Bilayer characteristics of a diether phosphonolipid analog of the major lung surfactant glycerophospholipid dipalmitoyl phosphatidylcholine.

Thermal and lyotropic phase behavior was studied by X-ray diffraction and differential scanning calorimetry for a diether phosphonolipid analog (DEPN-8) of the major lung surfactant glycerophospholipid dipalmitoyl phosphatidylcholine (DPPC). DEPN-8 differs in an ether, rather than an ester, bond at the acyl chain-backbone linkage and a headgroup phosphonate (isosteric methylene substitution) versus phosphate constituent. Analysis of lamellar diffraction maxima demonstrated that at high relative humidity (98%) and temperatures below the liquid crystal phase transition (approximately 45 degrees C), DEPN-8 formed interdigitated bilayers with a characteristic periodicity of 41.9-46.5 A. At low humidity the gel phase DEPN-8 bilayers were characteristic of a normal L beta phase with a periodicity equivalent to DPPC (57-59 A). Above the liquid crystal thermal phase transition, bilayer spacing for both DEPN-8 and DPPC was 51-52 A, characteristic of the L alpha phase. Complete assessments of both lamellar and in-plane X-ray scattering used to construct electron density profiles and structure-factor plots for DEPN-8 defined more fully the interdigitated bilayer state at high humidity and low temperature. Compared to DPPC, it is energetically favorable for DEPN-8 to form interdigitated bilayers under conditions of excess water and low temperature. The flexible character of the ether bonds in DEPN-8 allows increased hydrophobic interactions between acyl chains, without generating a steric penalty from the increased packing density of the molecules. Additionally, the ether bond and the phosphonate moiety may allow for more energetically favorable interactions between the choline portion of the headgroup and water. The DEPN-8 ether linkage may also contribute to the improved adsorption and film respreading found previously for this phosphonolipid compared to DPPC

Temperature dependence of magnetic anisotropy in Mn-substituted cobalt ferrite

The temperature variation of magnetic anisotropy and coercive field of magnetoelastic manganese-substituted cobaltferrites (CoMnxFe2−xO4 with 0⩽x⩽0.6) was investigated. Major magnetic hysteresis loops were measured for each sample at temperatures over the range 10–400 K, using a superconducting quantum interference device magnetometer. The high-field regimes of the hysteresis loops were modeled using the law of approach to saturation equation, based on the assumption that at sufficiently high field only rotational processes remain, with an additional forced magnetization term that was linear with applied field. The cubic anisotropy constant K1 was calculated from the fitting of the data to the theoretical equation. It was found that anisotropy increases substantially with decreasing temperature from 400 to 150 K, and decreases with increasing Mn content. Below 150 K, it appears that even under a maximum applied field of 5 T, the anisotropy of CoFe2O4 and CoMn0.2Fe1.8O4 is so high as to prevent complete approach to saturation, thereby making the use of the law of approach questionable in these cases

[11C]flumazenil Binding Is Increased in a Dose-Dependent Manner with Tiagabine-Induced Elevations in GABA Levels

Evidence indicates that synchronization of cortical activity at gamma-band frequencies, mediated through GABA-A receptors, is important for perceptual/cognitive processes. To study GABA signaling in vivo, we recently used a novel positron emission tomography (PET) paradigm measuring the change in binding of the benzodiazepine (BDZ) site radiotracer [11C]flumazenil associated with increases in extracellular GABA induced via GABA membrane transporter (GAT1) blockade with tiagabine. GAT1 blockade resulted in significant increases in [11C]flumazenil binding potential (BPND) over baseline in the major functional domains of the cortex, consistent with preclinical studies showing that increased GABA levels enhance the affinity of GABA-A receptors for BDZ ligands. In the current study we sought to replicate our previous results and to further validate this approach by demonstrating that the magnitude of increase in [11C]flumazenil binding observed with PET is directly correlated with tiagabine dose. [11C]flumazenil distribution volume (VT) was measured in 18 healthy volunteers before and after GAT1 blockade with tiagabine. Two dose groups were studied (n = 9 per group; Group I: tiagabine 0.15 mg/kg; Group II: tiagabine 0.25 mg/kg). GAT1 blockade resulted in increases in mean (± SD) [11C]flumazenil VT in Group II in association cortices (6.8±0.8 mL g−1 vs. 7.3±0.4 mL g−1;p = 0.03), sensory cortices (6.7±0.8 mL g−1 vs. 7.3±0.5 mL g−1;p = 0.02) and limbic regions (5.2±0.6 mL g−1 vs. 5.7±0.3 mL g−1;p = 0.03). No change was observed at the low dose (Group I). Increased orbital frontal cortex binding of [11C]flumazenil in Group II correlated with the ability to entrain cortical networks (r = 0.67, p = 0.05) measured via EEG during a cognitive control task. These data provide a replication of our previous study demonstrating the ability to measure in vivo, with PET, acute shifts in extracellular GABA

Identifying gene disruptions in novel balanced de novo constitutional translocations in childhood cancer patients by whole-genome sequencing

PurposeWe applied whole genome sequencing to children diagnosed with neoplasms and found to carry apparently balanced constitutional translocations, to discover novel genic disruptions.MethodsWe applied SV calling programs CREST, Break Dancer, SV-STAT and CGAP-CNV, and developed an annotative filtering strategy to achieve nucleotide resolution at the translocations.ResultsWe identified the breakpoints for t(6;12) (p21.1;q24.31) disrupting HNF1A in a patient diagnosed with hepatic adenomas and Maturity Onset Diabetes of the Young (MODY). Translocation as the disruptive event of HNF1A, a gene known to be involved in MODY3, has not been previously reported. In a subject with Hodgkin’s lymphoma and subsequent low-grade glioma, we identified t(5;18) (q35.1;q21.2), disrupting both SLIT3 and DCC, genes previously implicated in both glioma and lymphoma.ConclusionsThese examples suggest that implementing clinical whole genome sequencing in the diagnostic work-up of patients with novel but apparently balanced translocations may reveal unanticipated disruption of disease-associated genes and aid in prediction of the clinical phenotype

The effectiveness of manual stretching in the treatment of plantar heel pain: a systematic review

Background: Plantar heel pain is a commonly occurring foot complaint. Stretching is frequently utilised as a treatment, yet a systematic review focusing only on its effectiveness has not been published. This review aimed to assess the effectiveness of stretching on pain and function in people with plantar heel pain. Methods: Medline, EMBASE, CINAHL, AMED, and The Cochrane Library were searched from inception to July 2010. Studies fulfilling the inclusion criteria were independently assessed, and their quality evaluated using the modified PEDro scale. Results: Six studies including 365 symptomatic participants were included. Two compared stretching with a control, one study compared stretching to an alternative intervention, one study compared stretching to both alternative and control interventions, and two compared different stretching techniques and durations. Quality rating on the modified Pedro scale varied from two to eight out of a maximum of ten points. The methodologies and interventions varied significantly between studies, making meta-analysis inappropriate. Most participants improved over the course of the studies, but when stretching was compared to alternative or control interventions, the changes only reached statistical significance in one study that used a combination of calf muscle stretches and plantar fascia stretches in their stretching programme. Another study comparing different stretching techniques, showed a statistically significant reduction in some aspects of pain in favour of plantar fascia stretching over calf stretches in the short term. Conclusions: There were too few studies to assess whether stretching is effective compared to control or other interventions, for either pain or function. However, there is some evidence that plantar fascia stretching may be more effective than Achilles tendon stretching alone in the short-term. Appropriately powered randomised controlled trials, utilizing validated outcome measures, blinded assessors and long-term follow up are needed to assess the efficacy of stretching

The fables of pity: Rousseau, Mandeville and the animal-fable

Copyright @ 2012 Edinburgh University PressPrompted by Derrida’s work on the animal-fable in eighteenth-century debates about political power, this article examines the role played by the fiction of the animal in thinking of pity as either a natural virtue (in Rousseau’s Second Discourse) or as a natural passion (in Mandeville’s The Fable of the Bees). The war of fables between Rousseau and Mandeville – and their hostile reception by Samuel Johnson and Adam Smith – reinforce that the animal-fable illustrates not so much the proper of man as the possibilities and limitations of a moral philosophy that is unable to address the political realities of the state

Electronic Health Record Functionality Needed to Better Support Primary Care

Electronic health records (EHRs) must support primary care clinicians and patients, yet many clinicians remain dissatisfied with their system. This manuscript presents a consensus statement about gaps in current EHR functionality and needed enhancements to support primary care. The Institute of Medicine primary care attributes were used to define needs and Meaningful Use (MU) objectives to define EHR functionality. Current objectives remain disease- rather than whole-person focused, ignoring factors like personal risks, behaviors, family structure, and occupational and environmental influences. Primary care needs EHRs to move beyond documentation to interpreting and tracking information over time as well as patient partnering activities, support for team based care, population management tools that deliver care, and reduced documentation burden. While Stage 3 MU’s focus on outcomes is laudable, enhanced functionality is still needed including EHR modifications, expanded use of patient portals, seamless integration with external applications, and advancement of national infrastructure and policies

New Skull Material of Taeniolabis taoensis (Multituberculata, Taeniolabididae) from the Early Paleocene (Danian) of the Denver Basin, Colorado

Taeniolabis taoensis is an iconic multituberculate mammal of early Paleocene (Puercan 3) age from the Western Interior of North America. Here we report the discovery of significant new skull material (one nearly complete cranium, two partial crania, one nearly complete dentary) of T. taoensis in phosphatic concretions from the Corral Bluffs study area, Denver Formation (Danian portion), Denver Basin, Colorado. The new skull material provides the first record of the species from the Denver Basin, where the lowest in situ specimen occurs in river channel deposits ~730,000 years after the Cretaceous-Paleogene boundary, roughly coincident with the first appearance of legumes in the basin. The new material, in combination with several previously described and undescribed specimens from the Nacimiento Formation of the San Juan Basin, New Mexico, is the subject of detailed ana- tomical study, aided by micro-computed tomography. Our analyses reveal many previously unknown aspects of skull anatomy. Several regions (e.g., anterior portions of premaxilla, orbit, cranial roof, occiput) preserved in the Corral Bluffs specimens allow considerable revision of previous reconstructions of the external cranial morphology ofT. taoensis. Similarly, anatomical details of the ascending process of the dentary are altered in light of the new material. Although details of internal cranial anatomy (e.g., nasal and endocranial cavities) are difficult to discern in the available specimens, we provide, based on UCMP 98083 and DMNH.EPV 95284, the best evidence to date for inner ear structure in a taeniolabidoid multituberculate. The cochlear canal of T. taoensis is elongate and gently curved and the vestibule is enlarged, although to a lesser degree than in Lambdopsalis

'To live and die [for] Dixie': Irish civilians and the Confederate States of America

Around 20,000 Irishmen served in the Confederate army in the Civil War. As a result, they left behind, in various Southern towns and cities, large numbers of friends, family, and community leaders. As with native-born Confederates, Irish civilian support was crucial to Irish participation in the Confederate military effort. Also, Irish civilians served in various supporting roles: in factories and hospitals, on railroads and diplomatic missions, and as boosters for the cause. They also, however, suffered in bombardments, sieges, and the blockade. Usually poorer than their native neighbours, they could not afford to become 'refugees' and move away from the centres of conflict. This essay, based on research from manuscript collections, contemporary newspapers, British Consular records, and Federal military records, will examine the role of Irish civilians in the Confederacy, and assess the role this activity had on their integration into Southern communities. It will also look at Irish civilians in the defeat of the Confederacy, particularly when they came under Union occupation. Initial research shows that Irish civilians were not as upset as other whites in the South about Union victory. They welcomed a return to normalcy, and often 'collaborated' with Union authorities. Also, Irish desertion rates in the Confederate army were particularly high, and I will attempt to gauge whether Irish civilians played a role in this. All of the research in this paper will thus be put in the context of the Drew Gilpin Faust/Gary Gallagher debate on the influence of the Confederate homefront on military performance. By studying the Irish civilian experience one can assess how strong the Confederate national experiment was. Was it a nation without a nationalism

Liquid–Liquid Equilibria of Ionic Liquids–Water–Acetic Acid Mixtures

International audienceThe liquid–liquid equilibria of ionic liquid-based systems with water and/or acetic acid have been studied at 293.15 K and atmospheric pressure. One hydrophilic ionic liquid and a series of hydrophobic ionic liquids were investigated in order to examine their effect on the separation of water and acetic acid mixtures. The ionic liquids studied were [P666,14]Cl, [P666,14][NTf2], [C4mmim][NTf2], [Cnmim][NTf2] (n = 2, 4, 6, 8, or 10), [C4mpyrr][NTf2], [N1114][NTf2], and [C2mim][EtSO4]. [C2mim][EtSO4] is totally miscible with water and acetic acid in all compositions. Comparing [P666,14]Cl with [P666,14][NTf2], the former showed higher extraction selectivities; however, due to the larger viscosity of [P666,14]Cl, the [NTf2]− based ionic liquids offer a better solvent choice for the liquid extraction processes. As expected, as the solubility of water decreases with increasing the chain length of ionic liquids, this in turn leads to [C10mim][NTf2] showing greater acetic efficiency than [C2mim][NTf2] for the separation of water and acetic acid. The experimental data obtained for ternary systems containing the [C4mmim][NTf2] demonstrated that the modification of the C(2) position on the imidazolium ring does not significantly affect the selectivity compared with [C4mim][NTf2]. Tetraalkyl ammonium and N-alkyl pyrrolidinium based ionic liquids were also studied with the [NTf2]− anion with the results for the system containing the [C4mpyrr][NTf2] demonstrating a higher selectivity for the separation of water and acetic acid than the other [NTf2]− based systems studied. All experimental data were then correlated using the UNIQUAC model within an accuracy close to 1.6%. Finally, the ionic liquids were also compared with standard molecular extraction solvent, for example, methyl tert-butyl ether and methyl isobutyl ketone. The organic solvents showed an advantage over the [Cnmim][NTf2]-based ionic liquids but only over a narrow composition range. In all ionic liquid systems, the selectivity remains high at low acetic acid concentration compared with that found in the organic solvents, which is important for practical operation and demonstrates the advantages of using an ionic liquid for the extraction