bluuebunny/crossref_metadata_2025 huggingface dataset:
A Clear Advance in Soft Actuators
Authors: Rogers John A.
Published: August 2013

Soft, ionic hydrogels provide transparent, compliant electrodes that could be used in electrostatically controlled artificial muscles.

[Also see Report by

Keplinger
et al.

]
Lab Dishes Up Mini-Brains
Authors: Vogel Gretchen
Published: August 2013

Scientists have cultivated clumps of cells, dubbed cerebral organoids, that contain the rudiments of key parts of the human brain, including the hippocampus and prefrontal cortex.
Link to MERS Virus Underscores Bats' Puzzling Threat
Authors: Kupferschmidt Kai
Published: August 2013

Many new diseases seem to come from bats. What makes them so special?
European Hunter-Gatherers Dined on Domestic Pigs
Authors: Balter Michael
Published: August 2013

A study of DNA from prehistoric pigs suggests that when Near Eastern farmers moved into Europe about 8500 years ago, native fisher-folk may have adopted the newcomers' custom of keeping domesticated pigs.
Enhancement of Serum and Mucosal Immune Responses to a Haemophilus influenzae Type B Vaccine by Intranasal Delivery
Authors: Fernandez Stefan , Cisney Emily D. , Ulrich Robert G.
Published: August 2013

Intranasal (i.n.) vaccination is potentially the most direct method for conveying upper respiratory and mucosal immunity to respiratory pathogens. However, for unclear reasons, vaccines introduced into the nasal sinuses often have lower efficacy than vaccines administered by the more frequently used parenteral routes. We examined i.n. vaccination in a mouse immune-response model with a commonly used
Haemophilus influenzae
type B vaccine (Hibv) composed of the polyribosylribitol phosphate (PRP) capsule antigen conjugated to tetanus toxoid. Intranasal vaccination with Hibv using a Toll-like receptor 4 (TLR4) agonist as an adjuvant significantly increased the levels of IgA specific for the PRP capsule antigen in blood serum, saliva, and mucosal secretion specimens. In contrast, control mice vaccinated transdermally (t.d.) with Hibv did not produce significant levels of PRP-specific IgA in the blood serum and saliva, and anti-PRP IgG was increased only in serum. The i.n. and t.d. vaccinations resulted in equivalent bactericidal antibody responses in blood serum, suggesting that vaccine-derived IgG is protective against infection. Elevated levels of IgG specific for the tetanus toxoid carrier protein were measured in nasal sinuses and vaginal secretions in mice vaccinated by either the t.d. or i.n. route. Tissue culture studies confirmed that the nasopharynx-associated lymphoid tissue (NALT) was at least one of the sources of PRP-specific IgA and carrier-specific IgG within the nasal sinuses. We conclude that i.n. vaccination aided by a TLR4 agonist results in robust immune responses to both the carrier protein and bacterial polysaccharide components of the Hibv.
Increasing the Potency of an Alhydrogel-Formulated Anthrax Vaccine by Minimizing Antigen-Adjuvant Interactions
Authors: Watkinson Allan , Soliakov Andrei , Ganesan Ashok , Hirst Karie , LeButt Chris , Fleetwood Kelly , Fusco Peter C. , Fuerst Thomas R. , Lakey Jeremy H.
Published: August 2013

Aluminum salts are the most widely used vaccine adjuvants, and phosphate is known to modulate antigen-adjuvant interactions. Here we report an unexpected role for phosphate buffer in an anthrax vaccine (SparVax) containing recombinant protective antigen (rPA) and aluminum oxyhydroxide (AlOH) adjuvant (Alhydrogel). Phosphate ions bind to AlOH to produce an aluminum phosphate surface with a reduced rPA adsorption coefficient and binding capacity. However, these effects continued to increase as the free phosphate concentration increased, and the binding of rPA changed from endothermic to exothermic. Crucially, phosphate restored the thermostability of bound rPA so that it resembled the soluble form, even though it remained tightly bound to the surface. Batches of vaccine with either 0.25 mM (subsaturated) or 4 mM (saturated) phosphate were tested in a disease model at batch release, which showed that the latter was significantly more potent. Both formulations retained their potency for 3 years. The strongest aluminum adjuvant effects are thus likely to be via weakly attached or easily released native-state antigen proteins.
Inhibition of Mycobacterial GrowthIn Vitrofollowing Primary but Not Secondary Vaccination with Mycobacterium bovis BCG
Authors: Fletcher Helen A. , Tanner Rachel , Wallis Robert S. , Meyer Joel , Manjaly Zita-Rose , Harris Stephanie , Satti Iman , Silver Richard F. , Hoft Dan , Kampmann Beate , Walker K. Barry , Dockrell Hazel M. , Fruth Uli , Barker Lew , Brennan Michael J. , McShane Helen
Published: August 2013

Despite the widespread use of theMycobacterium bovisBCG vaccine, there are more than 9 million new cases of tuberculosis (TB) every year, and there is an urgent need for better TB vaccines. TB vaccine candidates are selected for evaluation based in part on the detection of an antigen-specific gamma interferon (IFN-γ) response. The measurement of mycobacterial growth in blood specimens obtained from subjects immunized with investigational TB vaccines may be a betterin vitrocorrelate ofin vivovaccine efficacy. We performed a clinical study with 30 United Kingdom adults who were followed for 6 months to evaluate the abilities of both a whole-blood- and a novel peripheral blood mononuclear cell (PBMC)-based mycobacterial growth inhibition assay to measure a response to primary vaccination and revaccination with BCG. Using cryopreserved PBMCs, we observed a significant improvement in mycobacterial growth inhibition following primary vaccination but no improvement in growth inhibition following revaccination with BCG (P< 0.05). Mycobacterial growth inhibition following primary BCG vaccination was not correlated with purified protein derivative (PPD) antigen-specific IFN-γ enzyme-linked immunospot (ELISPOT) responses. We demonstrate that a mycobacterial growth inhibition assay can detect improved capacity to control growth following primary immunization, but not revaccination, with BCG. This is the first study to demonstrate that anin vitrogrowth inhibition assay can identify a difference in vaccine responses by comparing both primary and secondary BCG vaccinations, suggesting thatin vitrogrowth inhibition assays may serve as better surrogates of clinical efficacy than the assays currently used for the assessment of candidate TB vaccines.
Development of a Treatment Algorithm for Streptococci and Enterococci from Positive Blood Cultures Identified with the Verigene Gram-Positive Blood Culture Assay
Authors: Alby Kevin , Daniels Lindsay M. , Weber David J. , Miller Melissa B.
Published: August 2013

Seventy-eight blood cultures with a Gram stain result of Gram-positive cocci in pairs and/or chains were evaluated with the Nanosphere Verigene Gram-positive blood culture (BC-GP) assay. The overall concordance of the assay with culture was 89.7% (70/78 cultures), allowing for the development of a targeted treatment algorithm.
Simultaneous Detection of Major Drug Resistance Mutations in the Protease and Reverse Transcriptase Genes for HIV-1 Subtype C by Use of a Multiplex Allele-Specific Assay
Authors: Zhang Guoqing , Cai Fangping , Zhou Zhiyong , DeVos Joshua , Wagar Nick , Diallo Karidia , Zulu Isaac , Wadonda-Kabondo Nellie , Stringer Jeffrey S. A. , Weidle Paul J. , Ndongmo Clement B. , Sikazwe Izukanji , Sarr Abdoulaye , Kagoli Matthew , Nkengasong John , Gao Feng , Yang Chunfu
Published: August 2013

High-throughput, sensitive, and cost-effective HIV drug resistance (HIVDR) detection assays are needed for large-scale monitoring of the emergence and transmission of HIVDR in resource-limited settings. Using suspension array technology, we have developed a multiplex allele-specific (MAS) assay that can simultaneously detect major HIVDR mutations at 20 loci. Forty-five allele-specific primers tagged with unique 24-base oligonucleotides at the 5′ end were designed to detect wild-type and mutant alleles at the 20 loci of HIV-1 subtype C. The MAS assay was first established and optimized with three plasmid templates (C-wt, C-mut1, and C-mut2) and then evaluated using 148 plasma specimens from HIV-1 subtype C-infected individuals. All the wild-type and mutant alleles were unequivocally distinguished with plasmid templates, and the limits of detection were 1.56% for K219Q and K219E, 3.13% for L76V, 6.25% for K65R, K70R, L74V, L100I, K103N, K103R, Q151M, Y181C, and I47V, and 12.5% for M41L, K101P, K101E, V106A, V106M, Y115F, M184V, Y188L, G190A, V32I, I47A, I84V, and L90M. Analyses of 148 plasma specimens revealed that the MAS assay gave 100% concordance with conventional sequencing at eight loci and >95% (range, 95.21% to 99.32%) concordance at the remaining 12 loci. The differences observed were caused mainly by 24 additional low-abundance alleles detected by the MAS assay. Ultradeep sequencing analysis confirmed 15 of the 16 low-abundance alleles. This multiplex, sensitive, and straightforward result-reporting assay represents a new efficient genotyping tool for HIVDR surveillance and monitoring.
Alerting Physicians during Electronic Order Entry Effectively Reduces Unnecessary Repeat PCR Testing for Clostridium difficile
Authors: Luo Robert F. , Spradley Suzanne , Banaei Niaz
Published: August 2013

Hospital information systems (HIS) alerts restricting repeat
Clostridium difficile
PCR ordering by physicians in patients with a prior result within 7 days eliminated 91% of repeat tests, from 14.5% (282/1,949) repeats preintervention to 1.3% (135/10,285) postintervention. HIS alerting is an effective, targeted, patient-specific tool for improving the quality and utilization of
C. difficile
results.
Rapid Determination of Colistin Resistance in Clinical Strains of Acinetobacter baumannii by Use of the Micromax Assay
Authors: Tamayo Maria , Santiso Rebeca , Otero Fátima , Bou Germán , Lepe José Antonio , McConnell Michael J. , Cisneros José Miguel , Gosálvez Jaime , Fernández José Luis
Published: August 2013

Colistin is an old antibiotic which has been used as a therapeutic option for carbapenem- and multidrug-resistant Gram-negative bacteria, like
Acinetobacter baumannii
. This pathogen produces life-threatening infections, mainly in patients admitted to intensive care units. Rapid detection of resistance to colistin may improve patient outcomes and prevent the spread of resistance. For this purpose, Micromax technology was evaluated in four isogenic
A. baumannii
strains with known mechanisms of resistance to colistin and in 66 isolates (50 susceptible and 16 resistant). Two parameters were determined, DNA fragmentation and cell wall damage. To assess DNA fragmentation, cells trapped in a microgel were incubated with a lysing solution to remove the cell wall, and the released nucleoids were visualized under fluorescence microscopy. Fragmented DNA was observed as spots that diffuse from the nucleoid. To assess cell wall integrity, cells were incubated with a lysis solution which removes only weakened cell walls, resulting in nucleoid release exclusively in affected cells. A dose-response relationship was demonstrated between colistin concentrations and the percentages of bacteria with DNA fragmentation and cell wall damage, antibiotic effects that were delayed and less frequent in resistant strains. Receiver operating characteristic (ROC) curves demonstrated that both DNA fragmentation and cell wall damage were excellent parameters for identifying resistant strains. Obtaining ≤11% of bacteria with cell wall damage after incubation with 0.5 μg/ml colistin identified resistant strains of
A. baumannii
with 100% sensitivity and 96% specificity. Results were obtained in 3 h 30 min. This is a simple, rapid, and accurate assay for detecting colistin resistance in
A. baumannii
, with strong potential value in critical clinical situations.
The Toll and Imd Pathways Are Not Required for Wolbachia-Mediated Dengue Virus Interference
Authors: Rancès Edwige , Johnson Travis K. , Popovici Jean , Iturbe-Ormaetxe Iñaki , Zakir Tasnim , Warr Coral G. , O'Neill Scott L.
Published: August 2013

Wolbachia
blocks dengue virus replication in
Drosophila melanogaster
as well as in
Aedes aegypti
. Using the
Drosophila
model and mutations in the Toll and Imd pathways, we showed that neither pathway is required for expression of the dengue virus-blocking phenotype in the
Drosophila
host. This provides additional evidence that the mechanistic basis of
Wolbachia
-mediated dengue virus blocking in insects is more complex than simple priming of the host insect innate immune system.
Kaposi's Sarcoma-Associated Herpesvirus Encodes a Mimic of Cellular miR-23
Authors: Manzano Mark , Shamulailatpam Priscilla , Raja Archana N. , Gottwein Eva
Published: August 2013

Kaposi's sarcoma-associated herpesvirus (KSHV) expresses ∼20 viral microRNAs (miRNAs) in latently infected cells. We have previously shown that two of these miRNAs function as mimics of the cellular miRNAs miR-155 and miR-142-3p. Two additional KSHV miRNAs, miR-K3+1 and miR-K3, share perfect and offset 5′ homology with cellular miR-23, respectively. Here, we report a single nucleotide polymorphism that causes miR-K3+1 expression in a subset of KSHV-infected primary effusion lymphoma cell lines as a consequence of altered processing of the primary transcript by the Microprocessor complex. We confirm that miR-K3+1 regulates miR-23 targets, which is expected because these miRNAs share the entire seed region (nucleotides 2 to 8). Surprisingly, we found that miR-K3 also regulates miR-23 targets, despite offset seed sequences. In addition, the offset homology of miR-K3 to miR-23 likely allows this viral miRNA to expand its target repertoire beyond the targets of miR-23. Because miR-23 is highly expressed in endothelial cells but expressed at only low levels in B cells, we hypothesize that miR-K3 may function to introduce miR-23-like activities into KSHV-infected B cells. Together, our data demonstrate that KSHV has evolved at least three distinct viral miRNAs to tap into evolutionarily conserved cellular miRNA-regulatory networks. Furthermore, our data allow fundamental insights into the generation and functional impact of miRNA 5′ end variation.
The Current Hepatitis C Virus Prevalence in China May Have Resulted Mainly from an Officially Encouraged Plasma Campaign in the 1990s: a Coalescence Inference with Genetic Sequences
Authors: Lu Ling , Tong Wangxia , Gu Lin , Li Chunhua , Lu Teng , Tee Kok Keng , Chen Guihua
Published: August 2013

In this study, we investigated hepatitis C virus (HCV) molecular epidemiology and evolutionary dynamics. Both E1 and NS5B sequences were characterized in 379 of 433 patients in southern China and classified into five major subtypes: 1b in 256 patients, 6a in 67 patients, 2a in 29 patients, 3a in 14 patients, and 3b in 13 patients. Using the E1 sequences obtained, along with those from other studies using samples from China, we inferred the HCV epidemic history by means of coalescence strategies. Five Bayesian skyline plots (BSPs) were estimated for the five subtypes. They concurrently highlighted the rapid growth in the HCV-infected population size from 1993 to 2000, followed by an abrupt slowing. Although flanked on both sides by variable population sizes, the plots showed distinct patterns of rapid HCV growth. Coincidently, 1993 to 2000 was a period when contaminated blood transfusions were common in China due to a procedural error in an officially encouraged plasma campaign. The abrupt slowing in 1998 to 2000 corresponded to the central government outlawing paid blood donations in 1998. Using a parametric model, the HCV population growth rates were estimated during 1993 to 2000. It was revealed that the 6a rate was the highest, followed by those of 1b, 2a, 3b, and 3a. Because these rates differed significantly (P< 1e−9) from each other, they may help explain why 6a is increasingly prevalent in southern China and 1b is predominant nationwide. These rates are approximately 10-fold higher than those reported elsewhere. These findings suggested that during the plasma campaign, certain barriers to efficient viral transmission were removed, allowing wide HCV dissemination.
The Product of Kaposi's Sarcoma-Associated Herpesvirus Immediate Early Gene K4.2 Regulates Immunoglobulin Secretion and Calcium Homeostasis by Interacting with and Inhibiting pERP1
Authors: Wong Lai-Yee , Brulois Kevin , Toth Zsolt , Inn Kyung-Soo , Lee Sun-Hwa , O'Brien Kathryn , Lee Hyera , Gao Shou-Jiang , Cesarman Ethel , Ensser Armin , Jung Jae U.
Published: August 2013

Chaperones are proteins that assist the noncovalent folding and assembly of macromolecular polypeptide chains, ultimately preventing the formation of nonfunctional or potentially toxic protein aggregates. Plasma cell-induced-endoplasmic reticulum (ER)-resident protein 1 (pERP1) is a cellular chaperone that is preferentially expressed in marginal-zone B cells and is highly upregulated during plasma cell differentiation. While initially identified as a dedicated factor for the assembly of secreted IgM, pERP1 has since been implicated in suppressing calcium mobilization, and its expression is misregulated in multiple tumors. A number of herpesvirus immediate early gene products play important roles in the regulation of viral gene expression and/or evasion of host immune responses. Here, we report that the Kaposi's sarcoma-associated herpesvirus (KSHV) immediate early viral gene K4.2 encodes an endoplasmic reticulum-localized protein that interacts with and inhibits pERP1. Consequently, K4.2 expression interfered with immunoglobulin secretion by delaying the kinetics of immunoglobulin assembly and also led to increased responsiveness of B-cell receptor signal transduction by enhancing phosphotyrosine signals and intracellular calcium fluxes. Furthermore, K4.2 expression also appeared to contribute to maximal lytic replication by enhancing viral glycoprotein expression levels and ultimately promoting infectious-virus production. Finally, immunohistochemistry analysis showed that pERP1 expression was readily detected in KSHV-positive cells from multicentric Castleman's disease (MCD) and Kaposi's sarcoma (KS) lesions, suggesting that pERP1 may have potential roles in the KSHV life cycle and malignancy. In conclusion, our data suggest that K4.2 participates in lytic replication by enhancing calcium flux and viral glycoprotein expression, but also by interfering with immunoglobulin assembly to potentially dampen the adaptive immune response.
Vif Proteins from Diverse Primate Lentiviral Lineages Use the Same Binding Site in APOBEC3G
Authors: Letko Michael , Silvestri Guido , Hahn Beatrice H. , Bibollet-Ruche Frederick , Gokcumen Omer , Simon Viviana , Ooms Marcel
Published: August 2013

APOBEC3G (A3G) is a cytidine deaminase that restricts human immunodeficiency virus type 1 (HIV-1) and other lentiviruses. Most of these viruses encode a Vif protein that directly binds A3G and leads to its proteasomal degradation. Both Vif proteins of HIV-1 and African green monkey simian immunodeficiency virus (SIVagm) bind residue 128 of A3G. However, this position does not control the A3G degradation by Vif variants derived from HIV-2 and SIVmac, which both originated from SIV of sooty mangabey monkeys (SIVsmm), suggesting that the A3G binding site for Vif proteins of the SIVsmm/HIV-2 lineage differs from that of HIV-1. To map the SIVsmm Vif binding site of A3G, we performed immunoprecipitations of individual A3G domains, Vif/A3G degradation assays and a detailed mutational analysis of human A3G. We show that A3G residue 129, but not the adjacent position 128, confers susceptibility to degradation by SIVsmm Vif. An artificial A3G mutant, the P129D mutant, was resistant to degradation by diverse Vifs from HIV-1, HIV-2, SIVagm, and chimpanzee SIV (SIVcpz), suggesting a conserved lentiviral Vif binding site. Gorilla A3G naturally contains a glutamine (Q) at position 129, which makes its A3G resistant to Vifs from diverse lineages. We speculate that gorilla A3G serves as a barrier against SIVcpz strains. In summary, we show that Vif proteins from distinct lineages bind to the same A3G loop, which includes positions 128 and 129. The multiple adaptations within this loop among diverse primates underscore the importance of counteracting A3G in lentiviral evolution.
Assessing Activity and Inhibition of Middle East Respiratory Syndrome Coronavirus Papain-Like and 3C-Like Proteases Using Luciferase-Based Biosensors
Authors: Kilianski Andy , Mielech Anna M. , Deng Xufang , Baker Susan C.
Published: August 2013

Middle East respiratory syndrome coronavirus (MERS-CoV) is associated with an outbreak of more than 90 cases of severe pneumonia with high mortality (greater than 50%). To date, there are no antiviral drugs or specific therapies to treat MERS-CoV. To rapidly identify potential inhibitors of MERS-CoV replication, we expressed the papain-like protease (PLpro) and the 3-chymotrypsin-like protease (3CLpro) from MERS-CoV and developed luciferase-based biosensors to monitor protease activity in cells. We show that the expressed MERS-CoV PLpro recognizes and processes the canonical CoV-PLpro cleavage site RLKGG in the biosensor. However, existing CoV PLpro inhibitors were unable to block MERS-CoV PLpro activity, likely due to the divergence of the amino acid sequence in the drug binding site. To investigate MERS-CoV 3CLpro activity, we expressed the protease in context with flanking nonstructural protein 4 (nsp4) and the amino-terminal portion of nsp6 and detected processing of the luciferase-based biosensors containing the canonical 3CLpro cleavage site VRLQS. Importantly, we found that a small-molecule inhibitor that blocks replication of severe acute respiratory syndrome (SARS) CoV and murine CoV also inhibits the activity of MERS-CoV 3CLpro. Overall, the protease expression and biosensor assays developed here allow for rapid evaluation of viral protease activity and the identification of protease inhibitors. These biosensor assays can now be used to screen for MERS-CoV-specific or broad-spectrum coronavirus PLpro and 3CLpro inhibitors.
Antirepression System Associated with the Life Cycle Switch in the Temperate Podoviridae Phage SPC32H
Authors: Kim Minsik , Ryu Sangryeol
Published: August 2013

Prophages switch from lysogenic to lytic mode in response to the host SOS response. The primary factor that governs this switch is a phage repressor, which is typically a host RecA-dependent autocleavable protein. Here, in an effort to reveal the mechanism underlying the phenotypic differences between the
Salmonella
temperate phages SPC32H and SPC32N, whose genome sequences differ by only two nucleotides, we identified a new class of
Podoviridae
phage lytic switch antirepressor that is structurally distinct from the previously reported
Sipho
- and
Myoviridae
phage antirepressors. The SPC32H repressor (Rep) is not cleaved by the SOS response but instead is inactivated by a small antirepressor (Ant), the expression of which is negatively controlled by host LexA. A single nucleotide mutation in the consensus sequence of the LexA-binding site, which overlaps with the
ant
promoter, results in constitutive Ant synthesis and consequently induces SPC32N to enter the lytic cycle. Numerous potential Ant homologues were identified in a variety of putative prophages and temperate
Podoviridae
phages, indicating that antirepressors may be widespread among temperate phages in the order
Caudovirales
to mediate a prudent prophage induction.
Role of Interleukin-2 and Herpes Simplex Virus 1 in Central Nervous System Demyelination in Mice
Authors: Mott Kevin R. , Zandian Mandana , Allen Sariah J. , Ghiasi Homayon
Published: August 2013

We have reported previously that ocular infection of different strains of mice with recombinant herpes simplex virus 1 (HSV-1) constitutively expressing interleukin-2 (IL-2) provokes central nervous system (CNS) demyelination and optic neuropathy, as determined by changes in visual evoked cortical potentials and pathological changes in the optic nerve and CNS, whereas recombinant viruses expressing IL-4, gamma interferon, IL-12p35, IL-12p40, or IL-12p70 do not induce this neuropathy. The goal of this study was to dissect the mechanism underlying the interplay between the immune system (elevation of IL-2) and an environmental factor (infection with HSV-1) that elicits this pathology. Similar results were obtained upon delivery of IL-2 into the mouse brain using osmotic minipumps or injection of mice with recombinant IL-2 protein, IL-2 DNA, or IL-2 synthetic peptides prior to infection with wild-type (wt) HSV-1 strains McKrae and KOS. The critical role of IL-2 is further supported by our data, indicating that a single mutation at position T27A in IL-2 completely blocks the HSV-1-induced pathology. This study shows a novel model of autoimmunity in which viral infection and enhanced IL-2 cause CNS demyelination.
Perimetric demonstration of spontaneous visual field recovery following occipital lobe haemorrhage
Authors: Lin Siying , George Badie Z , Wilson-Holt Nicholas J
Published: August 2013

A 45-year-old patient on lifelong warfarin therapy after a metal aortic valve replacement developed a homonymous visual field defect following an occipital lobe haemorrhage. The patient received only conservative management and yet described continued improvement in her visual field defect for up to 20 months following the initial cerebral insult. We present the first conclusive illustrative documentation of visual recovery in a patient with an occipital lobe haemorrhage with sequential automated perimetric assessments over an extended period of time.
An unexpected cause of right heart strain
Authors: Saleh Aarash , Mohammed Ali A , Raines Phil
Published: August 2013

A 27-year-old woman was referred from her general practitioner (GP) 6 weeks postpartum with weight loss, dyspnoea and bilateral leg swelling. She had been treated by the GP for a chest infection the week before. On admission she was tachycardic, hypotensive and hypoxic with bilateral leg oedema and bibasal crackles. A chest radiograph showed diffuse multinodular opacification. A CT pulmonary angiogram showed dilated pulmonary artery. Echocardiogram confirmed right ventricular strain and dilation. Sputum microscopy was positive for acid-fast bacilli. The patient developed confusion and low-grade fever and the CT head scan showed meningeal involvement. One year of antituberculous therapy was started and she made a clinical recovery after 10 days and was discharged with regular follow-up. An echocardiogram showed resolution of the right heart strain 4 months later.
M2-polarised macrophages in infantile haemangiomas: correlation with promoted angiogenesis
Authors: Wang Feng-Qin , Chen Gang , Zhu Jun-Yi , Zhang Wei , Ren Jian-Gang , Liu Hui , Sun Zhi-Jun , Jia Jun , Zhao Yi-Fang
Published: August 2013

Aims

The pathogenesis of infantile haemangiomas (IHs) is still far from clear despite the fact that they are common vascular tumours distinctive for their perinatal presentation, rapid growth during the first year of life and subsequent slow involution.

Aims

To determine the role of M2-polarised macrophages in IHs.

Methods

M2-polarised macrophages were initially identified in 20 specimens of IHs by both immunochemistry and immunofluorescence for CD68 and CD163. The immunopositive M2-polarised macrophages in different phases of IHs were quantified, and further analysed for their correlations with the expression levels of Ki67, vascular endothelial growth factor (VEGF) and macrophage colony-stimulating factor (M-CSF).

Results

The infiltrating macrophages in proliferative IHs were predominantly CD68/CD163, thus of the M2-polarised phenotype, whereas the density of these cells was significantly decreased in the involuting IHs. The high density of M2-polarised macrophages in proliferative IHs was closely correlated with overexpression of M-CSF, one of the cytokines considered to induce macrophages to polarise towards an M2 phenotype. The infiltrating M2-polarised macrophages probably contributed to the proliferation and angiogenesis of haemangioma endothelial cells, as evidenced by their close correlations with the immunoreactivities of Ki67 and VEGF.

Conclusions

Results indicate that the infiltrating M2-polarised macrophages may contribute to the progression of IHs by promoting the angiogenic process.
Misdiagnosis of cutaneous leishmaniasis and recurrence after surgical excision
Authors: Bailey Mark S , Langman G
Published: August 2013

Cutaneous Leishmaniasis (CL) occurs in British troops deployed to Belize, Afghanistan, Iraq and elsewhere. From 1998 to 2009, 156 (45%) of 343 confirmed cases seen in the UK were in military personnel. CL is a rare disease and requires specialist clinical management because numerous pitfalls exist during diagnosis and treatment. A 19-year-old soldier developed CL on his neck 6 weeks after taking part in jungle warfare training in Belize. However, this was not suspected and the diagnosis was not made from either a skin biopsy or following surgical excision. The travel history and the patient's own photograph prompted retrospective investigations that confirmed this was CL due toLeishmania mexicana. Three months after surgery, the disease recurred locally and was treated appropriately with a good outcome. British military personnel with suspected CL should be referred to the UK Role 4 Military Infectious Diseases & Tropical Medicine Service.
Evaluation of a disposable sheath bronchoscope system for use in the deployed field hospital
Authors: Johnston Andrew McD , Batchelor N K , Wilson D
Published: August 2013

At present, UK field hospitals use standard flexible bronchoscopes which require specialised disinfection services that are not integral to the hospital. This leads to prolonged turnover of used bronchoscopes as they have to be sent away to external facilities, which takes 1–3 days and is dependent on air transport to other facilities. In contingency operations, off site sterilisation facilities may not be available. There is a need for a bronchoscope system which can be rapidly cleaned and reused. We evaluated the Vision Sciences EndoSheath Bronchoscopy system, which uses a disposable outer sheath to remove the need for specialised disinfection. We report our experience of using this system in a deployed field hospital in Afghanistan.
Modification of the anticancer drug tamoxifen to avoid CYP2D6 polymorphism
Authors: Gao Li , Sun Xianqiang , Tu Yaoquan , Ågren Hans , Eriksson Leif A.
Published: August 2013

The prodrug tamoxifen (TAM) is the most widely used drug to treat breast cancer, and is metabolised to the active 4-hydroxy derivatives dominantly by hepatic CYP2D6. However, the application to patients with different polymorphic CYP2D6 has been under debate, because the efficacy of TAM is suspected to be suppressed in patients who have diminished CYP2D6 activity, resulting in inadequate active metabolites. We here propose modified structures, such as 4-methylTAM, which is highly possible to be activated by CYP3A, the most abundant CYP isoforms in the liver, whereby the genetic polymorphism of CYP2D6 is avoided. The diversity of CYP catalyzed metabolic paths for TAM and its derivatives are studied by quantum chemistry calculations on the reaction energies of the initial H atom abstraction steps. The ability of forming DNA adducts is compared through the formation enthalpy of the carbocation intermediate. The results suggest that the modified structures are safe with regard to forming DNA adducts and may be used as prodrugs in a wide range of patients, due to CYP3A, rather than CYP2D6, mediated activation.
DEFECT ENGINEERING OF 2D MONATOMIC-LAYER MATERIALS
Authors: PENG QING , CREAN JARED , DEARDEN ALBERT K. , HUANG CHEN , WEN XIAODONG , BORDAS STÉPHANE P. A. , DE SUVRANU
Published: August 2013

Atomic-thick monolayer two-dimensional materials present advantageous properties compared to their bulk counterparts. The properties and behavior of these monolayers can be modified by introducing defects, namely defect engineering. In this paper, we review a group of common two-dimensional crystals, including graphene, graphyne, graphdiyne, graphn-yne, silicene, germanene, hexagonal boron nitride monolayers and MoS2monolayers, focusing on the effect of the defect engineering on these two-dimensional monolayer materials. Defect engineering leads to the discovery of potentially exotic properties that make the field of two-dimensional crystals fertile for future investigations and emerging technological applications with precisely tailored properties.
TOPOLOGY OF FAMILIES OF ALGEBRAIC CURVES CONTINUOUSLY DEPENDING ON A PARAMETER, AND APPLICATIONS
Authors: ALCAZAR JUAN G.
Published: August 2013

Given a family of algebraic curves whose coefficients depend continuously on a parameter t ∈ U ⊂ ℝ (U a union of real intervals) we address the problem of computing the topology types in the family. Under certain conditions, we provide a method to compute a univariate real function R*(t), with the property that the topology of the family stays invariant along every real interval I ⊂ U not containing any real root of R*(t). So, if R*(t) has finitely many real roots the topology types in the family can be computed. We apply this result to provide bounds on the number of topology types of the family in certain cases, including the important case when the coefficients belong to a Pfaffian chain, and to analyze the existence of certain degeneracies in the real part of a surface whose family of level curves corresponds to the type studied here. The results of the paper can be seen as generalizations of previous works [Alcázar, Applications of level curves to some problems on algebraic surfaces, in Contribuciones Científicas en Honor de Mirian Andrés Gòmez, eds. Lambán, Romero and Rubio (Universidad de La Rioja, Servicio de Publicaciones, 2010), pp. 105–122, Alcázar, Schicho and Sendra, A delineability-based method for computing critical sets of algebraic surfaces, J. Symbolic Comput.42 (2007) 678–691] on the topology of families algebraically depending on a parameter t.
Hamiltonian formulation for mechanical systems with nonholonomic constraints
Authors: Torres del Castillo G. F. , Sosa-Rodríguez O.
Published: August 2013

It is shown that for a mechanical system with a finite number of degrees of freedom, subject to nonholonomic constraints, there exists an infinite number of Hamiltonians and symplectic structures such that the equations of motion can be written as the Hamilton equations, with the original constraints incorporated in the Hamiltonian structure.
DATA FUSION IN SEVERAL ALGORITHMS
Authors: LIPOVETSKY STAN
Published: August 2013

Data fusion consists of the process of integrating several datasets with some common variables, and other variables available only in partial datasets. The main problem of data fusion can be described as follows. From one source, having X0 and Y0 datasets (with N0 observations by multiple x and y variables, n and m of those, respectively), and from another source, having X1 data (with N1 observations by the same nx-variables), we need to estimate the missing portion of the Y1 data (of size N1 by m variables) in order to combine all the data into one set. Several algorithms are considered in this work, including estimation of weights proportional to the distances from each ith observation in the X1 "recipients" dataset to all observations in the X0 "donors" dataset. Or we can use a sample balancing technique with the maximum effective base performed by applying ridge-regression for the Gifi system of binaries obtained from the x-variables for the best fit of the "donors" X0 data to the margins defined by each respondent in the "recipients" X1 dataset. Then the weighted regressions of each y in the Y0 dataset by all variables in the X0 are constructed. For each ith observation in the dataset X0, these regressions are used for predicting the y-variables in the Y1 "recipients" dataset. If X and Y are the same n variables from different sources, the dual partial least squares technique and a special regression model with dummies defining each of the three available sets are used for prediction of the Y1 data.
AN EFFECTIVE WAY TO CONTROL CONGESTION FOR RTI WITH HYBRID ARCHITECTURE
Authors: BIN XIAO , HONGBO SUN , TIANYUAN XIAO
Published: August 2013

Congestions brought by data explosion may suffer system performance or even cause fatal errors in large-scale simulation systems. This paper analyzes the reasons of generating congestion with queuing theory, and proposes a novel congestion control approach for RTI with hybrid architecture, including framework, sampling policy, queue length predicting, and congestion control algorithm. The framework promotes the usage of federate resources, and improves the performance of HLA simulation systems by dynamically distributing loads on RTIG and LRCs (Local RTI Components). At last, experimental results say that the proposed approach is a flexible, simple and efficient way to control congestion in RTI with hybrid architecture.
SYNTHESIS OF SUB-MICROMETER CARBON SUPPORTED Fe3O4 HOLLOW SPHERES WITH ENHANCED LITHIUM STORAGE PROPERTIES
Authors: ZHANG DONGYANG , ZHOU HAN , LIANG JIN , DING SHUJIANG
Published: August 2013

In this paper, we report an interesting approach for efficient synthesis of uniform sub-micrometer carbon supported Fe 3 O 4 hollow spheres. Fe 3 O 4 precursor was first coated on the surface of sulfonated polystyrene hollow microspheres. Then, the precursor and sulfonated polystyrene hollow microspheres were converted into Fe 3 O 4 and carbon hollow spheres when heated at 550°C in N 2 atmosphere. The obtained Fe 3 O 4 @ carbon hollow microspheres exhibit enhanced lithium storage properties compared with Fe 2 O 3 hollow spheres as anode materials, delivering a reversible capacity of 612 mA hg−1 after 50 cycles at a high current density of 400 mA g−1.
POLYOXOMETALATE-IONIC LIQUIDS (POM-ILs)–THE ULTIMATE SOFT POLYOXOMETALATES? A CRITICAL PERSPECTIVE
Authors: HERRMANN SVEN , SELIVERSTOV ANDREY , STREB CARSTEN
Published: August 2013

In this paper, a critical perspective on the state-of-the-art, current developments and future applications of polyoxometalate-ionic liquids (POM-ILs) is presented. This paper is focused on recent developments for true polyoxometalate ionic liquids, where the POM cluster acts as the anionic component in an ionic liquid. A brief overview of the initial development of POM-ILs is given and key features of the materials such as viscosity, conductivity and thermal stability are compared. Current applications of POM-ILs are exemplified and the advantages as well as limitations of POM-ILs for usage as catalysts, sensors and electrochemically active materials are discussed. Potential future areas of application are described and initial studies in these areas are highlighted.
Patterns of Selection in Plant Genomes
Authors: Hough Josh , Williamson Robert J. , Wright Stephen I.
Published: August 2013

Plants show a wide range of variation in mating system, ploidy level, and demographic history, allowing for unique opportunities to investigate the evolutionary and genetic factors affecting genome-wide patterns of positive and negative selection. In this review, we highlight recent progress in our understanding of the extent and nature of selection on plant genomes. We discuss differences in selection as they relate to variation in demography, recombination, mating system, and ploidy. We focus on the population genetic consequences of these factors and argue that, although variation in the magnitude of purifying selection is well documented, quantifying rates of positive selection and disentangling the relative importance of recombination, demography, and ploidy are ongoing challenges. Large-scale comparative studies that examine the relative and joint importance of these processes, combined with explicit models of population history and selection, are key and feasible goals for future work.
The Estuarine Circulation
Authors: Geyer W. Rockwell , MacCready Parker
Published: August 2013

Recent research in estuaries challenges the long-standing paradigm of the gravitationally driven estuarine circulation. In estuaries with relatively strong tidal forcing and modest buoyancy forcing, the tidal variation in stratification leads to a tidal straining circulation driven by tidal variation in vertical mixing, with a magnitude that may significantly exceed the gravitational circulation. For weakly stratified estuaries, vertical and lateral advection are also important contributors to the tidally driven residual circulation. The apparent contradiction with the conventional paradigm is resolved when the estuarine parameter space is mapped with respect to a mixing parameter M that is based on the ratio of the tidal timescale to the vertical mixing timescale. Estuaries with high M values exhibit strong tidal nonlinearity, and those with small M values show conventional estuarine dynamics. Estuaries with intermediate mixing rates show marked transitions between these regimes at timescales of the spring-neap cycle.
Radiation Effects on Human Heredity
Authors: Nakamura Nori , Suyama Akihiko , Noda Asao , Kodama Yoshiaki
Published: August 2013

In experimental organisms such as fruit flies and mice, increased frequencies in germ cell mutations have been detected following exposure to ionizing radiation. In contrast, there has been no clear evidence for radiation-induced germ cell mutations in humans that lead to birth defects, chromosome aberrations, Mendelian disorders, etc. This situation exists partly because no sensitive and practical genetic marker is available for human studies and also because the number of people exposed to large doses of radiation and subsequently having offspring was small until childhood cancer survivors became an important study population. In addition, the genome of apparently normal individuals seems to contain large numbers of alterations, including dozens to hundreds of nonfunctional alleles. With the number of mutational events in protein-coding genes estimated as less than one per genome after 1 gray (Gy) exposure, it is unsurprising that genetic effects from radiation have not yet been detected conclusively in humans.
Is There a Canon of Law and Society?
Authors: Seron Carroll , Coutin Susan Bibler , White Meeusen Pauline
Published: August 2013

As an interdisciplinary field, law and society has an ambivalent relationship with the notion of a canon: Being a field requires having a recognized set of key texts, even as this particular field's critique of doctrinal legal analysis creates an openness toward alternative perspectives. Within the interdisciplinary field of law and society itself, there is debate about the breadth of disciplines relevant to this domain of inquiry. To explore this tension, we analyze three sources: (a) addresses delivered by presidents of the US Law and Society Association (LSA), (b) LSA meeting calls, and (c) law and society/social science syllabi. Presidential addresses and meeting calls demonstrate how the boundaries of the field are established and contested, and course syllabi suggest a degree of consensus about key works. We conclude by discussing other national and regional research traditions and note that these critique law and society/social sciences canons for being overly United States focused or Eurocentric. We argue that such contestation underscores the health and vibrancy of law and society research.
Chronic carbon monoxide inhalation during pregnancy augments uterine artery blood flow and uteroplacental vascular growth in mice
Authors: Venditti Carolina C. , Casselman Richard , Murphy Malia S. Q. , Adamson S. Lee , Sled John G. , Smith Graeme N.
Published: August 2013

End-tidal breath carbon monoxide (CO) is abnormally low in women with preeclampsia (PE), while women smoking during pregnancy have shown an increase in CO levels and a 33% lower incidence of PE. This effect may be, in part, due to lowered sFLT1 plasma levels in smokers, and perhaps low-level CO inhalation can attenuate the development of PE in high-risk women. Our previous work showed maternal chronic CO exposure (<300 ppm) throughout gestation had no maternal or fetal deleterious effects in mice. Our current study evaluated the uteroplacental vascular effects in CD-1 maternal mice that inhaled CO (250 ppm) both chronically, gestation day (GD) 0.5 to 18.5, and acutely, 2.5 h on each of GD 10.5 and 14.5. We demonstrated, using microultrasound measurements of blood velocity and microcomputed tomography imaging of the uteroplacental vasculature, that chronic maternal exposure to CO doubled uterine artery blood flow and augmented uteroplacental vascular diameters and branching. This finding may be of benefit to women with PE, as they exhibit uteroplacental vascular compromise. The ratio of VEGF protein to its FLT1 receptor was increased in the placenta, suggesting a shift to a more angiogenic state; however, maternal circulating levels of VEGF, sFLT1, and their ratio were not significantly changed. Doppler blood velocities in the maternal uterine artery and fetal umbilical artery and vein were unaltered. This study provides in vivo evidence that chronic inhalation of 250 ppm CO throughout gestation augments uterine blood flow and uteroplacental vascular growth, changes that may protect against the subsequent development of preeclampsia.
Role of collecting duct endothelin in control of renal function and blood pressure
Authors: Kohan Donald E.
Published: August 2013

Over 26,000 manuscripts have been published dealing with endothelins since their discovery 25 years ago. These peptides, and particularly endothelin-1 (ET-1), are expressed by, bind to, and act on virtually every cell type in the body, influencing multiple biological functions. Among these actions, the effects of ET-1 on arterial pressure and volume homeostasis have been most extensively studied. While ET-1 modulates arterial pressure through regulation of multiple organ systems, the peptide's actions in the kidney in general, and the collecting duct in particular, are of unique importance. The collecting duct produces large amounts of ET-1 that bind in an autocrine manner to endothelin A and B receptors, causing inhibition of Na+and water reabsorption; absence of collecting duct ET-1 or its receptors is associated with marked salt-sensitive hypertension. Collecting duct ET-1 production is stimulated by Na+and water loading through local mechanisms that include sensing of salt and other solute delivery as well as shear stress. Thus the collecting duct ET-1 system exists, at least in part, to detect alterations in, and maintain homeostasis for, extracellular fluid volume. Derangements in collecting duct ET-1 production may contribute to the pathogenesis of genetic hypertension. Blockade of endothelin receptors causes fluid retention due, in large part, to inhibition of the action of ET-1 in the collecting duct; this side effect has substantially limited the clinical utility of this class of drugs. Herein, the biology of the collecting duct ET-1 system is reviewed, with particular emphasis on key issues and questions that need addressing.