Hijab and Muslim religious identity expression among Egyptian women in the Pacific Northwest

The purpose of this study was to examine the symbolic meaning of modest dress (referred to in a general sense as hijab) to Egyptian Muslim women living in America’s Pacific Northwest. In the diaspora, where Egyptian garments are not available, the women must mix headscarves with Western fashion, but it must be modest. Muslim women living in the USA need to integrate requirements for religious modesty when shopping for Western fashion which does not place a high value on modesty

SeeGH – A software tool for visualization of whole genome array comparative genomic hybridization data

BACKGROUND: Array comparative genomic hybridization (CGH) is a technique which detects copy number differences in DNA segments. Complete sequencing of the human genome and the development of an array representing a tiling set of tens of thousands of DNA segments spanning the entire human genome has made high resolution copy number analysis throughout the genome possible. Since array CGH provides signal ratio for each DNA segment, visualization would require the reassembly of individual data points into chromosome profiles. RESULTS: We have developed a visualization tool for displaying whole genome array CGH data in the context of chromosomal location. SeeGH is an application that translates spot signal ratio data from array CGH experiments to displays of high resolution chromosome profiles. Data is imported from a simple tab delimited text file obtained from standard microarray image analysis software. SeeGH processes the signal ratio data and graphically displays it in a conventional CGH karyotype diagram with the added features of magnification and DNA segment annotation. In this process, SeeGH imports the data into a database, calculates the average ratio and standard deviation for each replicate spot, and links them to chromosome regions for graphical display. Once the data is displayed, users have the option of hiding or flagging DNA segments based on user defined criteria, and retrieve annotation information such as clone name, NCBI sequence accession number, ratio, base pair position on the chromosome, and standard deviation. CONCLUSIONS: SeeGH represents a novel software tool used to view and analyze array CGH data. The software gives users the ability to view the data in an overall genomic view as well as magnify specific chromosomal regions facilitating the precise localization of genetic alterations. SeeGH is easily installed and runs on Microsoft Windows 2000 or later environments

Convergent diversity-oriented side-chain macrocyclization scan for unprotected polypeptides

Here we describe a general synthetic platform for side-chain macrocyclization of an unprotected peptide library based on the S[subscript N]Ar reaction between cysteine thiolates and a new generation of highly reactive perfluoroaromatic small molecule linkers. This strategy enabled us to simultaneously “scan” two cysteine residues positioned from i, i + 1 to i, i + 14 sites in a polypeptide, producing 98 macrocyclic products from reactions of 14 peptides with 7 linkers. A complementary reverse strategy was developed; cysteine residues within the polypeptide were first modified with non-bridging perfluoroaryl moieties and then commercially available dithiol linkers were used for macrocyclization. The highly convergent, site-independent, and modular nature of these two strategies coupled with the unique chemoselectivity of a S[subscript N]Ar transformation allows for the rapid diversity-oriented synthesis of hybrid macrocyclic peptide libraries with varied chemical and structural complexities.National Institutes of Health (U.S.) (GM101762)National Institutes of Health (U.S.) (GM046059)MIT Faculty Start-up FundSontag Foundation (Distinguished Scientist Award)Deshpande Center for Technological InnovationMassachusetts Institute of Technology (Charles E. Reed Faculty Initiative Fund)Damon Runyon Cancer Research Foundatio

An Open-Label, Multicenter, Phase I, Dose Escalation Study with Phase II Expansion Cohort to Determine the Safety, Pharmacokinetics, and Preliminary Antitumor Activity of Intravenous TKM-080301 in Subjects with Advanced Hepatocellular Carcinoma.

Lessons learnedTKM-080301 showed a favorable toxicity profile at the studied dose.TKM-080301 targeting PLK1 through small interfering RNA mechanism did not demonstrate improved overall survival in patients with advanced hepatocellular carcinoma compared with historical control. Preliminary antitumor activity as shown in this early-phase study does not support further evaluation as a single agent.BackgroundPolo-like kinase 1 (PLK1) is overexpressed in hepatocellular carcinoma (HCC). Knockdown of PLK1 expression by PLK1 small interfering RNA (siRNA) in an HCC cell line showed reduced expression in RNA-induced silencing complex and a reduction in cell proliferation.MethodsA 3 + 3 dose escalation plus expansion cohort at the maximum tolerated dose (MTD) was implemented. Patients with HCC, Eastern Cooperative Oncology Group (ECOG) performance status ≤2, and Child-Pugh score A received TKM-080301 as an intravenous infusion once every week for 3 consecutive weeks, repeated every 28 days.ResultsThe study enrolled 43 patients. The starting dose of TKM-080301 was 0.3 mg/kg, and MTD was declared at 0.75 mg/kg. Following the development of grade 4 thrombocytopenia in two subjects on the expansion cohort, the MTD was redefined at 0.6 mg/kg. Four patients did not have any evaluable postbaseline scan. Of the other 39 subjects who had received at least 0.3 mg/kg, 18 subjects (46.2%) had stable disease (SD) by independent RECIST 1.1 criteria. By Choi criteria, eight subjects (23.1%) had a partial response (PR). For 37 assessable subjects, with 2 subjects censored, median progression-free survival (PFS) was 2.04 months. Median survival for the whole study population was 7.5 months.ConclusionTKM-080301 was generally well tolerated. In this early-phase study, antitumor effect for TKM 080301 was limited. Further evaluation as a single agent in large randomized trials is not warranted

π-Clamp-mediated cysteine conjugation

Site-selective functionalization of complex molecules is one of the most significant challenges in chemistry. Typically, protecting groups or catalysts must be used to enable the selective modification of one site among many that are similarly reactive, and general strategies that selectively tune the local chemical environment around a target site are rare. Here, we show a four-amino-acid sequence (Phe-Cys-Pro-Phe), which we call the ‘π-clamp’, that tunes the reactivity of its cysteine thiol for site-selective conjugation with perfluoroaromatic reagents. We use the π-clamp to selectively modify one cysteine site in proteins containing multiple endogenous cysteine residues. These examples include antibodies and cysteine-based enzymes that would be difficult to modify selectively using standard cysteine-based methods. Antibodies modified using the π-clamp retained binding affinity to their targets, enabling the synthesis of site-specific antibody–drug conjugates for selective killing of HER2-positive breast cancer cells. The π-clamp is an unexpected approach to mediate site-selective chemistry and provides new avenues to modify biomolecules for research and therapeutics.Massachusetts Institute of Technology (Start-up Funds)National Institutes of Health (U.S.) (NIH R01GM110535)Sontag Foundation (Distinguished Scientist Award)Massachusetts Institute of Technology. Department of Chemistry (George Buchi Research Fellowship)David H. Koch Institute for Integrative Cancer Research at MIT (Graduate Fellowship)Bristol-Myers Squibb Company (Graduate Fellowship in Synthetic Organic Chemistry)National Science Foundation (U.S.) (Graduate Research Fellow

Boundary layers and emitted excitations in nonlinear Schrodinger superflow past a disk

The stability and dynamics of nonlinear Schrodinger superflows past a two-dimensional disk are investigated using a specially adapted pseudo-spectral method based on mapped Chebychev polynomials. This efficient numerical method allows the imposition of both Dirichlet and Neumann boundary conditions at the disk border. Small coherence length boundary-layer approximations to stationary solutions are obtained analytically. Newton branch-following is used to compute the complete bifurcation diagram of stationary solutions. The dependence of the critical Mach number on the coherence length is characterized. Above the critical Mach number, at coherence length larger than fifteen times the diameter of the disk, rarefaction pulses are dynamically nucleated, replacing the vortices that are nucleated at small coherence length

Instrumenter l’activité des élèves pour orienter la cognition et la métacognition lors des devoirs à domicile

À travers ce mémoire professionnel, nous nous sommes intéressées au fait que certains élèves rencontrent des difficultés lorsqu’ils se retrouvent seuls face à leurs devoirs. Nous nous sommes particulièrement intéressées aux élèves les plus en difficulté, qui ont déjà de la peine à suivre en classe et se retrouvent fréquemment avec un agenda rempli de devoirs de toutes sortes. Ainsi, sans aide externe, ils ne savent pas comment travailler et risquent de tomber dans le « faire » pour compléter plutôt que d’apprendre. Nous avons donc eu pour ambition de créer un outil permettant d’instrumenter l’activité de l’élève pour le soutenir dans son travail. Pour ce faire, nous sommes parties de la grille d’Anderson & Krathwohl, qui énumère six habiletés différentes touchant aux apprentissages. Ce travail s’est porté sur l’habileté « comprendre », qui selon nous, est une habileté essentielle à mobiliser dans de nombreux devoirs. Ensuite, dans le but d’outiller l’élève d’un aidemémoire, nous avons fait tout un travail en amont portant sur l’analyse de l’activité de l’élève d’un point de vue cognitif et métacognitif. Notre attention s’est portée d’une part sur la compréhension de l’élève (cognition), mais également sur sa stratégie de travail lorsqu’il planifie et régule son travail (métacognition). Pour parvenir à nos fins, nous avons mené plusieurs instructions aux sosies : une technique d’entretien qui a pour but d’accéder à l’activité de l’acteur, dans ce cas-ci l’élève. Notre recherche repose sur l’analyse de devoirs et de stratégies d’élèves démontrant certaines difficultés scolaires dans l’écologie d’une classe de 5ème HarmoS (H) et de 6ème HarmoS (H). Au sein de ces deux classes, nous avions la volonté d’apporter un dispositif externe qui permettrait aux élèves, particulièrement ceux en difficulté, de cibler l’attente des devoirs pour mieux les comprendre. Un travail ambitieux qui, par manque de temps, n’a pas pu être mené à terme. Nous avons toutefois été en mesure d’analyser l’activité des élèves et d’y apporter nos interprétations, une étape fondamentale avant d’intégrer un outil médiateur

A structural and mechanistic study of π-clamp-mediated cysteine perfluoroarylation

Natural enzymes use local environments to tune the reactivity of amino acid side chains. In searching for small peptides with similar properties, we discovered a four-residue π-clamp motif (Phe-Cys-Pro-Phe) for regio- and chemoselective arylation of cysteine in ribosomally produced proteins. Here we report mutational, computational, and structural findings directed toward elucidating the molecular factors that drive π-clamp-mediated arylation. We show the significance of a trans conformation prolyl amide bond for the π-clamp reactivity. The π-clamp cysteine arylation reaction enthalpy of activation (ΔH‡) is significantly lower than a non-π-clamp cysteine. Solid-state NMR chemical shifts indicate the prolyl amide bond in the π-clamp motif adopts a 1:1 ratio of the cis and trans conformation, while in the reaction product Pro3 was exclusively in trans. In two structural models of the perfluoroarylated product, distinct interactions at 4.7 Å between Phe1 side chain and perfluoroaryl electrophile moiety are observed. Further, solution 19F NMR and isothermal titration calorimetry measurements suggest interactions between hydrophobic side chains in a π-clamp mutant and the perfluoroaryl probe. These studies led us to design a π-clamp mutant with an 85-fold rate enhancement. These findings will guide us toward the discovery of small reactive peptides to facilitate abiotic chemistry in water.National Institutes of Health (U.S.) (Grant R01GM110535)National Institutes of Health (U.S.) (Grant GM088204)National Science Foundation (U.S.) (Award CHE-1464804

Dissipative Dynamics of a Josephson Junction In the Bose-Gases

The dissipative dynamics of a Josephson junction in the Bose-gases is considered within the framework of the model of a tunneling Hamiltonian. The effective action which describes the dynamics of the phase difference across the junction is derived using functional integration method. The dynamic equation obtained for the phase difference across the junction is analyzed for the finite temperatures in the low frequency limit involving the radiation terms. The asymmetric case of the Bose-gases with the different order parameters is calculated as well