cssi/SciSciGPT-SciSciNet huggingface dataset:
It’s All About Systems

This chapter revisits the examples in Chapter 2 from the standpoint of systems. It first examines what is and what isn’t a system. It then shows that every aspect of our being is part and parcel of complex, messy systems. The failure to think systemically is responsible for our inability to cope with the most complex, messy system of all—reality itself. Worst of all, it leads to crises that challenge our abilities to cope effectively.
Protein imbalance in the development of skeletal muscle wasting in tumour‐bearing mice

Background Cancer cachexia occurs in approximately 80% of cancer patients and is a key contributor to cancer-related death. The mechanisms controlling development of tumour-induced muscle wasting are not fully elucidated. Specifically, the progression and development of cancer cachexia are underexplored. Therefore, we examined skeletal muscle protein turnover throughout the development of cancer cachexia in tumour-bearing mice. Methods Lewis lung carcinoma (LLC) was injected into the hind flank of C57BL6/J mice at 8 weeks age with tumour allowed to develop for 1, 2, 3, or 4 weeks and compared with PBS injected control. Muscle size was measured by cross-sectional area analysis of haematoxylin and eosin stained tibialis anterior muscle. 2 H2 O was used to assess protein synthesis throughout the development of cancer cachexia. Immunoblot and RT-qPCR were used to measure regulators of protein turnover. TUNEL staining was utilized to measure apoptotic nuclei. LLC conditioned media (LCM) treatment of C2C12 myotubes was used to analyse cancer cachexia in vitro. Results Muscle cross-sectional area decreased ~40% 4 weeks following tumour implantation. Myogenic signalling was suppressed in tumour-bearing mice as soon as 1 week following tumour implantation, including lower mRNA contents of Pax7, MyoD, CyclinD1, and Myogenin, when compared with control animals. AchRδ and AchRe mRNA contents were down-regulated by ~50% 3 weeks following tumour implantation. Mixed fractional synthesis rate protein synthesis was ~40% lower in 4 week tumour-bearing mice when compared with PBS controls. Protein ubiquitination was elevated by ~50% 4 weeks after tumour implantation. Moreover, there was an increase in autophagy machinery after 4 weeks of tumour growth. Finally, ERK and p38 MAPK phosphorylations were fourfold and threefold greater than control muscle 4 weeks following tumour implantation, respectively. Inhibition of p38 MAPK, but not ERK MAPK, in vitro partially rescued LCM-induced loss of myotube diameter. Conclusions Our findings work towards understanding the pathophysiological signalling in skeletal muscle in the initial development of cancer cachexia. Shortly following the onset of the tumour-bearing state alterations in myogenic regulatory factors are apparent, suggesting early onset alterations in the capacity for myogenic induction. Cancer cachexia presents with a combination of a loss of protein synthesis and increased markers of protein breakdown, specifically in the ubiquitin-proteasome system. Also, p38 MAPK may be a potential therapeutic target to combat cancer cachexia via a p38-FOX01-atrogene-ubiquitin-proteasome mechanism.
Who, Mies?: Interrogating the Federal Center Courthouse and the Trial of the Chicago Seven

This essay interrogates Mies van der Rohe's Federal Center Courthouse vis-a-vis the events of the Trial of the Chicago Seven, which was held there beginning in 1969. In doing so, the essay reveals ...
Customizable two-species kinetic equilibria for nonuniform low-beta plasmas

Two methods are developed for constructing self-consistent two-species kinetic equilibria for low-beta electrostatic plasmas, in which the magnetic field is uniform and fixed in time. The first method uses Taylor series approximations to construct distribution functions that can be specified analytically. The second method relies on numerically solving a nonlinear ordinary differential equation and produces exact—to numerical precision—equilibria. In both methods, the equilibrium distribution functions for ions and electrons are expressed in terms of constants of motion and satisfy the steady-state Vlasov-Poisson equation system. Provided that the ion drift speed does not exceed the ion thermal speed, the equilibria can be specified with customizable density and electrostatic potential profiles. The methods can thereby be tailored to different applications and are successfully applied to construct kinetic equilibria for cross-field plasmas with sheared flows, large density variations, and different levels of magnetization. The equilibria are used to initialize fourth-order finite-volume Vlasov-Poisson simulations in (x, vx, vy) coordinates and the associated temporal evolution is used to assess the accuracy of each method. The low-amplitude deviations observed in these simulations demonstrate that the kinetic equilibria are robust and that they provide a valuable means of studying the dynamics of nonuniform magnetized plasmas.Two methods are developed for constructing self-consistent two-species kinetic equilibria for low-beta electrostatic plasmas, in which the magnetic field is uniform and fixed in time. The first method uses Taylor series approximations to construct distribution functions that can be specified analytically. The second method relies on numerically solving a nonlinear ordinary differential equation and produces exact—to numerical precision—equilibria. In both methods, the equilibrium distribution functions for ions and electrons are expressed in terms of constants of motion and satisfy the steady-state Vlasov-Poisson equation system. Provided that the ion drift speed does not exceed the ion thermal speed, the equilibria can be specified with customizable density and electrostatic potential profiles. The methods can thereby be tailored to different applications and are successfully applied to construct kinetic equilibria for cross-field plasmas with sheared flows, large density variations, and different levels...
Motor Competence Levels and Developmental Delay in Early Childhood: A Multicenter Cross-Sectional Study Conducted in the USA.

Developmental delay in motor competence may limit a child’s ability to successfully participate in structured and informal learning/social opportunities that are critical to holistic development. Current motor competence levels in the USA are relatively unknown. The purposes of this study were to explore motor competence levels of US children aged 3–6 years, report percentages of children demonstrating developmental delay, and investigate both within and across childcare site predictors of motor competence, including sex, race, geographic region, socioeconomic status, and body mass index percentile classification. Potential implications from results could lead to a greater awareness of the number of children with developmental delay, the impetus for evidence-based interventions, and the creation of consistent qualification standards for all children so that those who need services are not missed. Participants included children (N = 580, 296 girls) aged 3–6 years (Mage = 4.97, standard deviation = 0.75) from a multi-state sample. Motor competence was assessed using the Test of Gross Motor Development, Second Edition and the 25th and 5th percentiles were identified as developmental delay-related cutoffs. For both Test of Gross Motor Development, Second Edition subscales, approximately 77% of the entire sample qualified as at risk for developmental delay (≤ 25th percentile), while 30% of the entire sample were at or below 5th percentile. All groups (e.g., sex, race, socioeconomic status) were prone to developmental delay. Raw object control scores differed by sex. Developmental delay in motor competence is an emerging epidemic that needs to be systematically acknowledged and addressed in the USA. By shifting norms based upon current data, there may be a lower standard of “typical development” that may have profound effects on factors that support long-term health.
A non-linear damage accumulation fatigue model for predicting strain life at variable amplitude loadings based on constant amplitude fatigue data

Abstract A new phenomenological technique for using constant amplitude loading data to predict fatigue life from a variable amplitude strain history is presented. A critical feature of this reversal-by-reversal model is that the damage accumulation is inherently non-linear. The damage for a reversal in the variable amplitude loading history is predicted by approximating that the accumulated damage comes from a constant amplitude loading that has the strain range of the particular variable amplitude reversal. A key feature of this approach is that overloads at the beginning of the strain history have a more substantial impact on the total lifetime than overloads applied toward the end of the cycle life. This technique effectively incorporates the strain history in the damage prediction and has the advantage over other methods in that there are no fitting parameters that require substantial experimental data. The model presented here is validated using experimental variable amplitude fatigue data for three different metals.
With a little help from my (Psittacidae) friends.

Understanding the distribution of and mechanisms underlying prosocial behavior in other species has been hampered by methodological differences among studies, questions about animals’ interpretations of the designs, and low phylogenetic diversity. Brucks and von Bayern’s recent report that African gray parrots are proactively prosocial reiterates the importance of social tolerance and suggests a role for perspective taking, but additional work using identical procedures across taxa is needed to verify the cognitive mechanisms underpinning prosocial behavior.
45RFSOI WLCSP Board Level Package Risk Assessment and Solder Joint Reliability Performance Improvement

The acceptance of Wafer Level Chip Scale Package (WLCSP) technology is significantly increasing for use in small devices such as mobile phones, wearable, RF antenna packages, and health monitor sensors. WLCSP structures can have a few thin redistribution layers (RDLs) between the chip surface and the printed circuit board (PCB), or the interconnectors can be placed in direction connection to the back end of the line (BEoL). Due to the high coefficient of thermal expansion (CTE) mismatch between the silicon chip and the organic laminate, the WLCSP chip’s board level reliability (BLR) can present a significant challenge.In this paper, BLR tests applying different board trace and bump array designs are discussed for a 45nm RFSOI WLCSP package. A fatigue model is developed utilizing the BLR qualification tests and numerical simulation is then used to correlate the BLR experimental data. A newly improved test vehicle configuration was built based on learning from the BLR test and FEM learning. The result shows significantly improved solder joint lifetime when compared with the initial design.
Hsa-miRNA-23a-3p promotes atherogenesis in a novel mouse model of atherosclerosis

Of the known regulators of atherosclerosis, miRNAs have been demonstrated to play critical roles in lipoprotein homeostasis and plaque formation. Here, we generated a novel animal model of atherosclerosis by knocking in LDLRW483X in C57BL/6 mice, as the W483X mutation in LDLR is considered the most common newly identified pathogenic mutation in Chinese familial hypercholesterolemia (FH) individuals. Using the new in vivo mouse model combined with a well-established atherosclerotic in vitro human cell model, we identified a novel atherosclerosis-related miRNA, miR-23a-3p, by microarray analysis of mouse aortic tissue specimens and human aortic endothelial cells (HAECs). miR-23a-3p was consistently downregulated in both models, which was confirmed by qPCR. Bioinformatics analysis and further validation experiments revealed that the TNFα-induced protein 3 (TNFAIP3) gene was the key target of miR-23a-3p. The miR-23a-3p-related functional pathways were then analyzed in HAECs. Collectively, the present results suggest that miR-23a-3p regulates inflammatory and apoptotic pathways in atherogenesis by targeting TNFAIP3 through the NF-κB and p38/MAPK signaling pathways.
Systematics of the Ixodida (Argasidae, Ixodidae, Nuttalliellidae): An Overview and Some Problems

The world’s tick fauna is composed of some 850 species in 3 families and 19 genera. All known tick species are obligate hematophagous ectoparasites of either warm- or cold-blooded animals during one or more stages of their life cycle. Interest in ticks has increased dramatically in recent years primarily due to the relationship between ticks of the Ixodes ricinus group and their ability to transmit the causative agent of Lyme disease to humans.
Moderately Elevated Glucocorticoids Increase Mate Choosiness But Do Not Affect Sexual Proceptivity Or Preferences In Female Gray Treefrogs

Abstract Glucocorticoids (GCs) are rarely studied in the context of female mate choice, despite the expression of receptors for these products in sexual, sensory and decision-making brain areas. Here we investigated the effects of GC concentrations on three aspects of female sexual behavior in breeding Cope's gray treefrogs (Hyla chrysoscelis): proceptivity—a measure of sexual motivation, intraspecific mate preferences, and mate choosiness. To our knowledge this is the first experimental study on the endocrine basis of mate choosiness. We predicted that mate choosiness—forfeiting an initial mate preference to pursue a suddenly more attractive mate—would be particularly impacted by elevated GCs with moderate GC levels associated with greater choosiness. We found support for this predicted inverted-U relationship. Females in the control group (no injection) showed no change in choosiness across timepoints. In contrast, females in the vehicle, Low (20 ng g−1) and High (180 ng g−1) corticosterone groups exhibited a nominal decline in choosiness after injection, suggesting that the experience of injection has little or perhaps slightly suppressive effects on female choosiness. Females in the moderate dose group (60 ng g−1), however, exhibited a significant increase (>100%) in choosiness. Further, we found no effect of elevated GCs on sexual proceptivity or the species-typical preference for longer calls. These findings may reflect a buffering of primary sensory areas in the brain against elevated GCs. The recruitment of other cognitive processes during active decision-making, however, may facilitate GC modulation of mate choosiness, thereby promoting tactical plasticity at this critical life history juncture.
Transcriptional Profiling of Porcine HCC Xenografts Provides Insights Into Tumor Cell Microenvironment Signaling.

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide, representing the most common form of liver cancer. As HCC incidence and mortality continue to increase, there is a growing need for improved translational animal models to bridge the gap between basic HCC research and clinical practice to improve early detection and treatment strategies for this deadly disease. Recently the Oncopig cancer model-a novel transgenic swine model that recapitulates human cancer through Cre recombinase induced expression of KRAS G12D and TP53 R167H driver mutations-has been validated as a large animal translational model for human HCC. Due to the similar size, anatomy, physiology, immunology, genetics, and epigenetics between pigs and humans, the Oncopig has the potential to improve translation of novel diagnostic and therapeutic modalities into clinical practice. Recent studies have demonstrated the importance of tumor cells in shaping its surrounding microenvironment into one that is more proliferative, invasive, and metastatic; however, little is known about the impact of microenvironment signaling on HCC tumor biology and differential gene expression between HCC tumors and its tumor microenvironment (TME). In this study, transcriptional profiling was performed on Oncopig HCC xenograft tumors (n = 3) produced via subcutaneous injection of Oncopig HCC cells into severe combined immunodeficiency (SCID) mice. To differentiate between gene expression in the tumor and surrounding tumor microenvironment, RNA-seq reads originating from porcine (HCC tumor) and murine (microenvironment) cells were bioinformatically separated using Xenome. Principle component analysis (PCA) demonstrated clustering by group based on the expression of orthologous genes. Genes contributing to each principal component were extracted and subjected to functional analysis to identify alterations in pathway signaling between HCC cells and the microenvironment. Altered expression of genes associated with hepatic fibrosis deposition, immune response, and neo angiogenesis were observed. The results of this study provide insights into the interplay between HCC and microenvironment signaling in vivo, improving our understanding of the interplay between HCC tumor cells, the surrounding tumor microenvironment, and the impact on HCC development and progression.
Attribution Time: Cal Tinney's 1937 Quip,

In the history of the United States Supreme Court, 1937 was a huge year—perhaps the Court’s most important year ever. Before 1933, the Supreme Court sometimes held that progressive policies enacted by political branches of government were unconstitutional. Such decisions became much more prevalent during President Franklin D. Roosevelt’s first term, 1933-1936. In those years, the Court struck down, often by narrow margins, both federal “New Deal” laws and state law counterparts that sought to combat the devastation of the Great Depression. Then President Roosevelt, in early 1937, proposed to “pack”—to enlarge—the Court, so that it would become supportive of New Deal laws. Within weeks, the Supreme Court changed course, announcing broader constitutional interpretations of federal and state government legislative powers. The Court’s switch took the air out of the Court-packing balloon. The change was—and here is the quip that everyone knows—“the switch in time that saved nine.” That line appeared in 1937. It was repeated by many, especially in Washington. It has been quoted ever since. Just who coined it has been debated and never established. Until now.
Prevalence and Landscape of Actionable Genomic Alterations in Renal Cell Carcinoma

Purpose: We report our experience with next-generation sequencing to characterize the landscape of actionable genomic alterations in renal cell carcinoma (RCC). Methods: A query of our institutional clinical sequencing database (MSK-IMPACT) was performed which included tumor samples from 38,468 individuals across all cancer types. Somatic variations were annotated using a precision knowledge database (OncoKB) and the available clinical data stratified by level of evidence. Alterations associated with response to immune-checkpoint blockade (ICB) were analyzed separately; these included DNA mismatch repair (MMR) gene alterations, tumor mutational burden (TMB) and microsatellite instability (MSI). Data from The Cancer Genome Atlas (TCGA) consortium as well as public data from several clinical trials in metastatic RCC were used for validation purposes. Multiregional sequencing data from the TRAcking Cancer Evolution through Therapy (TRACERx) RENAL cohort was used to assess the clonality of somatic mutations. Results: Of the 753 individuals with RCC identified in the MSK-IMPACT cohort, 115 showed evidence of targetable alterations, which represented a prevalence of 15.3% (95%CI 12.7 - 17.8%). When stratified by levels of evidence, the alterations identified corresponded to levels 2 (11.3%), 3A (5.2%), and 3B (83.5%). A low prevalence was recapitulated in the TCGA cohort at 9.1% (95%CI 6.9-11.2%). Copy-number variations predominated in papillary RCC tumors, largely due to amplifications in the MET gene. Notably, higher rates of actionability were found in individuals with metastatic disease (stage IV) compared to those with localized disease (OR 2.50, 95%CI 1.16 - 6.16, Fisher9s p=0.01). On the other hand, the prevalence of alterations associated with response to ICB therapy was found to be ~5% in both the MSK-IMPACT and TCGA cohorts and no associations with disease stage were identified (OR 1.35 [95%CI 0.46, 5.40], p=0.8). Finally, multiregional sequencing revealed that the vast majority of actionable mutations occurred later during tumor evolution and were only present subclonally in RCC tumors. Conclusions: RCC harbors a low prevalence of clinically actionable alterations compared to other tumors and the evidence supporting their clinical use is limited. These aberrations were found to be more common in advanced disease and seem to occur later during tumor evolution. Our study provides new insights on the role of targeted therapies for RCC and highlights the need for additional research to improve treatment selection using genomic profiling.
Diet as a risk factor and intervention for lower urinary tract symptoms secondary to benign prostatic hyperplasia

Abstract Benign prostatic hyperplasia (BPH) has a significant impact on the quality of life of affected patients as it often leads to debilitating lower urinary tract symptoms (LUTS). While pharmacologic and surgical interventions are the mainstays of treatment, a growing body of literature supports the impact of diet on BPH/LUTS. Prostatic inflammation appears to play an important role in the development of BPH, and dietary approaches aiming to decrease the inflammatory response have increasingly been utilized for treatment. Similarly, metabolic syndrome has been a target of therapeutic strategies, as evidence supports the notion that BPH/LUTS may be influenced by systemic changes associated with metabolic syndrome. Additionally, associations between certain food types and symptoms have been suggested and are a possible emerging therapeutic strategy. It is likely an interplay of various dietary factors that plays a role in the development and progression of LUTS/BPH, and this chapter explores this interconnected web.
Time scale disparity yielding acoustic nonreciprocity in a two-dimensional granular-elastic solid interface with asymmetry.

We study nonreciprocal wave transmission across the interface of two dissimilar granular media separated by an elastic solid medium. Specifically, a left, larger-scale and a right smaller-scale granular media composed of two-dimensional, initially uncompressed hexagonally packed granules are interfacing with an intermediate linearly elastic solid, modeled either as a thin elastic plate or a linear Euler-Bernoulli beam. The granular media are modeled by discrete elements and the elastic solid by finite elements assuming a plane stress approximation for the thin plate. Accounting for the combined effects of Hertzian, frictional and rotational interactions in the granular media, as well as the highly discontinuous interfacial effects between the (discrete) granular media and the (continuous) intermediate elastic solid, the nonlinear acoustics of the integrated system is computationally studied subject to a half-sine shock excitation applied to a boundary granule of either the left or right granular medium. The highly discontinuous and nonlinear interaction forces coupling the granular media to the elastic solid are accurately computed through an algorithm with interrelated iteration and interpolation at successive adaptive time steps. Numerical convergence is ensured by monitoring the (linearized) eigenvalues of a nonlinear map of interface forces at each (variable) time step. Due to the strong nonlinearity and hierarchical asymmetry of the left and right granular media, time scale disparity occurs in the response of the interface which breaks acoustic reciprocity. Specifically, depending on the location and intensity of the applied shock, propagating wavefronts are excited in the granular media, which, in turn, excite either (slow) low-frequency vibrations or (fast) high-frequency acoustics in the intermediate elastic medium. This scale disparity is due to the size disparity of the left and right granular media, which yields drastically different wave speeds in the resulting propagating wavefronts. As a result, the continuum part of the interface responds with either low-frequency vibrations---when the shock is applied to the larger-scale granular medium, or high-frequency waves---when the shock is applied to the smaller-scale granular medium. This provides the fundamental mechanism for breaking reciprocity in the interface. The nonreciprocal interfacial acoustics studied here apply to a broad class of asymmetric hybrid (discrete-continuum) nonlinear systems and can inform predictive designs of highly effective granular shock protectors or granular acoustic diodes.
Policy and principal turnover: The impact of the Texas special education cap

Accountability policies in education play a significant role for the principals tasked with facilitating the implementation of these reforms at the school-level. While these policies are most often intended to improve student outcomes, this is not always the case. In some instances, these policies can prove detrimental to schools, yet principals are still responsible for compliance. In Texas, a federal investigation found the Texas Education Agency (TEA) was restricting access to special education services by incentivizing districts to enroll fewer than 8.5% of students, utilizing these numbers as a measure of district performance. The implementation of the “8.5% cap” in 2004 resulted in a sharp decline in special education enrollment. Employing a sample of all principals in Texas before and after the 2004 law, this paper examines how the 8.5% cap impacted school leader attrition during its implementation. Prior to the implementation of the cap in 2004, we find little association between the proportion of students receiving services and principal turnover. After its implementation however, we find that principals in schools enrolling more than 8.5% of students in special education had a .39 higher odds ratio of switching districts and a .14 higher odds ratio of exiting the profession. We conclude by highlighting the scarcity of school labor market research that accounts for state-level education policies and note that policy may be more associated with principal turnover than student characteristics themselves.
Enzyme Studies with New Analogues of Folic Acid and Homofolic Acid

Many new analogues of dihydrofolate and dihydrohomofolate have been synthesized and tested as substrates of dihydrofolate reductase. Since all of the dihydro- derivatives were efficiently reduced by the action of dihydrofolate reductase from L1210 mouse leukemia cells, the tetrahydro- derivatives thus formed could be tested directly for cofactor and inhibitor activity with thymidylate synthetase. Although thymidylate synthetase of Escherichia coli showed relatively high sensitivity to changes in the amino acid part of the folate molecule, certain tetrahydro analogues were found to show cofactor activity. These included the aminoadipate, aminopimelate, β-methylglutamate, and lysine analogues of pteroylmonoglutamate. All of the tetrahydrohomofolates inhibited thymidylate synthetase to varying degrees, depending on the nature of the amino acid.
Toward human resource management in inter-professional health practice: linking organizational culture, group identity and individual autonomy.

SUMMARY The literature on team and inter-professional care practice describes numerous barriers to the institutionalization of inter-professional healthcare. Responses to slow institutionalization of inter-professional healthcare practice have failed to describe change variables and to identify change agents relevant to inter-professional healthcare practice. The purpose of this paper is to (1) describe individual and organizational level barriers to collaborative practice in healthcare; (2) identify change variables relevant to the institutionalization of inter-professional practice at individual and organizational levels of analysis; and (3) identify human resource professionals as change agents and describe how the strategic use of the human resource function could transform individual and organizational level change variables and therefore facilitate the healthcare system’s shift toward inter-professional practice. A proposed program of institutionalization includes the following components: a strategic plan to align human resource functions with organizational level inter-professional healthcare strategies, activities to enhance professional competencies and the organizational position of human resource personnel, activities to integrate inter-professional healthcare practices into the daily routines of institutional and individual providers, activities to stand up health provider champions as permanent leaders of interprofessional teams with human resource professionals as consultants and activities to bring all key players to the table including health providers. Copyright © 2012 John Wiley & Sons, Ltd.
Speculative Clustered Caches for Clustered Processors

Clustering is a technique for partitioning superscalar processor's execution resources to simultaneously allow for more in-flight instructions, wider issue width, and more aggressive clock speeds. As either the size of individual clusters or the total number of clusters increases, the distance to the first level data cache increases as well. Although clustering may expose more parallelism by allowing a greater number of instructions to be simultaneously analyzed and issued, the gains may be obliterated if the latencies to memory grow too large. We propose to augment each cluster with a small, fast, simple Level Zero (L0) data cache that is accessed in parallel with a traditional L1 data cache. The difference between our solution and other proposed caching techniques for clustered processors is that we do not support versioning or coherence. This may occasionally result in a load instruction that reads a stale value from the L0 cache, but the common case is a low latency hit in the L0 cache. Our simulation studies show that 4KB, 2-way set associative L0 caches provide a 6.5---12.3% IPC improvement over a wide range of processor configurations.
Topics in classical automorphic forms

Introduction The classical modular forms Automorphic forms in general The Eisenstein and the Poincare series Kloosterman sums Bounds for the Fourier coefficients of cusp forms Hecke operators Automorphic $L$-functions Cusp forms associated with elliptic curves Spherical functions Theta functions Representations by quadratic forms Automorphic forms associated with number fields Convolution $L$-functions Bibliography Index.
CRISPR-based screening of genomic island excision events in bacteria

Genomic analysis of Streptococcus thermophilus revealed that mobile genetic elements (MGEs) likely contributed to gene acquisition and loss during evolutionary adaptation to milk. Clustered regularly interspaced short palindromic repeats-CRISPR-associated genes (CRISPR-Cas), the adaptive immune system in bacteria, limits genetic diversity by targeting MGEs including bacteriophages, transposons, and plasmids. CRISPR-Cas systems are widespread in streptococci, suggesting that the interplay between CRISPR-Cas systems and MGEs is one of the driving forces governing genome homeostasis in this genus. To investigate the genetic outcomes resulting from CRISPR-Cas targeting of integrated MGEs, in silico prediction revealed four genomic islands without essential genes in lengths from 8 to 102 kbp, totaling 7% of the genome. In this study, the endogenous CRISPR3 type II system was programmed to target the four islands independently through plasmid-based expression of engineered CRISPR arrays. Targeting lacZ within the largest 102-kbp genomic island was lethal to wild-type cells and resulted in a reduction of up to 2.5-log in the surviving population. Genotyping of Lac(-) survivors revealed variable deletion events between the flanking insertion-sequence elements, all resulting in elimination of the Lac-encoding island. Chimeric insertion sequence footprints were observed at the deletion junctions after targeting all of the four genomic islands, suggesting a common mechanism of deletion via recombination between flanking insertion sequences. These results established that self-targeting CRISPR-Cas systems may direct significant evolution of bacterial genomes on a population level, influencing genome homeostasis and remodeling.
Transcriptional silencing of zinc finger protein 185 identified by expression profiling is associated with prostate cancer progression.

We profiled the expression of genes in benign and untreated human prostate cancer tissues using oligonucleotide microarrays. We report here 50 genes with distinct expression patterns in metastatic and confined tumors (Gleason score 6 and 9; lymph node invasive and noninvasive). Validation of expression profiles of 6 genes by quantitative PCR revealed a strong inverse correlation in the expression of zinc finger protein 185 ( ZNF185 ), bullous pemphigoid antigen gene ( BPAG1 ), and prostate secretory protein ( PSP94 ) with progression of prostate cancer. Treatment of prostate cancer cell lines with 5-aza-2′-deoxycytidine (5-Aza-CdR), an inhibitor of DNA methylation, restored ZNF185 expression levels. Moreover, methylation-specific PCR confirmed methylation of the 5′CpG islands of the ZNF185 gene in all of the metastatic tissues and 44% of the localized tumor tissues, as well as in the prostate cancer cell lines tested. Thus, transcriptional silencing of ZNF185 by methylation in prostate tumor tissues implicates the ZNF185 gene in prostate tumorigenesis.
Using the new jGRASP canvas of dynamic viewers for program understanding and debugging in Java courses

jGRASP is a lightweight IDE that provides automatic generation of visualizations that directly support the teaching of major concepts in CS1 and CS2. These concepts include control structures, classes, interfaces, objects, inheritance, polymorphism, composition, and data structures. This workshop will focus on the new canvas of dynamic viewers which allows students and instructors to create "custom" program visualizations by dragging any primitive or object of a running program stopped at a breakpoint onto the canvas and then saving the canvas. The canvas then comes to life when stepping through the program. Participants are encouraged to bring programs from their own courses. jGRASP is freely available (http://www.jgrasp.org/). All educators who teach Java will benefit from this workshop. However, it will be especially suitable for instructors who teach introduction to programming (CS1) and/or introduction to data structures and algorithms (CS2). The overall objective of the workshop is to introduce faculty to the advanced pedagogical features provided by jGRASP for teaching and learning Java, with special focus on the new canvas of dynamic viewers. The participants will be guided through numerous scenarios to see how creating visualizations of their programs can make learning to program a more enjoyable experience. Since the canvas can be populated with viewers for any primitive or object created by their programs, including object viewers for traditional data structures (e.g., stacks, queues, lists, and binary trees), the visualizations constructed by faculty and students are only limited by their creativity. As they step through their programs in canvas/debug mode, all viewers on the canvas are updated dynamically, which provides the opportunity for a much clearer understanding of the program. When "auto-step-in" is selected, the canvas becomes an animated visualization of a program's internal behavior. Since the canvas can be saved, instructors can provide program visualizations with their examples for students, or students can create visualizations of their own programs and even submit them as part of their assignments. For example, when arrays are introduced, students may be asked to write a simple program that reads in values from the keyboard (or a file) to populate an array, and then prints out the values in reverse order. The students could quickly create a visualization by dragging their Scanner object and their array object onto the canvas. Then as they step through their program, they will see the tokens being consumed in the Scanner and the array elements being set as the input loop is executed. Finally, they will see the values in the array going to System.out in reverse order as the output loop is executed. "Live" textbook-like renderings of key elements in their programs can provide students with exciting possibilities for learning.
Biometric Authentication in Infrastructure Security

This paper will identify and recommend biometric technologies that provide strong authentication, convenient usability, and versatility, in order to meet the demand of enterprise infrastructure security systems. We aim at validating suitability for one or more mainstream applications. Finger scan technology is mature and widely available. The combination of a finger scan and smart card gives true dual-factor authentication that provides a greater degree of security and simplifies authentication for end users while preserving privacy. Speaker Verification is the most natural biometric technology to use with voice-based systems. It takes advantage of the ubiquitous voice-grade telephone channel. The combination of speaker verification and token technology can provide convenient and secure access to voice portal applications. We also discuss cultural, legal, and privacy issues based on religious objections, health concerns, legal restrictions, and regulations on the use of biometric technology.
The Stag Hunt and the Evolution of Social Structure

Brian Skyrms, author of the successful Evolution of the Social Contract (which won the prestigious Lakatos Award) has written a sequel. The book is a study of ideas of cooperation and collective action. The point of departure is a prototypical story found in Rousseau's A Discourse on Inequality. Rousseau contrasts the pay-off of hunting hare where the risk of non-cooperation is small but the reward is equally small, against the pay-off of hunting the stag where maximum cooperation is required but where the reward is so much greater. Thus, rational agents are pulled in one direction by considerations of risk and in another by considerations of mutual benefit. Written with Skyrms's characteristic clarity and verve, this intriguing book will be eagerly sought out by students and professionals in philosophy, political science, economics, sociology and evolutionary biology.
Mathematical Property Prediction Models for Flexible Polyurethane Foams—A Comparison between Conventional Slabstock, High Resilience Slabstock and High Resilience Molded Foams

Flexible polyurethane foams of all types are a unique group of plastics materials, characterized by the fact that a multitude of different sets of properties can be obtained by varying the levels of a relatively small number of base components in the formulations. This has always made flexible polyurethane foams a highly suitable candidate for correlating these variations in the formulations with the resulting properties in a mathematical way, aimed at predicting these properties as accurately as possible, fine-tuning existing grades and designing new foam grades. Several such models have been reported before, and significant improvements have been achieved in the accuracy of the models and the predictions.This paper extends the models for conventional flexible slabstock beyond the previously reported key properties, namely density, hardness and fatigue, to other properties like elongation, tear strength, tensile strength, set properties and foam exothermic temperature. Some further influencing variables ...
A Difference-In-Differences Study of the Effects of a New Abandoned Building Remediation Strategy on Safety

Vacant and abandoned buildings pose significant challenges to the health and safety of communities. In 2011 the City of Philadelphia began enforcing a Doors and Windows Ordinance that required property owners of abandoned buildings to install working doors and windows in all structural openings or face significant fines. We tested the effects of the new ordinance on the occurrence of crime surrounding abandoned buildings from January 2011 to April 2013 using a difference-in-differences approach. We used Poisson regression models to compare differences in pre- and post-treatment measures of crime for buildings that were remediated as a result of the ordinance (n = 676) or permitted for renovation (n = 241), and randomly-matched control buildings that were not remediated (n = 676) or permitted for renovation (n = 964), while also controlling for sociodemographic and other confounders measured around each building. Building remediations were significantly associated with citywide reductions in overall crimes, total assaults, gun assaults and nuisance crimes (p <0.001). Building remediations were also significantly associated with reductions in violent gun crimes in one city section (p <0.01). At the same time, some significant increases were seen in narcotics sales and possession and property crimes around remediated buildings (p <0.001). Building renovation permits were significantly associated with reductions in all crime classifications across multiple city sections (p <0.001). We found no significant spatial displacement effects. Doors and windows remediation offers a relatively low-cost method of reducing certain crimes in and around abandoned buildings. Cities with an abundance of decaying and abandoned housing stock might consider some form of this structural change to their built environments as one strategy to enhance public safety.
Enhancing Bottom-up and Top-down Proteomic Measurements with Ion Mobility Separations

Proteomic measurements with greater throughput, sensitivity, and structural information are essential for improving both in-depth characterization of complex mixtures and targeted studies. While LC separation coupled with MS (LC–MS) measurements have provided information on thousands of proteins in different sample types, the introduction of a separation stage that provides further component resolution and rapid structural information has many benefits in proteomic analyses. Technical advances in ion transmission and data acquisition have made ion mobility separations an opportune technology to be easily and effectively incorporated into LC–MS proteomic measurements for enhancing their information content. Herein, we report on applications illustrating increased sensitivity, throughput, and structural information by utilizing IMS–MS and LC–IMS–MS measurements for both bottom-up and top-down proteomics measurements.
Diffusion of the Restriction Nuclease EcoRI along DNA

Abstract Many specific sequence DNA binding proteins locate their target sequence by first binding to DNA nonspecifically, then by linearly diffusing or hopping along DNA until either the protein dissociates from the DNA or it finds the recognition sequence. We have devised a method for measuring one-dimensional diffusion along DNA based on the ratio of the dissociation rate of protein from DNA fragments containing one specific binding site to the dissociation rate from DNA fragments containing two specific binding sites. Our extensive measurements of dissociation rates and specific–nonspecific relative binding constants of the restriction nuclease EcoRI enable us to determine the diffusion rate of nonspecifically bound protein along the DNA. By varying the distance between the two binding sites, we confirm a linear diffusion mechanism. The sliding rate is relatively insensitive to salt concentration and osmotic pressure, indicating that the protein moves smoothly along the DNA probably following the helical phosphate-sugar backbone of DNA. We calculate a diffusion coefficient for EcoRI of 3 × 10 4 bp 2 s − 1 EcoRI is able to diffuse ∼ 150 bp, on average, along the DNA in 1 s. This diffusion rate is about 2000-fold slower than the diffusion of free protein in solution. A factor of 40–50 can be accounted for by rotational friction resulting from following the helical path of the DNA backbone. Two possibilities could account for the remaining activation energy: salt bridges between the DNA and the protein are transiently broken, or the water structure at the protein–DNA interface is disrupted as the two surfaces move past each other.
Braudel's ecological perspective

Fernand Braudel, a leading figure in theAnnales school of French historiography, employed principles and practices from several social science disciplines in his historical studies. Significant among these was sociology. Although he did not formally recognize that a major element in his sociological perspective was human ecology, an analysis of his work reveals how extensively he employed an ecological paradigm. His success in using this paradigm demonstrates the utility of the principles of human ecology in historical and comparative studies and suggests strongly that fresh insights into contemporary social systems can be gained by combining Braudel's “total history” and ecology's “holistic” approaches.
Factor VIII inhibitor bypass activity and recombinant activated factor VII in cardiac surgery.

Objective Postcardiopulmonary bypass hemorrhage remains a serious complication of cardiac surgery. Given concerns regarding adverse effects of blood product transfusion and limited efficacy of current antifibrinolytics, procoagulant medications, including recombinant factor VIIa (rFVIIa) and factor eight inhibitor bypass activity (FEIBA), increasingly have been used in managing refractory bleeding. While effective, these medications are associated with thromboembolic complications. This study compared the efficacy and risk of adverse events of rFVIIa and FEIBA in cardiac surgical patients with refractory bleeding. Design This retrospective study evaluated 168 patients who underwent cardiac surgery and received either FEIBA or rFVIIa to manage postbypass hemorrhage. Demographic, clinical, and outcomes data were collected and statistical analysis performed to compare thromboembolic event rates, relative efficacy, and 30-day mortality following administration of these medications. Setting Single university hospital. Participants Patients undergoing cardiac surgery. Interventions None. Measurements and Main Result Sixty-one patients received rFVIIa, and 107 received FEIBA. Demographics, surgical procedures, and preoperative anticoagulation were similar between the cohorts; however, the rFVIIa cohort had longer durations of cardiopulmonary bypass (305.1 v 243.8 min, p Conclusions This study suggests that rFVIIa and FEIBA have similar efficacy and adverse event profiles in managing intractable postbypass hemorrhage in cardiac surgical patients. Further prospective studies are required.
Tolerance of Chicks for Dimethyl Sulfoxide

Abstract Studies were conducted to determine levels of dimethyl sulfoxide (DMSO) that could be administered to chicks without toxic effect. The LD50 of a single dose of DMSO in day-old chicks was between 10.0 and 12.5 ml. per kg. body weight (b.w.) by oral administration and between 7.5 and 10.0 ml. per kg. b.w. by subcutaneous injection. The maximum nonlethal single dose of DMSO was 7.5 ml. per kg. b.w. by oral administration and 5.0 ml. per kg. b.w. by subcutaneous injection. Injected for 14 consecutive days, subcutaneously, 1.25 ml. DMSO per kg. b.w. was the maximum level tolerated with no toxic effects. In male chicks, a level of DMSO greater than 1.25 ml. per kg. b.w. reduced growth rate and produced an apparent fibrosis at the injection site. In female chicks the fibrosis, but not the growth depression, was observed. Intramuscular injection of DMSO at levels as low as 0.625 ml. per kg. b.w. produced a severe local inflammation that prohibited the use of DMSO in this age chick. The advantages and limitations of DMSO as an injection solvent for chicks are discussed.
Oxytocin as a Potential Therapeutic Target for Schizophrenia and Other Neuropsychiatric Conditions

Oxytocin as a Potential Therapeutic Target for Schizophrenia and Other Neuropsychiatric Conditions