bluuebunny/crossref_metadata_2025 huggingface dataset:
Struggling with AIDS in South Africa: The Space of the Everyday as a Field of Recognition
Authors: Le Marcis Frédéric
Published: December 2012

The space of volunteering is often seen as a place for rebuilding a world for individuals for whom life has been destroyed by the discovery of AIDS infection. People living with AIDS get involved in HIV support groups, become volunteers, and take care for each other. Without denying the reality of these processes leading to a “positive life” this article questions narratives of the transformation of the self‐implied in the “caring for other” logic and argues that other spheres of life, less discernable because inscribed in the ordinary and in the intimacy of domestic life are at least as important as the involvement in biomedical care. The limits of voluntary work is highlighted and contrasted with a presentation of how life, love and affection is reconfigured within everyday life, leading to a consideration of people's struggles to build spaces of recognition. The argument of this article is built on a three year ethnography (2001–04) carried out in Soweto and Alexandra townships (South Africa).
The contribution of foliar endophytes to quantitative resistance to Melampsora rust
Authors: Raghavendra Anil K. H. , Newcombe George
Published: December 2012

Foliar endophytes of Populus do not induce the hypersensitive response associated with major genes for resistance to Melampsora leaf rust. But they could contribute to the quantitative resistance that represents a second line of defense. Quantitative resistance is thought to be determined by suites of minor genes in both host and pathogen that are influenced by the abiotic environment. Here, we determined the relative importance to quantitative resistance of foliar endophytes, one element of the biotic environment.

Leaves of six host genotypes differing in genetic resistance to Melampsora × columbiana were inoculated first with one of four foliar endophytes (Stachybotrys sp., Trichoderma atroviride, Ulocladium atrum or Truncatella angustata), and then with Melampsora.

These endophytes greatly reduced rust severity within inoculated leaves (i.e. local effects), but they had no systemic effect on rust of leaves not inoculated with endophytes. Differences among endophytes and their controls explained 54% of the total variation in quantitative resistance (i.e. rust severity); the six host/pathogen genotypes explained just 5%. In terms of magnitude of effect on rust severity, Stachybotrys, Trichoderma, Ulocladium and Truncatella were ranked in this order on all host/pathogen genotypes.

Endophytes may contribute significantly to quantitative resistance to Melampsora in leaves of Populus.
Accidental displacement of third molars; report of three cases, review of literature and treatment recommendations
Authors: Anand R. , Patil P.M.
Published: December 2012

The displaced third molar is a rare but potentially serious complication of extraction. Every dentist should treat it with care, and when the accident occurs, the general dentist should refer the patient to an oral and maxillofacial surgeon as soon as possible. The surgeon should localise the fragment by appropriate imaging and should remove it by a technique suited to the situation. We present our experience with three displaced third molars: one in the maxillary sinus, one in the submandibular space and one in the pterygomandibular space, all of which were all surgically retrieved without any surgical complications. A review of literature on the subject is examined and a treatment guideline is suggested for use when confronted with such accidents.
Use of a Noninvasive Continuous Monitoring Device in the Management of Atrial Fibrillation: A Pilot Study
Authors: ROSENBERG MICHAEL A. , SAMUEL MICHELLE , THOSANI AMIT , ZIMETBAUM PETER J.
Published: December 2012

Background

Outpatient ambulatory cardiac rhythm monitoring is a routine part of the management of patients with paroxysmal atrial fibrillation (AF). Current systems are limited by patient convenience and practicality.

Methods

We compared the Zio® Patch, a single‐use, noninvasive waterproof long‐term continuous monitoring patch, with a 24‐hour Holter monitor in 74 consecutive patients with paroxysmal AF referred for Holter monitoring for detection of arrhythmias.

Results

The Zio® Patch was well tolerated, with a mean monitoring period of 10.8 ± 2.8 days (range 4–14 days). Over a 24‐hour period, there was excellent agreement between the Zio® Patch and Holter for identifying AF events and estimating AF burden. Although there was no difference in AF burden estimated by the Zio® Patch and the Holter monitor, AF events were identified in 18 additional individuals, and the documented pattern of AF (persistent or paroxysmal) changed in 21 patients after Zio® Patch monitoring. Other clinically relevant cardiac events recorded on the Zio® Patch after the first 24 hours of monitoring, including symptomatic ventricular pauses, prompted referrals for pacemaker placement or changes in medications. As a result of the findings from the Zio® Patch, 28.4% of patients had a change in their clinical management.

Conclusions

The Zio® Patch was well tolerated, and allowed significantly longer continuous monitoring than a Holter, resulting in an improvement in clinical accuracy, the detection of potentially malignant arrhythmias, and a meaningful change in clinical management. Further studies are necessary to examine the long‐term impact of the use of the Zio® Patch in AF management.
Evaluating MRI‐Compatible Pacemakers: Patient Data Now Paves the Way to Widespread Clinical Application?
Authors: SANTINI LUCA , FORLEO GIOVANNI B. , SANTINI MASSIMO ,   on behalf of the World Society of Arrhythmias
Published: December 2012

The worldwide use of both magnetic resonance imaging (MRI) and pacing devices has vastly increased in recent years and an important number of implanted patients likely will need an MRI over the course of the lifetime of their device. Although some studies have demonstrated that, given appropriate precautions, MRI can be safely performed in patients with selected implantable pacemakers, MRI in pacemaker patients is still contraindicated. Recently, new pacing systems have been specifically designed for safe use in the MRI environment and the first experience reported suggests that the technology is safe and may allow patients to undergo MRI. This review will describe the outstanding issues and controversies surrounding the safety of MRI imaging in pacemaker patients and the potential benefits of the new MRI‐conditional technology. We will also discuss how to approach the decision whether or not an MRI‐conditional system should be implanted and highlight key issues that warrant further studies.
Effectiveness of a Heated Lidocaine/Tetracaine Topical Patch for Pain Associated with Myofascial Trigger Points: Results of an Open‐label Pilot Study
Authors: Rauck Richard , Busch Michael , Marriott Thomas
Published: December 2012

Objective

Evaluate potential usefulness of a heated lidocaine/tetracaine topical patch for treatment for pain associated with myofascial trigger points (MTPs).

Background

Depth and duration of analgesia when patch is used as indicated, on intact skin to provide local dermal analgesia for superficial venous access and dermatologic procedures, suggest utility in relief of MTP‐associated pain.

Methods

In this open‐label, single‐center outpatient pilot study, patients with ≥ 1‐month history of pain associated with up to 3 MTPs and average pain intensity ≥ 4 on 11‐point scale applied 1 patch to each MTP for 4 hours twice daily for 2 weeks, followed by 2 weeks with no treatment. Patients continued prescribed analgesic dosing regimens.

Results

Twenty patients enrolled; 17 completed the study. At baseline, mean ± SD average pain intensity was 6.3 ± 1.56. This decreased by 33% to 4.5 ± 2.31 (N = 20) at the end of treatment; 40% of patients had clinically significant (≥ 30%) decrease, and 25% had substantial (≥ 50%) decrease. Pain interference with general activity, mood, normal work, and enjoyment of life decreased by ≥ 50% in 35% of patients; and with walking, sleep, and relationship by ≥ 50% in 50% of patients (N = 20). Worst trigger point sensitivity improved in 45% of patients; 75% were satisfied or very satisfied with treatment; none required rescue medication. Two weeks after stopping treatment, average pain intensity was 5.0 ± 2.04; treatment benefit was maintained in 8 (40%) patients. The most common adverse event was erythema.

Conclusion

The heated lidocaine/tetracaine patch has potential utility as a noninvasive pharmacologic approach for managing MTP pain. Further studies are warranted.
Mapping quantitative trait loci for freezing tolerance in a recombinant inbred line population of Arabidopsis thaliana accessions Tenela and C24 reveals REVEILLE1 as negative regulator of cold acclimation
Authors: MEISSNER MEIKE , ORSINI ELENA , RUSCHHAUPT MORITZ , MELCHINGER ALBRECHT E. , HINCHA DIRK K. , HEYER ARND G.
Published: December 2012

A recombinant inbred line population for the accessions C24 and Tenela (Te), showing large variation in freezing tolerance, was established to study genetic determinants of cold acclimation capacity in Arabidopsis thaliana. Mapping of quantitative trait loci (QTL) revealed three QTL regions on chromosomes 2, 4 and 5. With the aid of gene expression data, the Myb family transcription factor REVEILLE1 (At5g17300) on chromosome 5 was identified as a novel negative regulator of freezing tolerance in Arabidopsis.
Central nervous system complications and neuroradiological findings in children with chronic active Epstein–Barr virus infection
Authors: Ishikawa Nobutsune , Kawaguchi Hiroshi , Nakamura Kazuhiro , Kobayashi Masao
Published: December 2012

Background

Although many neurological complications have been described in acute Epstein–Barr virus infection, few reports have discussed the central nervous system complications in chronic active Epstein–Barr virus (CAEBV) infection.

Methods

We retrospectively surveyed the medical records of 14 patients with CAEBV infection in our institute. Neuroradiological studies were performed in 10 of these patients.

Results

Five had no neurological symptoms, whereas two presented with posterior reversible encephalopathy syndrome, one presented with basal ganglia calcification, and one presented with falx cerebri hemorrhage. Although both of the posterior reversible encephalopathy syndrome cases developed epilepsy several years after recovering from prolonged neurological deterioration, the others had no neurological sequelae.

Conclusions

This study revealed that various central nervous system complications may occur during the clinical course in pediatric CAEBV patients.
Clinical analysis of combination therapy for febrile neutropenic patients in childhood cancer
Authors: Kobayashi Shogo , Ito Masaki , Sano Hideki , Mochizuki Kazuhiro , Akaihata Mitsuko , Waragai Tomoko , Hosoya Mitsuaki , Kikuta Atsushi
Published: December 2012

Background

The objective of this study was to evaluate the efficacy and safety of our combination therapy in febrile neutropenic children with cancer.

Methods

A total of 109 patients with 251 episodes of febrile neutropenia received antibiotic therapy between January 2003 and December 2008 at a single institution.

Results

Blood cultures were positive in 35 episodes (14%). Gram‐positive organisms predominated (23/38 organisms isolated). There were 15 gram‐negative isolates and no fungal isolates. The recommended empirical first‐line antibiotics (cefepime or cefozopran + piperacillin + amikacin) were used in 206 (82%), second‐line antibiotics (piperacillin‐tazobactam + carbapenem + amikacin + micafungin) in 73 (29%), and third‐line antibiotics (meropenem + glycopeptides + micafungin) in 24 (10%) episodes. The overall response rates were 71.4%, 50.7%, and 62.5% for the first‐, second‐, and third‐line antibiotic therapies, respectively. Granulocyte transfusion was performed in seven patients, and the response rate was 57%. Four deaths were recorded.

Conclusions

Although a significant improvement of mortality was not observed, our regimen of empirical antibiotic therapies led to a significant and clinically relevant decrease in glycopeptide use, and it is safe and well tolerated by pediatric neutropenic patients.
Parenteral‐nutrition‐associated liver disease after intestinal perforation in extremely low‐birthweight infants: Consequent lethal portal hypertension
Authors: Kubota Akio , Mochizuki Narutaka , Shiraishi Jun , Nakayama Masahiro , Kawahara Hisayoshi , Yoneda Akihiro , Tazuke Yuko , Goda Taro , Nakahata Kengo , Sano Hiroyuki , Hirano Shinya , Kitajima Hiroyuki
Published: December 2012

Background

Parenteral nutrition (PN)‐associated liver dysfunction (PNALD) in term infants usually manifests as intrahepatic cholestasis, which recovers with enteral nutrition (EN) in most cases; however, as the number of extremely low‐birthweight infants (ELBWI) has been increasing, and consequently intestinal diseases associated with ELBWI have been increasing, more intractable PNALD has been encountered after surgical treatment in ELBWI, which does not resolve or rather worsens with EN.

Methods

Three cases of ELBWI with intestinal perforation, which developed PNALD and eventually died of hepatic failure with intractable portal hypertension, were reviewed. Their gestational age and birthweight ranged from 23 to 26 weeks, and from 434 to 968 g, respectively. The intestinal diseases included necrotizing enteritis in two and meconium‐related ileus with focal intestinal perforation in one.

Results

The duration of total PN without EN in the three cases was 17, 24 and 24 days, respectively. The interval between the introduction of PN and the onset of PNALD was 14, 4 and 18 days, respectively. A marked elevation of serum endotoxin level was detected in both cases of necrotizing enteritis. Histopathological study of the liver revealed marked cholestasis, significant hepatic necrosis with fibrosis, and proliferation of ductules in all these cases, which was responsible for portal hypertension.

Conclusions

PN after gastrointestinal disorders in ELBWI may cause refractory PNALD, which does not resolve, or rather worsens with the resumption of EN. Portal hypertension secondary to hepatic necrosis may be responsible for the exacerbation with the resumption of EN.
Maternal Hypertensive Disorders during Pregnancy and Mild Cognitive Limitations in the Offspring
Authors: Heikura Ulla , Hartikainen Anna‐Liisa , Nordström Tanja , Pouta Anneli , Taanila Anja , Järvelin Marjo‐Riitta
Published: December 2012

Background

It remains unclear whether maternal hypertensive disorders could impact cognitive development of the child. The aim of this study was to explore the association between hypertensive disorders and other maternal biological and social factors on the risk of mild cognitive limitations (intelligence quotient 50–85) in the offspring.

Methods

An 11.5‐year follow‐up study of the Northern Finland Birth Cohort 1986 (n = 9432) was utilised. The analysis included 8847 singleton children, of whom 198 had mild cognitive limitations. Gestational hypertension was defined as de novo hypertension (blood pressure ≥ 140/90), diagnosed mid‐pregnancy in a previously normotensive woman. Data on intelligence level of the children were based on standardised intelligence test results.

Results

Eleven per cent (n = 20) of mothers having a child with mild cognitive limitations had gestational hypertension. Maternal gestational hypertension was independently associated with increased odds of mild cognitive limitation in the offspring (odds ratio 2.4 [95% confidence interval 1.4, 3.9]). Other independent maternal risk factors for mild cognitive limitation were high pre‐pregnancy body mass index (≥30 kg/m2), multiparity (≥4) and low education. In addition family's socio‐economic status lower than professional, male gender and small birthweight‐for‐gestational age appeared as independent risk factors for mild cognitive limitation.

Conclusions

Gestational hypertension should be considered as one of the adverse early risk factors that may predispose to impaired cognitive development in childhood.
Historical perspective and better regulatory governance: An agenda for institutional reform
Authors: Balleisen Edward J. , Brake Elizabeth K.
Published: December 2012

Compared to economics, sociology, political science, and law, the discipline of history has had a limited role in the wide‐ranging efforts to reconsider strategies of regulatory governance, especially inside regulatory institutions. This article explores how more sustained historical perspective might improve regulatory decisionmaking. We first survey how a set of American regulatory agencies currently rely on historical research and analysis, whether for the purposes of public relations or as a means of supporting policymaking. We then consider how regulatory agencies might draw on history more self‐consciously, more strategically, and to greater effect. Three areas stand out in this regard – the use of history to improve understanding of institutional culture; reliance on historical analysis to test the empirical plausibility of conceptual models that make assumptions about the likelihood of potential economic outcomes; and integration of historical research methods into program and policy evaluation.
Expanding the Role of K‐5 Science Instruction in Educational Reform: Implications of an Interdisciplinary Model for Integrating Science and Reading
Authors: Romance Nancy R. , Vitale Michael R.
Published: December 2012

Addressed is the current practice in educational reform of reducing time for science instruction in favor of traditional reading/language arts instruction. In contrast, presented is an evidence‐based rationale for increasing instructional time for K‐5 science instruction as an educational reform initiative. Overviewed are consensus interdisciplinary research and complementary multi‐year findings of the Science IDEAS model demonstrating the effectiveness of integrating conceptually‐relevant reading within science instruction in improving student achievement in both science and reading comprehension. Based on research summarized, increasing time for integrated K‐5 science is advocated as a meaningful reform‐based approach to science learning and reading comprehension proficiency that, in turn, better prepares students for subsequent success in science and content‐area reading comprehension across upper elementary and middle school grades (3–8).
Intra‐messinian gypsum palaeokarst in the Northern Apennines and its palaeogeographic implications
Authors: De Waele Jo , Pasini Giancarlo
Published: December 2012

A short intra‐Messinian continental period has been recognised in some North Italian gypsum areas, mostly under the form of palaeokarst deposits. This emersion appears to have occurred only locally, and is explained as caused by the intra‐Messinian tectonic phase and a major sea level lowering. Evidences of this palaeokarst are mostly small, although at some places the palaeontological content of its fillings is of great importance. The discovery near Zola Predosa (Bologna) of a new intra‐Messinian extensive karst system and of its infilling sheds new light on the importance of this karst episode.
Association between a functional polymorphism in Toll‐like receptor 3 and chronic hepatitis C in liver transplant recipients
Authors: Lee S.‐O. , Brown R.A. , Razonable R.R.
Published: December 2012

Background

Toll‐like receptor 3 (TLR3) is implicated in the pathogenesis of viral diseases owing to its ability to recognize viral double‐stranded RNA. We hypothesized that single nucleotide polymorphism (SNP) in TLR3 gene that impairs the function of the protein‐receptor influences the outcome of hepatitis C virus (HCV) infection after liver transplantation.

Methods

The clinical characteristics of 611 liver recipients (HCV‐infected: n = 153, non‐HCV‐infected: n = 458) were assessed to investigate the impact of TLR3 L412F SNP on transplant outcomes.

Results

TLR3 L412F is common, and it was significantly more prevalent among the HCV‐infected cohort (57.5% vs. 45.2%, P = 0.008). In a multivariate analysis, TLR3 L412F was significantly associated with chronic hepatitis C (odds ratio: 1.73, 95% confidence interval [CI]: 1.13–2.65, P = 0.01). In an analysis that compared HCV‐infected patients with wild‐type versus TLR3 L412F, a marginally higher rate of allograft failure and mortality was observed in the TLR3 L412F group (44.3% vs. 30.8%, P = 0.09). However, in a multivariate analysis, only donor age was significantly associated with allograft failure and mortality (relative risk: 1.04, 95% CI: 1.007–1.06, P = 0.02).

Conclusion

TLR3 L412F is significantly common in HCV‐infected liver recipients, and may be associated with worse outcomes. However, larger studies are needed to determine its significant association with allograft failure and mortality after liver transplantation for chronic hepatitis C.
Bladder transitional cell carcinoma and BK virus in a young kidney transplant recipient
Authors: Pino L. , Rijo E. , Nohales G. , Frances A. , Ubre A. , Arango O.
Published: December 2012

Kidney transplant recipients have a heightened risk of developing neoplasms. Immunosuppressive treatments decrease the incidence of transplant rejection but increase the risk of infections, including BK virus (BKV). This infection is acquired in childhood and remains latent in the renal and urinary epithelium. In cases of immunodeficiency, BKV has been implicated as a tumor virus, but the role of BKV in cancer is a controversial topic and is difficult to determine. In the tumor cells, it is possible to detect fragments of the viral genome that could alter the control mechanisms of the cell cycle and DNA repair. We report the case of a kidney transplant recipient who developed BKV nephropathy and carcinoma of the bladder, supporting a possible role for BKV in the oncogenic pathway in this clinical setting, but the role of BKV in cancer remains a controversial topic and difficult to determine.
ATR and MKP1 play distinct roles in response to UV‐B stress in Arabidopsis
Authors: González Besteiro Marina A. , Ulm Roman
Published: December 2012

Ultraviolet‐B (UV‐B) stress activates MAP kinases (MAPKs) MPK3 and MPK6 in Arabidopsis. MAPK activity must be tightly controlled in order to ensure an appropriate cellular outcome. MAPK phosphatases (MKPs) effectively control MAPKs by dephosphorylation of phosphothreonine and phosphotyrosine in their activation loops. Arabidopsis MKP1 is an important regulator of MPK3 and MPK6, and mkp1 knockout mutants are hypersensitive to UV‐B stress, which is associated with reduced inactivation of MPK3 and MPK6. Here, we demonstrate that MPK3 and MPK6 are hyperactivated in response to UV‐B in plants that are deficient in photorepair, suggesting that UV‐damaged DNA is a trigger of MAPK signaling. This is not due to a block in replication, as, in contrast to atr, the mkp1 mutant is not hypersensitive to the replication‐inhibiting drug hydroxyurea, hydroxyurea does not activate MPK3 and MPK6, and atr is not impaired in MPK3 and MPK6 activation in response to UV‐B. We further show that mkp1 leaves and roots are UV‐B hypersensitive, whereas atr is mainly affected at the root level. Tolerance to UV‐B stress has been previously associated with stem cell removal and CYCB1;1 accumulation. Although UV‐B‐induced stem cell death and CYCB1;1 expression are not altered in mkp1 roots, CYCB1;1 expression is reduced in mkp1 leaves. We conclude that the MKP1 and ATR pathways operate in parallel, with primary roles for ATR in roots and MKP1 in leaves.
Applying principles of formulary management to blood banking
Authors: Fagan Nancy L. , Malone Patrick M. , Baltaro Richard J. , Malesker Mark A.
Published: December 2012

The pharmacy and therapeutics (P&T) committee or its equivalent has been a long‐standing committee of the medical staff in almost every institution. The P&T committee is typically defined as the body that recommends policy to the medical staff and the administration of the organization on matters related to the safe and therapeutic use of medications as well as other matters relating to medication use. The Food and Drug Administration definition of a drug includes blood and blood components, and the American Society of Health‐System Pharmacists guidelines suggest including blood derivatives in their definition of a drug. Clinicians and other health care providers have needed to become more familiar with blood and blood component therapy as more prescription blood products have become available. As such, the P&T committee could work collaboratively with blood bank personnel, who are experts in this area, to help ensure that blood derivative products undergo the same evidence‐based formulary review process as other medications.
Aqueous humor fibrinolytic activity in dogs with cataracts
Authors: Escanilla Natàlia , Leiva Marta , Monreal Luís , Ríos José , Peña Teresa
Published: December 2012

Objective

To investigate fibrinolytic activity in aqueous humor (AH) of healthy and sick dogs, with and without cataracts.

Procedure

Prospective observational clinical study. A total of 45 dogs were included in the study. Physical and ophthalmic examinations, complete blood cell count (CBC) and serum biochemistry panel were performed in all animals. According to the ocular and systemic diagnoses, animals were classified into three groups: sick dogs without cataracts (20 dogs; 40 eyes), diabetic dogs with cataracts (11 dogs; 22 eyes), and healthy dogs with cataracts (14 dogs; 25 eyes). Bilateral AH and blood samples were collected during intraocular surgery (25 dogs; 47 eyes), or immediately after euthanasia (20 dogs; 40 eyes). Citrated samples were centrifuged and stored at −81 °C until analysis. Plasma and AH D‐dimer concentration were determined using a quantitative immunoturbidimetric latex agglutination assay.

Results

A total of 108 canine samples (45 plasma and 87 AH samples) were obtained. D‐dimer concentration in log‐scale, in AH of eyes with diabetic cataract was significantly higher thanAHof eyes with nondiabetic cataract, with a difference of 0.9 ng/mL 95% confidence interval (CI) (0.2; 1.6)P = 0.0116 and higher than that of sick animals with healthy eyes, with a estimated difference of −0.89 ng/mL 95% CI (−1.52; −0.25)P = 0.0061.

PlasmaD‐dimer concentration was significantly higher in the group of animals with systemic disease [median 606 ng/mL, Interquartil Range (IQR) 145–1956 ng/mL] than in healthy dogs (median 47.5 ng/mL, IQR 4–250 ng/mL) (P = 0.002) and diabetic dogs (median 60.5 ng/mL, IQR 0–147.5 ng/mL) (P < 0.001).

Conclusion

AH fibrinolysis is present in dogs, being significantly higher in animals with diabetic cataracts than in those without cataracts, and those with nondiabetic cataracts.
MORAL ECONOMY AND MAORI FISHERIES
Authors: McCormack Fiona
Published: December 2012

In this article I argue that the separation of commercial and customary fishing, which was a result of the 1992 Treaty of Waitangi Fisheries Settlement Act, denies their essential integration in the practices of small-scale fishers across time and space. Theorists who have analysed the moral economy and petty commodity production invariably conclude that commercial production (for money and/or profit) and customary production (for subsistence and the fulfilment of cultural activities and obligations) exist on a continuum and that both are indeed necessary for the survival of small-scale producers. The definition of customary activity as the absence of monetary transactions is not consistent with either international legal decisions, or with the social reality of small-scale Maori fishers, who operate in mixed economies, sometimes moral, sometimes capitalist, and exchange fish in much the same manner, sometimes in order to achieve a balance and sometimes for profit.
Comprehensive comparison of structural, electrical, and reliability characteristics of HfO2 gate dielectric with H2O or O3 oxidant
Authors: Cheng Yi-Lung , Chang You-Ling , Hsieh Cheng-Yang , Lin Jian-Run
Published: December 2012

The growth, composition, electrical characteristics, and reliability performance of high-k HfO2 dielectric films that were deposited by an atomic layer deposition technique are studied. The films were grown using tetrakis(ethylmethylamino)hafnium precursor and either H2O or ozone (O3) as the oxidant. When H2O was the oxidant, the resulting HfO2 film had a thinner interfacial layer than that obtained using the O3 oxidant, but the bulk HfO2 layer was of a poorer quality. Of the annealed HfO2 films with a comparable equivalent oxide thickness, the O3 oxidant-based HfO2 films had better electrical properties and reliability. The oxide charge density, the hysteresis, the leakage current, the breakdown electrical field, and the time to dielectric breakdown of the HfO2 film that was deposited with O3 oxidant were all better those of the film that was deposited with H2O oxidant. Additionally, the dynamic stress, including unipolar and bipolar stresses, increases the times to dielectric breakdown for both HfO2 films. However, the increase under bipolar stress was greater for the HfO2 films that were grown using the H2O oxidant because more detrapping occurred.
Aggravating Genetic Interactions Allow a Solution to Redundancy in a Bacterial Pathogen
Authors: O’Connor Tamara J. , Boyd Dana , Dorer Marion S. , Isberg Ralph R.
Published: December 2012

Resolving Redundancy

Many intracellular bacterial pathogens, like
Salmonella, Legionella
, and
Chlamydia
, make their homes within a host cell vacuole. Although we have cataloged many of the effector proteins secreted by these bacteria and their individual effects on host cell pathways, it is often not clear how the effectors work in concert to optimize bacterial growth.

O'Connor
et al.

(p.
1440
) tackled this complexity problem in
Legionella pneumophila.
This pathogen has an exceptionally long list of apparently redundant effector proteins to its name and, indeed, initial screening produced a library of 678
Legionella
genes important for intracellular growth. Using bacterial mutagenesis to manipulate effector proteins and RNA interference in host cells to inhibit specific cellular membrane-trafficking pathways allowed systematic prediction by cluster analysis of sets of bacterial proteins with common targets required for intracellular growth.
Casting a Wider Net
Networked Life
20 Questions and Answers

by Mung Chiang

Cambridge University Press, Cambridge, 2012. 504 pp. $45, £27.99. ISBN 9781107024946.
Authors: Stein Lynn Andrea
Published: December 2012

In this text intended for both classroom and online learning, Chiang uses questions about our online lives to explore the technology and computer science behind the Internet, wireless, and Web industries.
Epigenetic Regulation by Long Noncoding RNAs
Authors: Lee Jeannie T.
Published: December 2012

Long Noncoding RNAs

The past 5 years have uncovered thousands of long (>100 nucleotides) noncoding RNAs (lncRNAs) outpacing our understanding of their functions and mechanisms in regulating the genome.
Lee
(p.
1435
) reviews the known and suspected means by which these intriguing molecules control gene expression locally and at great distances, considers potential universal roles for lncRNAs, and warns that classifying these intriguing molecules may be quite challenging given their diversity. The very long noncoding RNA,
Airn
, silences the
Igf2r
(insulin-like growth factor 2 receptor) imprinted gene cluster in mammals.

Latos
et al.

(p.
1469
) show in mouse cells that, rather than recruiting enzymes that modify histones to repress the locus, it is the act of transcription of
Airn
(and not the
Airn
gene product) that results in the silencing.
EZH2 Goes Solo
Authors: Cavalli Giacomo
Published: December 2012

A transcriptional repressor switches to an activator function in an aggressive form of prostate cancer.
Japan Stands Alone in Bid for $10 Billion Collider
Authors: Normile Dennis
Published: December 2012

Almost 2 decades before the Large Hadron Collider at CERN caught a glimpse of the long-sought Higgs boson, physicists began planning a machine that would examine the Higgs in detail and probe for even more elusive particles. Now, the design for that machine, the International Linear Collider, is nearing completion. But can it be built?
University of Texas Revamps Conflict Rules After Critical Review
Authors: Marshall Eliot
Published: December 2012

It's rare to see the accused and the accusers in a conflict of interest case end up on the same note. But that appears to be what happened last week when the University of Texas, Austin, accepted an independent review panel's harsh findings, echoing outside critics, about a controversial study conducted earlier this year by the university's Energy Institute.
Beyond TALENs
Authors: Pennisi Elizabeth
Published: December 2012

Zinc finger nucleases and TALENS are not the only up-and-coming genome engineering tools. There are meganucleases that are DNA-cutting enzymes encoded by certain mobile elements, nucleases that might do the job solo, and a potential bacterial defense system.
How to Build a Smarter Rock
Authors: Underwood Emily
Published: December 2012

Predicting when and where rivers will move gigatons of rock and sediment has proved a murky problem; a new generation of electronic smart rocks could clarify matters.
Experimental Landscapes Raise Stakes at Biosphere 2
Authors: Stokstad Erik
Published: December 2012

The University of Arizona is betting that a unique trio of artificial hillsides will put an iconic greenhouse back on the map.
Evaluation of Protective Potential of Yersinia pestis Outer Membrane Protein Antigens as Possible Candidates for a New-Generation Recombinant Plague Vaccine
Authors: Erova Tatiana E. , Rosenzweig Jason A. , Sha Jian , Suarez Giovanni , Sierra Johanna C. , Kirtley Michelle L. , van Lier Christina J. , Telepnev Maxim V. , Motin Vladimir L. , Chopra Ashok K.
Published: December 2012

Plague caused by
Yersinia pestis
manifests itself in bubonic, septicemic, and pneumonic forms. Although the U.S. Food and Drug Administration recently approved levofloxacin, there is no approved human vaccine against plague. The capsular antigen F1 and the low-calcium-response V antigen (LcrV) of
Y. pestis
represent excellent vaccine candidates; however, the inability of the immune responses to F1 and LcrV to provide protection against
Y. pestis
F1
−
strains or those which harbor variants of LcrV is a significant concern. Here, we show that the passive transfer of hyperimmune sera from rats infected with the plague bacterium and rescued by levofloxacin protected naive animals against pneumonic plague. Furthermore, 10 to 12 protein bands from wild-type (WT)
Y. pestis
CO92 reacted with the aforementioned hyperimmune sera upon Western blot analysis. Based on mass spectrometric analysis, four of these proteins were identified as attachment invasion locus (Ail/OmpX), plasminogen-activating protease (Pla), outer membrane protein A (OmpA), and F1. The genes encoding these proteins were cloned, and the recombinant proteins purified from
Escherichia coli
for immunization purposes before challenging mice and rats with either the F1
−
mutant or WT CO92 in bubonic and pneumonic plague models. Although antibodies to Ail and OmpA protected mice against bubonic plague when challenged with the F1
−
CO92 strain, Pla antibodies were protective against pneumonic plague. In the rat model, antibodies to Ail provided protection only against pneumonic plague after WT CO92 challenge. Together, the addition of
Y. pestis
outer membrane proteins to a new-generation recombinant vaccine could provide protection against a wide variety of
Y. pestis
strains.
Human Cytomegalovirus pUL29/28 and pUL38 Repression of p53-Regulated p21CIP1 and Caspase 1 Promoters during Infection
Authors: Savaryn John P. , Reitsma Justin M. , Bigley Tarin M. , Halligan Brian D. , Qian Zhikang , Yu Dong , Terhune Scott S.
Published: December 2012

During infection by human cytomegalovirus (HCMV), the tumor suppressor protein p53, which promotes efficient viral gene expression, is stabilized. However, the expression of numerous p53-responsive cellular genes is not upregulated. The molecular mechanism used to manipulate the transcriptional activity of p53 during infection remains unclear. The HCMV proteins IE1, IE2, pUL44, and pUL84 likely contribute to the regulation of p53. In this study, we used a discovery-based approach to identify the protein targets of the HCMV protein pUL29/28 during infection. Previous studies have demonstrated that pUL29/28 regulates viral gene expression by interacting with the chromatin remodeling complex NuRD. Here, we observed that pUL29/28 also associates with p53, an additional deacetylase complex, and several HCMV proteins, including pUL38. We confirmed the interaction between p53 and pUL29/28 in both the presence and absence of infection. HCMV pUL29/28 with pUL38 altered the activity of the 53-regulatable p21CIP1 promoter. During infection, pUL29/28 and pUL38 contributed to the inhibition of p21CIP1 as well as caspase 1 expression. The expression of several other p53-regulating genes was not altered. Infection using a UL29-deficient virus resulted in increased p53 binding and histone H3 acetylation at the responsive promoters. Furthermore, expression of pUL29/28 and its interacting partner pUL38 contributed to an increase in the steady-state protein levels of p53. This study identified two additional HCMV proteins, pUL29/28 and pUL38, which participate in the complex regulation of p53 transcriptional activity during infection.
Estimating the Rate of Intersubtype Recombination in Early HIV-1 Group M Strains
Authors: Ward Melissa J. , Lycett Samantha J. , Kalish Marcia L. , Rambaut Andrew , Leigh Brown Andrew J.
Published: December 2012

West Central Africa has been implicated as the epicenter of the HIV-1 epidemic, and almost all group M subtypes can be found there. Previous analysis of early HIV-1 group M sequences from Kinshasa in the Democratic Republic of Congo, formerly Zaire, revealed that isolates from a number of individuals fall in different positions in phylogenetic trees constructed from sequences from opposite ends of the genome as a result of recombination between viruses of different subtypes. Here, we use discrete ancestral trait mapping to develop a procedure for quantifying HIV-1 group M intersubtype recombination across phylogenies, using individuals'
gag
(p17) and
env
(gp41) subtypes. The method was applied to previously described HIV-1 group M sequences from samples obtained in Kinshasa early in the global radiation of HIV. Nine different p17 and gp41 intersubtype recombinant combinations were present in the data set. The mean number of excess ancestral subtype transitions (NEST) required to map individuals' p17 subtypes onto the gp14 phylogeny samples, compared to the number required to map them onto the p17 phylogenies, and vice versa, indicated that excess subtype transitions occurred at a rate of approximately 7 × 10
−3
to 8 × 10
−3
per lineage per year as a result of intersubtype recombination. Our results imply that intersubtype recombination may have occurred in approximately 20% of lineages evolving over a period of 30 years and confirm intersubtype recombination as a substantial force in generating HIV-1 group M diversity.
Identification of Novel Influenza A Virus Proteins Translated from PA mRNA
Authors: Muramoto Yukiko , Noda Takeshi , Kawakami Eiryo , Akkina Ramesh , Kawaoka Yoshihiro
Published: December 2012

Many replication events are involved in the influenza A virus life cycle, and they are accomplished by different virus proteins with specific functions. However, because the size of the influenza virus genome is limited, the virus uses different mechanisms to express multiple viral proteins from a single gene segment. The M2 and NS2 proteins are produced by splicing, and several novel influenza A virus proteins, such as PB1-F2, PB1-N40, and PA-X, have recently been identified. Here, we identified novel PA-related proteins in influenza A virus-infected cells. These newly identified proteins are translated from the 11th and 13th in-frame AUG codons in the PA mRNA and are, therefore, N-terminally truncated forms of PA, which we named PA-N155 and PA-N182, respectively. The 11th and 13th AUG codons are highly conserved among influenza A viruses, and the PA-N155 and PA-N182 proteins were detected in cells infected with various influenza A viruses isolated from different host species, suggesting the expression of these N-truncated PAs is universal in nature among influenza A viruses. These N-truncated PAs did not show polymerase activity when expressed together with PB1 and PB2; however, mutant viruses lacking the N-truncated PAs replicated more slowly in cell culture and had lower pathogenicity in mice than did wild-type virus. These results suggest that these novel PA-related proteins likely possess important functions in the replication cycle of influenza A virus.
Effects of Defective Interfering RNA on Symptom Induction by, and Replication of, a Novel Partitivirus from a Phytopathogenic Fungus, Rosellinia necatrix
Authors: Chiba Sotaro , Lin Yu-Hsin , Kondo Hideki , Kanematsu Satoko , Suzuki Nobuhiro
Published: December 2012

A novel mycovirus termed Rosellinia necatrix partitivirus 2 (RnPV2), isolated from a phytopathogenic fungus,
Rosellinina necatrix
strain W57, was molecularly and biologically characterized in both natural and experimental host fungi. Three double-stranded RNA (dsRNA) segments, dsRNA1, dsRNA2, and defective interfering dsRNA1 (DI-dsRNA1), whose sizes were approximately 2.0, 1.8, and 1.7 kbp, respectively, were detected in W57. While the dsRNA2 sequence, encoding the coat protein, was reported previously, dsRNA1 and DI-dsRNA1 were shown to encode competent and defective (truncated) RNA-dependent RNA polymerase, respectively. Artificial introduction of RnPV2 into an RNA silencing-defective, Dicer-like 2 knockout mutant (Δ
dcl-2
) of a nonnatural host,
Cryphonectria parasitica
(chestnut blight fungus), resulted in successful infection by the DI-dsRNA1-carrying and -free RnPV2. The DI-dsRNA1-free RnPV2 strain was characterized by a higher ratio of accumulation of the intact dsRNA1 to dsRNA2, enhanced replication and severer symptom expression, compared with the DI-carrying strain. These findings confirmed the nature of DI-dsRNA1 as a DI-RNA. Both viral strains replicated to higher levels in a Δ
dcl-2
mutant than in a wild-type
C. parasitica
fungal strain (EP155) and induced severe symptoms in the Δ
dcl-2
mutant but subtle symptoms in EP155, indicating that the host RNA silencing targets the partitivirus. No obvious phenotypic effects of infection by either virus strain were detected in the natural host fungus. These combined results represent the first example of a partitivirus with DI-RNA that alters viral symptom induction in a host-dependent manner.
Vitamin D3 as a novel treatment for irritable bowel syndrome: single case leads to critical analysis of patient-centred data
Authors: Sprake Eleanor F , Grant Vicky A , Corfe Bernard M
Published: December 2012

Irritable bowel syndrome (IBS) is a chronic and debilitating functional disorder of the gastrointestinal tract with serious and detrimental impacts on quality of life. Its aetiology is largely unknown and the identification of effective management strategies remains far from complete. This paper first reports, a case of a 41-year-old woman IBS sufferer who reported significant symptom improvements with high-dose vitamin D3 supplementation. The sufferer identified a substantial body of patient data surrounding this potential therapy on social media sites, and this paper, therefore, also reports the findings from a systematic analysis of patient-centred, internet-based data surrounding this phenomenon. Data from 37 IBS sufferers commenting on the effect of vitamin D supplementation on their condition were located; approximately 70% of these reported that high-dose supplementation improved their IBS symptoms. A randomised controlled trial into the effect of vitamin D supplementation on IBS symptomatology to test this association scientifically is merited.
Divergent associations of drinking frequency and binge consumption of alcohol with mortality within the same cohort
Authors: Graff-Iversen Sidsel , Jansen Mona Dverdal , Hoff Dominic Anthony , Høiseth Gudrun , Knudsen Gun Peggy , Magnus Per , Mørland Jørg , Normann Per Trygve , Næss Øyvind Erik , Tambs Kristian
Published: December 2012

Background

Observational studies show beneficial effects of moderate alcohol drinking on all-cause and cardiovascular disease (CVD) mortality, while binge drinking has been linked with increased mortality. The aim of this study was to assess the associations of alcohol use with mortality in a population with a hybrid of drinking patterns.

Method

Participants in a population based cardiovascular health survey in Finnmark county in 1987–1988, aged 20–62 years, constituted the study cohort. Alcohol use was self-reported by use of questions on frequency of beer, wine and liquor intake, and one question on intake of around five drinks or more per occasion (binge drinking). Information on education, income and use of alcohol in an earlier and in a later survey was linked to the file. Mortality was assessed throughout 2009 by Cox regression, with adjustment for potential confounding factors. In the analysis of mortality by frequency of any alcohol use, we adjusted for binge consumption and vice versa.

Results

Two opposite trends appeared: a higher all-cause mortality in both sexes, and higher CVD mortality in men, with increasing frequency of binge drinking, compared with non-bingers. Second, in both sexes low-frequent use of any alcohol was associated with lower all-cause and CVD mortality, compared with abstention. The combination of any use of alcohol at least weekly and binge consumption at least monthly was common, particularly in men.

Conclusions

Questions on drinking frequency and a specific question on binge drinking capture different effects of alcohol use on all-cause and CVD mortality.
Weight change associated with antiepileptic drugs
Authors: Pickrell William Owen , Lacey Arron S , Thomas Rhys H , Smith Philip E M , Rees Mark I
Published: December 2012

Aim

To investigate antiepileptic drug (AED)-related weight changes in patients with epilepsy through a retrospective observational study.

Method

We analysed the anonymised electronic primary care records of 1.1 million adult patients in Wales. We included patients aged 18 years and over with a diagnosis of epilepsy, whose body weight had been measured up to 12 months before starting, and between 3 and 12 months after starting, one of five AEDs. We calculated the weight difference after starting the AED for each patient.

Results

1423 patients were identified in total. The mean difference between body weight after and before starting each AED (together with 95% CI and p values for no difference) were: carbamazepine (CBZ) 0.43 (−0.19 to 1.05) p=0.17; lamotrigine (LTG) 0.31 (−0.38 to 1.00) p=0.38; levetiracetam (LEV) 1.00 (0.16 to 1.84) p=0.02; sodium valproate (VPA) 0.74 (0.10 to 1.38) p=0.02; topiramate (TPM) −2.30 (−4.27 to −0.33) p=0.02.

Conclusions

LEV and VPA were associated with significant weight gain, TPM was associated with significant weight loss, and LTG and CBZ were not associated with significant weight change.