Plasticity of Foot Muscle and Cardiac Thermal Limits in the Limpet \u3cem\u3eLottia limatula\u3c/em\u3e from Locations with Differing Temperatures

Species distributions are shifting in response to increased habitat temperatures as a result of ongoing climate change. Understanding variation in physiological plasticity among species and populations is important for predicting these distribution shifts. Interspecific variation in intertidal ectotherms’ short-term thermal plasticity has been well established. However, intraspecific variation among populations from differing thermal habitats remains a question pertinent to understanding the effects of climate change on species’ ranges. In this study, we explored upper thermal tolerance limits and plasticity of those limits using a foot muscle metric and 2 cardiac metrics (Arrhenius breakpoint temperature, ABT, and flatline temperature, FLT) in adult file limpets Lottia limatula. Limpets were collected from thermally different coastal and inland-estuarine habitats and held for 2 wk at 13, 17 or 21°C prior to thermal performance assays. Compared to limpets from the warm estuary site, limpets from the cold outer coast site had similar foot muscle critical thermal maxima (CTmax; 35.2 vs. 35.6°C) but lower cardiac thermal tolerances (ABT: 30.5 vs. 35.1°C). Limpets from the cold coast site had higher acclimation responses in foot muscle CTmax (0.22°C per 1°C rise in acclimation) than those of the warm estuary site (0.07°C per 1°C rise in acclimation), but lower acclimation responses in cardiac thermal tolerance (ABT: -0.85°C per 1°C rise in acclimation) than those of the estuary site (ABT: 0.10°C per 1°C rise in acclimation). Since outer coast populations had lower cardiac plasticity and higher mortalities in the warm acclimation, we predict L. limatula from colder habitats will be more susceptible to rising temperatures. Our findings illustrate the importance of population-specific variation in short-term thermal plasticity when considering the effects of climate change on ectotherms

Kleptoparasitic melees--modelling food stealing featuring contests with multiple individuals

Kleptoparasitism is the stealing of food by one animal from another. This has been modelled in various ways before, but all previous models have only allowed contests between two individuals. We investigate a model of kleptoparasitism where individuals are allowed to fight in groups of more than two, as often occurs in real populations. We find the equilibrium distribution of the population amongst various behavioural states, conditional upon the strategies played and environmental parameters, and then find evolutionarily stable challenging strategies. We find that there is always at least one ESS, but sometimes there are two or more, and discuss the circumstances when particular ESSs occur, and when there are likely to be multiple ESSs

Aeronautic Instruments. Section IV : Direction Instruments

Part one points out the adequacy of a consideration of the steady state gyroscopic motion as a basis for the discussion of displacements of the gyroscope mounted on an airplane, and develops a simple theory on this basis. Principal types of gyroscopic inclinometers are described and requirements stated. Part two describes a new type of stabilizing gyro mounted on top of a spindle by means of a universal joint, the spindle being kept in a vertical position by supporting it as a pendulum of which the bob is the driving motor. Methods of tests and the difficulties in designing a satisfactory and reliable compass for aircraft use in considered in part three. Part four contains a brief general treatment of the important features of construction of aircraft compasses and description of the principal types used

Scavenging in Northwestern Europe: A Survey of UK Police Specialist Search Officers

Physical search methods used by police specialist searchers are based on counter-terrorism methods and not on the search and recovery of outdoor surface deposited human remains, nevertheless these methods are applied to scenes involving human remains. Additionally, there is limited published forensic literature within Northwestern Europe on the potential taphonomic agents within this region that are capable of modifying human remains through scavenging, scattering and removal. The counter-terrorism basis in physical search methods and the gap in published forensic literature regarding scavenging in this region can potentially impede searchers’ abilities to adapt physical search methods to their full efficiency in the search and recovery of scavenged human remains. This paper analysed through a questionnaire survey of 111 police specialist searchers, within the U.K., the impact of animal scavenging on the search and recovery of human remains.According to questionnaire respondents’ experiences and knowledge, the occurrence of scavenging at scenes in which respondents took part in a physical search for human remains was common (63.46%,n= 66) and happened most frequently with surface deposits (68.25%,n= 43). Scavenging resulted in the recovery of incomplete sets of remains (59.79%, n= 58) and influenced search perimeters (58.33%, n= 35). Scavenging also affected recovery rates at scene searches (80.43%,n= 74) that included the use of cadaver dogs with police handlers. The impact scavengers within this region have on different crime scene scenarios and search methods is not reflected in current published literature or search standards

Follow-up Analyses for the ANTT Review.

Early in FY04, the Advanced Nuclear Transformation Technology (ANTT) subcommittee of the Nuclear Energy Research Advisory Committee (NERAC) requested a report on repository benefits for recycling of key transuranics in existing light water-cooled reactors (LWRs). The ANTT reviewers specifically requested a quantification of how such a campaign would impact (improve) the achievable loading of nuclear waste in the Yucca Mountain facility. The request stipulated that the transuranics be separated from commercial spent nuclear fuel (CSNF) and recycled a finite number of times in LWR-compatible fuel forms. The spent fuel remaining at the end of the recycling campaign, as well as all other nuclear waste generated by spent fuel reprocessing, would be permanently disposed in a geologic repository. In response, two reports have been prepared and distributed as deliverables for the AFCI program. Reference 1 provides the final report which addresses the original ANTT sub-committee request. Plutonium, neptunium, and americium recycling strategies in assemblies fabricated from mixed-oxide (MOX), CORAIL (heterogeneous UO{sub 2} and MOX), and inert-matrix fuel (IMF) forms were evaluated; the focus of the report is the time-dependent thermal response of the repository to a given loading of nuclear waste in the storage tunnels (drifts), as well as a quantification of how the loading could be increased relative to the reference direct disposal of CSNF. Reference 2 provides a more complete description of the neutronics and mass flow analyses which were completed as part of the study. That report also provides an analysis of the differences between the various recycling strategies and the underlying reactor physics

Responsive glyco-poly(2-oxazoline)s: synthesis, cloud point tuning, and lectin binding

A new sugar-substituted 2-oxazoline monomer was prepared using the copper-catalyzed alkyne-azide cycloaddition (CuAAC) reaction. Its copolymerization with 2-ethyl-2-oxazoline as well as 2-(dec-9-enyl)-2-oxazoline, yielding well-defined copolymers with the possibility to tune the properties by thiol-ene "click" reactions, is described. Extensive solubility studies on the corresponding glycocopolymers demonstrated that the lower critical solution temperature behavior and pH-responsiveness of these copolymers can be adjusted in water and phosphate-buffered saline (PBS) depending on the choice of the thiol. By conjugation of 2,3,4,6-tetra-O-acetyl-1-thio-beta-D-glucopyranose and subsequent deprotection of the sugar moieties, the hydrophilicity of the copolymer could be increased significantly, allowing a cloud-point tuning in the physiological range. Furthermore, the binding capability of the glycosylated copoly(2-oxazoline) to concanavalin A was investigated

Cryo-EM structure of a helicase loading intermediate containing ORC-Cdc6-Cdt1-MCM2-7 bound to DNA

In eukaryotes, the Cdt1-bound replicative helicase core MCM2-7 is loaded onto DNA by the ORC-Cdc6 ATPase to form a prereplicative complex (pre-RC) with an MCM2-7 double hexamer encircling DNA. Using purified components in the presence of ATP-γS, we have captured in vitro an intermediate in pre-RC assembly that contains a complex between the ORC-Cdc6 and Cdt1-MCM2-7 heteroheptamers called the OCCM. Cryo-EM studies of this 14-subunit complex reveal that the two separate heptameric complexes are engaged extensively, with the ORC-Cdc6 N-terminal AAA+ domains latching onto the C-terminal AAA+ motor domains of the MCM2-7 hexamer. The conformation of ORC-Cdc6 undergoes a concerted change into a right-handed spiral with helical symmetry that is identical to that of the DNA double helix. The resulting ORC-Cdc6 helicase loader shows a notable structural similarity to the replication factor C clamp loader, suggesting a conserved mechanism of action

Hospitalizations and Costs Incurred at the Facility Level After Scale-Up of Malaria Control: Pre-Post Comparisons From Two Hospitals in Zambia

There is little evidence on the impact of malaria control on the health system, particularly at the facility level. Using retrospective, longitudinal facility-level and patient record data from two hospitals in Zambia, we report a pre-post comparison of hospital admissions and outpatient visits for malaria and estimated costs incurred for malaria admissions before and after malaria control scale-up. The results show a substantial reduction in inpatient admissions and outpatient visits for malaria at both hospitals after the scale-up, and malaria cases accounted for a smaller proportion of total hospital visits over time. Hospital spending on malaria admissions also decreased. In one hospital, malaria accounted for 11% of total hospital spending before large-scale malaria control compared with \u3c 1% after malaria control. The findings demonstrate that facility-level resources are freed up as malaria is controlled, potentially making these resources available for other diseases and conditions

Ferritins: furnishing proteins with iron

Ferritins are a superfamily of iron oxidation, storage and mineralization proteins found throughout the animal, plant, and microbial kingdoms. The majority of ferritins consist of 24 subunits that individually fold into 4-α-helix bundles and assemble in a highly symmetric manner to form an approximately spherical protein coat around a central cavity into which an iron-containing mineral can be formed. Channels through the coat at inter-subunit contact points facilitate passage of iron ions to and from the central cavity, and intrasubunit catalytic sites, called ferroxidase centers, drive Fe2+ oxidation and O2 reduction. Though the different members of the superfamily share a common structure, there is often little amino acid sequence identity between them. Even where there is a high degree of sequence identity between two ferritins there can be major differences in how the proteins handle iron. In this review we describe some of the important structural features of ferritins and their mineralized iron cores and examine in detail how three selected ferritins oxidise Fe2+ in order to explore the mechanistic variations that exist amongst ferritins. We suggest that the mechanistic differences reflect differing evolutionary pressures on amino acid sequences, and that these differing pressures are a consequence of different primary functions for different ferritins

Targeted Doxorubicin Delivery to Brain Tumors via Minicells: Proof of Principle Using Dogs with Spontaneously Occurring Tumors as a Model

BACKGROUND: Cytotoxic chemotherapy can be very effective for the treatment of cancer but toxicity on normal tissues often limits patient tolerance and often causes long-term adverse effects. The objective of this study was to assist in the preclinical development of using modified, non-living bacterially-derived minicells to deliver the potent chemotherapeutic doxorubicin via epidermal growth factor receptor (EGFR) targeting. Specifically, this study sought to evaluate the safety and efficacy of EGFR targeted, doxorubicin loaded minicells (designated EGFRminicellsDox) to deliver doxorubicin to spontaneous brain tumors in 17 companion dogs; a comparative oncology model of human brain cancers. METHODOLOGY/PRINCIPLE FINDINGS: EGFRminicellsDox were administered weekly via intravenous injection to 17 dogs with late-stage brain cancers. Biodistribution was assessed using single-photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI). Anti-tumor response was determined using MRI, and blood samples were subject to toxicology (hematology, biochemistry) and inflammatory marker analysis. Targeted, doxorubicin-loaded minicells rapidly localized to the core of brain tumors. Complete resolution or marked tumor regression (>90% reduction in tumor volume) were observed in 23.53% of the cohort, with lasting anti-tumor responses characterized by remission in three dogs for more than two years. The median overall survival was 264 days (range 49 to 973). No adverse clinical, hematological or biochemical effects were observed with repeated administration of EGFRminicellsDox (30 to 98 doses administered in 10 of the 17 dogs). CONCLUSIONS/SIGNIFICANCE: Targeted minicells loaded with doxorubicin were safely administered to dogs with late stage brain cancer and clinical activity was observed. These findings demonstrate the strong potential for clinical applications of targeted, doxorubicin-loaded minicells for the effective treatment of patients with brain cancer. On this basis, we have designed a Phase 1 clinical study of EGFR-targeted, doxorubicin-loaded minicells for effective treatment of human patients with recurrent glioblastoma