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Reliable neutron star mass measurements are key to determining the equation-of-state of cold nuclear matter, but these are rare. "Black Widows" and "Redbacks" are compact binaries consisting of millisecond pulsars and semi-degenerate companion stars. Spectroscopy of the optically bright companions can determine their radial velocities, providing inclination-dependent pulsar mass estimates. While inclinations can be inferred from subtle features in optical light curves, such estimates may be systematically biased due to incomplete heating models and poorly-understood variability. Using data from the Fermi Large Area Telescope, we have searched for gamma-ray eclipses from 49 spider systems, discovering significant eclipses in 7 systems, including the prototypical black widow PSR B1957$+$20. Gamma-ray eclipses require direct occultation of the pulsar by the companion, and so the detection, or significant exclusion, of a gamma-ray eclipse strictly limits the binary inclination angle, providing new robust, model-independent pulsar mass constraints. For PSR B1957$+$20, the eclipse implies a much lighter pulsar ($M_{\rm psr} = 1.81 \pm 0.07\,M_{\odot}$) than inferred from optical light curve modelling., Comment: 31 pages, 4 figures, includes supplementary tables; published in Nature Astronomy

Ultrasound-enhanced delivery of therapeutic-loaded echogenic liposomes is under development for vascular applications using the EkoSonic Endovascular System. In this study, fibrin-targeted echogenic liposomes loaded with an anti-inflammatory agent were characterized before and after infusion through an EkoSonic catheter. Cavitation activity was nucleated by Definity or fibrin-targeted, drug-loaded echogenic liposomes infused and insonified with EkoSonic catheters. Passive cavitation imaging was used to quantify and map bubble activity in a flow phantom mimicking porcine arterial flow. Cavitation was sustained during 3-min infusions of Definity or echogenic liposomes along the distal 6 cm treatment zone of the catheter. Though the EkoSonic catheter was not designed specifically for cavitation nucleation, infusion of drug-loaded echogenic liposomes can be employed to trigger and sustain bubble activity for enhanced intravascular drug delivery.

We recently discovered that the expression of PRKN, a young-onset Parkinson disease-linked gene, confers redox homeostasis. To further examine the protective effects of parkin in an oxidative stress model, we first combined the loss of prkn with Sod2 haploinsufficiency in mice. Although adult prkn−/−//Sod2± animals did not develop dopamine cell loss in the S. nigra, they had more reactive oxidative species and a higher concentration of carbonylated proteins in the brain; bi-genic mice also showed a trend for more nitrotyrosinated proteins. Because these redox changes were seen in the cytosol rather than mitochondria, we next explored the thiol network in the context of PRKN expression. We detected a parkin deficiency-associated increase in the ratio of reduced glutathione (GSH) to oxidized glutathione (GSSG) in murine brain, PRKN-linked human cortex and several cell models. This shift resulted from enhanced recycling of GSSG back to GSH via upregulated glutathione reductase activity; it also correlated with altered activities of redox-sensitive enzymes in mitochondria isolated from mouse brain (e.g., aconitase-2; creatine kinase). Intriguingly, human parkin itself showed glutathione-recycling activity in vitro and in cells: For each GSSG dipeptide encountered, parkin regenerated one GSH molecule and was S-glutathionylated by the other (GSSG + P-SH $$\to$$ → GSH + P-S-SG), including at cysteines 59, 95 and 377. Moreover, parkin’s S-glutathionylation was reversible by glutaredoxin activity. In summary, we found that PRKN gene expression contributes to the network of available thiols in the cell, including by parkin’s participation in glutathione recycling, which involves a reversible, posttranslational modification at select cysteines. Further, parkin’s impact on redox homeostasis in the cytosol can affect enzyme activities elsewhere, such as in mitochondria. We posit that antioxidant functions of parkin may explain many of its previously described, protective effects in vertebrates and invertebrates that are unrelated to E3 ligase activity.

The Scanning Habitable Environments with Raman and Luminescence for Organics and Chemicals (SHERLOC) is a robotic arm-mounted instrument onboard NASA’s Perseverance rover. SHERLOC combines imaging via two cameras with both Raman and fluorescence spectroscopy to investigate geological materials at the rover’s Jezero crater field site. SHERLOC requires in situ calibration to monitor the health and performance of the instrument. These calibration data are critically important to ensure the veracity of data interpretation, especially considering the extreme martian environmental conditions where the instrument operates. The SHERLOC Calibration Target (SCT) is located at the front of the rover and is exposed to the same atmospheric conditions as the instrument. The SCT includes 10 individual targets designed to meet all instrument calibration requirements. An additional calibration target is mounted inside the instrument’s dust cover. The targets include polymers, rock, synthetic material, and optical pattern targets. Their primary function is calibration of parameters within the SHERLOC instrument so that the data can be interpreted correctly. The SCT was also designed to take advantage of opportunities for supplemental science investigations and includes targets intended for public engagement. The exposure of materials to martian atmospheric conditions allows for opportunistic science on extravehicular suit (i.e., “spacesuit”) materials. These samples will be used in an extended study to produce direct measurements of the expected service lifetimes of these materials on the martian surface, thus helping NASA facilitate human exploration of the planet. Other targets include a martian meteorite and the first geocache target to reside on another planet, both of which increase the outreach and potential of the mission to foster interest in, and enthusiasm for, planetary exploration. During the first 200 sols (martian days) of operation on Mars, the SCT has been analyzed three times and has proven to be vital in the calibration of the instrument and in assisting the SHERLOC team with interpretation of in situ data.

Natural killer (NK) cells are innate immune cells that recognize malignant cells through a wide array of germline-encoded receptors. Triggering of activating receptors results in cytotoxicity and broad immune system activation. The former is achieved through release of cytotoxic granules and presentation of death receptor ligands, while the latter is mediated by inflammatory cytokines, such as interferon-γ and tumor necrosis factor α. Early success with ex vivo activation of NK cells and adoptive transfer suggest they are a safe therapeutic with promising responses in advanced hematologic malignancies. In particular, adoptive NK cell therapies can serve as a ‘bridge’ to potentially curative allogeneic stem cell transplantation. In addition, strategies are being developed that expand large numbers of cells from limited starting material and mature NK cells from precursors. Together, these make ‘off-the-shelf’ NK cells possible to treat a wide range of cancers. Research efforts have focused on creating a range of tools that increase targeting of therapeutic NK cells toward cancer—from therapeutic antibodies that drive antibody-dependent cellular cytotoxicity, to chimeric antigen receptors. As these novel therapies start to show promise in clinical trials, the field is rapidly moving toward addressing other challenges that limit NK cell therapeutics and the goal to treat solid tumors. This review describes the state of therapeutic NK cell targeting of tumors; discusses the challenges that need to be addressed before NK cells can be applied as a wide-ranging treatment for cancer; and points to some of the innovations that are being developed to surmount these challenges. Suppressive cells in the tumor microenvironment pose a direct threat to therapeutic NK cells, through presentation of inhibitory ligands and secretion of suppressive cytokines and metabolites. The nutrient- and oxygen-starved conditions under which NK cells must function necessitate an understanding of therapeutic NK cell metabolism that is still emerging. Prior to these challenges, NK cells must find their way into and persist in the tumor itself. Finally, the desirability of a ‘single-shot’ NK cell treatment and the problems and benefits of a short-lived rejection-prone NK cellular product are discussed.

Factors underlying gastroparesis are not well defined. We hypothesized that multiple systems may be involved in patients with gastroparesis symptoms and performed a comparative physiologic study. We studied 43 consecutive eligible patients with gastroparetic symptoms categorized by GI symptoms, metabolic status, illness quantification, and gastric physiology. Patients were evaluated by two methods in each of five core areas: inflammatory, autonomic, enteric, electrophysiologic, and hormonal with abnormalities examined by correlations. Patients had similar GI symptoms regardless of baseline gastric emptying or diabetic/idiopathic status, and all patients demonstrated abnormalities in each of the 5 areas studied. Nearly all patients presented with elevated markers of serum TNFα (88%) and serum IL-6 (91%); elevated cutaneous electrogastrogram frequency (95%); and interstitial cells of Cajal count abnormalities (inner: 97%, outer: 100%). Measures of inflammation correlated with a number of autonomic, enteric anatomy, electrophysiologic and hormonal abnormalities. We conclude that patients with the symptoms of gastroparesis have multiple abnormalities, when studied by traditional, as well as newer, diagnostic assessments. Inflammation appears to be a fundamental abnormality that affects other organ systems in symptomatic patients. Future work on gastroparetic syndromes and their treatment may benefit from a focus on the diffuse nature of their illness, diverse pathophysiologic mechanisms involved, especially the possible causes of underlying inflammation and disordered hormonal status. This study is registered with Clinicaltrials.gov under study # NCT03178370 https://clinicaltrials.gov/ct2/show/NCT03178370 .

The Scanning Habitable Environments with Raman and Luminescence for Organics and Chemicals (SHERLOC) is a robotic arm-mounted instrument on NASA’s Perseverance rover. SHERLOC has two primary boresights. The Spectroscopy boresight generates spatially resolved chemical maps using fluorescence and Raman spectroscopy coupled to microscopic images (10.1 μm/pixel). The second boresight is a Wide Angle Topographic Sensor for Operations and eNgineering (WATSON); a copy of the Mars Science Laboratory (MSL) Mars Hand Lens Imager (MAHLI) that obtains color images from microscopic scales (∼13 μm/pixel) to infinity. SHERLOC Spectroscopy focuses a 40 μs pulsed deep UV neon-copper laser (248.6 nm), to a ∼100 μm spot on a target at a working distance of ∼48 mm. Fluorescence emissions from organics, and Raman scattered photons from organics and minerals, are spectrally resolved with a single diffractive grating spectrograph with a spectral range of 250 to ∼370 nm. Because the fluorescence and Raman regions are naturally separated with deep UV excitation (−1 (250 to 273 nm) and the fluorescence region (274 to ∼370 nm) are acquired simultaneously without time gating or additional mechanisms. SHERLOC science begins by using an Autofocus Context Imager (ACI) to obtain target focus and acquire 10.1 μm/pixel greyscale images. Chemical maps of organic and mineral signatures are acquired by the orchestration of an internal scanning mirror that moves the focused laser spot across discrete points on the target surface where spectra are captured on the spectrometer detector. ACI images and chemical maps (< 100 μm/mapping pixel) will enable the first Mars in situ view of the spatial distribution and interaction between organics, minerals, and chemicals important to the assessment of potential biogenicity (containing CHNOPS). Single robotic arm placement chemical maps can cover areas up to 7x7 mm in area and, with the < 10 min acquisition time per map, larger mosaics are possible with arm movements. This microscopic view of the organic geochemistry of a target at the Perseverance field site, when combined with the other instruments, such as Mastcam-Z, PIXL, and SuperCam, will enable unprecedented analysis of geological materials for both scientific research and determination of which samples to collect and cache for Mars sample return.

The aim of this study was to report a method that quantifies axon reflex sweating from individual sweat glands with nanoliter precision. Measurement of the axon reflex is generally expressed as a single variable (e.g., the flare area or total sweat volume). High-definition videography enables precise measurement of sweating from single, axon reflex-stimulated sweat glands (SGs). The sudomotor axon reflex was activated in healthy subjects and subjects with peripheral neuropathy by iontophoresis of 10% acetylcholine. Sweating was simultaneously imaged for 5 min in a 2.5-cm2 area of iodine-coated skin to one side of the stimulus, using a customized high-resolution camera with starch-coated transparent tape over a rigid viewing screen. A second video then imaged the directly stimulated sweating. The indirect sweat response was quantified in terms of sweat gland number and distance from the stimulation site (radius), sweat rate per gland, and total sweat. Fifty-two healthy control and twenty subjects with neuropathy underwent testing at the foot, calf, thigh, and hand. Normal ranges were calculated for SG density, mean sweat rate per SG, and total sweat volume. Neuropathy subjects demonstrated reduced sweating, and values differed between body sites. The described method precisely measures the total and individual sweat output of hundreds of SGs in response to a standard, axon reflex-mediated stimulus, and quantifies alterations in axon reflex sweating seen in peripheral neuropathy.

Closed-cell foams were produced from re-melted aluminum alloy scrap that contained 0.13 wt pct Mg magnesium in the as-received state and higher levels after adding 1, 2, or 5 wt pct Mg. The excess Mg gave rise to the fragmentation of long oxide filaments present in the scrap alloy into smaller filaments and improved its distribution and wetting by the Al matrix. Foaming the re-melted scrap alloy containing 1, 2, and 5 wt pct Mg excess showed stability and good expansion in comparison to the scrap alloy containing 0.13 wt pct Mg only, but the cells became non-equiaxed when the Mg concentration was high (≥2 wt pct excess) due to cell wall rupture during solidification. Compressibility and energy absorption behavior were studied for scrap alloy foams containing 1 wt pct Mg excess, which is the optimum level to obtain good expansion, stability, and uniform cell size. Foams with densities in the range of 0.2 to 0.4 g cm−1 produced by holding at the foaming temperature for different times were used for the investigation. A uniform cell structure led to flatter stress plateaus, higher energy absorption efficiencies, and reduced “knockdown” in strength compared with commercial foams made by gas bubbling. The mechanical performance found is comparable to that of commercial foams made by a similar method but the expected costs are lower.

This research outlines the application of an enzyme-linked immunosorbent assay (ELISA) for the analysis of clenbuterol in animal products. Our assay showed good sensitivity for clenbuterol (0.4 ng/g or 0.4 ppb) and low detection limit (0.09 ng/g or 0.09 ppb). A low cross-reactivity for other β2-agonist drugs such as salbutamol, terbutaline, and epinephrine led to formatting an ELISA kit considered to have a high specificity for clenbuterol. A survey of Ho Chi Minh City pork market was conducted as part of the validation of our ELISA. ELISA results showed a surprisingly high value of contamination. However, it will be necessary to conduct a more statistically valid replicated survey with evaluation by other instrumental methods to obtain a definite conclusion. This ELISA kit will be used to monitor growth promoter residues in Vietnam's animal products.

The purpose of this study is to report our institutional experience using radiotherapy in the treatment of ameloblastoma and ameloblastic carcinoma. Three patients with ameloblastoma and 3 patients with ameloblastic carcinoma were treated with radiotherapy alone (2 patients) or surgery and postoperative radiotherapy (4 patients) at the University of Florida between 1973 and 2007. Follow-up ranged from 4.0 to 13.1 years with a median of 7.8 years. Radiotherapy complications were scored using the Common Terminology Criteria for Adverse Events, version 4.0. Local control was achieved in 4 of the 6 patients. One patient treated with RT alone for an unresectable ameloblastoma developed a local recurrence and metastases in both the cervical lymph nodes and lungs, but had excellent response to dual BRAF/MEK inhibition with dabrafenib and trametinib. Another patient treated with surgery and postoperative radiotherapy for an ameloblastic carcinoma recurred locally without metastasis, but was not salvaged. No significant treatment-related complications were observed. For patients with local recurrence or inadequate margins after surgery, adjuvant radiotherapy provides the potential for disease control. In the setting of metastatic disease, targeted therapies may provide an additional opportunity for salvage.

Affiliation of authors Lindsay McElmurray, Dr. Michael Hughes, Dr. Hani Rashed, Dr. William Kennedy, Dr. Gwen Wendelschafer-Crabb, Dr. Xiu Yang, Dr. Mostafa Fraig and Christina Pinkston are updated through this erratum.

This study investigates the pressure-drop behaviour associated with airflow through bulk and structurally tailored multi-layered, open-cell porous Inconel structures over a wide airflow velocity range (0textendash50 m s-1). The effect of airflow velocity on the pressure-drop behaviour as a function of the sample thickness is presented and related to the flow behaviour corresponding to the relevant flow regimes (Darcy, Forchheimer, Turbulent and Postturbulent). Entrance effects are highlighted as a source of the pressure-drop increase for porous structures with air gaps, regardless of their sizes, as long as they are larger than those generated by loosely-stacked structures. The pressure-drops for gapped porous structures and the mathematical-summation of the pressure drop for the corresponding individual components, were in very good agreement, at lower airflow velocities. The potential for mass-efficient porous structures, providing a high pressure drop, was demonstrated using multiple thin porous laminates separated by air gaps.

The purpose of this study is to update our institution's experience with ipsilateral radiation therapy (RT) for squamous cell carcinoma of the tonsillar area. Outcome study of 76 patients treated between 1984 and 2012 with ipsilateral RT for squamous cell carcinoma of the tonsil. Patients had either cT1 (n = 41, 54 %) or cT2 (n = 35, 46 %) primaries and cN0 (n = 27, 36 %), cN1 (n = 15, 20 %), cN2a (n = 8, 11 %), or cN2b (n = 26, 34 %) nodal disease. Of these, 32 (42 %) patients underwent a planned neck dissection and 21 (28 %) patients received concomitant chemotherapy. Median follow-up for all patients was 7.1 years (range 0.1-27.2) and 7.8 years (range 2.1-27.2 years) for living patients. The 2- and 5-year control and survival rates were as follows: local control, 98.6 and 96.9 %; local-regional control 95.8 and 92.6 %; cause-specific survival 95.9 and 93.1 %; and overall survival, 92.1 and 83.8 %. One patient failed in the contralateral, non-radiated neck 3 years after primary treatment. Univariate analysis revealed that overall survival was significantly influenced by whether the patient had a primary tumor in the anterior tonsillar pillar versus the tonsillar fossa with the latter performing better. The incidence of severe late complications was 16 %. Ipsilateral RT for patients with squamous cell carcinoma of the anterior tonsillar pillar or tonsillar fossa with no base of tongue or soft palate extension is an efficacious treatment that provides excellent control rates with a relatively low incidence of late complications.

Porous Al structures have been made using a porogen leaching method but with additional novel steps. In this way, Al-0.25Cu-0.6Si-1.0Mg alloys with interconnected, open cells have been made, with high levels of porosity (up to 89%). The use of 4 to 5 mm diameter sodium chloride droplets combined with interspersion of the metal powder and droplets in the die and dissolution of the salt before sintering was found to enable easier interspersion of the two components, resulting in good connectivity of the beads via the formation of “windows” between the pores, and rapid elimination of salt from the structure. Porous Al with densities in the range of 0.28–0.86 g/cm3 exhibited compressive yield strengths in the range of 0.14 to 7.5 MPa, with no difference being observed between the samples made by this route and by more conventional dissolution of the salt after sintering. These novel steps widen the possibility for porous metal manufacture to other materials, not limited by the need to have a sintering temperature below that for the melting point of salt.

In agricultural catchments, aquatic ecosystems can experience a pulse exposure to pesticides. Following such exposure, non-target organisms that are not extirpated may recover. This paper investigates the potential of two duckweed species (Lemna minor and Lemna gibba) to recover from a 7-day exposure to different concentrations (0.4-208 µg L(-1)) of the herbicide diuron. There was significant inhibition in the growth and biomass after the initial 7-day exposure (e.g. frond number EC50=59.2 and 52.2 µg L(-1) for L. minor and L. gibba, respectively). Following transfer to clean media, recovery (the highest concentration yielding no significant difference in the effect endpoint from the control) was observed for all effects endpoints at concentrations ranging 60-111 µg L(-1) for L. minor and 60-208 µg L(-1) for L. gibba. These results suggest that recovery is possible for primary producers at environmentally relevant concentrations considered significant in ecological risk assessment.

To examine the feasibility of a breast cancer-related lymphoedema (BCRL) screening programme. Additionally, to investigate the efficacy of bioimpedance analysis (BIA) compared to circumferential measurements (CM) in detecting BCRL. This was a 12-month prospective feasibility study. Participants were recruited from two diagnostic breast clinics and consented to be screened for BCRL. Pre-surgical assessments were conducted, and participants were followed up at quarterly intervals. BIA and CM measurements were conducted at all time points. An L-Dex score of >10 or a 10-U increase from baseline or a ≥5 % increase in proximal, distal or total percentage volume difference (PVD) from baseline was indicative of BCRL. Information was collected on subjective symptoms, potential risk factors, demographics and medical data. Feasibility was based on uptake and retention. One hundred twenty-six participants were recruited with an attrition rate of 16.2 %. Participants’ mean age was 59 years with the majority having stage I (63.9 %), infiltrating ductal carcinoma (87.4 %). 31.6 % were identified as having BCRL, 90.3 % detected by CM and 35.5 % by BIA (p = ≤0.0001). We found no significant correlation between BIA and CM. Participants identified as having BCRL had a higher BMI, a recent injury to their ‘at-risk’ arm and more lymph nodes excised (p =

Surgeons have attempted to minimize postoperative anastomotic complications by employing intraoperative tests and manoeuvres to assess colorectal anastomotic integrity. These have evolved over time with improvement in operative technology and techniques. This systematic review aims to examine the impact of such intraoperative assessments. A systematic review of studies assessing intraoperative anastomotic assessments and their impact on postoperative anastomotic complications was performed. Intraoperative measures undertaken as a result of intraoperative assessments and postoperative anastomotic complications were analysed. 37 Studies were identified. 13 studies evaluated basic mechanical patency tests, ten studies evaluated endoscopic visualisation techniques and 14 studies evaluated microperfusion techniques. Postoperative anastomotic complications were significantly lower in patients tested with basic mechanical patency tests compared to those untested (non-RCT: 4.1 vs. 8.1 %, p = 0.03, RCTs: 5.8 vs. 16.0 %, p = 0.024). There were no differences in postoperative anastomotic complications between tested and non-tested cohorts in non-randomised cohort studies evaluating endoscopic visualisation techniques. However, intraoperative measures taken after abnormal intraoperative tests may have reduced the number of postoperative complications. Perfusion analysis techniques are not in routine widespread clinical practice as yet, but newer techniques such as fluorescent dyes and imaging under near infrared light show technical feasibility. Intraoperative colorectal anastomotic assessment has evolved together with advancement of technology in the surgical setting. Moderate benefit in terms of lower postoperative anastomotic complications has been shown with basic mechanical patency testing and more recently with intraoperative endoscopic visualisation of colorectal anastomoses. The next advance and possible introduction into routine practice may include the use of microperfusion techniques. The latest in this group of techniques, which utilise autofluorescent dyes such as Indocyanine green, hold great potential. Well-planned controlled studies or ideally, randomised controlled trials need to be conducted to further assess the benefit of these latest techniques.

Background: Sialophorin is a transmembrane sialoglycoprotein. Normally, the molecule is only produced by white blood cells where it regulates functions such as intercellular adhesion, intracellular signalling, apoptosis, migration and proliferation. Methods: Normal breast tissue and primary breast tumours were analysed by immunohistochemistry for sialophorin expression. The sialophorin-positive breast cancer cell line MCF7 was engineered to stably express either non-targeted or sialophorin-targeted small interfering RNA (siRNA). Assays were then performed in vitro to assess apoptosis, intracellular adhesion, transendothelial migration and cytotoxicity. An orthotopic mouse model assayed ability to produce tumours in vivo. Results: Normal breast epithelial cells exhibit expression of the N-terminal domain of sialophorin in the cytoplasm but not the nucleus. The majority of these normal cells are also negative for expression of the C-terminal domain. In contrast, malignant breast epithelial cells exhibit N-terminal expression both in the cytoplasm and nucleus and the majority express the C-terminus in the nucleus. Using differential patterns of intracellular expression of the N and C termini of sialophorin, we define six subtypes of breast cancer that are independent of histological and receptor status classification. Targeting sialophorin with siRNA resulted in the MCF7 breast cancer cell line exhibiting increased homotypic adhesion, decreased transendothelial migration, increased susceptibility to apoptosis, increased vulnerability to lysis by natural killer cells and decreased ability to produce tumours in mice. Conclusion: Our results indicate that intracellular patterns of sialophorin expression define a new molecular classification of breast cancer and that sialophorin represents a novel therapeutic target.

We have developed a simple and fast immuno- chromatographic test strip for the simultaneous quantitation of aflatoxin B1 and aflatoxin B2 in corn and rice. The strip contains three pads (sample, conjugate, and absorbing pad) and uses the respective polyclonal antibodies immobilized on gold nanoparticles. Matrix interferences were minimized by appli- cation of fugacity theory. Clean-up of samples and pre- treatment of strip pads is not required. The visual detection limit is 0.1 ng mL �1 , and the process can be completed within 5 min. Out of 113 natural samples, 16 rice and 27 corn samples (38% in total) were aflatoxin positive and the test results were confirmed by HPLC. The strip shows, however, high cross reactivity to aflatoxins G1 ,G 2 ,a nd M1. We consider this strip to possess wide applicability because of its ease of use, sensi- tivity, stability, and low cost.

Werner syndrome (WS) is the canonical adult human progeroid (‘premature aging’) syndrome. Patients with this autosomal recessive Mendelian disorder display constitutional genomic instability and an elevated risk of important age-associated diseases including cancer. Remarkably few analyses of WS patient tissue and tumors have been performed to provide insight into WS disease pathogenesis or the high risk of neoplasia. We used autopsy tissue from four mutation-typed WS patients to characterize pathologic and genomic features of WS, and to determine genomic features of three neoplasms arising in two of these patients. The results of these analyses provide new information on WS pathology and genomics; provide a first genomic characterization of neoplasms arising in WS; and provide new histopathologic and genomic data to test several popular models of WS disease pathogenesis.

Alumina ceramic foams have been infiltrated with an Al-10 Mg alloy, by a capillarity-driven process, to create interpenetrating composites. Infiltration maps are presented for three different foam types which depict the temperature and time required for successful infiltration. The Young’s modulus of “fully” infiltrated composites containing approximately 18, 25, and 36 vol.% ceramic were measured and found to be 96, 110, and 124 GPa, respectively. Porosimetry of the foams revealed a significant fraction of closed porosity within the cell walls, the quantity of which increases with foam density, which accounts for the lower density and stiffness values that were measured, compared with those predicted by a simple model.

The first North American Comparison of absolute gravimeters (NACAG-2010) was hosted by the National Oceanic and Atmospheric Administration at its newly renovated Table Mountain Geophysical Observatory (TMGO) north of Boulder, Colorado, in October 2010. NACAG-2010 and the renovation of TMGO are part of NGS’s GRAV-D project (Gravity for the Redefinition of the American Vertical Datum). Nine absolute gravimeters from three countries participated in the comparison. Before the comparison, the gravimeter operators agreed to a protocol describing the strategy to measure, calculate, and present the results. Nine sites were used to measure the free-fall acceleration of g. Each gravimeter measured the value of g at a subset of three of the sites, for a total set of 27 g-values for the comparison. The absolute gravimeters agree with one another with a standard deviation of 1.6 μGal (1 Gal ≡ 1 cm s −2). The minimum and maximum offsets are −2.8 and 2.7 μGal. This is an excellent agreement and can be attributed to multiple factors, including gravimeters that were in good working order, good operators, a quiet observatory, and a short duration time for the experiment. These results can be used to standardize gravity surveys internationally.

In this study, scrap from the automotive industry was used to produce aluminium foams under vacuum. Chips of an aluminium alloy LM26 were melted and 1wt. % of Mg was added for creating a viscous casting with uniform distribution of oxides. An ingot was obtained of this alloy after casting and solidification. Trials for foaming this alloy were performed by re-melting pieces under vacuum at different temperatures. A window in the vacuum chamber allowed observation of the foaming and collapse of the porous structures was observed during cooling. Characterization of the aluminum foams revealed different levels of expansion, porous structures and degrees of drainage. The best foams were obtained at 680 °C with a density of 0.78 g/cm3. This technique appears to be a feasible low cost route for producing Al foams based on scrap material.

This article reviews diagnosis and treatment in the Commonwealth of Independent States in three clinical areas: tuberculosis, substance misuse, and neurological disorders in children. While the specific problems in each of these areas differ greatly, commonalities emerge, pointing to the continued influence of the Soviet past. Although progress in developing evidence-based medicine is being made, the isolation of Soviet science from Western developments has resulted in the widespread use of outdated diagnostic procedures and treatment protocols, while finance mechanisms still encourage unnecessary hospitalizations and treatments. A hierarchical medical system, as well as underdeveloped patient rights and medical ethics, mean that patients have little information and ability to participate in decision-making. The continued use of outdated approaches to diagnosis and treatment contributes to poor population health outcomes in the region.

[Preview] Reduced health-related quality of life (HrQoL), including impaired cognitive, social, physical, behavioural and emotional functioning, is common in children treated for medulloblastoma and has been associated with clinical factors such as surgical resection and treatment modality]. recent biological advances have allowed the distinction of medulloblastomas into four consensus molecular subgroups—WNT, sHH, Group 3 and Group 4—which display distinct molecular, clinical, and pathological disease characteristics. Together, these observations raise the hypothesis that HrQoL in medulloblastoma survivors may be related to their underlying tumour biology.

Achieving specific counting of plant growth promoting (PGP) microorganisms maintained at high numbers in inert carriers such as peat is an important objective for the inoculation of field crops such as cereals. In this paper, methods based on selective media together with strain-specific counting using enzyme-linked immunoassay (ELISA) were examined. Selective plate counting was developed by screening four commercial PGP biofertiliser strains for resistance to antibiotics. ELISAs for each strain were developed and calibrated by purifying polyclonal antibodies, testing sample pre-treatment strategies, and investigating the effect of culture age on standard curves. Selective plate counting proved to be more accurate than the ELISA methodology, confirming that all microbial strains survived for at least 1 month in sterile peat without loss in viable numbers, and further demonstrated growth inhibition of the strain Candida tropicalis HY when co-inoculated with the other strains Pseudomonas fluorescens 1 N, Bacillus amyloliquefaciens E19 and Bacillus subtilis B9. This is the first known study to have investigated the dynamics of PGP microorganisms in multi-strain inoculants and demonstrates the utility and hitherto unmentioned drawbacks of two different low-cost counting methods for biofertiliser quality control. Such information is vital for the adoption and success of non-rhizobial PGP biofertilisers for sustainable agriculture.

17α-ethynyl-5α-androstane-3α, 17β-diol (HE3235, Apoptone) is an orally bioavailable synthetic analogue of 3β-androstanediol, that is active in rodent models of prostate and breast cancer, and is in Phase IIa clinical trials for the treatment of early- and late-stage prostate cancer. In preparation for clinical studies, nuclear hormone receptor and P450 interactions for HE3235 and major metabolites were characterized in vitro, and pharmacokinetics and metabolite profiles were studied in rodents, dogs, and monkeys. Four-week safety studies conducted in rats and dogs indicated a substantial margin of safety for clinical use, and no evidence of electrocardiographic or neurological effects, although anorexia, thrombocytopenia, and hypokalemia were identified as potentially dose-limiting toxicities at superpharmacological exposures. Pharmacokinetics and drug metabolism have been studied in prostate cancer patients.

The effect of a K–Al–F-based flux was investigated on the wettability of TiC by an Al–7 wt%Si alloy in the interval of temperatures between 660 and 900 °C in Ar and in atmospheric air. Null spreading was observed without flux whereas perfect wetting was enabled by the flux in both atmospheres. The liquid flux, which provides a locally protective atmosphere by spreading on the surfaces of the substrate and eventually on the Al alloy, dissolves the aluminium oxide covering the molten alloy enabling thus direct contact between the liquid alloy and the TiC substrate. The low tensions for the solid/flux and liquid metal/flux interfaces facilitate spontaneous spreading and instantaneous wetting. Meanwhile, the flux is displaced to the lateral periphery of the substrate and to the surface of the liquid. Under the resolution of the scanning electron microscope, microstructural examination of the interfaces did not reveal reaction products. Rapid infiltration of the alloy into TiC/flux compacts, at low temperatures, correlated well with the flux-assisted spreading kinetics observed.

Pesticide residues were measured in stockpiled cotton gin trash (CGT) over a 2-year period. Samples were analysed by GC/MS/MS and interpretation of the results was aided by the presence of DDE residues, remnant from prior DDT use. Fourteen pesticide residues from current agricultural practice were detected in CGT. Several of these, including indoxacarb, profenofos, chlorpyrifos, propargite, bifenthrin, ethion and cyhalothrin, were more persistent than expected on the basis of published data for soil dissipation. The results showed a complex pattern of pesticide residue decay over time because of the simultaneous decomposition of the CGT matrix.

Metallic alloys show great potential to serve as transmutation fuels that could be used to burn long-lived and high-heat-producing minor actinides and fission products in nuclear reactors as part of the Global Nuclear Energy Partnership program. To implement these fuels, work is ongoing to develop fuel fabrication processes, characterize alloy microstructures, measure fuel properties, determine the compatibility of fuel and cladding alloys, and understand the performance of the fuel alloys during irradiation.

Nerve growth studies in adults usually rely upon nerve regeneration that follows axon disruption. In this study elongation of the epidermal nerve fibers occurred in human and pig epidermis stimulated to hypertrophy by removing the stratum corneum with repetitive applications of tape (tape stripping). Epidermal thickening was accompanied by elongation of the epidermal nerve fibers. This study demonstrates that changing the cellular and chemical environment of nerves by tape stripping is a feasible method to study nerve fiber growth in a physiological manner.

An Al-based composite reinforced with 20%SiCp was welded using the MIG welding process with direct and indirect application of the electric arc (DEA and IEA respectively). The welds were made on 12.5 mm thick plates in three welding passes for the DEA joint whereas only one pass was required for the IEA joint. Microstructural examination of the joints revealed DEA welds with light signs of matrix/reinforcement reaction whilst in the IEA welds the SiC particles remained with their initial angular morphology. Mechanical failure occurred consistently and independently of the type of joint in the weld zone and the measured strengths were 209 and 234 MPa for DEA and IEA welds respectively. The greater strength measured for the IEA weld was due to reduced porosity and good incorporation and dispersion of the SiC particles into the weld pool.

Bowman-Birk inhibitor concentrate (BBIC), a soy extract with high protease inhibitor activity, is efficacious in the treatment of colitis in mice and has been used in numerous clinical trials. A randomized, double blind, placebo-controlled trial was performed to investigate the safety and possible benefits of BBIC in patients with active ulcerative colitis. The Sutherland Disease Activity Index (SDAI) was used to assess disease activity, response (Index decrease > or = 3), and remission (Index < or = 1 with no rectal bleeding) in patients receiving 12 weeks of therapy. The Index scores of patients receiving BBIC decreased more than those of the patients receiving placebo (P = 0.067). Beneficial trends were observed in the rates of remission (P = 0.082) and clinical response (P = 0.22). No severe adverse events were observed. This trial suggests a potential benefit over placebo for both achieving clinical response and induction of remission in patients with active ulcerative colitis without apparent toxicity.

Ionizing radiation can produce adverse biological effects in astronauts during space travel. Of particular concern are the types of radiation from highly energetic, heavy, charged particles known as HZE particles. The aims of our studies are to characterize HZE particle radiation induced biological effects and evaluate the effects of L-selenomethionine (SeM) on these adverse biological effects. In this study, microarray technology was used to measure HZE radiation induced changes in gene expression, as well as to evaluate modulation of these changes by SeM. Human thyroid epithelial cells (HTori-3) were irradiated (1 GeV/n iron ions) in the presence or in the absence of 5 microM SeM. At 6 h post-irradiation, all cells were harvested for RNA isolation. Gene Chip U133Av2 from Affymetrix was used for the analysis of gene expression, and ANOVA and EASE were used for a determination of the genes and biological processes whose differential expression is statistically significant. Results of this microarray study indicate that exposure to small doses of radiation from HZE particles, 10 and 20 cGy from iron ions, induces statistically significant differential expression of 196 and 610 genes, respectively. In the presence of SeM, differential expression of 77 out of 196 genes (exposure to 10 cGy) and 336 out of 610 genes (exposure to 20 cGy) is abolished. In the presence or in the absence of SeM, radiation from HZE particles induces differential expression of genes whose products have roles in the induction of G1/S arrest during the mitotic cell cycle, as well as heat shock proteins. Some of the genes, whose expressions were affected by radiation from HZE particles and were unchanged in irradiated cells treated with SeM, have been shown to have altered expression levels in cancer cells. The conclusions of this report are that radiation from HZE particles can induce differential expression of many genes, some of which are known to play roles in the same processes that have been shown to be activated in cells exposed to radiation from photons (like cell cycle arrest in G1/S), and that supplementation with SeM abolishes HZE particle-induced differential expression of many genes. Understanding the roles that these genes play in the radiation-induced transformation of cells may help to decipher the origins of radiation-induced cancer.

The use of vegetated wetlands for accelerating pesticide removal from agricultural runoff is gaining acceptance as a best management practice. In this study, the dissipation of five cotton pesticides – endosulfan, chlorpyrifos, aldicarb, prometryn and diuron – was quantified in cotton field runoff water contained in glasshouse columns, under light or dark conditions. Two water samples sourced from large, non-vegetated storage dams were compared with two other water samples obtained from vegetated wetlands receiving runoff from cotton fields. All pesticides studied except chlorpyrifos dissipated significantly faster from the storage dam samples than the vegetated wetland samples. Suggested reasons include a greater number of pesticide-degrading microorganisms in the storage dam waters and/or the presence of more organic matter in the wetland samples, limiting contaminant volatilisation and hydrolysis. Exposure to light significantly reduced the rate of endosulfan removal, whereas light increased the rate of chlorpyrifos removal. Half-lives are presented for each pesticide where appropriate.

The exceptional property sets of macroporous materials are leading to an increasing number of applications, particularly in the biomedical sector. Apart from the underlying material properties, it is the characteristics of the porous structure that dictate the properties of fabricated devices. Conventional methods of examining the pore structure have a number of inherent disadvantages such as low sampling volume, laborious and frequently destructive sample preparation, tedious and subjective image analysis. Recently, industrial microtomographic methods have become important tools for interrogating porous materials. However, one of the limitations of micro-CT methods is the non-specific nature of commercially available image analysis software coupled with the complicated nature of the key parameters. This paper presents some progress towards the development of a novel analysis tool that aims to characterise specific parameters over a wide range of macroporous materials. This paper focuses on aspects directly relevant to the characterisation of Hydroxyapatite macroporous (HA) foams and demonstrates the capability to obtain statistically meaningful parameters essential for process development and pre-implantation quality assurance.

Adequate adhesion is thesine qua non for good practical performance in surface coatings systems such as paint. By far the majority of tests used in the coatings industry are destructive and difficult to correlate with performance. Moreover, destructive tests are incompatible with best practice in inspection and quality control. A range of non-destructive testing techniques was appraised for their ability to investigate different types of coating failure involving adhesion. Three techniques were selected for preliminary investigation, namely acoustic emission, pulse thermography and laser interferometry. All three techniques were capable of investigating different aspects of adhesive failure. Pulse thermography could detect subsurface damage not apparent to visual inspection, and acoustic emission could, under some circumstances, give information of damage initiation prior to catastrophic failure. Electronic speckle pattern shearing interferometry (ESPSI) was also able to detect sub-surface damage, and showed promise of detecting differences in strain transfer prior to any detachment failure.

This study details trials to produce aluminium metal matrix composites reinforced with TiC particles by means of a flux-assisted infiltration technique. Whilst no infiltration of TiC beds occurred, by using a K-Al-F flux infiltration was successful at temperatures as low as 680°C. Some reaction of TiC with the Al matrix, forming TiAl2.3Si0.1 and Al4C3, was observed in the microstructure along with flux trapped within the Al-6063 matrix. DSC showed exothermic oxidation of TiC to occur, until the flux melts at 545°C arresting and preventing further oxidation by spreading over, coating and cleaning the particle surfaces. As soon as the flux melts, it also starts dissolving the oxide layer on the Al alloy and prevents any re-oxidation by isolating the surface from the surrounding atmosphere. Sessile drop experiments suggest that when the alloy melts and the oxide layer has been dissolved by the flux, intimate contact occurs between the liquid and the particles. The low tensions for the solid/flux and liquid metal/flux interfaces facilitates spreading and wetting of liquid Al on the TiC particles, followed by infiltration of the bed and the displacement of the flux to the outer surfaces of the sample.

Pomphorhynchus laevis is believed on ecological evidence to exist as three strains in the British Isles. However, the strains have never been shown to be capable of being distinguished using morphological characters. A morphological comparison was made between a sample of P. laevis from Salmo trutta in L. Feeagh in the west of Ireland and a sample from Leuciscus cephalus in R. Culm in the south of England. The length and width of the trunk, neck, bulb, proboscis and hooks were measured. The number of hooks per row, the number of rows and the positions of the stoutest and longest hooks were also recorded. A Principal Components Analysis based on the morphological measurements confirmed the separation of the two populations and showed that two characters successfully identified the populations: the position of the stoutest hook and the ratio of numbers of anterior to posterior hooks.

Al foams have been manufactured via a PM route and compression tested. Testing has shown that density-properties relationships can be constructed which are then valid for the prediction of mechanical response for a sample of given density. The scatter in the density can also be used to predict, with reasonable confidence, the scatter in properties. Testing has shown that little or no difference in processing time can give rise to foams with significantly different densities and hence an undesirable, but nevertheless quantifiable and predictable, scatter in mechanical properties. This demonstrates the sensitivity of the very rapid foaming process and highlights the requirement for improving foam stability. The mechanical response of foams with similar densities is, however, reproducible suggesting that this is a more suitable way in which to control the process rather than by fixing the foaming time.

The N requirement of rice crops is well known. To overcome acute N deficiency in rice soils, this element is usually supplied to the rice crop as the commercially available fertilizer urea. But unfortunately a substantial amount of the urea-N is lost through different mechanisms causing environmental pollution problems. Utilization of biological N fixation (BNF) technology can decrease the use of urea-N, reducing the environmental problems to a considerable extent. Different BNF systems have different potentials to provide a N supplement, and it is necessary to design appropriate strategies in order to use BNF systems for efficient N supply to a rice crop. Research has been conducted around the world to evaluate the potential of different BNF systems to supply N to rice crops. This paper reviews salient findings of these works to assess all the current information available. This review indicates that the aquatic biota Cyanobacteria and Azolla can supplement the N requirements of plants, replacing 30–50% of the required urea-N. BNF by some diazotrophic bacteria like Azotobacter, Clostridium, Azospirillum, Herbaspirillum and Burkholderia can substitute for urea-N, while Rhizobium can promote the growth physiology or improve the root morphology of the rice plant. Green manure crops can also fix substantial amounts of atmospheric N. Among the green manure crops, Sesbania rostrata has the highest atmospheric N2-fixing potential, and it has the potential to completely substitute for urea-N in rice cultivation.

B4C particles have been added to molten Al- 7wt% Si- 0.3 wt% Mg alloys, at levels of 5 and 10 wt%, using a propriatory K-Al-Ti-F flux. The resulting composites were examined metallographically and mechanically tested in the as-manufactured condition and after heat treatment for 48 hours at 500°C and 700°C. During incorporation into the melt, a complex Ti-B-C reaction layer was formed on the particle surfaces. The reaction layer remained intact during heat treatment and the stable, protective nature of this layer gave rise to a significantly reduced rate of particle degradation compared to other Al-B4C composites. Significant increases in stiffness were observed; modulus increases per volume percent of particles added were similar to those for the Al-TiC system where strong interfacial bonding occurs. Improved adhesion between the solidified matrix and the B4C reinforcement was encouraged by the enhanced metallic character of the reaction layer. Solid state reaction at 500°C produced little change in mechanical properties. Heat treatment and reaction at 700°C resulted in an increase in the volume fraction of stiff, brittle reinforcing phases, leading to an increase in stiffness and a decrease in ductility.

Background Surgical resection is the primary treatment for colorectal carcinoma. Laparoscopically assisted colon resection technically is feasible for both benign and malignant disease. However, the role of laparoscopically assisted colon resection for carcinoma is controversial.

Adhesive coating failure arises when various internal or external forces overcome the resistance provided by work of adhesion and other energy dissipation mechanisms. Typical examples include blistering and slow or fast delamination (eg flaking and impact damage). Furthermore a loss of adhesion under wet conditions can be the precursor to corrosion. Tests used by the coatings industry are often relatively crude, such as simple tape and cross hatch tests. The tests may distort the results and are usually destructive. Not only is this inconvenient but it raises questions of relevance if the destructive process is outside the normal operating parameters, or introduces testing artefacts such as an additional bonded surface. A range of non-destructive techniques (eg thermography, ultrasonics, acoustic emission and laser shearography) is reviewed against their potential for meeting the criteria for different end-use applications in such areas as quality control, product development, fault diagnosis and service life prediction.

Infiltration trials have been conducted by filling Cu tubes withceramic powders and melting them under argon. No externalforces were applied; successful infiltration of the ceramicrelied solely upon favourable metal-ceramic wetting conditions.Oxides and covalently bonded compounds could not bespontaneously infiltrated but transition metal compounds such asNbC, Cr3C2, WC, NbB2 and Cr2N were. It was impossible toinfiltrate any ceramics when oxygen was present in the system.Contact angle data in the literature were found to predict, withfair reliability, infiltration events in Cu-ceramic systems.The good correlation is thought to be due to the ease with whichthe oxide film can be prevented from forming on molten Cu duringboth sessile droplet experiments and infiltration processing.

Archival research reveals that it is highly probably that the first discovery of a fossil ape was made by Hugh Falconer and his associates in the 1830s during surveys of Neogene deposits in the Siwalik hills of British Colonial India. However, priority is commonly awarded to Edouard Lartet who, in 1837, brought to light a fossil primate specimen from the Miocene beds at Sansan in France to which Paul Gervais gave the namePliopithecus. Falconer's letters and scientific papers announcing the find of a fossil primate group from the Siwalik Hills were antecedent to Lartet's report to the French Academy of Sciences, Paris. The circumstances surrounding this misconception over priority of discovery of fossil apes are reviewed with attention to the historic significance of the Siwalik fossil primates and with respect to the development of paleoanthropology in South Asia.