On the use of fixed point theory to design coupled core walls

The use of Fixed Point Theory (FPT) to optimize the design of coupling beams in coupled core wall (CCW) systems is demonstrated. The basis for optimization is minimizing the transmissibility of horizontal ground motion by appropriately linking two coupled wall piers having different dynamic properties with beams having appropriate stiffness and damping characteristics. Using 21 example CCW structures illustrating a range of pier properties, it was shown that the resulting optimization of coupling stiffness is quite small and other design considerations will require stiffer, non-optimal coupling beams. Nonetheless, the potential to leverage the small amount of coupling available in a 'slab-coupled' series of wall piers in order to reduce transmissibility is suggested by the findings of this study

Design of coupled wall structures as evolving structural systems

Coupled wall (CW) structures are outstanding lateral load resisting systems that not only reduce the deformation demands on the building, but also distribute inelastic deformation both vertically and in plan, between the coupling beams and the wall piers. When subjected to large seismic loads, coupling beams may deteriorate relatively quickly exhibiting both strength and stiffness degradation. This results in a rapid evolution in the performance of the CW system from behaving as a coupled wall system to behaving as a system of linked wall piers (LWP). This evolution of behavior is the focus of this work which considers a prototype 12-storey reinforced concrete coupled core wall (CCW) building. Five prototype variations, having the same wall pier pairs but degrading degrees of coupling were designed to study the effects of decayed coupling action. Elastic analyses using the equivalent lateral force (ELF) procedure and the continuous medium method (CMM) were used to establish initial proportions for the CCW prototype, and to determine the design forces and moments. Nonlinear static and dynamic analyses were conducted to investigate the CCW structural behavior, adequacy of the design, and the effect of the evolution of the structural form from a CCW system to a collection of LWPs. As expected, the structures having weaker coupling beams exhibited yield at lower lateral loads. The accompanying reduction in coupling stiffness, however, mitigated this effect although the wall pier demand clearly rose with reduced coupling. In every case, however, the walls embodied sufficient overstrength to permit the overall structure to perform well. An additional aspect of this work is that the wall piers in the CCW were significantly different in terms of their dynamic and geometric properties: the moments of inertia of the two wall piers of the CCW differed by almost an order of magnitude. The different wall pier capacities affected performance and require bi-directional pushover analyses but did not result in a significant reduction in capacity as may be initially intuited. © 2014 Elsevier Ltd

2007 Annual progress report synopsis of the Center for Structures of Membrane Proteins

A synopsis of the 2007 annual progress report for the Center for Structures of Membrane Proteins, a specialized center of the Protein Structure Initiative

Independent Origins of Cultivated Coconut (Cocos nucifera L.) in the Old World Tropics

As a portable source of food, water, fuel, and construction materials, the coconut (Cocos nucifera L.) played a fundamental role in human migrations and the development of civilization across the humid tropics. Here we investigated the coconut's domestication history and its population genetic structure as it relates to human dispersal patterns. A sample of 1,322 coconut accessions, representing the geographical and phenotypic diversity of the species, was examined using ten microsatellite loci. Bayesian analyses reveal two highly genetically differentiated subpopulations that correspond to the Pacific and Indo-Atlantic oceanic basins. This pattern suggests independent origins of coconut cultivation in these two world regions, with persistent population structure on a global scale despite long-term human cultivation and dispersal. Pacific coconuts show additional genetic substructure corresponding to phenotypic and geographical subgroups; moreover, the traits that are most clearly associated with selection under human cultivation (dwarf habit, self-pollination, and “niu vai” fruit morphology) arose only in the Pacific. Coconuts that show evidence of genetic admixture between the Pacific and Indo-Atlantic groups occur primarily in the southwestern Indian Ocean. This pattern is consistent with human introductions of Pacific coconuts along the ancient Austronesian trade route connecting Madagascar to Southeast Asia. Admixture in coastal east Africa may also reflect later historic Arab trading along the Indian Ocean coastline. We propose two geographical origins of coconut cultivation: island Southeast Asia and southern margins of the Indian subcontinent

Outcome of ATP-based tumor chemosensitivity assay directed chemotherapy in heavily pre-treated recurrent ovarian carcinoma

BACKGROUND: We wished to evaluate the clinical response following ATP-Tumor Chemosensitivity Assay (ATP-TCA) directed salvage chemotherapy in a series of UK patients with advanced ovarian cancer. The results are compared with that of a similar assay used in a different country in terms of evaluability and clinical endpoints. METHODS: From November 1998 to November 2001, 46 patients with pre-treated, advanced ovarian cancer were given a total of 56 courses of chemotherapy based on in-vitro ATP-TCA responses obtained from fresh tumor samples or ascites. Forty-four patients were evaluable for results. Of these, 18 patients had clinically platinum resistant disease (relapse < 6 months after first course of chemotherapy). There was evidence of cisplatin resistance in 31 patients from their first ATP-TCA. Response to treatment was assessed by radiology, clinical assessment and tumor marker level (CA 125). RESULTS: The overall response rate was 59% (33/56) per course of chemotherapy, including 12 complete responses, 21 partial responses, 6 with stable disease, and 15 with progressive disease. Two patients were not evaluable for response having received just one cycle of chemotherapy: if these were excluded the response rate is 61%. Fifteen patients are still alive. Median progression free survival (PFS) was 6.6 months per course of chemotherapy; median overall survival (OAS) for each patient following the start of TCA-directed therapy was 10.4 months (95% confidence interval 7.9-12.8 months). CONCLUSION: The results show similar response rates to previous studies using ATP-TCA directed therapy in recurrent ovarian cancer. The assay shows high evaluability and this study adds weight to the reproducibility of results from different centre

Cyclic Behavior of HPFRCC Coupling Beams with Bundled Diagonal Bars

Coupled shear walls are efficient in resisting lateral forces induced by winds and earthquakes. However, it is difficult to construct coupled shear walls particularly because current design codes require complex reinforcing details within coupling beams. The objective of this study was to develop simple reinforcement details for diagonally reinforced coupling beams; reducing transverse steel by use of high-performance fiber-reinforced cementitious composites (HPFRCCs) and bundling diagonal bars are explored. Four coupling beam specimens with length-to-depth aspect ratios of 2.0 or 3.5 were fabricated and tested under cyclic lateral displacements. The test results revealed that HPFRCC coupling beams with bundled diagonal bars and widely spaced transverse reinforcement (one-half the amount of reinforcement required by current seismic codes) exhibited excellent seismic performance compared with ordinary concrete coupling beams having code-required distributed diagonal reinforcement and transverse reinforcement

Total serum N-glycans associate with response to immune checkpoint inhibition therapy and survival in patients with advanced melanoma

Background Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of melanoma and other cancers. However, no reliable biomarker of survival or response has entered the clinic to identify those patients with melanoma who are most likely to benefit from ICIs. Glycosylation affects proteins and lipids’ structure and functions. Tumours are characterized by aberrant glycosylation which may contribute to their progression and hinder an effective antitumour immune response. Methods We aim at identifying novel glyco-markers of response and survival by leveraging the N-glycome of total serum proteins collected in 88 ICI-naive patients with advanced melanoma from two European countries. Samples were collected before and during ICI treatment. Results We observe that responders to ICIs present with a pre-treatment N-glycome profile significantly shifted towards higher abundancy of low-branched structures containing lower abundances of antennary fucose, and that this profile is positively associated with survival and a better predictor of response than clinical variables alone. Conclusion While changes in serum protein glycosylation have been previously implicated in a pro-metastatic melanoma behaviour, we show here that they are also associated with response to ICI, opening new avenues for the stratification of patients and the design of adjunct therapies aiming at improving immune response

The Impact of Global Warming and Anoxia on Marine Benthic Community Dynamics: an Example from the Toarcian (Early Jurassic)

The Pliensbachian-Toarcian (Early Jurassic) fossil record is an archive of natural data of benthic community response to global warming and marine long-term hypoxia and anoxia. In the early Toarcian mean temperatures increased by the same order of magnitude as that predicted for the near future; laminated, organic-rich, black shales were deposited in many shallow water epicontinental basins; and a biotic crisis occurred in the marine realm, with the extinction of approximately 5% of families and 26% of genera. High-resolution quantitative abundance data of benthic invertebrates were collected from the Cleveland Basin (North Yorkshire, UK), and analysed with multivariate statistical methods to detect how the fauna responded to environmental changes during the early Toarcian. Twelve biofacies were identified. Their changes through time closely resemble the pattern of faunal degradation and recovery observed in modern habitats affected by anoxia. All four successional stages of community structure recorded in modern studies are recognised in the fossil data (i.e. Stage III: climax; II: transitional; I: pioneer; 0: highly disturbed). Two main faunal turnover events occurred: (i) at the onset of anoxia, with the extinction of most benthic species and the survival of a few adapted to thrive in low-oxygen conditions (Stages I to 0) and (ii) in the recovery, when newly evolved species colonized the re-oxygenated soft sediments and the path of recovery did not retrace of pattern of ecological degradation (Stages I to II). The ordination of samples coupled with sedimentological and palaeotemperature proxy data indicate that the onset of anoxia and the extinction horizon coincide with both a rise in temperature and sea level. Our study of how faunal associations co-vary with long and short term sea level and temperature changes has implications for predicting the long-term effects of “dead zones” in modern oceans

Reasons of general practitioners for not prescribing lipid-lowering medication to patients with diabetes: a qualitative study

Background: Lipid-lowering medication remains underused, even in high-risk populations. The objective of this study was to determine factors underlying general practitioners' decisions not to prescribe such drugs to patients with type 2 diabetes. Methods: A qualitative study with semi-structured interviews using real cases was conducted to explore reasons for not prescribing lipid-lowering medication after a guideline was distributed that recommended the use of statins in most patients with type 2 diabetes. Seven interviews were conducted with general practitioners (GPs) in The Netherlands, and analysed using an analytic inductive approach. Results: Reasons for not-prescribing could be divided into patient and physician-attributed factors. According to the GPs, some patients do not follow-up on agreed medication and others object to taking lipid-lowering medication, partly for legitimate reasons such as expected or perceived side effects. Furthermore, the GPs themselves perceived reservations for prescribing lipid-lowering medication in patients with short life expectancy, expected compliance problems or near goal lipid levels. GPs sometimes postponed the start of treatment because of other priorities. Finally, barriers were seen in the GPs' practice organisation, and at the primary-secondary care interface. Conclusion: Some of the barriers mentioned by GPs seem to be valid reasons, showing that guideline non-adherence can be quite rational. On the other hand, treatment quality could improve by addressing issues, such as lack of knowledge or motivation of both the patient and the GP. More structured management in general practice may also lead to better treatment