bluuebunny/crossref_metadata_2025 huggingface dataset:
Identifying practices and ideas to improve the implementation of maternal mortality reduction programmes: findings from five South Asian countries
Authors: Hussein J , Newlands D , D’Ambruoso L , Thaver I , Talukder R , Besana G
Published: January 2010

Please cite this paper as: Hussein J, Newlands D, D’Ambruoso L, Thaver I, Talukder R, Besana G. Identifying practices and ideas to improve the implementation of maternal mortality reduction programmes: findings from five South Asian countries. BJOG 2010;117:304–313.

Objective  The successful implementation of programmes to reduce maternal mortality is constrained by a ‘know–do’ gap: the disparity between what is known and the application of that knowledge in policy and practice. This study identified innovations, practices and ideas aimed to improve project and programme implementation.

Design  Cross‐sectional.

Setting  Five South Asian countries: Afghanistan, Bangladesh, India, Nepal and Pakistan.

Sample  Sixteen projects and programmes, and 100 key informants.

Methods  In‐depth review of documents, key informant interviews and focus‐group discussions.

Main outcome measures  Innovations and ideas to improve programme implementation, and their perceived effects.

Results  Delegation of duties to intermediate‐level health workers, incentivisation of health workers, providing the means to overcome financial barriers for accessing care, quality improvements and knowledge transfer were examples of ideas put into practice to improve programme implementation. There was a perception that these improved service use and availability, but objective evidence was lacking.

Conclusions  Some innovations, practices and ideas are supported by evidence of effect, and could be replicated, whereas others have not been formally evaluated. Testing of these innovations is required before more widespread adoption can be recommended, although experiences should be shared to narrow the ‘know–do’ gap, even though the evidence on beneficial effects remains unclear.
Bivalent phenethylamines as novel dopamine transporter inhibitors: evidence for multiple substrate‐binding sites in a single transporter
Authors: Schmitt Kyle C. , Mamidyala Sreeman , Biswas Swati , Dutta Aloke K. , Reith Maarten E. A.
Published: January 2010

J. Neurochem.(2010)112, 1605–1618.

Bivalent ligands – compounds incorporating two receptor‐interacting moieties linked by a flexible chain – often exhibit profoundly enhanced binding affinity compared with their monovalent components, implying concurrent binding to multiple sites on the target protein. It is generally assumed that neurotransmitter sodium symporter (NSS) proteins, such as the dopamine transporter (DAT), contain a single domain responsible for recognition of substrate molecules. In this report, we show that molecules possessing two substrate‐like phenylalkylamine moieties linked by a progressively longer aliphatic spacer act as progressively more potent DAT inhibitors (rather than substrates). One compound bearing two dopamine (DA)‐like pharmacophoric ‘heads’ separated by an 8‐carbon linker achieved an 82‐fold gain in inhibition of [3H] 2β‐carbomethoxy‐3β‐(4‐fluorophenyl)‐tropane (CFT) binding compared with DA itself; bivalent compounds with a 6‐carbon linker and heterologous combinations of DA‐, amphetamine‐ and β‐phenethylamine‐like heads all resulted in considerable and comparable gains in DAT affinity. A series of short‐chain bivalent‐like compounds with a singleN‐linkage was also identified, the most potent of which displayed a 74‐fold gain in binding affinity. Computational modelling of the DAT protein and docking of the two most potent bivalent (‐like) ligands suggested simultaneous occupancy of two discrete substrate‐binding domains. Assays with the DAT mutants W84L and D313N – previously employed by our laboratory to probe conformation‐specific binding of different structural classes of DAT inhibitors – indicated a bias of the bivalent ligands for inward‐facing transporters. Our results strongly indicate the existence of multiple DAT substrate‐interaction sites, implying that it is possible to design novel types of DAT inhibitors based upon the ‘multivalent ligand’ strategy.
Quaternary vegetation changes derived from a loess‐like permafrost palaeosol sequence in northeast Siberia using alkane biomarker and pollen analyses
Authors: ZECH MICHAEL , ANDREEV ANDREI , ZECH ROLAND , MÜLLER STEFANIE , HAMBACH ULRICH , FRECHEN MANFRED , ZECH WOLFGANG
Published: January 2010

Zech, M., Andreev, A., Zech, R., Müller, S., Hambach, U., Frechen, M. & Zech, W.: Quaternary vegetation changes derived from a loess‐like permafrost palaeosol sequence in northeast Siberia using alkane biomarker and pollen analyses. Boreas, Vol. 39, pp. 540–550. 10.1111/j.1502‐3885.2009.00132.x. ISSN 0300‐9483

Alkane biomarker and pollen data were obtained from a 15‐m‐high and probably c. 240‐kyr‐old loess‐like permafrost palaeosol sequence (‘Tumara Palaeosol Sequence’, TPS) in northeast Siberia. The alkane results were corrected for degradation effects by applying an end‐member model and were evaluated by comparing them with the palynological results. The two data sets are generally in good agreement and suggest that the lower part of the TPS developed mainly under larch forests, whereas the upper part of the sequence reflects the expansion of mammoth steppes during the Weichselian glaciation and finally reforestation during the Lateglacial and the early Holocene. For the lower part of the TPS, the palaeoclimatic interpretation according to modern analogue methods would indicate warm, interglacial conditions, but this is at odds with the climate chronostratigraphy based on a multi‐proxy palaeopedological approach and numeric dating. Provided that the correlation of the discussed stratigraphic unit with the Late Saalian glaciation and the Marine Oxygen Isotope Stage 6 is correct, our results suggest that temperature was not a limiting factor for tree growth at that time. Furthermore, it seems very likely that it was not mainly temperature changes but rather increasing aridity and continentality during the course of the last glacial that favoured the expansion of the mammoth steppe.
Potential negative impacts of introduced rainbow trout on endangered Sakhalin taimen through redd disturbance in an agricultural stream, eastern Hokkaido
Authors: Nomoto K. , Omiya H. , Sugimoto T. , Akiba K. , Edo K. , Higashi S.
Published: January 2010

Nomoto K, Omiya H, Sugimoto T, Akiba K, Edo K, Higashi S. Potential negative impacts of introduced rainbow trout on endangered Sakhalin taimen through redd disturbance in an agricultural stream, eastern Hokkaido. Ecology of Freshwater Fish 2010: 19: 116–126. © 2009 John Wiley & Sons A/S

Abstract –  Sakhalin taimen (Hucho perryi) populations have decreased in Hokkaido, northernmost Japan, primarily because of overexploitation and habitat degradation. Here we document another threat to this species, that of spawning redd superimposition by artificially introduced rainbow trout (Oncorhynchus mykiss). Sakhalin taimen and rainbow trout are the only spring‐spawning salmonid species in Hokkaido. In 2006–2008, spawning activities of both these species were observed in a Hokkaido stream, and it was determined that their spawning periods overlapped during mid‐late April. They also spawned at similar water velocities, depths and substrate compositions. Although female Sakhalin taimen were larger than female rainbow trout, their egg burial depths were nearly identical. During the observation period, rainbow trout redds were approximately five times more abundant than Sakhalin taimen redds, and about 30% of the observed Sakhalin taimen redds were superimposed by rainbow trout redds. The high degree of spatial and temporal overlap in spawning, the similar egg burial depths of both species, and the high proportion of superimposed redds suggest that the introduced rainbow trout impact the endangered Sakhalin taimen in Hokkaido, and possibly, in other areas where the two species occur together.
ORIGINAL ARTICLE: Estradiol Limits Viral Replication Following Intravaginal Immunization Leading to Diminished Mucosal IgG Response and Non‐sterile Protection Against Genital Herpes Challenge
Authors: Gillgrass Amy , Chege Duncan , Bhavanam Sudha , Kaushic Charu
Published: January 2010

Citation Gillgrass A, Chege D, Bhavanam S, Kaushic C. Estradiol limits viral replication following intravaginal immunization leading to diminished mucosal IgG response and non‐sterile protection against genital herpes challenge. Am J Reprod Immunol 2010; 63: 299–309

Problem  Previously we reported that ovariectomized (OVX) mice receiving estradiol (E) prior to immunization with an attenuated strain of HSV‐2 (TK‐HSV‐2) were not protected. Lack of protection in the E group was because of the inability of TK‐HSV‐2 to penetrate the thick keratinized epithelium. In this study, we determined the outcome of immunization after the thickening of vaginal epithelium following E‐treatment waned. OVX, C57BL/6 mice were given Progesterone (P), E or saline (S) for 3 days and immunized with IVAG TK‐HSV‐2.

Method of study  To determine the time point at which E‐treated mice could be successfully immunized, the mice were inoculated with TK‐HSV‐2 between days 1 and 7 (ED1–ED7) post‐E‐treatment and challenged with IVAG HSV‐2 three weeks later.

Results  The level of infection post‐immunization correlated with HSV‐2‐specific IgG antibody level, which correlated with sterile protection. No viral infection was observed in ED1–ED3 groups and no specific antibodies were detected, resulting in no protection. Moderate infection was seen in ED5 group, resulting in low antibody production and non‐sterile protection in 87.5% of mice. High antibody titers and sterile protection were observed in all groups that experienced robust infection post‐immunization.

Conclusion  The results show that estradiol leads to limited viral replication and diminished mucosal IgG response, resulting in non‐sterile immune protection against genital herpes infection.
Public school educator’s knowledge of initial management of dental trauma
Authors: Vergotine Rodney J. , Govoni Robert
Published: January 2010

Abstract –  Objectives:  To compare the level of knowledge of physical education teachers/athletic coaches (PETs) and academic teachers (ATs) regarding dental trauma management.

Methods:  Surveys were sent to all high schools (17) and all middle schools (23) in the Milwaukee public school system. All PETs and approximately 20 ATs at each school were invited to participate. The survey evaluated knowledge of dental trauma management via two case scenarios.

Results:  Survey was completed by 140 ATs and 119 PETs. For the urgency of treatment for tooth fractures 81% of ATs and 53% of PETs responded correctly, a significant difference (P < .0001). With regards to avulsions, 56% of ATs and 46% of PETs responded that immediate professional assistance was needed. Only 7% of PETs would replant an avulsed tooth compared with 12% of ATs, a difference that was significant (P = .0062). Milk was chosen as a transportation medium for an avulsed tooth by 25% of ATs and 23% of PETs.

Conclusions:  Knowledge regarding the initial management of dental trauma was low for both groups. Educational campaigns regarding dental trauma should be targeted at all teachers.
Prevalence and characteristics of injuries to the head and orofacial region in physically abused children and adolescents – a retrospective study in a city of the Northeast of Brazil
Authors: Cavalcanti Alessandro Leite
Published: January 2010

Abstract –  The aim of this study was to evaluate the prevalence and characteristics of injuries to the head and orofacial region in physically abused children and adolescents from a city of the Northeast of Brazil, based on the review of forensic medical reports. This retrospective study was undertaken by the analysis of expert medical reports derived from medical forensic exams performed at the Department of Forensic Medicine of the city of Campina Grande, PB, Brazil, between January 2003 and December 2006. From a universe of 11 624 reports issued in this time span, the study sample consisted of 1070 reports referring to children and adolescents aged 0–17 years that were confirmedly victims of physical abuse. Male children (52.8%) in the 13‐ to 17‐year‐old range (72.4%) were the most frequent victims, with an association between gender and age group (P = 0.039). Most children (58.2%) presented a single type of injury, with a statistically significant association between number of injuries and gender (P = 0.040), but no significant association between number of injuries and age (P = 0.163). The percentage of victims injured in the head and face corresponded to 56.3%, with a statistically significant association between the presence of injury in the head and face and gender (P = 0.046). As much as 12.4% of the children and adolescents presented intraoral injuries, with no significant difference between genders (P = 0.543). However, a statistically significant association was observed between the number of existing injuries and the presence of oral injuries (P = 0.005). The maxilla was predominantly affected (55.6%), most injuries (94.8%) being soft‐tissue lacerations located mainly in the upper lip (46.4%). The findings of this survey revealed a high prevalence of injuries to the head and orofacial region of physically abused children and adolescents.
COMPUTER VISION CLASSIFICATION OF POTATO CHIPS BY COLOR
Authors: PEDRESCHI FRANCO , MERY DOMINGO , BUNGER ANDREA , YAÑEZ VERÓNICA
Published: January 2010

In this research the automatic classification of commercial potato chips by computer vision was studied. The general objective was to design a tool that would be able to classify objectively potato chips according to their color in different categories. For this purpose, sensory measurements of color in 100 potato chips were correlated with the corresponding objective measurements obtained by computer vision system. Potato chips with and without ruffles of different brands were used for training and validation experiments. Sensory evaluations were done with a special chart that classifies potato chips in seven color categories. Simultaneously, the color of the same potato chips classified by the sensory panel, was determined objectively by a computer vision system in L*, a*, b* units. A linear regression model was good enough to predict potato chip sensory color values from the corresponding instrumental measurements by computer vision. The linear model after following the process of crossed validation crossed presented an error of ∼4% for smooth chips (without ruffles) and ∼7% for chips with ruffles.

PRACTICAL APPLICATIONS

The automatic classification methodology presented for potato chips is general and has a wide range of potential uses. It could be applied not only to other potato cultivars and frying conditions but also to other less heterogeneous raw materials and unit operations different than potato and frying, respectively. The computer vision system used in this research could as well be very useful in the food industry as a large amount of information can now be obtained from measurements at the pixel level that allows a better characterization of foods and thus improves quality control.
Innate pathways to B‐cell activation and tolerance
Authors: Crampton Steve P. , Voynova Elisaveta , Bolland Silvia
Published: January 2010

B cells represent an important link between the adaptive and innate immune systems as they express both antigen‐specific B‐cell receptors (BCRs) as well as various Toll‐like receptors (TLRs). Several checkpoints in B‐cell development ensure that self‐specific cells are eliminated from the mature B‐cell repertoire to avoid harmful autoreactive responses. These checkpoints are controlled by BCR‐mediated events but are also influenced by TLR‐dependent signals from the innate immune system. Additionally, B‐cell‐intrinsic and extrinsic TLR signaling are critical for inflammatory events required for the clearance of microbial infections. Factors secreted by TLR‐activated macrophages or dendritic cells directly influence the fate of protective and autoreactive B cells. Additionally, naive and memory B cells respond differentially to TLR ligands, as do different B‐cell subsets. We review here recent literature describing intrinsic and extrinsic effects of TLR stimulation on the fate of B cells, with particular attention to autoimmune diseases.
Development of thymically derived natural regulatory T cells
Authors: Bettini Matthew L. , Vignali Dario A.A.
Published: January 2010

Natural regulatory T cells (nTregs) are defined by their inherent ability to establish and maintain peripheral self‐tolerance. In recent years, the development of nTregs has come under close examination with the advent of Forkhead Box P3 protein (FOXP3)‐green fluorescent protein reporter mice that pinpointed the initiation of FOXP3 expression within the thymus. The mechanism and pathway of nTreg development has only recently been studied in detail and to a large degree remains unclear. In this review, we will discuss our current understanding of nTreg lineage choice and development from a cellular and intracellular standpoint.
FcγRIIB, FcγRIIIB, and systemic lupus erythematosus
Authors: Niederer Heather A. , Clatworthy Menna R. , Willcocks Lisa C. , Smith Kenneth G.C.
Published: January 2010

The autoimmune disease systemic lupus erythematosus (SLE) is characterized by the deposition of immune complexes in organs such as the kidney. This occurs as a result of multiple immunological abnormalities, including the production of high levels of autoantibody and dysregulated handling of immune complexes. Receptors for the Fc portion of IgG are critically involved in immune complex handling and clearance and in the regulation of B‐cell activation. Polymorphisms in the low‐affinity Fcγ receptors have been associated with susceptibility to a number of autoimmune diseases, including SLE. We review the role of two such receptors in the pathogenesis of lupus—the inhibitory receptor FcγRIIB and the glycosylphosphatidylinositol‐linked activatory receptor FcγRIIIB. Recent work has enhanced our understanding of the mechanism of action of the FcγRIIB I232T polymorphism and the overall role of this receptor in SLE. The human neutrophil antigen‐1 allotypes of FcγRIIIB and the role of the receptor in SLE are discussed with regard to the recent determination of copy number variation in FCGR3B and the association of low copy number with SLE.
Phosphoinositide 3‐kinase and the mammalian target of rapamycin pathways control T cell migration
Authors: Finlay David , Cantrell Doreen
Published: January 2010

The established role for phosphatidylinositol (3,4,5) triphosphate (PI(3,4,5)P3) signaling pathways is to regulate cell metabolism. More recently it has emerged that PI(3,4,5)P3 signaling via mammalian target of rapamycin and Foxo transcription factors also controls lymphocyte trafficking by determining the repertoire of adhesion and chemokine receptors expressed by T lymphocytes. In quiescent T cells, nonphosphorylated active Foxos maintain expression of KLF2, a transcription factor that regulates expression of the chemokine receptors CCR7 and sphingosine 1 phosphate receptor, and the adhesion receptor CD62L that together control T‐cell transmigration into secondary lymphoid tissues. PI(3,4,5)P3 mediates activation of protein kinase B, which phosphorylates and inactivates Foxos, thereby terminating expression of KLF2 and its target genes. The correct localization of lymphocytes is essential for effective immune responses, and the ability of phosphoinositide 3‐kinase and mammalian target of rapamycin to regulate expression of chemokine receptors and adhesion molecules puts these signaling molecules at the core of the molecular mechanisms that control lymphocyte trafficking.
Cross‐presentation of peptides from intracellular pathogens by MHC class I molecules
Authors: Blanchard Nicolas , Shastri Nilabh
Published: January 2010

Many prokaryotic and eukaryotic parasites multiply in specialized subcellular niches in the host cell. The invading microbes hijack key cellular functions to establish the intracellular niches but, unlike viruses, do not need the protein synthesis machinery of host cells to replicate. Circulating CD8+ T cells provide protective immunity by recognizing pathogen‐derived peptide major histocompatibility complex class I molecules (pMHC I) expressed by infected cells. Here, we review studies on the complex and varied pathways that produce the appropriate pMHC I as ligands for the CD8+ T cells. We also discuss possible explanations for the curious observations that CD8+ T cells are specific for fewer pMHC I ligands in parasite infections compared to the diversity of pMHC I ligands in viral infections.
New immune pathways from chronic post‐viral lung disease
Authors: Benoit Loralyn A. , Holtzman Michael J.
Published: January 2010

To better understand the immunopathogenesis of chronic inflammatory lung disease, we established a mouse model of disease that develops after respiratory viral infection. The disease that develops in this model is similar to chronic obstructive lung disease in humans. Using this model we have characterized two distinct phases in the chronic disease process. The first phase appears at three weeks after viral infection and depends on type I interferon‐dependent expression and then subsequent activation of the high‐affinity IgE receptor (FcɛRI) on conventional lung dendritic cells, which in turn recruit IL‐13‐producing CD4+ T cells to the lower airways. The second phase becomes maximal at seven weeks after infection and depends on invariant natural killer T (iNKT) cells and lung macrophages. Cellular cross‐talk relies on interactions between the semi‐invariant Vα14Jα18 T‐cell receptor on lung iNKT cells and CD1d on macrophages as well as iNKT cell‐derived IL‐13 and IL‐13 receptor on macrophages. These interactions drive macrophages to a pattern of alternative activation and overproduction of IL‐13. This innate immune axis is also activated in patients with chronic obstructive lung disease, as evidenced by increased numbers of iNKT cells and IL‐13‐producing alternatively activated macrophages marked by chitinase 1 production. Together the findings identify two new immune pathways responsible for early and late phases of chronic inflammatory lung disease in experimental and clinical settings. These findings extend our understanding of the complex mechanisms that underlie chronic obstructive lung disease and provide useful targets for diagnosis and therapy of this common disorder.
Opportunistic autoimmune disorders
Authors: Kong Yi‐chi M. , Wei Wei‐Zen , Tomer Yaron
Published: January 2010

Rapid advances in our understanding of the immune network have led to treatment modalities for malignancies and autoimmune diseases based on modulation of the immune response. Yet therapeutic modulation has resulted in immune dysregulation and opportunistic autoimmune sequelae, despite prescreening efforts in clinical trials. This review focuses on recent clinical data on opportunistic autoimmune disorders arising from three immunotherapeutic modalities: (1) systemic immunomodulators, including interferon‐α (also used to treat hepatitis C patients) and interferon‐β; (2) monoclonal antibodies to CTLA‐4 and CD52, and (3) hematopoietic stem cell transplantation. Uncategorized predisposing factors in these patients include major histocompatibility complex and gender genetics, prevalence of different autoimmune diseases, prior chemotherapy, underlying disorder (e.g., hepatitis C), and preconditioning regimens as part of organ and stem cell transplants. Not unexpectedly, the prevalent autoimmune thyroid disease surfaced frequently. Our combination models to study the balance between thyroid autoimmunity and tumor immunity upon regulatory T‐cell perturbation are briefly described.
One year follow‐up of contrast sensitivity following conventional laser in situ keratomileusis and laser epithelial keratomileusis
Authors: Townley Deirdre , Kirwan Caitriona , O’Keefe Michael
Published: January 2010

Purpose:  To determine the effect of conventional laser in situ keratomileusis (LASIK) and laser epithelial keratomileusis (LASEK) for myopia on contrast sensitivity (CS) using the Pelli‐Robson and Vector Vision CSV‐1000E CS tests.

Methods:  A prospective, comparative study was conducted on 36 eyes of 36 patients with myopia undergoing LASIK (18 eyes) and LASEK (18 eyes). Surgery was performed using the Technolas 217z laser (Bausch & Lomb). CS was recorded preoperatively and at 3, 6 and 12 months postoperatively.

Results:  No statistically significant difference was found in LogMAR uncorrected visual acuity post‐LASIK (−0.02 ± 0.16) and LASEK (−0.04 ± 0.14). Using the Pelli‐Robson, CS was significantly lower in the LASIK group 3 and 6 months postoperatively. No significant postoperative reduction in CS was observed in either treatment group. Using the CSV‐1000E test, CS was significantly reduced post‐LASIK at 3 (p = 0.05) and 6 (p = 0.05) cycles/degree under photopic conditions. No significant postoperative change occurred in the LASEK group under photopic or scotopic conditions. There was no significant difference in postoperative CS between the LASIK and LASEK groups at 3, 6, 12 or 18 cycles/degree using the CSV‐1000E test.

Conclusion:  One year postoperatively, there was no difference in CS between both treatment groups using the Pelli‐Robson and CSV‐1000E tests. CS was reduced postoperatively in the LASIK group at the lower spatial frequencies under photopic conditions. No postoperative change was detected in CS following LASIK or LASEK using the Pelli‐Robson test.
Contribution of afferent feedback and descending drive to human hopping
Authors: Zuur Abraham T. , Lundbye‐Jensen Jesper , Leukel Christian , Taube Wolfgang , Grey Michael J. , Gollhofer Albert , Nielsen Jens Bo , Gruber Markus
Published: January 2010

During hopping an early burst can be observed in the EMG from the soleus muscle starting about 45 ms after touch‐down. It may be speculated that this early EMG burst is a stretch reflex response superimposed on activity from a supra‐spinal origin. We hypothesised that if a stretch reflex indeed contributes to the early EMG burst, then advancing or delaying the touch‐down without the subject's knowledge should similarly advance or delay the burst. This was indeed the case when touch‐down was advanced or delayed by shifting the height of a programmable platform up or down between two hops and this resulted in a correspondent shift of the early EMG burst. Our second hypothesis was that the motor cortex contributes to the first EMG burst during hopping. If so, inhibition of the motor cortex would reduce the magnitude of the burst. By applying a low‐intensity magnetic stimulus it was possible to inhibit the motor cortex and this resulted in a suppression of the early EMG burst. These results suggest that sensory feedback and descending drive from the motor cortex are integrated to drive the motor neuron pool during the early EMG burst in hopping. Thus, simple reflexes work in concert with higher order structures to produce this repetitive movement.
An acid‐sensing ion channel from shark (Squalus acanthias) mediates transient and sustained responses to protons
Authors: Springauf Andreas , Gründer Stefan
Published: January 2010

Acid‐sensing ion channels (ASICs) are proton‐gated Na+ channels. They are implicated in synaptic transmission, detection of painful acidosis, and possibly sour taste. The typical ASIC current is a transient, completely desensitizing current that can be blocked by the diuretic amiloride. ASICs are present in chordates but are absent in other animals. They have been cloned from urochordates, jawless vertebrates, cartilaginous shark and bony fish, from chicken and different mammals. Strikingly, all ASICs that have so far been characterized from urochordates, jawless vertebrates and shark are not gated by protons, suggesting that proton gating evolved relatively late in bony fish and that primitive ASICs had a different and unknown gating mechanism. Recently, amino acids that are crucial for the proton gating of rat ASIC1a have been identified. These residues are completely conserved in shark ASIC1b (sASIC1b), prompting us to re‐evaluate the proton sensitivity of sASIC1b. Here we show that, contrary to previous findings, sASIC1b is indeed gated by protons with half‐maximal activation at pH 6.0. sASIC1b desensitizes quickly but incompletely, efficiently encoding transient as well as sustained proton signals. Our results show that the conservation of the amino acids crucial for proton gating can predict proton sensitivity of an ASIC and increase our understanding of the evolution of ASICs.
Purinergic neuromuscular transmission is selectively attenuated in ulcerated regions of inflamed guinea pig distal colon
Authors: Strong Derek S. , Cornbrooks Carson F. , Roberts Jane A. , Hoffman Jill M. , Sharkey Keith A. , Mawe Gary M.
Published: January 2010

This study was undertaken to investigate neuromuscular transmission in regions of the inflamed colon in which motility is disrupted. Propulsive motility was evaluated in segments of control guinea pigs and those treated 6 days previously with trinitrobenzene sulfonic acid. Intracellular recordings were then obtained from circular muscle cells to examine excitatory and inhibitory junction potentials (EJPs and IJPs). In inflamed preparations, propulsion of fecal pellets was temporarily halted or obstructed at sites of mucosal damage, whereas the propulsive motility was linear in control colons. The amplitudes of evoked and spontaneous IJPs were significantly reduced in ulcerated regions of inflamed preparations, but EJPs were comparable to controls. Pharmacological dissection of the IJP revealed that the purinergic component was reduced, while the nitrergic IJP was slightly increased. Furthermore, the reduction in the purinergic IJP in inflamed preparations persisted in the presence of hexamethonium, suggesting that the deficit involved the inhibitory motor neuron and/or smooth muscle. Nerve fibre density was not altered in the circular muscle, and pre‐contracted rings of inflamed colon relaxed normally to ATP, suggesting that the deficit involves altered ATP release and/or degradation. The P2Y1 receptor antagonist MRS2179 slowed propulsive motility indicating that decreased purinergic neuromuscular transmission could contribute to the inflammation‐induced motor deficit. We conclude that purinergic inhibitory neuronal input to the circular muscle is selectively reduced in regions of the colon in experimental colitis where the mucosa is damaged, and this is likely to contribute to altered motility in colitis by diminishing downstream relaxation during the peristaltic reflex.
Vorticity Dynamics in Axial Compressor Flow Diagnosis and Design—Part II: Methodology and Application of Boundary Vorticity Flux
Authors: Li Qiushi , Wu Hong , Guo Ming , Wu Jie-Zhi
Published: January 2010

In a companion paper (2008, “Vorticity Dynamics in Axial Compressor Flow Diagnosis and Design,” ASME J. Fluids Eng., 130, p. 041102), a study has been made on the critical role of circumferential vorticity (CV) in the performance of axial compressor in through-flow design (TFD). It has been shown there that to enhance the pressure ratio, the positive and negative CV peaks should be pushed to the casing and hub, respectively. This criterion has led to an optimal TFD that indeed improves the pressure ratio and efficiency. The CV also has great impact on the stall margin as it reflects the end wall blockage, especially at the tip region of the compressor. While that work was based on inviscid and axisymmetric theory, in this paper, we move on to the diagnosis and optimal design of fully three-dimensional (3D) viscous flow in axial compressors, focusing on the boundary vorticity flux (BVF), which captures the highly localized peaks of pressure gradient on the surface of the compressor blade, and thereby signifies the boundary layer separation and dominates the work rate done to the fluid by the compressor. For the 2D cascade flow we show that the BVF is directly related to the blade geometry. BVF-based 2D and 3D optimal blade design methodologies are developed to control the velocity diffusion, of which the results are confirmed by Reynolds-averaged Navier–Stokes simulations to more significantly improve the compressor performance than that of CV-based TFD. The methodology enriches the current aerodynamic design system of compressors.
Slip Flow in the Hydrodynamic Entrance Region of Circular and Noncircular Microchannels
Authors: Duan Zhipeng , Muzychka Y. S.
Published: January 2010

Microscale fluid dynamics has received intensive interest due to the emergence of micro-electro-mechanical systems (MEMS) technology. When the mean free path of the gas is comparable to the channel’s characteristic dimension, the continuum assumption is no longer valid and a velocity slip may occur at the duct walls. Noncircular cross sections are common channel shapes that can be produced by microfabrication. The noncircular microchannels have extensive practical applications in MEMS. The paper deals with issues of hydrodynamic flow development. Slip flow in the entrance of circular and parallel plate microchannels is first considered by solving a linearized momentum equation. It is found that slip flow is less sensitive to analytical linearized approximations than continuum flow and the linearization method is an accurate approximation for slip flow. Also, it is found that the entrance friction factor Reynolds product is of finite value and dependent on the Kn and tangential momentum accommodation coefficient but independent of the cross-sectional geometry. Slip flow and continuum flow in the hydrodynamic entrance of noncircular microchannels has been examined and a model is proposed to predict the friction factor and Reynolds product f Re for developing slip flow and continuum flow in most noncircular microchannels. It is shown that the complete problem may be easily analyzed by combining the asymptotic results for short and long ducts. Through the selection of a characteristic length scale, the square root of cross-sectional area, the effect of duct shape has been minimized. The proposed model has an approximate accuracy of 10% for most common duct shapes.
Liquid Sheet Breakup in Gas-Centered Swirl Coaxial Atomizers
Authors: Kulkarni V. , Sivakumar D. , Oommen C. , Tharakan T. J.
Published: January 2010

The study deals with the breakup behavior of swirling liquid sheets discharging from gas-centered swirl coaxial atomizers with attention focused toward the understanding of the role of central gas jet on the liquid sheet breakup. Cold flow experiments on the liquid sheet breakup were carried out by employing custom fabricated gas-centered swirl coaxial atomizers using water and air as experimental fluids. Photographic techniques were employed to capture the flow behavior of liquid sheets at different flow conditions. Quantitative variation on the breakup length of the liquid sheet and spray width were obtained from the measurements deduced from the images of liquid sheets. The sheet breakup process is significantly influenced by the central air jet. It is observed that low inertia liquid sheets are more vulnerable to the presence of the central air jet and develop shorter breakup lengths at smaller values of the air jet Reynolds number Reg. High inertia liquid sheets ignore the presence of the central air jet at smaller values of Reg and eventually develop shorter breakup lengths at higher values of Reg. The experimental evidences suggest that the central air jet causes corrugations on the liquid sheet surface, which may be promoting the production of thick liquid ligaments from the sheet surface. The level of surface corrugations on the liquid sheet increases with increasing Reg. Qualitative analysis of experimental observations reveals that the entrainment process of air established between the inner surface of the liquid sheet and the central air jet is the primary trigger for the sheet breakup.
Estimating errors reliably in Monte Carlo simulations of the Ehrenfest model
Authors: Ambegaokar Vinay , Troyer Matthias
Published: January 2010

We use the Ehrenfest urn model to illustrate the subtleties of error estimation in Monte Carlo simulations. We discuss how the smooth results of correlated sampling in Markov chains can fool one’s perception of the accuracy of the data and show via numerical and analytical methods how to obtain reliable error estimates from correlated samples.
Analyzing jump phenomena and stability in nonlinear oscillators using renormalization group arguments
Authors: Banerjee Dhruba , Bhattacharjee Jayanta K.
Published: January 2010

We study the stability of a damped Duffing oscillator by employing a renormalization group method for solving nonlinear differential equations. This approach is direct and makes the study of the amplitude equation smooth, obvious, and not based on any initial ansatz for the periodic form of the final solution. An introduction to the renormalization method is given.
A constructive formulation of the one-way speed of light
Authors: Iyer Chandru , Prabhu G. M.
Published: January 2010

A formulation of the one-way speed of light in three-dimensional Euclidean space is derived by a constructive approach. This formulation is consistent with the result of the Michelson–Morley experiment in that the harmonic mean of the outward and return speeds is equal to c, the standard value for the speed of electromagnetic radiation in vacuum. It is also shown that a shift in synchronization, proportional to the distance along the line of motion, renders this speed a constant along all directions.
Ratting Out a Diabetes Gene
Authors: Kiberstis Paula A.
Published: January 2010

Sequence variations in an adrenergic receptor gene cause reduced insulin secretion and contribute to type 2 diabetes.
High Fat Content
Authors: Foley John F.
Published: January 2010

The increased abundance of the lipase MAGL and of signaling lipids in aggressive tumor cells contributes to their malignancy.
Basal Release of ATP: An Autocrine-Paracrine Mechanism for Cell Regulation
Authors: Corriden Ross , Insel Paul A.
Published: January 2010

Responses to ATP play an important role in regulating the signaling and function of a diverse array of cells and tissues.
Comparative
In Vitro
Activities of Nemonoxacin (TG-873870), a Novel Nonfluorinated Quinolone, and Other Quinolones against Clinical Isolates
Authors: Lauderdale Tsai-Ling , Shiau Yih-Ru , Lai Jui-Fen , Chen Hua-Chien , King Chi-Hsin R.
Published: January 2010

The
in vitro
antibacterial activities of nemonoxacin (TG-873870), a novel nonfluorinated quinolone, against 770 clinical isolates were investigated. Nemonoxacin (tested as its malate salt, TG-875649) showed better
in vitro
activity than ciprofloxacin and levofloxacin against different species of staphylococci, streptococci, and enterococci,
Neisseria gonorrhoeae
, and
Haemophilus influenzae
. The
in vitro
activity of TG-875649 was also comparable to or better than that of moxifloxacin against these pathogens, which included ciprofloxacin-resistant, methicillin-resistant
Staphylococcus aureus
and levofloxacin-resistant
Streptococcus pneumoniae
.
Resistance to Linezolid in a Porcine
Clostridium perfringens
Strain Carrying a Mutation in the
rplD
Gene Encoding the Ribosomal Protein L4
Authors: Hölzel Christina S. , Harms Katrin S. , Schwaiger Karin , Bauer Johann
Published: January 2010

Coresistance to human reserve antibiotics can be selected by antibiotics used in veterinary medicine. A
Clostridium perfringens
strain isolated from pig manure was resistant to the reserve drug linezolid and, simultaneously, resistant against florfenicol and erythromycin. We detected a new mutation in a highly conserved region of
rpl
D
, encoding protein L4 of the 50S ribosomal subunit. This is the first genetic substantiation of linezolid resistance in the genus
Clostridium
.
GES-13, a β-Lactamase Variant Possessing Lys-104 and Asn-170 in
Pseudomonas aeruginosa
Authors: Kotsakis S. D. , Papagiannitsis C. C. , Tzelepi E. , Legakis N. J. , Miriagou V. , Tzouvelekis L. S.
Published: January 2010

GES-13 β-lactamase, a novel GES variant possessing Lys-104 and Asn-170, was identified in
Pseudomonas aeruginosa. bla
GES-13
was the single gene cassette of a class 1 integron probably located in the chromosome. GES-13 efficiently hydrolyzed broad-spectrum cephalosporins and aztreonam. Imipenem was a potent inhibitor of GES-13 but was not hydrolyzed at measurable rates.
Three Decades of β-Lactamase Inhibitors
Authors: Drawz Sarah M. , Bonomo Robert A.
Published: January 2010

Since the introduction of penicillin, β-lactam antibiotics have been the antimicrobial agents of choice. Unfortunately, the efficacy of these life-saving antibiotics is significantly threatened by bacterial β-lactamases. β-Lactamases are now responsible for resistance to penicillins, extended-spectrum cephalosporins, monobactams, and carbapenems. In order to overcome β-lactamase-mediated resistance, β-lactamase inhibitors (clavulanate, sulbactam, and tazobactam) were introduced into clinical practice. These inhibitors greatly enhance the efficacy of their partner β-lactams (amoxicillin, ampicillin, piperacillin, and ticarcillin) in the treatment of seriousEnterobacteriaceaeand penicillin-resistant staphylococcal infections. However, selective pressure from excess antibiotic use accelerated the emergence of resistance to β-lactam-β-lactamase inhibitor combinations. Furthermore, the prevalence of clinically relevant β-lactamases from other classes that are resistant to inhibition is rapidly increasing. There is an urgent need for effective inhibitors that can restore the activity of β-lactams. Here, we review the catalytic mechanisms of each β-lactamase class. We then discuss approaches for circumventing β-lactamase-mediated resistance, including properties and characteristics of mechanism-based inactivators. We next highlight the mechanisms of action and salient clinical and microbiological features of β-lactamase inhibitors. We also emphasize their therapeutic applications. We close by focusing on novel compounds and the chemical features of these agents that may contribute to a “second generation” of inhibitors. The goal for the next 3 decades will be to design inhibitors that will be effective for more than a single class of β-lactamases.
ThesmpB-ssrAMutant ofYersinia pestisFunctions as a Live Attenuated Vaccine To Protect Mice against Pulmonary Plague Infection
Authors: Okan Nihal A. , Mena Patricio , Benach Jorge L. , Bliska James B. , Karzai A. Wali
Published: January 2010

The bacterial SmpB-SsrA system is a highly conserved translational quality control mechanism that helps maintain the translational machinery at full capacity. Here we present evidence to demonstrate that thesmpB-ssrAgenes are required for pathogenesis ofYersinia pestis, the causative agent of plague. We found that disruption of thesmpB-ssrAgenes leads to reduction in secretion of the type III secretion-related proteins YopB, YopD, and LcrV, which are essential for virulence. Consistent with these observations, thesmpB-ssrAmutant ofY. pestiswas severely attenuated in a mouse model of infection via both the intranasal and intravenous routes. Most significantly, intranasal vaccination of mice with thesmpB-ssrAmutant strain ofY. pestisinduced a strong antibody response. The vaccinated animals were well protected against subsequent lethal intranasal challenges with virulentY. pestis. Taken together, our results indicate that thesmpB-ssrAmutant ofY. pestispossesses the desired qualities for a live attenuated cell-based vaccine against pneumonic plague.
Intracellular Trafficking ofBordetella pertussisin Human Macrophages
Authors: Lamberti Yanina A. , Hayes Jimena Alvarez , Perez Vidakovics Maria L. , Harvill Eric T. , Rodriguez Maria Eugenia
Published: January 2010

AlthoughBordetella pertussishas been observed to survive inside macrophages, its ability to resist or evade degradation in phagolysosomes has not been defined. We here investigated the trafficking ofB. pertussisupon entry into human macrophages. During the first hours following phagocytosis, a high percentage of bacteria were destroyed within acidic compartments positive for the lysosome-associated membrane proteins (LAMP). However, roughly one-fourth of the bacteria taken up evade this initial killing event, remaining in nonacidic compartments. Forty-eight hours after infection, the number of intracellular bacteria per cell increased, suggesting thatB. pertussisis capable of replicating in this type of compartment. Viable bacteria accumulated within phagosomal compartments positive for the early endosomal marker Rab5 but not the late endosomal marker LAMP. Moreover,B. pertussis-containing phagosomes acquired exogenously added transferrin, indicating that intracellular bacteria have access to extracellular components and essential nutrients via the host cell recycling pathway. Overall, these results suggest thatB. pertussissurvives and eventually replicates in compartments with characteristics of early endosomes, potentially contributing to its extraordinary ability to persist within hosts and populations.
Management of hepatic encephalopathy in children
Authors: Arya Ravindra , Gulati Sheffali , Deopujari Satish
Published: January 2010

Hepatic encephalopathy is a common metabolic condition in children, having a significantly different aetiopathogenesis from that in adults. The present paper reviews the medical interventions of proven efficacy and also discusses recent advances from various fields as applicable to management of children with this disorder, focusing on measures other than liver transplant. The most important component of managing a child with hepatic encephalopathy is basic intensive care with regulation of fluid status, glucose and electrolyte homeostasis. Specific management includes measures to reduce serum ammonia concentrations, and the prevention and prompt treatment of complications. Methods to reduce ammonia target various steps in its metabolism. This includes reducing its production in and absorption from the intestine and promoting its metabolism in the liver. Significant secondary complications occurring in fulminant hepatic failure which require urgent recognition and management include coagulopathy, cerebral oedema and renal dysfunction. Children with hepatic encephalopathy also have several other paediatric care issues such as fever, requirement for sedation, etc, where the choice of drug is not straightforward and is often different from other settings. This is reviewed here along with an attempt to provide rational choices based on available evidence. Certain controversial and experimental approaches to treatment of fulminant hepatic failure are also discussed, but clearly delineated from the established management protocol. Finally, the role of artificial liver support devices is discussed, with the realisation that they can provide an effective bridge during the time when a patient is waiting for a suitable donor for liver transplant.
Cardiac resynchronisation therapy: what a hospital practitioner needs to know?
Authors: Albouaini Khaled , Alkarmi Amr , Wright David Justin
Published: January 2010

The incidence and prevalence of heart failure are rapidly rising. Despite the improvement in pharmacologic treatment, many patients have severe persistent symptoms, and their prognosis remains poor. One of the most recent advances in heart failure management is the concept of cardiac resynchronisation therapy (CRT). This therapy aims to pace the right and left ventricles synchronously to contract simultaneously and therefore enhances cardiac output. Clinical trials on CRT have demonstrated both morbidity and mortality benefits. This article reviews the evidence for CRT, the current indications, and important information relevant to the clinician treating patients with heart failure. It also highlights some of the current controversies in this field as well as the need for future research.