Movement Intention Is Better Predicted than Attention in the Posterior Parietal Cortex

We decoded on a trial-by-trial basis the location of visual targets, as a marker of the locus of attention, and intentions to reach and to saccade in different directions using the activity of neurons in the posterior parietal cortex of two monkeys. Predictions of target locations were significantly worse than predictions of movement plans for the same target locations. Moreover, neural signals in the parietal reach region (PRR) gave better predictions of reaches than saccades, whereas signals in the lateral intraparietal area (LIP) gave better predictions of saccades than reaches. Taking together the activity of both areas, the prediction of either movement in all directions became nearly perfect. These results cannot be explained in terms of an attention effect and support the idea of two segregated populations in the posterior parietal cortex, PRR and LIP, that are involved in different movement plans

Gene delivery to in situ veins: Differential effects of adenovirus and adeno-associated viral vectors

AbstractPurpose: Gene transfer offers the potential to modify vein graft biology at the time of surgical implantation. Efficiency of gene delivery, stability of expression, and host responses are critical parameters for candidate vectors. We compared the effects of intraluminal exposure with adenovirus (AD) and adeno-associated virus (AAV) vectors on transgene expression and monocyte adhesion (MA) in treated vein segments. Methods: Adult New Zealand white rabbits (N = 51) were anesthetized, and the jugular veins were cannulated bilaterally. Veins were gently distended with either vector (2·108 to 1·1010 infective particles/mL) or vehicle (control) for 30 minutes, after which venous flow was restored. AD and AAV vectors encoding for the marker genes β-galactosidase (LacZ) and green fluorescent protein (GFP) were used. Vessels were explanted 2 to 40 days postinfection for analysis of gene expression (X-gal staining, reverse transcriptase-polymerase chain reaction), MA, and immunohistochemistry. Ex vivo adhesion assays used 51Cr-labeled THP-1 cells. Statistical significance was tested by using analysis of variance with a P value less than.05. Results: All animals survived, and all treated veins were patent at sacrifice. Intraluminal exposure to AD at a titer of 1·109 resulted in near complete transduction of the endothelium at 2 days, with no detectable expression by day 14. At an equal titer of infectious particles, transgene expression was markedly less for AAV at 2 to 7 days, but improved at 2 weeks and persisted to 40 days. MA was significantly increased 2 days after AD exposure (2.7-fold vs control, *P <.002); AAV treatment had no discernible effect on MA. Conclusion: AD-mediated gene transfer to vein segments resulted in robust, transient gene expression that disappeared after 2 weeks. In comparison, AAV-mediated gene delivery was less efficient, but resulted in delayed onset, persistent expression beyond 30 days. AD exposure induced an early increase in MA to the vein surface that was not seen with AAV treatment. Current generations of both AD and AAV vectors have significant, albeit different, limitations for vascular gene therapy. (J Vasc Surg 2000;31:1149-59.

Prion disease induced alterations in gene expression in spleen and brain prior to clinical symptoms

Prion diseases are fatal neurodegenerative disorders that affect animals and humans. There is a need to gain understanding of prion disease pathogenesis and to develop diagnostic assays to detect prion diseases prior to the onset of clinical symptoms. The goal of this study was to identify genes that show altered expression early in the disease process in the spleen and brain of prion disease-infected mice. Using Affymetrix microarrays, we identified 67 genes that showed increased expression in the brains of prion disease-infected mice prior to the onset of clinical symptoms. These genes function in many cellular processes including immunity, the endosome/lysosome system, hormone activity, and the cytoskeleton. We confirmed a subset of these gene expression alterations using other methods and determined the time course in which these changes occur. We also identified 14 genes showing altered expression prior to the onset of clinical symptoms in spleens of prion disease infected mice. Interestingly, four genes, Atp1b1, Gh, Anp32a, and Grn, were altered at the very early time of 46 days post-infection. These gene expression alterations provide insights into the molecular mechanisms underlying prion disease pathogenesis and may serve as surrogate markers for the early detection and diagnosis of prion disease

Experts\u27 Advice to Information Systems Doctoral Students

This paper summarizes the results of a panel discussion offering advice to doctoral students in advancing through their programs and getting a start on their career. The panel was held at the 2003 Annual Conference of the Southern Association for Information Systems, and panelists included five senior MIS faculty members who, combined, have chaired over 80 dissertations. Topics included choosing a dissertation topic, dealing with the dissertation committee, completing the dissertation, the job hunt, marketability, building a publication record, and advice for new faculty

An hydrodynamic shear instability in stratified disks

We discuss the possibility that astrophysical accretion disks are dynamically unstable to non-axisymmetric disturbances with characteristic scales much smaller than the vertical scale height. The instability is studied using three methods: one based on the energy integral, which allows the determination of a sufficient condition of stability, one using a WKB approach, which allows the determination of the necessary and sufficient condition for instability and a last one by numerical solution. This linear instability occurs in any inviscid stably stratified differential rotating fluid for rigid, stress-free or periodic boundary conditions, provided the angular velocity $\Omega$ decreases outwards with radius $r$. At not too small stratification, its growth rate is a fraction of $\Omega$. The influence of viscous dissipation and thermal diffusivity on the instability is studied numerically, with emphasis on the case when $d \ln \Omega / d \ln r =-3/2$ (Keplerian case). Strong stratification and large diffusivity are found to have a stabilizing effect. The corresponding critical stratification and Reynolds number for the onset of the instability in a typical disk are derived. We propose that the spontaneous generation of these linear modes is the source of turbulence in disks, especially in weakly ionized disks.Comment: 19 pages, 13 figures, to appear in A&

ELM Characteristics in MAST

Edge localized mode (ELM) characteristics in a large spherical tokamak (ST) with significant auxiliary heating are explored. High confinement is achieved in mega ampere spherical tokamak (MAST) at low ELM frequencies even though the ELMs exhibit many type III characteristics. These ELMs are associated with a reduction in the pedestal density but no significant change in the pedestal temperature or temperature profile, indicating that energy is convected from the pedestal region into the scrape-off layer. Power to the targets during an ELM arrives predominantly at the low field outboard side. ELM effluxes are observed up to 20 cm from the plasma edge at the outboard mid-plane and are associated with the radial motion of a feature at an average velocity of 0.75 km s-1. The target balance observed in MAST is potentially rather favourable for the ST since H-mode access is facilitated in a regime where ELM losses flow mostly to the large wetted area, outboard targets and, in addition, the target heat loads are reduced by an even distribution of power between the upper and lower targets

Escape of HIV-1 from a Small Molecule CCR5 Inhibitor Is Not Associated with a Fitness Loss

Fitness is a parameter used to quantify how well an organism adapts to its environment; in the present study, fitness is a measure of how well strains of human immunodeficiency virus type 1 (HIV-1) replicate in tissue culture. When HIV-1 develops resistance in vitro or in vivo to antiretroviral drugs such as reverse transcriptase or protease inhibitors, its fitness is often impaired. Here, we have investigated whether the development of resistance in vitro to a small molecule CCR5 inhibitor, AD101, has an associated fitness cost. To do this, we developed a growth-competition assay involving dual infections with molecularly cloned viruses that are essentially isogenic outside the env genes under study. Real-time TaqMan quantitative PCR (QPCR) was used to quantify each competing virus individually via probes specific to different, phenotypically silent target sequences engineered within their vif genes. Head-to-head competition assays of env clones derived from the AD101 escape mutant isolate, the inhibitor-sensitive parental virus, and a passage control virus showed that AD101 resistance was not associated with a fitness loss. This observation is consistent with the retention of the resistant phenotype when the escape mutant was cultured for a total of 20 passages in the absence of the selecting compound. Amino acid substitutions in the V3 region of gp120 that confer complete AD101 resistance cause a fitness loss when introduced into an AD101-sensitive, parental clone; however, in the resistant isolate, changes elsewhere in env that occurred prior to the substitutions within V3 appear to compensate for the adverse effect of the V3 changes on replicative capacity. These in vitro studies may have implications for the development and management of resistance to other CCR5 inhibitors that are being evaluated clinically for the treatment of HIV-1 infection

Potent Host-Directed Small-Molecule Inhibitors of Myxovirus RNA-Dependent RNA-Polymerases

Therapeutic targeting of host cell factors required for virus replication rather than of pathogen components opens new perspectives to counteract virus infections. Anticipated advantages of this approach include a heightened barrier against the development of viral resistance and a broadened pathogen target spectrum. Myxoviruses are predominantly associated with acute disease and thus are particularly attractive for this approach since treatment time can be kept limited. To identify inhibitor candidates, we have analyzed hit compounds that emerged from a large-scale high-throughput screen for their ability to block replication of members of both the orthomyxovirus and paramyxovirus families. This has returned a compound class with broad anti-viral activity including potent inhibition of different influenza virus and paramyxovirus strains. After hit-to-lead chemistry, inhibitory concentrations are in the nanomolar range in the context of immortalized cell lines and human PBMCs. The compound shows high metabolic stability when exposed to human S-9 hepatocyte subcellular fractions. Antiviral activity is host-cell species specific and most pronounced in cells of higher mammalian origin, supporting a host-cell target. While the compound induces a temporary cell cycle arrest, host mRNA and protein biosynthesis are largely unaffected and treated cells maintain full metabolic activity. Viral replication is blocked at a post-entry step and resembles the inhibition profile of a known inhibitor of viral RNA-dependent RNA-polymerase (RdRp) activity. Direct assessment of RdRp activity in the presence of the reagent reveals strong inhibition both in the context of viral infection and in reporter-based minireplicon assays. In toto, we have identified a compound class with broad viral target range that blocks host factors required for viral RdRp activity. Viral adaptation attempts did not induce resistance after prolonged exposure, in contrast to rapid adaptation to a pathogen-directed inhibitor of RdRp activity

A10 – Human Factors Considerations of UAS Procedures and Control Stations: Tasks PC-1 through PC-3 Pilot and Crew (PC) Subtask, Recommended Requirements and Operational Procedures

The Alliance for System Safety of UAS through Research Excellence (ASSURE) conducted research focused on minimum pilot procedures and operational practices used by unmanned aircraft systems (UAS) operators today for the purpose of developing recommendations. This research recommends four pilot and 46 operational minimum procedures to operate a civil single-engine, fixed-wing, single-pilot-configured UAS flying in beyond visual line-of-sight (BVLOS) conditions. These recommendations are anticipated to support potential future aircrew procedure requirements for UAS larger than 55 lbs. operating in the National Airspace System (NAS). These procedures were validated using representative Control Stations in simulated environments

The Grizzly, April 6, 1984

Loyalty Fund Phon-a-thon, Successful • Parsons Re-elected VP of Historical Society • Nagy\u27s Stellar Lecture • McQuaid Presents Views on Candidates • Letters to the Editor: Fraternities Help to Combat Apathy; Bubble World ; UC Social Life Needs Help; Pledging Not Destructive; Pledging Enhances Development; To Ban Pledging not a Positive Aspect; In Memory of Zeta Chi; Pledging to Expand Socially • Patrol Pattern Changed, Woman is Assaulted • The Limerick Syndrome: What Would UC do? • Mardi Gras Ball Declared Success • Changing Picture of Health in \u2780\u27s • Ride for Your Life! • Two Views on the Bussing Situation • Women\u27s Tennis Splits in Opening Matches • Softball Undefeated at 6-0 • Tennis Team Nets Two Victories • Denning Captures Fencing Title • Strizke, Rosenberg Qualify for Gymnastics Championship • Men\u27s Track Kicks off \u2784 Season • Men\u27s Lacrosse Thumps Bloomsburg • Hot Hitting Leads Bears Batsmen to Victories • Baseball Team Raises Record to 6-3 • Women\u27s Track Promisinghttps://digitalcommons.ursinus.edu/grizzlynews/1116/thumbnail.jp