bluuebunny/crossref_metadata_2025 huggingface dataset:
Charcot Neuroarthropathy of the Foot and Ankle
Authors: Madan Simerjit Singh , Pai Dinker R
Published: May 2013

Charcot neuroarthropathy (CN) is a rare, progressive, deforming disease of bone and joints, especially affecting the foot and ankle and leading to considerable morbidity. It can also affect other joints such as the wrist, knee, spine and shoulder. This disease, described originally in reference to syphilis, is now one of the most common associates of diabetes mellitus. As the number of diabetics increase, the incidence of CN is bound to rise. Faster initial diagnosis and prompt institution of treatment may help to reduce its sequelae. There should be a low threshold for ordering investigations to assist coming to this diagnosis. No single investigation is the gold standard. Recent studies on pathogenesis and development of newer investigation modalities have helped to clarify the mystery of its pathogenesis and of its diagnosis in the acute phase. Various complementary investigations together allow the correct diagnosis to be made. Osteomyelitis continues to be confused with acute CN. Hybrid positron emission tomography has shown some promise in differentiating these conditions. A multispecialty approach involving diabetologists, orthopaedists and podiatrists should be used to tackle this difficult problem. The aim of this article is to describe current knowledge about CN with particular reference to the status of diagnostic indicators and management options.
Distal Femoral Fractures in Post‐poliomyelitis Patients Treated with Locking Compression Plates
Authors: Wang Wei‐jun , Shi Hong‐fei , Chen Dong‐yang , Chen Yi‐xin , Wang Jun‐fei , Wang Shou‐feng , Qiu Yong , Xiong Jin
Published: May 2013

Objective

Treatment of distal femoral fracture in post‐polio patients is difficult because the bone is usually osteopenic, small and deformed. This retrospective study aimed to investigate the outcomes of distal femoral fracture in post‐polio patients treated by locking compression plates (LCP).

Methods

The medical records of 19 post‐polio patients (mean age 49 years at time of surgery) were reviewed and intraoperative data retrieved. Fracture union and callus formation were evaluated on radiographs taken at each postoperative visit. Functional outcome assessments included range of motion and Hospital for Special Surgery (HSS) score of the ipsilateral knee joint.

Results

Sixteen femoral fractures occurred in the poliomyelitis‐affected limbs. The mean duration of operation was 86 min and mean blood loss 120 mL. All fractures healed (mean, four months) but union was delayed in one. At the final follow‐up 2 yrs after surgery, the mean range of knee flexion was 105° (range, 90°–130°), and mean HSS score 76 points (range, 60–93). There were no cases of nonunion, implant cutout, or other complications.

Conclusions

LCP provides stable fixation of distal femoral fractures in post‐polio patients. Bony union and good functional outcomes are achieved, but delayed union and minimal callus may occur.
Surgical Treatment of Basicervical Intertrochanteric Fractures of the Proximal Femur with Cephalomeduallary Hip Nails
Authors: Hu Sun‐jun , Yu Guang‐rong , Zhang Shi‐min
Published: May 2013

Objective

To study the outcome of basicervical intertrochanteric fractures of the proximal femur treated with cephalomeduallary hip nails.

Methods

The clinical outcomes of 32 cases of basicervical intertrochanteric fractures treated with cephalomeduallary hip nails from January 2008 to June 2010 were retrospectively reviewed and the progress of fracture healing and occurrence of complications recorded. The function of the hip joints was evaluated by the Harris social index 2 years postoperatively.

Results

Thirty patients were followed up until fracture union for at least 24 months. Twenty‐seven fractures had healed with no loss of position by 12 months postoperatively; the remaining three had mild varus deformity of the hip joint. No patient had evidence of avascular necrosis of the femoral head. No cut out of the helical blade was visible on radiographs. The mean Harris score was 86.5 (75–96) two years postoperatively, 11 patients having excellent scores, 15 good and 4 fair.

Conclusion

Closed reduction and proximal femur intramedullary nail fixation for basicervical intertrochanteric fractures provides stable fixation and allows early exercise. It appears to have excellent outcomes in the short and medium term.
Traumatic Vertebral Fractures with Concomitant Fractures of the First Rib
Authors: Wang Hong‐wei , Xiang Qiang , Li Chang‐qing , Zhou Yue
Published: May 2013

Objective

To investigate the characteristics of patients with traumatic vertebral fractures and concomitant fractures of the first rib and their management.

Methods

From January 2001 to December 2010, 17/3142 patients (0.5%) with traumatic vertebral fractures who presented to our hospitals had concomitant fractures of the first rib.

Results

The study included 14 men (82.4%) and 3 women (17.6%) patients of age 32–57 years (mean, 46.6 years). The mechanisms of trauma were falls from heights in seven, motor vehicle accidents in five and direct collisions with blunt objects in five. Thirteen patients (76.5%) presented initially with pulmonary complications after sustaining trauma. Three patients sustained one rib fracture, two three rib fractures, three four rib fractures and 10 > five rib fractures. The injuries were right‐sided in three cases, left‐sided in three and bilateral in eleven. Four patients (23.5%) presented with craniocerebral injuries. According to the American Spinal Injury Association (ASIA) classification, 10 patients (58.8% of the total study group) had motor and sensory deficits (ASIA A–D). There were no vascular injuries or deaths.

Conclusion

Traumatic vertebral fractures with concomitant fractures of the first rib are associated with multisystem injuries, but not always with morbidity and mortality. A multidisciplinary approach, early diagnosis, appropriate treatment and observation in the intensive care unit may prevent morbidity and/or mortality.
Physiological mechanisms of seasonal and rapid cold‐hardening in insects
Authors: TEETS NICHOLAS M. , DENLINGER DAVID L.
Published: May 2013

Insects have evolved a number of physiological mechanisms for coping with the detrimental effects of low temperature. As autumn progresses, insects use environmental signals such as shortening day lengths and gradually decreasing temperatures to trigger seasonal cold‐hardening adaptations. These mechanisms include dramatic changes in biochemistry, cell function and gene expression that permit improved cell function and viability at low temperature. Insects are also capable of enhancing cold tolerance on a much shorter time scale, in a process called rapid cold‐hardening (RCH). Rapid cold‐hardening allows insects to improve cold tolerance almost instantaneously (i.e. within minutes to hours) to cope with sudden cold snaps and regularly‐occurring diurnal drops in temperature. Initially, it was assumed that RCH would share many of the same basic mechanisms as seasonal cold‐hardening, albeit on a shorter time scale. Although there is some evidence supporting this, recent work has called into question some of the original hypotheses concerning the mechanisms of RCH. Also, some mechanisms important for seasonal cold‐hardening, such as up‐regulation of stress proteins, are unlikely to function at the temperatures and time scales at which RCH occurs. In the present review, the current understanding of the physiological mechanisms governing both seasonal cold‐hardening and RCH are summarized. A synthesis of the current literature suggests that these two forms of cold‐hardening may be more mechanistically distinct than originally anticipated.
Cardiovascular down‐regulation in essential hypotension: Relationships with autonomic control and sleep
Authors: Covassin Naima , de Zambotti Massimiliano , Cellini Nicola , Sarlo Michela , Stegagno Luciano
Published: May 2013

In this work, we aimed to clarify the autonomic involvement in the cardiovascular down‐regulation in essential hypotension. The relationships between cardiovascular response and sleep quality were also examined. Thirteen female hypotensives and 13 female normotensives performed a stress task followed by polysomnography. Measures derived from blood pressure monitoring, impedance cardiography, and heart rate variability were collected. Hypotensives exhibited lower cardiovascular and autonomic activation than controls during the task. While a better sleep quality (i.e., higher sleep efficiency and lower nocturnal wakefulness) correlated with a reduced reactivity in normotensives, the opposite pattern occurred in hypotensives. The results suggest that a blunted response in both autonomic branches underlies the cardiovascular hypoactivation in hypotension. Further, good sleep seems to be associated with optimal levels of physiological reactivity.
The Informal European Parliamentary Working Group on Risk—History, Remit, and Future Plans: A Personal View
Authors: Löfstedt Ragnar E.
Published: May 2013

On September 5, 2012 the inaugural meeting of the European Parliamentary Working Group on Risk (WGR) took place in the European Parliament in Brussels. It is chaired by Mrs. Julie Girling (U.K. Conservative), Member of the European Parliament (MEP), and involves some 10–12 other MEPs representing a wide array of European political parties from across the EU member state countries, including Sweden, the Netherlands, and Hungary. The WGR is supported by a small secretariat reporting directly to Julie Girling MEP. In this background article of WGR, I discuss the background to why WGR was set up, the remit of the committee, and some of its possible future plans. I do this very much in a personal capacity, having suggested the formation of the committee in the first place and persuaded Mrs. Girling to chair it.
The Generalized Unit Value Index Family
Authors: von Auer Ludwig
Published: May 2013

This study introduces a group of Generalized Unit Value indices that evaluate price level changes. The approach is to transform the original price and quantity data into numbers that all relate to a common unit which provides the same intrinsic worth to the consumers. When, in the transformed data, an equivalence of worth is present, then even incommensurables can be aggregated by the standard unit value method. The group of Generalized Unit Value indices includes some well‐known (Laspeyres, Paasche, Banerjee), barely known (Lehr, Davies), and previously quite unknown price indices. Using a Generalized Unit Value price index as a deflator yields a particularly appealing and useful quantity index.
Improving the in vivo Persistence, Distribution and Function of Cytotoxic T Lymphocytes by Inhibiting the Tumor Immunosuppressive Microenvironment
Authors: Xu W. , Cai J. , Li S. , Zhang H. , Han J. , Wen M. , Wen J. , Gao F.
Published: May 2013

Adoptive cell transfer immunotherapy of malignant tumors has the problem of symbiosis between effector cells and tumor cells, a short in vivo residence time, and a poor killing efficiency of effector cells. Thus, releasing effector cells from the cancer immunosuppressive microenvironment and improving their effective time and functional status in vivo would seem to be ideal strategies for facilitating immunotherapy. Low‐dose cyclophosphamide administration can effectively break immunotolerance by inhibiting regulatory T cells. In the present study, in order to verify whether the persistence, distribution and function of effector cells can be improved by inhibiting immunosuppressive microenvironment, low‐dose cyclophosphamide was previously intraperitoneally injected into melanoma‐bearing C57BL/6 mice, thereafter, CFSE‐labeled cytotoxic T lymphocytes were transfused intravenously, and their effective time, distributive pattern, and killing efficiency in different groups were observed by measuring the fluorescence intensity and cell cycle of cytotoxic T lymphocytes distributed in various organs, in comparison with tumor growth. We found down‐regulating Tregs in vivo can simultaneously reduce the levels of interleukin‐10 and transforming growth factor‐β. Migration and distribution of cytotoxic T lymphocytes in vivo was found to vary with time. Inhibition of immunotolerance can significantly improve the persistence, distribution, and function of cytotoxic T lymphocytes. Correspondingly, significantly higher secretion of perforin, granzyme B, IL‐2, and IFN‐γ in tumor tissues with decreased tumor growth was seen in the cyclophosphamide injection group than in the control group. Our study may provide useful information on the cyclophosphamide‐mediated mechanism for facilitating tumor immunotherapy by inhibiting the immunosuppressive tumor microenvironment.
Phylogeny and systematics of the bee genus Osmia (Hymenoptera: Megachilidae) with emphasis on North American Melanosmia: subgenera, synonymies and nesting biology revisited
Authors: RIGHTMYER MOLLY G. , GRISWOLD TERRY , BRADY SEÁN G.
Published: May 2013

The predominantly Holarctic bee genus Osmia Panzer is species‐rich and behaviourally diverse. A robust phylogeny of this genus is important for understanding the evolution of the immense variety of morphological and behavioural traits exhibited by this group. We infer a phylogeny of Osmia using DNA sequence data obtained from three nuclear genes (elongation factor 1‐α, LW‐rhodopsin and CAD) and the mitochondrial gene COI. Our taxon sampling places special attention on North American members of the subgenus Melanosmia Schmiedeknecht; we discuss the novel placement of a number of species traditionally assigned to O. (Melanosmia) and examine the relative support for alternative classifications of this species‐rich subgenus. We use this new phylogeny to guide a reassessment of morphological and behavioural characters within Osmia. Our results provide support for the recognition of Osmia (Hapsidosmia), subgen.n., a monotypic subgenus containing Osmia iridis Cockerell & Titus. We synonymize Osmia (Mystacosmia) Snelling under O. (Melanosmia), syn.n. We synonymize Osmia (Acanthosmioides) Ashmead under O. (Melanosmia), syn.n., propose ‘odontogaster species group’ as a replacement for the subgeneric name Acanthosmioides, and refine the morphological characters that serve to diagnose the species group. We additionally propose ‘nigrifrons species group’ for a clade within O. (Melanosmia) containing most species formerly placed in Osmia (Centrosmia) Robertson. We demonstrate more cohesive patterns of nest substrate use in the nigrifrons and odontogaster species groups than was previously believed to occur, reconsider character polarity of aspects of the female mandible, and show that a large number of morphological characters have evolved convergently within the genus. In order to facilitate discussion of relevant taxa, we propose the following 15 new synonymies: O. bakeri Sandhouse under O. melanopleura Cockerell; O. crenulaticornis Michener under O. pinorum Cockerell; O. claremontensis Michener under O. sedula Sandhouse; O. cockerelli Sandhouse under O. dakotensis Michener; O. francisconis White under O. enixa Sandhouse; O. hurdi White under O. austromaritima Michener; O. sladeni Sandhouse under O. nifoata Cockerell; O. titusi Cockerell under O. phenax Cockerell; O. subtrevoris Cockerell, O. physariae Cockerell, and O. erecta Michener under O. giliarum Cockerell; and O. universitatis Cockerell, O. integrella Cockerell, O. amala Cockerell, and O. metitia Cockerell under O. nigrifrons Cresson, syn.n. We remove O. wyomingensis Michener from synonymy with O. nifoata Cockerell, stat.n., and O. pinorum Cockerell from synonymy with O. physariae Cockerell, stat.n.

This published work has been registered in ZooBank, http://zoobank.org/urn:lsid:zoobank.org:pub:A3E7D63B‐5C4C‐4ACF‐BF33‐48E5C5DD1B0D.
Enhanced inhibitory neurotransmission in the cerebellar cortex of Atp1a3‐deficient heterozygous mice
Authors: Ikeda Keiko , Satake Shin’Ichiro , Onaka Tatsushi , Sugimoto Hiroki , Takeda Naoki , Imoto Keiji , Kawakami Kiyoshi
Published: May 2013

Key points

Mutations of ATP1A3 cause rapid‐onset dystonia with parkinsonism (RDP) and alternating hemiplegia of childhood (AHC).

The mRNA of Atp1a3 was highly expressed in molecular‐layer interneurons and Purkinje cells in the developing mouse cerebellar cortex, and the gene product was observed as dots in the molecular layer, on the surface of Purkinje cell soma and the pinceaux.

Here we report that Atp1a3+/− mice showed increased symptoms of dystonia when being administrated kainate into cerebellum. We also found enhanced inhibitory neurotransmission between molecular‐layer interneurons and Purkinje cells in the developing cerebellum of Atp1a3+/− mice.

These findings suggest that ATP1A3 haploinsufficiency in the cerebellum has some effect on the inhibitory, but not the excitatory, circuitry and the interaction among different cell types during development. Disturbances of the cerebellar inhibitory network seem to be the underlying pathophysiological mechanism of dystonia among the increasing spectrum of complex neurological symptoms in RDP and AHC.

Abstract  Dystonia is characterized by excessive involuntary and prolonged simultaneous contractions of both agonist and antagonist muscles. Although the basal ganglia have long been proposed as the primary region, recent studies indicated that the cerebellum also plays a key role in the expression of dystonia. One hereditary form of dystonia, rapid‐onset dystonia with parkinsonism (RDP), is caused by loss of function mutations of the gene for the Na pump α3 subunit (ATP1A3). Little information is available on the affected brain regions and mechanism for dystonia by the mutations in RDP. The Na pump is composed of α and β subunits and maintains ionic gradients of Na+ and K+ across the cell membrane. The gradients are utilized for neurotransmitter reuptake and their alteration modulates neural excitability. To provide insight into the molecular aetiology of RDP, we generated and analysed knockout heterozygous mice (Atp1a3+/−). Atp1a3+/− showed increased symptoms of dystonia that is induced by kainate injection into the cerebellar vermis. Atp1a3 mRNA was highly expressed in Purkinje cells and molecular‐layer interneurons, and its product was concentrated at Purkinje cell soma, the site of abundant vesicular γ‐aminobutyric acid transporter (VGAT) signal, suggesting the presynaptic localization of the α3 subunit in the inhibitory synapse. Electrophysiological studies showed that the inhibitory neurotransmission at molecular‐layer interneuron–Purkinje cell synapses was enhanced in Atp1a3+/− cerebellar cortex, and that the enhancement originated via a presynaptic mechanism. Our results shed light on the role of Atp1a3 in the inhibitory synapse, and potential involvement of inhibitory synaptic dysfunction for the pathophysiology of dystonia.
The role of α‐adrenergic receptors in mediating beat‐by‐beat sympathetic vascular transduction in the forearm of resting man
Authors: Fairfax Seth T. , Holwerda Seth W. , Credeur Daniel P. , Zuidema Mozow Y. , Medley John H. , Dyke II Peter C. , Wray D. Walter , Davis Michael J. , Fadel Paul J.
Published: May 2013

Key points

Sympathetic support of blood pressure demands the efficient control of vascular tone; however, little is known regarding how spontaneously occurring bursts of muscle sympathetic nerve activity (MSNA) dynamically influence forearm vascular conductance.

This study examined the extent to which spontaneous MSNA bursts evoke changes in forearm vascular conductance and blood pressure with and without local α‐adrenergic blockade in young healthy men during supine rest.

We observed that under resting conditions, forearm vascular conductance increases briefly and then significantly decreases in association with the total amount of the preceding MSNA; however, during α‐adrenergic blockade the decrease in vascular conductance is eliminated.

These results indicate that normal variations in spontaneous MSNA burst activity are systematically followed by transient and robust responses of forearm vasoconstriction and that this influence is mediated via α‐adrenergic receptor mechanisms.

Abstract  Sympathetic vascular transduction is commonly understood to act as a basic relay mechanism, but under basal conditions, competing dilatory signals may interact with and alter the ability of sympathetic activity to decrease vascular conductance. Thus, we determined the extent to which spontaneous bursts of muscle sympathetic nerve activity (MSNA) mediate decreases in forearm vascular conductance (FVC) and the contribution of local α‐adrenergic receptor‐mediated pathways to the observed FVC responses. In 19 young men, MSNA (microneurography), arterial blood pressure and brachial artery blood flow (duplex Doppler ultrasound) were continuously measured during supine rest. These measures were also recorded in seven men during intra‐arterial infusions of normal saline, phentolamine (PHEN) and PHEN with angiotensin II (PHEN+ANG). The latter was used to control for increases in resting blood flow with α‐adrenergic blockade. Spike‐triggered averaging was used to characterize beat‐by‐beat changes in FVC for 15 cardiac cycles following each MSNA burst and a peak response was calculated. Following MSNA bursts, FVC initially increased by +3.3 ± 0.3% (P= 0.016) and then robustly decreased to a nadir of −5.8 ± 1.6% (P < 0.001). The magnitude of vasoconstriction appeared graded with the number of consecutive MSNA bursts; while individual burst size only had a mild influence. Neither PHEN nor PHEN+ANG infusions affected the initial rise in FVC, but both infusions significantly attenuated the subsequent decrease in FVC (–2.1 ± 0.7% and –0.7 ± 0.8%, respectively; P < 0.001 vs. normal saline). These findings indicate that spontaneous MSNA bursts evoke robust beat‐by‐beat decreases in FVC that are exclusively mediated via α‐adrenergic receptors.
Forming Limits of a Sheet Metal After Continuous-Bending-Under-Tension Loading
Authors: He Ji , Cedric Xia Z. , Zeng Danielle , Li Shuhui
Published: May 2013

Forming limit diagrams (FLD) have been widely used as a powerful tool for predicting sheet metal forming failure in the industry. The common assumption for forming limits is that the deformation is limited to in-plane loading and through-thickness bending effects are negligible. In practical sheet metal applications, however, a sheet metal blank normally undergoes a combination of stretching, bending, and unbending, so the deformation is invariably three-dimensional. To understand the localized necking phenomenon under this condition, a new extended Marciniak–Kuczynski (M–K) model is proposed in this paper, which combines the FLD theoretical model with finite element analysis to predict the forming limits after a sheet metal undergoes under continuous-bending-under-tension (CBT) loading. In this hybrid approach, a finite element model is constructed to simulate the CBT process. The deformation variables after the sheet metal reaches steady state are then extracted from the simulation. They are carried over as the initial condition of the extended M–K analysis for forming limit predictions. The obtained results from proposed model are compared with experimental data from Yoshida et al. (2005, “Fracture Limits of Sheet Metals Under Stretch Bending,” Int. J. Mech. Sci., 47(12), pp. 1885–1986) under plane strain deformation mode and the Hutchinson and Neale's (1978(a), “Sheet Necking—II: Time-Independent Behavior,” Mech. Sheet Metal Forming, pp. 127–150) M–K model under in-plane deformation assumption. Several cases are studied, and the results under the CBT loading condition show that the forming limits of post-die-entry material largely depends on the strain, stress, and hardening distributions through the thickness direction. Reduced forming limits are observed for small die radius case. Furthermore, the proposed M–K analysis provides a new understanding of the FLD after this complex bending-unbending-stretching loading condition, which also can be used to evaluate the real process design of sheet metal stamping, especially when the ratio of die entry radii to the metal thickness becomes small.
Forming Limit Diagram Determination of Al 3105 Sheets and Al 3105/Polypropylene/Al 3105 Sandwich Sheets Using Numerical Calculations and Experimental Investigations
Authors: Parsa M. H. , Ettehad M. , Matin P. H.
Published: May 2013

Sandwich sheet structures are gaining a wide array of applications in the aeronautical, marine, automotive, and civil engineering fields. Since such sheets can be subjected to forming/stamping processes, it is crucial to characterize their limiting amount of deformation before trying out any forming/stamping process. To achieve this goal, sandwich sheets of Al 3105/polymer/Al 3105 were prepared using thin film hot melt adheres. Through an experimental effort, forming limit diagrams (FLDs) of the prepared sandwich sheets were evaluated. In addition, simulation efforts were conducted to predict the FLDs of the sandwich sheets using finite element analysis (FEA) by considering the Gurson–Tvergaard–Needleman (GTN) damage model. The agreement among the experimental results and simulated predictions was promising. The effects of different parameters such as polymer core thickness, aluminum face sheet thickness, and shape constraints were investigated on the FLDs.
Three-Dimensional Constraint Effects on the Slitting Method for Measuring Residual Stress
Authors: Aydıner C. Can , Prime Michael B.
Published: May 2013

The incremental slitting or crack compliance method determines a residual stress profile from strain measurements taken as a slit is incrementally extended into the material. To date, the inverse calculation of residual stress from strain data conveniently adopts a two-dimensional, plane strain approximation for the calibration coefficients. This study provides the first characterization of the errors caused by the 2D approximation, which is a concern since inverse analyses tend to magnify such errors. Three-dimensional finite element calculations are used to study the effect of the out-of-plane dimension through a large scale parametric study over the sample width, Poisson's ratio, and strain gauge width. Energy and strain response to point loads at every slit depth is calculated giving pointwise measures of the out-of-plane constraint level (the scale between plane strain and plane stress). It is shown that the pointwise level of constraint varies with slit depth, a factor that makes the effective constraint a function of the residual stress to be measured. Using a series expansion inverse solution, the 3D simulated data of a representative set of residual stress profiles are reduced with 2D calibration coefficients to yield the error in stress. The sample width below which it is better to use plane stress compliances than plane strain is shown to be about 0.7 times the sample thickness; however, even using the better approximation, the rms stress errors sometimes still exceed 3% with peak errors exceeding 6% for Poisson's ratio 0.3, and errors increase sharply for larger Poisson's ratios. The error is significant, yet, error magnification from the inverse analysis in this case is mild compared to, e.g., plasticity based errors. Finally, a scalar correction (effective constraint) over the plane-strain coefficients is derived to minimize the root-mean-square (rms) stress error. Using the posed scalar correction, the error can be further cut in half for all widths and Poisson's ratios.
Spin-Optical Metamaterial Route to Spin-Controlled Photonics
Authors: Shitrit Nir , Yulevich Igor , Maguid Elhanan , Ozeri Dror , Veksler Dekel , Kleiner Vladimir , Hasman Erez
Published: May 2013

Making Metamaterials

Controlling the propagation of electromagnetic waves is a key requirement in communication technologies. The components tend to be bulky, however, which can make it difficult to integrate with microelectronics circuits. Using arrays of metallic nanoantennae patterned on a substrate surface,

Shitrit
et al.

(p.
724
) fabricated a novel class of metamaterials: anisotropic materials without inversion symmetry. The materials may pave the way to polarization-dependent nanophotonics.
Crowdsourcing Immunity
Authors: Crowe James E.
Published: May 2013

Computational methods reveal the nature and diversity of antibodies in HIV-infected individuals.

[Also see Report by

Georgiev
et al.

]
China Heads Off Deadly Blood Disorder
Authors: Hvistendahl Mara
Published: May 2013

To combat the spread of thalassemia, a Chinese province screens millions.
Ethics, Error, and Initial Trials of Efficacy
Authors: Hey Spencer Phillips , Kimmelman Jonathan
Published: May 2013

Clinical trial reforms aimed at boosting phase 2 positive predictivity may entail ethical and social trade-offs.
Eavesdropping on Communications Between Liver and β Cells
Authors: Voight Benjamin F.
Published: May 2013

A hormone expressed in liver and fat promotes pancreatic β cell proliferation, cell mass, and glucose tolerance in a mouse model.
Concentration and High Avidity of Pneumococcal Antibodies Persist at Least 4 Years after Immunization with Pneumococcal Conjugate Vaccine in Infancy
Authors: Ekström Nina , Åhman Heidi , Palmu Arto , Grönholm Sinikka , Kilpi Terhi , Käyhty Helena
Published: May 2013

To provide more extensive evidence of long-term effects of vaccination on immunity againstStreptococcus pneumoniae, a follow-up study of the Finnish Otitis Media (FinOM) Vaccine Trial was conducted. One of the objectives was to assess the persistence and avidity of pneumococcal antibodies 4 years after pneumococcal vaccination given in infancy. Children with complete follow-up in the FinOM trial up to 24 months of age were invited to a single visit in their fifth year of life. A blood sample was taken from all children for determination of anticapsular antibody concentrations to vaccine serotypes and avidity of antibodies to three serotypes. Children had been vaccinated at 2, 4, 6, and 12 months of age with 7-valent pneumococcal capsular polysaccharide, CRM197 conjugate vaccine (PCV7), or a control vaccine. Serum IgG antibody concentrations to vaccine serotypes remained significantly higher in children who had received PCV7 than in control children for 4 years after the fourth PCV7 dose. Concentrations of antibodies to frequently carried serotypes (6B and 19F) declined less than those of antibodies to a rarely carried serotype (4), suggesting that natural boosting contributed to antibody persistence. Furthermore, antibody avidity was significantly higher in PCV7 than control vaccine recipients. Four doses of PCV7 given in infancy elicit long-lasting antibody responses with high avidity. (This study has been registered at ClinicalTrials.gov under registration no. NCT00378417.)
Use of Luminex MagPlex Magnetic Microspheres for High-Throughput Spoligotyping of Mycobacterium tuberculosis Isolates in Port-au-Prince, Haiti
Authors: Ocheretina Oksana , Merveille Yves Mary , Mabou Marie-Marcelle , Escuyer Vincent E. , Dunbar Sherry A. , Johnson Warren D. , Pape Jean W. , Fitzgerald Daniel W.
Published: May 2013

Genotyping of
Mycobacterium tuberculosis
strains became indispensable for understanding tuberculosis transmission dynamics and designing measures to combat the disease. Unfortunately, typing involves sophisticated laboratory analysis, is expensive, and requires a high level of technical expertise, which limited its use in the resource-poor countries where the majority of tuberculosis cases occur. Spoligotyping is a PCR-based
M. tuberculosis
complex genotyping method with advantages of technical simplicity, numerical output, and high reproducibility. It is based on the presence or absence of 43 distinct “spacers” separating insertion elements in the direct repeat region of the
M. tuberculosis
genome. The spoligotyping assay involves reverse hybridization of PCR products to the capture spacers attached to nitrocellulose membranes or to microspheres. Here we report modification of the classic 43-spacer method using the new generation of Luminex multiplexing technology with magnetic microspheres. The method was successfully established and validated on strains with known spoligotypes in our laboratory in Haiti. The distribution of spoligotypes determined in a collection of 758 recent
M. tuberculosis
isolates was in accordance with previous data for Haitian isolates in the SITWITWEB international database, which were obtained with the traditional membrane-based method. In the present form, spoligotyping may be suitable as a high-throughput, first-line tool for genotyping of
Mycobacterium tuberculosis
in countries with limited resources.
A Novel Bivalent Vaccine Based on a PB2-Knockout Influenza Virus Protects Mice from Pandemic H1N1 and Highly Pathogenic H5N1 Virus Challenges
Authors: Uraki Ryuta , Kiso Maki , Iwatsuki-Horimoto Kiyoko , Fukuyama Satoshi , Takashita Emi , Ozawa Makoto , Kawaoka Yoshihiro
Published: May 2013

Vaccination is an effective means to protect against influenza virus. Although inactivated and live-attenuated vaccines are currently available, each vaccine has disadvantages (e.g., immunogenicity and safety issues). To overcome these problems, we previously developed a replication-incompetent PB2-knockout (PB2-KO) influenza virus that replicates only in PB2 protein-expressing cells. Here, we generated two PB2-KO viruses whose PB2-coding regions were replaced with the HA genes of either A/California/04/2009 (H1N1pdm09) or A/Vietnam/1203/2004 (H5N1). The resultant viruses comparably, or in some cases more efficiently, induced virus-specific antibodies in the serum, nasal wash, and bronchoalveolar lavage fluid of mice relative to a conventional formalin-inactivated vaccine. Furthermore, mice immunized with these PB2-KO viruses were protected from lethal challenges with not only the backbone virus strain but also strains from which their foreign HAs originated, indicating that PB2-KO viruses with antigenically different HAs could serve as bivalent influenza vaccines.
Lysine Trimethylation of EF-Tu Mimics Platelet-Activating Factor To Initiate Pseudomonas aeruginosa Pneumonia
Authors: Barbier Mariette , Owings Joshua P. , Martínez-Ramos Inmaculada , Damron F. Heath , Gomila Rosa , Blázquez Jesús , Goldberg Joanna B. , Albertí Sebastián
Published: May 2013

Pseudomonas aeruginosa
is a ubiquitous microorganism and the most common Gram-negative bacterium associated with nosocomial pneumonia, which is a leading cause of mortality among critically ill patients. Although many virulence factors have been identified in this pathogen, little is known about the bacterial components required to initiate infection in the host. Here, we identified a unique trimethyl lysine posttranslational modification of elongation factor Tu as a previously unrecognized bacterial ligand involved in early host colonization by
P. aeruginosa
. This modification is carried out by a novel methyltransferase, here named elongation factor Tu-modifying enzyme, resulting in a motif that is a structural mimic of the phosphorylcholine present in platelet-activating factor. This novel motif mediates bacterial attachment to airway respiratory cells through platelet-activating factor receptor and is a major virulence factor, expression of which is a prerequisite to pneumonia in a murine model of respiratory infection.

IMPORTANCE
Phosphorylcholine is an interesting molecule from the microbiological and immunological point of view. It is a crucial epitope for the virulence of many important human pathogens, modulates the host immune response, and is involved in a wide number of processes ranging from allergy to inflammation. Our current work identifies a novel bacterial surface epitope structurally and functionally similar to phosphorylcholine. This novel epitope is crucial for initial colonization of the respiratory tract by
Pseudomonas aeruginosa
and for development of pneumonia. This opens up new targets for the development of novel drugs to prevent
P. aeruginosa
pneumonia, which is particularly important given the frequent emergence of multidrug-resistant strains.
Keto-Mycolic Acid-Dependent Pellicle Formation Confers Tolerance to Drug-Sensitive Mycobacterium tuberculosis
Authors: Sambandan Dhinakaran , Dao Dee N. , Weinrick Brian C. , Vilchèze Catherine , Gurcha Sudagar S. , Ojha Anil , Kremer Laurent , Besra Gurdyal S. , Hatfull Graham F. , Jacobs William R.
Published: May 2013

The chronic nature of tuberculosis (TB), its requirement of long duration of treatment, its ability to evade immune intervention, and its propensity to relapse after drug treatment is discontinued are reminiscent of other chronic, biofilm-associated bacterial diseases. Historically,
Mycobacterium tuberculosis
was grown as a pellicle, a biofilm-like structure, at the liquid-air interface in a variety of synthetic media. Notably, the most widely administered human vaccine, BCG, is grown as a pellicle for vaccine production. However, the molecular requirements for this growth remain ill defined. Here, we demonstrate that keto-mycolic acids (keto-MA) are essential for pellicle growth, and mutants lacking in or depleted of this MA species are unable to form a pellicle. We investigated the role of the pellicle biofilm in the reduction of antibiotic sensitivity known as drug tolerance using the pellicle-defective Δ
mmaA4
mutant strain. We discovered that the Δ
mmaA4
mutant, which is both pellicle defective and highly sensitive to rifampicin (RIF) under planktonic growth, when incorporated within the wild-type pellicle biofilm, was protected from the bactericidal activity of RIF. The observation that growth within the
M. tuberculosis
pellicle biofilm can confer drug tolerance to a drug-hypersensitive strain suggests that identifying molecular requirements for pellicle growth could lead to development of novel interventions against mycobacterial infections. Our findings also suggest that a class of drugs that can disrupt
M. tuberculosis
biofilm formation, when used in conjunction with conventional antibiotics, has the potential to overcome drug tolerance.

IMPORTANCE
Two of the most important questions in tuberculosis (TB) research are (i) how does
Mycobacterium tuberculosis
persist in the human host for decades in the face of an active immune response and (ii) why does it take six months and four drugs to treat uncomplicated TB. Both these aspects of
M. tuberculosis
biology are reminiscent of infections caused by organisms capable of forming biofilms.
M. tuberculosis
is capable of growing as a biofilm-like structure called the pellicle. In this study, we demonstrate that a specific cell wall component, keto-mycolic acid, is essential for pellicle growth. We also demonstrate that a strain of
M. tuberculosis
that is both drug sensitive and pellicle defective exhibits commensal behavior and becomes drug tolerant by becoming part of a heterogeneous pellicle, a characteristic of multispecies biofilms. These observations could have important implications for identifying novel pathways for
M. tuberculosis
drug tolerance and the design of new modalities to rapidly treat TB.
Development of sustainable irrigation planning with multi-objective fuzzy linear programming for Ukai–Kakrapar irrigation project, Gujarat, India
Authors: Mirajkar A.B. , Patel P.L.
Published: May 2013

Multi-objective fuzzy linear programming (MOFLP) approach is applied with four conflicting objectives, viz maximization of net benefits, employment generation, minimization of cost of cultivation and maximization of revenue generation from municipal and industrial supplies (M and I), on a water resources project (Ukai), Gujarat, India. The results from the model are reported for the most critical year (90% exceedance probability), critical year (85% exceedance probability), normal year (75% exceedance probability), and wet year (60% exceedance probability) inflow conditions. The degree of satisfaction of the proposed MOFLP model, considering all objectives together, for wet year, normal year, critical year and most critical year are found to be 0.527, 0.515, 0.50, and 0.46 respectively; and corresponding net irrigation benefits for different inflow conditions are computed as 10 611.91 Million Rs, 10 476.67 Million Rs, 8 311.0044 Million Rs, and 6 900.051 Million Rs, respectively. The proposed MOFLP model indicated that probable inflow corresponding to 75% dependability level is marginally sufficient to meet the requirement of the study area, and water availability becomes deficit in the command area for 85% dependability inflow condition. The optimized crop areas from the model, complying with the requirement of existing flood rules, and satisfying relevant conflicting objectives would help the decision makers in sustainable management of water resources in Ukai command area.
Thermochronological constraints on the Eocene exhumation of the Grand Forks complex, British Columbia, based on 40Ar/39Ar and apatite fission track geochronology
Authors: Cubley J.F. , Pattison D.R.M. , Archibald D.A. , Jolivet M.
Published: May 2013

The Grand Forks complex (GFC) is a metamorphic core complex within the composite Shuswap complex in the southern Omineca belt of the Canadian Cordillera. It is juxtaposed against the surrounding low-grade rocks of the pericratonic Quesnel terrane by outward-dipping Eocene normal faults. The GFC attained peak metamorphic conditions of 750–800 °C and 5.5–6.0 kbar (1 kbar = 100 MPa) in the late Paleocene to early Eocene, followed by ∼2.5 kbar of near-isothermal decompression at upper-amphibolite to granulite facies conditions (∼725–750 °C) in the early Eocene. Subsequent low-temperature greenschist-facies exhumation (∼0.7–1.5 kbar) was accommodated by the brittle–ductile Kettle River normal fault (KRF) on the east flank of the complex and the Granby fault (GF) on the west flank. This study presents 16 new 40Ar/39Ar hornblende and biotite dates from the GFC and low-grade rocks in the hanging walls to the KRF and GF. Cooling of the GFC through the closure temperature of hornblende (∼ 530 °C) is constrained to the interval between ∼54 and 51.4 ± 0.5 Ma, whereas cooling through the closure temperature of biotite (∼280 °C) occurred at 51.4 ± 0.2 Ma. In the hanging wall of the KRF, cooling through the closure temperature of hornblende and biotite occurred nearly coevally at 51.7 ± 0.6 Ma and 51.0 ± 1.0 Ma, respectively. Five apatite fission track dates (closure temperature ∼110 °C) from the GFC and adjacent hanging walls are indistinguishable within error, yielding an average age of 34.6 ± 2.0 Ma. The lack of difference in biotite and apatite ages between the GFC and the low-grade hanging wall rocks against which it is juxtaposed suggests no significant movement on the KRF and GF after ca. 51 Ma. Results from this study and a previous study on U–Pb dating of the GFC document rapid cooling of the GFC in excess of 200 °C/Ma in a 4 Ma interval between 55 and 51 Ma (Eocene). This rapid phase of exhumation of the GFC was followed by 15 Ma of slow cooling (∼10 °C/Ma) of the joined GFC and hanging wall between ∼280 °C (biotite closure) and ∼110 °C (apatite closure).
A SELF-CONSISTENT MODEL OF THE BLACK HOLE EVAPORATION
Authors: KAWAI HIKARU , MATSUO YOSHINORI , YOKOKURA YUKI
Published: May 2013

We construct a self-consistent model which describes a black hole from formation to evaporation including the backreaction from the Hawking radiation. In the case where a null shell collapses, at the beginning the evaporation occurs, but it stops eventually, and a horizon and singularity appear. On the other hand, in the generic collapse process of a continuously distributed null matter, the black hole evaporates completely without forming a macroscopically large horizon nor singularity. We also find a stationary solution in the heat bath, which can be regarded as a normal thermodynamic object.
CROSSOVER FROM SPONTANEOUSLY GENERATED COHERENCE TO AUTLER–TOWNES SPLITTING IN THREE-LEVEL ATOMIC SYSTEMS
Authors: DU QIONG , HANG CHAO , HUANG GUOXIANG
Published: May 2013

We investigate spontaneously generated coherence (SGC) and Autler–Townes Splitting (ATS) in various three-level systems. Through detailed analytical calculations on absorption spectrum of probe laser field, we show that in V-type system the SGC can completely eliminate the absorption of the probe field and at the same time significantly reduce the group velocity. By using residue theorem and spectrum decomposition method, we prove that there exists a crossover from SGC to ATS for both cold and warm atoms when the magnitude of SGC is changed. Different contributions of SGC and ATS to probe-field absorption spectrum are clearly clarified in different parameter regions. In addition, our results show that there is no SGC and hence no SGC-ATS crossover in Λ- and Ξ-type systems.
FAILURE MODELING OF CONSTANT FRACTION DISCRIMINATOR USING PHYSICS OF FAILURE APPROACH
Authors: THADURI ADITHYA , VERMA A. K. , GOPIKA V. , GOPINATH RAJESH , KUMAR UDAY
Published: May 2013

Due to several advancements in the technology trends in electronics, the reliability prediction by the constant failure methods and standards no longer provide accurate time to failure. The physics of failure methodology provides a detailed insight on the operation, failure point location and causes of failure for old, existing and newly developed components with consideration of failure mechanisms. Since safety is a major criteria for the nuclear industries, the failure modeling of advanced custom made critical components that exists on signal conditioning module are need to be studied with higher confidence. One of the components, constant fraction discriminator, is the critical part at which the failure phenomenon and modeling by regression is studied in this paper using physics of failure methodology.
SPARE PARTS ESTIMATION FOR MACHINE AVAILABILITY IMPROVEMENT ADDRESSING ITS RELIABILITY AND OPERATING ENVIRONMENT — CASE STUDY
Authors: GHODRATI BEHZAD , AHMADI ALIREZA , GALAR DIEGO
Published: May 2013

Industrial operation cost analysis shows that, in general, maintenance represents a significant proportion of the overall operating costs. Therefore, the improvement of maintenance follows the final goal of any company, namely, to maximize profit. This paper studies spare parts availability, an issue of the maintenance process, which is an important way to improve production through increased availability of functional machinery and subsequent minimization of the total production cost. Spare parts estimation based on machine reliability characteristics and operating environment is performed. The study uses an improved statistical-reliability (S-R) approach which incorporates the system/machine operating environment information in systems reliability analysis. For this purpose, two methods of Poisson process and renewal process are introduced and discussed. The renewal process model uses a multiple regression type of analysis based on Cox's proportional hazards modeling (PHM). The parametric approaches with baseline Weibull hazard functions and time-independent covariates are considered, and the influence of operating environment factors on this model is analyzed. The outputs represent a significant difference in the required spare parts estimation when considering or ignoring the influence of the relevant system operating environment. The difference is significant in the sense of spare parts forecasting and inventory management which can enhance the parts and consequently machine availability, leading to economical operation and savings.