Ultrafast quantum coherent control apparatus

Department Head: Anthony A. Maciejewski.2007 Fall.Includes bibliographical references (pages 90-92).In recent years, the availability of ultrafast laser sources has opened up a number of opportunities for exploring molecular dynamics that take place on femtosecond time scales. Coherent control experiments involve creating, manipulating, and measuring these ultrafast phenomena. Such controllable processes include second harmonic generation (SHG), creation of vibrational wavepackets, high-harmonic generation, photodissociation, and more.The foundation to all these experiments is an ultrafast pulse shaper and a high-dimensional search algorithm. Here we present the design and construction of a spectral phase-only pulse shaper, including details on alignment and calibration. We also demonstrate the functionality of the device by producing several pulse profiles that could be potentially useful in coherent control experiments. A covariance matrix analysis evolutionary strategy (CMAES) is also implemented, and demonstrated to optimize SHG in a nonlinear crystal. Finally, recognizing that phase-only shapers cannot produce the full range of temporal shapes available to a given input pulse, we show the design and construction of a pulse shaper which uses only a single linear phase mask to gain control over both spectral phase and amplitude by use of phase gratings

Functional assessment for acute stroke trials: properties, analysis, and application

A measure of treatment effect is needed to assess the utility of any novel intervention in acute stroke. For a potentially disabling condition such as stroke, outcomes of interest should include some measure of functional recovery. There are many functional outcome assessments that can be used after stroke. In this narrative review, we discuss exemplars of assessments that describe impairment, activity, participation, and quality of life. We will consider the psychometric properties of assessment scales in the context of stroke trials, focusing on validity, reliability, responsiveness, and feasibility. We will consider approaches to the analysis of functional outcome measures, including novel statistical approaches. Finally, we will discuss how advances in audiovisual and information technology could further improve outcome assessment in trials

The coarse geometry of the Kakimizu complex

We show that the Kakimizu complex of minimal genus Seifert surfaces for a knot in the 3-sphere is quasi-isometric to a Euclidean integer lattice $\mathbb Z^n$ for some $n \geq 0$.Comment: 12 pages. Improvements to the exposition made in version

Identification and RNA Binding Characterization of Plant Virus RNA Silencing Suppressor Proteins

Suppression is a common mechanism employed by viruses to evade the antiviral effects of the host’s RNA silencing pathway. The activity of suppression has commonly been localized to gene products in the virus, but the variety of mechanisms used in suppression by these viral proteins spans nearly the complete biochemical pathway of RNA silencing in the host. This review describes the agrofiltration assay and a slightly modified version of the agro-infiltration assay called co-infiltration, which are common methods used to observe RNA silencing and identify viral silencing suppressor proteins in plants, respectively. In addition, this review will provide an overview of two methods, electrophoretic mobility shift assay and fluorescence polarization, used to assess the binding of a suppressor protein to siRNA which has been shown to be a general mechanism to suppress RNA silencing by plant viruses

Angiogenic gene signature in human pancreatic cancer correlates with TGF-beta and inflammatory transcriptomes

Pancreatic ductal adenocarcinomas (PDACs) are hypovascular, but overexpress pro-angiogenic factors and exhibit regions of microvasculature. Using RNA-seq data from The Cancer Genome Atlas (TCGA), we previously reported that ~12% of PDACs have an angiogenesis gene signature with increased expression of multiple pro-angiogenic genes. By analyzing the recently expanded TCGA dataset, we now report that this signature is present in ~35% of PDACs but that it is mostly distinct from an angiogenesis signature present in pancreatic neuroendocrine tumors (PNETs). These PDACs exhibit a transcriptome that reflects active TGF-β signaling, and up-regulation of several pro-inflammatory genes, and many members of JAK signaling pathways. Moreover, expression of SMAD4 and HDAC9 correlates with endothelial cell abundance in PDAC tissues. Concomitantly targeting the TGF-β type I receptor (TβRI) kinase with SB505124 and JAK1-2 with ruxolitinib suppresses JAK1 phosphorylation and blocks proliferative cross-talk between human pancreatic cancer cells (PCCs) and human endothelial cells (ECs), and these anti-proliferative effects were mimicked by JAK1 silencing in ECs. By contrast, either inhibitor alone does not suppress their enhanced proliferation in 3D co-cultures. These findings suggest that targeting both TGF-β and JAK1 signaling could be explored therapeutically in the 35% of PDAC patients whose cancers exhibit an angiogenesis gene signature

Pharmacy workers in Kenya need training and support on medical abortion information and referrals to prevent unsafe service provision

Despite the centrality of pharmacists in the provision of abortion services in Kenya, little is known about their medical abortion (MA) knowledge, attitudes, or practices. This policy brief reports on a study that set out to bridge this gap in the evidence. The report concludes that comprehensive training for pharmacy workers could improve the quality of MA provision and referrals, and help pharmacy workers identify opportunities to simultaneously provide clients with information on contraception and STI prevention. Such efforts would be in line with current Kenyan government policies to reduce the public health burden caused by the prevalence of unsafe abortion and HIV, and within the boundaries of the current legal framework

Increasing Collisional Activation of Protein Complexes Using Smaller Aperture Source Sampling Cones on a Synapt Q-IM-TOF Instrument with a Stepwave Source

Quadrupole-ion mobility-time-of-flight (Q-IM-TOF) mass spectrometers have revolutionized investigation of native biomolecular complexes. High pressures in the sources of these instruments aid transmission of protein complexes through damping of kinetic energy by collisional cooling. Since adducts are removed through collisional heating (declustering), excessive collisional cooling can prevent removal of non-specific adducts from protein ions, leading to inaccurate mass measurements, broad mass spectral peaks, and obfuscation of ligand binding. We show that reducing the source pressure using smaller aperture source sampling cones (SC) in a Waters Synapt G2-Si instrument increases protein ion heating by decreasing collisional cooling, providing a simple way to enhance removal of adducted salts from soluble proteins (GroEL 14-mer) and detergents from a transmembrane protein complex (heptameric Staphylococcus aureus α-hemolysin, αHL). These experiments are supported by ion heating and cooling simulations which demonstrate reduced collisional cooling at lower source pressures. Using these easily-swapped sample cones of different apertures is a facile approach to reproducibly extend the range of activation in Synapt-type instruments