Off-Highway Vehicle (OHV) use is rapidly becoming one of the most difficult and contentious issues for federal, state, and local land management agencies to address. This article adds to a growing body of literature specific to the activity by addressing two distinct questions. First, do individuals' motivations for participating in OHV riding vary depending upon their level of specialization within the activity? Second, do OHV riders at varying levels of specialization hold significantly different beliefs about the environment? Data for this study come from a statewide survey of OHV owners in Utah. Drawing a sample from a state-provided list of registrations, 1,500 OHV riders were sent a survey instrument by mail. A total of 600 surveys were returned completed, the data from which are used in this analysis. The analysis identified three specialization groups, identified as low, medium, and high. Results were mixed for the association between OHV riders' specialization level and their motivations for participation. More highly specialized OHV riders exhibited stronger motivations for personal achievement and meeting, teaching, and leading others than did less specialized riders. The data also show no significant relationship between an OHV riders' level of involvement in the activity and their general level of environmental concern. Results do, however, show significant differences across specialization groups in the belief that humans are severely abusing the environment and that an ecological crisis is imminent. These findings can assist recreation managers and planners in several regards. First, OHV riders are a heterogeneous group of recreationists that vary in their behavior, skills, and commitment to the activity. These variations correspond to specific desired recreation experiences. Highly specialized riders desire a sense of personal achievement and a forum where they can teach and lead others. Recreation planners should be cognizant of these differences and provide OHV trails and areas that facilitate both skill development and the opportunity for riders to teach and meet with others. Secondly, recreation planners should realize general beliefs about the environment do not differ relative to an individual's level of engagement in the activity. Environmental education efforts therefore might not need to be targeted at any one specific type of OHV rider.?


OBJECTIVE
A pilot case-control study was conducted to examine the possible association between dietary fat intake and the development of postmenopausal breast cancer.

BACKGROUND
Studies regarding the association between dietary fat intake and the development of breast cancer among postmenopausal women are lacking in Puerto Rico.

METHODS
Eighteen cases and eighteen controls were interviewed to obtain sociodemographic information, medical history and dietary fat intake. A semiquantitative food frequency questionnaire containing 67 food items was used to collect the dietary information.

RESULTS
Unadjusted odds ratios (OR) and their 95% confidence intervals (CI) showed a non-significant positive association for total fat intake and the development of postmenopausal breast cancer (OR = 1.57; 95% CI: 0.42-5.90, p = 0.25). The same non significant positive association was found for saturated fat intake (OR = 1.57; 95% CI: 0.42-5.90, p = 0.25). Polyunsaturated fat (OR = 1.25; 95% CI: 0.34-4.64, p = 0.37) and monounsaturated fat (OR = 1.25; 95% CI: 0.34-4.64, p = 0.37) were also positively associated with postmenopausal breast cancer, although the associations were not statistically significant.

CONCLUSIONS
These results are consistent with other case-control studies that have shown non-significant positive associations between total fat and the different components of dietary fat and postmenopausal breast cancer.


Teachers have a very important role in determining the quality of the teaching-learning process and the students' learning outcomes. Learning outcomes will optimally be achieved if it is supported by qualified teachers. One way to enhance the teachers' performance is through instructional supervision which can be divided into two techniques, namely group and individual supervision techniques. Therefore, this study aims to find out the influence of instructional supervision techniques on the work motivation and performance of elementary school teachers. This study was conducted in East Java, Indonesia, and an explanatory research design was used. The sample was taken from 80 elementary school teachers in Malang and Blitar using a multi-stage random sampling technique. Data were collected through the use of questionnaires and documentation, and then they were analyzed by using the structural equation modeling technique. The result of this study showed that group supervision has a significant effect on teachers' performance, whereas individual supervision influenced teachers' work motivation and it affected their performance.


Alzheimer's disease (AD) is a neurodegenerative disorder characterized by Aβ-driven synaptic dysfunction in the early phases of pathogenesis. In the synaptic context, the actin cytoskeleton is a crucial element to maintain the dendritic spine architecture and to orchestrate the spine's morphology remodeling driven by synaptic activity. Indeed, spine shape and synaptic strength are strictly correlated and precisely governed during plasticity phenomena in order to convert short-term alterations of synaptic strength into long-lasting changes that are embedded in stable structural modification. These functional and structural modifications are considered the biological basis of learning and memory processes. In this review we discussed the existing evidence regarding the role of the spine actin cytoskeleton in AD synaptic failure. We revised the physiological function of the actin cytoskeleton in the spine shaping and the contribution of actin dynamics in the endocytosis mechanism. The internalization process is implicated in different aspects of AD since it controls both glutamate receptor membrane levels and amyloid generation. The detailed understanding of the mechanisms controlling the actin cytoskeleton in a unique biological context as the dendritic spine could pave the way to the development of innovative synapse-tailored therapeutic interventions and to the identification of novel biomarkers to monitor synaptic loss in AD.


Many tasks in fluids engineering require knowledge of the turbulence in jets. There is a strong, although fragmented, literature base for low order statistics, such as jet spread and other meanvelocity field characteristics. Some sources, particularly for low speed cold jets, also provide turbulence intensities that are required for validating Reynolds-averaged Navier-Stokes (RANS) Computational Fluid Dynamics (CFD) codes. There are far fewer sources for jet spectra and for space-time correlations of turbulent velocity required for aeroacoustics applications, although there have been many singular publications with various unique statistics, such as Proper Orthogonal Decomposition, designed to uncover an underlying low-order dynamical description of turbulent jet flow. As the complexity of the statistic increases, the number of flows for which the data has been categorized and assembled decreases, making it difficult to systematically validate prediction codes that require high-level statistics over a broad range of jet flow conditions. For several years, researchers at NASA have worked on developing and validating jet noise prediction codes. One such class of codes, loosely called CFD-based or statistical methods, uses RANS CFD to predict jet mean and turbulent intensities in velocity and temperature. These flow quantities serve as the input to the acoustic source models and flow-sound interaction calculations that yield predictions of far-field jet noise. To develop this capability, a catalog of turbulent jet flows has been created with statistics ranging from mean velocity to space-time correlations of Reynolds stresses. The present document aims to document this catalog and to assess the accuracies of the data, e.g. establish uncertainties for the data. This paper covers the following five tasks: Document acquisition and processing procedures used to create the particle image velocimetry (PIV) datasets. Compare PIV data with hotwire and laser Doppler velocimetry (LDV) data published in the open literature. Compare different datasets acquired at roughly the same flow conditions to establish uncertainties. Create a consensus dataset for a range of hot jet flows, including uncertainty bands. Analyze this consensus dataset for self-consistency and compare jet characteristics to those of the open literature. One final objective fulfilled by this work was the demonstration of a universal scaling for the jet flow fields, at least within the region of interest to aeroacoustics. The potential core length and the spread rate of the half-velocity radius were used to collapse of the mean and turbulent velocity fields over the first 20 jet diameters in a highly satisfying manner.


This survey was designed to determine the prevalence of Plasmodium falciparum and Salmonella Typhi among febrile HIV/AIDS patients in Ekpoma. Malaria and typhoid risk factors in Ekpoma included occupation, poor health facilities and poor sanitation. Malaria and typhoid are highly prevalent among Ekpoma HIV/AIDS patients.


Colon complications are a potential source of serious morbidity to the immunosuppressed patient. Because of multiple predisposing factors, renal transplant patients are a high-risk group for the development of acute colonic pseudo-obstruction. During a recent 18-month period, 290 renal transplants (79 living, 211 cadaveric donors) were performed and prospectively analyzed for colonic dysmotility. A total of 34 episodes of acute colonic ileus (30 primary, 4 recurrent) occurred in 30 (10.3%) renal transplant recipients. Acute colonic ileus was more frequent after living-donor transplantation (19.0% vs. 7.1%, p = 0.006). Analysis of multiple variables revealed that the incidence of acute colonic ileus was directly related to mean cumulative prednisone dosage (p less than 0.05). Medical therapy (rapid steroid reduction, bowel rest) resulted in a 76.7% response, whereas 8 patients underwent colonoscopy because of progression to acute pseudo-obstruction. The success rate for colonoscopic decompression was 87.5%; in 1 patient cecal perforation developed after unsuccessful decompression. Overall, 33 of 34 (97.1%) episodes of acute colonic ileus were successfully treated. Steroid-induced ileus (pseudo-obstruction) is a potentially malignant early form of colonic dysmotility infrequently reported in transplant recipients. Successful management requires early clinical recognition, reduction in steroid dosage, bowel rest, and urgent colonoscopic decompression in select cases.


In the present study, a convenient, low-cost, sensitive and environmentally friendly method for the determination of four benzoylurea insecticides (BUs) in water and tea beverage samples was developed. The alkalized luffa sponge fibers (AL) were modified by the ionic liquid 1-hexadecyl-3-methylimidazolium bromide ([C16MIM]Br) through physisorption and used as the sorbent of dispersive solid-phase extraction (DSPE). The sorbent was characterized by Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM) and thermogravimetric analysis (TGA). The retained analytes were eluted using 200 μL of methanol and then quantified by high performance liquid chromatography-ultraviolet detection (HPLC-UVD). The influences of extraction parameters of [C16MIM]Br-AL-DSPE on the BUs were thoroughly studied. Under the optimal conditions, good linearity was observed over the concentration range of 1–500 ng mL−1, with coefficients of determination greater than 0.99. The limits of detection (LODs) of the developed method were 0.14–0.21 ng mL−1 in water and 0.19–0.23 ng mL−1 in tea beverage samples. Satisfactory recoveries were achieved in the range of 72.8–89.3%, with relative standard deviations lower than 10%. Finally, the established [C16MIM]Br-AL-DSPE-HPLC-UVD method was successfully applied for the determination of BU residues in environmental water and tea beverage samples.


The gap between the number of protein sequences and protein structures is increasing rapidly, exacerbated by the completion of numerous genome projects now flooding into public databases. To fill this gap, comparative protein modelling is widely considered the most accurate technique for predicting the three-dimensional shape of proteins. High-throughput, automatic protein modelling should considerably increase our access to protein structures other than those determined by experimental techniques such as X-ray crystallography and NMR (nuclear magnetic resonance) spectroscopy. The uses for these complete three-dimensional models are growing rapidly, ranging from guiding site-directed mutagenesis experiments to protein-protein interaction predictions. In recognition of this, a number of very useful comparative modelling servers have begun to emerge on the Web. Molecular biologists now have a powerful web-based toolkit to construct models, assess their accuracy, and use them to explain and predict experiments. There is, however, still much to do by those engaged in algorithmic development if comparative modelling is to compete on an equal footing with experimental protein structure determination techniques.


We examine the use of publicly available voter rolls for household survey sampling as an alternative to household listings or field-based sampling methods. Using voter rolls for sampling can save most of the cost of constructing a sampling frame relative to a household listing, but there is limited evidence about their accuracy and completeness. We conducted a household listing in 13 polling stations in India comprising 2,416 households across four states and compared the listing to voter rolls for the same polling stations. We show that voter rolls include 91% of the households found in the household listing. We conduct simulations to show that sampling from voter rolls produces estimates of household-level economic variables with minimal bias. These results suggest that voter rolls may be suitable for constructing household sampling frames, particularly in rural India.


The superficial circumflex iliac artery perforator (SCIP) flap has been
used for scrotal reconstruction after Fournier's gangrene, skin cancer or
infections. However, there are few publications on regard to penoscrotal
reconstruction after a traumatic injury with this flap. In this article, we
propose a new SCIP flap variation, the "extended" or "direct" SCIP flap,
to effectively reconstruct a wide scrotal defect after a traumatic injury.
The "extended" SCIP flap is designed medial and cranial to the
anterosuperior iliac spine (ASIS) using the superficial branch of the
superficial circumflex iliac artery (SCIA) as the main pedicle.


Pregnancy is a physiological condition that takes a defined period of time in a woman's life. For nine months, the mother's heart works under conditions of daily additional load, which is necessary to ensure placental blood flow. In this regard, structural and functional adaptation of the heart develops in a healthy woman with a normal pregnancy. A pregnant woman with some heart diseases is less likely to adapt. That leads to greater susceptibility to stress resulting in pathological changes of pregnancy. In addition, each pregnancy may develop new heart diseases, which in some cases may be relatively innocent, but in others — fatal. In this regard echocardiography (EchoCG) is a necessary procedure for assessing a woman's health status that needs before bearing a fetus, during and after pregnancy.


The organotin(IV) compounds [Me(2)Sn(L)(2)] (1), [Et(2)Sn(L)(2)] (2), [(n)Bu(2)Sn(L)(2)] (3), [(n)Oct(2)Sn(L)(2)] (4), [Ph(2)Sn(L)(2)] (5), and [PhOSnL](6) (6) have been synthesized from the reactions of 1-(4-chlorophenyl)-1-cyclopentanecarboxylic acid (HL) with the corresponding diorganotin(IV) oxide or dichloride. They were characterized by IR and multinuclear NMR spectroscopies, elemental analysis, cyclic voltammetry, and, for 2, 3, 4 and 6, single crystal X-ray diffraction analysis. While 1-5 are mononuclear diorganotin(IV) compounds, the X-ray diffraction of 6 discloses a hexameric drumlike structure with a prismatic Sn(6)O(6) core. All these complexes undergo irreversible reductions and were screened for their in vitro antitumor activities toward HL-60, BGC-823, Bel-7402, and KB human cancer cell lines. Within the mononuclear compounds, the most active ones (3, 5) are easiest to reduce (least cathodic reduction potentials), while the least active ones (1, 4) are the most difficult to reduce. Structural rearrangements (i.e., Sn-O bond cleavages and trans-to-cis isomerization) induced by reduction, which eventually can favor the bioactivity, are disclosed by theoretical/electrochemical studies.


We consider a basic teletraffic model, which has applications to integrated multirate services on ATM and wireless systems. In the "finite-sources" version of the model an unbuffered resource with C channels is shared by heterogeneous sources which alternate between arbitrarily distributed random periods in the on and off states, and in the on state require a fixed number of channels. If a source does not find enough free channels when it turns on, then it is blocked and the burst is lost. In the "infinite-sources" version of the model requests for connections form Poisson streams and connections hold fixed numbers of channels for random periods. The stationary distribution of the system has the product-form and the insensitivity property. Our main results for the finite-sources model are for the asymptotic scaling in which C and the number of sources of each type are large. The central result is a uniform asymptotic approximation (UAA) for the blocking probabilities. It is uniformly effective for the complete range of loadings, simple to calculate and gives accurate results even for relatively small systems. The UAA is also specialized to the overloaded, critical and underloaded regimes. For the admission control of the system we calculate its Erlang capacity, i.e., the set of combinations of sources of various types such that the blocking probabilities for all types do not exceed specified values. For the first two regimes we obtain the boundaries of the admissible sets in the form of hyperplanes, and thus the effective bandwidths of sources of each type. For the underloaded regime the boundary is nonlinear and we obtain a convenient parameterized characterization. Finally, various numerical results are presented. >


Environmental pollution is a recent social problem with oŠensive odors, and food contamination is also a new social problem. The odor sensing system for detecting and controlling an oŠensive odor at an early stage is required. On using simple monitoring gas sensor in environment measurement, gas detecting tubes and semiconductor gas sensors are widely used in general. The quartz crystal microbalance gas sensor mainly detects gases by an electrode and a thin detection ˆlm. Therefore, detection ˆlms of the sensor depend on the characteristics of the sensing devices using material and processing technology. In addition, the new analyzers using surface plasmon resonance and millimeterwave technologies (Terahertz radiation) attract attention. The new sensor technologies are expected to detect extremely low concentration from ppm to ppb level with low atmospheric interference.


In this work we present a system that enables flexible coupling of distributed simulations as well as an immersive visualization solution for connected simulation results. Using this technology allows us to simulate entire production process chains, considering the various aspects at once rather than examining them separately one by one. The simulation experts that are involved get the opportunity to discuss and analyze their results inside a greater context with all the other experts. This is meant to further a scientific examination of the complete simulated process chain as an integral result. The post processing and visualization both rely on a concept that allows for the seamless integration of the expertly crafted individual visualizations, while still guaranteeing stable and interactive frame rates required in virtual environments. Using level of detail management,as well as selective refinement, the user(s) will be able to identify and mark important phenomena occurring within a certain space and time area of the simulation data with the so called widgets. Those can then be linked to other widgets and phenomena that provide an explanation. Using annotation techniques causal, relation based visualization combines the simulation data, its representation, and the explanations required to understand them.


By leveraging the additive manufacturing platform, development time and costs for turbine component testing can be reduced relative to traditional investment casting. Surface roughness is a key characteristic of the additive manufacturing process that can impact flow, heat transfer, and mechanical integrity of printed components. There are multiple design and build considerations that result in variability in surface roughness especially when additively fabricating complicated three-dimensional vanes and internal cooling passages. This study characterizes the surface roughness of internal cooling passages, vanes, and flat external surface samples made using additive manufacturing, specifically the direct metal laser sintering process. The samples were manufactured with various wall thicknesses, layer thicknesses, build locations, build directions, and on different AM machines. A combination of computed tomography scanning and optical profilometry were used to evaluate surface roughness levels. The data indicates that the dominate factors in roughness for a given layer thickness are a function of wall thickness, build location, and build direction.


Developing an anti-infective shape-memory hemostatic sponge with ability of guiding in situ tissue regeneration for noncompressible hemorrhage in civilian and battlefield settings remains a challenge. Here, hemostatic chitosan sponge with highly interconnective microchannels was engineered by combining 3D printed fiber leaching and freeze-drying methods and then modified with hydrophobic alkyl chains. The microchannelled alkylated chitosan sponge (MACS) exhibited a strong capacity for water/blood absorption and rapid shape recovery. Compared to clinically used gauze, gelatin sponge, CELOX, and CELOX-gauze, the MACS demonstrated higher pro-coagulant and hemostatic capacities in lethally normal/heparinized rat and pig liver perforation models. Also, it exhibited strong anti-infective activity against S. aureus and E. coli. Additionally, it promoted liver parenchymal cell infiltration, vascularization, and tissue integration in a rat liver defect model. Overall, the MACS demonstrated promising clinical translational potential in cost effectively treating lethal noncompressible hemorrhage and in facilitating wound healing.


Osseous metaplasia is rarely detected in benign and malignant lesions in the gastrointestinal tract, especially in the pediatric population under the age of six. Here, we report the case of a four-year-old boy with a history of constipation associated with painless bleeding per rectum for six months which was excised successfully. Microscopically, there was osseous metaplasia with no malignant changes. Further reporting is needed due to the limited cases of osseous metaplasia in colorectal polyps, with unknown mechanisms of pathogenesis and prognostic factors, specifically in the pediatric population.


The procedure introduced by Donald Nuss in 1997 at the American Pediatric Surgical Association meeting has now been adopted by pediatric, thoracic, and plastic surgeons around the globe. Since its introduction, the Nuss procedure has been the subject of intense scrutiny. More than 20 years since the original publication, medical centers from around the world have reported their experience with the procedure and robust evidence now supports its safety and efficacy. Additionally, in collaboration with psychologists in Norfolk, a methodology was devised to measure the psychosocial as well as the physical benefits of the procedure. Extensive independent multinational and multi-institutional data demonstrate repair of pectus excavatum using the Nuss procedure results in marked improvement in both physical function and body image. This report reviews the outcomes, quality of life, and long-term results of numerous centers worldwide since the introduction of the procedure.


Over the past decade, multilayer ceramic capacitors (MLCCs) have been able to achieve very high volumetric capacitance due to continuous improvement in their process technology. However, the performance of these devices is severely limited by the presence of electrode defects such as electrode porosity and roughness. To assess the effect of microstructure on MLCC performance, two sets of multilayer capacitors subjected to different processing conditions are compared for their microstructure and electrical properties. It is shown that more continuous and planar electrode morphology leads to lower local electric fields and thus, superior performance. These computational predictions are verified using electrical property measurements. Capacitors with higher electrode continuity exhibit proportionally higher capacitance, provided the grain-size distributions are similar. From the leakage current measurements, it is found that the Schottky barrier at the electrode–dielectric interface controls the conduction mechanism. This barrier height is adversely affected by the microstructural defects such as electrode discontinuities and roughness. These results are further supported by frequency-dependent impedance measurements.


The purpose of this paper is to present a new approach, based on the study of a particular solution of non-linear matrix equation, to investigate stationary network properties and to use the concept of closed-loop balanced realization to characterize some classes of symmetric systems. It is shown that it is possible to characterize symmetric electrical networks by using suitable quantities as regards passivity, lossless and relaxation. Propositions are pfioposed in order to give new characterizations of some classes of electrical networks. Suitable software has been developed to test the considered classes of systems.


Background and Aims: Stable vitiligo can be treated by various surgical procedures. Non-cultured melanocyte grafting techniques were developed to overcome the time-consuming process of culture while at the same time providing acceptable results. All the techniques using non-cultured melanocyte transfer involve trypsinisation as an integral step. Jodhpur technique used by the author is autologous, non-cultured, non-trypsinised, epidermal cell grafting. Settings and Design: The study was conducted on patients visiting the dermatology outpatient department of a tertiary health centre in Western Rajasthan. Materials and Methods: At the donor site, mupirocin ointment was applied and dermabrasion was done with the help of micromotor dermabrader till pinpoint bleeding was seen. The paste-like material obtained by this procedure containing melanocytes and keratinocytes admixed with the ointment base was harvested with spatula and was subsequently spread over the recipient area. Recipient site was prepared in the same manner by dermabrasion. After 10 days, dressing at both sites was removed taking utmost care at the recipient site as there was a theoretical risk of dislodging epidermal cells. Results: In a study of 437 vitiligo patches, more than 75% re-pigmentation (excellent improvement) was seen in 41% of the patches. Lesions on thigh (100%), face (75%) and trunk (50%) showed maximal excellent improvement, whereas patches on joints and acral areas did not show much improvement. Conclusions: This technique is a simplified, cost effective, less time-consuming alternative to other techniques which involve tryspsinisation of melanocytes and at the same time provides satisfactory uniform pigmentation.


Microbes can trigger chronic immune disorders to dietary antigens, such as in celiac disease Immune tolerance to dietary antigens is key to preventing undesirable responses to innocuous antigens ingested with food. On page 44 of this issue, Bouziat et al. (1) report how viral infection may break oral tolerance to dietary proteins. The findings provide an explanation for the known epidemiological association between viral infections and the onset of food sensitivities, such as celiac disease. The results are of great interest considering the recent increase in prevalence of food allergies and autoimmune disorders, which suggests an unknown environmental risk modifier.


A new fluorescence probe for distinguishing Zn(2+) and Cd(2+) is designed and synthesized. For the first time to our knowledge, this probe can recognize similar metal ions by coherently utilizing intramolecular charge transfer (ICT) and different electronic affinities of various metal ions, instead of by selective coordination alone, which may be interfered with and lose its selectivity easily in a complicated environment, providing a distinct recognition even by the naked eye for Zn(2+) and Cd(2+) with the sensitivity at the ppb level. This design strategy may initiate a straightforward approach for the selective detection of various metal ions with similar chemical properties in extensive applications such as environmental, industrial, and bio-science.


Dermatitis artefacta is the dermatological variant of a disorder that is classified in psychiatry as a factitious disorder. Patients with a factitious disorder intentionally feign or self-induce medical symptoms with the aim of being recognized and treated as a patient. There is a substantial risk for severe iatrogenic complications. A good prognosis depends on early recognition of the disorder. In practice this is difficult because the patients present without any objective signs. Awareness of the signals of a pathological interaction between doctor and patient, such as feelings of frustration, distrust or abnormal positive feelings, can therefore be very useful. Also recognition of other alarm symptoms can be helpful. Doctors are advised to consider a factitious disorder in the differential diagnosis as early as possible and to discuss this openly with their patients. Furthermore consulting a psychiatrist is important. Goal of an intervention is primarily the ending of the pathological patient doctor interaction and the resulting iatrogenic complications. The prognosis can be positively influenced when the treating physician together with a psychiatrist confront the patient in a professional manner.


Understanding narrated instructional videos is important for both research and real-world web applications. Motivated by video dense captioning, we propose a model to generate procedure captions from narrated instructional videos which are a sequence of step-wise clips with description. Previous works on video dense captioning learn video segments and generate captions without considering transcripts. We argue that transcripts in narrated instructional videos can enhance video representation by providing fine-grained complimentary and semantic textual information. In this paper, we introduce a framework to (1) extract procedures by a cross-modality module, which fuses video content with the entire transcript; and (2) generate captions by encoding video frames as well as a snippet of transcripts within each extracted procedure. Experiments show that our model can achieve state-of-the-art performance in procedure extraction and captioning, and the ablation studies demonstrate that both the video frames and the transcripts are important for the task.


A new machine learning approach has been developed in this study for sequence-based prediction of DNA-binding residues in proteins. The approach used both the labeled data instances collected from the available structures of protein-DNA complexes and the abundant unlabeled data found in protein sequence databases. The evolutionary information contained in the unlabeled sequence data was represented as position-specific scoring matrices and several new descriptors. The sequence-derived features were used to train random forests, which could handle a large number of input variables and avoid model overfitting. The use of evolutionary information was found to significantly improve classifier performance. The RF classifier was further evaluated using a separate test dataset. The results suggest that the RF-based approach gives rise to more accurate prediction of DNA-binding residues than previous studies.


Acute Myeloid Leukemia (AML) is an aggressive malignancy of the blood system, wherein somatic mutations in epigenetic modifier and chromatin remodeling genes are common. Recurrent somatic mutations in the DNA methyltransferase 3 alpha (DNMT3A) gene are detected in about 30% of AML cases, and predict poor outcomes in patients treated with anthracycline-based induction chemotherapy, due to suboptimal response to therapy and subsequent early disease relapse. DNA methylation profiling in both primary AML samples and in animal models carrying a DNMT3A mutation detected modest DNA hypomethylation that did not fully explain how mutant DNMT3A contributed to AML pathogenesis. Recent studies have uncovered disordered nucleosome remodeling in response to DNA topological stress in DNMT3A-mutant cells, which was most pronounced during DNA replication. These changes were accompanied by negative enrichment of the cell cycle-associated gene expression signatures and attenuated CHK1 signaling, implicated in DNA damage response and replication fork integrity. Therefore, we hypothesized that targeting the S-phase in leukemic cells with DNMT3A mutations by pharmacologic agents that stall replication may offer enhanced therapeutic benefit. Indeed, our studies show increased sensitivity to replication stalling pharmacological treatments such as nucleoside analogues cytarabine and fludarabine in different cellular systems harboring DNMT3A mutations. This was accompanied by increased apoptosis as measured by PARP cleavage and annexin V binding.Analysis of the DNA damage signaling revealed elevated CHK1 phosphorylation signaling and accumulation of the DNA damage marker gammaH2A.X. A similar drug sensitivity trend was observed in murine Dnmt3a-mutant bone marrow cells treated with cytarabine, using clonogenic survival in MethoCult as readout. In order to examine this, we are developing isogenic cellular systems with differing DNMT3A mutational status via the CRISPR-Cas9 gene-editing approach. Further, these isogenic cell lines will be used as a tool to characterize the effect of mutant DNMT3A on replication progression, arrest, and resolution under pharmacologically induced replication stress. This will include analysis of the chromatin remodeling at the replication forks, proficiency of DNA damage repair, and dynamic localization of wild-type and mutant DNMT3A within the cells throughout the cell cycle. Finally, we will test the efficacy of replication stress inducing therapies in vivo in a genetically accurate mouse model of Dnmt3a-mutant AML. These studies will shed light on the mechanism of a potential vulnerability in DNMT3A-mutant leukemia cells and may lead to a more effective treatment strategy for this common subtype of AML. Citation Format: Kartika Venugopal, Daphne Dupere-Richer, Jonathan Licht, Olga Guryanova. Targeting DNA replication as a therapeutic strategy for acute myeloid leukemia with DNMT3A mutations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 343.


We propose neural trace photography, a novel framework to automatically learn high-quality scanning of non-planar, complex anisotropic appearance. Our key insight is that free-form appearance scanning can be cast as a geometry learning problem on unstructured point clouds, each of which represents an image measurement and the corresponding acquisition condition. Based on this connection, we carefully design a neural network, to jointly optimize the lighting conditions to be used in acquisition, as well as the spatially independent reconstruction of reflectance from corresponding measurements. Our framework is not tied to a specific setup, and can adapt to various factors in a data-driven manner. We demonstrate the effectiveness of our framework on a number of physical objects with a wide variation in appearance. The objects are captured with a light-weight mobile device, consisting of a single camera and an RGB LED array. We also generalize the framework to other common types of light sources, including a point, a linear and an area light.


The Nsp1 protein of SARS-CoV-2 regulates the translation of host and viral mRNAs in cells. Nsp1 inhibits host translation initiation by binding to the entry channel of the 40S ribosome subunit. The structural study of SARS-CoV-2 Nsp1-ribosomal complexes reported post-termination 80S complex containing Nsp1 and the eRF1 and ABCE1 proteins. Considering the presence of Nsp1 in the post-termination 80S ribosomal complex simultaneously with eRF1, we hypothesized that Nsp1 may be involved in translation termination. We show the direct influence of Nsp1 on translation termination. Using a cell-free translation system and reconstituted in vitro translation system, we reveal that Nsp1 stimulates translation termination in the stop codon recognition stage. We identify that activity of Nsp1 in translation termination is localized in its N-terminal domain. The data obtained will enable an investigation of new classes of potential therapeutic agents from coronavirus infection competing with Nsp1 for binding with the termination complex.


"In Evil Hour" is the thrilling story of a Colombian society menaced by rumour and paranoia by the Nobel Laureate Gabriel Garcia Marquez, author of the "One Hundred Years of Solitude" and "Love in the Time of Cholera". As a small South American town sweats under an oppressive heat, an unknown person creeps through the night sticking malicious posters to walls and doors. When the contents of one poster lead to a murder, everyone knows that the town is threatened by a malevolent presence - but is there anything that the mayor, the doctor or the priest can do about it? ""In Evil Hour" was the book which was to inspire my own career as a novelist. I owe my writing voice to that one book!" (Jim Crace). "Belongs to the very best of Marquez's work...should on no account be missed." ("Financial Times"). "A splendid achievement." ("The Times"). As one of the pioneers of magic realism and perhaps the most prominent voice of Latin American literature, Gabriel Garcia Marquez has received international recognition for his novels, works of non-fiction and collections of short stories. Those published in translation by Penguin include "Autumn of the Patriarch", "Bon Voyage Mr. President", "Chronicle of a Death Foretold", "Collected Stories", "The General in his Labyrinth", "Innocent Erendira and Other Stories", "Leaf Storm", "Living to Tell the Tale", "Love in the Time of Cholera", "Memories of My Melancholy Whores", "News of a Kidnapping", "No-one Writes to the Colonel", "Of Love and Other Demons", "The Story of a Shipwrecked Sailor" and "Strange Pilgrims".


Errors in stratospheric bending angles retrieved from GPS radio occultations can be significantly reduced by using statistical optimization. In order for this technique to work optimally, the error covariance of the observations and the error covariance of the first guess must be known. This is generally not the case, and it is therefore common practice to assume that each of these errors is uncorrelated. In this study, it is shown that when this assumption is applied together with dynamical error estimation, it is important to account for the fact that first guess and the observation bending angle errors are not damped equally when refractivity profiles are computed through the Abel transform. It is demonstrated that this difference in damping can be accounted for by scaling the ratio of observation to first‐guess bending angle error variances. It is shown that the scaling factor can be related to the ratio between the error correlation lengths of the observation errors and the first‐guess errors. We present a simple procedure where both correlation lengths and variances are estimated dynamically and are scaled as described above. It is found that the relative errors can be reduced by up to 30% when compared to a standard statistical optimization scheme where the relative error in the first‐guess bending angle profile is assumed to be 20%. However, it was also found that if the first guess is properly adjusted, the need for corrections is greatly reduced.


Introduction

Many community services have been implemented over the past five years to support patients with COPD at home when exacerbating, including the use of telemonitoring. The evaluation of these new technologies is limited, variable and controversial (Wootton 2012, Journal of Telemedicine and Telecare 18: (4) 211-220).

Aim

To evaluate an IVRS used within a local service providing early discharge and admission avoidance to patients with COPD. To assess the effect of telehealth delivered in this way on admission rates of this group of patients.

Method

A service evaluation was conducted examining retrospective data comparing the admission rates of patients who had access to the IVRS and usual care (n =20) and those who had access to usual care alone (n =20). Demographic data and admission frequency 12 months before and after the instigation of the IVRS and twelve months before and after engagement with the team without IVRS were examined.

Results

Data is presented as mean +- SEM. Data analysed using Mann Whitney u test. When comparing the admission history of the group receiving IVRS and those receiving usual care alone there was a significant reduction in admissions within the telehealth group (-0.3 +0.28 v 0.7 +0.35 p= 0.0287). Telehealth appeared to provide a positive influence on the number of admissions that the group experienced after its introduction although within the IVRS group alone this did not achieve statistical significance (p = 0.336).

Conclusion

Whilst it appears that the use of the IVR in patients with COPD assists in reducing admission rates, further evaluation is needed to be confident of its effects.


This paper studies in experiment and theory the breakdown of argon, nitrogen, air and oxygen in a uniform dc electric field at different discharge gaps L, discharge tube radii R and cathode materials. At arbitrary geometric dimensions of the cylindrical discharge vessel and cathode materials the ratio of the breakdown electric field value to the gas pressure p at the minimum of the breakdown curves is shown to remain constant, (Edc/p)min≈constant. A modified breakdown law for the low-pressure dc discharge Udc = f(pL,L/R) is obtained. That is, the breakdown voltage Udc is shown to depend not only on the product pL, but also on the ratio L/R. A method is presented enabling one to predict a dc breakdown curve in the cylindrical discharge vessel possessing arbitrary L and R values from the measured data on the dc breakdown.


This article focuses on Anglo-American relations during, what US Secretary of State Henry Kissinger termed, the 'Year of Europe'. In particular, Anglo-American interaction leading up to, and during, the Washington Energy Conference (11–13 February 1974) is examined. By doing this, subtle nuances in the foreign policy of Edward Heath, British Prime Minister, 1970–1974, can be better appreciated. Traditionally viewed by commentators as varying between lukewarm and antagonistic towards the Anglo-American 'special relationship', this article highlights that Heath was more than capable with working closely with Washington when he believed British interests were best promoted by doing so. Heath showed throughout the Arab oil embargo of 1973–1974 an ability to work in close cooperation with Washington. Indeed, Heath demonstrated that he was prepared to sacrifice his wider European ambitions in order to secure this. This was largely driven by Heath's overriding concern that US support was imperative to prevent the outbreak of 'beggar thy neighbour' oil policies that he concluded would result if the European Economic Community approach, predominantly driven by French thinking, was endorsed.


We define two novel iterative models of social networks. The models are deterministic processes that generate graphs over discrete time-steps, and the properties of these graphs will be explored. The first model generalizes two known models: the Iterated Local Tran- sitivity Model and the Iterated Local Anti-Transitivity Model. The Iterated Local Model includes as input an infinite binary sequence that determines the way the graphs are constructed over time. These models each utilize the underlying graph structure in previous time-steps. Subsequently, we define a model that is independent of the structure of the graph at the previous time-step. The Iterated Global Model creates new adjacencies based on subsets of vertices of a prescribed cardinality. We prove complex network properties of the Iterated Local Model, such as the small- world property and bad spectral expansion. We also present graph-theoretic properties of the model, such as bounds on the chromatic number, domination number, and Hamiltonicity properties. Analogously, for the Iterated Global Model, we prove both complex network and graph-theoretic properties.


Increasing demand from consumers plus European Union (EU) legislation has raised awareness within the automotive production sector of the urgent need to reduce the environmental impacts from the three main stages in vehicle life – car manufacture, car use and end-of life vehicle processing. The paper reviews how the originator and manufacturer of the smart automobile has worked directly with its main system partners to address environmental issues in these three stages while optimizing performance across the parameters of commercial viability. This required the creation of strategic relationships within the supply chain. Overall, this innovative approach is viewed in the context of a total product system. The smart car highlights the following critical areas: use of modularity in product design and production facility layout; emphasis on partner participation from product creation to after sales; and use of a highly customized build-to-order product system to 'green' the entire supply chain. In particular, the case study compares the process characteristics employed at the smart car factory, called 'smartville', to more 'traditional' approaches to vehicle manufacture. It examines these issues in a preliminary attempt to establish the actual or potential reduction of environmental impact in the three stages of vehicle life, including the role of main suppliers in this process.


Introduction/Background Niraparib improves progression-free survival (PFS) in patients (pts) with newly diagnosed advanced ovarian cancer after 1st-line (1L) platinum-based chemotherapy (CT). We report the efficacy of niraparib in pts by biomarker status. Methodology This double-blind, placebo (PBO)-controlled, phase 3 study randomized 733 pts with newly diagnosed advanced ovarian, primary peritoneal, or fallopian tube cancer with a complete or partial response (CR or PR) to 1L platinum-based CT. Stratification factors were best response to the 1L CT (CR/PR), receipt of neoadjuvant CT (yes/no), and homologous recombination status (deficient/proficient/not determined). Pts received niraparib or PBO once daily. The primary endpoint of PFS assessed by blinded independent central review was analyzed using a stratified Cox proportional hazards model and hierarchically tested in homologous recombination deficient pts, then the overall population. Results Of 733 randomized pts (niraparib, 487; PBO, 246), 373 (51%) were homologous recombination deficient (niraparib, 247; PBO, 126) and 249 (34%) were homologous recombination proficient (niraparib, 169; PBO, 80). Overall, 35% had stage IV disease, 67% received NACT, and 31% had a PR to 1L CT. Niraparib-treated pts in all the biomarkers groups had a statistically significant and clinically meaningful benefit in PFS (table 1). The most common grade ≥3 adverse events were anemia (31%), thrombocytopenia (29%), and neutropenia (13%). Abstract – Table 1 Disease characteristics Hazard ratio (95% CI) P Value Overall 0.62 (0.502–0.755) <0.0001 Homologous recombination deficient 0.43 (0.310–0.588) <0.0001 BRCAmut 0.40 (0.265–0.618) <0.0001 BRCAwt 0.50 (0.305–0.831) 0.0064 Homologous recombination proficient 0.68 (0.492–0.944) 0.0203 Conclusion Niraparib improved PFS as evidenced by reduction in the risk of recurrence or death due to any cause in the overall population of advanced ovarian cancer. No new safety signals were identified. CI=confidence interval; mut=mutated; wt=wild type Disclosure AMG: Consulting: AstraZeneca, TESARO, Roche, Pharmamar, Clovis, Merck, Genmab, ImmunoGen, Oncoinvent AS BP, RDC: Advisory: TESARO IV: Personal: Advaxis, Eisai, MSD Belgium, Roche NV, Genmab, Roche, Pharmamar, Millennium Pharmaceuticals, Clovis, Astrazeneca NV, Tesaro, Immunogen, Sotio. Grants: Amgen, Stichting tegen Kanker, Roche. Contracted Research: Oncoinvent AS, Genmab WG: Consulting: TESARO MM: Leadership/Other ownership: Karyopharm Therapeutics, Sera Prognostics. Personal Fees: Roche, AstraZeneca, Clovis, Pfizer, TESARO, Genmab, BioCad, Sotio, Geneos Therapeutics, Merck, Oncology Venture, Seattle Genetics, Sera Prognostics, Takeda, Zailab. Grants: AstraZeneca, Clovis, Pfizer, TESARO, Boehringer Ingelheim CCM, PH, KHB, KJ, CGAV, BL, AFH, MJR-P, WHB, IB: none DL: Personal: AstraZeneca, Clovis, Genmab, Immunogen, Pharma Mar SA, Amgen, Merck. Grants: Pharma Mar SA, Merck GF: Personal: TESARO, AstraZeneca, Clovis, Roche, Bristol-Meyers Squibb, MSD, Pfizer, Novartis. Grants: AstraZeneca, Roche AR: Research funding/Advisory role: Pharmamar, Roche, Eisai,AstraZeneca, TESARO RGM: Research: Angle PLC. Consulting: Fujirebio Diagnostics REO: Advisory: Clovis, TESARO, GlaxoSmithKline FB: Advisory: TESARO, Clovis, Agenus, Merck, Eisai. Grant: Clovis, Merck, Eisai, Immunogen. Lecture: CEC Oncology MPBG: Lecture/Advisory board: TESARO, AstraZeneca, Roche, Clovis, Pharmamar, MSD. MSS: Personal: TESARO, Merck, Astra Zeneca, Clovis, Pacira Pharamceuticals. Grant: TESARO GM: Personal: AstraZeneca, TESARO. Non-Financial Support: TESARO, Roche. BJM: Speaker bureau, Grant: TESARO KS, IM, YL, DG: TESARO employee.


Background

A set of superior parental lines is the key to high-performing recombinant inbred lines (RILs) for biparental crossing in a rice breeding program. The number of possible crosses in such a breeding program is often far greater than the number that breeders can handle in the field. A practical parental selection method via genomic prediction (GP) is therefore developed to help breeders identify a set of superior parental lines from a candidate population before field trials.
Results

The parental selection via GP often involves truncation selection, selecting the top fraction of accessions based on their genomic estimated breeding values (GEBVs). However, the truncation selection inevitably causes a loss of genomic diversity in the breeding population. To preserve genomic variation, the selection of closely related accessions should be avoided. We first proposed a new index to quantify the genomic diversity for a set of candidate accessions. Then, we compared the performance of three classes of strategy for the parental selection, including those consider (a) GEBV only, (b) genomic diversity only, and (c) both GEBV and genomic diversity. We analyzed two rice (Oryza sativa L.) genome datasets for the comparison. The results show that the strategies considering both GEBV and genomic diversity have the best or second-best performance for all the traits analyzed in this study.
Conclusion

Combining GP with Monte Carlo simulation can be a useful means of parental selection for rice pre-breeding programs. Different strategies can be implemented to identify a set of superior parental lines from a candidate population. In consequence, the strategies considering both GEBV and genomic diversity that can balance the starting GEBV average with maintenance of genomic diversity should be recommended for practical use.


Our hospitals of all types and sizes present a dismal picture and have miserably failed to meet the rising demands of its consumers, in terms of technology, quality, quantity and cost of care. The situation prevailing has been documented in various press reports and cases registered to the consumer forums in the country. The author while presenting the maladies involving the hospitals has made an attempt to analyse the cause and effect relationship of the maladies and suggested remedial measures. More emphasis has been laid on economic use of resources, cost containment, training and motivation of all categories of staff, and introduction of quality management techniques to improve functional efficiency for better output, in terms of quality, quantity, cost of care and consumer satisfaction.


This report discusses the Economic Growth and Tax Relief Reconciliation Act of 2001, the Jobs and Growth Tax Relief Reconciliation Act of 2003 (JGTRRA, and the Working Family Tax Relief Act of 2004 (WFTRA). Since all of the tax reductions provisions of all three of these acts expire at some point in the future, Congress faces the issue of whether to extend and/or make the reductions permanent. Extending these tax reductions, however, is likely to significantly reduce federal revenues in the future.


We demonstrate for the first time a 1.3-/spl mu/m wavelength optoelectronic InGaAsP-InP smart pixel switching circuit using monolithically integrated p-i-n photodiodes and heterojunction bipolar transistors, along with surface-mounted folded-cavity surface-emitting lasers. The circuit functions as a cascadable optical switch with an on/off ratio of 6, and a maximum optical input/output differential gain of 6. At a bit rate of 100 Mb/s, a record low switching energy of 30 fJ was observed while maintaining circuit gain and cascadability. This switching energy is the lowest reported to date for an optoelectronic smart pixel.<<ETX>>


This thesis addresses observer design for nonlinear dynamical systems which can be approximated with dissipative Hamiltonian realizations. The design methods builds upon earlier developments that allow the approximate dissipative potential to be extracted using a homotopy operator. This potential is obtained by decomposition of the observer error associated one-form using the homotopy operator which generates the potential. A time-varying differential metric equation dependent on the Hessian of the potential and the measured output function is proposed, which is used to design a state observer. The stability of both the observer and metric equation are assessed using Lyapunov theory. A time-invariant metric is then proposed making use of the Hessian of the potential on a metric-state based observer. Using several process simulations, the approach is shown to provide an effective design alternative for nonlinear observer design.


Abstract The aim of this study was to determine whether behaviour problems in indoor cats depend on the number of cats in a household or rearing one or more cats in a household together with a dog. The study was carried out on animals which were divided for the purpose of this study into 4 groups: (1) households with one cat; (2) households with two cats; (3) households with three or more cats; (4) households with one or more cats and a dog. Altogether 91 cats were included in the study. The practical part of this investigation was based on a questionnaire. It was observed that the probability of behaviour problems was not related unambiguously to the number of cats in a household or the company of a dog. The percentage of the occurrence of changed behaviour did not differ significantly between the groups.


A general formulation for the spectral calculations of the Hamiltonian operator of a Quantum Fractal Network (QFN) is presented. The QFN can be constructed by placing artificial neurons on each site of the fractal lattice. An artificial neuron may consist of a cell of a quantum cellular automaton or a quantum dot, which confines a single electron. The Coulomb interaction or the spin-spin interaction between neurons can be used to transmit signals and perform logic operations. The recursive formulas of the eigenvalues and eigenvectors between sub-lattices are obtained explicitly. As the application of the formulations, the eigenvalues and eigenvectors of the Hamiltonian operator for the Sierpinski gasket are calculated.


Lafora disease (LD) is a teenage-onset fatal progressive myoclonus epilepsy caused by loss-of-function mutations in the EPM2A gene encoding the glycogen phosphatase laforin or EPM2B encoding the laforin-interacting ubiquitin E3 ligase malin. Concerted actions of glycogen synthase (GS) and branching enzyme generate normal short-branched soluble glycogen. In LD, some glycogen molecules develop long branches, precipitate, and accumulate into pathognomonic and pathogenic Lafora bodies (LBs). The precise mechanism by which the laforin-malin complex mitigates this is unknown, but thought to involve GS downregulation. In fact, transgenic GS downregulation in LD mouse models reduces LB formation and rescues the disease.1,2


A high-resolution threshold-electron spectrometer was used to study excitation of HCl molecules O-10 meV above the thresholds for electronically excited states. The spectrum is obtained in an energy region from 4.2-14 eV corresponding to the excitation of lower valence states and Rydberg states below and just above the 2 Pi 3/2, 1/2, ionisation threshold. This first study of threshold excitation of HCl molecules reveals a considerable difference in relative intensities of some of the states compared with the case of higher-energy collisions. The transition into the lowest 3 Pi valence state is reported for the first time. The threshold ionisation region is discussed in terms of the superposition of the correlation-dominated direct ionisation process and the excitation function of an autoionising level decaying by releasing a zero-energy electron.


Abstract Background Encyrtidae and Mymaridae of India have not been surveyed in depth and hosts are not known for most of the species as the methods of collections used are passive and do not yield firsthand information on the hosts. Based on our ongoing surveys on the Encyrtidae and Mymaridae of India, we report here new distribution and host records for some species. New information Acmopolynema campylurum Xu and Lin, Litus cynipseus Haliday, Omyomymar glabrum Lin and Chiappini and Platystethynium Ogloblin (Mymaridae), and Rhytidothorax purpureiscutellum (Girault) (Encyrtidae) are reported for the first time from India. Anagyrus aquilonaris (Noyes and Hayat) is recorded as new to Arunachal Pradesh and Meghalaya. Paraphaenodiscus indicus Singh and Agarwal and Paraphaenodiscus monawari Bhuiya are recorded from south India for the first time, the latter on a new host, Pulvinaria polygonata. Chorizococcus sorghi Williams (Pseudococcidae) is reported as a host for Cryptanusia ajmerensis (Fatma & Shafee), for which no hosts are hitherto known and the male of Cryptanusia is documented for the first time. Aclerda sp. is recorded as a new host for Neastymachus axillaris Singh, Agarwal and Basha.


Dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase, has anti-tumor properties in various carcinoma models. Diisopropylamine dichloroacetate (DADA), an over-the-counter drug for chronic liver disease, is a derivative of DCA. To date, few studies have evaluated the anticancer potential of DADA in breast cancer. In this study, MDA-MB-231 cells, a breast adenocarcinoma cell line, were used in in vitro and in vivo experiments to evaluate the anti-tumor efficacy of DADA and DCA. The half maximal inhibitory concentration (IC50) of DADA (7.1 ± 1.1 mmol/L) against MDA-MB-231 cells was significantly lower than that of DCA (15.6 ± 2.0 mmol/L); 100 mg/kg (0.0004 mol/kg) DADA was better than 100 mg/kg (0.0008 mol/kg) DCA at suppressing the growth of subcutaneous transplantation breast tumor at the same dose after 24 days intervention. Histological examination showed that both DCA and DADA interventions led to necrosis, inflammation, and fibrosis of tumor tissue in a mouse subcutaneous transplantation breast tumor model. DADA treatment inhibited Ki67 expression in tumor tissue. In vitro experiments showed that DADA could inhibit lactic acid production and glucose uptake in MDA-MB-231 cells at 10 mmol/L and these effects were stronger than DCA. DADA administration also induced complete autophagy during early treatment stages and incomplete autophagy and cell death at later treatment stages. In conclusion, DADA showed better anti-tumor efficacy than DCA in a breast cancer model.


The seriousness and the difficult care of the alcohol-dependent persons often occult an other category of persons drinking too much: the problem drinkers. Nevertheless, these persons are as many in the practice of all the physicians and their various pathologies concern all the medical specialties. Their identifying is based on the self declared consumption. Their lack of dependence and their attendance with their general practitioner make their care easier. A brief intervention aiming to reduce their consumption is a primary or secondary prevention which is more often enough to resolve all or part of their complaints.


Aquatic organisms have been used to investigate the safety of chemicals worldwide. One such assessment is an algal growth inhibition test. Algal growth inhibition tests are commonly performed using a growth chamber with fluorescent lamps as the lighting source, as test guidelines require continuous uniform fluorescent illumination. However, fluorescent lamps contain mercury, which has been identified as hazardous to humans and other organisms. The Minamata Convention (adopted in 2013) requires reduction or prohibition of products containing mercury. On the other hand, light-emitting diodes do not contain mercury and provide a photosynthetically effective wavelength range of 400–700 nm which is an adequate light intensity for algal growth. Light-emitting diodes are thus preferable to fluorescent lamps as a potential light source in algal growth inhibition tests. In this study, we investigated if light-emitting diodes could be substituted for fluorescent lamps in growth inhibition studies with green alga (Pseudokirchneriella subcapitata), diatom (Navicula pelliculosa), and cyanobacteria (Anabaena flos-aquae). Algal growth inhibition tests were performed using five different chemicals known to have different modes of action and are assigned as reference substances in the test guidelines. The results of each algal test showed similar values between light-emitting diodes and fluorescent lamps in terms of conditions for the growth inhibition rate and percent inhibition in yield of each chemical. It was therefore concluded that using light-emitting diodes instead of fluorescent lamps as a lighting source had no effect on the algal growth inhibition test results.


Angiotensin II (Ang II) acts on central angiotensin type 1 (AT1) receptors to increase water and saline intake. Prolonged exposure to Ang II in cell culture models results in a desensitization of the AT1 receptor that is thought to involve receptor internalization, and a behavioural correlate of this desensitization has been shown in rats after repeated central injections of Ang II. Specifically, rats given repeated injections of Ang II drink less water than control animals after a subsequent test injection of Ang II. In the same conditions, however, repeated injections of Ang II have no effect on Ang II‐induced saline intake. Given earlier studies indicating that separate intracellular signalling pathways mediate Ang II‐induced water and saline intake, we hypothesized that the desensitization observed in rats may be incomplete, leaving the receptor able to activate mitogen‐activated protein (MAP) kinases (ERK1/2), which play a role in Ang II‐induced saline intake without affecting water intake. In support of this hypothesis, we found no difference in MAP kinase phosphorylation after an Ang II test injection in rats given prior treatment with repeated injections of vehicle, Ang II or Sar1,Ile4,Ile8‐Ang II (SII), an Ang II analogue that activates MAP kinase without G protein coupling. In addition, we found that pretreatment with the MAP kinase inhibitor U0126 completely blocked the desensitizing effect of repeated Ang II injections on water intake. Furthermore, Ang II‐induced water intake was reduced to a similar extent by repeated injections of Ang II or SII. The results suggest that G protein‐independent signalling is sufficient to produce behavioural desensitization of the angiotensin system and that the desensitization requires MAP kinase activation.


Abstract Carbonate rocks have been sampled through predominantly siliciclastic sediments above the Precambrian-Cambrian global stratotype level in southeastern Newfoundland to assess their potential for oxygen and carbon isotope stratigraphy. Comparable successions were sampled at Nuneaton and Comley in England. Greatly depleted δ18O signals are attributed to widespread thermal alteration during deep burial and granitic intrusion, including within the stratotype region. Carbon isotope ratios appear to have been less affected and these are described from nine sections. A provisional, composite δ13C curve is based on non-ferroan, pink nodular and bedded micrites. Several δ13C excursions occur in the fossiliferous Bonavista Group and allow the position of the Tommotian-Atdabanian boundary to be identified. Chemostratigraphic correlation of the new Precambrian-Cambrian boundary stratotype may, however, prove difficult because of the lack of suitable, well-preserved carbonates. The search must begin for a comparable reference section allowing global correlation of the boundary level using chemostratigraphy as well as biostratigraphy.


A number of interesting bird records were made by a team of ten biologists from Cambridge University (UK), Universitas Pattimura (Ambon, Maluku), and Wetlands International, (Indonesia), during a three month research and conservation project in 1996 in the proposed Cagar Alam (Nature Reserve) of Wae Bula in northeast Seram. This paper documents five species previously unrecorded on the island and provides information concerning several species of interest in terms of distribution or conservation. Seram still holds large tracts of unexplored and unsurveyed forest which are likely to hold important populations of threatened and endemic species; future visitors are encouraged to extend our limited knowledge of the avifauna of this island.


The article examines one of the main directions of the implementation of a large-scale program of economic reforms in Saudi Arabia (Saudi Vision-2030), aimed at ridding the Kingdom's economy of an alarming dependence on oil export revenues – the digital transformation of society, governing structures, and the economy as a whole. In the past few years, the information and communication technology (ICT) sector, which has become the largest in the Middle East, is increasingly visible not only in this region. Its development is particularly dynamic due to large investments in the latest technologies. The success of the ICT sector was also facilitated by the creation of new supervisory bodies and the improvement of the regulatory framework for various areas of digitalization. The country's leadership aims to make Saudi Arabia one of the world's leading countries in the field of ICT by building a digital economy based on the principles of the Fourth Industrial Revolutionanddigitalgovernanceofsociety. The five-year digital development strategy (2019–2023) provides for the growth of the ICT sector by 50% and an increase in the rate of "Saudization" of this sector to 50% by 2023. This strategy is expected to increase the contribution of the ICT sector to the economy by at least $13.3 billion. Assessing the prospects for the development of digitalization in Saudi Arabia, the author found four factors that make it possible to assess them as very favorable – sufficient funding, acceleration of the privatization process, the impact of the COVID-19 pandemic, and the inevitability of the diversification of the national economy, which is impossible without digitalization.


In contrast to theory, speckle imaging has proven an effective tool for scene recovery over long horizontal paths where imaging distortions are highly anisoplanatic. One possible explanation for this efficacy is that the atmospheric bispectrum transfer function is less attenuated at higher spatial frequencies when the object is extended and not a pair of point sources, as examined by theory. In this work, I empirically evaluate the speckle, cross-spectrum, and bispectrum transfer functions by comparing these quantities as derived from both field and simulation data to a simulated diffraction-limited reference image. The empirical transfer function relationships are found by comparing turbulence quantities to those of their diffraction-limited counterparts.


The quantitation of effort both within and among surgical pathology laboratories is data which is being increasingly sought by physician managers, hospital administrators and managed care organizations. Simple measurement of case numbers fails to adequately represent the work of a laboratory. The complexity of the cases reviewed is likely to explain a significant portion of the variance in the time required to bring a case to final diagnosis. Measures which adequately reflect complexity in surgical pathology cases have not been developed. We have studied a variety of extractable report features and correlated these with the time required for case sign-out. Numbers of slides reviewed and total lines of factual data provided were strong correlates of the time required to complete case review, report construction and verification. Such data suggests that models can be constructed based on data that can be gleaned from case reports and records which will relate such data to actual work time.


Immunity jamu consists of ginger, turmeric, Centella, and cinnamon, that act as immunostimulant agents. However, the infusion is impractical and used a limited dose of the extract, so it is necessary to develop drug delivery to resolve that problem. The SNEDDS technique is expected to increase the solubility, drug release, and absorption of active substances in the body, especially for low solubility of an active substance. SNEDDS consists of oil, surfactant, and co-surfactant. A surfactant is a substance that can reduce surface tension so that emulsion globules form in nanoparticle size. Tween 80 can produce a more transparent solution for oil-in-water emulsions than surfactants with low HLB values. This study aimed to determine the effect of surfactant concentration on the physical properties of SNEDDS to obtain the most loading dose but the smallest particle size. The formula consists of tamanu oil tween 80-propylene glycol of 1:7:1; 1:8:1; and 1:9:1 that incorporated extracts were 75, 150, and 375 mg. The physical tests included transmittance percentage, emulsification time on AGF media, phase separation, and stability test using the cycling test method. SNEDDS, then followed by the Particle Size Analyzer test. The results showed that the greater surfactant concentration produced a better transmittance value, a faster emulsification time, and stability. Formula with oil: surfactant: co-surfactant of 1:8:1 is a system that meets the requirement for immunity jamu with an optimal loading dose and small particle size compared to another formula. The extract's loading dose of 375 mg has a particle size of 27.17 nm and a polydispersity ind ex of 0.25.


Accurate and sensitive fluorescence imaging of intracellular miRNA is essential for understanding the mechanism underlying some physiological and pathological events, as well as the prevention and diagnosis of diseases. Herein, a highly sensitive ratiometric fluorescent nanoprobe for intracellular miRNA imaging was fabricated by integrating a Ru-SiO2@polydopamine (Ru-SiO2@PDA) nanoplatform with a near-infrared light (NIR)-assisted DNA strand displacement signal amplification strategy. The Ru-SiO2@PDA spheres have excellent biosafety, high photothermal effect, and unique photophysical properties that can both emit a stable red fluorescence and well quench the fluorophores getting closer to them. So, when the fuel DNA and carboxyfluorescein (FAM)-labeled signal DNA are co-assembled on their outer surfaces, the FAM's green fluorescence is quenched, and a low ratiometric signal is obtained. However, in the presence of miRNA, the target displaces the signal DNA from the capture DNA, releasing the signal DNA far away from the Ru-SiO2@PDA. Then, the green fluorescence recovers and leads to an enhanced Igreen/Ired value. Under NIR light irradiation, the Ru-SiO2@PDA increases the local temperature around the probe and triggers the release of fuel DNA, which thus recycles the target miRNA and effectively amplifies the ratiometric signal. Using A549 cells as a model, the nanoprobe realizes the highly sensitive ratiometric fluorescence imaging of miRNA let-7a, as well as its in vivo up- and down-regulation expressions. It provides a facile tool for highly sensitive and accurate intracellular miRNA detection through one-step incubation and may pave a new avenue for single-cell analysis.


Human serum albumin was able to hydrolyze the organophosphorus compounds paraoxon, chlorpyrifos-oxon, and diazoxon at toxicologically relevant concentrations. Human serum displayed two paraoxon hydrolyzing activities: the so-called paraoxonase, which is associated with the lipoprotein fraction and is calcium dependent and EDTA sensitive, and the activity associated with albumin, which is EDTA resistant and sensitive to fatty acids. Human serum albumin hydrolyzed these compounds with the same relative efficacy as lipoproteins (chlorpyrifos-oxon > diazoxon > paraoxon). The capability of detoxication of activity associated with human serum albumin was similar or even higher than paraoxonase associated with lipoproteins in the case of paraoxon at concentrations as low as those noted in an acute in vivo intoxication. However, paraoxonase activity associated with lipoprotein was more effective than paraoxonase activity associated with albumin at toxicologically relevant chlorpyrifos-oxon concentrations. These results explain why mice deficient in paraoxonase associated with lipoprotein are not more sensitive to paraoxon than wild animals.


The origins of conjugated catecholamines remain poorly known. The aim of the present study was to see whether a major contribution comes from the sympathetic nervous system. We have assumed some kind of parallelism between the activity of the sympathetic nervous system, the amount of catecholamines released and taken up, and the amount of conjugated catecholamines circulating in plasma. Accordingly, an increase in sympathetic activity should be followed by an increase in the plasma level of conjugated catecholamines. The plasma levels of sulfoconjugated and glucuroconjugated catecholamines were measured in 10 patients with mental disease resistant to drug treatment, before and after electroconvulsive therapy. As expected, blood pressure, norepinephrine concentration, and epinephrine concentration in plasma were transiently increased. Neither sulfoconjugated nor glucuroconjugated catecholamines were significantly changed. Conjugated catecholamines were measured in 10 volunteers before and at the nadir of insulin-induced hypoglycemia. As expected, plasma levels of norepinephrine and epinephrine were drastically increased. Plasma levels of sulfoconjugates were decreased and glucuroconjugates increased; these were narrow but statistically significant variations. Data reported in the present article do not support a major role for the activity of the sympathetic system in fixing the level of conjugated catecholamines in human plasma. This is a negative, but nonetheless important, observation. In human subjects, currently available information suggests an important role for the intestinal wall and renal function in determining the level of circulating sulfoconjugates.


Jasmonates are essential modulators of plant defences but the role of JA-derivatives has been scarcely studied, particularly in the plant-pest interplay. To deepen into the JA catabolism and its impact on plant responses to spider mite infestation, we selected the Arabidopsis JAO2 gene as a key element involved in the first step of the JA-catabolic route. JAO2 is responsible for the hydroxylation of JA into 12-OH-JA, contributes to attenuate JA and JA-Ile content and consequently, determines the formation of other JA-catabolites. JAO2 was up-regulated in Arabidopsis by mite infestation. Mites also induced JA-derivative accumulation in plants. In jao2 mutant lines, and in the triple mutant jaoT (jao2-1, jao3-1, jao4-2), mite feeding produced less leaf damage, minor callose deposition and lower mite fecundity rates than in Col-0 plants. The impairment of JA oxidation in jao2 lines not only diminished the 12-OH-JA levels but turned off further sulfation as shown the significant reduction of 12-HSO4-JA form. Thus, JAO2 acts as a negative modulator of defences to spider mites mediated by changes in the generation of JA catabolic molecules, and the consequent production of defensive metabolites such as glucosinolates or camalexin.


Research has been conducted in March to July 2013 in the Mangrove Ecosystem Pancer Cengkrong, Trenggalek, East Java, Indonesia. The objective was to obtain composition of mangrove vegetation and potential carbon stocks. There were three stations for composition of vegetation analysis. Potential carbon stock was calculated by allometric equations. The total of 26 species were identified (17 true mangroves and 9 association mangroves). The vegetation dominated by Sonneratia alba with an average density of 596 trees/ha, followed by Rhizophora apiculata (221 trees/ha) and Avicennia alba (149 trees/ha). The Saplings and seedlings dominated by Ceriops tagal (with average density of 1,745 Saplings/ha; 34,745 seedlings/ha). More than 75 % stand structure of mangrove have tree diameter of 4–9.9 cm. Total biomass and carbon stocks were 400.45 ton/ha and 185.81 ton/ha (equivalent to the total amount of CO2 uptake by 681.91 ton/ha). Sonneratia alba was tree that contribute the largest carbon storage.


PURPOSE
To design, manufacture, and evaluate a dynamic magnetic resonance imaging/computed tomography (MRI/CT)-compatible anthropomorphic thorax phantom used to credential MR image-guided radiotherapy (MRIgRT) systems participating in NCI-sponsored clinical trials.

METHOD
The dynamic anthropomorphic thorax phantom was constructed from a water-fillable acrylic shell that contained several internal structures representing radiation-sensitive organs within the thoracic region. A custom MR/CT visible cylindrical insert was designed to simulate the left lung with a centrally located tumor target. The surrounding lung tissue was constructed from a heterogeneous in-house mixture using petroleum jelly and miniature (2-4 mm diameter) styrofoam balls and the tumor structure was manufactured from liquid PVC plastic. An MR conditional pneumatic system was developed to allow the MRIgRT insert to move in similar inhale/exhale motions. TLDs and radiochromic EBT3 film were inserted into the phantom to measure absolute point doses and dose distributions, respectively. The dynamic MRIgRT thorax phantom was evaluated through a reproducibility study and a feasibility study. Comprehensive end-to-end examinations were done where the phantom was imaged on a CT, an IMRT treatment plan was created and an MR image was captured to verify treatment setup. Then, the phantom was treated on an MRIgRT system. The reproducibility study evaluated how well the phantom could be reproduced in an MRIgRT system by irradiating three times on an Elekta's 1.5 T Unity system. The phantom was shipped to three independent institutions and was irradiated on either an MRIdian cobalt-60 (60 Co) or an MRIdian linear accelerator system. Treatment evaluations used TLDs and radiochromic film to compare the planned treatment reported on the treatment planning software against the measured dose on the dosimeters.

RESULTS
The phantom on the Unity system had reproducible TLD doses measurements (SD < 1.5%). The measured TLD to calculated dose ratios from the reproducibility and feasibility studies ranged from 0.93 to 1.01 and 0.96 to 1.03, respectively. Using a 7%/5 mm gamma analysis criteria, the reproducibility and feasibility studies resulted in an average passing rate of 93.3% and 96.8%, respectively. No difference was noted in the results between the MRIdian 60 Co and MRIdian 6 MV linac delivery to the phantom and all treatment evaluations were within IROC-Houston's acceptable criterion.

CONCLUSIONS
A dosimetrically tissue equivalent, CT/MR visible, motion-enabled anthropomorphic MRIgRT thorax phantom was constructed to simulate a lung cancer patient and was evaluated as an appropriate NIH credentialing tool used for MRIgRT systems.


Sir .—Congenital generalized fibromatosis (CGF) is a rare disease characterized by multiple fibromatous tumors that are present at birth, often showing proliferation and growth during infancy, with subsequent spontaneous regression if the patient survives. This peculiar natural history presents serious management dilemmas for the clinician, with uncertainty regarding the distribution of lesions and probable course. Herein, we communicate the ability of magnetic resonance imaging (MRI) to clearly delineate the precise location of fibromas in all parts of the body, and we present evidence that this new imaging modality may provide insights into the biologic stage (proliferation/regression) of individual lesions in critical areas. This represents a significant advance in the management of infants with CGF and allows frequent follow-up without exposure to ionizing radiation. In addition, we suggest that previous prognostic subclassifications of the disease were in error. Patient Report .—The patient was a vigorous boy with CGF who was originally


Wastewater from wet market is mainly composed of suspended solids, high levels of organic pollutants, fats, oil, and grease and often being classified as "high strength". This wastewater must be treated in a manner that minimizes potential harm to public health and detrimental impacts on the environment. The conventional technologies require high cost. Increasing volumes of wastewater combined with limited space availability and tightening environmental standards has promoted the development of biotechnological processes for the treatment of wastewater. A laboratory-scaled shake-flask systems experiment was conducted to test the potential of using Agro-Based Mixed Culture (ABMC) to treat biodegradable organic matter in wastewater from wet market. Different variables were tested for 13 days treatment optimization including: types of agro-base material, mixture, concentration (%v/v) and agitation (rpm). The results were subsequently compared with wastewater sample without adding ABMC as the control. All water quality parameters analyzed showed significant difference (improving water quality) compared to untreated sample (P<0.01). Treatment for all parameters tested were highest using non-sterile ABMC.50% ABMC mixture, 100% ABMC concentration, 150 rpm agitation speed for 13 days. Highest percentage reduction of water quality parameter can best be observed for Biochemical Oxygen Demand (BOD) and Chemical Oxygen Demand (COD) with 86% and 63%, respectively, followed by Ammoniacal Nitrogen (AN) with 55% reduction. Dissolved Oxygen (DO) and turbidity gives only 36% improvement and 44% reduction. The pH turns acidic from 6.10 to 5.24. Optimized ABMC treats better than Commercial EM. A larger scale and long-term treatment was tested using suspended growth batch bioreactor for 31 days treatment. At day 13, treatment performance for all parameter was better in bioreactor as compared to shake-flask system. However, by prolonging the treatment time, treatment efficiency for DO and turbidity reduced. For BOD, COD and AN, the value became constant after certain period of time. The reduction of BOD, COD and AN achieved was up to 91%, 72% and 62%, respectively. DO improve only by 14% while turbidity reduction was 48%. This study indicated that ABMC has potential to treat biodegradable organic matter in wastewater from wet market. The application of ABMC in wastewater treatment is capable of being a cost-effective biological treatment method because it is from local agricultural product which is cheap and easy to obtain.


Purpose – The purpose of this paper is to study the managing of emergencies pertinent to public health which is critical to the well-being of a society; as such, the management mechanisms employed should be of great interest and significance for research. Design/methodology/approach – This paper first relies on extensive literature to describe the mechanism used in the USA from three aspects – organizational structure, management system, and logistics network. For the purpose of comparison, the Chinese version of the mechanism is presented from the same three aspects. The two management systems are then compared both qualitatively and quantitatively. Findings – Deficient areas in Chinese public-health management mechanism as well as challenging issues associated with supply chain design and coordination for emergency supplies in the context of large-scale public health emergencies with low frequency but catastrophic impacts are found. Specifically, the following three important research problems are revealed from the comparative study: how to establish an efficient organizational structure that incorporates all the relevant entities in public-health emergency management? How to establish an information system for emergency management that integrates disease surveillance, control, and prevention? How to design an efficient and cost-effective logistics network to ensure prompt and sufficient delivery of emergency supplies? Originality/value – To date, this research has been the first of its kind that compares two countries' emergency management systems in the context of public health management.


This study aims to test a photodynamic protocol based on a gel containing aminolevulinic acid followed by red-LED (ALAD-PDT) irradiation on human gingival fibroblasts (hGFs) and osteoblasts (hOBs) cultured on a porcine acellular dermal matrix membrane (PADMM). In the previous literature, ALAD-PDT showed solid antibacterial activity and proliferative induction on HGFs cultured on plates and HOBs cultured on a cortical lamina. PADMMs are used in dentistry and periodontology to treat gingival recessions and to increase the tissue thickness in the case of a thin biotype without the risks or postoperative discomfort associated with connective tissue grafts. However, one of the possible complications in this type of surgery is represented by bacterial invasion and membrane exposition during the healing period. We hypothesized that the addition of ALAD-PDT to PADMMs could enhance more rapid healing and decrease the risks connected with bacterial invasion. In periodontal surgery, PADMMs are inserted after a full-thickness flap elevation between the bone and the flap. Consequently, all procedures were performed in parallel on hOBs and hGFs obtained by dental patients. The group control (CTRL) was represented by the unexposed cells cultured on the membranes, group LED (PDT) were the cells subjected to 7 min of red LED irradiation, and ALAD-PDT were the cells subjected to 45 min of ALAD incubation and then to 7 min of red LED irradiation. After treatments, all groups were analyzed for MTT assay and subjected to histological examination at 3 and 7 days and to the SEM observations at 3, 7, and 14 days. Different bone mineralization assays were performed to quantify the effects of ALAD-PDT on hOBs: ALP activity, ALP gene expression, osteocalcin, and alizarin red. The effects of ALAD-PDT on hGFs were evaluated by quantifying collagen 1, fibronectin, and MMP-8. Results showed that ALAD-PDT promoted cellular induction, forming a dense cellular network on hOBs and hGFs, and the assays performed showed statistically significantly higher values for ALAD-PDT with respect to LED alone and CTRLs. In conclusion, ALAD-PDT could represent a promising aid for enhancing the healing of gingival tissues after PADMM applications.


Abstract Esketamine is dextrorotatory ketamine, which is an enantiomer of ketamine. Compared with ketamine, it has the advantages of a fast metabolism, fewer side effects, and strong pharmacological effects, so it is more suitable for clinical use. Esketamine has a powerful analgesic effect and has little effect on breathing. It has a wide range of applications in the fields of pediatric anesthesia, conscious sedation anesthesia, and emergency analgesia. In addition, it is also used for pain that is difficult to relieve with conventional drugs and to prevent postoperative pain. Various routes of administration are also suitable for patients who need short‐term analgesia and sedation. As a drug, esketamine inevitably brings some side effects when it is used clinically. In this article, by introducing the mechanism of action and pharmacological characteristics of esketamine, its clinical application is reviewed, and it provides a reference for the more reasonable and safe clinical application of esketamine.


This article, which is an annual review of the Supreme Court's work in the employment area, examines in detail every decision of the Court's 2013-2014 term relating to employment and labor law, with commentary on each case and additional information about the Court's work during that term and the upcoming one. Detailed examination of the 2013 Term's employment decisions, of course, can be much more revealing than a simple box score of wins and losses for employers and employees. The author therefore uses the latest term's cases as a lens for examining broader aspects of the Court's jurisprudence, such as the continued vitality of our framework of employment regulation. What this closer look discloses is a deeply divided Court that belies a unanimity hailed by many observers as a new development this term. The article concludes that the Roberts Court's signature continues to be written by a bare, but energetic, majority bent on deregulation of the employment relationship.


Background : Advanced cancers including triple-negative breast cancer (TNBC), the most aggressive breast cancer subtype, contain a self-renewing, tumorigenic cancer stem cell (CSC) population. CSCs contribute to tumor progression and therapeutic resistance. Despite an effective early response to chemotherapy, TNBC relapses with a highly heterogeneous and refractory metastatic disease enriched in CSCs. Apart from being chemo- and radio-resistant, CSCs display a high degree of multipotency, heterogeneity and plasticity. Due to the complex nature of CSCs, elucidating the characteristics of CSCs in TNBC progression continues to be a challenge. Thus, developing anti-CSC therapies to be integrated into clinical paradigms represents an immediate priority. Rationale : A major obstacle to the identification of CSC regulatory mechanisms is the lack of experimental systems that enable the reliable enrichment of CSCs from non-CSCs for comparative analysis. While CSCs have been isolated from TNBC using CD44+/CD24- and/or ALDH+ phenotype, this enrichment paradigm requires refinement as it is not universally applicable and lacks the ability to study CSCs in real time. The limitations of these systems have excluded their application in studying the molecular heterogeneity among breast cancer tumors. CSCs are molecularly characterized based on the expression of cell surface receptors and the embryonic stem cell transcription factors NANOG, OCT4 and SOX2. NANOG, the master regulator of stem cell self-renewal, has emerged as a pro-carcinogenic factor in cancer cell lines with CSC behavior. Our previous studies have shown that silencing NANOG in cancer cells leads to reduced proliferation and self-renewal based on in vitro and in vivo experiments. Hypothesis : We hypothesized that a Nanog promoter could be used to effectively enrich for TNBC CSCs. Results : We generated two TNBC cell lines (MDA-MB-231 and HCC70) harboring NanogGFP reporter gene by lentiviral transductions. Increased NANOG mRNA and protein expression was observed in flow cytometry-sorted GFP+ cells compared with GFP- cells. GFP+ cells were enriched for the CSC markers CD49f and CD44+/CD24-. GFP+ cells also demonstrated an increased protein expression of the stem cell transcription factors NANOG, SOX2 and OCT4. Limiting dilution analyses revealed increased self-renewal and significantly higher stem cell frequencies in GFP+ cells. GFP+ cells demonstrated a mesenchymal phenotype with increased invasive capacity. Subcutaneous injections of GFP+ cells showed significantly higher in vivo tumor initiation and progression than GFP- cells. Flow cytometry-sorted GFP+ and GFP- cells enriched for CSCs and non-CSCs, respectively. Using this system, we performed a high-throughput flow cytometry screen and identified an additional novel CSC marker for TNBC. Conclusion : We have developed a novel TNBC CSC reporter system using a GFP reporter driven by the Nanog promoter and identified a novel CSC marker. We have defined and validated this robust system wherein we have characterized and monitored the role of CSCs and non-CSCs in TNBC tumor initiation and progression. Using this approach, identifying CSC targets in TNBC could unravel the potential for development of innovative therapeutic strategies. Citation Format: Praveena S Thiagarajan, Masahiro Hitomi, James S Hale, Alvaro G Alvarado, Baltin Otvos, Kevin Stoltz, Maksim Sinyuk, Awad Jarrar, Qiao Zheng, Dustin Thomas, Thomas Egelhoff, Jeremy N Rich, Justin D Lathia, Ofer Reizes. Development of a fluorescent reporter system to delineate self-renewing cells in triple negative breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-06-01.


Agarwood, a resinous heartwood with valuable fragrance, is formed when the Aquilaria trees are injured. In the past two decades, many Aquilaria plants were cultivated for the induction of agarwood in Taiwan. Plenty of Aquilaria seeds are generated annually, and seem to be a reliable agricultural source. However, the constituents of these seeds have not been analyzed. Proximate composition of fresh Aquilaria seeds was analyzed as 44.4% moisture, 24.9% crude lipid, 16.7% carbohydrate, 10.3% crude fiber, 2.4% crude protein, and 1.3% ash. Two major subcellular organelles, abundant oil bodies and large protein bodies, were observed in electron microscopy. Protein bodies are possibly composed of soluble 2 S albumin and insoluble 11 globulin storage proteins. Oil bodies presumably encapsulate abundant storage lipids with oleosin and caleosin. The storage lipids in oil bodies were mainly neutral lipids (> 90% triacylglycerols and ~5% diacylglycerols). Fatty acids released from these neutral lipids were highly unsaturated with approximately 80% of oleic acid. Oily Aquilaria seed is an adequate source of neutral lipids rich in unsaturated oleic acid, and its oil bodies may serve as storage pools for the accumulation of unique agarwood lipid compounds after the tree is substantially injured for years.


A confined system of noninteracting electrons, subject to the combined effect of a time-dependent potential and different external chemical potentials, is considered. The current flowing through such a system is obtained by using the adiabatic approximation in an iterative manner. A formula is derived for the charge pumped through an unbiased system (all external chemical potentials are kept at the same value); it reproduces the Brouwer formula for a two-terminal nanostructure. The formalism presented yields the effect of the chemical-potential bias on the pumped charge on one hand, and the modification of the Landauer formula (which gives the current in response to a constant chemical-potential difference) brought about by the modulating potential on the other. Corrections to the adiabatic approximation are derived and discussed.