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The ability to gradually modify the atomic structures of nanomaterials and directly identify such structural variation is important in nanoscience research. Here, we present the first example of a high-pressure single-crystal X-ray diffraction analysis of atomically precise metal nanoclusters. The pressure-dependent, subangstrom structural evolution of an ultrasmall gold nanoparticle, Au

The development of high energy-density Ni-rich (Ni ≥ 90%) layered cathodes has remained difficult because of the rapid capacity fading that occurs during cycling. This study demonstrates that limiting the primary particle size of the cathode resolves the capacity fading problem as nano-sized primary particles effectively relieve the high internal strain associated with the phase transition near charge end and fracture-toughen the cathode. A linear relationship is observed between battery cycling stability and cathode primary particle size. The introduction of Mo inhibits the growth/consolidation of primary particles and limits their size to a submicrometer scale thus improving the cycle life of Li[Ni0.95Co0.04Mo0.01]O2 to a commercially viable level. The Li[Ni0.95Co0.04Mo0.01]O2 cathode, whose microstructure is engineered to mitigate the inherent mechanical instability of Ni-rich layered cathodes, represents a next-generation high energy-density cathode with fast charging capability for electric vehicles with a material cost advantage over current commercial cathodes as Co, a relatively expensive and increasingly scarce resource, is replaced with Ni without compromising battery capacity and battery life.

BACKGROUND AND OBJECTIVE: To report the long-term anatomic and visual outcomes of patients with Stickler syndrome undergoing retinal detachment (RD) surgery. PATIENTS AND METHODS: Retrospective, interventional, consecutive case series of patients with Stickler syndrome undergoing RD repair from 1999 to 2017 at the Long Island Vitreoretinal Consultants, New York. Retinal attachment status and visual acuity (VA) at 1-year and last follow-up were assessed. RESULTS: Successful reattachment was achieved in 28 of 29 eyes (97%) with an average of 2.3 surgeries (including silicone oil removal surgeries). Redetachment after the first surgery occurred in 13 eyes (45%). Mean Snellen VA at initial presentation, 1-year follow-up, and last follow-up were 20/289, 20/118 ( P = .012), and 20/103 ( P = .022), respectively. CONCLUSIONS: Anatomic success can be achieved in most eyes. However, redetachments are common, and multiple surgeries are often required. Reasonable visual recovery is possible in many eyes. [ Ophthalmic Surg Lasers Imaging Retina. 2020;51:612–616.]

Arsenic (As) is a common contaminant in soils, and analysis of soils by inductively coupled plasma-mass spectrometry (ICP-MS) is often used to detect As in soil extracts. Internal standards (ISs) are part of ICP-MS analyses to enhance precision and accuracy by compensating for instrument variability; however, an improper choice of IS can result in negative analytical bias. The goal of this study was to develop a protocol for evaluating ISs commonly used in ICP-MS. Three soils of varying clay content and total As were extracted with a dilute electrolyte [0.005 mol L

The use of intravitreal bevacizumab in pediatric retinal and uveitic disease has become more widespread over the past decade. This article serves to outline the rationale underlying the use of intravitreal bevacizumab, and which disease entities it should be appropriately thought of as a primary or solo therapy, as opposed to an adjuvant one. Also presented is the relevant literature regarding each of these retinopathies.

Purpose: To present a series of cases of corneal chemical burns associated with the use of likely improperly buffered corneal lubricant gel, Goniovisc, during uncomplicated, posterior segment surgery. Methods: Cases of postoperative corneal complications following surgeries in which Goniovisc was used were collected from 6 retina practices across the United States between January and August 2016. The preoperative diagnosis, type of procedure, postoperative day 1 corneal findings, treatment method, and time to resolution of the corneal irregularity were recorded. pH testing of Goniovisc lots from this time period was performed using Hydrion litmus paper. Results: A total of 157 eyes of 156 patients were found to have corneal complications following relatively simple posterior segment surgeries in which Goniovisc was used. Findings included one or more of the following: corneal epithelial defect (84% of cases), Descemet folds (34%), stromal edema (14%), and superficial punctate keratitis (3%). Time to resolution ranged from 2 to 90 days (mean, 12 days; median, 7 days). Treatment methods included artificial tears (37%), bandage contact lens (28%), antibiotic drops (17%), antibiotic ointment (16%), and patching (9%). Two cases were treated with amniotic membrane grafts. One case required a penetrating keratoplasty due to an old laser-assisted in situ keratomileusis (LASIK) flap with a nonhealing epithelial defect that scarred significantly. Litmus testing of Goniovisc lots from this time period revealed a pH of 4 to 5. Conclusion: Chemical burns secondary to improperly buffered corneal lubricant solution should be considered in the differential when corneal injury is encountered following posterior segment surgery.

We describe a case of bilateral angle closure glaucoma following the infusion of daratumumab, a monoclonal antibody used to treat relapsing multiple myeloma.This is an interventional case report.A 59-year-old woman presented with bilateral angle closure glaucoma one day following her first infusion of daratumumab. B-scan echography showed ciliochoroidal effusions in both eyes. Cycloplegia was implemented given the suspicion for drug-induced angle closure, which resulted in prompt deepening of the anterior chambers and normalization of intraocular pressures. The ciliochoroidal effusions resolved 16 days following the cessation of daratumumab.Daratumumab may be associated with drug-induced secondary angle closure glaucoma.

Large-scale infrastructures are prone to simultaneous faults when struck by a natural or man-made event. The current operating procedure followed by many utilities needs improvement, both in terms of monitoring performance and time to repair. Motivated by the recent technological progress on small Unmanned Aerial Systems (sUAS), we propose a practical framework to integrate the monitoring capabilities of sUAS into standard utility repair operations. A key aspect of our framework is the use of monitoring locations for sUAS-based inspection of failures within a certain spatial zone (called a localization set). This set is defined based on the alerts from fixed sensors or customer calls. The positioning of monitoring locations is subject to several factors such as sUAS platform, network topology, and airspace restrictions. We formulate the problem of minimizing the maximum time to respond to all failures by routing repair vehicles to various localization sets and exploring these sets using sUAS. The formulation admits a natural decomposition into two sub-problems: the sUAS Network Exploration Problem (SNEP); and the Repair Vehicle Routing Problem (RVRP). Standard solvers can be used to solve the RVRP in a scalable manner; however, solving the SNEP for each localization set can be computationally challenging. To address this limitation, we propose a set cover based heuristic to approximately solve the SNEP. We implement the overall framework on a benchmark network.

The U.S. Department of Energy and Transportation considers pipeline security and the timely containment of leaks as a top priority for the oil and natural gas industry. However, despite significant investment in network sensing and maintenance, utilities still incur significant delays (and associated losses) in managing failures. This article focuses on the use of small Unmanned Aerial Systems (sUASs) for the inspection of network components and to facilitate timely repair of failures. Our framework integrates sUAS-enabled sensing with fixed sensing systems and ground-based maintenance crews, and aims to minimize the time to repair multiple network failures. It also reduces human effort in network inspection (e.g. manned reconnaissance, ground patrols, and leak surveys). We consider inspection tasks on a set of failure regions (localization sets) that are generated from fixed sensors installed on the network (e.g. pressure sensors). We focus on the problem of routing a set of available maintenance vehicles at specified yard (base) locations carrying sUASs to optimally identify and repair the network failures. To address this problem, we propose two Mixed- Integer Programming (MIP) formulations: (a) the multi-trip sUAS exploration problem, and (b) maintenance vehicle routing problem. We show that these formulations can be integrated to optimally route the sUASs for identification of multiple network failures that may occur anywhere within the localization sets (MIP-a); and to optimally dispatch maintenance vehicles to repair the identified network failures (MIP-b). We illustrate this approach on a benchmark pipeline network, and demonstrate the inherent tradeoffs between sUAS exploration time and maintenance vehicle travel time in our solution.

A high temperature electrochemical cell with a bed of solid carbon at the anode and steam at the cathode is proposed for carbon-assisted hydrogen production. This scheme eliminates the uphill potential barrier and provides a significant reduction in the required electrical work input to produce hydrogen from steam. The electrochemical cell is made of an yttria stabilized zirconia electrolyte with porous platinum electrodes. Current–voltage measurements and gas chromatographic analysis indicate steam utilization and production of carbon-free hydrogen. Measured open circuit potentials of 0.1–0.6 V agree with theoretical values. This downhill driving force allows for spontaneous hydrogen production and cogeneration of electricity.

This study describes a novel electrochemical approach for the simultaneous and spontaneous production of carbon-free hydrogen and electricity. Hydrogen was generated from steam at the cathode of a yttria stabilized zirconia electrolyte by utilizing a solid carbonaceous fuel at the cell anode to maintain low oxygen activity levels within the anode chamber. The results verified that a steam-carbon cell is capable of producing carbon-free hydrogen in a fuel cell mode while generating electric power at the same time. The open circuit voltages of the cells agreed with expected values. The current-voltage behavior indicated that cell performance was governed mostly by resistive losses. A gas transport model of the solid carbon bed based on known Boudouard kinetics was developed and analyzed. The model demonstrates that the fuel bed is capable of supporting a cell current density in excess of 700 mA/cm2 while maintaining a fuel utilization rate of over 85%.

The gasification-driven direct carbon fuel cell (GD-DCFC) system is compared with systems using separate gasification steps prior to work extraction, under autothermal or indirect constraints. Using simple system exergy analysis, the maximum work output of the indirect gasification scheme is 4–7% lower than the unconstrained direct approach, while the work output of the autothermal gasification approach is 12–13% lower than the unconstrained case. A more detailed calculation for the DCFC and indirect gasification plants, using common solid fuel compositions, gives conversion efficiencies in the range of 51–58% at an operating voltage of 0.7 V selected for both systems in this study. In contrast, the conversion efficiency of the autothermal gasification approach is estimated to be 33–35% at 0.7 V. DCFC efficiencies can be increased to over 60% by an increase in operating voltage and/or inclusion of a bottoming cycle. The thermodynamic model also indicates that steam gasification yields similar work output and thermal efficiency as for CO2 gasification. Open circuit potential measurements agree with equilibrium calculations both for the C–O and C–H–O gasification systems, confirming the governing mechanism and feasibility of the GD-DCFC. Current–voltage measurements on an un-optimized system demonstrate power densities of 220 mW cm−2 at 0.68 V during operation at 1178 K.

This modeling study focuses on gasification of carbon by CO2 in a minimally fluidized bed containing a solid oxide fuel cell (SOFC). Kinetic parameters for a five-step reaction mechanism characterizing the Boudouard reaction (C + CO2 2CO) were determined thermogravimetrically at 1 atm from 973 to 1273 K. Experimentally determined kinetic parameters are employed in a transport model that predicts velocities and gas concentration profiles established in the carbon bed as a consequence of convection, diffusion, and heterogeneous reaction. The model is used to simulate the effect of an imbedded SOFC, in contact with the carbon bed. Although the model does not assume particular I-V characteristics for the fuel cell, it indicates that current densities in the practical range of 100–1000 mA/cm2 can be supported. Results show that temperature strongly affects the current density, whereas CO2 flow rate has only a weak effect. © 2009 American Institute of Chemical Engineers AIChE J, 2009

A solid oxide fuel cell based fluidized bed configuration is employed for the first time to convert solid carbon directly into electricity. Current–voltage characteristics exhibited typical fuel cell behavior with large ohmic losses. Chromatographic analysis of the product gases in the flue stream confirmed conversion of carbon. This is also verified by oxygen mass balance. Peak power densities for carbon compared well with benchmarking tests that employed only gaseous fuels. A possible mechanistic pathway is proposed to explain the observed behavior.

Brief Secondhand Smoke Exposure Depresses Endothelial Progenitor Cells Activity and Endothelial Function: Sustained Vascular Injury and Blunted Nitric Oxide ProductionChristian Heiss, Nicolas Amabi...

Group work in an academic setting can consist of projects or problems students can work on collaboratively. Although pedagogical studies have shown the potential benefits of group work for learning, not a lot of studies examine which group selection method is best for certain types of learning. At the U.S. Military Academy, Cadets are not only expected to graduate as adaptive leaders, but also as individuals who can communicate and interact effectively in diverse settings as outlined in the West Point Leadership Development System (WPLDS). Three group selection methods were investigated using a short survey in a sophomore level math course: self-selection, selection using a measure of academic and geographic proximity, and random selection by the instructor. The data suggests a distinct advantage for Cadets in gaining confidence to work with others if the instructor uses geographic and academic proximity to select project partners.

The way a unit defines an area of operation (AO) can restrict or facilitate a unit's ability to influence the population; however, units may not have access to accurate census data. An AO developed through a cursory mission analysis could misrepresent current tribal boundaries, population densities, district boundaries, and residential areas. Recent research has demonstrated that given anonymized call data records of mobile subscribers, units may be able to circumvent the need for an accurate census to feed into the mission analysis in determining an optimal AO. Furthermore, mobile data also provides the added benefit of allowing us to assess changing population patterns over time.

Anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare congenital cardiovascular defect that occurs in approximately 1/300 000 live births or 0.5% of children with congenital heart disease. The mortality of untreated ALCAPA has been estimated to range from 35% to greater than 85% in the first year of life. However, in some cases patients can survive past infancy and into adulthood and do not present with symptoms until later in life. These older patients often manifest their anomalies as congestive heart failure, malignant arrhythmias, or even sudden death. We report a series of 3 cases from our institution illustrating the various late presentations of this unusual diagnosis. We review the pathophysiology of this rare congenital anomaly and discuss some of the signs, symptoms, and diagnostic tests that can help diagnose this unusual condition in adults.

During the past decade, the perception flourished that lipid and antioxidant therapy were 2 independent avenues for cardiovascular protection. However, studies have shown that commonly used antioxidant vitamin regimens do not prevent cardiovascular events. We found that the addition of antioxidant vitamins to simvastatin-niacin therapy substantially blunts the expected rise in the protective high density lipoprotein (HDL)2 cholesterol and lipoprotein(A-I) subfractions of HDL, with apparent adverse effects on the progression of coronary artery disease. To better understand this effect, 12 apolipoproteins, receptors, or enzymes that contribute to reverse cholesterol transport have been examined in terms of their relationship to HDL2 and lipoprotein(A-I) levels and the potential for antioxidant modulation of their gene expression. Three plausible candidate mechanisms are identified: (1) antioxidant stimulation of cholesteryl ester transfer protein expression/activity, (2) antioxidant suppression of macrophage ATP binding cassette transmembrane transporter A1 expression, and/or (3) antioxidant suppression of hepatic or intestinal apolipoprotein A-I synthesis or increase in apolipoprotein A-I catabolism. In summary, antioxidant vitamins E and C and β-carotene, alone or in combination, do not protect against cardiovascular disease. Their use for this purpose may create a diversion away from proven therapies. Because these vitamins blunt the protective HDL2 cholesterol response to HDL cholesterol–targeted therapy, they are potentially harmful in this setting. We conclude that they should rarely, if ever, be recommended for cardiovascular protection.

12 páginas, 6 figuras.-- et al., Most studies of European genetic diversity have focused on large-scale variation and interpretations based on events in prehistory, but migrations and invasions in historical times could also have had profound effects on the genetic landscape. The Iberian Peninsula provides a suitable region for examination of the demographic impact of such recent events, because its complex recent history has involved the long-term residence of two very different populations with distinct geographical origins and their own particular cultural and religious characteristics—North African Muslims and Sephardic Jews. To address this issue, we analyzed Y chromosome haplotypes, which provide the necessary phylogeographic resolution, in 1140 males from the Iberian Peninsula and Balearic Islands. Admixture analysis based on binary and Y-STR haplotypes indicates a high mean proportion of ancestry from North African (10.6%) and Sephardic Jewish (19.8%) sources. Despite alternative possible sources for lineages ascribed a Sephardic Jewish origin, these proportions attest to a high level of religious conversion (whether voluntary or enforced), driven by historical episodes of social and religious intolerance, that ultimately led to the integration of descendants. In agreement with the historical record, analysis of haplotype sharing and diversity within specific haplogroups suggests that the Sephardic Jewish component is the more ancient. The geographical distribution of North African ancestry in the peninsula does not reflect the initial colonization and subsequent withdrawal and is likely to result from later enforced population movement—more marked in some regions than in others—plus the effects of genetic drift., M.A.J. was supported by a Wellcome Trust Senior Fellowship in Basic Biomedical Science (grant no. 057559), and S.M.A., E.B., P.L.B., S.J.B., and A.C.L. were supported by the Wellcome Trust.

The genetic structures of past human populations are obscured by recent migrations and expansions, and can been observed only indirectly by inference from modern samples. However, the unique link between a heritable cultural marker, the patrilineal surname, and a genetic marker, the Y chromosome, provides a means to target sets of modern individuals that might resemble populations at the time of surname establishment. As a test case, we studied samples from the Wirral peninsula and West Lancashire, in northwest England. Place names and archaeology show clear evidence of a past Viking presence, but heavy immigration and population growth since the Industrial Revolution are likely to have weakened the genetic signal of a thousand-year-old Scandinavian contribution. Samples ascertained on the basis of two generations of residence were compared with independent samples based on known ancestry in the region, plus the possession of a surname known from historical records to have been present there in medieval times. The Y-chromosomal haplotypes of these two sets of samples are significantly different, and in admixture analyses the surname-ascertained samples show markedly greater Scandinavian ancestry proportions, supporting the idea that northwest England was once heavily populated by Scandinavian settlers. The method of historical surname-based ascertainment promises to allow investigation of the influence of migration and drift over the last few centuries in changing the population structure of Britain, and will have general utility in other regions where surnames are patrilineal and suitable historical records survive.

This study sought to analyze the effects of acute secondhand smoke (SHS) exposure on the number and function of endothelial progenitor cells (EPCs) over 24 h.Secondhand smoke increases the risk of vascular disease and is a major public health concern, but the mechanism(s) of action are not fully understood.Healthy nonsmokers (age SEM 30.3 +/- 1.3 years, n = 10) were exposed to 30 min of SHS yielding cotinine levels commonly observed in passive smokers and to smokefree air on 2 separate days. Measurements were taken before exposure (baseline), immediately after (0 h), and at 1 h, 2.5 h, and 24 h after. The EPCs (CD133(+)/KDR(+), CD34(+)/KDR(+)) and endothelial microparticles (EMPs: CD31(+)/CD41(-), CD144(+), CD62e(+)) were determined in blood using flow cytometry. The EPC chemotaxis toward vascular endothelial growth factor was measured. Endothelial function was assessed as flow-mediated dilation (FMD) using ultrasound.Secondhand smoke exposure increased EPCs and plasma vascular endothelial growth factor and completely abolished EPC chemotaxis during 24 h after exposure. Secondhand smoke increased EMPs and decreased FMD. Although FMD returned to baseline at 2.5 h, EMPs and vascular endothelial growth factor levels remained elevated at 24 h, suggesting endothelial activation and injury with functional impairment of the vascular endothelium. Exposure to smokefree air had no effect. Incubation of EPCs from nonexposed subjects with plasma isolated from SHS-exposed subjects in vitro decreased chemotaxis by blockade of vascular endothelial growth factor-stimulated nitric oxide production.Brief exposure to real-world levels of SHS leads to sustained vascular injury characterized by mobilization of dysfunctional EPCs with blocked nitric oxide production. Our results suggest that SHS not only affects the vascular endothelium, but also the function of EPCs.

Our goal is to develop a state-of-the-art secondary structure predictor with an intuitive and biophysically-motivated energy model through the use of Hidden Markov Support Vector Machines (HM- SVMs), a recent innovation in the field of machine learning. We focus on the prediction of alpha helices and show that by using HM-SVMs, a simple 7-state HMM with 302 parameters can achieve a Qα value of 77.6% and a SOVα value of 73.4%. As detailed in an accompanying technical report [11], these performance numbers are among the best for techniques that do not rely on external databases (such as multiple sequence alignments).

The human Hairy Ears phenotype has traditionally been regarded as the only Y-linked heritable trait. Here, we use Y-chromosomal DNA binary-marker haplotyping to show that a cohort of southern Indian Hairy-Eared males carries Y chromosomes from many haplogroups of the Y-phylogeny, which, under a hypothesis of Y linkage, would require multiple independent mutations within a single population. We further show that there is no significant difference between the Y-haplogroup spectrum in Hairy-Eared males and that in a geographically matched control sample of unaffected males. The trait cannot, therefore, be Y-linked in southern Indians, and by extension, is unlikely to be so in any population.

Nineteen Y-specific short tandem repeat (STR) loci have been amplified in 768 samples from the Iberian Peninsula in order to evaluate their usefulness in forensic casework. Two previously published multiplex reactions by Thomas et al. [Hum. Genet. 6 (1999) 577] (MS1, modified here: DYS19, DYS388, DYS390, DYS391, DYS392 and DYS393) and by Ayub et al. [Nucl. Acids Res. 28 (2000) e8] (CTS: DYS434, DYS435, DYS436, DYS437, DYS438 and DYS439) plus a novel one reported here (EBF: DYS385, DYS389, DYS460, DYS461, DYS462 and amelogenin) have been used. DYS385, DYS439 and DYS391 were the most informative loci with allele diversities of 0.7997, 0.6683 and 0.5940, respectively. A total of 635 different haplotypes were observed, of which 573 (90.24%) were found in single individuals. The overall haplotype diversity was 0.9988 and that obtained by each multiplex system was 0.9812 for EBF, 0.9292 for MS1 and 0.9089 for CTS.

Metadata only record This paper discusses the potential value of seasonal climate forecasts for ranchers in West Texas, based on the assessment of a focus group and ecological-economic modeling. The conclusion of the focus group was that the forecasts could potentially increase their ranch productivity by providing information to use in stocking, brush control, and deer herd management decisions. However, because there was also concern that "value-added" forage forecasts could be misused, the authors suggest that the concept of "value-added" should be reassessed by the climate-forecasting community. The authors estimate the value of seasonal forage forecasts in guiding stocking rate choices. The results confirmed their hypothesis that numerous economic factors , including restocking and destocking prices, influence the value of the forecasts. Based on the economic model and the results from the focus group, the authors conclude that multiyear modeling is needed to better assess the potential of climate forecasts.

Elastic scattering or spectroscopy offers the possibility of distinguishing between cancerous and noncancerous tissue in suspicious breast lumps with a relatively simple optical measurement. The measurement of the relative reflection of light has previously been shown to be sensitive to both the size and distribution of intra and intercellular structures as well as absorption from chromophores present in the tissue. Coupling a white tight source and spectrometer to optic fibres makes it possible to construct probes that can be inserted through the skin or used during the operation or on excised tissue such as the sentinel node. This ‘optical biopsy' is correlated with a conventional histopathological specimen obtained at the same point. Spectra have been obtained from a large number of patients with benign and malignant lesions. Some of the differences that appear in these spectra have been identified and these are discussed. To a relatively high degree of sensitivity and specificity it is shown to be possible to distinguish between malignant tumours, benign lesions and normal tissue.

Human diploid fibroblasts eventually lose the capacity to replicate in culture and enter a viable but nonproliferative state of senescence. Recently, it has been demonstrated that retroviral-mediated gene transfer into primary fibroblasts of an activated ras gene (V12ras) rapidly accelerates development of the senescent phenotype. Using this in vitro system, we have sought to define the mediators of Ras-induced senescence. We demonstrate that expression of V12Ras results in an increase in intracellular and in particular, mitochondrial reactive oxygen species. The ability of V12Ras to induce growth arrest and senescence is shown to be partially inhibited by coexpression of an activated rac1 gene. A more dramatic rescue of V12Ras-expressing cells is demonstrated when the cells are placed in a low oxygen environment, a condition in which reactive oxygen species production is inhibited. In addition, in a 1% oxygen environment, Ras is unable to trigger an increase in the level of the cyclin-dependent kinase inhibitor p21 or to activate the senescent program. Under normoxic (20% O2) conditions, the V12Ras senescent phenotype is demonstrated to be unaffected by scavengers of superoxide but rescued by scavengers of hydrogen peroxide. These results suggest that in normal diploid cells, Ras proteins regulate oxidant production and that a rise in intracellular H2O2 represents a critical signal mediating replicative senescence.

Over the last several years, there has been a dramatic increase in the use of anesthesia human patient simulators for educational purposes. Full-scale, computer run simulators are currently being used to teach courses ranging from basic instruction of non-anesthesiologists to the more complicated Anesthesia Crisis Resource Management™,1 for continuing medical education of attending anesthesiologists. At the University of Rochester, the emphasis of our simulator program has been in the education of medical students and anesthesia residents. This chapter will not only provide an outline of the different courses for which we have used the simulator as an educational adjunct, but also to share some of the lessons we have learned that will help in creating a successful educational program.

Ingenol-3-angelate (PEP005), extracted from Euphorbia peplus, is currently in clinical trials for eradicating basal cell carcinoma (BCC), actinic keratosis and squamous cell carcinoma (SCC) in situ by topical application. Although structurally related to phorbol esters and a PKC activator, topical PEP005, but not phorbol 12-myristate 13-acetate (PMA), inhibited the growth of subcutaneous tumors derived from PAM212 (mouse SCC) and B16 (mouse melanoma). PEP005 and PMA both induced acute neutrophilic inflammation on mouse skin, but only PEP005 caused subcutaneous hemorrhage and vascular damage. Both PEP005 and PMA activated Erk1/2 in epidermis, but PEP005 also activated Erk1/2 in skin dermal fibroblasts and endothelial cells. Pretreatment with topical cyclosporin A (CsA), verapamil or XR9576, modulators of P-glycoprotein (P-gp), prevented PEP005-induced hemorrhage but not neutrophil infiltration. CsA also impaired Ing3A's anti-cancer activity while the anti-inflammatory dexamethasone did not. PEP005, but not PMA, blocked photoaffinity labeling of human P-gp with [125I]-Iodoaryazidoprazosin and inhibited P-gp mediated drug resistance to HCT-15 cells. The intracellular levels of PEP005 were significantly lower in P-gp expressing cells and treatment with XR9576 increased the levels to those of cells that do not express P-gp, demonstrating that PEP005 binds to and is transported by P-gp. Taken together, our results suggest that P-gp mediated absorptive transport, dermal penetration and vascular damage contribute to the anti-cancer activity of PEP005 in vivo. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1777.

A fluidized bed direct carbon fuel cell was employed to achieve direct conversion of solid fuels into electricity. Power was generated from pulverized Lower Kittanning (bituminous) coal, synthetic carbon, and biomass in a single process step. Current-voltage characteristics exhibited typical fuel cell behavior. Fluidization in flowing CO{sub 2} overcomes the difficulty of attaining solid fuel-to-anode contact and generates CO in situ via the Boudouard reaction. A mechanistic reaction pathway is proposed for anodic oxidation of the solid fuel. Conversion was verified by gas analysis of oxidation products in the flue stream and by oxygen mass balance.

We have screened the nearly complete DNA sequence of the human Y chromosome for microsatellites (short tandem repeats) that meet the criteria of having a repeat-unit size ofor = 3 and a repeat count ofor = 8 and thus are likely to be easy to genotype accurately and to be polymorphic. Candidate loci were tested in silico for novelty and for probable Y specificity, and then they were tested experimentally to identify Y-specific loci and to assess their polymorphism. This yielded 166 useful new Y-chromosomal microsatellites, 139 of which were polymorphic, in a sample of eight diverse Y chromosomes representing eight Y-SNP haplogroups. This large sample of microsatellites, together with 28 previously known markers analyzed here--all sharing a common evolutionary history--allowed us to investigate the factors influencing their variation. For simple microsatellites, the average repeat count accounted for the highest proportion of repeat variance (approximately 34%). For complex microsatellites, the largest proportion of the variance (again, approximately 34%) was explained by the average repeat count of the longest homogeneous array, which normally is variable. In these complex microsatellites, the additional repeats outside the longest homogeneous array significantly increased the variance, but this was lower than the variance of a simple microsatellite with the same total repeat count. As a result of this work, a large number of new, highly polymorphic Y-chromosomal microsatellites are now available for population-genetic, evolutionary, genealogical, and forensic investigations.

Background Our goal is to develop a state-of-the-art protein secondary structure predictor, with an intuitive and biophysically-motivated energy model. We treat structure prediction as an optimization problem, using parameterizable cost functions representing biological "pseudo-energies". Machine learning methods are applied to estimate the values of the parameters to correctly predict known protein structures. Results Focusing on the prediction of alpha helices in proteins, we show that a model with 302 parameters can achieve a Qα value of 77.6% and an SOVα value of 73.4%. Such performance numbers are among the best for techniques that do not rely on external databases (such as multiple sequence alignments). Further, it is easier to extract biological significance from a model with so few parameters. Conclusion The method presented shows promise for the prediction of protein secondary structure. Biophysically-motivated elementary free-energies can be learned using SVM techniques to construct an energy cost function whose predictive performance rivals state-of-the-art. This method is general and can be extended beyond the all-alpha case described here.