VOT2013 challenge, but introduces the following novelties: (i) the newly collected LTIR (Link - ping TIR) dataset is used, (ii) the VOT2013 attributes are adapted to TIR data, (iii) the evaluation is performed using insights gained during VOT2013 and VOT2014 and is similar to VOT2015

アイヅチ コウドウ ニオケル カチカン ノ カンニチ ヒカク

本稿は、韓国人と日本人のあいづちの頻度、あいづちのイメージや先取りのイメージなどについて、聞き取り調査とアンケート調査を行ない、その運用の実態を対照社会言語学的な観点から具体的に明らかにしたものである。ここで、今回の調査から明らかにし得たことを例示すると、次のようである。まず、韓国人のあいづちの打ち方は日本人によく似ているが、その頻度においては日本人のほうが高い。また、韓日とも、くだけた話題のインフォーマルな場面 では、そうでない場面に比べてあいづちの頻度が多くなる。 次に、あいづちの多く打つ人に対する評価では、韓国人はマイナス評価を、日本人はプラス評価を下している。逆に、あいづちを少なく打つ人に対して韓国人はプラス評価を、日本人はマイナス評価を下している。この点、韓国と日本とはまったく異なっている。そして、注目しなければならないことは、韓国人は日本人より先取りや言いかえを多用するということである。なお、先取りに関する違和感は日本人のほうが高いが、先取りの現われる確率は、日韓ともに、話し手と聞き手の間に情報が共有されている場合やくだけた話題のインフォーマルな場面 で高くなる、という傾向がうかがえた。This thesis examines the practices of back-channel behavior from the sociolinguistic viewpoint. Through interviews and questionnaires on the frequency of back-channel behavior, the images of back-channel behavior and anticipatory expressions among Koreans and Japanese have been studied. Some of the examples clarified in this research are as follows: First, back-channel behavior of Koreans is very similar to that of Japanese; however, its frequency is higher on the part of Japanese. Both Koreans and Japanese tend to use back-channel behavior more frequently in intimate conversations or informal situations than in other situations. Next, Koreans tend to judge those who frequently use back-channel behavior negatively, while the Japanese view them positively. Conversely, those who make little use of back-channel behavior Koreans tend to judge positively while the Japanese negatively. Here lies a great difference between Koreans and Japanese. Finally, what deserves note is that Koreans tend to use anticipatory expressions or speaking-in-other-words more frequently than Japanese do. Also, a sense of incongruity toward anticipatory expressions is higher on the part of the Japanese ; however, among both Koreans and Japanese, the probability of using anticipatory expressions tends to increase in intimate conversations or informal situations when a common ownership of information exists between the speaker and the listener

Development and validation of HERWIG 7 tunes from CMS underlying-event measurements

This paper presents new sets of parameters (“tunes”) for the underlying-event model of the HERWIG7 event generator. These parameters control the description of multiple-parton interactions (MPI) and colour reconnection in HERWIG7, and are obtained from a fit to minimum-bias data collected by the CMS experiment at s=0.9, 7, and 13Te. The tunes are based on the NNPDF 3.1 next-to-next-to-leading-order parton distribution function (PDF) set for the parton shower, and either a leading-order or next-to-next-to-leading-order PDF set for the simulation of MPI and the beam remnants. Predictions utilizing the tunes are produced for event shape observables in electron-positron collisions, and for minimum-bias, inclusive jet, top quark pair, and Z and W boson events in proton-proton collisions, and are compared with data. Each of the new tunes describes the data at a reasonable level, and the tunes using a leading-order PDF for the simulation of MPI provide the best description of the dat

Search for top squark pair production using dilepton final states in pp collision data collected at root s=13TeV

A search is presented for supersymmetric partners of the top quark (top squarks) in final states with two oppositely charged leptons (electrons or muons), jets identified as originating from bquarks, and missing transverse momentum. The search uses data from proton-proton collisions at root s = 13 TeV collected with the CMS detector, corresponding to an integrated luminosity of 137 fb(-1). Hypothetical signal events are efficiently separated from the dominant top quark pair production background with requirements on the significance of the missing transverse momentum and on transverse mass variables. No significant deviation is observed from the expected background. Exclusion limits are set in the context of simplified supersymmetric models with pair-produced lightest top squarks. For top squarks decaying exclusively to a top quark and a lightest neutralino, lower limits are placed at 95% confidence level on the masses of the top squark and the neutralino up to 925 and 450 GeV, respectively. If the decay proceeds via an intermediate chargino, the corresponding lower limits on the mass of the lightest top squark are set up to 850 GeV for neutralino masses below 420 GeV. For top squarks undergoing a cascade decay through charginos and sleptons, the mass limits reach up to 1.4 TeV and 900 GeV respectively for the top squark and the lightest neutralino.Peer reviewe

Measurement of the W gamma Production Cross Section in Proton-Proton Collisions at root s=13 TeV and Constraints on Effective Field Theory Coefficients

A fiducial cross section for W gamma production in proton-proton collisions is measured at a center-of-mass energy of 13 TeV in 137 fb(-1) of data collected using the CMS detector at the LHC. The W -> e nu and mu nu decay modes are used in a maximum-likelihood fit to the lepton-photon invariant mass distribution to extract the combined cross section. The measured cross section is compared with theoretical expectations at next-to-leading order in quantum chromodynamics. In addition, 95% confidence level intervals are reported for anomalous triple-gauge couplings within the framework of effective field theory.Peer reviewe