Sarcoma immunotherapy.

Much of our knowledge regarding cancer immunotherapy has been derived from sarcoma models. However, translation of preclinical findings to bedside success has been limited in this disease, though several intriguing clinical studies hint at the potential efficacy of this treatment modality. The rarity and heterogeneity of tumors of mesenchymal origin continues to be a challenge from a therapeutic standpoint. Nonetheless, sarcomas remain attractive targets for immunotherapy, as they can be characterized by specific epitopes, either from their mesenchymal origins or specific alterations in gene products. To date, standard vaccine trials have proven disappointing, likely due to mechanisms by which tumors equilibrate with and ultimately escape immune surveillance. More sophisticated approaches will likely require multimodal techniques, both by enhancing immunity, but also geared towards overcoming innate mechanisms of immunosuppression that favor tumorigenesis

Roles of estrogen receptor-alpha in mediating life span: the hypothalamic deregulation hypothesis.

In several species caloric restriction (CR) extends life span. In this paper we integrate data from studies on CR and other sources to articulate the hypothalamic deregulation hypothesis by which estrogen receptor-alpha (ER-α) signaling in the hypothalamus and limbic system affects life span under the stress of CR in mammals. ER-α is one of two principal estrogen-binding receptors differentially expressed in the amygdala, hippocampus, and several key hypothalamic nuclei: the arcuate nucleus (ARN), preoptic area (POA), ventromedial nucleus (VMN), antero ventral periventricular nucleus (AVPV), paraventricular nucleus (PVN), supraoptic nucleus (SON), and suprachiasmatic nucleus (SCN). Estradiol signaling via ER-α is essential in basal level functioning of reproductive cycle, sexually receptive behaviors, physiological stress responses, as well as sleep cycle, and other nonsexual behaviors. When an organism is placed under long-term CR, which introduces an external stress to this ER-α signaling, the reduction of ER-α expression is attenuated over time in the hypothalamus. This review paper seeks to characterize the downstream effects of ER-α in the hypothalamus and limbic system that affect normal endocrine functioning

Effects of mixing on evolution of hydrocarbon ratios in the troposphere

Nonmethane hydrocarbon (NMHC) concentration ratios provide useful indicators of tropospheric oxidation and transport processes. However, the influences of both photochemical and mixing processes are inextricably linked in the evolution of these ratios. We present a model for investigating these influences by combining the transport treatment of the Lagrangian particle dispersion model FLEXPART with an ultrasimple (i.e., constant OH concentration) chemical treatment. Required model input includes NMHC emission ratios, but not ad hoc assumed background NMHC concentrations. The model results give NMHC relationships that can be directly compared, in a statistical manner, with measurements. The measured concentration ratios of the longest-lived alkanes show strong deviations from purely kinetic behavior, which the model nicely reproduces. In contrast, some measured aromatic ratio relationships show even stronger deviations that are not well reproduced by the model for reasons that are not understood. The model-measurement comparisons indicate that the interaction of mixing and photochemical processing prevent a simple interpretation of "photochemical age," but that the average age of any particular NMHC can be well defined and can be approximated by a properly chosen and interpreted NMHC ratio. In summary, the relationships of NMHC concentration ratios not only yield useful measures of photochemical processing in the troposphere, but also provide useful test of the treatment of mixing and chemical processing in chemical transport models. Copyright 2007 by the American Geophysical Union

Scheduling of a computer integrated manufacturing system: a simulation study

Purpose: The purpose of this paper is to study the effect of selected scheduling dispatching rules on the performance of an actual CIM system using different performance measures and to compare the results with the literature. Design/methodology/approach: To achieve this objective, a computer simulation model of the existing CIM system is developed to test the performance of different scheduling rules with respect to mean flow time, machine efficiency and total run time as performance measures. Findings: Results suggest that the system performs much better considering the machine efficiency when the initial number of parts released is maximum and the buffer size is minimum. Furthermore, considering the average flow time, the system performs much better when the selected dispatching rule is either Earliest Due Date (EDD) or Shortest Process Time (SPT) with buffer size of five and the initial number of parts released of eight. Research limitations/implications: In this research, some limitations are: a limited number of factors and levels were considered for the experiment set-up; however the flexibility of the model allows experimenting with additional factors and levels. In the simulation experiments of this research, three scheduling dispatching rules (First In/First Out (FIFO), EDD, SPT) were used. In future research, the effect of other dispatching rules on the system performance can be compared. Some assumptions can be relaxed in future work. Practical implications: This research helps to identify the potential effect of a selected number of dispatching rules and two other factors, the number of buffers and initial number of parts released, on the performance of the existing CIM systems with different part types where the machines are the major resource constraints. Originality/value: This research is among the few to study the effect of the dispatching rules on the performance of the CIM systems with use of terminating simulation analysis. This is also significant given the nature of the CIM systems that are mostly used to produce different parts in varying quantities and thus do not produce parts on a continuing basis. This research is amongst the first to study the combined effect of dispatching rule and the buffer size in the CIM systems where the job arrivals are predetermined and depend on the completion of the existing parts in the system. A description of how buffer size and initial part release is related to the performance of the CIM system under study for the studied priority dispatching rule is also provided.Peer Reviewe

Analisa Pengaruh Penggunaan Serat Serabut Kelapa dalam Presentase Tertentu pada Beton Mutu Tinggi

The use of additional material as ingredients in the manufacture of concrete mixes is increasingly growing. The material used is also increasingly varied, depending on the expected results. This research aims to know the influence of the addition of coconut fibres material with percentage of 1,5 %, 2 %, 2,5 %, and 3 % as an alternative to the strength of high-quality concrete. Research methods done by producing cylindrical and beam concrete samples for testing against the force then conducted concrete. Furthermore, the analysis has been done and the results of testing and comparing the respective strength of the composition of concrete produced. Based on the test results of data concrete cylinder compression strength and tensile strength concrete beams, it was concluded that the increasing of compressive strength up to 9% can be reached by use of additional material coconut fibers 1,5%and increasing of tensile strength up to 19,7% can be reached by use of additional coconut fiber 2%. Therefore, the additional coconut fibers on concrete mixture has strong relationship to increase tensile strength of high strength concrete

Determination of urban volatile organic compound emission ratios and comparison with an emissions database

During the NEAQS-ITCT2k4 campaign in New England, anthropogenic VOCs and CO were measured downwind from New York City and Boston. The emission ratios of VOCs relative to CO and acetylene were calculated using a method in which the ratio of a VOC with acetylene is plotted versus the photochemical age. The intercept at the photochemical age of zero gives the emission ratio. The so determined emission ratios were compared to other measurement sets, including data from the same location in 2002, canister samples collected inside New York City and Boston, aircraft measurements from Los Angeles in 2002, and the average urban composition of 39 U.S. cities. All the measurements generally agree within a factor of two. The measured emission ratios also agree for most compounds within a factor of two with vehicle exhaust data indicating that a major source of VOCs in urban areas is automobiles. A comparison with an anthropogenic emission database shows less agreement. Especially large discrepancies were found for the C2-C4 alkanes and most oxygenated species. As an example, the database overestimated toluene by almost a factor of three, which caused an air quality forecast model (WRF-CHEM) using this database to overpredict the toluene mixing ratio by a factor of 2.5 as well. On the other hand, the overall reactivity of the measured species and the reactivity of the same compounds in the emission database were found to agree within 30%. Copyright 2007 by the American Geophysical Union

The eukaryotic linear motif resource - 2018 update.

Short linear motifs (SLiMs) are protein binding modules that play major roles in almost all cellular processes. SLiMs are short, often highly degenerate, difficult to characterize and hard to detect. The eukaryotic linear motif (ELM) resource (elm.eu.org) is dedicated to SLiMs, consisting of a manually curated database of over 275 motif classes and over 3000 motif instances, and a pipeline to discover candidate SLiMs in protein sequences. For 15 years, ELM has been one of the major resources for motif research. In this database update, we present the latest additions to the database including 32 new motif classes, and new features including Uniprot and Reactome integration. Finally, to help provide cellular context, we present some biological insights about SLiMs in the cell cycle, as targets for bacterial pathogenicity and their functionality in the human kinome

Global atmospheric budget of acetaldehyde: 3-D model analysis and constraints from in-situ and satellite observations

We construct a global atmospheric budget for acetaldehyde using a 3-D model of atmospheric chemistry (GEOS-Chem), and use an ensemble of observations to evaluate present understanding of its sources and sinks. Hydrocarbon oxidation provides the largest acetaldehyde source in the model (128 Tg a<sup>−1</sup>, a factor of 4 greater than the previous estimate), with alkanes, alkenes, and ethanol the main precursors. There is also a minor source from isoprene oxidation. We use an updated chemical mechanism for GEOS-Chem, and photochemical acetaldehyde yields are consistent with the Master Chemical Mechanism. We present a new approach to quantifying the acetaldehyde air-sea flux based on the global distribution of light absorption due to colored dissolved organic matter (CDOM) derived from satellite ocean color observations. The resulting net ocean emission is 57 Tg a<sup>−1</sup>, the second largest global source of acetaldehyde. A key uncertainty is the acetaldehyde turnover time in the ocean mixed layer, with quantitative model evaluation over the ocean complicated by known measurement artifacts in clean air. Simulated concentrations in surface air over the ocean generally agree well with aircraft measurements, though the model tends to overestimate the vertical gradient. PAN:NO<sub>x</sub> ratios are well-simulated in the marine boundary layer, providing some support for the modeled ocean source. We introduce the Model of Emissions of Gases and Aerosols from Nature (MEGANv2.1) for acetaldehyde and ethanol and use it to quantify their net flux from living terrestrial plants. Including emissions from decaying plants the total direct acetaldehyde source from the land biosphere is 23 Tg a<sup>−1</sup>. Other terrestrial acetaldehyde sources include biomass burning (3 Tg a<sup>−1</sup>) and anthropogenic emissions (2 Tg a<sup>−1</sup>). Simulated concentrations in the continental boundary layer are generally unbiased and capture the spatial gradients seen in observations over North America, Europe, and tropical South America. However, the model underestimates acetaldehyde levels in urban outflow, suggesting a missing source in polluted air. Ubiquitous high measured concentrations in the free troposphere are not captured by the model, and based on present understanding are not consistent with concurrent measurements of PAN and NO<sub>x</sub>: we find no compelling evidence for a widespread missing acetaldehyde source in the free troposphere. We estimate the current US source of ethanol and acetaldehyde (primary + secondary) at 1.3 Tg a<sup>−1</sup> and 7.8 Tg a<sup>−1</sup>, approximately 60{%} and 480% of the corresponding increases expected for a national transition from gasoline to ethanol fuel