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Freeway service patrol (FSPs) programs have been considered as an effective tool for traffic incident management in minimizing the adverse effects of traffic incidents. In this study, random parameters hazard-based duration modeling method was used to evaluate the impact of the newly implemented Alabama Service and Assistance Patrol (ASAP) program, using incident clearance time as a performance measure. It was determined that there is a statistically significant difference in the factors that influence incidents clearance times between incidents that occurred inside and outside the ASAP regions. A total of five variables (on-road, nighttime, peak hours, rain, and fire response present) were observed to have random effects along with ten fixed effects variables on incidents occurring inside the ASAP regions. On the other hand, incidents that occurred outside the ASAP regions were found to have three random effects variables (on-road, nighttime, and fire response present) and seven fixed effects variables. The estimation results indicate a significant association of incident clearance times to incident related variables such as involvement of CMVs, fatality, vehicle towing, seat belt indicated as involved, and on-road incidents that occurred both inside and outside the ASAP regions. The results also reveal that incident clearance times are influenced strongly by temporal variables (e.g., nighttime), traffic factors (e.g., AADT), and operational variables (e.g., fire response present) for incidents both inside and outside the ASAP area models. Overall, it was observed that the incident clearance times recorded in the regions where the ASAP program is in effect are significantly different. The findings of this study are expected to be useful for the state traffic incident management (TIM) agencies in developing and executing strategies to minimize incident clearance times. Ultimately, the study provides a data-driven evidence-based assessment of the ASAP program in the state., Author(s): Naima Islam (corresponding author) [1]; Emmanuel K. Adanu [1]; Alexander M. Hainen [2]; Steve Burdette [3]; Randy Smith [4]; Steven Jones [2] 1. Introduction Nonrecurrent traffic incidents cause acute [...]

The Fairest of Them All: Snow White and 21 Tales of Mothers and Daughters. By Maria Tatar. (Cambridge, MA: Belknap Press of Harvard University, 2020. Pp. xi + 225, preface, [...]

The role of staff involved with undergraduate admissions and recruitment has changed since the turn towards marketisation in higher education. This article focuses on the system in England following both a sharp rise in student fees and an associated tendency for the public university agenda and related social priorities, such as widening participation, to come up against more private and commercial priorities, such as business engagement, league table performance and internationalisation. Drawing on evidence from detailed interviews with admissions personnel, both academic and non-academic, across three disciplines within one higher prestige university, we revisit the notion of selectivity and the practice of selection. Tensions are revealed between two opposing approaches: a more traditional model of university admissions, as based on local knowledge and sensitivity towards underrepresented groups, and a purportedly merit-driven model, as driven by perceived market position. We explore the intricate and often unexpected ways in which staff reconcile their professed beliefs with their professional practices, and the complex identity work needed to renegotiate personal values in light of shifting institutional needs. Findings are offered as a microcosm for broader trends in the higher education sector., Author(s): Steven Jones [sup.1] , David Hall [sup.2] , Joanna Bragg [sup.1] Author Affiliations: (Aff1) 0000000121662407, grid.5379.8, Manchester Institute of Education, The University of Manchester, , Oxford Road, M13 9PL, [...]

Like many countries in sub-Saharan Africa, Ghana has witnessed an increase in the use of motorcycles for both commercial transport and private transport of people and goods. The rapid rise in commercial motorcycle activities has been attributed to the problem of urban traffic congestion and the general lack of reliable and affordable public transport in rural areas. This study investigates and compares factors that are associated with motorcycle crash injury outcomes in rural and urban areas of Ghana. This comparison is particularly important because the commercial use of motorcycles and their rapid growth in urban areas are a new phenomenon, in contrast to rural areas where people have long relied on motorcycles for their transportation needs. Preliminary analysis of the crash data revealed that more of the rural area crashes occurred under dark and unlit roadway conditions, while urban areas recorded more intersection-related crashes. Additionally, it was found that more pedestrian collisions happened in urban areas, while head-on collisions happened more in rural areas. The model estimation results show that collisions with a pedestrian, run-off-road, and collisions that occur under dark and unlit roadway conditions were more likely to result in fatal injury. Findings from this study are expected to help in crafting and targeting appropriate countermeasures to effectively reduce the occurrence and severity of motorcycle crashes throughout the country and, indeed, sub-Saharan Africa., Author(s): William Agyemang [1]; Emmanuel Kofi Adanu (corresponding author) [2]; Steven Jones [3] 1. Introduction Globally, road crashes are a leading cause of deaths and injuries, the burden of which [...]

Annually, side impact crashes contribute to a significant proportion of road fatalities. These crashes typically occur as a result of traffic violations at intersections. This study contributes to efforts in addressing side impact crashes at unsignalized intersections by performing a path analysis to unravel some behavioral trajectories through which these crashes occur. The study further investigated how these behavioral pathways influence the severity of the crashes. Crashes that occurred at unsignalized four-way intersections and T-junctions in Alabama were used for model estimations. Three precrash actions, failed to yield right-of-way at the stop sign, failed to yield right-of-way at a turn, and running stop sign, were considered. The model estimation results reveal that some of the crash factors were more associated with certain precrash factors but not others at either four-way intersections or T-junctions or both. It was observed that side impact crashes that occurred under daylight conditions at four-way intersections, for instance, were less likely to involve running a stop sign but more likely to involve failure to yield at the stop sign and failure to yield right-of-way at a turn, but under dark and unlit roadway conditions, the at-fault drivers were more likely to run a stop sign or fail to yield at a stop sign but less likely to be involved in failure to yield right-of-way at a turn. This approach to injury severity analysis uncovers complex underlying relationships between precrash actions, other contributing factors, and crash outcomes., Author(s): Emmanuel Kofi Adanu (corresponding author) [1]; Xiaobing Li [1]; Jun Liu [2]; Steven Jones [2] 1. Introduction In 2018, side impact crashes accounted for about 23% of passenger vehicle [...]

Current therapies for medulloblastoma, a highly malignant childhood brain tumour, impose debilitating effects on the developing child, and highlight the need for molecularly targeted treatments with reduced toxicity. Previous studies have been unable to identify the full spectrum of driver genes and molecular processes that operate in medulloblastoma subgroups. Here we analyse the somatic landscape across 491 sequenced medulloblastoma samples and the molecular heterogeneity among 1,256 epigenetically analysed cases, and identify subgroup-specific driver alterations that include previously undiscovered actionable targets. Driver mutations were confidently assigned to most patients belonging to Group 3 and Group 4 medulloblastoma subgroups, greatly enhancing previous knowledge. New molecular subtypes were differentially enriched for specific driver events, including hotspot in-frame insertions that target KBTBD4 and enhancer hijacking events that activate PRDM6. Thus, the application of integrative genomics to an extensive cohort of clinical samples derived from a single childhood cancer entity revealed a series of cancer genes and biologically relevant subtype diversity that represent attractive therapeutic targets for the treatment of patients with medulloblastoma., Author(s): Paul A. Northcott [1, 2]; Ivo Buchhalter [3, 4, 5]; A. Sorana Morrissy [6]; Volker Hovestadt [7]; Joachim Weischenfeldt [8]; Tobias Ehrenberger [9]; Susanne Grbner [1, 10]; Maia Segura-Wang [...]

Cervical cancer remains one of the leading causes of cancer-related deaths worldwide. Here we report the extensive molecular characterization of 228 primary cervical cancers, one of the largest comprehensive genomic studies of cervical cancer to date. We observed notable APOBEC mutagenesis patterns and identified SHKBP1, ERBB3, CASP8, HLA-A and TGFBR2 as novel significantly mutated genes in cervical cancer. We also discovered amplifications in immune targets CD274 (also known as PD-L1) and PDCD1LG2 (also known as PD-L2), and the BCAR4 long non-coding RNA, which has been associated with response to lapatinib. Integration of human papilloma virus (HPV) was observed in all HPV18-related samples and 76% of HPV16-related samples, and was associated with structural aberrations and increased target-gene expression. We identified a unique set of endometrial-like cervical cancers, comprised predominantly of HPV-negative tumours with relatively high frequencies of KRAS, ARID1A and PTEN mutations. Integrative clustering of 178 samples identified keratin-low squamous, keratin-high squamous and adenocarcinoma-rich subgroups. These molecular analyses reveal new potential therapeutic targets for cervical cancers., Author(s): The Cancer Genome Atlas Research Network; Albert Einstein College of Medicine; Robert D. Burk [1]; Zigui Chen [1]; Analytical Biological Services; Charles Saller [2]; Katherine Tarvin [2]; Barretos Cancer [...]

Factors related to drivers and their driving habits dominate the causation of traffic crashes. An in-depth understanding of the human factors that influence risky driving could be of particular importance to facilitate the application of effective countermeasures. This paper sought to investigate effects of human-centered crash contributing factors on crash outcomes. To select the methodology that best accounts for unobserved heterogeneity between crash outcomes, latent class (LC) logit model and random parameters logit (RPL) model were developed. Model estimation results generally show that serious injury crashes were more likely to involve unemployed drivers, no seatbelt use, old drivers, fatigued driving, and drivers with no valid license. Comparison of model fit statistics shows that the LC logit model outperformed the RPL model, as an alternative to the traditional multinomial logit (MNL) model., 1. Introduction Road traffic crashes occur from a combination of factors related to elements of the transportation system, made up of the road and its environment, vehicles, and road users, [...]

Background: Despite the different preoperative imaging modalities available for parathyroid adenoma localization, there is currently no uniform consensus on the most appropriate preoperative imaging algorithm that should be routinely followed prior to the surgical management of primary hyperparathyroidism (PHPT). We sought to determine the incremental value of adding neck ultrasonography to scintigraphy-based imaging tests. Methods: In a single institution, surgically naive patients with PHPT underwent the following localization studies before parathyroidectomy: 1) Tc-99m sestamibi imaging with single photon emission computed tomography/computed tomography (SPECT/CT) or Tc-99m sestamibi imaging with SPECT alone, or 2) ultrasonography in addition to those tests. We retrospectively collected data and performed a multivariate analysis comparing group I (single study) to group II (addition of ultrasonography) and risk of bilateral (BNE) compared with unilateral (UNE) neck exploration. Results: Our study included 208 patients. Group II had 0.45 times the odds of BNE versus UNE compared with group I (unadjusted odds ratio [OR] 0.45, 95% confidence interval [CI] 0.25-0.81, p = 0.008). When adjusting for patient age, sex, preoperative calcium level, use of intraoperative PTH monitoring, preoperative PTH level, adenoma size, and number of abnormal parathyroid glands, Group II had 0.48 times the odds of BNE versus UNE compared with group I (adjusted OR 0.48, 95% CI 0.23-1.03, p = 0.06). In a subgroup analysis, only the addition of ultrasonography to SPECT decreased the risk of undergoing BNE compared with SPECT alone (unadjusted OR 0.40, 95% CI 0.19-0.84, p = 0.015; adjusted OR 0.38, 95% CI 0.150.96, p= 0.043). Conclusion: The addition of ultrasonography to SPECT, but not to SPECT/CT, has incremental value in decreasing the extent of surgery during parathyroidectomy, even after adjusting for multiple confounding factors. Contexte : Malgre l'existence de diverses modalites dimagerie preoperatoire pour la localisation de l'adenome parathyroidien, on deplore actuellement l'absence de consensus en ce qui concerne l'algorithme le plus approprie a suivre au chapitre de l'imagerie prealable a une prise en charge chirurgicale de l'hyperparathyroidie primaire (HPTP). Nous avons voulu verifier si l'ajout de l'echographie du cou aux tests dima-gerie scintigraphique offrait une valeur ajoutee. Methodes : Dans un etablissement, des patients atteints d'HPTP n'ayant jamais subi d'intervention chirurgicale ont ete soumis a des examens de localisation preparathyroidectomie : 1) imagerie au moyen du sestamibi marque au Tc-99m avec tomographie paremission monophotonique/tomodensitometrie (SPECT/CT), ou imagerie au moyen du sestamibi marque au Tc-99m avec SPECT seule, our 2) echographie en plus de ces tests. Nous avons recueilli les donnees retrospectivement et effectue une analyse multivariee pour comparer le Groupe I (examen seul) au Groupe II (ajout de l'echographie) et la probabilite qu'ils subissent une exploration cervicale bilaterale (ECB) plutot qu'unilaterale (ECU). Resultats : Notre etude a recrute 208 patients. Le Groupe II s'est trouve expose a un risque 0,45 fois plus grand d'etre soumis a une ECB plutot qu'a une ECU, comparativement au Groupe I (rapport des cotes [RC] non ajuste 0,45, intervalle de confiance [IC] de 95 % 0,25-0,81, p = 0,008). Apres ajustement pour tenir compte de l'ge et du sexe des patients, de leur taux preoperatoire de calcium, de la surveillance peroperatoire de l'HPT, du taux preoperatoire de l'HPT, de la taille de l'adenome et du nombre de ganglions parathyroidiens anormaux, le Groupe II s'est revele expose a un risque 0,48 fois plus grand a l'egard de l'ECB plutot que de l'ECU comparativement au Groupe I (RC ajuste 0,48, IC de 95 % 0,23-1,03, p = 0,06). Selon une analyse de sous-groupe, seul l'ajout de l'echographie a la SPECT a reduit le risque de subir une ECB comparativement a la SPECT seule (RC non ajuste 0,40, IC de 95 % 0,19-0,84, p= 0,015; RC ajuste 0,38, IC de 95% 0,15-0,96, p = 0,043). Conclusion : L'ajout de l'echographie a la SPECT, mais non a la SPECT/CT, a offert une valeur ajoutee pour ce qui est de reduire l'etendue de l'operation durant la parathyroidectomie, meme apres ajustement pour tenir compte de plusieurs facteurs de confusion., Primary hyperparathyroidism (PHPT) is a common endocrine disorder characterized by an elevated parathyroid hormone (PTH) level and hypercalcemia. (1-3) Currently, the most common presentation of PHPT is an asymptomatic individual [...]

An outbreak of atypical pneumonia, referred to as severe acute respiratory syndrome (SARS) and first identified in Guangdong Province, China, has spread to several countries. The severity of this disease [...], We sequenced the 29,751-base genome of the severe acute respiratory syndrome (SARS)--associated coronavirus known as the Tor2 isolate. The genome sequence reveals that this coronavirus is only moderately related to other known coronaviruses, including two human coronaviruses, HCoV-OC43 and HCoV-229E. Phylogenetic analysis of the predicted viral proteins indicates that the virus does not closely resemble any of the three previously known groups of coronaviruses. The genome sequence will aid in the diagnosis of SARS virus infection in humans and potential animal hosts (using polymerase chain reaction and immunological tests), in the development of antivirals (including neutralizing antibodies), and in the identification of putative epitopes for vaccine development.

Background: Fine needle aspiration biopsy represents the critical initial diagnostic test used for evaluation of thyroid nodules. Our objectives were to determine the cytological distribution, the utility of clinicopathologic characteristics for predicting malignancy and the true proportion of cancer among individuals who presented with indeterminate cytology and had undergone thyroid surgery for suspicion of cancer. Methods: We retrospectively reviewed 1040 consecutive primary thyroid operations carried out over an 8-year period at a tertiary care endocrine referral centre. Follicular neoplasm (FN), Hiirthle cell neoplasm (HN), neoplasms suspicious for but not diagnostic of papillary carcinoma (IP) and neoplasms with cellular atypia (IA) were reviewed. Results: In all, 380 individuals presented with cytologically indeterminate thyroid nodules. Of these, 252 (66%) patients had FN, 47 (12%) HN, 44 (12%) IP, 26 (7%) IA and 11 (4%) had mixed diagnoses. Biopsied lesions were found to be malignant on pathological evaluation in 102 (27%) patients: 49 (19%) with FN, 11 (23%) HN, 28 (64%) IP and 9 (35%) with IA. Hemithyroidectomy was adequate definitive treatment in 196 of 225 (87%) patients with FN and 39 of 42 (93%) with HN. Significant associations with a cancer diagnosis were identified for smaller tumour size in patients with FN (p = 0.004) and right thyroid lobe location in patients with IP (p = 0.012), although these factors were nonsignificant in the corrected analyses for multiple comparisons. Conclusion: In a review of the experience at a Canadian centre, 4 operations were carried out to identify each cancer, and hemithyroidectomy was the optimal initial and definitive surgical approach for most patients. Contexte : La biopsie par aspiration a l'aiguille fine represente un test diagnostique initial crucial pour evaluer les nodules de la thyroide. Nos objectifs consistaient a determiner la distribution cytologique, l'utilite des caracteristiques clinico-pathologiques pour la prediction des cancers et la proportion reelle de cancers chez des personnes dont les resultats cytologiques etaient indetermines et qui ont subi une chirurgie de la thyroide pour un cancer presume. Methodes : Nous avons passe en revue de facon retrospective 1040 interventions thyroidiennes primaires consecutives effectuees sur une periode de 8 ans dans un centre de soins endocriniens tertiaires. Nous avons examine les cas de neoplasie folliculaire (NF), de neoplasie a cellules de Hirthle (NCH), de neoplasies papillaires presumees mais non averees (indeterminees, NPI), de meme que les neoplasies a cellules atypiques (NCA). Resultats : En tout, 380 patients ont presente des nodules thyroidiens indetermines a la cytologie. Parmi eux, 252 (66 %) presentaient une NF, 47 (12 %) une NCH, 44 (12 %) une NPI, 26 (7 %) une NCA et 11 (4 %) presentaient un diagnostic mixte. Les lesions soumises a la biopsie se sont revelees malignes a l'examen anatomopathologique chez 102 patients (27 %) : 49 (19 %) presentant une NF, 11 (23 %) une NCH, 28 (64 %) une NPI et 9 (35 %) une NCA. Pour 196 patients sur 225 (87 %) presentant une NF et 39 sur 42 (93 %) presentant une NCH, l'hemithyroidectomie a ete le traitement definitif adequat. Des liens significatifs ont ete etablis entre, d'une part, le diagnostic de cancer et, d'autre part, la taille plus petite des nodules chez les patients presentant une NF (p = 0,004) et la localisation au lobe thyroidien droit chez les patients atteints de NI (p = 0,012), bien que ces facteurs n'aient pas eu de portee significative aux analyses corrigees en fonction de multiples comparaisons. Conclusion : Lors d'une revue de l'experience accumulee dans un centre canadien, 4 interventions ont ete effectuees pour reconnaitre chaque cancer et l'hemithyroidectomie a ete l'approche chirurgicale initiale et definitive optimale chez la plupart des patients., Thyroid nodules are common in the general population; they are identified in about 5% of patients by palpation and 50% by ultrasound examination. (1) Fine needle aspiration biopsy (FNAB) represents [...]

Chromosomal translocations are critically involved in the molecular pathogenesis of B-cell lymphomas, and highly recurrent and specific rearrangements have defined distinct molecular subtypes linked to unique clinicopathological features (1,2). In [...]

An X chromosome single-nucleotide variant (SNV) scan of family members giving consent to the protocol (H07-02142) was performed to identify linkage to Xq28, an X-linked CK syndrome (CKS) recessive intellectual disability syndrome characterized by dysmorphism, cortical brain malformation and an asthenic build. The finding for CKS provides better insight into the spectrum of cholesterol-related disorders and the role of cholesterol in human development.

The study attempts to evaluate the data derived from the RNA sequencing of 18 ovarian carcinomas to identify variants in ARID1A mutations. The results indicate that ARIDIA mutations are present in ovarian carcinomas and that it is indicative of an early event in the transformation of endometriosis into cancer.

The failing heart is subject to elevated metabolic demands, adverse remodeling, chronic apoptosis, and ventricular dysfunction. The interplay among such pathologic changes is largely unknown. Several laboratories have identified a unique posttranslational modification that may have significant effects on cardiovascular function. The O-linked [beta]-N-acetylglucosamine (O-GlcNAc) posttranslational modification (O-GlcNAcylation) integrates glucose metabolism with intracellular protein activity and localization. Because O-GlcNAc is derived from glucose, we hypothesized that altered O-GlcNAcylation would occur during heart failure and figure prominently in its pathophysiology. After 5 d of coronary ligation in WT mice, cardiac O-GlcNAc transferase (OGT; which adds O-GlcNAc to proteins) and levels of OGlcNAcylation were significantly (P < 0.05) elevated in the surviving remote myocardium. We used inducible, cardiac myocyte-specific Cre recombinase transgenic mice crossed with loxP-flanked OGT mice to genetically delete cardiomyocyte OGT (cmOGT KO) and ascertain its role in the failing heart After tamoxifen induction, cardiac O-GlcNAcylation of proteins and OGT levels were significantly reduced compared with WT, but not in other tissues. WT and cardiomyocyte OGT KO mice underwent nonreperfused coronary ligation and were followed for 4 wk. Although OGT deletion caused no functional change in sham-operated mice, OGT deletion in infarcted mice significantly exacerbated cardiac dysfunction compared with WT. These data provide keen insights into the pathophysiology of the failing heart and illuminate a previously unrecognized point of integration between metabolism and cardiac function in the failing heart. heart failure | metabolism | O-GlcNAc | remodeling | infarct doi/ 10.1073/pnas.1001907107

There is a consensus that Gag-specific cytotoxic T lymphocyte (CTL) response plays a key role in the immune control of human immunodeficiency virus type 1 (HIV-1) infection. In this study, we analyzed all currently available gag sequences in the Los Alamos HIV sequence database and identified positive selection (PS) sites likely restricted by the host immune responses. We found that between 23.4% and 47.4% of PS sites were shared by clades A, B, and C of Gag, indicating similar positive selection pressure on Gag in different subtypes of HIV-1. Furthermore, a significant correlation was observed between the combined CTL and antibody responses and PS sites. The Gag regions of free from PS contained 9 CTL epitopes restricted by 11 HLA class I alleles associated with disease progression to acquired immune deficiency syndrome (AIDS). These analyses provide information important for the identification of cross-clade epitopes and development of a global HIV-1 vaccine. Key words: human immunodeficiency virus type 1, Gag, positive selection, cytotoxic T lymphocyte response. Resume : Il existe un consensus sur le fait que la reponse des lymphocytes T cytotoxiques (LTC) specifique a Gag joue un role cle dans le controle immunitaire de l'infection au virus d'immunodeficience humaine de type 1 (VIH-1). Dans cette etude, nous avons analyse toutes les sequences gag disponibles a partir de la banque de donnees de sequences du VIH de Los Alamos et avons identified des sites sous selection positive (SP) probablement restreints par les reponses immunes de l'hote. Nous avons trouve qu'entre 23.4% et 47.4% des sites sous SP etaient partages par les clades A, B et C de Gag, indiquant l'existence d'une pression de selection positive similaire sur Gag des differents sous-types de VIH-1. De plus, une correlation significative a ete observee entre les reponses LTC et anticorps combinees, et les sites SP. Les regions de Gag sans SP contenaient neuf epitopes generant une reponse LTCrestreinte par 11 alleles du CMH classe I associes a la progression de la maladie vers le SIDA. Les analyses fournissent une information importante pour identifier des epitopes partages par les clades et le developpement d'un vaccin global contre le HIV-1. Mots-cles: virus d'immunideficience humaine de type I, Gag, selection positive, reponse des lymphocytes T cytotoxiques. [Traduit par la Redaction], Introduction There are many challenges in developing an effective human immunodeficiency virus (HIV) vaccine. One of the greatest challenges is the genetic diversity of HIV, which is derived from the [...]

Although it is known that the methylation of DNA in 5' promoters suppresses gene expression, the role of DNA methylation in gene bodies is unclear (1-5). In mammals, tissue- and cell type-specific methylation is present in a small percentage of 5' CpG island (CGI) promoters, whereas a far greater proportion occurs across gene bodies, coinciding with highly conserved sequences (5-10). Tissue-specific intragenic methylation might reduce (3), or, paradoxically, enhance transcription elongation efficiency (1,2,4,5). Capped analysis of gene expression (CAGE) experiments also indicate that transcription commonly initiates within and between genes (11-15). To investigate the role of intragenic methylation, we generated a map of DNA methylation from the human brain encompassing 24.7 million of the 28 million CpG sites. From the dense, high-resolution coverage of CpG islands, the majority of methylated CpG islands were shown to be in intragenic and intergenic regions, whereas less than 3% of CpG islands in 5' promoters were methylated. The CpG islands in all three locations overlapped with RNA markers of transcription initiation, and unmethylated CpG islands also overlapped significantly with trimethylation of H3K4, a histone modification enriched at promoters (16). The general and CpG-island-specific patterns of methylation are conserved in mouse tissues. An in-depth investigation of the human SHANK3 locus (17,18) and its mouse homologue demonstrated that this tissue-specific DNA methylation regulates intragenic promoter activity in vitro and in vivo. These methylation-regulated, alternative transcripts are expressed in a tissue- and cell type-specific manner, and are expressed differentially within a single cell type from distinct brain regions. These results support a major role for intragenic methylation in regulating cell context-specific alternative promoters in gene bodies., To determine if intragenic DNA methylation is functional, we first generated high-resolution methylome maps of the human brain frontal cortex grey matter from two individuals. We developed two complementary next-generation [...]

A study was conducted to evaluate the efficacy of correlating cellular signatures with treatment outcome in the cases of patients with classic Hodgkin's lymphoma. Results indicated that an increased number of tumor-associated macrophages were related to a shortened survival rate in the case of such patients, thereby showing a new biomarker.

We previously demonstrated that the O-linked [beta]-N-acetylglucosamine (O-GlcNAc) posttranslational modification confers cardioprotection at least partially through mitochondrial-dependent mechanisms, but it remained unclear if O-GlcNAc signaling interfered with other mechanisms of cell death. Because ischemia/hypoxia causes endoplasmic reticulum (ER) stress, we ascertained whether O-GlcNAc signaling could attenuate ER stress-induced cell death per se. Before induction of ER stress (with tunicamycin or brefeldin A), we adenovirally overexpressed O-GlcNAc transferase (AdOGT) or pharmacologically inhibited O-GlcNAcase [via O-(2-acetamido-2-deoxy-D-glucopyranosylidene) amino-N-phenylcarbamate] to augment O-GlcNAc levels or adenovirally overexpressed O-GlcNAcase to reduce O-GlcNAc levels. AdOGT significantly (P < 0.05) attenuated the activation of the maladaptive arm of the unfolded protein response [according to C/EBP homologous protein (CHOP) activation] and cardiomyocyte death (reflected by percent propidium iodide positivity). Moreover, pharmacological inhibition of O-GlcNAcase significantly (P < 0.05) mitigated ER stress-induced CHOP activation and cardiac myocyte death. Interestingly, overexpression of GCA did not alter ER stress markers but exacerbated brefeldin A-induced cardiomyocyte death. We conclude that enhanced O-GlcNAc signaling represents a partially proadaptive response to reduce ER stress-induced cell death. These results provide new insights into a possible interaction between O-GlcNAc signaling and ER stress and may partially explain a mechanism of O-GlcNAc-mediated cardioprotection. O-linked [beta]-N-acetylglucosamine; endoplasmic reticulum doi: 10.1152/ajpheart.00553.2009.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.jbusres.2008.09.002 Byline: Steven L. Jones (a), John C. Yeoman (b) Keywords: Rationing; Decision making under risk and uncertainty; Option pricing; Marketing Abstract: We consider the problem of pricing event tickets for initial sale when demand is uncertain. It is a standard industry practice for a performer to contract with a promoter who underwrites the event and offers the tickets for sale at a posted price that is sticky in that it is either fixed or costly to adjust once sales begin. Promoters, therefore, bear price risk, and we show that bearing the risk associated with posting a sticky offer price amounts to writing a put option on the ticket revenue. Further, we show that optimal posted-offer prices can be expected to result in rationing (surpluses) if price uncertainty and price elasticity of demand are material (immaterial), even when the demand forecast is accurate. Our results have implications for a more general set of pricing problems in which items are offered for sale at sticky posted prices. Author Affiliation: (a) Kelley School of Business, Indiana University, Indianapolis, IN 46202, United States (b) Mike Cottrell School of Business, North Georgia College & State University, Dahlonega, GA 30597, United States Article History: Received 22 March 2008; Accepted 10 September 2008 Article Note: (footnote) [star] This paper has benefited from the helpful comments of Tony Cox, Ray De Gennaro, Phillip Powell, Eric Rasmussen, and participants at the Eastern Finance Association meeting and the Southern Finance Association meeting, as well as two anonymous referees and the editor. All errors remain the responsibility of the authors.

Recent advances in next generation sequencing (1-4} have made it possible to precisely characterize all somatic coding mutations that occur during the development and progression of individual cancers. Here we used these approaches to sequence the genomes (>43-fold coverage) and transcriptomes of an oestrogen-receptor-α-positive metastatic lobular breast cancer at depth. We found 32 somatic non-synonymous coding mutations present in the metastasis, and measured the frequency of these somatic mutations in DNA from the primary tumour of the same patient, which arose 9 years earlier. Five of the 32 mutations (in ABCB11, HAUS3, SLC24A4, SNX4 and PALB2) were prevalent in the DNA of the primary tumour removed at diagnosis 9years earlier, six (in KIFI C, USP28, MYH8, MORCI, KMA1468 and RNASEH2A) were present at lower frequencies (1-13%), 19 were not detected in the primary tumour, and two were undetermined. The combined analysis of genome and transcriptome data revealed two new RNA-editing events that recode the amino acid sequence of SRP9 and COG3. Taken together, our data show that single nucleotide mutational heterogeneity can be a property of low or intermediate grade primary breast cancers and that significant evolution can occur with disease progression., Lobular breast cancer is an oestrogen-receptor-positive ([ER.sup.+], also known as [ESRl.sup.+]) subtype of breast cancer (approximately 15% of all breast cancers). It is usually of low-intermediate histological grade and can [...]

Although sleep and circadian rhythm disturbances are significant features of bipolar disorder and are associated with illness severity and recurrence, less is known about their significance prior to illness onset. Therefore, this study investigated these variables using objective assessment methods within a sample at high-risk of bipolar spectrum disorders. Thirty-one high-risk and 24 age- and gender-matched control participants wore an actigraph for 7 days to obtain sleep and circadian activity data. Self-report measures of mood, bed and get-up times, and cognitive style were also obtained. High-risk participants exhibited greater variability in duration, fragmentation, and efficiency of sleep, shorter sleep duration, and later and more variable bedtimes than controls. They also had lower relative amplitude of activity patterns and made more positive self-appraisals for hypomanic experiences. Logistic regression showed that positive self-appraisal and variability in bedtime significantly discriminated between the two groups. Results suggest that sleep and circadian activity differences are apparent in high-risk participants and, therefore, may not simply represent an artifact of the illness. Such individuals also report cognitive styles consistent with those observed in bipolar patients. Relevance of these results to current evolutions of the instability theory of bipolar disorder is discussed. Keywords: actigraphy; hypomania; circadian rhythms; positive self-appraisal; cognitive style

Several measures of cognitive style have been shown to be elevated among persons diagnosed with bipolar disorder and those at risk for bipolar disorder. Several of these scales capture responses to positive affect, success, and hypomanic symptoms. We had two goals: (a) to use factor analyses to assess whether the constructs within these scales were statistically independent and (b) to examine whether the factors identified uniquely related to mania risk. A cross-national sample of 638 participants completed measures of cognitive style, including the Responses to Positive Affect scale, the Positive Overgeneralization Scale, and the Hypomanic Interpretations Questionnaire. To assess whether these measures might simply reflect more impulsive reactions to positive mood states, participants also completed the Barratt Impulsivity Scale. To measure risk of mania, participants completed the Hypomanic Personality Scale (HPS). Factor analyses suggested seven factors of cognitive style and impulsivity. Four factors uniquely correlated with HPS. That is, risk for mania related to higher scores on separable factors of acting before thinking, being overly positive in interpreting manic symptoms, being overly confident in response to success, and tendencies to dampen positive affect. Current findings suggest the need to consider multifaceted aspects of cognition in refining psychological treatments of bipolar disorder. Keywords: bipolar disorder; mania; cognition; confidence; attributions

The study aims to investigate four adult-type granulosa-cell tumors (GCTs) of the ovary and the role of FOXL2 mutation in the pathogenesis of GCTs. The results indicate that mutant FOXL2 is responsible for adult-type GCTs of the ovary.

OBJECTIVE: Concern for children exposed to elemental mercury prompted the Agency for Toxic Substances and Disease Registry and the Centers for Disease Control and Prevention to review the sources of [...]

During ischemia and heart failure, there is an increase in cardiac glycolysis. To understand if this is beneficial or detrimental to the heart, we chronically elevated glycolysis by cardiac-specific overexpression of phosphatase-deficient 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK-2) in transgenic mice. PFK-2 controls the level of fructose-2,6-bisphosphate (Fm-2,6-[P.sub.2]), an important regulator of phosphofructokinase and glycolysis. Transgenic mice had over a threefold elevation in levels of Fru-2,6-[P.sub.2]. Cardiac metabolites upstream of phosphofructokinase were significantly reduced, as would be expected by the activation of phosphofructokinase. In perfused hearts, the transgene caused a significant increase in glycolysis that was less sensitive to inhibition by palmitate. Conversely, oxidation of palmitate was reduced by close to 50%. The elevation in glycolysis made isolated cardiomyocytes highly resistant to contractile inhibition by hypoxia, but in vivo the transgene had no effect on ischemia-reperfusion injury. Transgenic hearts exhibited pathology: the heart weight-to-body weight ratio was increased 17%, cardiomyocyte length was greater, and cardiac fibrosis was increased. However, the transgene did not change insulin sensitivity. These results show that the elevation in glycolysis provides acute benefits against hypoxia, but the chronic increase in glycolysis or reduction in fatty acid oxidation interferes with normal cardiac metabolism, which may be detrimental to the heart. glycolysis; transgenic

Civil engineering departments in the United States were surveyed to ascertain the range of practices for conducting seminars for graduate students. Two separate internet-based survey instruments were developed and utilized. One survey targeted department heads to determine if the responding program had a seminar for graduate students and, if so, details about the program. In the instance where a program did not have a graduate student seminar, the survey solicited reasons for the program choosing to cancel or not have one. A second survey was disseminated to graduate students. It was intended to gather opinions of students regarding their experience with the graduate student seminar. Forty eight civil engineering department heads and 231 graduate students responded. The consensus among respondents is that a graduate seminar can be a valuable part of the student experience. DOI: 10.1061/(ASCE)1052-3928(2008)134:2(193) CE Database subject headings: Engineering education; Graduate study; Surveys.

Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a comprehensive molecular analysis of 164 carcinomas of the oesophagus derived from Western and Eastern populations. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. Oesophageal squamous cell carcinomas resembled squamous carcinomas of other organs more than they did oesophageal adenocarcinomas. Our analyses identified three molecular subclasses of oesophageal squamous cell carcinomas, but none showed evidence for an aetiological role of human papillomavirus. Squamous cell carcinomas showed frequent genomic amplifications of CCND1 and SOX2 and/or TP63, whereas ERBB2, VEGFA and GATA4 and GATA6 were more commonly amplified in adenocarcinomas. Oesophageal adenocarcinomas strongly resembled the chromosomally unstable variant of gastric adenocarcinoma, suggesting that these cancers could be considered a single disease entity. However, some molecular features, including DNA hypermethylation, occurred disproportionally in oesophageal adenocarcinomas. These data provide a framework to facilitate more rational categorization of these tumours and a foundation for new therapies., Author(s): The Cancer Genome Atlas Research Network; Analysis Working Group: Asan University; Jihun Kim [1]; BC Cancer Agency; Reanne Bowlby [2]; Andrew J. Mungall [2]; A. Gordon Robertson [2]; Brigham [...]

High-speed intersections pose a safety and operational challenge. Currently, no specific guidance for treating high-speed intersections exists, particularly in the case of intersections with substantial truck traffic. To fill in this gap, this paper presents a synthesis of findings from a literature review and a survey of practitioners. Results indicate that the primary safety concerns at high-speed intersections relate to red-light running and rear-end collisions. Further, operational and safety concerns at high-speed intersections were identified as being related to the different characteristics of trucks (e.g., accelerating/decelerating capabilities). The survey indicates no consensus among practitioners on how best to improve operations and safety at high-speed signalized intersections. Specific concerns over the liability and system/equipment reliability issues were raised. This note summarizes the findings from the literature review and survey and offers recommendations to increase awareness and acceptance for high-speed intersection treatments. CE Database subject headings: Traffic safety; Traffic control devices; Intersections; Traffic surveys.

Leukotriene [A.sub.4] (LT[A.sub.4]) hydrolase catalyzes a rate-limiting final biosynthetic step of leukotriene [B.sub.4] (LT[B.sub.4]), a potent lipid chemotatic agent and proinflammatory mediator. LT[B.sub.4] has been implicated in the pathogenesis of [...]

Author(s): Darwyn Kobasa [1]; Steven M. Jones [2, 3]; Kyoko Shinya [5]; John C. Kash [6]; John Copps [8]; Hideki Ebihara [2, 9, 10, 11]; Yasuko Hatta [12]; Jin Hyun [...]

Author(s): Darwyn Kobasa [sup.1] , Steven M. Jones [sup.2] [sup.3] , Kyoko Shinya [sup.5] , John C. Kash [sup.6] , John Copps [sup.8] , Hideki Ebihara [sup.2] [sup.9] [sup.10] [sup.11] [...], The deadly 1918 flu virus The 1918 &apos;Spanish flu&apos; influenza pandemic was unusually severe, causing about 50 million deaths. Why was it so destructive? The lack of antibiotics to fight secondary infections, and socioeconomic factors may be relevant. But experimental infection of nonhuman primates with reconstructed 1918 virus suggests that the lethal nature of the virus itself was a big factor. It is in fact the only influenza virus lethal to experimentally infected nonhuman primates, and the 1918 virus, unlike other strains, suppresses innate immune responses. The H5N1 viruses now circulating cause a severe lung infection similar to that caused by the 1918 virus and also suppress innate immunity, so therapies that protect this type of host immunity might reduce the severity of infection due to these influenza viruses. The 1918 influenza pandemic was unusually severe, resulting in about 50 million deaths worldwide.sup.1. The 1918 virus is also highly pathogenic in mice, and studies have identified a multigenic origin of this virulent phenotype in mice.sup.2,3,4. However, these initial characterizations of the 1918 virus did not address the question of its pathogenic potential in primates. Here we demonstrate that the 1918 virus caused a highly pathogenic respiratory infection in a cynomolgus macaque model that culminated in acute respiratory distress and a fatal outcome. Furthermore, infected animals mounted an immune response, characterized by dysregulation of the antiviral response, that was insufficient for protection, indicating that atypical host innate immune responses may contribute to lethality. The ability of influenza viruses to modulate host immune responses, such as that demonstrated for the avian H5N1 influenza viruses.sup.5, may be a feature shared by the virulent influenza viruses.

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors increase endothelial nitric oxide synthase (eNOS) activity by multiple mechanisms. We previously reported that genetic overexpression of eNOS improves survival and cardiac function in congestive heart failure (CHF). In the present study, we tested the hypothesis that low-dose treatment with an 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor exerts beneficial effects on survival and/or cardiac function in a murine model of CHF. Mice were subjected to permanent ligation of the left coronary artery and randomized to receive either saline vehicle or simvastatin (0.25 mg/kg) 2 h after myocardial infarction and daily (0.25 mg/kg) for 7 days, followed by 21 days of administration every other day for a total duration of 28 days. Myocardial infarct size was not reduced by simvastatin therapy (P = not significant between groups). Simvastatin treatment did significantly (P < 0.05) improve survival (45%) compared with vehicle treatment (25%). In addition, simvastatin treatment significantly improved (P < 0.01) left ventricular function and significantly (P < 0.01) abrogated cardiac hypertrophy and pulmonary edema compared with vehicle treatment. The protective effects of simvastatin were abrogated by delayed initiation of treatment or genetic ablation of eNOS. In conclusion, low-dose simvastatin therapy significantly improves survival and cardiac function and reduces both cardiac hypertrophy and pulmonary edema via an eNOS-dependent mechanism in a murine model of CHF. nitric oxide; 3-hydroxy-3-methylglutaryl coenzyme A; myocardial infarction; ventricular remodeling; echocardiography

Rhodococcus sp. RHA1 (RHA1) is a potent polychlorinated biphenyl-degrading soil actinomycete that catabolizes a wide range of compounds and represents a genus of considerable industrial interest. RHA1 has one of the largest bacterial genomes sequenced to date, comprising 9,702,737 bp (67% G+C) arranged in a linear chromosome and three linear plasmids. A targeted insertion methodology was developed to determine the telomeric sequences. RHA1's 9,145 predicted protein-encoding genes are exceptionally rich in oxygenases (203) and ligases (192). Many of the oxygenases occur in the numerous pathways predicted to degrade aromatic compounds (30) or steroids (4). RHA1 also contains 24 nonribosomal peptide synthase genes, six of which exceed 25 kbp, and seven polyketide synthase genes, providing evidence that rhodococci harbor an extensive secondary metabolism. Among sequenced genomes, RHA1 is most similar to those of nocardial and mycobacterial strains. The genome contains few recent gene duplications. Moreover, three different analyses indicate that RHA1 has acquired fewer genes by recent horizontal transfer than most bacteria characterized to date and far fewer than Burkholderia xenovorans LB400, whose genome size and catabolic versatility rival those of RHA1. RHA1 and LB400 thus appear to demonstrate that ecologically similar bacteria can evolve large genomes by different means. Overall, RHA1 appears to have evolved to simultaneously catabolize a diverse range of plant-derived compounds in an [O.sub.2]-rich environment. In addition to establishing RHA1 as an important model for studying actinomycete physiology, this study provides critical insights that facilitate the exploitation of these industrially important microorganisms. biodegradation | actinomycete | linear chromosome | aromatic pathways | oxygenase

Whole-genome sampling analysis with Affymetrix GeneChip Human Mapping 100K arrays is used to study 100 children with idiopathic mental retardation and normal results of standard chromosomal analysis. It is found that this technology can detect at least twice as many potentially pathogenic de novo copy-number variants, as conventional cytogenetic analysis can in people with mental retardation.

We analyzed 8.55 million LongSAGE tags generated from 72 libraries. Each LongSAGE library was prepared from a different mouse tissue. Analysis of the data revealed extensive overlap with existing gene data sets and evidence for the existence of [approximately equal to] 24,000 previously undescribed genomic loci. The visual cortex, pancreas, mammary gland, preimplantation embryo, and placenta contain the largest number of differentially expressed transcripts, 25% of which are previously undescribed loci. alternative transcripts | development | serial analysis of gene expression

Author(s): Steven M Jones [1, 2, 9]; Heinz Feldmann (corresponding author) [1, 3, 9]; Ute Stroher [1, 3]; Joan B Geisbert [4]; Lisa Fernando [1]; Allen Grolla [1]; Hans-Dieter Klenk [...]

Cryptococcus neoformans is a basidiomycetous yeast ubiquitous in the environment, a model for fungal pathogenesis, and an opportunistic human pathogen of global importance. We have sequenced its ~20-megabase genome, which contains ~6500 intron-rich gene structures and encodes a transcriptome abundant in alternatively spliced and antisense messages. The genome is rich in transposons, many of which duster at candidate centromeric regions. The presence of these transposons may drive karyotype instability and phenotypic variation. C. neoformans encodes unique genes that may contribute to its unusual virulence properties, and comparison of two phenotypically distinct strains reveals variation in gene content in addition to sequence polymorphisms between the genomes., With an increased immunocompromised population as a result of AIDS and widespread immunosuppressive therapy, Cryptococcus neoformans has emerged as a major pathogenic microbe in patients with impaired immunity (1). C. [...]

Stenosis-induced thrombosis and abandonment of the hemodialysis synthetic graft is an important cause of morbidity and mortality. The graft vascular circuit is a unique low-resistance shunt that has not yet been systematically evaluated. In this study, we developed a mathematical model of this circuit. Pressure losses ([DELTA]Ps) were measured in an in vitro experimental apparatus and compared with losses predicted by equations from the engineering literature. We considered the inflow artery, arterial and venous anastomoses, graft, stenosis, and outflow vein. We found significant differences between equations and experimental results, and attributed these differences to the transitional nature of the flow. Adjustment of the equations led to good agreement with experimental data. The resulting mathematical model predicts relations between stenosis, blood flow, intragraft pressure, and important clinical variables such as mean arterial blood pressure and hematocrit. Application of the model should improve understanding of the hemodynamics of the stenotic graft vascular circuit. [DOI: 10.1115/1.1835353]

Inducible nitric oxide synthase (iNOS) has been implicated in the pathophysiology of congestive heart failure (CHF). Given the extensive evidence supporting this concept, we hypothesized that iNOS deficiency (iNO[S.sup.-/-]) would attenuate the severity of CHF in mice. Mice were subjected to permanent occlusion [myocardial infarction (MI)] of the proximal left anterior descending coronary artery to produce CHF. Cardiac function was assessed in vivo using echocardiography and ultraminiature ventricular pressure catheters. Sham wild-type (n = 17), sham iNO[S.sup.-/-] (n = 8), MI wild-type (n = 56), and MI iNO[S.sup.-/-] (n = 48) mice were subjected to MI (or sham MI) and followed for 1 mo. Deficiency of iNOS did not alter survival during CHF compared with wild type (35% vs. 32%, P = not significant). Furthermore, fractional shortening and cardiac output were not significantly different between wild-type (9.6 [+ or -] 2.0% and 441 [+ or -] 20 [micro]l x [min.sup.-1] x [g.sup.-1]) and iNO[S.sup.-/-](9.8 [+ or -] 1.3% and 471 [+ or -] 26 [micro]l x [min.sup.-1] x [g.sup.-1]) mice. The extent of cardiac hypertrophy and pulmonary edema was also similar between wild-type and iNO[S.sup.-/-] mice. None of the indexes demonstrated any significant differences between iNO[S.sup.-/-] and wild-type mice subjected to MI. These findings indicate that deficiency of iNOS does not significantly affect severe CHF in mice after MI. myocardial infarction; nitric oxide; physiology; inducible nitric oxide synthase

We address the problem of providing guaranteed quality-of-service (QoS) connections over a multifrequency time-division multiple-access (MF-TDMA) system that employs differential phase-shift keying (DPSK) with various modulation modes. The problem can be divided into two parts--resource calculation and resource allocation. We present algorithms for performing these two tasks and evaluate their performance in the case of a Milstar extremely high frequency satellite communication (EHF-SATCOM) system. In the resource-calculation phase, we calculate the minimum number of timeslots required to provide the desired level of bit-error rate (BER) and data rate. The BER is directly affected by the disturbance in the link parameters. We use a Markov modeling technique to predict the worst case disturbance over the connection duration. The Markov model is trained offline to generate a transition-probability matrix, which is then used for predicting the worst case disturbance level. We provide simulation results to demonstrate that our scheme outperforms the scheme currently implemented in the EHF-SATCOM system. The resource-allocation phase addresses the problem of allocating actual timeslots in the MF-TDMA channel structure (MTCS). If we view the MTCS as a collection of bins, then the allocation of the timeslots can be considered as a variant of the dynamic bin-packing problem. Because the this problem is known to be NP-complete, obtaining an optimal packing scheme requires a prohibitive amount of computation. We propose a novel packing heuristic called reserve channel with priority (RCP) fit and show that it outperforms two common bin-packing heuristics. Index Terms--Bin packing, Markov modeling, multifrequency time-division multiple-access (MF-TDMA), prediction, quality of service (QoS), resource allocation, satellite.

Serial Analysis of Gene Expression (SAGE) has proven to be an important alternative to micro-array techniques for global profiling of mRNA populations. We have developed preprocessing methodologies to address problems in analyzing SAGE data due to noise caused by sequencing error, normalization methodologies to account for libraries sampled at different depths, and missing tag imputation methodologies to aid in the analysis of poorly sampled SAGE libraries. We have also used subspace selection using the Wilcoxon rank sum test to exclude tags that have similar expression levels regardless of source. Using these methodologies we have clustered, using the OPTICS algorithm, 88 SAGE libraries derived from cancerous and normal tissues as well as cell line material. Our results produced eight dense clusters representing ovarian cancer cell line, brain cancer cell line, brain cancer bulk tissue, prostate tissue, pancreatic cancer, breast cancer cell line, normal brain, and normal breast bulk tissue. The ovarian cancer and brain cancer cell lines clustered closely together, leading to a further investigation on possible associations between these two cancer types. We also investigated the utility of gene expression data in the classification between normal and cancerous tissues. Our results indicate that brain and breast cancer libraries have strong identities allowing robust discrimination from their normal counterparts. However, the SAGE expression data provide poor predictive accuracy in discriminating between prostate and ovarian cancers and their respective normal tissues. Categories and Subject Descriptors: J3 [Life and Medical Sciences]--Biology and genetics; H.3.3 [Information Storage and Retrieval]: Information Search and Retrieval--Clustering General Terms: Algorithms, Experimentation Additional Key Words and Phrases: Gene expression, clustering, classification, cancer profiling

Aerogel collectors have been deployed in low-Earth orbit to collect orbital debris and micrometeorites. An array of silica aerogel collectors is currently en-route back to Earth following an encounter with the Comet Wild-2 on board the Stardust spacecraft. Stardust is returning, for laboratory analysis, cometary and interstellar dust grains which impacted into the aerogel collectors at hypervelocities. While the morphology of impact craters in aerogels has been studied empirically, a theoretical understanding of the physical mechanisms responsible for the formation of impact craters in these solids is lacking. Here we propose and test a model of compaction driven impact cratering in aerogels. Our model derives impact crater dimensions directly from energy and momentum deposition. Keywords: Cratering; Impact processes; Comets; Asteroids

Genome sequences of chicken (low pathogenic avian influenza [LPAI] and highly pathogenic avian influenza [HPAI]) and human isolates from a 2004 outbreak of H7N3 avian influenza in Canada showed a [...]

Rhodococcus sp. strain RHA1, a potent polychlorinated-biphenyl (PCB)-degrading strain, contains three linear plasmids ranging in size from 330 to 1,100 kb. As part of a genome sequencing project, we report here the complete sequence and characterization of the smallest and least-well-characterized of the RHA1 plasmids, pRHL3. The plasmid is an actinomycete invertron, containing large terminal inverted repeats with a tightly associated protein and a predicted open reading frame (ORF) that is similar to that of a mycobacterial rep gene. The pRHL3 plasmid has 300 putative genes, almost 21% of which are predicted to have a catabolic function. Most of these are organized into three clusters. One of the catabolic clusters was predicted to include limonene degradation genes. Consistent with this prediction, RHA1 grew on limonene, carveol, or carvone as the sole carbon source. The plasmid carries three cytochrome P450-encoding (CYP) genes, a finding consistent with the high number of CYP genes found in other actinomycetes. Two of the CYP genes appear to belong to novel families; the third belongs to CYP family 116 but appears to belong to a novel class based on the predicted domain structure of its reductase. Analyses indicate that pRHL3 also contains four putative 'genomic islands' (likely to have been acquired by horizontal transfer), insertion sequence elements, 19 transposase genes, and a duplication that spans two ORFs. One of the genomic islands appears to encode resistance to heavy metals. The plasmid does not appear to contain any housekeeping genes. However, each of the three catabolic clusters contains related genes that appear to be involved in glucose metabolism.

Previous studies indicate that deficiency of endothelial nitric oxide (NO) synthase (eNOS)-derived NO exacerbates myocardial reperfusion injury. We hypothesized that overexpression of eNOS would reduce the extent of myocardial ischemia-reperfusion (MI/R) injury. We investigated two distinct strains of transgenic (TG) mice overexpressing the eNOS gene (eNOS TG). Bovine eNOS was overexpressed in one strain (eNOS TG-Kobe), whereas the human eNOS gene was overexpressed in the other strain (eNOS TG-RT). Non-TG (NTG) and eNOS TG mice were subjected to 30 min of coronary artery occlusion followed by 24 h of reperfusion, and the extent of myocardial infarction was determined. Myocardial infarct size was reduced by 33% in the eNOS TG-Kobe strain (P < 0.05 vs. NTG) and by 32% in the eNOS TG-RT strain (P < 0.05 vs. NTG). However, postischemic cardiac function (cardiac output, fractional shortening) was not improved in the eNOS TG-Kobe mouse at 24 h of reperfusion [P = not significant (NS) vs. NTG]. In additional studies, eNOS TG-Kobe mice were subjected to 30 min of myocardial infarction and 7 days of reperfusion. Fractional shortening and the first derivative of left ventricular pressure were measured in eNOS TG-Kobe and NTG mice, and no significant differences in contractility were observed (P = NS) between the eNOS TG mice and NTG controls. Left ventricular end-diastolic pressure was significantly (P < 0.05 vs. NTG) reduced in the eNOS TG-Kobe strain at 7 days of reperfusion. The cardioprotective effects of eNOS overexpression on myocardial infarct size were ablated by [N.sup.[omega]]-nitro-L-arginine methyl ester (300 mg/kg) pretreatment. Thus genetic overexpression of eNOS in mice attenuates myocardial infarction after MI/R but falls to significantly protect against postischemic myocardial contractile dysfunction in mice. myocardial infarction; cardiac dysfunction; murine model