cssi/SciSciGPT-SciSciNet huggingface dataset:
Chromatin Dynamics and DNA Repair

DNA damage from endogenous and exogenous sources threatens the genome and the epigenome, requiring chromatin-based DNA damage response pathways (DDR) to operate within structurally and functionally diverse chromatin environments. DDR pathways are essential for sensing, processing and repairing DNA damage. We describe how chromatin dynamics, including those regulated by histone modifications, histone variants and chromatin-associated proteins, promote DNA repair within chromatin. We will also discuss how DNA damage regulates transcription, alters the chromatin environment and affects the mobility of chromosomes to promote the DDR, and how genome organization impacts DNA repair and chromosome translocations. Finally, we explore the use of site-specific DNA damage systems and methodologies to measure histone dynamics to study the DDR and chromatin. This chapter provides an overview of how the DDR operates within the chromatin landscape to maintain genome and epigenome integrity, functions critical for cellular homeostasis and averting diseases including cancer.
Child Soldiers - Both Victims and Combatants: Is There Anything IHL Can Do?

The proliferation of child soldiers has raised a number of troubling questions for the laws of war. These children are the victims of international crimes committed by those who unlawfully enlist and deploy them. These children are also “combatants” under international law and like all combatants they lose the many protections afforded civilians. Apart from the physical and psychological harm caused to children by exposure to combat, child soldiers have also been the intentional victims of crimes perpetrated by members of the armed formation that incorporated them. Crimes specifically directed at them such as rape, sexual slavery and inhuman treatment. Some children have been summarily executed for indiscipline or attempting to escape. Yet, others have been used as disposable weapons in an emerging trend to use children as suicide bombers, sometimes remotely detonated by their adult handlers.This article examines the unique situation of child soldiers, and the several simultaneous yet inconsistent characterizations they embody. A child soldier can be at the same time: a lawful target of the enemy, an individual with the potential to commit international crimes, a victim of the international offense of child conscription and finally, often the intended victim of other acts constituting war crimes but for their unlawful conscription. This article examines the relevant laws and customs of war and questions whether International Humanitarian Law’s (IHL) rigid binary classification of actors as either combatants or civilians appropriately reflects the reality for children, the most vulnerable victims of contemporary conflicts.The article makes the argument that IHL must develop a third status in addition to the combatant/civilian distinction. A hybrid status for children unlawfully incorporated into an armed force or group. This hybrid status retains the child’s combatant status vis-a-vis belligerent forces as defined by well-established tests, yet treats them as civilians vis-a-vis members of the armed force that has unlawfully incorporated them. Perpetrators of crimes against child soldiers should not be able to strip children of the protections intended for them by committing the crime of unlawful conscription against them. The laws of war should be interpreted to deny them the ability to insulate themselves from criminal liability by virtue of their commission of another crime. There is no theoretical or conceptual barrier preventing an interpretation of IHL that affords children this hybrid status. This proposed hybrid status preserves the clarity necessary for the effective application of IHL and ensures that these children remain within the protections of international law.
Campus-Library Collaboration with Makerspaces.

Column description. The Technology column examines current and developing technology topics in libraries. The column’s focus is creative uses of technology, introductions to new technologies, and critiques of current technologies, their uses, or their future. Readers interested in contributing ideas or writings to this column may contact column co-editors Suzanne Townsdin and Susan Whitmer.
The Effect of a Limited-Edition Offer Following Brand Dilution on Consumer Attitudes Toward a Luxury Brand

Abstract This research examines the impact of a luxury limited-edition offer in the face of core brand image dilution of a luxury brand. Through utilizing two millennial subgroups (college- vs. post-college age) as research participants in two studies, the findings suggest that in a brand dilution condition, the limited-edition product enhances consumers’ attitudes toward the luxury brand and that these effects are more pronounced for consumers with a higher self-presentation motive. We also find that college-age millennials are more strongly influenced by social influences than post-college age millennials. The implications for academic researchers and luxury brand retail managers are discussed.
Heroin-induced suppression of saccharin intake in OPRM1 A118G mice.

The single nucleotide polymorphism of the μ-opioid receptor, OPRM1 A118G, has been associated with greater drug and alcohol use, increased sensitivity to pain, and reduced sensitivity to the antinociceptive effects of opiates. In the present studies, we employed a ‘humanized’ mouse model containing the wild-type (118AA) or variant (118GG) allele to examine behavior in a model of heroin-induced devaluation of an otherwise palatable saccharin cue when repeated saccharin-heroin pairings occurred every 24 h (Experiment 1) or every 48 h (Experiment 2). The results showed that, while both the 118AA and 118GG mice demonstrated robust avoidance of the heroin-paired saccharin cue following daily taste-drug pairings, only the 118AA mice suppressed intake of the heroin-paired saccharin cue when 48 h elapsed between each taste-drug pairing. Humanized 118GG mice, then, defend their intake of the sweet cue despite saccharin-heroin pairings and this effect is illuminated by the use of spaced, rather than massed, trials. Given that this pattern of strain difference is not evident with saccharin-cocaine pairings (Freet et al., 2015), reduced avoidance of the heroin-paired saccharin cue by the 118GG mice may be due to an interaction between the opiate and the subjects’ drive for the sweet or, alternatively, to differential downstream sensitivity to the aversive kappa mediated properties of the drug. These alternative hypotheses are addressed.
UVB-induced nuclear translocation of TC-PTP by AKT/14-3-3σ axis inhibits keratinocyte survival and proliferation.

// Mihwa Kim 1 , Liza D. Morales 1,2 , Minwoo Baek 1 , Thomas J. Slaga 3 , John DiGiovanni 4 and Dae Joon Kim 1 1 Department of Biomedical Sciences, School of Medicine, University of Texas Rio Grande Valley, Edinburg, TX, USA 2 South Texas Diabetes and Obesity Institute, School of Medicine, University of Texas Rio Grande Valley, Edinburg, TX, USA 3 Department of Pharmacology, School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA 4 Division of Pharmacology & Toxicology, College of Pharmacy, The University of Texas at Austin, Austin, TX, USA Correspondence to: Dae Joon Kim, email: // Keywords : TC-PTP, nuclear translocation, AKT, 14-3-3σ, keratinocytes Received : June 26, 2017 Accepted : September 15, 2017 Published : October 11, 2017 Abstract Understanding protein subcellular localization is important to determining the functional role of specific proteins. T-cell protein tyrosine phosphatase (TC-PTP) contains bipartite nuclear localization signals (NLSI and NLSII) in its C-terminus. We previously have demonstrated that the nuclear form of TC-PTP (TC45) is mainly localized to the cytoplasm in keratinocytes and it is translocated to the nucleus following UVB irradiation. Here, we report that TC45 is translocated by an AKT/14-3-3σ-mediated mechanism in response to UVB exposure, resulting in increased apoptosis and decreased keratinocyte proliferation. We demonstrate that UVB irradiation increased phosphorylation of AKT and induced nuclear translocation of 14-3-3σ and TC45. However, inhibition of AKT blocked nuclear translocation of TC45 and 14-3-3σ. Site-directed mutagenesis of 14-3-3σ binding sites within TC45 showed that a substitution at Threonine 179 (TC45/T179A) effectively blocked UVB-induced nuclear translocation of ectopic TC45 due to the disruption of the direct binding between TC45 and 14-3-3σ. Overexpression of TC45/T179A in keratinocytes resulted in a decrease of UVB-induced apoptosis which corresponded to an increase in nuclear phosphorylated STAT3, and cell proliferation was higher in TC45/T179A-overexpressing keratinocytes compared to control keratinocytes following UVB irradiation. Furthermore, deletion of TC45 NLSII blocked its UVB-induced nuclear translocation, indicating that both T179 and NLSII are required. Taken together, our findings suggest that AKT and 14-3-3σ cooperatively regulate TC45 nuclear translocation in a critical step of an early protective mechanism against UVB exposure that signals the deactivation of STAT3 in order to promote keratinocyte cell death and inhibit keratinocyte proliferation.
Olfactory loss in chronic rhinosinusitis is associated with neuronal activation of c-Jun N-terminal kinase.

Background Olfactory inflammation in chronic rhinosinusitis (CRS) is associated with cytokines that may result in the death of olfactory sensory neurons. The principal signaling molecules involved in the apoptotic pathway are c-Jun N-terminal kinases (JNK). Although the JNK pathway has emerged as a key player in programmed cell death in neuroinflammation, its specific role in CRS-associated olfactory loss has not been thoroughly investigated. Methods JNK activation was studied in human tissue samples from 9 control and 11 CRS patients by immunohistochemical staining for phosphorylated c-Jun. A mouse model of inducible olfactory cytokine expression was used to experimentally control inflammation and assess JNK activation over time. Results In patients with CRS, activation of c-Jun is significantly increased relative to non-CRS control subjects, and there is an associated loss of sensory neurons. In the olfactory inflammation mouse model, prolonged induction of inflammation results in elevation of c-Jun expression and neuronal apoptosis. Conclusion Activation of neuronal JNK is a feature of chronic olfactory inflammation that is associated with neuronal apoptosis. Given that inhibition of JNK activity is neuroprotective in other settings, antagonism of this pathway may have therapeutic potential in the management of inflammatory olfactory loss or other disorders linked to olfactory neuronal apoptosis.
Fair Trade Towns USA: growing the market within a diverse economy

Fair trade is both a movement and a market, and the tension between these two domains reflects an ambiguity at the center of fair trade in the United States, resulting from long-standing debates within the contemporary movement. In practice, this ideological division produces a struggle between companies that offer a small number of fair trade products aside a vast number of conventional items, and those that sell only fair trade certified products. However, it also shapes the experience of on-the-ground fair trade advocacy work. This article uses Gibson-Graham's diverse economies framework to explore three arenas in which this is most clearly evidenced. First, some fair trade advocates are wary of Fair Trade USA's (FTUSA) power and strategies. They are aware that multiple fair trade certification frameworks currently exist; however they aren't always sure which ones are most desirable and why. This confusion can be problematic in Fair Trade Towns (FTT) advocacy work which involves convincing community members, institutions and governments to purchase more fair trade products. Second, in light of FTUSA's strategic marketization of fair trade and the entry of large corporate players into the U.S. fair trade market, fair trade advocates increasingly find themselves in the equivocal position of providing free labor and marketing for large corporations. Third, the efforts of some FTT advocates are stymied by the determined localvores in their community who are more focused on minimizing carbon footprints and supporting local farmers than promoting social justice and environmental stewardship in the developing world. These tensions raise important questions about the scalar politics of alternative markets and diverse economies. Keywords: fair trade, social movements, localism, ethical consumption, Gibson-Graham
Time Integration Schemes

It is basically incorrect to consider only the time-dependent character of a partial differential equation, since the space differencing and time differencing are closely related for stability. However, when low-order spectral studies are integrated, the space dependence of the dependent variables has been explicitly chosen a priori, and only a set of coupled nonlinear ordinary differential equations need to be solved. There is a great body of literature on the numerical solution of ordinary differential equations. Here we will consider some of the simplest schemes.
Comparison of the Space-Time Signatures of Air Quality Data From Different Monitoring Networks

Ambient air quality in the United States is measured by several regional air quality monitoring networks. Yet, differences in sampling protocol between the networks may not allow joint use of the data reported by different networks. In this study, we compare the space-time signatures of sulfate and nitrate fine particle mass concentrations reported by the Clean Air Status and Trend Network (CASTNet) and the Interagency Monitoring of PROtected Visual Environment Network (IMPROVE). First, a spectral decomposition technique was used to separate the low and high frequency variations in time series of pollutant concentrations at collocated IMPROVE and CASTNet sites. Through Principal Component Analysis (PCA) and Varimax orthogonal rotation, we determined the number of significant sulfate and nitrate modes of variation identifiable with both networks, and identify the mode of variation characterizing each monitoring site. In the case of sulfate, both networks allow identification of seven distinct modes of variation, each of which corresponds to a well-defined geographic area. PCA also suggests the existence of seven modes of variation for nitrate but, in contrast to sulfate, these modes of variations could not be linked to any unified geographic area. A combination of spectral decomposition and PCA reveals that the long-term fluctuations in sulfate at both networks are virtually identical — when they are averaged in homogeneous regions defined by PCA — between both networks.
Abstract IA21: Small cell carcinomas of the ovary: Strengths and weaknesses

Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare and very aggressive malignancy that occurs mostly in young women. We and others previously described SCCOHT as a SMARCA4-mutated monogenic disease and unraveled other important molecular features, including apparent universal loss of SMARCA2 through epigenetic silencing. Typically, SMARCA4 and SMARCA2 are redundant catalytic subunits of the SWI/SNF complex and loss of either will result in the overexpression of the other. However, SCCOHT is unique in having concomitant loss of both subunits with restoration of either leading to tumor suppression. Nonetheless, despite these advances in understanding the biology of SCCOHT, there are few effective treatment options and survival rates remain poor. In this presentation we will discuss the role of SMARCA4 and SMARCA2 on tumor growth. We will also present therapeutic options to manipulate SWI/SNF complex dependencies. We will present case histories of patients who have had positive responses to targeted therapies. We will also discuss responses to anti-PD1 immunotherapy and characterize the immune landscape of SCCOHT tumors using quantitative immunofluorescence and gene expression profiling. Unexpectedly for a low mutation burden cancer, the majority of the tumors demonstrated PD-L1 expression with strong associated T-cell infiltration. PD-L1 expression can be detected in both tumor and stromal cells, with macrophages being the most abundant PD-L1 positive cells in some tumors. These findings suggest that although SCCOHT are low-mutational-burden tumors, their immunogenic microenvironment that resembles the landscape of tumors that respond well to treatment with PD-1/PD-L1 blockade. Citation Format: Douglas A. Levine. Small cell carcinomas of the ovary: Strengths and weaknesses. [abstract]. In: Proceedings of the AACR Conference: Addressing Critical Questions in Ovarian Cancer Research and Treatment; Oct 1-4, 2017; Pittsburgh, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(15_Suppl):Abstract nr IA21.
netome: a computational framework for metabolite profiling and omics network analysis

Advances in metabolomics technologies have enabled comprehensive analyses of associations between metabolites and human disease and have provided a means to study biochemical pathways and processes in detail using model systems. Liquid chromatography tandem mass spectrometry (LC-MS) is an analytical technique commonly used by metabolomics labs to measure hundreds of metabolites of known identity and thousands of "peaks" from yet to be identified compounds that are tracked by their measured masses and chromatographic retention times. netome is a computational framework that provides tools for analyzing processed LC-MS data. In this framework, we develop and provide various computational resources including individual software modules to inspect and adjust trends in raw data, align unknown peaks between separately acquired data sets, and to remove redundancies in nontargeted LC-MS data arising from multiple ionization products of a single metabolite. These tools are deployed through computing resources such as web servers and virtual machines with detailed documentation in order to support researchers.
Impact of size, location, symptomatic-nature and gender on the rupture of saccular intracranial aneurysms

Ruptured intracranial aneurysms are associated with a high rate of mortality and disability due to the difficulty in predicting the rupture and complexity of the condition itself. Clinical narratives such as progress summaries and radiological reports, etc. contain key biomarkers, medical signs, and symptoms. By applying ontology-based information extraction on clinical narratives to extract important evidences and subsequently using machine learning can help to make decision support tools for complex decision making such as prediction of aneurysm rupture. According to best of our knowledge, there doesn't exist any work to extract clinical features from clinical narratives to predict the rupture of intracranial/Brain aneurysms (BA). While no single factor individually contributes to the risk of rupture of a BA, it is important to consider the combined impact of these aspects to understand the rupture probability of the aneurysm. In this paper, we explore the impact of size as a relative factor in saccular aneurysms with respect to location, gender and symptomatic/asymptomatic aspects of BA. Our study involves descriptive and inferential statistical data analysis on features extracted from retrospective electronic health records (EHRs) using natural language processing (NLP) and ontology-based information extraction techniques. Our analysis shows that size alone is not the sole contributor for rupture but the combination of size, location and patient's gender can influence aneurysm ruptures. Our results also show interesting insight that on same vasculature location, the average size of ruptured aneurysms for females is always smaller than that of males.
FRI0270 Identification of novel dysregulated interferon-inducible non-coding rnas in sjÖgren’s syndrome

Background Sjogren’s syndrome (SS) is a chronic, heterogeneous disease with hallmark features of auto-inflammation and autoantibody production. Upregulation of type I and II interferon-stimulated genes (ISGs), known as the “Interferon (IFN) Signature” is correlated with anti-Ro titers and has been observed both in the salivary glands and peripheral blood of SS patients. Within the 2 p25.2 genomic interval, the long non-coding RNA (lncRNA) negative regulator of the interferon response (NRIR) has been identified as inducible by type I IFN and is responsible for the downregulation of the ISGs CMPK2 and RSAD2[.1 Objectives We sought to identify additional unannotated ISGs lncRNAs that are differentially expressed (DE) in SS patients utilising correlated expression of RSAD2. Methods We evaluated and compared the transcriptome of anti-Ro(+) patients (n=27) and healthy controls (n=27) using RNA-seq with DE defined as q Results One of the most overexpressed type I ISGs in the SS Ro(+) is RSAD2 (FC=8.05, p=3.29x10E-07). Because of its role in the type I IFN pathway, pairwise correlation coefficients between all DE transcripts and RSAD2 for SS Ro(+) patients were calculated. In total, we found 223 transcripts exhibiting correlation with RSAD2 expression (Pearson’s r>+0.70 or Conclusions Given the importance of the IFN signature to disease pathogenesis in the autoantibody positive patients, it is critical that we better understand how this complex pathway is coordinately regulated. Since one critical function of lncRNAs is to regulate the genome, characterising the mechanisms by which these 14 identified by this study regulate the ISG coordinately could result in new diagnostic and/or therapeutic options. Reference [1] Kambara H, et al. Nucleic Acids Res2014;42(16):10668–80. Disclosure of Interest None declared
Parameter map error due to normal noise and aliasing artifacts in MR fingerprinting

Purpose To introduce a quantitative tool that enables rapid forecasting of T1 and T2 parameter map errors due to normal and aliasing noise as a function of the MR fingerprinting (MRF) sequence, which can be used in sequence optimization. Theory and methods The variances of normal noise and aliasing artifacts in the collected signal are related to the variances in T1 and T2 maps through derived quality factors. This analytical result is tested against the results of a Monte-Carlo approach for analyzing MRF sequence encoding capability in the presence of aliasing noise, and verified with phantom experiments at 3 T. To further show the utility of our approach, our quality factors are used to find efficient MRF sequences for fewer repetitions. Results Experimental results verify the ability of our quality factors to rapidly assess the efficiency of an MRF sequence in the presence of both normal and aliasing noise. Quality factor assessment of MRF sequences is in agreement with the results of a Monte-Carlo approach. Analysis of MRF parameter map errors from phantom experiments is consistent with the derived quality factors, with T1 (T2 ) data yielding goodness of fit R2 ≥ 0.92 (0.80). In phantom and in vivo experiments, the efficient pulse sequence, determined through quality factor maximization, led to comparable or improved accuracy and precision relative to a longer sequence, demonstrating quality factor utility in MRF sequence design. Conclusion The here introduced quality factor framework allows for rapid analysis and optimization of MRF sequence design through T1 and T2 error forecasting.
Absolute requirement for polyamines for growth of Escherichia coli mutants (mnmE/G) defective in modification of the wobble anticodon of transfer-RNA

The genes mnmE and mnmG are responsible for the modification of uridine 34, 'the wobble position' of many aminoacyl-tRNAs. Deletion of these genes affects the strength of the codon-anticodon interactions of the aminoacyl-tRNAs with the mRNAs and the ribosomes. However, deletion of these genes does not usually have a significant effect on the growth rate of the standard Escherichia coli strains. In contrast, we have found that if the host E. coli strain is deficient in the synthesis of polyamines, deletion of the mnmE or mnmG gene results in complete inhibition of growth unless the medium contains polyamines. The finding of an absolute requirement for polyamines in our current work will be significant in studies on polyamine function, in studies on the function of the mnmE/G genes, and in studies on the role of aminoacyl-tRNAs in protein biosynthesis.
Technique of Funicular Lymphography without the Use of Indicator Dyes

We have developed a method of doing funicular (testicular) lymphography without injecting indicator dye into the tunica albuginea which carries the potential danger of disseminating tumor cells. Since our preliminary report (4), further experiences have been obtained which are summarized herewith.
Promoting Student Awareness of Green Chemistry Principles via Student-Generated Presentation Videos

This paper addresses the use of student-generated instructional videos to promote awareness of green chemistry principles during remote instruction. For this activity, we used Flipgrid as an asynchronous platform for students to create their videos based on assigned case studies from the Green Chemistry Challenge award winners. The Flipgrid platform was used to engage students in scientific discourse with their peers. The activity was viewed favorably by students with most indicating that they would like to see similar assignments implemented in future courses. This project increased student awareness of the 12 green chemistry principles. While this project was used in an Organic Chemistry II laboratory course with chemistry majors, it is our hope that other instructors who find the need to move their instruction online can use this activity either directly or with modifications to fit their course needs.
A Generalization of The Secant Condition for Stability of Interconnected Network of Fractional-order Systems

Motivated by biochemical reaction networks, a generalization of the classical secant condition for the stability analysis of cyclic interconnected fractional-order systems is provided. The main result presents a necessary and sufficient condition for stability of networks of cyclic interconnection of fractional-order systems when the digraph describing the network conforms to a single circuit. Finally, the theoretical results are confirmed via some numerical illustrations.
Establishing a High Throughput Epidermal Spheroid Culture System to Model Keratinocyte Stem Cell Plasticity.

Epithelial dysregulation is a node for a variety of human conditions and ailments, including chronic wounding, inflammation, and over 80% of all human cancers. As a lining tissue, the skin epithelium is often subject to injury and has evolutionarily adapted by acquiring the cellular plasticity necessary to repair damaged tissue. Over the years, several efforts have been made to study epithelial plasticity using in vitro and ex vivo cell-based models. However, these efforts have been limited in their capacity to recapitulate the various phases of epithelial cell plasticity. We describe here a protocol for generating 3D epidermal spheroids and epidermal spheroid-derived cells from primary neonatal human keratinocytes. This protocol outlines the capacity of epidermal spheroid cultures to functionally model distinct stages of keratinocyte generative plasticity and demonstrates that epidermal spheroid re-plating can enrich heterogenous normal human keratinocytes (NHKc) cultures for integrinα6hi/EGFRlo keratinocyte subpopulations with enhanced stem-like characteristics. Our report describes the development and maintenance of a high throughput system for the study of skin keratinocyte plasticity and epidermal regeneration.
When Dullscreen is Too Dull

Dullscreen as an interface design concept suggests minimizing colors to avoid interface confusion and clutter. Dullscreen designs have been applied in several of the author’s efforts to modernize legacy control rooms in nuclear power plants with digital upgrades. A study on system overviews revealed an unexpected finding. One set of screens followed a vendor’s human-computer interface style guide, which featured a series of colorful elements on the screens. Another set of screens followed an in-house style guide that adhered to dullscreen principles. The discovery that the colorful elements were more visually salient, especially when seen across the control room, pointed to a need to reconsider strict adherence to dullscreen design principles.
Examining patient specific factors associated with inpatient hospital length of stay for solid tumor oncology patients from low socioeconomic communities in Milwaukee, WI.

232Background: In a retrospective analysis at the Medical College of Wisconsin’s Cancer Center, we identified longer inpatient length of stay (LOS) for patients residing in low-socioeconomic (SES) ...
Self-rotation of animate beings.

Consideration of the ability of both animals and humans to perform well-controlled self-rotation maneuvers while falling freely for short periods of time in the neighborhood of the earth's surface. Specifically, an analytical theory dealing with the righting movements of falling cats is constructed, and the validity of this theory is tested by reference to photographs. Pitch, yaw, and roll motions generated by arm and leg motions of humans are studied analytically and, in the case of yaw motions, experimentally.
Space Matters: The 2010 Winter Olympics and ITS Discontents:

The history of the Olympic Games is fraught with racism, class privilege, and questionable leadership from the International Olympic Committee (IOC). In the modern era, the Olympics have generated ...
The airborne positioning and planning system: an architecture for future avionics systems design

In this paper, the functional architecture of the airborne positioning and planning system (APAPS) is presented at an introductory level. This system is comprised of a set of basic navigation and communication functions which are organized in such a way as to (1) assist the pilot in positioning and moving his aircraft through the airspace in pursuit of the goals that he has established for the flight, and (2) provide the basis to coordinate such movement with other aircraft in the context of a revised philosophy of air traffic management. The functional architecture presented here is the result of a holistic design approach which jointly considers the needs of the pilot and the air traffic system, and makes possible a whole new array of innovative, cost-effective, and convenient methods for coordinating aircraft movement. It was also designed with the full spectrum of airspace users in mind to ensure that benefits from improved safety, flexibility, and airspace access and utilization are realized by all segments of the user community. >
Applicability of the integrated waveform (IW) for the integrated broadcast service (IBS)

The paper "Applicability of demand assigned multiple access (DAMA) waveforms for the integrated broadcast service (IBS)" concluded that currently defined DAMA standards could not support the time-critical requirements of UHF SATCOM intelligence dissemination. These DAMA standards were partitioned into two separate waveforms: 5-kHz DAMA (documented by MIL-STD-188-182A) and 25-kHz DAMA (documented by MIL-STD-188-183A). Since the publishing of the paper, the Defense Information Systems Agency's (DISA) Interoperability Directorate has continued work on the DAMA standards. Their Technical Working Groups (TWGs) have re-architected the waveforms to be sliced horizontally into a demand assignment layer (MlL-STD188-182B) and a multiple access layer (MIL-STD-188-183B). These efforts have standardized functions across channels sizes into an "integrated waveform", selecting the best components of each legacy DAMA waveform and allowing each layer to be developed, analyzed and perhaps certified independently. A comparison of IBS requirements to this new DAMA architecture can again ensure prudent decisions can be made regarding use of defense satellite communications resources.
Hindlimb immobilization: length-tension and contractile properties of skeletal muscle

The effect of hindlimb immobilization (IM) on the contractile properties of fast and slow skeletal muscle was studied in rats following various periods of IM ranging from 1 to 42 days; muscle atrophy, muscle, fiber, and sarcomere length, and the length-tension characteristics were determined after 42 days of IM. The slow-twitch soleus (SOL), the fast-twitch extensor digitorum longus (EDL), and the fast-twitch superficial region of the vastus lateralis (SVL) all showed rapid atrophy following the onset of IM, reaching a new reduced steady-state weight by day 21. After 42 days of IM the passive tension (g) and active twitch tension (g/cm2) plotted vs. muscle length (cm) were shifted to the left for the slow-twitch SOL, indicating a decreased extensibility compared with control muscles. The peak tetanic tension of the slow SOL declined to 47% of the control level of 2,893 +/- 125 g/cm2, whereas the fast EDL maintained 72% of its initial force of 4,392 +/- 229 g/cm2, and the fast SVL was unaltered by IM. Peak twitch tension and peak rate of tension development and decline fell rapidly in the slow SOL while remaining relatively unaltered in the fast-twitch muscles. Surprisingly, maximal isotonic shortening velocity was elevated in both fast and slow muscles with IM. These results indicate that IM produces muscle atrophy in fast as well as slow skeletal muscle and, in addition, causes fiber type-specific changes in the contractile properties.
Specific Increase in Potency via Structure-Based Design of a TCR

Adoptive immunotherapy with Ag-specific T lymphocytes is a powerful strategy for cancer treatment. However, most tumor Ags are nonreactive "self" proteins, which presents an immunotherapy design challenge. Recent studies have shown that tumor-specific TCRs can be transduced into normal PBLs, which persist after transfer in ∼30% of patients and effectively destroy tumor cells in vivo. Although encouraging, the limited clinical responses underscore the need for enrichment of T cells with desirable antitumor capabilities prior to patient transfer. In this study, we used structure-based design to predict point mutations of a TCR (DMF5) that enhance its binding affinity for an agonist tumor Ag-MHC (peptide-MHC [pMHC]), Mart-1 (27L)-HLA-A2, which elicits full T cell activation to trigger immune responses. We analyzed the effects of selected TCR point mutations on T cell activation potency and analyzed cross-reactivity with related Ags. Our results showed that the mutated TCRs had improved T cell activation potency while retaining a high degree of specificity. Such affinity-optimized TCRs have demonstrated to be very specific for Mart-1 (27L), the epitope for which they were structurally designed. Although of somewhat limited clinical relevance, these studies open the possibility for future structural-based studies that could potentially be used in adoptive immunotherapy to treat melanoma while avoiding adverse autoimmunity-derived effects.
The relationship between body weight, body condition, and survival in cats with heart failure.

Background: Obese people with heart failure have improved survival compared with their normal or underweight counterparts. The purpose of this study was to determine if there is a relationship between body weight or body condition and survival in cats with heart failure. Hypothesis: Body weight and body condition score (BCS) are predictors of survival in cats with heart failure. Animals: One-hundred and one cats with heart failure (International Small Animal Cardiac Health Council Classes II, IIIa, or IIIb) evaluated between March 2007 and June 2009. Methods: Data regarding initial body weight and BCS, subsequent changes in body weight, and treatment were collected from records and compared with survival times. Results: Median initial body weight was 5.1 kg (range, 2.2–9.5 kg). Median BCS was 5 (range, 3–9). Of the 68 cats that were discharged from the hospital, median body weight change was 0.0 kg (range, −2.6 to +2.3 kg). Survival time for all 101 cats was 93 days (0–811 days). Survival could be predicted using a model combining initial body weight (P= .02), body weight squared (P= .02), and survival to discharge (P < .001) with a resulting global P value for this model of P < .0001. Conclusions and Clinical Importance: Cats with the lowest and highest body weights had reduced survival times compared with those with body weights in the intermediate ranges, suggesting a U-shaped relationship between body weight and survival. Additional research into the effects of body composition could help to determine optimal management of cats with heart failure.
Roles of helix H69 of 23S rRNA in translation initiation

Initiation of translation involves the assembly of a ribosome complex with initiator tRNA bound to the peptidyl site and paired to the start codon of the mRNA. In bacteria, this process is kinetically controlled by three initiation factors—IF1, IF2, and IF3. Here, we show that deletion of helix H69 (∆H69) of 23S rRNA allows rapid 50S docking without concomitant IF3 release and virtually eliminates the dependence of subunit joining on start codon identity. Despite this, overall accuracy of start codon selection, based on rates of formation of elongation-competent 70S ribosomes, is largely uncompromised in the absence of H69. Thus, the fidelity function of IF3 stems primarily from its interplay with initiator tRNA rather than its anti-subunit association activity. While retaining fidelity, ∆H69 ribosomes exhibit much slower rates of overall initiation, due to the delay in IF3 release and impedance of an IF3-independent step, presumably initiator tRNA positioning. These findings clarify the roles of H69 and IF3 in the mechanism of translation initiation and explain the dominant lethal phenotype of the ∆H69 mutation.
ON THE “GLOBALITY HYPOTHESIS” ABOUT SOCIAL/CULTURAL STRUCTURE: AN ALGEBRAIC SOLUTION

ABSTRACT Starting from a formal definition of structure departing from the tradition of structuralist anthropology, I argue first against the idea that partial structural parallels across cultural and social domain directly induce a global structure. Second, reconstruct the idea of globality on the basis of the shared subsets of axioms that motivate these parallelisms as the hierarchy induced by the differential distribution of such axiom subsets across the domains. 1 1I am grateful to Dwight Read and other readers for useful corrections. I particularly am indebted to David Kronenfeld for remarks on the first draft and for having me made a press reader for his masterful overview of structure in anthropology (Kronenfeld 2003).
Design comparisons for procurement systems

We use experimental techniques to compare first-price auctions to a common but previously unexamined exchange process that we term "multilateral negotiations." Initially, we find that transaction prices are statistically indistinguishable in the two institutions with four sellers, but that prices are higher in multilateral negotiations than in first-price auctions with two sellers. Surprisingly, we find in two-seller environments that a history of multilateral negotiations leads to higher auction prices, which suggests that buyers may see little price effect by moving from negotiations to auctions.
Heat-transfer predictions in the cooling passages of nuclear rocket nozzles.

Heat transfer coefficients in rocket nozzle cooling passages predicted by equation developed from hydrogen flow experiments
Mechanism of expansion associated with ettringite formation

Abstract Ettringite formation in portland cement concretes can be responsible for both deleterious and beneficial phenomena. Several hypotheses on the mechanism of expansion associated with ettringite formation are reviewed, and a new hypothesis is proposed. Experimental evidence is presented in support of the new hypothesis. It is shown that in the presence of lime the nature of ettringite formed is colloidal, and not long lath-like crystals. It is proposed that colloidal ettringite is able to attract a large number of water molecules which cause interparticle repulsion, thus causing an overall expansion of the system.
Pathophysiological consequences of VEGF-induced vascular permeability

Although vascular endothelial growth factor (VEGF) induces angiogenesis, it also disrupts vascular barrier function in diseased tissues. Accordingly, VEGF expression in cancer and ischaemic disease has unexpected pathophysiological consequences. By uncoupling endothelial cell-cell junctions VEGF causes vascular permeability and oedema, resulting in extensive injury to ischaemic tissues after stroke or myocardial infarction. In cancer, VEGF-mediated disruption of the vascular barrier may potentiate tumour cell extravasation, leading to widespread metastatic disease. Therefore, by blocking the vascular permeability promoting effects of VEGF it may be feasible to reduce tissue injury after ischaemic disease and minimize the invasive properties of circulating tumour cells.
Spatial and Temporal Patterns of Thunderstorm Events that Produce Cloud-to-Ground Lightning in the Interior Southeastern United States

Abstract Cloud-to-ground (CG) lightning data are used in this study to trace the daily patterns of thunderstorms in time and space across the topographically diverse southeastern United States. Four reoccurring patterns of thunderstorms (i.e., local, multilocal, regional, and widespread) are identified on the basis of the size of the region of CG lightning as well as the spatial pattern of the flashes within this region. To identify these patterns, hourly maps of CG flashes are produced over five summer seasons (June–August) and used to identify thunderstorm events on all days in which at least one CG lightning is observed. Thunderstorm events are defined by a temporally and spatially clustered hourly pattern of lightning flashes. The spatial pattern of lightning associated with each event is examined during the hour in which the flash density is the highest and is used to classify the event. The geographical and temporal patterns of each thunderstorm type are described. Also, flash densities are calculat...
SAS macros for estimation of direct adjusted cumulative incidence curves under proportional subdistribution hazards models

The cumulative incidence function is commonly reported in studies with competing risks. The aim of this paper is to compute the treatment-specific cumulative incidence functions, adjusting for potentially imbalanced prognostic factors among treatment groups. The underlying regression model considered in this study is the proportional hazards model for a subdistribution function [1]. We propose estimating the direct adjusted cumulative incidences for each treatment using the pooled samples as the reference population. We develop two SAS macros for estimating the direct adjusted cumulative incidence function for each treatment based on two regression models. One model assumes the constant subdistribution hazard ratios between the treatments and the alternative model allows each treatment to have its own baseline subdistribution hazard function. The macros compute the standard errors for the direct adjusted cumulative incidence estimates, as well as the standard errors for the differences of adjusted cumulative incidence functions between any two treatments. Based on the macros' output, one can assess treatment effects at predetermined time points. A real bone marrow transplant data example illustrates the practical utility of the SAS macros.
Newer Treatment Options for Skin and Soft Tissue Infections

In recent years, serious skin and soft tissue infections (SSTIs) caused by multidrug resistant pathogens have become more common. While the majority of SSTIs are caused by Staphylococcus aureus or β-haemolytic streptococci that are methicillin/oxacillin susceptible, the emergence of methicillin-resistant and vancomycin-resistant community-acquired and nosocomial Gram-positive pathogens has created a need for different therapeutic agents, such as linezolid, quinupristin/dalfopristin, daptomycin, and newer generation carbapenems and fluoroquinolones. This review focuses on agents presently in clinical development for the treatment of SSTIs caused by Gram-positive pathogens such as staphylococci, streptococci and enterococci including methicillin-resistant S. aureus (MRSA) and vancomycin-resistant enterococci (VRE). Newer-generation carbapenems, such as meropenem and ertapenem, are characterised by a broad-spectrum of activity against Gram-positive and -negative aerobes and anaerobes, and are resistant to hydrolysis by many β-lactamases. Current-generation fluoroquinolones, such as levofloxacin, moxifloxacin and gatifloxacin, have demonstrated better eradication rates for S. aureus than conventional penicillin and cephalosporins. These antimicrobial agents can be used to treat methicillin-susceptible staphylococcal and streptococcal strains. Oxazolidinones, streptogramin combinations and cyclic lipopeptides have novel mechanisms of action and have been studied in several multinational phase III clinical trials in the treatment of complicated and uncomplicated SSTIs. They possess a broad spectrum of activity against multidrug-resistant pathogens, including MRSA and VRE. Linezolid has been shown to be active against a wide variety of community-acquired and nosocomial antimicrobial-resistant pathogens with comparability to vancomycin, as well as resulting in reduced lengths of hospital stay. Cyclic lipopeptides such as daptomycin have a unique mechanism of action by disruption of bacterial membrane electric potentials with less likelihood for development of cross-resistance. Daptomycin has recently been US FDA approved for the treatment of complicated SSTI. However, rapid development of resistance to some of these newer agents has already been reported and this trend magnifies the importance of further need for effective antimicrobial agents. Several investigational agents, such as dalbavancin, oritavancin and tige-cycline, are in advanced stages of development and are likely to proceed to licensing in the next few years. With their long half-lives, these agents have an advantage of less frequent dose administration with more rapid bactericidal activity and less likelihood for development of resistance. However, because of their proven activity against highly resistant organisms, these antibacterial agents should be reserved only for life-threatening situations and/or when resistant pathogens are suspected. Rational antimicrobial use coupled with awareness of infection control measures is paramount to avert the emergence of multidrug-resistant organisms.
Novel Valved Graft Modification of Cabrol Fistula for Bleeding After Aortic Root Surgery

The Cabrol fistula, which shunts blood from the perigraft space to the right atrium in cases of refractory bleeding after ascending aortic replacement, is a useful technique. A drawback is the potential for troublesome venous back-bleeding into the perigraft space. We describe a modification using a valved Contegra graft, which obligates unidirectional flow and eliminates venous back-bleeding. This renders the Cabrol fistula an even more useful technique.
Addressing the hemodynamic dilemma of combined mitral and aortic stenosis

Accurate assessment of valvular hemodynamics is essential in the decision-making process when referring a patient for cardiac surgery who has suspected coexistent aortic and mitral valve disease. Often times, one valvular lesion is worse than the other, and the question of “prophylactically” replacing the less severe valve at the time of surgery is controversial. In these situations and because of uncertainty regarding noninvasive assessment, hemodynamic evaluation in the cardiac catheterization laboratory provides critical information in guiding therapy. © 2008 Wiley-Liss, Inc.