bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

ABSTRACT

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

ABSTRACT
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

BackgroundEmergency 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.MethodsA questionnaire based survey of the perception of violence among nurses working in six tertiary hospitals’ EDs across five states in Nigeria was conducted.Results81 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.ConclusionsThere 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

AimsDOG1 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.MethodsWe 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).ResultsDOG1 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.ConclusionsSince 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.
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.
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

Abstract
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

Abstract
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.
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

AbstractThe 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

Abstract
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.
Effect of the MDM2 promoter polymorphisms SNP309T>G and SNP285G>C on the risk of ovarian cancer in BRCA1 mutation carriers
Authors: Bjørnslett Merete , Knappskog Stian , Lønning Per Eystein , Dørum Anne 
Published: October 2012

Abstract

Background
While BRCA mutation carriers possess a 20-40% lifetime risk of developing ovarian cancer, knowledge about genetic modifying factors influencing the phenotypic expression remains obscure. We explored the distribution of the MDM2 polymorphisms SNP309T>G and the recently discovered SNP285G>C in Norwegian patients with BRCA related ovarian cancer.

Methods
221 BRCA related ovarian cancer cases (BRCA1; n = 161 and BRCA2; n = 60) were tested for the MDM2 polymorphisms. Results were compared to healthy controls (n = 2,465).

Results
The SNP309G allele was associated with elevated OR for ovarian cancer in BRCA1 mutation carriers (SNP309TG: OR 1.53; CI 1.07-2.19; p = 0.020; SNP309GG: OR 1.92; CI 1.19-3.10; p = 0.009; SNP309TG+GG combined: OR 1.61; CI 1.15-2.27; p = 0.005). In contrast, the SNP285C allele reduced risk of BRCA1 related ovarian cancer in carriers of the SNP309G allele (OR 0.50; CI 0.24-1.04; p = 0.057). Censoring individuals carrying the SNP285C/309G haplotype from the analysis elevated the OR related to the SNP309G allele (OR 1.73; CI 1.23-2.45; p = 0.002). The mean age at disease onset was 3.1 years earlier in carriers of SNP309TG+GG as compared to carriers of SNP309TT (p = 0.068). No such associations were found in BRCA2 related ovarian cancer.

Conclusions
Our results indicate the SNP309G allele to increase and the SNP285C allele to reduce the risk of BRCA1 related ovarian cancer. If confirmed in independent studies, this finding may have implications to counseling and decision-making regarding risk reducing measures in BRCA1 mutation carriers.
“Souls of the ancestor that knock us out” and other tales. A qualitative study to identify demand-side factors influencing malaria case management in Cambodia
Authors: O’Connell Kathryn A , Samandari Ghazaleh , Phok Sochea , Phou Mean , Dysoley Lek , Yeung Shunmay , Allen Henrietta , Littrell Megan 
Published: October 2012

Abstract

Background
Appropriate case management of suspected malaria in Cambodia is critical given anti-malarial drug resistance in the region. Improving diagnosis and the use of recommended malarial treatments is a challenge in Cambodia where self-treatment and usage of drug cocktails is widespread, a notable difference from malaria treatment seeking in other countries. This qualitative study adds to the limited evidence base on Cambodian practices, aiming to understand the demand-side factors influencing treatment-seeking behaviour, including the types of home treatments, perceptions of cocktail medicines and reasons for diagnostic testing. The findings may help guide intervention design.

Methods
The study used in-depth interviews (IDIs) (N = 16) and focus group discussions (FGDs) (N = 12) with Cambodian adults from malaria-endemic areas who had experienced malaria fever in the previous two weeks. Data were analysed using NVivo software.

Results
Findings suggest that Cambodians initially treat suspected malaria at home with home remedies and traditional medicines. When seeking treatment outside the home, respondents frequently reported receiving a cocktail of medicines from trusted providers. Cocktails are perceived as less expensive and more effective than full-course, pre-packaged medicines. Barriers to diagnostic testing include a belief in the ability to self-diagnose based on symptoms, cost and reliance on providers to recommend a test. Factors that facilitate testing include recommendation by trusted providers and a belief that anti-malarial treatment for illnesses other than malaria can be harmful.

Conclusions
Treatment-seeking behaviour for malaria in Cambodia is complex, driven by cultural norms, practicalities and episode-related factors. Effective malaria treatment programmes will benefit from interventions and communication materials that leverage these demand-side factors, promoting prompt visits to facilities for suspected malaria and challenging patients’ misconceptions about the effectiveness of cocktails. Given the importance of the patient-provider interaction and the pivotal role that providers play in ensuring the delivery of appropriate malaria care, future research and interventions should also focus on the supply side factors influencing provider behaviour.
Supportive development of functional tissues for biomedical research using the MINUSHEET® perfusion system
Authors: Minuth Will W , Denk Lucia 
Published: October 2012

AbstractFunctional tissues generated under in vitro conditions are urgently needed in biomedical research. However, the engineering of tissues is rather difficult, since their development is influenced by numerous parameters. In consequence, a versatile culture system was developed to respond the unmet needs.Optimal adhesion for cells in this system is reached by the selection of individual biomaterials. To protect cells during handling and culture, the biomaterial is mounted onto a MINUSHEET® tissue carrier. While adherence of cells takes place in the static environment of a 24 well culture plate, generation of tissues is accomplished in one of several available perfusion culture containers. In the basic version a continuous flow of always fresh culture medium is provided to the developing tissue. In a gradient perfusion culture container epithelia are exposed to different fluids at the luminal and basal sides. Another special container with a transparent lid and base enables microscopic visualization of ongoing tissue development. A further container exhibits a flexible silicone lid to apply force onto the developing tissue thereby mimicking mechanical load that is required for developing connective and muscular tissue. Finally, stem/progenitor cells are kept at the interface of an artificial polyester interstitium within a perfusion culture container offering for example an optimal environment for the spatial development of renal tubules.The system presented here was evaluated by various research groups. As a result a variety of publications including most interesting applications were published. In the present paper these data were reviewed and analyzed. All of the results point out that the cell biological profile of engineered tissues can be strongly improved, when the introduced perfusion culture technique is applied in combination with specific biomaterials supporting primary adhesion of cells.