A relationship between US healthcare worker smallpox vaccination rates in 2003 and presidential election results in 2004

A statistical relationship exists between state per capita smallpox vaccination rates of healthcare workers in 2003 and state presidential election results in 2004. The potential implications of political influence on national biosecurity decision making are discussed

MEF: Malicious Email Filter: A UNIX Mail Filter that Detects Malicious Windows Executables

We present Malicious Email Filter, MEF, a freely distributed malicious binary filter incorporated into Procmail that can detect malicious Windows attachments by integrating with a UNIX mail server. The system has three capabilities: detection of known and unknown malicious attachments, tracking the propagation of malicious attachments and efficient model update algorithms. The system filters multiple malicious attachments in an email by using detection models obtained from data mining over known malicious attachments. It leverages preliminary research in data mining applied to malicious executables which allows the detection of previously unseen, malicious attachments. In addition, the system provides a method for monitoring and measurement of the spread of malicious attachments. Finally, the system also allows for the efficient propagation of detection models from a central server. These updated models can be downloaded by a system administrator and easily incorporated into the current model. The system will be released under GPL in June 2001

Effects of Preventative Ankle Taping on Planned Change-of-Direction and Reactive Agility Performance and Ankle Muscle Activity in Basketballers

This study investigated the effects of preventative ankle taping on planned change-of-direction and reactive agility performance and peak ankle muscle activity in basketballers. Twenty male basketballers (age = 22.30 ± 3.97 years; height = 1.84 ± 0.09 meters; body mass = 85.96 ± 11.88 kilograms) with no ankle pathologies attended two testing sessions. Within each session, subjects completed six planned and six reactive randomized trials (three to the left and three to the right for each condition) of the Y-shaped agility test, which was recorded by timing lights. In one session, subjects had both ankles un-taped. In the other, both ankles were taped using a modified subtalar sling. Peak tibialis anterior, peroneus longus (PL), peroneus brevis (PB), and soleus muscle activity was recorded for both the inside and outside legs across stance phase during the directional change, which was normalized against 10-meter sprint muscle activity (nEMG). Both the inside and outside cut legs during the change-of-direction step were investigated. Repeated measures ANOVA determined performance time and nEMG differences between un-taped and taped conditions. There were no differences in planned change-of-direction or reactive agility times between the conditions. Inside cut leg PL nEMG decreased when taped for the planned left, reactive left, and reactive right cuts (p = 0.01). Outside leg PB and soleus nEMG increased during the taped planned left cut (p = 0.02). There were no other nEMG changes during the cuts with taping. Taping did not affect change-of-direction or agility performance. Inside leg PL activity was decreased, possibly due to the tape following the line of muscle action. This may reduce the kinetic demand for the PL during cuts. In conclusion, ankle taping did not significantly affect planned change-of-direction or reactive agility performance, and did not demonstrate large changes in activity of the muscle complex in healthy basketballers

Mentalizing and motivation neural function during social interactions in autism spectrum disorders

AbstractAutism Spectrum Disorders (ASDs) are characterized by core deficits in social functions. Two theories have been suggested to explain these deficits: mind-blindness theory posits impaired mentalizing processes (i.e. decreased ability for establishing a representation of others' state of mind), while social motivation theory proposes that diminished reward value for social information leads to reduced social attention, social interactions, and social learning. Mentalizing and motivation are integral to typical social interactions, and neuroimaging evidence points to independent brain networks that support these processes in healthy individuals. However, the simultaneous function of these networks has not been explored in individuals with ASDs. We used a social, interactive fMRI task, the Domino game, to explore mentalizing- and motivation-related brain activation during a well-defined interval where participants respond to rewards or punishments (i.e. motivation) and concurrently process information about their opponent's potential next actions (i.e. mentalizing). Thirteen individuals with high-functioning ASDs, ages 12–24, and 14 healthy controls played fMRI Domino games against a computer-opponent and separately, what they were led to believe was a human-opponent. Results showed that while individuals with ASDs understood the game rules and played similarly to controls, they showed diminished neural activity during the human-opponent runs only (i.e. in a social context) in bilateral middle temporal gyrus (MTG) during mentalizing and right Nucleus Accumbens (NAcc) during reward-related motivation (Pcluster<0.05 FWE). Importantly, deficits were not observed in these areas when playing against a computer-opponent or in areas related to motor and visual processes. These results demonstrate that while MTG and NAcc, which are critical structures in the mentalizing and motivation networks, respectively, activate normally in a non-social context, they fail to respond in an otherwise identical social context in ASD compared to controls. We discuss implications to both the mind-blindness and social motivation theories of ASD and the importance of social context in research and treatment protocols

High‐Throughput Screen of Natural Product Extracts in A Yeast Model of Polyglutamine Proteotoxicity

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106714/1/cbdd12259.pd

MYC Overexpression Induces Prostatic Intraepithelial Neoplasia and Loss of Nkx3.1 in Mouse Luminal Epithelial Cells

Lo-MYC and Hi-MYC mice develop prostatic intraepithelial neoplasia (PIN) and prostatic adenocarcinoma as a result of MYC overexpression in the mouse prostate[1]. However, prior studies have not determined precisely when, and in which cell types, MYC is induced. Using immunohistochemistry (IHC) to localize MYC expression in Lo-MYC transgenic mice, we show that morphological and molecular alterations characteristic of high grade PIN arise in luminal epithelial cells as soon as MYC overexpression is detected. These changes include increased nuclear and nucleolar size and large scale chromatin remodeling. Mouse PIN cells retained a columnar architecture and abundant cytoplasm and appeared as either a single layer of neoplastic cells or as pseudo-stratified/multilayered structures with open glandular lumina—features highly analogous to human high grade PIN. Also using IHC, we show that the onset of MYC overexpression and PIN development coincided precisely with decreased expression of the homeodomain transcription factor and tumor suppressor, Nkx3.1. Virtually all normal appearing prostate luminal cells expressed high levels of Nkx3.1, but all cells expressing MYC in PIN lesions showed marked reductions in Nkx3.1, implicating MYC as a key factor that represses Nkx3.1 in PIN lesions. To determine the effects of less pronounced overexpression of MYC we generated a new line of mice expressing MYC in the prostate under the transcriptional control of the mouse Nkx3.1 control region. These “Super-Lo-MYC” mice also developed PIN, albeit a less aggressive form. We also identified a histologically defined intermediate step in the progression of mouse PIN into invasive adenocarcinoma. These lesions are characterized by a loss of cell polarity, multi-layering, and cribriform formation, and by a “paradoxical” increase in Nkx3.1 protein. Similar histopathological changes occurred in Hi-MYC mice, albeit with accelerated kinetics. Our results using IHC provide novel insights that support the contention that MYC overexpression is sufficient to transform prostate luminal epithelial cells into PIN cells in vivo. We also identified a novel histopathologically identifiable intermediate step prior to invasion that should facilitate studies of molecular pathway alterations occurring during early progression of prostatic adenocarcinomas

Detecting Traffic Data Anomalies in Longitudinal Signal Performance Measures

21-840521-8404The Utah Department of Transportation (UDOT) has continuously invested in traffic signal performance evaluation in Utah. The Brigham Young University (BYU) transportation research team developed a high-level scoring system to evaluate signal performance using four Automated Traffic Signal Performance Measures (ATSPM), including platoon ratio, split failures, arrivals on green, and red-light actuations. The scoring system helps UDOT engineers and planners to evaluate the performance of each signal. However, there is still a need to understand how intersections and corridors perform over time. Therefore, the purpose of this research was to use the scoring system developed in the previous research to analyze the signal performance longitudinally. The method described in this research expanded the study area from 20 to 32 signalized intersections and the study period from 24 days to 2 years. One additional ATSPM (approach volume) was also included. The BYU research team developed an interactive data visualization tool to show the change in signal performance measures over time, and several data anomalies were discovered in the ATSPM datasets. The research team applied linear regression, moving average and standard deviation, and distribution comparison methods to identify the data anomalies. However, due to the various types of data anomalies, only the moving average and standard deviation method was successful in identifying most of the data anomalies. Future investigation is needed to address the data anomalies and improve the data accuracy

Catalytic C(sp3)-H bond activation in tertiary alkylamines.

The development of robust catalytic methods to assemble tertiary alkylamines provides a continual challenge to chemical synthesis. In this regard, transformation of a traditionally unreactive C-H bond, proximal to the nitrogen atom, into a versatile chemical entity would be a powerful strategy for introducing functional complexity to tertiary alkylamines. A practical and selective metal-catalysed C(sp3)-H activation facilitated by the tertiary alkylamine functionality, however, remains an unsolved problem. Here, we report a Pd(II)-catalysed protocol that appends arene feedstocks to tertiary alkylamines via C(sp3)-H functionalization. A simple ligand for Pd(II) orchestrates the C-H activation step in favour of deleterious pathways. The reaction can use both simple and complex starting materials to produce a range of multifaceted γ-aryl tertiary alkylamines and can be rendered enantioselective. The enabling features of this transformation should be attractive to practitioners of synthetic and medicinal chemistry as well as in other areas that use biologically active alkylamines

Neratinib protects pancreatic beta cells in diabetes

The loss of functional insulin-producing β-cells is a hallmark of diabetes. Mammalian sterile 20-like kinase 1 (MST1) is a key regulator of pancreatic β-cell death and dysfunction; its deficiency restores functional β-cells and normoglycemia. The identification of MST1 inhibitors represents a promising approach for a β-cell-protective diabetes therapy. Here, we identify neratinib, an FDA-approved drug targeting HER2/EGFR dual kinases, as a potent MST1 inhibitor, which improves β-cell survival under multiple diabetogenic conditions in human islets and INS-1E cells. In a pre-clinical study, neratinib attenuates hyperglycemia and improves β-cell function, survival and β-cell mass in type 1 (streptozotocin) and type 2 (obese Leprdb/db) diabetic mouse models. In summary, neratinib is a previously unrecognized inhibitor of MST1 and represents a potential β-cell-protective drug with proof-of-concept in vitro in human islets and in vivo in rodent models of both type 1 and type 2 diabetes