Local hunting and the conservation of large mammals in India.
Hunting by local communities is among the most widespread threats to Indian wildlife, yet, the understanding of its nature, extent, and impacts on wildlife has been poor. We surveyed 2 protected areas--Kudremukha and Nagara-holé--in southern India to assess the impacts of local hunting on large mammals. Detailed interviews with retired and active hunters were employed to describe hunting patterns. Impacts of hunting were assessed by comparing large-mammal abundance in adjacent sites differing in their vulnerability to hunting. In Kudremukha, at least 26 species of mammals were hunted, mostly with guns, at an estimated intensity of 216 hunter-days per month per village. In Nagaraholé, 6 of the 9 focal species of large mammals occurred at significantly lower densities at the heavily hunted site where enforcement capabilities were poorer. Our data underscore the importance of preservationist programs in the conservation of large mammals in a context of extensive local hunting.


Differentiating between descriptive and interpretive phenomenological research approaches.
To provide insight into how descriptive and interpretive phenomenological research approaches can guide nurse researchers during the generation and application of knowledge. Phenomenology is a discipline that investigates people's experiences to reveal what lies 'hidden' in them. It has become a major philosophy and research method in the humanities, human sciences and arts. Phenomenology has transitioned from descriptive phenomenology, which emphasises the 'pure' description of people's experiences, to the 'interpretation' of such experiences, as in hermeneutic phenomenology. However, nurse researchers are still challenged by the epistemological and methodological tenets of these two methods. The data came from relevant online databases and research books. A review of selected peer-reviewed research and discussion papers published between January 1990 and December 2013 was conducted using CINAHL, Science Direct, PubMed and Google Scholar databases. In addition, selected textbooks that addressed phenomenology as a philosophy and as a research methodology were used. Evidence from the literature indicates that most studies following the 'descriptive approach' to research are used to illuminate poorly understood aspects of experiences. In contrast, the 'interpretive/hermeneutic approach' is used to examine contextual features of an experience in relation to other influences such as culture, gender, employment or wellbeing of people or groups experiencing the phenomenon. This allows investigators to arrive at a deeper understanding of the experience, so that caregivers can derive requisite knowledge needed to address such clients' needs. Novice nurse researchers should endeavour to understand phenomenology both as a philosophy and research method. This is vitally important because in-depth understanding of phenomenology ensures that the most appropriate method is chosen to implement a study and to generate knowledge for nursing practice. This paper adds to the current debate on why it is important for nurse researchers to clearly understand phenomenology as a philosophy and research method before embarking on a study. The paper guides novice researchers on key methodological decisions they need to make when using descriptive or interpretive phenomenological research approaches.


Recovery of impaired endothelium-dependent relaxation after fluid-percussion brain injury in cats.
The effect of a moderate level of fluid-percussion brain injury on acetylcholine-induced cerebral arteriolar vasodilation was examined for 12 hours after trauma in anesthetized cats equipped with cranial windows. The cats were then perfused with aldehydes, and the pial arteries were prepared for electron microscopy. Immediately after brain injury, the normal vasodilator response to topical application of acetylcholine was converted to vasoconstriction. By 4 hours after trauma, the ability of small pial arterioles (diameters less than 100 microns) to dilate after acetylcholine application had returned to the pretrauma level and was observed to be normal at both 8 and 12 hours after trauma (p less than 0.05). The vasodilator response of large caliber arterioles (diameters greater than or equal to 100 microns) at 4, 8, and 12 hours after injury was reduced relative to the pretrauma response but was significantly improved relative to their response at 30 minutes after trauma (p less than 0.05). Moreover, the response of large vessels at 4, 8, and 12 hours in injured animals was equal to that observed in noninjured control animals assessed at 4, 8, and 12 hours after window implantation. At 12 hours after injury, the ultrastuctural characteristics of both large and small vessels resembled their preinjury state. These data suggest that the impairment of acetylcholine-induced endothelium-dependent relaxation observed in cats after fluid-percussion brain injury is not irreversible but returns to normal (small arterioles) or exhibits significant recovery (large arterioles) within 4 hours after injury.


AN EXPERIMENTAL STUDY OF THE EFFECT OF CHOLE-CYSTGASTROSTOMY ON GASTRIC ACIDITY.
It has been shown that small amounts of the digestive secretions normally present in the duodenum regurgitate into the stomach following operative anastomosis between the stomach and the upper intestinal tract. As the duodenal contents are alkaline in reaction this reflux is thought by many to result in a decrease in the acidity of the gastric contents. The purpose of the investigations reported here has been to determine the effect of bile on the acid chyme of the stomach. By means of a cholecystgastrostomy with ligation and division of the common bile duct in six dogs the bile was diverted from the duodenum into the stomach. The secretion of gastric juice and the acidity of the gastric contents throughout the period of digestion were followed before and after the anastomoses. For this purpose three of the dogs were provided with Pawlow stomach pouches. In the three remaining animals the test meals were recovered by using apomorphin injections. The results from the two series of experiments agree. They indicate, at least with a diet of meat and water, that bile when it is present in the stomach throughout the course of digestion has no appreciable effect on the acidity of the gastric contents. While the anastomosis of the gall bladder to the stomach occasioned some temporary anorexia and vomiting in two of the dogs, the four remaining animals bore the operation well. Three or four weeks subsequent to the operation the digestion and the nutrition appeared normal in each instance. Postmortem examinations revealed no pathological changes in the gastric mucosa.


Autologous tumor-specific cytotoxic T lymphocytes in the infiltrate of human metastatic melanomas. Activation by interleukin 2 and autologous tumor cells, and involvement of the T cell receptor.
TIL from metastatic melanoma proliferated by greater than 1,000-fold (840-3,675, mean 1,543) after 6 wk in culture of mixtures of TIL and tumor cells with rIL-2 alone. Cytolysis was restricted to autologous tumor cells. CD8+ T cells were the predominant population of TIL before and after expansion, and were primarily responsible for autologous tumor-specific CTL activity. No other rIL-2-activated lymphocytes from peripheral blood, lymph nodes with melanoma metastasis, or TIL from sarcoma or renal cell carcinoma had autologous tumor-specific CTL activity. There were few or no CD16+ NK cells in TIL from metastatic melanoma before or after incubation with rIL-2, respectively. However, TIL from sarcoma or renal cell carcinoma contained a substantial proportion of CD3-CD16+ NK cells, which increased in number in culture with rIL-2. Purified CD16+ NK cells as well as CD3+CD16- T cells from rIL-2-activated TIL of renal cell carcinoma displayed MHC-nonrestricted cytotoxicity. At the clonal level as determined by limiting dilution, 8 of 10 clones from melanoma TIL displayed cytotoxicity restricted to autologous tumor cells, while all 13 clones from renal cancer TIL equally lysed autologous and allogeneic tumor cells. Anti-T cell receptor (TCR)-alpha/beta(WT31) mAb as well as anti-CD3 mAb inhibited autologous melanoma cell-specific CTL activity mediated by rIL-2-activated TIL at the effector phase. These two mAbs also inhibited rIL-2-dependent proliferation of these TIL when added to the culture. Pretreatment of fresh melanoma cells with mAb to MHC antigens followed by washing inhibited specific CTL activity. These results suggest that both TCR-alpha/beta on effector TIL and MHC antigens on fresh tumor cells are involved in the specific immune-recognition. After reaching maximum propagation, TIL from metastatic melanoma responded poorly to rIL-2 alone. However, stimulation with fresh autologous melanoma cells restored both CTL activity and proliferation in response to rIL-2. The latter is associated with IL-2 receptor (Tac antigen) expression on the surface. These results indicate that TIL from metastatic melanomas may have unique characteristics different from lymphocytes obtained from the other sources, and may contain precursor CTL sensitized in vivo to autologous tumor cells, and thus can be propagated in larger numbers with rIL-2 alone while retaining autologous tumor-specific CTL activity.


Study of novel mechano-chemical activation process of red mud to optimize nitrate removal from water.
Red mud (RM) is the industrial waste of alumina production and causes serious environmental risks. In this paper, a novel activation procedure for RM (mechano-chemical processing) is proposed in order to improve the nitrate adsorption from water. High-energy milling and acidification were selected as mechanical and chemical activation methods, respectively. Synthesized samples of adsorbent were produced considering two parameters of activation: acid concentrations and acidification time in two selected milling times. Optimization of the activation process was based on nitrate removal from a stock solution. Experimental data were analyzed with two-way analysis of variance and Kruskal-Wallis methods to verify and discover the accuracy and probable errors. Best conditions (acceptable removal percentage > 75) were 17.6% w/w for acid concentrate and 19.9 minutes for acidification time in 8 hours for milling time. A direct relationship between increase in nitrate removal and increasing the acid concentration and acidification time was observed. The adsorption isotherms were studied and compared with other nitrate adsorbents. Characterization tests (X-ray fluorescence, X-ray diffraction, Fourier transform infrared spectrophotometry, dynamic light scattering, surface area analysis and scanning electron microscopy) were conducted for both raw and activated adsorbents. Results showed noticeable superiority in characteristics after activation: higher specific area and porosity, lower particle size and lower agglomeration in structure.


Free body analysis, beam mechanics, and finite element modeling of the mandible of Alligator mississippiensis.
The mechanical behavior of mammalian mandibles is well-studied, but a comprehensive biomechanical analysis (incorporating detailed muscle architecture, accurate material properties, and three-dimensional mechanical behavior) of an extant archosaur mandible has never been carried out. This makes it unclear how closely models of extant and extinct archosaur mandibles reflect reality and prevents comparisons of structure-function relationships in mammalian and archosaur mandibles. We tested hypotheses regarding the mechanical behavior of the mandible of Alligator mississippiensis by analyzing reaction forces and bending, shear, and torsional stress regimes in six models of varying complexity. Models included free body analysis using basic lever arm mechanics, 2D and 3D beam models, and three high-resolution finite element models of the Alligator mandible, incorporating, respectively, isotropic bone without sutures, anisotropic bone with sutures, and anisotropic bone with sutures and contact between the mandible and the pterygoid flange. Compared with the beam models, the Alligator finite element models exhibited less spatial variability in dorsoventral bending and sagittal shear stress, as well as lower peak values for these stresses, suggesting that Alligator mandibular morphology is in part designed to reduce these stresses during biting. However, the Alligator models exhibited greater variability in the distribution of mediolateral and torsional stresses than the beam models. Incorporating anisotropic bone material properties and sutures into the model reduced dorsoventral and torsional stresses within the mandible, but led to elevated mediolateral stresses. These mediolateral stresses were mitigated by the addition of a pterygoid-mandibular contact, suggesting important contributions from, and trade-offs between, material properties and external constraints in Alligator mandible design. Our results suggest that beam modeling does not accurately represent the mechanical behavior of the Alligator mandible, including important performance metrics such as magnitude and orientation of reaction forces, and mediolateral bending and torsional stress distributions. J.Morphol. 2011. © 2011 Wiley-Liss, Inc.


Structure Property Analysis of the Solution and Solid-State Properties of Bistable Photochromic Hydrazones.
The development of new photochromic compounds and the optimization of their photophysical and switching properties are prerequisites for accessing new functions and opportunities that are not possible with currently available systems. To this end we recently developed a new bistable hydrazone switch that undergoes efficient photoswitching and emission ON/OFF toggling in both solution and solid-state. Here, we present a systematic structure-property analysis using a family of hydrazones and show how their properties, including activation wavelengths, photostationary states (PSSs), photoisomerization quantum yields, thermal half-lives (τ1/2), and solution/solid-state fluorescence characteristics vary as a function of electron donating (EDG) and/or withdrawing (EWG) substituents. These studies resulted in the red-shifting of the absorption profiles of the Z and E isomers of the switches, while maintaining excellent PSSs in almost all of the compounds. The introduction of para-NMe2 and/or para-NO2 groups improved the photoisomerization quantum yields, and the extremely long thermal half-lives (tens to thousands of years) were maintained in most cases, even in a push-pull system, which can be activated solely with visible light. Hydrazones bearing EDGs at the stator phenyl group are an exception and show up to 6 orders of magnitude acceleration in τ1/2 (i.e., days) because of a change in the isomerization mechanism. Moreover, we discovered that a para-NMe2 group is required to have reasonable fluorescence quantum yields in solution and that rigidification enhances the emission in the solid-state. Finally, X-ray crystallography analysis showed that the switching process is more efficient in the solid-state when the hydrazone is loosely packed.


Norms and practices within marriage which shape gender roles, HIV/AIDS risk and risk reduction strategies in Cabo Delgado, Mozambique.
Despite increasing HIV/AIDS rates among married individuals, minimal research has been conducted on how men and women respond to risk in a marriage. This paper examines strategies used by married individuals to combat HIV/AIDS risk against prevailing gender norms. Qualitative data were gathered in four villages of Cabo Delgado province, Mozambique. Group discussions were held with 160 men and women to explore gender norms, HIV/AIDS knowledge and risk determinants. From the group discussions, 29 individuals were selected for further in-depth interviews to explore relationships between gender norms and risk reduction efforts within marriages. Findings illustrate how infidelity and social limitations placed on condom use not only increase HIV/AIDS risk but also entrench gender disparities. Although power differences between genders can make it difficult to negotiate safe sex, men and women are taking measures to reduce perceived HIV/AIDS risk in their marriage. Married men are reconstructing norms and taking responsibility to protect their family from HIV/AIDS by remaining faithful. For women, responses to HIV/AIDS risk in a marriage are more closely related to their ability to generate an income. Financially dependent women tend to leave a risky marriage altogether in contrast to financially autonomous women who will negotiate condom use with their husband. Factors such as experience with a risky partner, the desire to maintain a good social standing, fear of HIV/AIDS acquisition and parental guidance and support influence men and women to reduce perceived HIV/AIDS risk, despite constraining gender norms and power imbalances in a marriage. Nuanced understandings of the ways in which men and women are already taking measures to decrease noted HIV/AIDS risk, despite gender norms that make this a challenge, should be incorporated into localised responses.


Effects of CO(2) enrichment on photosynthesis, growth, and nitrogen metabolism of the seagrass Zostera noltii.
Seagrass ecosystems are expected to benefit from the global increase in CO(2) in the ocean because the photosynthetic rate of these plants may be C(i)-limited at the current CO(2) level. As well, it is expected that lower external pH will facilitate the nitrate uptake of seagrasses if nitrate is cotransported with H(+) across the membrane as in terrestrial plants. Here, we investigate the effects of CO(2) enrichment on both carbon and nitrogen metabolism of the seagrass Zostera noltii in a mesocosm experiment where plants were exposed for 5 months to two experimental CO(2) concentrations (360 and 700 ppm). Both the maximum photosynthetic rate (P(m)) and photosynthetic efficiency (α) were higher (1.3- and 4.1-fold, respectively) in plants exposed to CO(2)-enriched conditions. On the other hand, no significant effects of CO(2) enrichment on leaf growth rates were observed, probably due to nitrogen limitation as revealed by the low nitrogen content of leaves. The leaf ammonium uptake rate and glutamine synthetase activity were not significantly affected by increased CO(2) concentrations. On the other hand, the leaf nitrate uptake rate of plants exposed to CO(2)-enriched conditions was fourfold lower than the uptake of plants exposed to current CO(2) level, suggesting that in the seagrass Z. noltii nitrate is not cotransported with H(+) as in terrestrial plants. In contrast, the activity of nitrate reductase was threefold higher in plant leaves grown at high-CO(2) concentrations. Our results suggest that the global effects of CO(2) on seagrass production may be spatially heterogeneous and depend on the specific nitrogen availability of each system. Under a CO(2) increase scenario, the natural levels of nutrients will probably become limiting for Z. noltii. This potential limitation becomes more relevant because the expected positive effect of CO(2) increase on nitrate uptake rate was not confirmed.


As-Projective-As-Possible Image Stitching with Moving DLT.
The success of commercial image stitching tools often leads to the impression that image stitching is a "solved problem". The reality, however, is that many tools give unconvincing results when the input photos violate fairly restrictive imaging assumptions; the main two being that the photos correspond to views that differ purely by rotation, or that the imaged scene is effectively planar. Such assumptions underpin the usage of 2D projective transforms or homographies to align photos. In the hands of the casual user, such conditions are often violated, yielding misalignment artifacts or "ghosting" in the results. Accordingly, many existing image stitching tools depend critically on post-processing routines to conceal ghosting. In this paper, we propose a novel estimation technique called Moving Direct Linear Transformation (Moving DLT) that is able to tweak or fine-tune the projective warp to accommodate the deviations of the input data from the idealized conditions. This produces as-projective-as-possible image alignment that significantly reduces ghosting without compromising the geometric realism of perspective image stitching. Our technique thus lessens the dependency on potentially expensive postprocessing algorithms. In addition, we describe how multiple as-projective-as-possible warps can be simultaneously refined via bundle adjustment to accurately align multiple images for large panorama creation.


Toward understanding the impact of artificial intelligence on labor.
Rapid advances in artificial intelligence (AI) and automation technologies have the potential to significantly disrupt labor markets. While AI and automation can augment the productivity of some workers, they can replace the work done by others and will likely transform almost all occupations at least to some degree. Rising automation is happening in a period of growing economic inequality, raising fears of mass technological unemployment and a renewed call for policy efforts to address the consequences of technological change. In this paper we discuss the barriers that inhibit scientists from measuring the effects of AI and automation on the future of work. These barriers include the lack of high-quality data about the nature of work (e.g., the dynamic requirements of occupations), lack of empirically informed models of key microlevel processes (e.g., skill substitution and human-machine complementarity), and insufficient understanding of how cognitive technologies interact with broader economic dynamics and institutional mechanisms (e.g., urban migration and international trade policy). Overcoming these barriers requires improvements in the longitudinal and spatial resolution of data, as well as refinements to data on workplace skills. These improvements will enable multidisciplinary research to quantitatively monitor and predict the complex evolution of work in tandem with technological progress. Finally, given the fundamental uncertainty in predicting technological change, we recommend developing a decision framework that focuses on resilience to unexpected scenarios in addition to general equilibrium behavior.


Systematic protein-protein interaction and pathway analyses in the idiopathic inflammatory myopathies.
The idiopathic inflammatory myopathies (IIM) are autoimmune diseases characterised by acquired proximal muscle weakness, inflammatory cell infiltrates in muscle and myositis-specific/associated autoantibodies. It is unclear which pathways are involved in IIM, and the functional relationship between autoantibody targets has not been systematically explored. Protein-protein interaction and pathway analyses were conducted to identify pathways relevant to disease, using autoantibody targets and gene products of IIM-associated single nucleotide polymorphism (SNP) loci. Protein-protein interactions were analysed using Disease Association Protein-Protein Link Evaluator (DAPPLE). Gene ontology and pathway analyses were conducted using Database for Annotation Visualisation and Integrated Discovery (DAVID) and Gene Relationships Across Implicated Loci (GRAIL). Analyses were undertaken including the targets of published autoantibodies, significant and suggestive SNPs from an IIM association study and autoantibody targets plus SNPs combined. The protein-protein interaction networks formed by autoantibody targets and associated SNPs showed significant direct and/or indirect connectivity (p < 0.05). Autoantibody targets plus associated SNPs combined resulted in more significant indirect and common interactor connectivity, suggesting autoantibody targets and proteins encoded by IIM-associated loci may be involved in common pathways. Tumour necrosis factor receptor-associated factor 6 (TRAF6) was identified as a hub protein, and UBE3B, HSPA1A, HSPA1B and PSMD3 also were identified as genes with significant connectivity. Pathway analysis identified that autoantibody targets and associated SNP regions are significantly interconnected (p < 0.01), and confirmed autoantibody target involvement in translational and post-translational processes. 'Ubiquitin' was the only keyword strongly linking significant genes across regions in all three GRAIL analyses of autoantibody targets and IIM-associated SNPs. Autoantibody targets and IIM-associated loci show significant connectivity and inter-relatedness, and identify several key genes and pathways in IIM pathogenesis, possibly mediated via the ubiquitination pathway.


Factors associated with persistent colonisation with methicillin-resistant Staphylococcus aureus.
We conducted a prospective cohort study between 1 January 2010 and 31 December 2012 at five adult and paediatric academic medical centres to identify factors associated with persistent methicillin-resistant Staphylococcus aureus (MRSA) colonisation. Adults and children presenting to ambulatory settings with a MRSA skin and soft tissue infection (i.e. index cases), along with household members, performed self-sampling for MRSA colonisation every 2 weeks for 6 months. Clearance of colonisation was defined as two consecutive negative sampling periods. Subjects without clearance by the end of the study were considered persistently colonised and compared with those who cleared colonisation. Of 243 index cases, 48 (19·8%) had persistent colonisation and 110 (45·3%) cleared colonisation without recurrence. Persistent colonisation was associated with white race (odds ratio (OR), 4·90; 95% confidence interval (CI), 1·38-17·40), prior MRSA infection (OR 3·59; 95% CI 1·05-12·35), colonisation of multiple sites (OR 32·7; 95% CI 6·7-159·3). Conversely, subjects with persistent colonisation were less likely to have been treated with clindamycin (OR 0·28; 95% CI 0·08-0·99). Colonisation at multiple sites is a risk factor for persistent colonisation and may require more targeted decolonisation efforts. The specific effect of clindamycin on MRSA colonisation needs to be elucidated.


Feasibility of Implementing the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events in a Multicenter Trial: NCCTG N1048.
Purpose The US National Cancer Institute (NCI) Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) was developed to enable patient reporting of symptomatic adverse events in oncology clinical research. This study was designed to assess the feasibility and resource requirements associated with implementing PRO-CTCAE in a multicenter trial. Methods Patients with locally advanced rectal cancer enrolled in the National Cancer Institute-sponsored North Central Cancer Treatment Group (Alliance) Preoperative Radiation or Selective Preoperative Radiation and Evaluation before Chemotherapy and Total Mesorectal Excision trial were asked to self-report 30 PRO-CTCAE items weekly from home during preoperative therapy, and every 6 months after surgery, via either the Web or an automated telephone system. If participants did not self-report within 3 days, a central coordinator called them to complete the items. Compliance was defined as the proportion of participants who completed PRO-CTCAE assessments at expected time points. Results The prespecified PRO-CTCAE analysis was conducted after the 500th patient completed the 6-month follow-up (median age, 56 years; 33% female; 12% nonwhite; 43% high school education or less; 5% Spanish speaking), across 165 sites. PRO-CTCAE was reported by participants at 4,491 of 4,882 expected preoperative time points (92.0% compliance), of which 3,771 (77.2%) were self-reported by participants and 720 (14.7%) were collected via central coordinator backup. Compliance at 6-month post-treatment follow-up was 333 of 468 (71.2%), with 122 (26.1%) via backup. Site research associates spent a median of 15 minutes on PRO-CTCAE work for each patient visit. Work by a central coordinator required a 50% time commitment. Conclusion Home-based reporting of PRO-CTCAE in a multicenter trial is feasible, with high patient compliance and low site administrative requirements. PRO-CTCAE data capture is improved through centralized backup calls.


Anti-proliferative effects of lichen-derived inhibitors of 5-lipoxygenase on malignant cell-lines and mitogen-stimulated lymphocytes.
Several lichen species have been used traditionally as medicinal plants. It has previously been shown that two low-molecular-weight lichen metabolites, lobaric acid isolated from Stereocaulon alpinum Laur. and protolichesterinic acid isolated from Cetraria islandica L. (Ach.), have in-vitro inhibitory effects on arachidonate 5-lipoxygenase. We have studied the effects of these compounds on cultured cells from man, including three malignant cell-lines (T-47D and ZR-75-1 from breast carcinomas and K-562 from erythro-leukaemia), as well as normal skin fibroblasts and peripheral blood lymphocytes. Both test substances caused a significant reduction in DNA synthesis, as measured by thymidine uptake, in all three malignant cell-lines; the dose inducing 50% of maximum inhibition (ED50) was between 1.1 and 24.6 microg mL(-1) for protolichesterinic acid and between 14.5 and 44.7 microg mL(-1) for lobaric acid. The breast-cancer cell-lines were more sensitive than K-562. The proliferative response of mitogen-stimulated lymphocytes was inhibited with a mean ED50 of 8.4 microg mL(-1) and 24.5 microg mL(-1) for protolichesterinic acid and lobaric acid, respectively. These concentrations are of the same order of magnitude as the IC50 values in the 5-lipoxygenase assay. Significant cell death (assessed by the MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-( 4-sulfophenyl)-2H-tetrazolium) assay and trypan blue exclusion) occurred in the three malignant cell-lines at protolichesterinic acid and lobaric acid concentrations above 20 and 30 microg mL(-1), respectively. In K-562 morphological changes consistent with apoptosis were detected. Up to 38% cell death was observed at 20 microg mL(-1) for protolichesterinic acid and 15 microg mL(-1) for lobaric acid in mitogen-stimulated lymphocytes but unstimulated lymphocytes were clearly less sensitive. In contrast, the DNA synthesis, proliferation and survival of normal skin fibroblasts were not affected at doses up to 20 microg mL(-1) for protolichesterinic acid and 30 microg mL(-1) for lobaric acid. We conclude that the anti-proliferative and cytotoxic effects observed might be related to the 5-lipoxygenase inhibitory activity of protolichesterinic acid and lobaric acid. These results open up the opportunity for future studies of these lichen metabolites with regard to their anti-tumour and anti-inflammatory properties.


Knowledge apartheid in disaster risk management discourse: Is marrying indigenous and scientific knowledge the missing link?
Indigenous knowledge (IK) is a key component of disaster risk management (DRM) and development planning, yet it is often overlooked, with practitioners preferring to use scientific knowledge. Critics of IK have termed it archaic, primitive, a constraint to development and inferior to scientific knowledge, which has contributed to its widespread marginalisation. However, smallholder farmers in rural Zimbabwe have utilised IK for generations, especially in predicting rainfall patterns and managing drought conditions, showing that IK can be a useful tool in DRM. This article presents findings from research on drought vulnerability and coping conducted in Zimbabwe's Buhera and Chikomba districts in 2009, particularly relating to utilisation of IK in smallholder farming communities, and argues that unless IK is documented and preserved, its marginalisation will persist. The research followed a mixed-methods approach whereby both quantitative and qualitative data were collected and analysed. Whilst smallholder respondents were randomly selected for household surveys, snowball sampling was employed for key informant interviews. Respondents indicated that they utilised some indigenous rainfall pattern predictions gained from observing and interpreting plant and animal behaviour. Some cultural practices that were critical to development and utilisation of certain IK were also threatened with extinction. The article argues for 'marrying' IK and scientific knowledge, in the hope that the two will offset each other's weaknesses, resulting in some kind of hybrid knowledge that will be critical for promoting sustainable agricultural production in Zimbabwe. However, this is not for disregard the challenges associated with knowledge hybridisation, as these two types of knowledge are grounded on differing foundations.


Avian influenza A(H10N7) virus involvement in mass mortality of harbour seals (Phoca vitulina) in Sweden, March through October 2014.
We provide the first scientific report of influenza A virus involvement in a mass mortality event among harbour seals (Phoca vitulina) off the west coast of Sweden. Avian influenza A (H10N7) virus was detected in the lungs of two affected animals. This subtype has not been reported in seals to date, nor has influenza A-associated mortality been reported in seals in Europe. Circulation of avian influenza viruses in mammals may have implications for public health.


Maternal treatment of rats with the new pyridoindole antioxidant during pregnacy and lactation resulting in improved offspring hippocampal resistance to ischemia in vitro.
Damage to the developing brain may be caused by maternal environment, nutritional deficiencies, failure of protective mechanisms, etc. Further, the developing brain may be damaged by intrauterine ischemia or by ischemia in newborns complicated by perinatal asphyxia. There is an effort to find agents with neuroprotective effect on the developing brain. The aim was to study the effect of the new pyridoindole antioxidant SMe1EC2 on the resistance of offspring hippocampus exposed to ischemia in vitro after treatment of mothers. The electrically evoked responses were determined by extracellular recording from offspring hippocampal slices. The effect of oral treatment of rats with SMe1EC2 over 18 consecutive days, from day 15 of gestation to day 10 post partum (PP) was analyzed in the model of ischemia in vitro measured on the hippocampus of 21-day-old pups, with focus on neuronal function recovery in reoxygenation. Increased recovery of neuronal response was found at the end of 20-min reoxygenation in offspring hippocampal slices exposed to 10-min hypoxia/hypoglycemia from rats whose mothers were treated with the dose of 50 and 250 mg/kg of SMe1EC2, compared to control offspring slices (mothers received vehicle over the same time). The increased offspring hippocampus resistance to hypoxia/hypoglycemia due to 18-day maternal treatment with SMe1EC2 might have been obtained via the transplacental way as well as in the neonatal period via breast milk, skin and saliva. The manifested neuroprotective effect of SMe1EC2 on the developing brain might find exploitation during risk pregnancy and delivery.


Evaluation of chronic atelectasis in children using chest computed tomography and bronchoscopy.
A heterogeneous group of 11 children with atelectasis persisting longer than one month were investigated for the causes using chest computed tomography and fiberoptic bronchoscope. Four young infants had right upper lobe (RUL) posterior segmental atelectasis simulating RUL lobar collapse in plain chest films; all had only two visible segmental bronchi by bronchoscopic examination. Intraluminal obstruction in the central airway was not a common cause of pediatric chronic atelectasis in this small series of patients. Only one obstructive atelectasis caused by dilated pulmonary arteries was detected in this study. Two patients with pre-existing neuromuscular diseases showed multiple atelectasis. The atelectatic lobes do not spontaneously re-inflate following flexible bronchoscopy. Investigations involving a larger number of cases are needed to substantiate the etiologies and to guide specific therapy for those children with chronic atelectasis.


Echocardiographic and biochemical analysis of cardiac function and injury among female amateur runners post-marathon.
Numerous studies with male amateur runners have determined negative changes in their cardiac function/of their myocard following long endurance loads. This study aims to examine such potential changes in women, specifically, after running a marathon. A total of 18 female amateur runners (39.5 ± 10.5 years) were examined before (T1), immediately after (T2) and 24 h post-marathon (T3). An echocardiography was performed using Tissue Doppler (TD) imaging. In addition, the concentration of cardiac troponin T (cTnT) and the activity of the myocardial muscle creatine kinase (CK-MB) were determined at T1 and T2. The echocardiographic parameters revealed impairment of the diastolic function, without, however, documenting a diastolic dysfunction (in accordance with the classification of Nagueh (J Am Soc Echocardiogr, 22:107-33, 2009)). The ratio of blood flow velocity through the mitral valve during early versus late diastole (MV E/A ratio), for example, decreased. The values measured at T3 were similar to those measured at T1. The ratio of early transmitral diastolic filling velocity and of the transmitral diastolic filling velocity by TD imaging (MV E/E') did not indicate any change from T1 to T2, but a significant increase at T3 (in comparison with T1). The systolic function (measured by the left ventricular ejection fraction) did not change significantly. The cTnT concentration and CK-MB activity were significantly higher in T2 than in T1. The data collected does not provide any solid evidence of pathological changes in the cardiac function of female amateur runners post-marathon, although the lab values indicate a strongly increased myocardial stimulation.


Magnetic orientation of nontronite clay in aqueous dispersions and its effect on water diffusion.
The diffusion rate of water in dilute clay dispersions depends on particle concentration, size, shape, aggregation and water-particle interactions. As nontronite clay particles magnetically align parallel to the magnetic field, directional self-diffusion anisotropy can be created within such dispersion. Here we study water diffusion in exfoliated nontronite clay dispersions by diffusion NMR and time-dependant 1H-NMR-imaging profiles. The dispersion clay concentration was varied between 0.3 and 0.7 vol%. After magnetic alignment of the clay particles in these dispersions a maximum difference of 20% was measured between the parallel and perpendicular self-diffusion coefficients in the dispersion with 0.7 vol% clay. A method was developed to measure water diffusion within the dispersion in the absence of a magnetic field (random clay orientation) as this is not possible with standard diffusion NMR. However, no significant difference in self-diffusion coefficient between random and aligned dispersions could be observed.


Intravitreal anti-vascular endothelial growth factor for choroidal neovascularization in ocular histoplasmosis.
To report eight cases of long-term successful treatment of choroidal neovascularization because of ocular histoplasmosis syndrome with intravitreal anti-vascular endothelial growth factor agents. Retrospective case series. This article reviewed the course of eight eyes in seven patients who underwent intravitreal injection of bevacizumab and/or ranibizumab for treatment of choroidal neovascularization secondary to ocular histoplasmosis syndrome. Outcomes were assessed using pre- and post-anti-vascular endothelial growth factor visual acuities. Eight eyes in seven patients were found to have new ocular histoplasmosis syndrome-associated subfoveal choroidal neovascularization lesions, as evidenced on clinical examination, fluorescein angiography, and optical coherence tomography. Intravitreal anti-vascular endothelial growth factor injections were used as initial or early treatment with successful resolution of the choroidal neovascularization lesions in most cases. Mean visual acuity improved from 20/60 to 20/47 over an average of 121.4 weeks. Either bevacizumab or ranibizumab was administered with an average of 2.6 injections per year of follow-up. Three eyes (37.5%) experienced a gain in visual acuity with a mean increase of 7.7 lines, 1 eye (12.5%) experienced no change, and 2 eyes (25%) experienced a loss of visual acuity of 2 or more lines. Six eyes (75%) were able to avoid mild visual loss (2 lines or less). Intravitreal anti-vascular endothelial growth factor agents may successfully treat or at least stabilize neovascular complications of ocular histoplasmosis syndrome when used as a first-line treatment.


Infection and vaccine-induced neutralizing antibody responses to the SARS-CoV-2 B.1.617.1 variant.
SARS-CoV-2 has caused a devastating global pandemic. The recent emergence of SARS-CoV-2 variants that are less sensitive to neutralization by convalescent sera or vaccine-induced neutralizing antibody responses has raised concerns. A second wave of SARS-CoV-2 infections in India is leading to the expansion of SARS-CoV-2 variants. The B.1.617.1 variant has rapidly spread throughout India and to several countries throughout the world. In this study, using a live virus assay, we describe the neutralizing antibody response to the B.1.617.1 variant in serum from infected and vaccinated individuals. We found that the B.1.617.1 variant is 6.8-fold more resistant to neutralization by sera from COVID-19 convalescent and Moderna and Pfizer vaccinated individuals. Despite this, a majority of the sera from convalescent individuals and all sera from vaccinated individuals were still able to neutralize the B.1.617.1 variant. This suggests that protective immunity by the mRNA vaccines tested here are likely retained against the B.1.617.1 variant. As the B.1.617.1 variant continues to evolve, it will be important to monitor how additional mutations within the spike impact antibody resistance, viral transmission and vaccine efficacy.


Spatial normalization improves the quality of genotype calling for Affymetrix SNP 6.0 arrays.
Microarray measurements are susceptible to a variety of experimental artifacts, some of which give rise to systematic biases that are spatially dependent in a unique way on each chip. It is likely that such artifacts affect many SNP arrays, but the normalization methods used in currently available genotyping algorithms make no attempt at spatial bias correction. Here, we propose an effective single-chip spatial bias removal procedure for Affymetrix 6.0 SNP arrays or platforms with similar design features. This procedure deals with both extreme and subtle biases and is intended to be applied before standard genotype calling algorithms. Application of the spatial bias adjustments on HapMap samples resulted in higher genotype call rates with equal or even better accuracy for thousands of SNPs. Consequently the normalization procedure is expected to lead to more meaningful biological inferences and could be valuable for genome-wide SNP analysis. Spatial normalization can potentially rescue thousands of SNPs in a genetic study at the small cost of computational time. The approach is implemented in R and available from the authors upon request.


Acute aquatic treadmill exercise improves gait and pain in people with knee osteoarthritis.
To examine the acute effects of aquatic and land treadmill exercise on gait kinematics as well as the level of disease-specific and movement-related pain for individuals with osteoarthritis. Quasi-experimental crossover design. Biomechanics laboratory. Participants (N=14; age, 43-64y) diagnosed with osteoarthritis at the knee (n=12), osteoarthritis at the knee and ankle (n=1), or osteoarthritis at the knee and hip (n=1). Participants performed 3 exercise sessions separated by at least 24 hours in 1 week for each mode of exercise (aquatic treadmill and land treadmill). Gait kinematics and pain were measured before and after each intervention. The angular velocity gain score during stance for left knee extension was improved by 38% after aquatic treadmill exercise (P=.004). Similarly, during swing, the gain scores for angular velocity were also greater for left knee internal rotation and extension by 65% and 20%, respectively (P=.004, P=.008, respectively). During stance, the joint angle gain score for left hip flexion was 7.23% greater after land exercise (P=.007). During swing, the angular velocity gain score for right hip extension was significantly greater for aquatic exercise by 28% (P=.01). Only the joint angle gain score for left ankle abduction during stance was significantly higher after land exercise (4.72%, P=.003). No other joint angle gain scores for either stance or swing were significantly different for either condition (P=.06-.96). Perceived pain was 100% greater after land than aquatic treadmill exercise (P=.02). Step rate and step length were not different between conditions (P=.31-.92). An acute training period on an aquatic treadmill positively influenced joint angular velocity and arthritis-related joint pain. Acute aquatic treadmill exercise may be useful as a conservative treatment to improve angular speed of the lower-extremity joints and pain related to osteoarthritis.


Telomerase RNA biogenesis involves sequential binding by Sm and Lsm complexes.
In most eukaryotes, the progressive loss of chromosome-terminal DNA sequences is counteracted by the enzyme telomerase, a reverse transcriptase that uses part of an RNA subunit as template to synthesize telomeric repeats. Many cancer cells express high telomerase activity, and mutations in telomerase subunits are associated with degenerative syndromes including dyskeratosis congenita and aplastic anaemia. The therapeutic value of altering telomerase activity thus provides ample impetus to study the biogenesis and regulation of this enzyme in human cells and model systems. We have previously identified a precursor of the fission yeast telomerase RNA subunit (TER1) and demonstrated that the mature 3'-end is generated by the spliceosome in a single cleavage reaction akin to the first step of splicing. Directly upstream and partly overlapping with the spliceosomal cleavage site is a putative binding site for Sm proteins. Sm and like-Sm (LSm) proteins belong to an ancient family of RNA-binding proteins represented in all three domains of life. Members of this family form ring complexes on specific sets of target RNAs and have critical roles in their biogenesis, function and turnover. Here we demonstrate that the canonical Sm ring and the Lsm2-8 complex sequentially associate with fission yeast TER1. The Sm ring binds to the TER1 precursor, stimulates spliceosomal cleavage and promotes the hypermethylation of the 5'-cap by Tgs1. Sm proteins are then replaced by the Lsm2-8 complex, which promotes the association with the catalytic subunit and protects the mature 3'-end of TER1 from exonucleolytic degradation. Our findings define the sequence of events that occur during telomerase biogenesis and characterize roles for Sm and Lsm complexes as well as for the methylase Tgs1.


Induction of cardiogenesis in embryonic stem cells via downregulation of Notch1 signaling.
Embryonic stem cells represent an attractive source of cardiomyocytes for cell-replacement therapies. However, before embryonic stem cells can be successfully used for the treatment of cardiac diseases, the precise molecular mechanisms that underlie their cardiogenic differentiation must be identified. A network of intrinsic and extrinsic factors regulates embryonic stem cell self-renewal and differentiation into a variety of different cell lineages. Here, we show that Notch signaling takes place in some but not all embryonic stem cells and that the Notch pathway is shut down during the course of differentiation concomitantly with downregulation of Notch receptor and ligand expression. Moreover, gain- and loss-of-function experiments for Notch signaling components show that this pathway is a crucial regulator of cardiomyocyte differentiation within ES cells. Differentiation of ES cells into cardiomyocytes is favored by inactivation of the Notch1 receptor, whereas endogenous Notch signaling promotes differentiation of ES cells into the neuronal lineage. We conclude that Notch signaling influences the cell fate decision between mesodermal and the neuroectodermal cell fates during embryonic stem cell differentiation. These findings should help to optimize the production of specific cell types via modulation of the Notch pathways and, in particular, to improve the production of embryonic stem cell-derived cardiomyocytes.


Short-term glucocorticoid manipulations affect neuronal morphology and survival in the adult dentate gyrus.
In order to determine whether short-term glucocorticoid manipulations influence the morphology and survival of neurons in the adult mammalian hippocampal formation, we performed quantitative analyses of Golgi-impregnated and Nissl-stained tissue from the brains of sham operated male rats, adrenalectomized male rats and adrenalectomized male rats which received corticosterone replacement. Three days after adrenalectomy, massive cell death, as detected by a dramatic increase in number of pyknotic cells, was observed in the granule cell layer of the dentate gyrus. By seven days following adrenalectomy, the numbers of pyknotic cells were even greater. Moreover, significant decreases in cross-sectional cell body area and numbers of dendritic branch points of Golgi-impregnated dentate gyrus granule cells were detected at seven days after adrenalectomy. Replacement of corticosterone to adrenalectomized rats prevented the appearance of large numbers of pyknotic cells as well as the decrease in granule cell cross-sectional cell body area and the numbers of dendritic branch points. In contrast, no obvious signs of degeneration were detected in the pyramidal cell layers of the CA1 and CA3 regions of the hippocampus at either three or seven days following adrenalectomy. In addition, no significant changes in morphological characteristics were observed in CA1 or CA3 pyramidal cells with adrenalectomy. These results show that dentate gyrus granule cells require glucocorticoids for their survival and for the maintenance of normal morphology and suggest that granule cell morphology and/or survival may undergo constant fluctuation in response to diurnal rhythms or stress-induced changes in glucocorticoid levels.


Vaccinia virus proteins A52 and B14 Share a Bcl-2-like fold but have evolved to inhibit NF-kappaB rather than apoptosis.
Vaccinia virus (VACV), the prototype poxvirus, encodes numerous proteins that modulate the host response to infection. Two such proteins, B14 and A52, act inside infected cells to inhibit activation of NF-kappaB, thereby blocking the production of pro-inflammatory cytokines. We have solved the crystal structures of A52 and B14 at 1.9 A and 2.7 A resolution, respectively. Strikingly, both these proteins adopt a Bcl-2-like fold despite sharing no significant sequence similarity with other viral or cellular Bcl-2-like proteins. Unlike cellular and viral Bcl-2-like proteins described previously, A52 and B14 lack a surface groove for binding BH3 peptides from pro-apoptotic Bcl-2-like proteins and they do not modulate apoptosis. Structure-based phylogenetic analysis of 32 cellular and viral Bcl-2-like protein structures reveals that A52 and B14 are more closely related to each other and to VACV N1 and myxoma virus M11 than they are to other viral or cellular Bcl-2-like proteins. This suggests that a progenitor poxvirus acquired a gene encoding a Bcl-2-like protein and, over the course of evolution, gene duplication events have allowed the virus to exploit this Bcl-2 scaffold for interfering with distinct host signalling pathways.


[The association between obesity indices in adolescence and carotid intima-media thickness in young adults: Kangwha Study].
The aim of this study is to investigate the association between obesity indices (body mass index, weight, waist-hip ratio and waist circumference) in adolescents and the carotid intima-media thickness (C-IMT) in early adulthood. We also wanted to identify the best predictor for C-IMT among these obesity indices. This study used community-based prospective cohort study, known as the Kangwha Study, and the data we used were from subjects who were 16-years old in 1996 (defined as "adolescence") and 25 years-old in 2005 (defined as "early adulthood"). The 256 subjects (113 men and 143 women) who were used for analysis participated in both follow-ups, and they underwent B-mode ultrasonography of the carotid arteries at the early adulthood follow-up. Obesity indices were defined as the body mass index, weight, waist-hip ratio and waist circumference. The C-IMT was defined as the mean of the maximal IMT of each common carotid artery. The C-IMT and obesity indices associations were evaluated via multivariable regression, logistic regression and the receiver-operator characteristic curve analyses. In men, all the obesity indices in adolescence were showed to have statistically significant positive association with C-IMT in early adulthood. However, no such relationship was showed in women. On multiple regression and logistic regression analysis, the waist-hip ratio showed the biggest relationship with the C-IMT among the 4 obesity indices. However, there were no statistical significant differences and no best predictor was found. For the women, the obesity incidences and C-IMT showed no relationships. This study suggested that obesity in adolescence was related to an increase C-IMT in healthy young Korean men.


Characteristics of patients adhering to a hospital's no-smoking policy.
The purpose of this paper is to examine the characteristics of smokers who adhere to a hospital smoking ban, compared to those who do not. The data presented in this paper are baseline and discharge survey data collected among hospitalized smokers. This study was conducted in two teaching hospitals in a northeastern city. The subjects were 358 smokers who participated in a larger smoking intervention trial. Seventy-six percent of the subjects reported adhering to the smoke-free policy during their hospital stay. In a multivariate model, demographic factors that predicted adherence included being older, having shorter length of stay, not reporting recreational drug use in the previous 12 months, and not having alcohol-related problems. Smoking history variables that predicted adherence included having had at least 24 h of abstinence in the 7 days prior to hospitalization; self-efficacy variables (e.g., confidence in ability to quit smoking in 1 month and less anticipated difficulty refraining from smoking during hospitalization) also predicted adherence. Understanding the factors that predict adherence to health care policies can provide useful information for health promotion interventions in a medical setting. The implications of these findings are discussed.


Manganese biofouling and the corrosion behavior of stainless steel.
Manganese- and iron-oxidizing bacteria (MFOB) are widely implicated in microbially influenced corrosion, often in association with sulfate-reducing bacteria (SRB). Traditionally MFOB have been assigned a passive role in the corrosion process, promoting differential aeration cells, and providing oxygen depleted conditions conducive to the growth and corrosive attack of SRB. Recent work, summarized in this article, demonstrates that manganese biofouling alters the electrochemical behavior of stainless steel (SS), and suggests that MFOB are more active in localized corrosion than traditionally held. The paper discusses the chemistry and potentially corrosive impact of manganese and iron oxides on SS, explores the possible relationship between MFOB and SRB, and proposes a model to describe the synergistic influence these organisms may exert in the corrosion process.


Efficiency of laminar and turbulent mixing in wall-bounded flows.
A turbulent flow mixes in general more rapidly a passive scalar than a laminar flow does. From an energetic point of view, for statistically homogeneous or periodic flows, the laminar regime is more efficient. However, the presence of walls may change this picture. We consider in this investigation mixing in two-dimensional laminar and turbulent wall-bounded flows using direct numerical simulation. We show that for sufficiently large Schmidt number, turbulent flows more efficiently mix a wall-bounded scalar field than a chaotic or laminar flow does. The mixing efficiency is shown to be a function of the Péclet number, and a phenomenological explanation yields a scaling law, consistent with the observations.


Impact of osteopathic manipulative treatment on secretory immunoglobulin a levels in a stressed population.
High levels of human secretory immunoglobulin A (sIgA) have been shown to decrease the incidence of acquiring upper respiratory tract infections. Osteopathic manipulative treatment (OMT) has been shown to improve cardiac indices, increase lymph flow rates through the thoracic duct, and decrease sympathetic tone in postoperative patients and those in intensive care. Therefore, we hypothesized that OMT may also increase sIgA levels in people under high levels of emotional and psychological stress, thereby enhancing immunity and potentially preventing subsequent infections. To determine if OMT increases sIgA levels in highly stressed individuals. Twenty-five second-year osteopathic medical students were randomly assigned to an experimental group (n=12) or a control group (n=13). All participants were scheduled to take their national board examination (Comprehensive Osteopathic Medical Licensing Examination-USA) within 2 to 3 weeks after the experiment. After each participant submitted a saliva sample for a baseline sIgA level assessment, the experimental group received 20 minutes of OMT while the control group sat quietly and relaxed in a separate area for 20 minutes. Participants in both groups rested quietly for 1 hour after the 20-minute session and then submitted a second saliva sample. A 2 × 2 repeated measures analysis of variance revealed that the experimental group displayed a statistically significant greater increase in postintervention sIgA levels than the control group (F₁,₂₃), 5.92; P<.025). This study demonstrates the positive effect of OMT on sIgA levels in persons experiencing high stress. Results suggest that OMT may then have therapeutic preventive and protective effects on both healthy and hospitalized patients, especially those experiencing high levels of emotional or physiological stress and those at higher risk of acquiring upper respiratory tract infections.


Analysis of vertical radiation loss and far-field pattern for microcylinder lasers with an output waveguide.
Vertical radiation loss and far-field pattern are investigated for microcylinder lasers by 3D FDTD simulation and experimentally. The numerical results show that an output waveguide connected to the microcylinder resonator can result in additional vertical radiation loss for high Q coupled modes and affect the far field pattern. The vertical radiation loss can be controlled by adjusting the up cladding layer thickness. Furthermore, two lobes of vertical far-field patterns are observed for a 15-μm-radius microcylinder laser connected with an output waveguide, which confirms the vertical radiation loss.


The economic impact of chronic fatigue syndrome.
BACKGROUND: Chronic fatigue syndrome (CFS) is a chronic incapacitating illness that affects between 400,000 and 800,000 Americans. Despite the disabling nature of this illness, scant research has addressed the economic impact of CFS either on those affected or on the national economy. METHODS: We used microsimulation methods to analyze data from a surveillance study of CFS in Wichita, Kansas, and derive estimates of productivity losses due to CFS. RESULTS: We estimated a 37% decline in household productivity and a 54% reduction in labor force productivity among people with CFS. The annual total value of lost productivity in the United States was $9.1 billion, which represents about $20,000 per person with CFS or approximately one-half of the household and labor force productivity of the average person with this syndrome. CONCLUSION: Lost productivity due to CFS was substantial both on an individual basis and relative to national estimates for other major illnesses. CFS resulted in a national productivity loss comparable to such losses from diseases of the digestive, immune and nervous systems, and from skin disorders. The extent of the burden indicates that continued research to determine the cause and potential therapies for CFS could provide substantial benefit both for individual patients and for the nation.


Scandinavian glutamine trial: a pragmatic multi-centre randomised clinical trial of intensive care unit patients.
Low plasma glutamine concentration is an independent prognostic factor for an unfavourable outcome in the intensive care unit (ICU). Intravenous (i.v.) supplementation with glutamine is reported to improve outcome. In a multi-centric, double-blinded, controlled, randomised, pragmatic clinical trial of i.v. glutamine supplementation for ICU patients, we investigated outcomes regarding sequential organ failure assessment (SOFA) scores and mortality. The hypothesis was that the change in the SOFA score would be improved by glutamine supplementation. Patients (n=413) given nutrition by an enteral and/or a parenteral route with the aim of providing full nutrition were included within 72 h after ICU admission. Glutamine was supplemented as i.v. l-alanyl-l-glutamine, 0.283 g glutamine/kg body weight/24 h for the entire ICU stay. Placebo was saline in identical bottles. All included patients were considered as intention-to-treat patients. Patients given supplementation for >3 days were considered as predetermined per protocol (PP) patients. There was a lower ICU mortality in the treatment arm as compared with the controls in the PP group, but not at 6 months. For change in the SOFA scores, no differences were seen, 1 (0,3) vs. 2 (0.4), P=0.792, for the glutamine group and the controls, respectively. In summary, a reduced ICU mortality was observed during i.v. glutamine supplementation in the PP group. The pragmatic design of the study makes the results representative for a broad range of ICU patients.


Vascular endothelial growth factor signalling in endothelial cell survival: a role for NFkappaB.
Angiogenesis is the development of blood capillaries from pre-existing vessels. Vascular endothelial growth factor (VEGF) is a key regulator of vessel growth and regression, and acts as an endothelial survival factor by protecting endothelial cells from apoptosis. Many genes involved in cell proliferation and apoptosis are regulated by the nuclear factor kappa B (NFkappaB) transcription factor family. This study aimed to address the hypothesis that VEGF-mediated survival effects on endothelium involve NFkappaB. Using an NFkappaB-luciferase reporter adenovirus, we observed activation of NFkappaB following VEGF treatment of human umbilical vein endothelial cells. This was confirmed using electrophoretic mobility shift assay and found to involve nuclear translocation of NFkappaB sub-unit p65. However, NFkappaB activation occurred without degradation of inhibitory IkappaB proteins (IkappaBalpha, IkappaBbeta, and IkappaBepsilon). Instead, tyrosine phosphorylation of IkappaBalpha was observed following VEGF treatment, suggesting NFkappaB activation was mediated by degradation-independent dissociation of IkappaBalpha from NFkappaB. Adenovirus-mediated over-expression of either native IkappaBalpha, or of IkappaBalpha in which tyrosine residue 42 was mutated to phenylalanine, inhibited induction of NFkappaB-dependent luciferase activity in response to VEGF. Furthermore, VEGF-induced upregulation of mRNA for the anti-apoptotic protein Bcl-2 and cell survival following serum withdrawal was reduced following IkappaBalpha over-expression. This study highlights that different molecular mechanisms of NFkappaB activation may be involved downstream of stimuli which activate the endothelial lining of blood vessels.


Seed hemicelluloses tailor mucilage properties and salt tolerance.
While Arabidopsis seed coat epidermal cells have become an excellent genetic system to study the biosynthesis and structural roles of various cell wall polymers, the physiological function of the secreted mucilaginous polysaccharides remains ambiguous. Seed mucilage is shaped by two distinct classes of highly substituted hemicelluloses along with cellulose and structural proteins, but their interplay has not been explored. We deciphered the functions of four distinct classes of cell wall polymers by generating a series of double mutants with defects in heteromannan, xylan, cellulose, or the arabinogalactan protein SALT-OVERLY SENSITIVE 5 (SOS5), and evaluating their impact on mucilage architecture and seed germination during salt stress. We discovered that muci10 seeds, lacking heteromannan branches, had elevated tolerance to salt stress, while heteromannan elongation mutants exhibited reduced germination in calcium chloride (CaCl2 ). By contrast, xylan made by MUCILAGE-RELATED21 (MUCI21) was found to be required for the adherence of mucilage pectin to microfibrils made by CELLULOSE SYNTHASE5 (CESA5) as well as to a SOS5-mediated network. Our results indicate that the substitution of xylan and glucomannan in seeds can fine-tune mucilage adherence and salt tolerance, respectively. The study of germinating seeds can thus provide insights into the synthesis, modification and function of complex glycans.


Content analysis of medical students' seminars: a unique method of analyzing clinical thinking.
The study of communication skills of Asian medical students during structured Problem-based Learning (PBL) seminars represented a unique opportunity to assess their critical thinking development. This study reports the first application of the health education technology, content analysis (CA), to a Japanese web-based seminar (webinar). The authors assigned twelve randomly selected medical students from two universities and two clinical instructors to two virtual classrooms for four PBL structured tutoring sessions that were audio-video captured for CA. Both of the instructors were US-trained physicians. This analysis consisted of coding the students' verbal comments into seven types, ranging from trivial to advanced knowledge integration comments that served as a proxy for clinical thinking. The most basic level of verbal simple responses accounted for a majority (85%) of the total students' verbal comments. Only 15% of the students' comments represented more advanced types of critical thinking. The male students responded more than the female students; male students attending University 2 responded more than male students from University 1. The total mean students' verbal response time for the four sessions with the male instructor was 6.9%; total mean students' verbal response time for the four sessions with the female instructor was 19% (p < 0.05). This report is the first to describe the application of CA to a multi-university real time audio and video PBL medical student clinical training webinar in two Japanese medical schools. These results are preliminary, mostly limited by a small sample size (n = 12) and limited time frame (four sessions). CA technology has the potential to improve clinical thinking for medical students. This report may stimulate improvements for implementation.


Stages of sleep pathology in spinocerebellar ataxia type 2 (SCA2).
Autosomal dominant spinocerebellar ataxia type 2 (SCA2) bears clinical and neuropathologic similarities to sporadic multisystem atrophy (MSA) or Parkinson disease, in which sleep pathology is well documented. However, those clinical entities have a marked variability of the reported sleep disturbances, and their etiology is heterogeneous. In contrast, the study of SCA2 provides an opportunity to examine a molecularly homogeneous patient group, in which disease stages can be defined not only based on disease duration and ataxia scores, but also with regard to modulatory effects of mutation size. To examine the presence and progression of sleep pathology in SCA2. We analyzed eight patients with disease durations of 3 to 31 years, all with medium size SCA2 expansions (CAG 38 to 49), using clinical scores, sleep interviews, and video-polysomnography (VPSG) recordings. Almost all patients reported good subjective sleep quality and negated incidents of REM behavior disorder (RBD). At early disease stages, however, REM without atonia in four patients' VPSG suggested subclinical RBD. This was accompanied by a consistent reduction of REM density. In three patients at later SCA2 stages, REM sleep was undetectable, whereas slow wave sleep (SWS) was markedly increased at the cost of light sleep. Periodic leg movements, apnea, or hypopnea were not prominent. Progressive loss of dream recall in spinocerebellar ataxia type 2 was found and correlated with stages of REM more than non-REM pathology in video-polysomnography. These stages correspond to the progressive atrophy from the pons, nigrostriatal projection, and locus ceruleus to the thalamus.


Effect of vibration on forward split flexibility and pain perception in young male gymnasts.
Serious stretching in many sports involves discomfort and is often an early ceiling on improvements. To continue investigation of the use of vibration to enhance acute range of motion while assessing the influence of vibration and stretching on pressure-to-pain threshold perception. Ten young male gymnasts were assessed for split range of motion. One side split was randomly assigned as the experimental condition, and the other side split was assigned as the control. Both side splits were performed on a vibration device; the experimental condition had the device turned on and the control condition was performed with the device turned off. In addition, the athletes were assessed for pressure-to-pain transition using an algometer on the biceps femoris (stretched muscle) and vastus lateralis (nonstretched muscle) bilaterally. Pre-post difference scores between the vibrated split (most improved) and the nonvibrated split were statistically different (P=.001, 95% confidence interval of the difference 2.3 to 5.8 cm). Following the stretching protocol, the force values for the pressure-to-pain threshold comparing the vibrated and nonvibrated biceps femoris muscle were not statistically different. The nonstretched vastus lateralis muscle also showed no statistical difference in pressure-to-pain threshold between the vibration and nonvibration conditions. This study showed that vibration improved split range of motion over stretching alone, but did not show a difference in pressure-to-pain perception in either the stretched or nonstretched muscles.


Single or multiple frequency generators in on-going brain activity: A mechanistic whole-brain model of empirical MEG data.
During rest, envelopes of band-limited on-going MEG signals co-vary across the brain in consistent patterns, which have been related to resting-state networks measured with fMRI. To investigate the genesis of such envelope correlations, we consider a whole-brain network model assuming two distinct fundamental scenarios: one where each brain area generates oscillations in a single frequency, and a novel one where each brain area can generate oscillations in multiple frequency bands. The models share, as a common generator of damped oscillations, the normal form of a supercritical Hopf bifurcation operating at the critical border between the steady state and the oscillatory regime. The envelopes of the simulated signals are compared with empirical MEG data using new methods to analyse the envelope dynamics in terms of their phase coherence and stability across the spectrum of carrier frequencies. Considering the whole-brain model with a single frequency generator in each brain area, we obtain the best fit with the empirical MEG data when the fundamental frequency is tuned at 12Hz. However, when multiple frequency generators are placed at each local brain area, we obtain an improved fit of the spatio-temporal structure of on-going MEG data across all frequency bands. Our results indicate that the brain is likely to operate on multiple frequency channels during rest, introducing a novel dimension for future models of large-scale brain activity.


PBAF chromatin-remodeling complex requires a novel specificity subunit, BAF200, to regulate expression of selective interferon-responsive genes.
PBAF and BAF are two chromatin-remodeling complexes of the SWI/SNF family essential for mammalian transcription and development. Although these complexes share eight identical subunits, only PBAF can facilitate transcriptional activation by nuclear receptors in vitro. Here we show that these complexes have selectivity in mediating transcription of different interferon-responsive genes. The selectivity by PBAF requires a novel subunit, BAF200, but not the previously described PBAF-specificity subunit, BAF180 (Polybromo). Our study provides in vivo evidence that PBAF and BAF regulate expression of distinct genes, and suggests that BAF200 plays a key role in PBAF function.


A Feasibility Study of Quantifying Longitudinal Brain Changes in Herpes Simplex Virus (HSV) Encephalitis Using Magnetic Resonance Imaging (MRI) and Stereology.
To assess whether it is feasible to quantify acute change in temporal lobe volume and total oedema volumes in herpes simplex virus (HSV) encephalitis as a preliminary to a trial of corticosteroid therapy. The study analysed serially acquired magnetic resonance images (MRI), of patients with acute HSV encephalitis who had neuroimaging repeated within four weeks of the first scan. We performed volumetric measurements of the left and right temporal lobes and of cerebral oedema visible on T2 weighted Fluid Attenuated Inversion Recovery (FLAIR) images using stereology in conjunction with point counting. Temporal lobe volumes increased on average by 1.6% (standard deviation (SD 11%) in five patients who had not received corticosteroid therapy and decreased in two patients who had received corticosteroids by 8.5%. FLAIR hyperintensity volumes increased by 9% in patients not receiving treatment with corticosteroids and decreased by 29% in the two patients that had received corticosteroids. This study has shown it is feasible to quantify acute change in temporal lobe and total oedema volumes in HSV encephalitis and suggests a potential resolution of swelling in response to corticosteroid therapy. These techniques could be used as part of a randomized control trial to investigate the efficacy of corticosteroids for treating HSV encephalitis in conjunction with assessing clinical outcomes and could be of potential value in helping to predict the clinical outcomes of patients with HSV encephalitis.


Limited One-time Sampling Irregularity Map (LOTS-IM) for Automatic Unsupervised Assessment of White Matter Hyperintensities and Multiple Sclerosis Lesions in Structural Brain Magnetic Resonance Images.
We present the application of limited one-time sampling irregularity map (LOTS-IM): a fully automatic unsupervised approach to extract brain tissue irregularities in magnetic resonance images (MRI), for quantitatively assessing white matter hyperintensities (WMH) of presumed vascular origin, and multiple sclerosis (MS) lesions and their progression. LOTS-IM generates an irregularity map (IM) that represents all voxels as irregularity values with respect to the ones considered "normal". Unlike probability values, IM represents both regular and irregular regions in the brain based on the original MRI's texture information. We evaluated and compared the use of IM for WMH and MS lesions segmentation on T2-FLAIR MRI with the state-of-the-art unsupervised lesions' segmentation method, Lesion Growth Algorithm from the public toolbox Lesion Segmentation Toolbox (LST-LGA), with several well established conventional supervised machine learning schemes and with state-of-the-art supervised deep learning methods for WMH segmentation. In our experiments, LOTS-IM outperformed unsupervised method LST-LGA on WMH segmentation, both in performance and processing speed, thanks to the limited one-time sampling scheme and its implementation on GPU. Our method also outperformed supervised conventional machine learning algorithms (i.e., support vector machine (SVM) and random forest (RF)) and deep learning algorithms (i.e., deep Boltzmann machine (DBM) and convolutional encoder network (CEN)), while yielding comparable results to the convolutional neural network schemes that rank top of the algorithms developed up to date for this purpose (i.e., UResNet and UNet). LOTS-IM also performed well on MS lesions segmentation, performing similar to LST-LGA. On the other hand, the high sensitivity of IM on depicting signal change deems suitable for assessing MS progression, although care must be taken with signal changes not reflective of a true pathology.


Higher harmonic anisotropic flow measurements of charged particles in Pb-Pb collisions at sqrt(s(NN)) = 2.76 TeV.
We report on the first measurement of the triangular v3, quadrangular v4, and pentagonal v5 charged particle flow in Pb-Pb collisions at sqrt(s(NN)) = 2.76 TeV measured with the ALICE detector at the CERN Large Hadron Collider. We show that the triangular flow can be described in terms of the initial spatial anisotropy and its fluctuations, which provides strong constraints on its origin. In the most central events, where the elliptic flow v2 and v3 have similar magnitude, a double peaked structure in the two-particle azimuthal correlations is observed, which is often interpreted as a Mach cone response to fast partons. We show that this structure can be naturally explained from the measured anisotropic flow Fourier coefficients.


Identification of a selective inhibitor of human monocarboxylate transporter 4.
The human monocarboxylate transporters (hMCTs/SLC16As) mediate the uptake of various monocarboxylates. Several isoforms of hMCTs are expressed in cancerous tissue as well as in normal tissue. In cancerous tissue, hypoxia induces the expression of hMCT4, which transports the energetic metabolite l-lactate across the plasma membrane. Since hMCT4 is involved in pH regulation and the transport of l-lactate in cancer cells, an hMCT4 inhibitor could function as an anticancer agent. Although several non specific hMCT inhibitors have been developed, a selective hMCT4 inhibitor has not yet been identified. The aim of this study was therefore to identify a selective hMCT4 inhibitor for use as a pharmacological tool for studying hMCT4. The heterologous expression system of the Xenopus oocyte was used to assess the effects of test compounds on hMCT4, whereupon isobutyrate derivatives, fibrates, and bindarit (2-[(1-benzyl-1H-indazol-3-yl)methoxy]-2-methylpropanoic acid) were demonstrated to exhibit selective inhibitory effects against this transporter. It is suggested that the structure formed from the joining of an isobutyrate moiety and two aromatic rings by appropriate linkers is important for acquiring the selective hMCT4-inhibiting activity. These findings provide novel insights into the ligand recognition of hMCT4, and contribute to the development of novel anticancer agents.


Interferon-alpha therapy for chronic hepatitis B in children: a meta-analysis.
A meta-analysis of six randomized clinical trials involving 240 children with chronic hepatitis B treated with recombinant interferon-alpha (IFN-alpha) was performed. IFN-alpha treatment was effective in blocking viral replication. Clearance of hepatitis B virus (HBV) DNA from sera occurred in 44 of 127 treated patients (P < .00001), and clearance of hepatitis B e antigen (HBeAg) occurred in seven of 74 treated patients (P = .099). IFN-alpha normalized serum levels of alanine aminotransferase (ALT) in 33 of 85 treated patients (P = .017). At the end of the follow-up period, viral replication was still reduced in IFN-alpha-treated patients, HBV DNA clearance occurred in 36 of 126 patients (P = .014), and HBeAg clearance occurred in 29 of 126 patients (P = .026). Regarding these virological and biochemical endpoints, we found that prolonged therapy (> 6 months) was associated with a better response, whereas high dosages of IFN-alpha were not. These findings could be biased by limited follow-up. Children with high ALT levels had a better response. However, these randomized clinical trials had some methodological flaws, including the lack of information on histologic response to IFN-alpha treatment by pediatric patients and the absence of "hard outcomes" (such as survival or development of cirrhosis or hepatocellular carcinoma).


Stable isotope labeling confirms mixotrophic nature of streamer biofilm communities at alkaline hot springs.
Streamer biofilm communities (SBC) are often observed within chemosynthetic zones of Yellowstone hot spring outflow channels, where temperatures exceed those conducive to photosynthesis. Nearest the hydrothermal source (75-88°C) SBC comprise thermophilic Archaea and Bacteria, often mixed communities including Desulfurococcales and uncultured Crenarchaeota, as well as Aquificae and Thermus, each carrying diagnostic membrane lipid biomarkers. We tested the hypothesis that SBC can alternate their metabolism between autotrophy and heterotrophy depending on substrate availability. Feeding experiments were performed at two alkaline hot springs in Yellowstone National Park: Octopus Spring and "Bison Pool," using various (13)C-labeled substrates (bicarbonate, formate, acetate, and glucose) to determine the relative uptake of these different carbon sources. Highest (13)C uptake, at both sites, was from acetate into almost all bacterial fatty acids, particularly into methyl-branched C15, C17 and C19 fatty acids that are diagnostic for Thermus/Meiothermus, and some Firmicutes as well as into universally common C16:0 and C18:0 fatty acids. (13)C-glucose showed a similar, but a 10-30 times lower uptake across most fatty acids. (13)C-bicarbonate uptake, signifying the presence of autotrophic communities was only significant at "Bison Pool" and was observed predominantly in non-specific saturated C16, C18, C20, and C22 fatty acids. Incorporation of (13)C-formate occurred only at very low rates at "Bison Pool" and was almost undetectable at Octopus Spring, suggesting that formate is not an important carbon source for SBC. (13)C-uptake into archaeal lipids occurred predominantly with (13)C-acetate, suggesting also that archaeal communities at both springs have primarily heterotrophic carbon assimilation pathways. We hypothesize that these communities are energy-limited and predominantly nurtured by input of exogenous organic material, with only a small fraction being sustained by autotrophic growth.


Microbial control of the cotton leafworm Spodoptera littoralis (Boisd.) by Egyptian Bacillus thuringiensis isolates.
Four local Bacillus thuringiensis (Bt) isolates that had been serologically identified as Bt var. kurstaki (Btk2, Btk3, and Btk66) and Bt var. mexicanensis (Btm27), in addition to two reference strains (4D20 and 4AC1), were laboratory assayed as microbial control agents against the Egyptian cotton leafworm Spodoptera littoralis (Boisd.). Polymerase chain reaction (PCR) amplification analysis revealed that each of the six experimental strains carries, at least, a cry1 type gene which expresses a protein toxin active against lepidopterous insects. Additionally, PCR amplification results demonstrated that 4D20 and Btk66 contain the Lepidoptera- and Diptera-active cry2 type gene and that Btk66 contains Coleoptera-active cry7 and cry8 genes. Among the six strains, Btk66 and Btm27 were the most promising microbial control agents against S. littoralis. The present findings were the first to report that Btm27 (classified as B. thuringiensis var. mexicanensis) is a very potent microbial control agent against S. littoralis-tested larvae. For more characterization of these two isolates, the sspO gene was investigated as a molecular chronometer. The DNA sequencing results proved that Btk66 and Btm27 carry sspO open reading frames with identical nucleotide sequences, suggesting a strong phylogenetic relationship between the two strains.


Is a dense mammographic parenchymal pattern a contraindication to hormonal replacement therapy?
The aim of the study was to find out whether the effect of hormonal replacement therapy (HRT) is modified by the mammographic parenchymal patterns on the risk of breast cancer. Subjects were 4163 Finnish women aged 40-47 years at entry who were invited to breast cancer screening every second year from 1982 to 1990. Mammographic parenchymal patterns (Wolfe's classification) were recorded at each screening round. The information, on use of HRT, was recorded from 1984. The follow-up ended in 1993 and up until that time 68 new breast cancers were diagnosed. A Poisson regression model was used in the analysis of the data. Use of HRT was not related to the risk of breast cancer (RR = 0.7, 95% CI 0.4-1.4), whereas mammographic parenchymal pattern was statistically significantly associated with risk of breast cancer. The age-adjusted relative risk of breast cancer among women with P2 versus N1 pattern was 2.5 (95% CI 1.3-4.8) and with DY versus N1 pattern 4.9 (951% CI 1.6-15.1). Women using HRT and with DY pattern were at substantially increased risk of breast cancer (RR = 11.6, 95% CI 2.5-53.6) compared with women not using HRT and with N1 pattern. There was an increased risk of breast cancer among women with DY mammographic parenchymal pattern who used HRT, which was consistent with a synergistic joint effect.


Domino: Extracting, Comparing, and Manipulating Subsets Across Multiple Tabular Datasets.
Answering questions about complex issues often requires analysts to take into account information contained in multiple interconnected datasets. A common strategy in analyzing and visualizing large and heterogeneous data is dividing it into meaningful subsets. Interesting subsets can then be selected and the associated data and the relationships between the subsets visualized. However, neither the extraction and manipulation nor the comparison of subsets is well supported by state-of-the-art techniques. In this paper we present Domino, a novel multiform visualization technique for effectively representing subsets and the relationships between them. By providing comprehensive tools to arrange, combine, and extract subsets, Domino allows users to create both common visualization techniques and advanced visualizations tailored to specific use cases. In addition to the novel technique, we present an implementation that enables analysts to manage the wide range of options that our approach offers. Innovative interactive features such as placeholders and live previews support rapid creation of complex analysis setups. We introduce the technique and the implementation using a simple example and demonstrate scalability and effectiveness in a use case from the field of cancer genomics.


Caregiver perceptions of children who have complex communication needs following a home-based intervention using augmentative and alternative communication in rural Kenya: an intervention note.
A high level of unmet communication need exists amongst children with developmental disabilities in sub-Saharan Africa. This study investigated preliminary evidence of the impact associated with a home-based, caregiver-implemented intervention employing AAC methods, with nine children in rural Kenya who have complex communication needs. The intervention used mainly locally-sourced low-tech materials, and was designed to make use of the child's strengths and the caregiver's natural expertise. A pretest-posttest design was used in the study. Data were gathered using an adapted version of the Communication Profile, which was based on the International Classification of Functioning, Disability, and Health (ICF) framework. The non-parametric Wilcoxon signed-rank test was applied to data from the first two sections of the Communication Profile-Adapted. Qualitative analysis was conducted on the final section. The data provided evidence of statistically significant positive changes in caregiver perceptions of communication at the levels of Body Structure and Function, and Activities for Communication. Also, analysis of the Participation for Communication section revealed some expansion to the children's social activities. The potential impact of the home-based intervention would benefit from investigation on a larger scale. Limitations of the study are discussed.


Functional Characterization of Alternative and Classical Pathway C3/C5 Convertase Activity and Inhibition Using Purified Models.
Complement is essential for the protection against infections; however, dysregulation of complement activation can cause onset and progression of numerous inflammatory diseases. Convertase enzymes play a central role in complement activation and produce the key mediators of complement: C3 convertases cleave C3 to generate chemoattractant C3a and label target cells with C3b, which promotes phagocytosis; C5 convertases cleave C5 into chemoattractant C5a, and C5b, which drives formation of the membrane attack complex. Since convertases mediate nearly all complement effector functions, they are ideal targets for therapeutic complement inhibition. A unique feature of convertases is their covalent attachment to target cells, which effectively confines complement activation to the cell surface. However, surface localization precludes detailed analysis of convertase activation and inhibition. In our previous work, we developed a model system to form purified alternative pathway (AP) C5 convertases on C3b-coated beads and quantify C5 conversion via functional analysis of released C5a. Here, we developed a C3aR cell reporter system that enables functional discrimination between C3 and C5 convertases. By regulating the C3b density on the bead surface, we observe that high C3b densities are important for conversion of C5, but not C3, by AP convertases. Screening of well-characterized complement-binding molecules revealed that differential inhibition of AP C3 convertases (C3bBb) and C5 convertases [C3bBb(C3b)n] is possible. Although both convertases contain C3b, the C3b-binding molecules Efb-C/Ecb and FHR5 specifically inhibit C5 conversion. Furthermore, using a new classical pathway convertase model, we show that these C3b-binding proteins not only block AP C3/C5 convertases but also inhibit formation of a functional classical pathway C5 convertase under well-defined conditions. Our models enable functional characterization of purified convertase enzymes and provide a platform for the identification and development of specific convertase inhibitors for treatment of complement-mediated disorders.


Rice actin-binding protein RMD is a key link in the auxin-actin regulatory loop that controls cell growth.
The plant hormone auxin plays a central role in plant growth and development. Auxin transport and signaling depend on actin organization. Despite its functional importance, the mechanistic link between actin filaments (F-actin) and auxin intracellular signaling remains unclear. Here, we report that the actin-organizing protein Rice Morphology Determinant (RMD), a type II formin from rice (Oryza sativa), provides a key link. Mutants lacking RMD display abnormal cell growth and altered configuration of F-actin array direction. The rmd mutants also exhibit an inhibition of auxin-mediated cell elongation, decreased polar auxin transport, altered auxin distribution gradients in root tips, and suppression of plasma membrane localization of auxin transporters O. sativa PIN-FORMED 1b (OsPIN1b) and OsPIN2 in root cells. We demonstrate that RMD is required for endocytosis, exocytosis, and auxin-mediated OsPIN2 recycling to the plasma membrane. Moreover, RMD expression is directly regulated by heterodimerized O. sativa auxin response factor 23 (OsARF23) and OsARF24, providing evidence that auxin modulates the orientation of F-actin arrays through RMD. In support of this regulatory loop, osarf23 and lines with reduced expression of both OsARF23 and OsARF24 display reduced RMD expression, disrupted F-actin organization and cell growth, less sensitivity to auxin response, and altered auxin distribution and OsPIN localization. Our findings establish RMD as a crucial component of the auxin-actin self-organizing regulatory loop from the nucleus to cytoplasm that controls rice cell growth and morphogenesis.


Identification of the aggregation pheromone of the melon thrips, Thrips palmi.
The objective of this study was to identify the aggregation pheromone of the melon thrips Thrips palmi, a major pest of vegetable and ornamental plants around the world. The species causes damage both through feeding activities and as a vector of tospoviruses, and is a threat to world trade and European horticulture. Improved methods of detecting and controlling this species are needed and the identification of an aggregation pheromone will contribute to this requirement. Bioassays with a Y-tube olfactometer showed that virgin female T. palmi were attracted to the odour of live males, but not to that of live females, and that mixed-age adults of both sexes were attracted to the odour of live males, indicating the presence of a male-produced aggregation pheromone. Examination of the headspace volatiles of adult male T. palmi revealed only one compound that was not found in adult females. It was identified by comparison of its mass spectrum and chromatographic details with those of similar compounds. This compound had a structure like that of the previously identified male-produced aggregation pheromone of the western flower thrips Frankliniella occidentalis. The compound was synthesised and tested in eggplant crops infested with T. palmi in Japan. Significantly greater numbers of both males and females were attracted to traps baited with the putative aggregation pheromone compared to unbaited traps. The aggregation pheromone of T. palmi is thus identified as (R)-lavandulyl 3-methyl-3-butenoate by spectroscopic, chromatographic and behavioural analysis.


Prognostic value of FDG PET metabolic tumor volume in human papillomavirus-positive stage III and IV oropharyngeal squamous cell carcinoma.
The purpose of this study was to establish the prognostic utility in human papillomavirus (HPV)-positive stage III and IV oropharyngeal squamous cell carcinoma (SCC) of the (18)F-FDG parameters maximal, mean, and peak standardized uptake value (SUVmax, SUVmean, and SUVpeak, respectively); metabolic tumor volume (MTV); and total lesion glycolysis (TLG). We included 70 patients in the present study who had a biopsy-proven HPV-positive (by in situ hybridization) stage III and IV oropharyngeal SCC and had a baseline PET/CT examination at our institution. Outcome endpoint was event-free survival (EFS), which included recurrence-free and overall survival. Cox proportional hazards multivariate regression analyses were performed. Survival analysis was performed using Kaplan-Meier survival curves. In Cox regression proportional hazard univariate analysis, total MTV (hazard ratio [HR], 1.02; p = 0.008), primary-tumor MTV (HR, 1.02; p = 0.024), neck nodal MTV (HR, 1.03; p = 0.006), neck nodal TLG (HR, 1.01; p = 0.006), and neck node status (HR, 4.45; p = 0.03) showed a statistically significant association with EFS. There was no statistically significant association of EFS with SUVmax, SUVmean, SUVpeak, and primary-tumor or overall TLG. In Cox regression proportional hazard multivariate model I, total MTV remained an independent prognostic marker for EFS when adjusted for every other variable individually in the model; in model II, primary-tumor MTV, neck node status, and SUVpeak are independent prognostic markers for EFS. The Kaplan-Meier survival curves using optimum cut point of 41 mL of total MTV were not significant (p = 0.09). Total MTV and primary-tumor MTV are associated with survival outcomes in patients with HPV-positive stage III and IV oropharyngeal SCC.


Effect of torso morphology on maximum hydrodynamic resistance in front crawl swimming.
The aim of this study was to determine the influence of torso morphology on maximum instantaneous hydrodynamic resistance in front crawl swimming. Outlines of the torso in the frontal and anteroposterior planes were calculated from photographic images to determine continuous form gradients (m/m) for the anterior, posterior and lateral aspects of the torso. Torso cross-sectional areas at each vertical sample (0.001 m) were used to calculate maximal rate of change in cross-sectional area (m2/m) in the chest-waist and waist-hip segments. During the non-propulsive hand phase in middle-long distance front crawl, kicking propulsion is negligible and therefore the net force is equal to the drag. Drag coefficients were calculated at the instant of maximum horizontal deceleration of centre of mass during the non-propulsive hand phase of 400 m pace front crawl. Maximal rate of change in cross-sectional area (r = 0.44, p = 0.014) and posterior form gradient (r = 0.50, p = 0.006) of the waist-hip torso segment had moderate positive correlations with the maximal drag coefficient. A regression model including these variables explained 41% of the variance (p = 0.001). Indentation at the waist and curvature of the buttocks may result in greater drag force and influence swimming performance.


Interictal executive dysfunction in migraineurs without aura: relationship with duration and intensity of attacks.
Subjects with migraine are at increased risk of subcortical white matter lesions (WML). Reports of cognitive testing in adults with migraine have yielded inconsistent results. We performed a cross-sectional study to assess whether migraine without aura (MwA) is associated with impairment in executive functioning, a typical cognitive correlate of subcortical WML. Forty-five subjects with MwA and 90 controls, matched for age and education, underwent a cognitive battery of tests evaluating executive functions. The following migraine characteristics were collected: age at onset and length of migraine history, and frequency, duration and intensity of attacks. Subjects with MwA performed significantly lower than controls in tests evaluating complex, multifactorial executive functions. After multiple adjustments, the duration and intensity of migraine attacks significantly predicted cognitive disturbances. In the interictal phase of MwA there is evidence of mild executive dysfunction. The cumulative effects of repeated migraine attacks on prefronto-cerebellar loop probably account for our results.