bluuebunny/crossref_metadata_2025 huggingface dataset:
Cognitive function after several years of antiretroviral therapy with stable central nervous system penetration score
Authors: Kahouadji Y , Dumurgier J , Sellier P , Lapalus P , Delcey V , Bergmann JF , Hugon J , Paquet C
Published: October 2012

Objectives

Previous studies in HIV‐infected populations have yielded conflicting results on the effect of antiretroviral therapy (ART) on cognition. Our objective was to investigate the effect of several years of ART with stable central nervous system penetration effectiveness (CPE) score on neuropsychological performance in HIV‐infected individuals.

Methods

We analysed a clinical cohort of HIV‐infected patients who initiated ART between June 2003 and December 2006 and maintained stable CPE scores. Patients were evaluated with a short neuropsychological battery. Using linear regression, we examined the relationship between results of cognitive tests and CPE scores in all patients.

Results

Patients were divided into three similarly sized groups (CPE ≤ 1, CPE between 1.5 and 2.5, and CPE ≥ 2.5). We found that ART with high CPE scores was associated with poorer executive performances in HIV‐1‐infected patients.

Conclusion

These results suggest that cognitive performance in treated HIV‐infected patients could be influenced by ART.
Nurses as withdrawers of life sustaining treatment in paediatric intensive care
Authors: Birchley Giles , Cejer Bev
Published: October 2012

Background: Withdrawal of life saving medical treatment is a common modality of death within UK paediatric intensive care units (PICUs). The majority of treatment withdrawals are carried out by medical staff, usually the consultant in charge of the child's care.

Aim: To assess current practice of experienced PICU nurses performing the key tasks in treatment withdrawal once the decision has been made and its legal implications.

Design and Method: The study was divided into three chronologically successive phases. In phase 1, a 12‐item paper survey was circulated to nursing staff on a UK PICU. In phase 2, a three‐item survey regarding current practice was sent to nurse managers on 22 UK PICUs. In phase 3, analysis of legal issues related to nurses withdrawing treatment was undertaken.

Results: Poor response rates to both surveys limited their value; however, they may stimulate discussion of the issue within nursing. Phase 1 received 15 of 100 (15%) responses; open‐ended questions highlighted practitioner concerns. Eight of twenty‐two (36%) responses for phase 2 showed no consistent approach to the issue nationally. Legal analysis indicated that the law was untested in this area and nurses would be advised to withdraw treatment only if following a documented medical plan. Risks of legal and regulatory action could be reduced by formulating clear guidelines.

Conclusion: PICU nurses could potentially enact withdrawal, but discussion is needed to resolve uncertainties.

Relevance to Clinical Practice: National Guidelines from within the PICU community could assist nurses participating in treatment withdrawal.
“They Don't Get Speak Our Language Right”: Language Standardization, Power And Migration among the Q'eqchi' Maya
Authors: Romero Sergio
Published: October 2012

This article examines the effect of emerging vernaculars on the social diffusion and cultural roles of standardization projects in multi‐dialectal migrant communities. I explore the impact of Standard Q'eqchi', a standard variety crafted by language activists, on Lowland Q'eqchi', a new vernacular variety of Q'eqchi' Mayan spoken in migrant rural communities in northwestern and northern Guatemala. Rather than being innovations, the sociolinguistic history of highland migrants backgrounds the social meanings associated with both varieties. The enregisterment of Lowland Q'eqchi' and Standard Q'eqchi' occurred concurrently in the lowlands, reinforcing and enabling each other. I discuss the congruent articulation of successful standardization projects with emerging local regimes of social indexicality and the way ethnic ideologies and their linguistic expression mediate changes in cultural representations of ethnicity, authority and education among the Q'eqchi' Maya. [Language ideologies, dialectology, Q'eqchi', Mayan languages, Mesoamerica]
Impact of Polymers on Texture Properties of Cosmetic Emulsions: A Methodological Approach
Authors: Gilbert Laura , Picard Celine , Savary Geraldine , Grisel Michel
Published: October 2012

A methodology, particularly well adapted to the evaluation of cosmetic creams containing various texturing agents, is defined here using the Spectrum Descriptive Analysis method. The objectives were to describe and to understand the contributions of the texturing agents to the texture attributes of oil‐in‐water emulsions. The study focused on eight hydrophilic polymers, either natural (e.g., xanthan), semi‐synthetic (e.g., hydroxypropyl guar) or synthetic (e.g., carbomer), incorporated each one in an o/w emulsion. Eight texture attributes were selected and precisely defined, with strict evaluation procedures and notation scales. These attributes were gloss, integrity of shape, penetration and compression forces, stringiness, difficulty of spreading, absorbency and stickiness. A quantitative frame of reference was also developed. The methodology accuracy was evaluated through statistical analysis thus proving the sensory panel was highly discriminative, reproducible and repetitive. Principal component analysis underlined that polymers conferred to creams a very different skin feel when compared to the “control” emulsion without polymer. Synthetic polymers were characterized by higher consistency and lower gloss; semi‐synthetic polymers and xanthan by higher degrees of stringiness, whereas carob exhibited intermediate properties.

Practical Applications

This study may concern all the actors of the cosmetic industry, either the marketing, the quality control or the research and development departments. The developed methodology with precise definitions, strict and reproducible protocols, and with a frame of reference will be an accurate and useful tool to improve or optimize sensory evaluations of cosmetic creams, especially to investigate all the sensory aspects conferred to products by texturing agents. In the present study, the eight polymers were chosen as frequently used in cosmetic applications. As a consequence, both the methodology and the results are precious tools for product development and product optimization in order to meet consumers' texture quality requirements.
Computational Fluid Dynamics Modeling of a Self-Recuperative Burner and Development of a Simplified Equivalent Radiative Model
Authors: Sayah Haytham , Nemer Maroun , Nehmé Wassim , Clodic Denis
Published: October 2012

The solution for dynamic modeling of reheating furnaces requires a burner model, which is simultaneously accurate and fast. Based on the fact that radiative heat transfer is the most dominant heat transfer mode in high-temperature processes, the present study develops a simplified flame representation model that can be used for dynamic simulation of heat transfer in reheating furnaces. The first part of the paper investigates, experimentally and computationally, gas combustion in an industrial burner. Experiments aim at establishing an experimental database of the burner characteristics. This database is compared with numerical simulations in order to establish a numerical model for the burner. The numerical burner model was solved using a commercial computational fluid dynamics (CFD) software (FLUENT 6.3.26). A selection of results is presented, highlighting the usefulness of CFD as a modeling tool for industrial scale burners. In the second part of the paper, a new approach called the “emissive volume approach” is established. This approach consists of replacing the burner flame by a number of emissive volumes that replicates the radiative effect of the flame. Comparisons with CFD results show a difference smaller than 1% is achieved with the emissive volume approach, while computational time is divided by 40.
Pumping Energy Saving Using Nanoparticle Suspensions as Heat Transfer Fluids
Authors: Corcione Massimo , Cianfrini Marta , Quintino Alessandro
Published: October 2012

The pumping power diminution consequent to the use of nanoparticle suspensions as heat transfer fluids is analyzed theoretically assuming that nanofluids behave like single-phase fluids. In this hypothesis, all the heat transfer and friction factor correlations originally developed for single-phase flows can be used also for nanoparticle suspensions, provided that the thermophysical properties appearing in them are the nanofluid effective properties calculated at the reference temperature. In this regard, two empirical equations, based on a wide variety of experimental data reported in the literature, are used for the evaluation of the nanofluid effective thermal conductivity and dynamic viscosity. Conversely, the other effective properties are computed by the traditional mixing theory. Both laminar and turbulent flow regimes are investigated, using the operating conditions, the nanoparticle diameter, and the solid–liquid combination as control parameters. The fundamental result obtained is the existence of an optimal particle loading for minimum cost of operation at constant heat transfer rate. A set of empirical dimensional algebraic equations is proposed to determine the optimal particle loading of water-based nanofluids.
Genetic Subpopulations of Rift Valley Fever Virus Strains ZH548 and MP-12 and Recombinant MP-12 Strains
Authors: Lokugamage Nandadeva , Freiberg Alexander N. , Morrill John C. , Ikegami Tetsuro
Published: October 2012

Rift Valley fever virus strain MP-12 was generated by serial plaque passages of parental strain ZH548 12 times in MRC-5 cells in the presence of a chemical mutagen, 5-fluorouracil. As a result, MP-12 encoded 4, 9, and 10 mutations in the S, M, and L segments, respectively. Among them, mutations in the M and L segments were responsible for attenuation, while the MP-12 S segment still encoded a virulent phenotype. We performed high-throughput sequencing of MP-12 vaccine, ZH548, and recombinant MP-12 (rMP-12) viruses. We found that rMP-12 contains very low numbers of viral subpopulations, while MP-12 and ZH548 contain 2 to 4 times more viral genetic subpopulations than rMP-12. MP-12 genetic subpopulations did not encode the ZH548 sequence at the 23 MP-12 consensus mutations. On the other hand, 4 and 2 mutations in M and L segments of MP-12 were found in ZH548 subpopulations. Thus, those 6 mutations were no longer MP-12-specific mutations. ZH548 encoded several unique mutations compared to other Egyptian strains, i.e., strains ZH501, ZH1776, and ZS6365. ZH548 subpopulations shared nucleotides at the mutation site common with those in the Egyptian strains, while MP-12 subpopulations did not share those nucleotides. Thus, MP-12 retains unique genetic subpopulations and has no evidence of reversion to the ZH548 sequence in the subpopulations. This study provides the first information regarding the genetic subpopulations of RVFV and shows the genetic stability of the MP-12 vaccine manufactured in MRC-5 cells.
Development of Neurological Disease Is Associated with Increased Immune Activation in Simian Immunodeficiency Virus-Infected Macaques
Authors: Dang Que , Whitted Sonya , Goeken Robert M. , Brenchley Jason M. , Matsuda Kenta , Brown Charles R. , Lafont Bernard A. P. , Starost Matthew F. , Iyengar Ranjini , Plishka Ronald J. , Buckler-White Alicia , Hirsch Vanessa M.
Published: October 2012

Simian immunodeficiency virus (SIV) infection of macaques can result in central nervous system disorders, such as meningitis and encephalitis. We studied 10 animals inoculated with brain-derived virus from animals with SIV encephalitis. Over half of the macaques developed SIV-induced neurologic disease. Elevated levels of systemic immune activation were observed to correlate with viral RNA in the cerebral spinal fluid but not with plasma viral load, consistent with a role for SIV in the pathogenesis of neurologic disease.
A Small-RNA Enhancer of Viral Polymerase Activity
Authors: Perez Jasmine T. , Zlatev Ivan , Aggarwal Shilpa , Subramanian Sailakshmi , Sachidanandam Ravi , Kim Baek , Manoharan Muthiah , tenOever Benjamin R.
Published: October 2012

Influenza A virus (IAV) is an unremitting virus that results in significant morbidity and mortality worldwide. Key to the viral life cycle is the RNA-dependent RNA polymerase (RdRp), a heterotrimeric complex responsible for both transcription and replication of the segmented genome. Here, we demonstrate that the viral polymerase utilizes a small RNA enhancer to regulate enzymatic activity and maintain stoichiometric balance of the viral genome. We demonstrate that IAV synthesizes small viral RNAs (svRNAs) that interact with the viral RdRp in order to promote genome replication in a segment-specific manner. svRNAs localize to the nucleus, the site of IAV replication, are synthesized from the positive-sense genomic intermediate, and interact within a novel RNA binding channel of the polymerase PA subunit. Synthetic svRNAs promote polymerase activity
in vitro
, while loss of svRNA inhibits viral RNA synthesis in a segment-specific manner. Taking these observations together, we mechanistically define svRNA as a small regulatory enhancer RNA, which functions to promote genome replication and maintain segment balance through allosteric modulation of polymerase activity.
Reduced Infectivity of Adenovirus Type 5 Particles and Degradation of Entering Viral Genomes Associated with Incomplete Processing of the Preterminal Protein
Authors: Kato Sayuri E. , Chahal Jasdave S. , Flint S. J.
Published: October 2012

To investigate further the contribution of the adenovirus type 5 (Ad5) E1B 55-kDa protein to genome replication, viral DNA accumulation was examined in primary human fibroblasts and epithelial cells infected with Ad5 or the E1B 55-kDa-null mutant Hr6. Unexpectedly, all cell types were observed to contain a significantly higher concentration of entering Hr6 than of Ad5 DNA, as did an infectious unit of Hr6. However, the great majority of the Hr6 genomes were degraded soon after entry. As this unusual phenotype cannot be ascribed to the Hr6 E1B frameshift mutation (J. S. Chahal and S. J. Flint, J. Virol. 86:3064–3072, 2012), the sequences of the Ad5 and Hr6 genomes were compared by using high-throughput sequencing. Seven previously unrecognized mutations were identified in the Hr6 genome, two of which result in substitutions in virion proteins, G315V in the preterminal protein (preTP) and A406V in fiber protein IV. Previous observations and the visualization by immunofluorescence of greater numbers of viral genomes entering the cytosol of Hr6-infected cells than of Ad5-infected cells indicated that the fiber mutation could not be responsible for the low-infectivity phenotype of Hr6. However, comparison of the forms of terminal protein present in purified virus particles indicated that the production of mature terminal protein from a processing intermediate is impaired in Hr6 particles. We therefore propose that complete processing of preTP within virus particles is necessary for the ability of viral genomes to become localized at appropriate sites and persist in infected cells.
Violence in the emergency department: a multicentre survey of nurses’ perceptions in Nigeria
Authors: Ogundipe Kolawole Olubunmi , Etonyeaku Amarachukwu Chiduziem , Adigun Ismaila , Ojo Emmanuel O , Aladesanmi Tunde , Taiwo Jones O , Obimakinde Obitade Sunday
Published: October 2012

Background

Emergency department (ED) violence is common and widespread. ED staff receive both verbal and physical abuse, with ED nurses bearing the brunt of this violence. The violence is becoming increasingly common and lethal and many institutions are still improperly prepared to deal with it.

Methods

A questionnaire based survey of the perception of violence among nurses working in six tertiary hospitals’ EDs across five states in Nigeria was conducted.

Results

81 nurses were interviewed with a male to female ratio of 1:4. Most were right about the definition of violence. About 88.6% of respondents have witnessed ED violence while 65.0% had been direct victims before. Nurses followed by doctors were the usual victims. The acts were carried out mostly by visitors to the ED. Men were usually responsible for the violence, which usually occurred in the evenings. Weapons were not commonly utilised: only 15.8% of the nurses had been threatened with a weapon over a 1-year period. The main perceived reasons for violence were overcrowded emergency rooms, long waiting time and inadequate system of security. All the institutions were lacking in basic strategies for prevention. While most of the nurses were not satisfied with the EDs that were considered not safe, few would wish for redeployment to other departments/units.

Conclusions

There is a need to make the EDs safer for all users. This can be achieved by a deliberate management policy of ‘zero’ tolerance to workplace violence, effective reporting systems, adequate security and staff training on prevention of violence.
DOG1 immunoreactivity in uterine leiomyosarcomas
Authors: Sah Shatrughan P , McCluggage W Glenn
Published: October 2012

Aims

DOG1 is a recently described marker of gastrointestinal stromal tumour (GIST) which is considered to be extremely sensitive and, among mesenchymal neoplasms, quite specific for this tumour type. Following the identification of DOG1 immunoreactivity in a uterine leiomyosarcoma, we wished to ascertain how prevalent DOG1 immunoreactivity was in this tumour type.

Methods

We stained a series of uterine leiomyosarcomas (n=26) with DOG1 and with CD117 (c-kit), another marker of GIST. Staining with both markers was classified as negative, focal (<50% tumour cells positive) or diffuse (≥50% tumour cells positive).

Results

DOG1 immunoreactivity was present in seven of 26 (27%) leiomyosarcomas. Staining was focal in five cases and diffuse in two. CD117 was positive in three of 26 (11.5%) cases, two focal and one diffuse. Two cases were positive with DOG1 and CD117. One of five uterine leiomyomas was focally positive with DOG1, and one extrauterine pelvic leiomyoma was diffusely positive with this marker.

Conclusions

Since GISTs have rarely been described as primary uterine neoplasms, the presence of DOG1 immunoreactivity in a uterine leiomyosarcoma may result in diagnostic confusion, and a panel of markers is necessary for diagnosis. Uterine leiomyosarcomas should be added to the list of mesenchymal neoplasms which may be DOG1 positive.
AUTOMATIC IMAGE ANNOTATION BASED ON SEMI-SUPERVISED CLUSTERING AND MEMBERSHIP-BASED CROSS MEDIA RELEVANCE MODEL
Authors: ISMAIL MOHAMED MAHER BEN , BCHIR OUIEM
Published: October 2012

In this paper, we propose a system for automatic image annotation that has two main components. The first component consists of a novel semi-supervised possibilistic clustering and feature weighting algorithm based on robust modeling of the generalized Dirichlet (GD) finite mixture. This algorithm is used to group image regions into prototypical region clusters that summarize the training data and can be used as the basis of annotating new test images. The constraints consist of pairs of image regions that should not be included in the same cluster. These constraints are deduced from the irrelevance of all concepts annotating the training images to help in guiding the clustering process. The second component of our system consists of a probabilistic model that relies on the possibilistic membership degrees, generated by the clustering algorithm, to annotate unlabeled images. The proposed system was implemented and tested on a data set that include thousands of images using four-fold cross validation.
Staged circuit switching for network computers
Authors: Arango Mauricio , Gelernter David , Badr Hussein , Bernstein Arthur J.
Published: October 2012

Staged circuit switching (SCS) is a message-switching technique that combines a new protocol with new communication hardware. Protocol and hardware are designed specifically for networks that are intended to function as integrated, general-purpose MIMD machines, i.e. for "network computers".

The SCS protocol is a form of circuit switching that degrades automatically into packet switching when unavailable output lines make further extension of a partial circuit impossible. The SCS hardware uses a front-end crossbar switch to multipex some small number of communication channels among all of a given node's incident links. Together, hardware and protocol represent an attempt to convert spare bandwidth into lower network delays. They also allow experimentation with networks that reconfigure themselves dynamically in response to measured traffic patterns. We compare SCS to packet switching, circuit switching and the "virtual cut-through" protocol of Kermani and Kleinrock, and discuss an SCS implementation designed for the SBN network computer.
Relationship between performance parameters for transport and network services
Authors: Raghunathan K. S. , Barchanski J. A. , Bochmann G. V.
Published: October 2012

Various performance parameters are defined which characterize the quality of service offered by a layer of the OSI model. In particular the parameters for the Transport and Network are considered. The set of parameters are classified into:

i) Connection related parameters; and ii) Access point related parameter;

We further make an analysis of the relation between the parameters of the service provided by the Transport layer and the parameters of the Network service used by the Transport protocol, depending on the class of Transport protocol used. This is an example of a hierarchical approach to the evaluation of performance measures for the N-layer service in terms of performance measures of the (N-1)-layer service in conjunction with the performance measures of the N-layer protocol entity.
Simulation studies of the behavior of multihop broadcast networks
Authors: Elsanadidi M. Y. , Chu Wesley W.
Published: October 2012

The performance (throughput and delay) of the multihop broadcast communication networks is studied via a simulation model that includes channel access, transmission scheduling, buffer, management, and hop-by-hop acknowledgment protocols. The parameters considered are the data and acknowledgment packets transmission probabilities, timeout periods, and buffer sizes. The performance of echo acknowledgment, all-active acknowledgment, and a mixed acknowledgment scheme based on nodes connectivities are also studied.

Systems parameters that yield best performance for each configuration are given. Our studies reveal that the string configuration yielded better throughput than the star configuration; further, echo acknowledgment yield better performance than active acknowledgment in a string multihop broadcast network.
Distributed co-operating processes and transactions
Authors: Sha Lui , Jensen E. Douglas , Rashid Richard F. , Northcutt J. Duane
Published: October 2012

As part of our research in the Archons [Jensen 82] project on decentralized computers, we have developed a relational model of data consistency to replace the conventional serialization model for reasoning about the relationships among distributed system data objects in general and state variables in particular. We not only permit but encourage such relationships to be probabilistic, in the interest of efficiency. This model leads to a new formulation of co-operating processes, and thence to the notion of co-operating transactions: co-operating processes whose actions are made atomic for the sake of reliability. We believe that co-operating processes are valuable in a computer network, but essential in a decentralized computer [Jensen 82] where the conceptually singular but physically dispersed global operating system requires a transaction facility in the kernel [Jensen 80]. These ideas are illustrated by examples from our initial experience in applying the model to the Accent network operating system and other system software of the Spice personal computing network. This document is intended to be an overview of the synchronization effort in the Archons project, and future publications will elaborate on many of the individual points touched on here.
Asynchronous multiple access tree algorithms
Authors: Molle Mart L.
Published: October 2012

Random access protocols allow large numbers of low duty cycle stations to exchange messages over a shared communications channel under distributed control. Recently, a new class of random access protocols called 'tree algorithms' has emerged. Tree algorithms offer several performance advantages over other random access protocols (e.g. ALOHA and CSMA), namely higher capacity and inherently stable operation. However, only synchronous (slotted) tree algorithms have so far been defined. Any practical implementation of a synchronous protocol is complicated by the need for stations to perform the steps of the algorithm synchronously. Thus asynchronous (unslotted) protocols are of greater practical importance, especially for local networks. Here we show how to construct asynchronous versions of several well-known tree algorithms, and describe some of the performance limitations that result from asynchronous operation.
An improved access protocol for data communication bus networks with control wire
Authors: Fratta Luigi
Published: October 2012

An efficient algorithm is presented to achieve a conflict-free round-robin access scheme for use in a local area communication network based on the architecture of a Bidirectional Broadcast System to which an unidirectional control wire is added. This algorithm has its origins in the access control algorithm A2 proposed in [1], but it achieves a more efficient use of the bus bandwidth. In fact the time required to switch from one active station to the next in a round is of the order of signal detection time and is independent of the end-to-end network propagation delay.
Handling temporal information in web search engines
Authors: Manica Edimar , Dorneles Carina F. , Renata Galante Renata
Published: October 2012

TheWeb can be considered a vast repository of temporal information, as it daily receives a huge amount of new pages. Generally, users are interested in information related to a specific temporal interval. In the information retrieval area, researches have newly incorporated the temporal dimension to the search engines. This paper presents a comprehensive study that describes the evolution of search engines on the exploitation of temporal information. Research directions and future perspectives are also presented, considering the authors' point of view.
A high-throughput in-memory index, durable on flash-based SSD
Authors: Kissinger Thomas , Schlegel Benjamin , Boehm Matthias , Habich Dirk , Lehner Wolfgang
Published: October 2012

Growing memory capacities and the increasing number of cores on modern hardware enforces the design of new in-memory indexing structures that reduce the number of memory transfers and minimizes the need for locking to allow massive parallel access. However, most applications depend on hard durability constraints requiring a persistent medium like SSDs, which shorten the latency and throughput gap between main memory and hard disks. In this paper, we present our winning solution of the SIGMOD Programming Contest 2011. It consists of an in-memory indexing structure that provides a balanced read/write performance as well as non-blocking reads and single-lock writes. Complementary to this index, we describe an SSD-optimized logging approach to fit hard durability requirements at a high throughput rate.
Alkylation Sensitivity Screens Reveal a Conserved Cross-species Functionome
Authors: Svilar David , Dyavaiah Madhu , Brown Ashley R. , Tang Jiang-bo , Li Jianfeng , McDonald Peter R. , Shun Tong Ying , Braganza Andrea , Wang Xiao-hong , Maniar Salony , Croix Claudette M. St , Lazo John S. , Pollack Ian F. , Begley Thomas J. , Sobol Robert W.
Published: October 2012

To identify genes that contribute to chemotherapy resistance in glioblastoma, we conducted a synthetic lethal screen in a chemotherapy-resistant glioblastoma-derived cell line with the clinical alkylator temozolomide (TMZ) and an siRNA library tailored toward “druggable” targets. Select DNA repair genes in the screen were validated independently, confirming the DNA glycosylases uracil-DNA glycosylase (UNG) and A/G-specific adenine DNA glycosylase (MYH) as well as methylpurine-DNA glycosylase (MPG) to be involved in the response to high dose TMZ. The involvement of UNG and MYH is likely the result of a TMZ-induced burst of reactive oxygen species. We then compared the human TMZ sensitizing genes identified in our screen with those previously identified from alkylator screens conducted in Escherichia coli and Saccharomyces cerevisiae. The conserved biologic processes across all three species compose an alkylation functionome that includes many novel proteins not previously thought to impact alkylator resistance. This high-throughput screen, validation and cross-species analysis was then followed by a mechanistic analysis of two essential nodes: base excision repair (BER) DNA glycosylases (UNG, human and mag1, S. cerevisiae) and protein modification systems, including UBE3B and ICMT in human cells or pby1, lip22, stp22 and aim22 in S. cerevisiae. The conserved processes of BER and protein modification were dual targeted and yielded additive sensitization to alkylators in S. cerevisiae. In contrast, dual targeting of BER and protein modification genes in human cells did not increase sensitivity, suggesting an epistatic relationship. Importantly, these studies provide potential new targets to overcome alkylating agent resistance. Mol Cancer Res; 10(12); 1580–96. ©2012 AACR.
How “Reversible” Is Telomeric Aging?
Authors: Epel Elissa
Published: October 2012

A critical question in human health is the malleability of telomere length. Telomere length, sampled at one point during adult life, is predictive of certain types of cancer and other immune and metabolic-related diseases. We now know from basic studies that the telomere/telomerase maintenance system plays a causal role in accelerating biologic aging and promoting disease processes. One can develop short telomeres for a multitude of reasons. Historical factors such as genetics, prenatal conditions, and early adversity, contribute to adult telomere length; however, current stress and lifestyle are also associated. If these modifiable predictors are causal factors in telomere shortening, there is a tremendous opportunity to improve maintenance and possibly even lengthen telomeres with behavioral interventions. This minireview discusses our current understanding of telomere lengthening and questions facing the field. Several small-scale stress reduction/wellness studies show promising findings, suggesting that cell aging can be slowed or reversed in vivo over short periods. Moreover, possible mechanisms are discussed, that take into account actual telomeric lengthening, such as that which occurs through telomerase-mediated elongation, or mechanisms resulting in "pseudo-telomeric lengthening" as might occur from changes in cell type distribution. There is a strong need for more translational clinical to bench research to address mechanistic questions in experimental models. In addition, well-designed intervention research that examines both telomeres and potential mediators of change can further enhance our understanding of malleability, mechanism, and clinical implications of telomere lengthening. Cancer Prev Res; 5(10); 1163–8. ©2012 AACR.
Pitfalls in the Management of Severe Hyponatraemia
Authors: MacEwen Clare , Watkinson Peter
Published: October 2012

The correction of severe hyponatraemia is complicated by practical and theoretical limitations of formulae used to predict response to treatment, and random errors in the measurement of sodium concentration. We report the case of an elderly woman with a symptomatic serum sodium concentration of 93 mmol/l. Correction of serum sodium unintentionally exceeded conventional targets but, as in the majority of such cases, there were no neurological sequelae.
Clinical and Myopathological Characteristics of Desminopathy Caused by a Mutation in Desmin Tail Domain
Authors: Maddison Paul , Damian Maxwell S. , Sewry Caroline , McGorrian Catherine , Winer John B. , Odgerel Zagaa , Shatunov Alexey , Lee Hee Suk , Goldfarb Lev G.
Published: October 2012

Background: Most of the previously described pathogenic mutations in desmin are located in highly conserved α-helical domains that play an important role in intermediate filament assembly. The role of the C-terminus non-α-helical ‘tail’ domain is much less investigated and until recently mutations in this domain have been implicated in only a few patients. The majority of reported desminopathy cases caused by the tail mutations were sporadic, creating a representation bias regarding the disease frequency and phenotypic characteristics. Methods: We performed detailed genotype-phenotype analysis of autosomal dominant desminopathy associated with tail domain mutations in a four-generation autosomal dominant family with 16 members affected by a progressive cardiac and/or skeletal myopathy caused by a c.1346A>C (p.Lys449Thr) mutation located in the tail domain of desmin. Results: Phenotypic features in patients with tail domain mutations are similar to those in patients with mutations localized in the 1B and 2B α-helical domains. Conclusion: We recommend that the tail domain is searched for mutations as intensely as desmin coil domains which until recently were considered to be more ‘functional’.
Monitoring of Therapy for Inflammatory Bowel Disease
Authors: Burri Emanuel , Beglinger Christoph , Lehmann Frank Serge
Published: October 2012

The monitoring of inflammatory bowel disease (IBD) based on clinical symptoms and activity scores alone has major drawbacks. Despite clinical remission, in many patients with ongoing low-grade inflammation and activity scores, there is a tendency to underestimate IBD activity as parameters depend on the subjective symptoms of the patients. C-reactive protein might identify patients with low-grade inflammation, especially in Crohn’s disease, but sensitivity remains limited. Recently, fecal markers of inflammation have been shown to correlate well with endoscopic disease activity and to predict relapse. However, data on serial measurements to guide therapy are scarce. The role of anti-TNF-α antibodies and plasma TNF-α concentrations in IBD therapy is currently unclear and needs to be defined further. The goal of improving disease outcome has not been demonstrated for any noninvasive biomarker so far.
Adolescents and Type 2 Diabetes Mellitus
Authors: Brouwer Amanda M. , Salamon Katherine S. , Olson Kimberly A. , Fox Michelle M. , Yelich-Koth Sara L. , Fleischman Katie M. , Hains Anthony A. , Davies W. Hobart , Kichler Jessica C.
Published: October 2012

Objective. Research on how adolescents with type 2 diabetes mellitus (T2DM) understand and use social support is limited. Therefore, we explored how adolescents with T2DM experience and perceive social support. Methods. Adolescents with T2DM were interviewed, and data were qualitatively analyzed using Consensual Qualitative Research methodology. Results. Four themes emerged: support for nondiabetes and diabetes-specific behaviors, feelings of belonging, and disclosure. All participants expressed emotional and self-care-specific support. For some, disclosure and a sense of belonging with others who had diabetes often led to support elicitation. Participants also expressed a fear of disclosing their diabetes to others. Discussion. Adolescents with T2DM value tangible and emotional support for behaviors both related and not related to diabetes. Fear of disclosure was a typical experience with disclosure often limited to close friends and family. Recommendations for health professionals to assist adolescents in promoting appropriate disclosure and means of requesting support are discussed.
Sexual Assault on the College Campus
Authors: Franklin Cortney A. , Bouffard Leana Allen , Pratt Travis C.
Published: October 2012

Research on college sexual assault has focused on offender behavior to understand why men perpetrate sexual violence. Dominant theories have incorporated forms of male peer support, paying particular attention to the impact of rape-supportive social relationships on woman abuse. In contrast, Gottfredson and Hirschi’s general theory of crime proposes that low self-control predicts crime and other related life outcomes—including the kinds of antisocial peer relationships that the male peer support model contends causes sexual violence. The exclusion of measures of self-control on sexual assault may result in a misspecified peer support model. Accordingly, the current research empirically tests Schwartz and DeKeseredy’s male peer support model and examines the role of self-control in the larger male peer support model of sexual assault. Implications for theory and research are discussed.
The new Tort Liability Law and the journey towards informed consent in China
Authors: Zhao Xiju
Published: October 2012

Chinese informed consent law is in a period of fundamental transition. The recently enacted Tort Liability Law offers a new way of thinking about Chinese informed consent law in the therapeutic setting. It includes distinctive provisions relevant to informed consent, thereby creating a generous duty to inform, including a duty to inform about alternative treatment options. However, the rule as presently cast suffers from a lack of detail and clarity, fails to clearly identify the distinctiveness of the duty to disclose, and may be criticised for being all-embracing and overambitious. Nevertheless, one has reason to be optimistic about the future of Chinese informed consent law. This article offers a detailed tour through the new Tort Liability Law in the specific context of disclosure to patients and sets out certain suggestions for future development. These suggestions include that Chinese law should clearly distinguish the task of information disclosure from diagnosis and treatment, should introduce the ‘materiality’ test of information disclosure, and should also acknowledge the role of professional regulation in honouring and promoting the doctrine of informed consent. In the course of this examination, the author draws comparisons with the laws of Japan and also Commonwealth countries, including Asian common law jurisdictions, such as Singapore and Malaysia.
Adult Educators’ Perceptions of Their Organization Promoting Learning Practices and Culture
Authors: Hunter-Johnson Yvonne , Closson Rosemary
Published: October 2012

Many organizations, whether private or public, invest extensively in training and development. Such investment in training and development does not guarantee that the organization is perceived as a learning organization. This study examined law enforcement adult educators’ (training facilitators’) perceptions of their organization promoting learning practices and culture. The theoretical framework guiding this study is based on Watkins and Marsick’s framework of learning organization. A total of 29 adult educators were administered the Dimensions of Learning Organization Questionnaire. The results and data revealed that of the 21 items on the questionnaire, 16 (76.2%) means were lower than 3 and the highest mean was 3.41, which suggest the adult educators (instructors) within this training academy do not perceive the organization as one that promotes learning practices and learning culture. Furthermore, as it relates to rank, years of services, and gender, there was no significant difference in their perceptions.
Valuing Romantic Relationships
Authors: MacDonald Geoff , Marshall Tara C. , Gere Judith , Shimotomai Atsushi , Lies July
Published: October 2012

Research has suggested that individuals lower in self-esteem restrain from fully valuing romantic relationships because of relatively low confidence in positive regard from their partners (i.e., positive reflected appraisals). MacDonald and Jessica (2006) provided evidence that in Indonesia, where family plays an important role in mate selection, low self-esteem also leads to doubts regarding family approval of the relationship that, in turn, places an additional constraint on fully valuing a romantic relationship. In the current research, Study 1 replicated these findings, showing that the positive relationship between self-esteem and value placed on a romantic relationship was mediated by both reflected appraisals and approval from a partner’s family in Indonesia but only reflected appraisals in Canada. In Study 2, the relationship between self-esteem and relationship value was mediated by reflected appraisals and approval from own, but not partner’s, family in Japan whereas only reflected appraisals played a mediating role in Australia. These data suggest that in cultures involving family in mate selection, placing full value on romantic relationships may be contingent on confidence in both reflected appraisals and family approval of the relationship.
Parallel Monte Carlo radiosity using scene partitioning
Authors: Sanjurjo José R. , Amor Margarita , Bóo Montserrat , Doallo Ramón
Published: October 2012

Global illumination provides realistic image synthesis but its high computational requirements limit its use in practice. In this paper we present a parallel method of the Monte Carlo radiosity method. Our proposal is based on the utilization of a convex partition to divide the whole scene into a set of disjoint sub-scenes which are allocated among processors of a distributed memory system. We have used two partitioning strategies: uniform and non-uniform. The convex partition employed permits the exploitation of data locality, and the optimization of the ray shooting procedure by minimizing the number of objects to be tested in the intersection calculation. We present three different techniques to increase the performance of parallel implementation and to solve the challenges that the distribution of the data among processors implies: minimization of communications, load balancing, and a distributed test for determining the end of each iteration. The obtained results are good in terms of quality and execution times, increasing the flexibility of previous solutions.
S&T indicators as a tool for formative evaluation of research programs
Authors: Lepori Benedetto , Reale Emanuela
Published: October 2012

The aim of this article is to review the potential of Science and Technology (S&T) Indicators for the evaluation of research programs. We suggest that indicators are a useful complement to other evaluation methodologies (surveys, case studies, panels) for summative evaluations, where the focus is on measuring program results and the degree of achievement of program objectives. However, we argue that indicators have a much broader potential to support formative evaluation, where the focus is on learning from past experience in order to design future research programs. Indicators, for example, are a valuable support for debates between social actors concerning strategic choices about research funding. We conclude by suggesting what needs to be done to realize this potential.
The temporal dimension of the credibility of EU conditionality and candidate states’ compliance with the acquis communautaire, 1998–2009
Authors: Böhmelt Tobias , Freyburg Tina
Published: October 2012

Existing research seems to agree that European Union (EU) accession conditionality facilitated processes of political and economic transformation for the recent enlargement rounds. However, despite its importance, systematic research beyond small- N qualitative studies that produces generalizable insights is scarce. Most strikingly, it remains unclear at which stage of the enlargement process and to what extent candidate countries complied with EU law in the context of accession conditionality. Building upon previous theoretical accounts, the authors argue that candidates’ compliance behaviour can be examined more thoroughly when focusing on the credibility of EU conditionality at different phases over the process of accession negotiations, which are characterized by varying degrees of membership probability. The article’s main contribution stems from the empirical analysis, which employs generalized additive models on new data of candidate countries’ compliance with EU law under accession conditionality from 1998 to 2009.
The transcription factor Th-POK negatively regulates Th17 differentiation in Vα14i NKT cells
Authors: Engel Isaac , Zhao Meng , Kappes Dietmar , Taniuchi Ichiro , Kronenberg Mitchell
Published: October 2012

The majority of mouse Vα14 invariant natural killer T (Vα14i NKT) cells produce several cytokines, including IFNγ and IL-4, very rapidly after activation. A subset of these cells, known as NKT17 cells, however, differentiates in the thymus to preferentially produce IL-17. Here, we show that the transcription factor—known as T helper, Poxviruses, and Zinc-finger and Krüppel family, (Th-POK)—represses the formation of NKT17 cells. Vα14i NKT cells from Th-POK–mutant helper deficient (hd/hd) mice have increased transcripts of genes normally expressed by Th17 and NKT17 cells, and even heterozygosity for this mutation leads to dramatically increased numbers of Vα14i NKT cells that are poised to express IL-17, especially in the thymus and lymph nodes. In addition, using gene reporter mice, we demonstrate that NKT17 cells from wild-type mice express lower amounts of Th-POK than the majority population of Vα14i NKT cells. We also show that retroviral transduction of Th-POK represses the expression of the Th17 master regulator RORγT in Vα14i NKT-cell lines. Our data suggest that NKT17-cell differentiation is intrinsically regulated by Th-POK activity, with only low levels of Th-POK permissive for the differentiation of NKT17 cells.
Selective inhibitors of nuclear export show that CRM1/XPO1 is a target in chronic lymphocytic leukemia
Authors: Lapalombella Rosa , Sun Qingxiang , Williams Katie , Tangeman Larissa , Jha Shruti , Zhong Yiming , Goettl Virginia , Mahoney Emilia , Berglund Caroline , Gupta Sneha , Farmer Alicia , Mani Rajeswaran , Johnson Amy J. , Lucas David , Mo Xiaokui , Daelemans Dirk , Sandanayaka Vincent , Shechter Sharon , McCauley Dilara , Shacham Sharon , Kauffman Michael , Chook Yuh Min , Byrd John C.
Published: October 2012

The nuclear export protein XPO1 is overexpressed in cancer, leading to the cytoplasmic mislocalization of multiple tumor suppressor proteins. Existing XPO1-targeting agents lack selectivity and have been associated with significant toxicity. Small molecule selective inhibitors of nuclear export (SINEs) were designed that specifically inhibit XPO1. Genetic experiments and X-ray structures demonstrate that SINE covalently bind to a cysteine residue in the cargo-binding groove of XPO1, thereby inhibiting nuclear export of cargo proteins. The clinical relevance of SINEs was explored in chronic lymphocytic leukemia (CLL), a disease associated with recurrent XPO1 mutations. Evidence is presented that SINEs can restore normal regulation to the majority of the dysregulated pathways in CLL both in vitro and in vivo and induce apoptosis of CLL cells with a favorable therapeutic index, with enhanced killing of genomically high-risk CLL cells that are typically unresponsive to traditional therapies. More importantly, SINE slows disease progression, and improves overall survival in the Eμ-TCL1-SCID mouse model of CLL with minimal weight loss or other toxicities. Together, these findings demonstrate that XPO1 is a valid target in CLL with minimal effects on normal cells and provide a basis for the development of SINEs in CLL and related hematologic malignancies.