bluuebunny/crossref_metadata_2025 huggingface dataset:
Neural stem cell‐based treatment for neurodegenerative diseases
Authors: Kim Seung U. , Lee Hong J. , Kim Yun B.
Published: February 2013

Human neurodegenrative diseases such as Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD) are caused by a loss of neurons and glia in the brain or spinal cord. Neurons and glial cells have successfully been generated from stem cells such as embryonic stem cells (ESCs), mesenchymal stem cells (MSCs) and neural stem cells (NSCs), and stem cell‐based cell therapies for neurodegenerative diseases have been developed. A recent advance in generatioin of a new class of pluripotent stem cells, induced pluripotent stem cells (iPSCs), derived from patients' own skin fibroblasts, opens doors for a totally new field of personalized medicine. Transplantation of NSCs, neurons or glia generated from stem cells in animal models of neurodegenrative diseases, including PD, HD, ALS and AD, demonstrates clinical improvement and also life extension of these animals. Additional therapeutic benefits in these animals can be provided by stem cell‐mediated gene transfer of therapeutic genes such as neurotrophic factors and enzymes. Although further research is still needed, cell and gene therapy based on stem cells, particularly using neurons and glia derived from iPSCs, ESCs or NSCs, will become a routine treatment for patients suffering from neurodegenerative diseases and also stroke and spinal cord injury.
Development of novel genetic cancer vaccines based on membrane‐attached β2 microglobulin
Authors: Cafri Gal , Margalit Alon , Tzehoval Esther , Eisenbach Lea , Gross Gideon
Published: February 2013

Cytotoxic T lymphocytes (CTLs) are the major effector arm of the immune system against tumors. Many tumor‐associated antigens (TAAs), known today as potential rejection antigens, were identified by their ability to induce CTL responses. CTLs utilize their clonotypic T cell receptor (TCR) to recognize short antigenic peptides presented on major histocompatibility complex (MHC)‐I proteins. These consist of a membrane‐attached α heavy chain, which forms the peptide binding pocket, and a noncovalently associated β2m light chain, not anchored to the cell membrane. CTL activation requires that antigenic peptides be presented initially on professional antigen presenting cells (APCs), primarily dendritic cells (DCs). Autologous DCs are a powerful tool for the induction of antitumor responses and are thus widely explored as vehicles for cancer vaccines. Although encouraging evidence for the induction of tumor‐specific CTLs by ex vivo–manipulated DCs came from numerous animal studies, reproducible objective clinical response in human trials is yet to be demonstrated.
Long‐distance abscisic acid signalling under different vertical soil moisture gradients depends on bulk root water potential and average soil water content in the root zone
Authors: PUÉRTOLAS JAIME , ALCOBENDAS ROSALÍA , ALARCÓN JUAN J. , DODD IAN C.
Published: February 2013

To determine how root‐to‐shoot abscisic acid (ABA) signalling is regulated by vertical soil moisture gradients, root ABA concentration ([ABA]root), the fraction of root water uptake from, and root water potential of different parts of the root zone, along with bulk root water potential, were measured to test various predictive models of root xylem ABA concentration [RX‐ABA]sap. Beans (Phaseolus vulgaris L. cv. Nassau) were grown in soil columns and received different irrigation treatments (top and basal watering, and withholding water for varying lengths of time) to induce different vertical soil moisture gradients. Root water uptake was measured at four positions within the column by continuously recording volumetric soil water content (θv). Average θv was inversely related to bulk root water potential (Ψroot). In turn, Ψroot was correlated with both average [ABA]root and [RX‐ABA]sap. Despite large gradients in θv, [ABA]root and root water potential was homogenous within the root zone. Consequently, unlike some split‐root studies, root water uptake fraction from layers with different soil moisture did not influence xylem sap (ABA). This suggests two different patterns of ABA signalling, depending on how soil moisture heterogeneity is distributed within the root zone, which might have implications for implementing water‐saving irrigation techniques.
Supporting the Posts in Development Discourse: Under‐development, Over‐development, Post‐development
Authors: Bennett Cary
Published: February 2013

This article seeks to introduce scholars outside of development studies to post‐development thought, and to restate its relevance and value to those working within the development field. It begins with an overview of post‐development thought and its critique of the post‐World War Two development project. Following this, specific critiques levelled at post‐development thought and various responses to these are considered. In the last section, the possibility or desirability of raising the living standards of Third World people to a level comparable to those of the First World through economically based development strategies is questioned. The article concludes by drawing attention to First World overdevelopment and the continued value of post‐development thinking in unsettling the development trajectory for either the First or Third World.
Strategically Locating Wildlife Crossing Structures for Florida Panthers Using Maximal Covering Approaches
Authors: Downs Joni , Horner Mark , Loraamm Rebecca , Anderson James , Kim Hyun , Onorato Dave
Published: February 2013

Crossing structures are an effective method for mitigating habitat fragmentation and reducing wildlife‐vehicle collisions, although high construction costs limit the number that can be implemented in practice. Therefore, optimizing the placement of crossing structures in road networks is suggested as a strategic conservation planning method. This research explores two approaches for using the maximal covering location problem (MCLP) to determine optimal sites to install new wildlife crossing structures. The first approach is based on records of traffic mortality, while the second uses animal tracking data for the species of interest. The objective of the first is to cover the maximum number of collision sites, given a specified number of proposed structures to build, while the second covers as many animal tracking locations as possible under a similar scenario. These two approaches were used to locate potential wildlife crossing structures for endangered Florida panthers (Puma concolor coryi) in Collier, Lee, and Hendry Counties, Florida, a population whose survival is threatened by excessive traffic mortality. Historical traffic mortality records and an extensive radio‐tracking dataset were used in the analyses. Although the two approaches largely select different sites for crossing structures, both models highlight key locations in the landscape where these structures can remedy traffic mortality and habitat fragmentation. These applications demonstrate how the MCLP can serve as a useful conservation planning tool when traffic mortality or animal tracking data are available to researchers.
CONSTAnT – A Conceptual Data Model for Semantic Trajectories of Moving Objects
Authors: Bogorny Vania , Renso Chiara , de Aquino Artur Ribeiro , de Lucca Siqueira Fernando , Alvares Luis Otavio
Published: February 2013

Several works have been proposed in the last few years for raw trajectory data analysis, and some attempts have been made to define trajectories from a more semantic point of view. Semantic trajectory data analysis has received significant attention recently, but the formal definition of semantic trajectory, the set of aspects that should be considered to semantically enrich trajectories and a conceptual data model integrating these aspects from a broad sense is still missing. This article presents a semantic trajectory conceptual data model named CONSTAnT, which defines the most important aspects of semantic trajectories. We believe that this model will be the foundation for the design of semantic trajectory databases, where several aspects that make a trajectory “semantic” are taken into account. The proposed model includes the concepts of semantic subtrajectory, semantic points, geographical places, events, goals, environment and behavior, to create a general concept of semantic trajectory. The proposed model is the result of several years of work by the authors in an effort to add more semantics to raw trajectory data for real applications. Two application examples and different queries show the flexibility of the model for different domains.
Populus endo‐beta‐mannanase PtrMAN6 plays a role in coordinating cell wall remodeling with suppression of secondary wall thickening through generation of oligosaccharide signals
Authors: Zhao Yunjun , Song Dongliang , Sun Jiayan , Li Laigeng
Published: February 2013

Endo‐1,4‐β‐mannanase is known to able to hydrolyze mannan‐type polysaccharides in cell wall remodeling, but its function in regulating wall thickening has been little studied. Here we show that a Populus endo‐1,4‐β‐mannanase gene, named PtrMAN6, suppresses cell wall thickening during xylem differentiation. PtrMAN6 is expressed specifically in xylem tissue and its encoded protein localizes to developing vessel cells. Overexpression of PtrMAN6 enhanced wall loosening as well as suppressed secondary wall thickening, whilst knockdown of its expression promoted secondary wall thickening. Transcriptional analysis revealed that PtrMAN6 overexpression downregulated the transcriptional program of secondary cell wall thickening, whilst PtrMAN6 knockdown upregulated transcriptional activities toward secondary wall formation. Activity of PtrMAN6 hydrolysis resulted in the generation of oligosaccharide compounds from cell wall polysaccharides. Application of the oligosaccharides resulted in cellular and transcriptional changes that were similar to those found in PtrMAN6 overexpressed transgenic plants. Overall, our results demonstrated that PtrMAN6 plays a role in hydrolysis of mannan‐type wall polysaccharides to produce oligosaccharides that may serve as signaling molecules to suppress cell wall thickening during wood xylem cell differentiation.
Lysosomal Membrane Proteins and Their Central Role in Physiology
Authors: Schwake Michael , Schröder Bernd , Saftig Paul
Published: February 2013

The lysosomal membrane was thought for a long time to primarily act as a physical barrier separating the luminal acidic milieu from the cytoplasmic environment. Meanwhile, it has been realized that unique lysosomal membranes play essential roles in a number of cellular events ranging from phagocytosis, autophagy, cell death, virus infection to membrane repair. This review provides an overview about the most interesting emerging functions of lysosomal membrane proteins and how they contribute to health and disease. Their importance is exemplified by their role in acidification, transport of metabolites and ions across the membrane, intracellular transport of hydrolases and the regulation of membrane fusion events. Studies in patient cells, non‐mammalian model organisms and knockout mice contributed to our understanding of how the different lysosomal membrane proteins affect cellular homeostasis, developmental processes as well as tissue functions. Because these proteins are central for the biogenesis of this compartment they are also considered as attractive targets to modulate the lysosomal machinery in cases where impaired lysosomal degradation leads to cellular pathologies. We are only beginning to understand the complex composition and function of these proteins which are tightly linked to processes occurring throughout the endocytic and biosynthetic pathways.
Biology of xenogeneic cell and organ transplantation – from bench to bedside – the new German research foundation (DFG) transregio collaborative research centre for the next 4 (ultimately 12) years
Authors: Reichart Bruno
Published: February 2013

Discordant xenotransplantation research started in Hanover/Mariensee and in Munich in the late nineties – the latter receiving a substantial grant from the Bavarian Research Foundation. In 2003 both groups were invited by the German Research Foundation (DFG) to make a joint application to further develop xenotransplantation technology. This was peer‐reviewed, approved and continued with considerable success from 2004 to 2012. The Paul‐Ehrlich and Robert‐Koch Institutes, the official bodies responsible for microbiological safety in Germany, were subsequently included.

Our unique interdisciplinary consortium combines basic scientists, animal biotechnologists and clinicians demonstrating an excellent co‐operation over the last 8 years. The tool box available to us includes pigs transgenic for human thrombomodulin, hemoxygenase‐1, A20, LEA 29Y, HLA‐E and TRAIL; key enabling technologies include gene targeting, large transgene vectors, transposon mediated transgenesis, zinc finger and TALE nuclease mediated gene targeting.

In July 2012 our new Collaborative Research Centre (again supported by the DFG) commenced, continuing in the first instance to 2016 and ultimately until 2024. The strong Diabetes group at the University of Dresden, which currently runs the only successful allogeneic pancreatic islet transplantation in Germany, has now been incorporated.

Our main goal is to translate preclinical studies into benefits for patients as quickly as possible. The consortium focuses on islet, cardiac and renal xenotransplantation; new biological heart valves for paediatric cases and young adults will be developed. Our endeavours will be supported by two ethicists to ensure best practice and promote public dialogue.
Differences in glucose‐stimulated insulin secretion in vitro of islets from human, nonhuman primate, and porcine origin
Authors: Mueller Kate R , Balamurugan A N , Cline Gary W , Pongratz Rebecca L , Hooper Rebecca L , Weegman Bradley P , Kitzmann Jennifer P , Taylor Michael J , Graham Melanie L , Schuurman Henk‐Jan , Papas Klearchos K
Published: February 2013

Porcine islet xenotransplantation is considered a potential cell‐based therapy for type 1 diabetes. It is currently being evaluated in diabetic nonhuman primates (NHP) to assess safety and efficacy of the islet product. However, due to a variety of distinct differences between the respective species, including the insulin secretory characteristics of islets, the suitability and predictive value of the preclinical model in the extrapolation to the clinical setting remain a critical issue. Islets isolated from human (n = 3), NHP (n = 2), adult pig (AP, n = 3), and juvenile pig (JP, n = 4) pancreata were perifused with medium at basal glucose (2.5 mm) followed by high glucose (16.7 mm) concentrations. The total glucose‐stimulated insulin secretion (GSIS) was calculated from generated insulin secretion profiles. Nonhuman primate islets exhibited GSIS 3‐fold higher than AP islets, while AP and JP islets exhibited GSIS 1/3 and 1/30 of human islets, respectively. The insulin content of NHP and AP islets was similar to that of human islets, whereas that of JP islets was 1/5 of human islets. Despite the fact that human, NHP, and AP islets contain similar amounts of insulin, the much higher GSIS for NHP islets than for AP and JP islets suggests the need for increased dosing of islets from JP and AP in pig‐to‐NHP transplantation. Porcine islet xenotransplantation to humans may require significantly higher dosing given the lower GSIS of AP islets compared to human islets.
Effect of Supercritical Carbon Dioxide Condition on Oil Yield and Solubility of Pithecellobium Jiringan (Jack) Prain Seeds
Authors: Che Yunus Mohd Azizi , Arsad Nur Husnina , Zhari Salman , Idham Zuhaili , Setapar Siti Hamidah , Mustapha Ana Najwa
Published: February 2013

Pithecellobium Jiringan (Jack) Prain (P.Jiringan) merupakan salah satu daripada sumber tumbuhtumbuhan yang mengandungi komponen antioksidan. Tujuan kajian ini dijalankan adalah untuk mengkaji kesan-kesan parameter kaedah penyarian bendalir lampau genting dengan menggunkan karbon dioksida sebagai pelarut (SC-CO2) ke atas hasil minyak dan untuk mengukur kebolehlarutan minyak P.Jiringan didalam (SC-CO2) dan mengkorelasi data kebolehlarutan minyak P.Jiringan dengan model Chrastil dan del Valle & Aguilera. Kajian ini telah dijalankan pada suhu antara 40oC sehingga 70oC dan pada tekanan antara 27.58 MPa sehingga 44.82 MPa. Tempoh pengekstrakan adalah 60 minit. Penemuan hasil kajian ini menunjukkan bahawa hasil minyak meningkat dengan peningkatan tekanan dan peningkatan suhu. Pada keadaan suhu malar, kebolehlarutan minyak meningkat dengan peningkatan kepadatan CO2. Analisis keputusan menunjukkan bahawa data keterlarutan minyak P.Jiringan telah berjaya dipadankan dengan model Chrastil. Di samping itu, SC-CO2 memberikan hasil minyak tertinggi berbanding dengan ASE dan proses pengekstrakan Soxhlet.

Kata kunci: Kebolehlarutan; Model Chrastil; penyarian bendalir lampau genting; Pithecellobium Jiringan (Jack) Prain

Pithecellobium Jiringan (Jack) Prain (P.Jiringan) is one of the medicinal plant sources that consist of antioxidant compounds. The aim of this study was to investigate the effects of supercritical carbon dioxide (SC-CO2) extraction parameters on oil yields and to measure the solubility of P.Jiringan oil in SC-CO2 and correlated the data with Chrastil and del Valle & Aguilera models. The experimental were conducted at temperatures ranging from 40oC to 70oC and pressure from 27.58 MPa to 44.82 MPa. The extraction duration was 60 minutes. The result shows that the oil yields increase as the pressure and temperature increase. The solubility of oil increased as the density of CO2 increased at constant temperature. An analysis of the results show that the solubility experimental data correlated with the Chrastil’s model was successfully matched. In addition, SC-CO2 give the highest oil yields compared to accelerated solvent extraction (ASE) and soxhlet extraction process.

Keywords: Chrastil’s model; Pithecellobium Jiringan (Jack) Prain; solubility; supercritical fluid extraction
Nilai Cipta–sama Sistem Pengurusan Pembelajaran
Awal
Authors: Nazul Ismail Mohamed , Yahya Yazrina , Mukhtar Muriati
Published: February 2013

The purpose of this study is to identify the value co-creation of a Learning Management System. Data were collected through a Laddering Technique based on Means-End Chain Theory, Service Dominant Logic and Rokeach Value List (1973). Value co-creation elements are important to identify the critical
feature during the design process of the Learning Management System. A number of 30 respondents were
selected using purposive data sampling technique. This is a case study based on Sistem Pengurusan
Pengajaran dan Pembelajaran Interaktif, UKM (SPIN). Research findings listed six value co-creation
elements consists of self directed, capability, intellectual, ambitious (hardworking), responsibility and
helpful. The findings were shown in an implication matrix and Value Hierarchy Map (VHM). Significant
of the study is to help identify co-creation value based on critical features such as Lecture Notes,
Annoucement and Course Profile. These critical features are able to provide great impact on the success of
a Learning Management System. The research findings could be developed into a generic model of value
co-creation model.

Keywords: Laddering technique; learning management system; value co-creation; means-end theory;servic dominant logic

Kajian ini bertujuan untuk mengenal pasti nilai cipta-sama dari sebuah sistem pengurusan pembelajaran. Data diperoleh melalui Teknik Laddering berlandaskan Teori Means-End, Service Dominant Logic dan Senarai Nilai Rokeach(1973). Elemen nilai cipta-sama ini penting dalam mengenal pasti fitur kritikal
semasa proses mereka bentuk sistem pengurusan pembelajaran yang berjaya. Seramai 30 orang responden
dipilih melalui teknik persampelan bertujuan. Reka bentuk kajian ini berasaskan kajian kes dengan
menjadikan Sistem Pengurusan Pengajaran dan Pembelajaran Interaktif, UKM (SPIN) sebagai medium
kajian. Dapatan kajian ini menyenaraikan 6 elemen nilai cipta-sama iaitu kawalan kendiri, berkebolehan,
intelektual, cita-cita (kesungguhan), tanggungjawab dan saling bantu. Hasil kajian ini dipaparkan dalam
bentuk matrik implikasi dan Rajah Hirarki Nilai (RHN). Sumbangan daripada kajian ini dapat membantu
mengenal pasti elemen nilai cipta-sama yang diwakili oleh fitur kritikal seperti Lecture Notes,
Annoucement dan Course Profile. Fitur kritikal ini berupaya memberi impak besar terhadap kejayaan
sesebuah sistem pengurusan pembelajaran. Hasil kajian ini penting untuk dikembangkan sehingga terbina
model generik berasaskan nilai cipta-sama.

Kata kunci: Teknik laddering; sistem pengurusan pembelajaran; nilai cipta-sama; teori means-end; service dominant logic
Factors Affecting Customer Satisfaction of the Wi–Fi Services
Authors: Muda Nora , Mohd Suradi Nur Riza
Published: February 2013

Measuring the quality of service and customer satisfaction is ultimately important for ISPs to remain in business. In order to achieve a good quality of service, understanding the two-way relationship among customers in a variety of patterns of quality of service is crucial. Three methods of analysis namely; Penalty Rewards Contrast Analysis (PRCA), Importance Performance Analysis (IPA) and Customer
Satisfaction Index (CSI) were used in the analysis to identify the causes of the main problems that affect
the level of customer satisfaction. For the PRCA analysis, factors that were categorized as onedimensional are service quality, promotion, as well as payment of bills of paid Wi-Fi services and the promotional factor of free Wi-Fi services. Based on the IPA results, there were eight attributes for paid Wi-Fi services and four attributes of free Wi-Fi services in the first quadrant. These attributes are important but their performance are low. Therefore, these attributes need to be emphasized further to increase their level of performance. Meanwile, the CSI analysis showed that all five factors are found to be at a good level and being categorized in the indifferent zone.

Keywords: Wi-Fi; customer satisfaction Index; penalty reward contrast analysis; important performance
analysis

Pengukuran kualiti perkhidmatan dan kepuasan pelanggan adalah sangat penting bagi ISP untuk kekal dalam perniagaan. Bagi mencapai kualiti perkhidmatan yang baik, memahami hubungan dua hala di
kalangan pelanggan di pelbagai corak kualiti perkhidmatan adalah penting. Tiga kaedah analisis iaitu Analisis Kontras Hukuman Ganjaran (PRCA), Analisis Kepentingan Prestasi (IPA) dan Indeks Kepuasan Pelanggan (CSI) telah digunakan dalam analisis bagi mengukur kepuasan pelanggan untuk mengenal pasti punca masalah utama yang memberi kesan kepada tahap kepuasan pelanggan. Untuk analisis PRCA, faktor-faktor yang telah dikategorikan sebagai satu dimensi adalah faktor kualiti perkhidmatan, kenaikan pangkat, serta pembayaran bil-bil perkhidmatan Wi-Fi berbayar dan faktor promosi perkhidmatan Wi-Fi percuma. Berdasarkan keputusan IPA, terdapat lapan atribut untuk perkhidmatan Wi-Fi berbayar dan empat atribut bagi perkhidmatan Wi-Fi percuma berada dalam kuadran pertama. Atribut-atribut ini
didapati penting tetapi prestasi mereka adalah rendah. Oleh itu, atribut-atribut ini perlu diberi penekanan
untuk meningkatkan lagi tahap prestasi mereka. Manakala, analisis CSI pula menunjukkan bahawa kesemua lima faktor didapati berada pada tahap yang baik dan yang dikategorikan dalam zon acuh tak
acuh.

Kata kunci: Wi-Fi; indeks kepuasan pelanggan; analisis kontras penalti ganjaran; analisis kepentingan
prestasi
Measurements of the Temperature Inside an Explosive Fireball
Authors: Lebel Luke S. , Brousseau Patrick , Erhardt Lorne , Andrews William S.
Published: February 2013

This paper discusses the development of a fiber optic probe that can obtain temperature measurements from the interior of explosive fireballs, which are generated when unreacted detonation products react with oxygen in the surrounding air. Signatures of the thermochemical environment and chemical species involved can often be deduced from their light emissions, but the limited optical depth of fireballs means that remote sensing techniques can only sample emissions from the outer shell. By developing a protected fiber optic probe that can be placed adjacent to an exploding charge, giving it the ability to become enveloped by the fireball, the thermal radiation from the interior of the fireball can be sampled. Measurement from five shots using Detasheet-C explosives were carried out and could be obtained over the course of about 20 ms. Blackbody-type radiation with temperatures in the 1600 K to 1900 K range were observed, peaking at about 1850 K after 12 ms. The magnitude and time behavior of the temperature was not significantly different when taken at different locations within the fireball, indicating that temperature is fairly uniform throughout. The lack of specific spectral emission lines implies that in the interior of the fireball any combustion that occurred was probably primarily with carbonaceous soot, though differences in optical depth at different locations in the fireball indicate that it was much more fuel-rich closer to the center.
Simple Si(111) surface preparation by thin wafer cleavage
Authors: Paul William , Miyahara Yoichi , Grütter Peter H.
Published: February 2013

We describe a simple method to obtain clean Si(111)2 × 1 surfaces with large terrace sizes, up to tens of microns, using commonly available wafers. The sample geometry and cleavage method make it possible to produce semiconductor samples in ultra-high vacuum systems: that are not explicitly designed to cleave samples or prepare semiconductor surfaces by other means. The force required to cleave the samples is sufficiently low such that they can be cleaved using any available transfer arm, manipulator, or wobble stick in the vacuum system. Large atomic terraces on the order of hundreds of nanometers to tens of microns are easily obtained in this way, as characterized by scanning tunneling microscopy.
Device instability of postannealed TiOx thin-film transistors under gate bias stresses
Authors: Du Ahn Byung , Ok Kyung-Chul , Park Jin-Seong , Chung Kwun-Bum
Published: February 2013

This paper investigates the negative bias instability (NBS) and positive bias instability (PBS) of titanium oxide (TiOx) thin-film transistors (TFTs) with different annealing temperatures. Structural analyses suggested that TiOx films annealed at 450 and 550 °C had average grain sizes of 200 and 400 nm, respectively. A TiOx TFT annealed at 550 °C exhibited respective threshold voltage (Vth) shifts of only −1.4 and 10.2 V under NBS and PBS conditions. The origin of the instability was found to be a charge trapping mechanism caused by different grain sizes, boundaries, and changes in band edge states below the conduction band, which acted as electron and hole trap sites.
DCs in the Driver’s Seat
Authors: Anandasabapathy Niroshana
Published: February 2013

Human inflammatory DCs drive T
H
17 T cells.
A Novel Selective LSD1/KDM1A Inhibitor Epigenetically Blocks Herpes Simplex Virus Lytic Replication and Reactivation from Latency
Authors: Liang Yu , Quenelle Debra , Vogel Jodi L. , Mascaro Cristina , Ortega Alberto , Kristie Thomas M.
Published: February 2013

Cellular processes requiring access to the DNA genome are regulated by an overlay of epigenetic modifications, including histone modification and chromatin remodeling. Similar to the cellular host, many nuclear DNA viruses that depend upon the host cell’s transcriptional machinery are also subject to the regulatory impact of chromatin assembly and modification. Infection of cells with alphaherpesviruses (herpes simplex virus [HSV] and varicella-zoster virus [VZV]) results in the deposition of nucleosomes bearing repressive histone H3K9 methylation on the viral genome. This repressive state is modulated by the recruitment of a cellular coactivator complex containing the histone H3K9 demethylase LSD1 to the viral immediate-early (IE) gene promoters. Inhibition of the activity of this enzyme results in increased repressive chromatin assembly and suppression of viral gene expression during lytic infection as well as reactivation from latency in a mouse ganglion explant model. However, available small-molecule LSD1 inhibitors are not originally designed to inhibit LSD1, but rather monoamine oxidases (MAO) in general. Thus, their specificity for and potency to LSD1 is low. In this study, a novel specific LSD1 inhibitor was identified that potently repressed HSV IE gene expression, genome replication, and reactivation from latency. Importantly, the inhibitor also suppressed primary infection of HSV
in vivo
in a mouse model. Based on common control of a number of DNA viruses by epigenetic modulation, it was also demonstrated that this LSD1 inhibitor blocks initial gene expression of the human cytomegalovirus and adenovirus type 5.

IMPORTANCE
Epigenetic mechanisms, including histone modification and chromatin remodeling, play important regulatory roles in all cellular processes requiring access to the genome. These mechanisms are often altered in disease conditions, including various cancers, and thus represent novel targets for drugs. Similarly, many viral pathogens are regulated by an epigenetic overlay that determines the outcome of infection. Therefore, these epigenetic targets also represent novel antiviral targets. Here, a novel inhibitor was identified with high specificity and potency for the histone demethylase LSD1, a critical component of the herpes simplex virus (HSV) gene expression paradigm. This inhibitor was demonstrated to have potent antiviral potential in both cultured cells and animal models. Thus, in addition to clearly demonstrating the critical role of LSD1 in regulation of HSV infection, as well as other DNA viruses, the data extends the therapeutic potential of chromatin modulation inhibitors from the focused field of oncology to the arena of antiviral agents.
Could Acupuncture at the So-Called Forbidden Points be Harmful to the Health of Pregnant Wistar Rats?
Authors: da Silva André Vilella Guerreiro , Nakamura Mary Uchiyama , da Silva João Bosco Guerreiro , Cordeiro José Antonio , Mendes Glória Elisa , Lima Luiz
Published: February 2013

Aim

This study is the second report from a single experiment planned to determine if acupuncture at LI4 and SP6, or at the sacral points, could produce any harm in the pregnancy outcome of Wistar rats, as has been hypothesised in traditional knowledge. Here, we observe if these points can be harmful to the health of pregnant Wistar rats.

Methods

A total of 48 pregnant Wistar rats were randomly divided into 4 groups: total control, where rats were left in cages without manipulation; anesthetised control, where rats were manipulated and anesthetised but did not receive electroacupuncture; and peripheral point and sacral point groups, where rats were anesthetised and received 6 sessions of electroacupuncture at 4 acupuncture points: LI4 and SP6, and BL27 and BL28, respectively. In the 19th day of pregnancy the rats were killed and examined. The primary endpoints were levels of glucose, aspartate aminotransferase (AST), alanine aminotransferase (ALT) creatinine and histological changes of liver and kidney.

Results

There were no differences between the levels of biochemical parameters. No differences were also seen regarding the histopathological analysis.

Conclusions

We found no evidence that acupuncture at the LI4, SP6 and sacral points could be harmful to the Wistar rat dams.
Cardiac tamponade as a presenting manifestation of severe hypothyroidism
Authors: Butala Ashvin , Chaudhari Shilpa , Sacerdote Alan
Published: February 2013

We report a patient who presented to our hospital with unusual symptoms of non-specific complaints and uncontrolled hypertension. Acute cardiac tamponade was suspected from cardiomegaly on routine chest x-ray and confirmed with an echocardiogram. Analysis of the pericardial fluid and other laboratory data ruled out all the common causes except for hypothyroidism as a cause of cardiac tamponade. Tamponade results from increased intrapericardial pressure caused by the accumulation of pericardial fluid. The rapidity of fluid accumulation is a greater factor in the development of tamponade than absolute volume of the effusion. Hypothyroidism is a well-known cause of pericardial effusion. However, tamponade rarely develops owing to a slow rate of accumulation of pericardial fluid. The treatment of hypothyroidic cardiac tamponade is different from other conditions. Thyroxine supplementation is all that is necessary. Rarely, pericardiocentesis is needed in a severely symptomatic patient.
Intrapancreatic accessory spleen: a misleading diagnosis
Authors: Loureiro Ana Luisa , Ferreira Alexandre Oliveira , Palmeiro Marta , Penedo José Pedro
Published: February 2013

Intrapancreatic accessory spleens are congenital malformations that occur in roughly 2% of individuals. Most of them are innocent until found. Lately, there have been a few case reports of intrapancreatic spleen misdiagnosis leading to unnecessary pancreatic surgery. We report the case of a 64-year-old woman who had a hypervascular pancreatic nodule diagnosed on dynamic CT and MRI after an episode of acute pancreatitis. The patient's progress was followed for 18 months, repeated the CT and MRI examinations and an endoscopic ultrasonography with fine needle aspiration was performed. Neoplastic cells were not identified on cytology. Despite the stability of the lesion,  a distal pancreatectomy was performed to exclude a neuroendocrinal tumour. An intrapancreatic accessory spleen was ultimately identified on histological examination.
Septic thrombophlebitis of the superior mesenteric vein with bacteraemia caused byBacteroides fragilisandStreptococcus intermediusas a complication of diverculitis
Authors: Hadano Yoshiro , Iwata Hiroyoshi
Published: February 2013

A 68-year-old Japanese man with alcoholic liver cirrhosis was admitted to our hospital because of fever and haematemesis. On day 3, his blood culture became positive for Gram-negative bacilli and Gram-positive cocci, and contrast-enhanced abdominal CT revealed acute septic thrombophlebitis of the superior mesenteric vein with caecal diverculitis. Antimicrobial therapy with ampicillin–sulbactam and anticoagulant therapy were started and the blood culture grewBacteroides fragilisandStreptococcus intermedius. On hospital day 7, the patient's condition began to improve in response to the therapy, therefore, the ampicillin–sulbactam and anticoagulant therapy was continued for 42 days. The patient was discharged home on hospital day 45.B fragilisbacteraemia of unknown source should caution the physician to search for an intra-abdominal focus, such as thrombosis of the portal vein or mesenteric vein.
Internalised homonegativity predicts HIV-associated risk behavior in European men who have sex with men in a 38-country cross-sectional study: some public health implications of homophobia
Authors: Ross Michael W , Berg Rigmor C , Schmidt Axel J , Hospers Harm J , Breveglieri Michele , Furegato Martina , Weatherburn Peter
Published: February 2013

Objectives

Internalised homonegativity (IH) is hypothesised to be associated with HIV risk behaviour and HIV testing in men who have sex with men (MSM). We sought to determine the social and individual variables associated with IH and the associations between IH and HIV-related behaviours.

Design and setting

We examined IH and its predictors as part of a larger Internet-delivered, cross-sectional study on HIV and health in MSM in 38 European countries.

Participants

181 495 MSM, IH data analysis subsample 144 177. All participants were male, over the age of consent for homosexual activity in their country of domicile, and have had at least one homosexual contact in the past 6 months.

Methodology

An anonymous Internet-based questionnaire was disseminated in 25 languages through MSM social media, websites and organisations and responses saved to a UK-based server. IH was measured using a standardised, cross-culturally appropriate scale.

Results

Three clusters of European countries based on the level of experienced discrimination emerged. IH was predicted by country LGB (lesbian, gay and bisexual) legal climate, Gini coefficient and size of place of settlement. Lower IH was associated with degree the respondent was ‘out’ as gay to others and older age. ‘Outness’ was associated with ever having an HIV test and age, education and number of gay friends, while IH (controlling for the number of non-steady unprotected sex partners and perceived lack of control over safe sex) was associated with condom use for anal intercourse.

Conclusions

IH is associated with LGB legal climate, economic development indices and urbanisation. It is also associated with ‘outness’ and with HIV risk and preventive behaviours including HIV testing, perceived control over sexual risk and condom use. Homonegative climate is associated with IH and higher levels of HIV-associated risk in MSM. Reducing IH through attention to LGB human rights may be appropriate HIV reduction intervention for MSM.
SP3, a reliable alternative to HercepTest in determining HER-2/neustatus in breast cancer patients
Authors: D'Alfonso Timothy Michael , Liu Yi-Fang , Chen Zhengming , Chen Ying-Bei , Cimino-Mathews Ashley , Shin Sandra Jean
Published: February 2013

Accurate assessment of HER-2/neugene status in breast cancer patients has important prognostic and therapeutic implications. Overexpression/gene amplification of HER-2 is associated with a more aggressive clinical course and eligibility for targeted therapy with trastuzumab. A variety of immunohistochemical (IHC) antibodies and in situ hybridisation (ISH) methods have been employed to assess HER-2 status. SP3 is a rabbit monoclonal antibody that has been shown to have a high level of agreement with other anti-HER-2 antibodies and ISH methods. We assessed HER-2 status by SP3 and HercepTest IHC stains and by fluorescence in situ hybridisation (FISH) on invasive breast carcinomas from paired needle core biopsy and excisional biopsy specimens from 100 patients. We compared the two antibodies with respect to concordance rates with FISH, concordance rates between samples of the same tumour, and sensitivity and specificity using FISH as the reference test. Concordance between SP3 and FISH in needle core biopsy and excisional biopsy specimens was 96% (95% CI 91.9% to 99.7%) (κ=0.89 (95% CI 0.73 to 1.00)) and 97% (95% CI 90.3% to 99.3%) (κ=0.84 (95% CI 0.66 to 1.00)), respectively. Sensitivity and specificity of SP3 for detecting HER-2 overexpression/gene amplification were 78.3% and 100%, respectively, in needle core biopsy and excisional biopsy specimens. Concordance between SP3 results assessed on the needle core biopsy and excisional biopsy was 89% (95% CI 81.2% to 94.4%) (κ=0.62 (95% CI 0.42 to 0.82)). Concordance between SP3 and HercepTest antibodies, after excluding 2+ cases, was 97.6% (95% CI 94.0% to 99.3%) (κ=0.88 (95% CI 0.77 to 1.00)). SP3 is a reliable alternative to HercepTest in evaluating HER-2 status in breast cancer patients. Like other anti-HER-2 antibodies, SP3 may serve as a diagnostic tool in breast pathology and has potential utility as an IHC biomarker in non-mammary malignancies.
Evaluation of the UNREST questionnaire for testing the social resistance framework
Authors: Factor Roni , Kawachi Ichiro , Williams David R
Published: February 2013

Background

The recently developed social resistance framework addresses a widespread pattern whereby non-dominant minority groups, such as ethnic/racial minorities and people of low socioeconomic status, often engage in unhealthy and risky behaviours at higher rates compared with society at large. The framework suggests that power relations within society may encourage members of non-dominant minority groups to actively engage in acts of everyday resistance, which may include risky and unhealthy behaviours.

Methods

The current paper develops and psychometrically evaluates a research tool to test this innovative framework. The UNREST questionnaire measures the key concepts of the framework, along with four high-risk and unhealthy behaviours, as well as demographic and socioeconomic characteristics. A pilot survey was conducted among representative subsamples of a non-dominant group (African–Americans) and a dominant group (Caucasians).

Results

Consistent with the general premises of the framework, the evaluation of the questionnaire produced six valid and reliable scales, which were significantly correlated with some criterion-related items as well as unhealthy and risky behaviours.

Conclusions

The preliminary results of our pilot study suggest that the new tool may be useful for testing the framework. The results also provide support for the framework in general.
Are health inequalities really not the smallest in the Nordic welfare states? A comparison of mortality inequality in 37 countries
Authors: Popham Frank , Dibben Chris , Bambra Clare
Published: February 2013

Background

Research comparing mortality by socioeconomic status has found that inequalities are not the smallest in the Nordic countries. This is in contrast to expectations given these countries’ policy focus on equity. An alternative way of studying inequality has been little used to compare inequalities across welfare states and may yield a different conclusion.

Methods

We used average life expectancy lost per death as a measure oftotal inequalityin mortality derived from death rates from the Human Mortality Database for 37 countries in 2006 that we grouped by welfare state type. We constructed a theoretical ‘lowest mortality comparator country’ to study, by age, why countries were not achieving the smallest inequality and the highest life expectancy. We also studied life expectancy as there is an important correlation between it and inequality.

Results

On average, Nordic countries had the highest life expectancy and smallest inequalities for men but not women. For both men and women, Nordic countries had particularly low younger age mortality contributing to smaller inequality and higher life expectancy. Although older age mortality in the Nordic countries is not the smallest. There was variation within Nordic countries with Sweden, Iceland and Norway having higher life expectancy and smaller inequalities than Denmark and Finland (for men).

Conclusions

Our analysis suggests that the Nordic countries do have the smallest inequalities in mortality for men and for younger age groups. However, this is not the case for women. Reducing premature mortality among older age groups would increase life expectancy and reduce inequality further in Nordic countries.
Is the GAIN Act a turning point in new antibiotic discovery?
Authors: Brown Eric D.
Published: February 2013

The United States GAIN (Generating Antibiotic Incentives Now) Act is a call to action for new antibiotic discovery and development that arises from a ground swell of concern over declining activity in this therapeutic area in the pharmaceutical sector. The GAIN Act aims to provide economic incentives for antibiotic drug discovery in the form of market exclusivity and accelerated drug approval processes. The legislation comes on the heels of nearly two decades of failure using the tools of modern drug discovery to find new antibiotic drugs. The lessons of failure are examined herein as are the prospects for a renewed effort in antibiotic drug discovery and development stimulated by new investments in both the public and private sector.
Charged anisotropic static cylindrically symmetric models
Authors: Sharif M. , Fatima H. Ismat
Published: February 2013

In this paper, we investigate exact solutions of the field equations for charged, anisotropic, static, cylindrically symmetric space–time. We use a barotropic equation of state linearly relating the radial pressure and energy density. The analysis of the matter variables indicates a physically reasonable matter distribution. In the most general case, the central densities correspond to realistic stellar objects in the presence of anisotropy and charge. Finally, we conclude that matter sources are less affected by the electromagnetic field.
MULTI-DOMAIN FEATURE EXTRACTION FOR SMALL EVENT-RELATED POTENTIALS THROUGH NONNEGATIVE MULTI-WAY ARRAY DECOMPOSITION FROM LOW DENSE ARRAY EEG
Authors: CONG FENGYU , PHAN ANH-HUY , ASTIKAINEN PIIA , ZHAO QIBIN , WU QIANG , HIETANEN JARI K. , RISTANIEMI TAPANI , CICHOCKI ANDRZEJ
Published: February 2013

Non-negative Canonical Polyadic decomposition (NCPD) and non-negative Tucker decomposition (NTD) were compared for extracting the multi-domain feature of visual mismatch negativity (vMMN), a small event-related potential (ERP), for the cognitive research. Since signal-to-noise ratio in vMMN is low, NTD outperformed NCPD. Moreover, we proposed an approach to select the multi-domain feature of an ERP among all extracted features and discussed determination of numbers of extracted components in NCPD and NTD regarding the ERP context.
SINGLE-TRIAL MOTOR IMAGERY CLASSIFICATION USING ASYMMETRY RATIO, PHASE RELATION, WAVELET-BASED FRACTAL, AND THEIR SELECTED COMBINATION
Authors: HSU WEI-YEN
Published: February 2013

An electroencephalogram (EEG) analysis system is proposed for single-trial classification of motor imagery (MI) data in this study. Applying event-related brain potential (ERP) data acquired from the sensorimotor cortices, the system mainly consists of enhanced active segment selection, feature extraction, feature selection and classification. In addition to the original use of continuous wavelet transform (CWT) and Student's two-sample t-statistics, the 2D anisotropic Gaussian filter is proposed to further refine the selection of active segments. We then extract several features, including spectral power and asymmetry ratio, coherence and phase-locking value, and multiresolution fractal feature vector, for subsequent classification. Next, genetic algorithm (GA) is used to select features from the combination of above-mentioned features. Finally, support vector machine (SVM) is used for classification. Compared with "without enhanced active segment selection," several potential features and linear discriminant analysis (LDA) on MI data from two data sets for 10 subjects, the results indicate that the proposed method achieves 86.7% average classification accuracy, which is promising in BCI applications.
SIMULATING INDIVIDUAL-BASED MODELS OF BACTERIAL CHEMOTAXIS WITH ASYMPTOTIC VARIANCE REDUCTION
Authors: ROUSSET MATHIAS , SAMAEY GIOVANNI
Published: February 2013

We discuss variance reduced simulations for an individual-based model of chemotaxis of bacteria with internal dynamics. The variance reduction is achieved via a coupling of this model with a simpler process in which the internal dynamics has been replaced by a direct gradient sensing of the chemoattractants concentrations. In the companion paper ["Individual-based models for bacterial chemotaxis in the diffusion limit" (to appear in Math. Models Methods Appl. Sci., DOI: 10.1142/S0218202513500243)], we have rigorously shown, using a pathwise probabilistic technique, that both processes converge towards the same advection–diffusion process in the diffusive asymptotics. In this work, a direct coupling is achieved between paths of individual bacteria simulated by both models, by using the same sets of random numbers in both simulations. This coupling is used to construct a hybrid scheme with reduced variance. We first compute a deterministic solution of the kinetic density description of the direct gradient sensing model; the deviations due to the presence of internal dynamics are then evaluated via the coupled individual-based simulations. We show that the resulting variance reduction is asymptotic, in the sense that, in the diffusive asymptotics, the difference between the two processes has a variance which vanishes according to the small parameter.