cssi/SciSciGPT-SciSciNet huggingface dataset:
LAND REGIMES AND THE STRUCTURE OF POLITICS: PATTERNS OF LAND-RELATED CONFLICT

This article proposes an analytic framework to describe variation in forms of land-related conflict that emerge in widely varying circumstances and settings. Focusing on conflict among smallholders, the article suggests that these social processes can often be thought of as redistributive conflicts that are shaped by the land tenure regimes that govern land access and allocation. Land tenure regimes can be conceptualized schematically as constituted by rules about property, authority, jurisdiction and citizenship, and as differentiated along these dimensions. They define a locus of political authority over land rights at the local level, a territorial arena, social groups with different land rights and interests, and the distribution of political and economic powers and rights among them. These arrangements vary across space and over time, shaping the political arenas in which land rights are contested and producing different forms of land-related conflict. In many situations, these dimensions of land regimes are blurred, layered and changing, adding additional dimensions of complexity to land politics that the analysis proposed here may help to illuminate.
Roles of specific amino acids in the N terminus of Pseudomonas aeruginosa flagellin and of flagellin glycosylation in the innate immune response.

The Toll-like receptor 5 (TLR5) binding site has been predicted to be in the N terminus of the flagellin molecule. In order to better define the interaction between the N-terminal amino acids of Pseudomonas aeruginosa flagellin and TLR5, site-specific mutations were generated between residues 88 and 97 of P. aeruginosa PAK flagellin as well as outside of this region. The mutant flagellins were expressed in Escherichia coli BL21(plysS), purified by affinity chromatography, and passed through a polymyxin B column to remove contaminating lipopolysaccharide (LPS). Their ability to stimulate interleukin-8 (IL-8) release from A549 cells was examined. The cloned mutated genes were used to complement a PAK fliC mutant in order to test for effects on motility and on IL-8 release by purified flagellar preparations. All the mutations, single or double, in the predicted TLR5 binding region reduced IL-8 signaling to less than 95% of the wild-type flagellin levels, but the single mutation outside the binding region had no effect. Changes made at two amino acid sites resulted in loss/reduction of motility; however, changes made at single sites, i.e., Q83A, L88A, R90A, M91A, L94A, and Q97A, had no effect on motility. The mutated genes encoding two of the motile but poorly signaling flagellins had no compensatory mutations to allow motility. Thus, while it is speculated that pathogen-associated molecular patterns (PAMPs) have evolved in locations that are essential to maintain function, it appears that there is tolerance for at least single amino acid changes in the PAMP of P. aeruginosa flagellin. The purpose of flagellin glycosylation in P. aeruginosa is unknown. In order to examine its role, if any, in signaling an inflammatory response, we used whole flagella from the motile chromosomal mutant strains PAKrfbC and PAO1rfbC, which are defective in flagellin glycosylation. IL-8 release from A549 cells stimulated with nonglycosylated flagellar preparations (having less then 1 picogram of LPS/μg) was significantly reduced compared to their respective wild-type flagellar preparations, indicating a role of flagellar glycosylation in the proinflammatory action of Pseudomonas flagellin. The basis of the latter activity is unknown, since the glycosylation sites are found in the D3 domain of flagellins and the TLR5 binding site is located in the D1 domain. Thus, P. aeruginosa flagellin has evolved additional flagellar signaling mechanisms over that described for Salmonella flagellin.
Plasmid-related quinolone resistance determinants in epidemic Vibrio parahaemolyticus, uropathogenic Escherichia coli, and marine bacteria from an aquaculture area in Chile.

Marine bacteria from aquaculture areas with industrial use of quinolones have the potential to pass quinolone resistance genes to animal and human pathogens. The VPA0095 gene, related to the quinolone resistance determinant qnrA, from clinical isolates of epidemic Vibrio parahaemolyticus conferred reduced susceptibility to quinolone after cloning into Escherichia coli K-12 either when acting alone or synergistically with DNA gyrase mutations. In addition, a plasmid-mediated quinolone resistance gene from marine bacteria, aac(6′)-Ib-cr, was identical to aac(6′)-Ib-cr from urinary tract isolates of E. coli, suggesting a recent flow of this gene between these bacteria isolated from different environments. aac(6′)-Ib-cr from E. coli also conferred reduced susceptibility to quinolone and kanamycin when cloned into E. coli K-12.
Mutagenicity studies with N-acetyl-L-aspartic acid.

Abstract Analytical studies have reported that N-acetyl- l -aspartic acid (NAA) is present at low concentrations in many foods. The current studies were conducted to assess the mutagenicity of NAA using standard OECD guideline in vitro bacterial and in vivo mammalian mutagenicity studies. For comparison and control data, mutagenicity studies were also conducted with its constituent amino acid l -aspartate (ASP) because NAA is metabolized to ASP. The combination of an in vitro method for assessing point mutations in bacteria and an in vivo method to assess clastogenicity in an animal model provided adequate evidence for mutagenicity hazard assessment of NAA. No evidence of mutagenicity was observed in either test system with either NAA or ASP. The results from the current studies demonstrate that the presence of NAA in foods is not likely to represent a risk for mutagenicity.
Passive avoidance: A variety of fear conditioning?

Step-in latencies and the proportion of time spent outside the shock situation were measured for three groups of rats. One group had received shock on stepping into the shock chamber, and had been allowed to escape the shock chamber. A yoked control group received the same number of shocks after being placed directly into the shock chamber. Escape was not permitted for these Ss. The final group had received no shock. Both shock groups differed reliably from the nonshocked group on both response measures. Differences between the two shocked groups were not significant. The results were interpreted as indicating that punishment of specific responses is not necessary for step-in passive avoidance performance.
Analysis of Dislocation Loops in Superlattices

A detailed computer analysis of dislocation loop behavior in DO3 and B2 type superlattices has been performed. This analysis shows that DO3 superlattice dislocation nucleation most probably proceeds by the independent nucleation of four 1/2 a0 〈111〉 loops while the same process in B2 superlattices occurs by the independent nucleation of two such loops. Thus, superlattice dislocation loop nucleation requires a greater amount of energy in the DO3 case than does loop nucleation in a comparable B2 superlattice. These processes may be thermally activated so that at sufficiently low temperatures, e.g. 243 °K for Fe3Si (DO3), insufficient thermal energy is available and imperfect dislocations are nucleated. Thus, subsequent deformation in DO3 structures can only occur at stress levels commensurate with antiphase boundary production while deformation of B2 structures can occur at lower stresses since nucleation is much easier. — An analysis of equilibrium dislocation loop configurations in DO3 and B2 superlattices has also been carried out for various applied stresses. This analysis shows that the stress required to maintain a given radius of curvature in disordered, B2, and DO3 structures increases approximately in the ratio 1 : 2: 3. It has also been shown that the equilibrium spacing of a superdislocation loop pair increases with decreasing applied stress until, at some critical stress, the inner loop becomes unstable and collapses. The above processes have been shown to markedly effect the deformation behavior of ordered alloys.
Specialist Osmia bees forage indiscriminately among hybridizing Balsamorhiza floral hosts

Pollinators, even floral generalists (=polyleges), typically specialize during individual foraging bouts, infrequently switching between floral hosts. Such transient floral constancy restricts pollen flow, and thereby gene flow, to conspecific flowers in mixed plant communities. Where incipient flowering species meet, however, weak cross-fertility and often similar floral traits can yield mixed reproductive outcomes among pollinator-dependent species. In these cases, floral constancy by polyleges sometimes serves as an ethological mating barrier. More often, their foraging infidelities instead facilitate host introgression and hybridization. Many other bee species are oligolectic (taxonomic specialists for pollen). Oligoleges could be more discriminating connoisseurs than polyleges when foraging among their limited set of related floral hosts. If true, greater foraging constancy might ensue, contributing to positive assortative mating and disruptive selection, thereby facilitating speciation among their interfertile floral hosts. To test this Connoisseur Hypothesis, nesting females of two species of oligolectic Osmia bees were presented with randomized mixed arrays of flowers of two sympatric species of their pollen host, Balsamorhiza, a genus known for hybridization. In a closely spaced grid, the females of both species preferred the larger flowered B. macrophylla, evidence for discrimination. However, both species’ females showed no floral constancy whatsoever during their individual foraging bouts, switching randomly between species proportional to their floral preference. In a wider spaced array in which the bouquets reflected natural plant spacing, foraging oligolectic bees often transferred pollen surrogates (fluorescent powders) both between conspecific flowers (geitonogamy and xenogamy) and between the two Balsamorhiza species. The Connoisseur Hypothesis was therefore rejected. Foraging infidelity by these oligolectic Osmia bees will contribute to introgression and hybridization where interfertile species of Balsamorhiza meet and flower together. A literature review reveals that other plant genera whose species hybridize also attract numerous oligolectic bees, providing independent opportunities to test the generality of this conclusion.
A Comparison of Two Interventions to Increase Completion of Advance Directives

The purpose of this study was to evaluate two different interventions on their ability to promote advance directive completion. Specifically, an intervention based on protection motivation theory, which involved presenting threatening information and coping information, was compared with a general healthy aging intervention, which spent little time actually discussing advance directives. Participants were obtained from a community sample involving church groups and senior centers. Participants were assigned to one of the two interventions. Participants were then asked several questions, including whether or not they had completed an advance directive at 3-month follow-up. Results indicated that those who participated in the healthy aging intervention completed more advance directives than did those in the protection motivation theory intervention. These results are consistent with the tenants of socioemotional selectivity theory, which states that older adults are focused more on maintaining their well-be...
Developmental Psychobiology special issue: "Gilbert Gottlieb's legacy: probabilistic epigenesis and the development of individuals and species".

A tribute to the career of Gilbert Gottlieb represented in the contributions to developmental science of his former students and colleagues. © 2007 Wiley Periodicals, Inc. Dev Psychobiol 49: 747–748, 2007.
ON A CONJECTURE OF FILL AND HOLST INVOLVING THE MOVE-TO-FRONT RULE AND CACHE FAULTS

Fill and Holst conjectured for the move-to-front rule that the probability that the search time is greater than c will be Schur concave in the stationary distribution for any value of c. This paper disproves the conjecture but proves some conclusions that would be implied by the conjecture.
Cdc15 integrates Tem1 GTPase-mediated spatial signals with Polo kinase-mediated temporal cues to activate mitotic exit

In budding yeast, a Ras-like GTPase signaling cascade known as the mitotic exit network (MEN) promotes exit from mitosis. To ensure the accurate execution of mitosis, MEN activity is coordinated with other cellular events and restricted to anaphase. The MEN GTPase Tem1 has been assumed to be the central switch in MEN regulation. We show here that during an unperturbed cell cycle, restricting MEN activity to anaphase can occur in a Tem1 GTPase-independent manner. We found that the anaphase-specific activation of the MEN in the absence of Tem1 is controlled by the Polo kinase Cdc5. We further show that both Tem1 and Cdc5 are required to recruit the MEN kinase Cdc15 to spindle pole bodies, which is both necessary and sufficient to induce MEN signaling. Thus, Cdc15 functions as a coincidence detector of two essential cell cycle oscillators: the Polo kinase Cdc5 synthesis/degradation cycle and the Tem1 G-protein cycle. The Cdc15-dependent integration of these temporal (Cdc5 and Tem1 activity) and spatial (Tem1 activity) signals ensures that exit from mitosis occurs only after proper genome partitioning.
The Biomechanical Function of the Anterolateral Ligament of the Knee

Background:Recent anatomic investigations of the lateral structures of the knee have identified a new ligament, called the anterolateral ligament (ALL). To date, the anterolateral ligament has not been biomechanically tested to determine its function.Hypothesis:The ALL of the knee will resist internal rotation at high angles of flexion but will not resist anterior drawer forces.Study Design:Controlled laboratory study.Methods:Eleven cadaveric knees were subjected to 134 N of anterior drawer at flexion angles between 0° and 90° and separately to 5 N·m of internal rotation at the same flexion angles. The in situ forces of the ALL, anterior cruciate ligament (ACL), and lateral collateral ligament (LCL) were determined by the principle of superposition.Results:The contribution of the ALL during internal rotation increased significantly with increasing flexion, whereas that of the ACL decreased significantly. At knee flexion angles greater than 30°, the contribution of the ALL exceeded that of the ACL. During ...
Inhibition of Oxygen-Induced Hypoxia-Inducible Factor-1α Degradation Unmasks Estradiol Induction of Vascular Endothelial Growth Factor Expression in ECC-1 Cancer Cells in Vitro

Estradiol (E(2)) rapidly and strongly induces vascular endothelial growth factor (VEGF) transcription in uterine endometrial epithelial cells in vivo. We have shown that this is mediated by both the estrogen receptor-alpha and hypoxia-inducible factor (HIF)-1alpha. By contrast, E(2) induces little or no VEGF expression in cultured breast or endometrial cancer cells, which lack HIF-1alpha due to the abnormally high concentration of oxygen ( approximately 20%) to which they are exposed. To test the hypothesis that restoring HIF-1alpha in cultured cells would restore the ability of E(2) to induce VEGF expression, we treated human endometrial cancer cells (ECC-1) with cobalt chloride (CoCl(2);100 microm), which prevents oxygen-induced HIF-1alpha degradation. HIF-1alpha was absent in untreated ECC-1 cells but detectable by 4 h after treatment with CoCl(2) alone, as was a significant increase in VEGF mRNA. E(2) plus CoCl(2) induced detectable HIF-1alpha expression at 2 h and an even higher level than that induced by CoCl(2) alone at 4 h; this HIF-1alpha was localized in the nuclei. This was accompanied by increasing VEGF expression, with the increase at 4 h severalfold higher than that induced by CoCl(2) alone and was concurrent with recruitment of both HIF-1alpha and estrogen receptor-alpha to the VEGF promoter. These results confirm that HIF-1alpha plays an essential role in E(2)-induced expression of VEGF. Through the induction of increased microvascular permeability and the consequent exudation of plasma growth factors, VEGF in turn may play an essential role in cancer cell proliferation in vivo.
Vitamin E and Prevention of Heart Disease in High-risk Patients

Several observational studies have suggested that high intake of vitamin E may slow the development and progression of atherosclerosis. Some clinical trials also reported beneficial effects of vitamin E supplementation in the secondary prevention of cardiovascular events. However, results of recent large, multicenter clinical trials reported that vitamin E supplementation was not effective in reducing the incidence of cardiovascular events in high-risk patients.
Structure and Activation of the Visual Pigment Rhodopsin

Rhodopsin is a specialized G protein-coupled receptor (GPCR) found in vertebrate rod cells. Absorption of light by its 11-cis retinal chromophore leads to rapid photochemical isomerization and receptor activation. Recent results from protein crystallography and NMR spectroscopy show how structural changes on the extracellular side of rhodopsin induced by retinal isomerization are coupled to the motion of membrane-spanning helices to create a G protein binding pocket on the intracellular side of the receptor. The signaling pathway provides a comprehensive explanation for the conservation of specific amino acids and structural motifs across the class A family of GPCRs, as well as for the conservation of selected residues within the visual receptor subfamily. The emerging model of activation indicates that, rather than being unique, the visual receptors provide a basis for understanding the common structural and dynamic elements in the class A GPCRs.
‘National Essence’ vs ‘Science’: Chinese Native Physicians' Fight for Legitimacy, 1912–37

The medical profession in modern China comprised two radically different schools—modern (Western) medicine and native medicine. The difference in philosophy, theory, and technique made a conflict between the two schools almost inevitable, and the conflict was intensified by the modernization process that was quickened during the Republican period. Western-trained or modern doctors advocated national salvation through science and denounced native medicine as superstitious, unscientific, and an impediment to the development of medical science in China. On the other hand, native medical practitioners insisted that what they learned and practiced was part of the national essence (guocui) and should be protected against the cultural invasion of imperialism (diguo zhuyi wenhua qinlue) including Western medicine. To be sure, both sides used such rhetoric to camouflage the business competition between them, but this rivalry and its implications did point to a profound cultural conflict between Chinese tradition and Western influence in China's modernization. It epitomized a burning issue of the day: whether or not China's modernization meant Westernization and whether a respectable position for China in the modern world was to be achieved through Westernization or preservation of what was regarded or claimed as national heritage.
Spironolactone for Hirsutism in Polycystic Ovary Syndrome

OBJECTIVE:To evaluate the level of evidence for treatment of hirsutism associated with polycystic ovary syndrome (PCOS) with spironolactone.DATA SOURCES:Studies and reports were located in MEDLINE (1966–January 2005%), EMBASE, and International Pharmaceutical Abstracts through the second week of January 2005.DATA SYNTHESIS:Hirsutism is a common clinical problem and is often associated with PCOS. Research has been performed to assess the efficacy of spironolactone therapy in patients with hirsute characteristics. Five studies that evaluated the effectiveness of spironolactone for hirsutism in PCOS were identified and reviewed.CONCLUSIONS:The effects of multiple treatment options on the subjective and objective measures of hirsutism have displayed varying results. The outcomes reported to date have shown a positive trend toward using spironolactone in women with PCOS and hirsutism.
SEASONALITY OF MICROBIAL FOULING ON ASCOPHYLLUM NODOSUM (L.) LEJOL., FUCUS VESICULOSUS L., POLYSIPHONIA LANOSA (L.) TANDY AND CHONDRUS CRISPUS STACKH1

The nature and seasonal extent of microbial fouling on Ascophyllum nodosum (L.) LeJol., Fucus vesiculosus L., Polysiphonia lanosa (L.) Tandy and Chondrus crispus Stackh. were observed by scanning electron microscopy. Bacterial filaments and smaller rod and coccoid forms dominated the fouling communities on all species, with pennate diatoms constituting a minor component in contrast to results with plastic substrates on which pennate diatoms dominated and preceded bacterial colonization. The total percent microbial coverage on the surfaces of all four seaweed species was determined by monthly stereological analyses of representative composite micrographs. These showed a simultaneous decline between April and May which could represent the die-off of the cold water bacterial flora when water temperature increased past the threshold for obligate psychrophiles. Microbial colonization patterns were directly correlated (P = 0.005) with maximum coverage in April and November–December and reduced levels from May to October. Significant inverse (P < 0.041) correlations between total percent coverage and water temperature indicate distinct seasonal cycles, however, the patterns of dominance by filamentous bacteria and rod and coccoid forms were markedly different. Total coverage patterns of both rhodophytes showed no apparent seasonal cycle and were not related to water temperature. Rod and coccoid bacteria were apparently suppressed year round on P. lanosa relative to the other species. These interspecific differences in seasonal fouling patterns are discussed in light of possible modes of regulation, especially algal antibiosis.
Psychiatric and Behavioral Genetics: A Useful Distinction?

Dr. Hallmayer began with a discussion of the Nuffield Council on Bioethics' work on genetics, mental disorders and human behavior. He further explored psychiatric genetics and urged against the oversimplification of dynamic interactions. To watch Dr. Hallmayer’s presentation, please see the "Google Video posting.":http://video.google.com/videoplay?docid=-5387564337084407366&hl=enTo watch the deliberative discussion concluding the first Symposium panel, please see the "Google Video posting.":http://video.google.com/videoplay?docid=3871777823134971240&hl=en
Potent neutralization of staphylococcal enterotoxin B by synergistic action of chimeric antibodies.

Staphylococcal enterotoxin B (SEB), a shock-inducing exotoxin synthesized by Staphylococcus aureus, is an important cause of food poisoning and is a class B bioterrorism agent. SEB mediates antigen-independent activation of a major subset of the T-cell population by cross-linking T-cell receptors (TCRs) with class II major histocompatibility complex (MHC-II) molecules of antigen-presenting cells, resulting in the induction of antigen independent proliferation and cytokine secretion by a significant fraction of the T-cell population. Neutralizing antibodies inhibit SEB-mediated T-cell activation by blocking the toxin's interaction with the TCR or MHC-II and provide protection against the debilitating effects of this superantigen. We derived and searched a set of monoclonal mouse anti-SEB antibodies to identify neutralizing anti-SEB antibodies that bind to different sites on the toxin. A pair of non-cross-reactive, neutralizing anti-SEB monoclonal antibodies (MAbs) was found, and a combination of these antibodies inhibited SEB-induced T-cell proliferation in a synergistic rather than merely additive manner. In order to engineer antibodies more suitable than mouse MAbs for use in humans, the genes encoding the VL and VH gene segments of a synergistically acting pair of mouse MAbs were grafted, respectively, onto genes encoding the constant regions of human Igκ and human IgG1, transfected into mammalian cells, and used to generate chimeric versions of these antibodies that had affinity and neutralization profiles essentially identical to their mouse counterparts. When tested in cultures of human peripheral blood mononuclear cells or splenocytes derived from HLA-DR3 transgenic mice, the chimeric human-mouse antibodies synergistically neutralized SEB-induced T-cell activation and cytokine production.
Treatment of Femoral Shaft Fracture with an Interlocking Humeral Nail in Older Children and Adolescents

Purpose: Rigid interlocking nailing for femoral shaft fracture is ideal for use in adolescents in terms of stability of the fracture and convenience for the patient. However, numerous authors have reported that rigid interlocking nailing has some limitations in this age group due to the risk of complications. We evaluated the results of intramedullary nailing for femoral shaft fractures with an interlocking humeral nail in older children and adolescents. Materials and Methods: We retrospectively reviewed records of patients treated with an interlocking humeral nail. Radiographs were examined for proximal femoral change and evidence of osteonecrosis. Outcomes were assessed by major or minor complications that occurred after operative treatment. Results: Twenty-four femoral shaft fractures in 23 patients were enrolled. The mean age at the time of operation was 12 years and 8 months and the mean follow-up period was 21 months. Bony union was achieved in all patients without any complications related to the procedure such as infection, nonunion, malalignment and limb length discrepancy. All fractures were clinically and radiographically united within an average eight weeks. No patients developed avascular necrosis of the femoral head and coxa valga. Conclusion: Intramedullary nailing through the greater trochanter using a rigid interlocking humeral nail is effective and safe for the treatment of femoral shaft fractures in older children and adolescents.
Overview of pediatric renal replacement therapy in acute kidney injury.

The disease spectrum leading to pediatric renal replacement therapy (RRT) provision has broadened over the last decade. In the 1980’s, intrinsic renal disease and burns comprised the most common pediatric acute kidney injury (AKI) etiologies. More recent data demonstrate that pediatric AKI most often results from complications of other systemic diseases resulting from the advancements in congenital heart surgery, neonatal care, and bone marrow and solid organ transplantation. In addition, RRT modality preferences to treat critically ill children have shifted from peritoneal dialysis to continuous renal replacement therapy (CRRT) as a result of improvements in CRRT technologies. Currently, multicenter prospective outcome studies for critically ill children with AKI are sorely lacking. The aims of this paper are to review the pediatric specific causes necessitating RRT provision with an emphasis on emerging practice patterns with respect to modality and the timing of treatment, and focus upon the application of the different RRT modalities and assessment of the outcome of children with AKI who receive RRT.
Gamma interferon dominates the murine cytokine response to the agent of human granulocytic ehrlichiosis and helps to control the degree of early rickettsemia.

The cytokine response to the agent of human granulocytic ehrlichiosis (HGE) was assessed in a murine infection model and the role of gamma interferon (IFN-γ), a cytokine that is crucial for host defenses against intracellular pathogens, was investigated by using IFN-γ-deficient mice. The agent of HGE (aoHGE) is an obligate intracellular bacterium that survives within neutrophils: morulae (vacuoles containing HGE organisms) are evident in polymorphonuclear leukocytes of experimentally infected immunocompetent mice for 1 to 2 weeks. We now show that IFN-γ levels increase during early infection of C3H/HeN or C57BL/6 mice with HGE bacteria. Moreover, in response to aoHGE extracts or concanavalin A, splenocytes from ehrlichia-infected mice produced more IFN-γ and less interleukin-4 than controls, suggesting that aoHGE partially skewed the immune response towards a Th1 phenotype. Absolute concentration of morulae containing neutrophils in blood was 122 ± 22 cells/μl on day 8. The bacterial DNA burden was also highest on day 8 and then declined after IFN-γ levels peaked. In contrast, IFN-γ-deficient mice had a markedly elevated HGE bacteria burden with morulae concentration of 282 ± 48 cells/μl on day 5 (P = 0.004) and 242 ± 63 cells/μl on day 8 (P = 0.005). Rickettsemia resolved in immunocompetent and IFN-γ deficient mice after 2 weeks, while both the immunocompetent and the IFN-γ-deficient mice had increased serum antibodies against aoHGE antigens at this time point. These data demonstrate that the HGE agent elicits a prominent IFN-γ response in mice and that IFN-γ is important in controlling the degree of rickettsemia during the early phase of infection, while IFN-γ independent mechanisms play a role at later time points.
Modeling the power rails in leading edge microprocessor packages

This paper discusses an electrical modeling methodology developed to deal with package power rail (supply) issues for high performance microprocessors. The basic approach is to create a SPICE model of the microprocessor package and IC power rails that mimics the actual physical structures. Grid array style packages with flip mounted dice conveniently partition into two dimensional arrays (planes) interconnected in the third dimension by flip chip bumps, package vias, pins, etc. The key issues are how to partition the system for modeling, how to create the model elements, and how to manage the integration of the model elements. Partitioning is done by choosing a two-dimensional "cell" dimension that provides both acceptable resolution and model complexity. Practical guidelines for creating model subcircuits are discussed. Simulation results representative of a leading edge microprocessor package are presented.
Is less more? Dual- versus single-chamber implantable cardioverter-defibrillators.

In this issue of the Journal , Dewland et al. ([1][1]) use the National Cardiovascular Data Registry (NCDR) Implantable Cardioverter-Defibrillator (ICD) Registry to evaluate the rate of in-hospital complications and death in patients who receive dual-chamber compared with single-chamber ICDs. As the
Experimental Techniques for Evaluation of the Effectiveness of Natural Enemies

The role of natural enemies in prey (or host) population regulation has long been debated by ecologists, and various methods of evaluation proposed and attempted. The fact that considerable disagreement remains is sufficient evidence of the need for adequate assessment of the efficiency of enemies. Precise means of evaluation are needed for several reasons: (1) to illuminate basic principles of population ecology, especially the role of biotic and abiotic factors, (2) to furnish a sound ecological basis for manipulation of natural enemies either by demonstrating the need for importation of new ones or by showing that the established ones are rendered ineffective due to interference phenomena, including pesticides, weather or cultural practices, and (3) to provide the proof of effectiveness of natural enemies that is necessary in applied biological control in order to justify needed increased research and development support.
Magnetic Field Induced Ultrasound from Colloidal Superparamagnetic Nanoparticles

Generating ultrasound remotely by means of magnetic fields is an important technological development to circumvent the drawbacks of the traditional means of ultrasound generation techniques. In this report, it is demonstrated that ultrasound is generated from colloidal superparamagnetic nanoparticles when exposed to pulsed and alternating magnetic fields. Comparison of the inhomogeneous and homogeneous magnetic fields indicates that both homogeneous and inhomogeneous magnetic fields could be important for efficient ultrasound generation; however, the latter is more important for dilute colloidal dispersion of magnetic nanoparticles. In strong magnetic fields, the ultrasound generated from the colloidal magnetic nanoparticles shows reasonable agreement with the magnetostriction effect commonly observed for bulk ferromagnetic materials. At low magnetic fields, the colloidal magnetic nanoparticle dispersion produces considerable amount of ultrasound when exposed to ac magnetic fields in the 20–5000 kHz frequ...
Should Capital Input Data Receive a Utilization Adjustment

A common procedure in productivity research is to use estimates of the stocks of physical capital as proxies for service flows. A number of authors propose cyclical adjustments for capital input which, if large enough, will eliminate findings of procyclicality in the behavior of TFP. This paper argues that for the preponderance of assets in the fixed capital stock, fluctuations in utilization have little effect on user costs. In the aggregate, adjustments to capital input data for utilization should consequently be small, much smaller, for example, than those suggested by Solow (1957), Griliches and Jorgenson (1966), Tatom (1980), Shapiro (1993), or Basu and Fernald. (2000).
Systemic Therapy for Metastatic Colorectal Cancer

In the treatment of advanced colorectal cancer (CRC), the addition of so-called "targeted" agents to irinotecan- and oxaliplatin-based regimens has resulted in statistically significant--but often clinically modest--improvements in progression-free and overall survival. This is true for the most recent additions to the treatment armamentarium, regorafenib and ziv-aflibercept. In his recent presentation at the NCCN 18th Annual Conference, Leonard Saltz, MD, reviewed the landmark trials establishing targeted agents as effective in metastatic CRC. However, he also noted that statistical significance does not necessarily equal clinical significance, and indicated that clinicians should consider the differential toxicity profiles of the regimens when individualizing treatment.
Randomization Inference and Sensitivity Analysis for Composite Null Hypotheses With Binary Outcomes in Matched Observational Studies

ABSTRACTWe present methods for conducting hypothesis testing and sensitivity analyses for composite null hypotheses in matched observational studies when outcomes are binary. Causal estimands discussed include the causal risk difference, causal risk ratio, and the effect ratio. We show that inference under the assumption of no unmeasured confounding can be performed by solving an integer linear program, while inference allowing for unmeasured confounding of a given strength requires solving an integer quadratic program. Through simulation studies and data examples, we demonstrate that our formulation allows these problems to be solved in an expedient manner even for large datasets and for large strata. We further exhibit that through our formulation, one can assess the impact of various assumptions about the potential outcomes on the performed inference. R scripts are provided that implement our methods. Supplementary materials for this article are available online.
A World without Why

Raymond Geuss, professor of philosophy, who specializes in political philosophy, has been teaching at the University of Cambridge since the mid-1970s. This volume is a collection of his essays, and...
Opsin Effect on the Electronic Structure of the Retinylidene Chromophore in Rhodopsin

Direct examination of experimental NMR parameters combined with electronic structure analysis was used to provide a first-principle interpretation of NMR experiments and give a precise evaluation of how the electronic perturbation of the protein environment affects the electronic properties of the retinylidene chromophere in rhodopsin. To this end, we pursued a theoretical analysis using a combination of tools including quantum mechanics/molecular mechanics (QM/MM) at the Density Functional Theory (DFT) level, in conjunction with gauge independent atomic orbital (GIAO) calculations of 13C NMR chemical shieldings and 1JCC spin–spin coupling constants obtained with the Coupled Perturbed DFT (CPDFT) method. The opsin effect on the retinylidene chromophere is interpreted as an inductive effect of Glu-113 which readjusts the weighting factors of resonance substructures of the conjugated chain of the chromophere. These changes give a rationalization to the alternating effect of the 13C chemical shifts magnitude...
Isolated Hearts from Obese Rats Show Impaired Function during Hypoxia

SummaryCardiac hemodynamic function of genetically obese male Zucker rats and lean male littermates was studied using an isolated ejecting whole heart preparation. Minimal differences in function were observed between hearts from 9-week-old lean and obese rats. In contrast, hearts from 19-week-old obese rats exhibited depressed ventricular function curves accom-panied by decreased stroke work, maximum power, and efficiency in hypoxia, and reduced response to dobutamine in hypoxia compared with controls. These findings suggest that chronic severe obesity in the Zucker rat is associated with the development of diminished cardiac resistance to hypoxic stress.
Therapy of inflammatory myopathy.

SUMMARY The management of the muscular and extramuscular manifestations of the inflammatory myopathies remains a challenge for the practicing rheumatologist. Although corticosteroids remain the first line of therapy, their side effects often limit their usefulness. Paradoxically, one of the side effects of steroids, muscle weakness, is the very symptom at which therapy is aimed. Other immunosuppressive agents are of proven benefit alone or in combination with corticosteroids. The identification of characteristic autoantibodies that identify poor prognostic outcomes and the availability of newer immunosuppressive regimens should contribute to a more aggressive but perhaps safer therapeutic approach to the patient with myositis.
Lower Silurian conodonts from the Shine Jinst region, southwestern Mongolia

Lower Silurian conodonts were recovered from carbonate beds in the upper Zalaa and lower Sharchuluut formations at Yamaan Us in the Shine Jinst region, Gobi-Altai Zone, of southwestern Mongolia. Conodonts are described from the Zalaa Formation for the first time; key taxa recovered include Distomodus kentuckyensis Branson and Branson, 1947, Ozarkodina hassi (Pollock, Rexroad, and Nicoll, 1970), Pranognathus siluricus (Pollock, Rexroad, and Nicoll, 1970), and Pseudolonchodina expansa (Armstrong, 1990). These species constrain the onset of the Silurian carbonate platform, upper Zalaa to lower Sharchuluut formations, to the Pranognathus tenuis Zone, middle Aeronian. The presence of a cosmopolitan conodont fauna places these strata from the Gobi-Altai Zone in a basin-shelf marine setting with connection and circulation to the open ocean during the Llandovery.
Results of a phase I trial of the proteasome inhibitor carfilzomib in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) and small lymphocytic leukemia (SLL).

7077 Background: CLL is an incurable malignancy, and survival for patients (pts) with relapsed disease is limited. Carfilzomib (CFZ) has shown efficacy in multiple myeloma, and our group has shown ...
Healthy Weight and Cardiovascular Health Promotion Interventions for Adolescent and Young Adult Males of Color: A Systematic Review:

Cardiovascular disease is the leading cause of mortality in the United States, accounting for one fourth of deaths. Higher rates of obesity put Hispanic and Black men at increased risk. The American Heart Association cites diet quality, physical activity, and body weight as alterations responsive to health promotion intervention. Prevention strategies need to begin in adolescence and the emerging adulthood years to impact cumulative risk factors. A scoping review identified search terms and this was followed by a systematic review of Cumulative Index to Nursing and Allied Health Literature (CINAHL) and PubMed databases for articles published in English from January 1, 2002, through May 11, 2017. This review explores community-based content, delivery, recruitment, or retention strategies used with young men of color aged 15 to 24 years. Of 17 articles describing 16 individual interventions and 1 describing multiple interventions (with samples ranging from 37 to 4,800), 13 reported significant results in one or more domains. No studies specifically targeted the needs of young men and only three had more than 50% male participants. There was a gap in studies that addressed young men in the ages of interest with most interventions reaching participants aged 11 to 19 years. Cultural tailoring was addressed through recruitment setting, interventionist characteristics, community involvement, and theoretical frameworks such as motivational interviewing that allow individual goal setting. Because young men seek access to preventive health services less than young women, it is suggested that interventions that are community based or use push technology (send information directly to the user) be increased.
Fit Synthesis for Robust Multiobjective Performance

Earlier in the book we saw how a number of performance specifications can be expressed as bounds on a particular transfer function or a specific combina-tion of transfer functions. Asymptotic tracking places a bound on the weighted sensitivity, noise attenuation on the weighted complementary sensitivity. The requirement of robust asymptotic tracking for plants with multiplicative norm bounded uncertaintFy is expressed as a bound on the sum of the weighted sensitivity and complementary sensitivity. In these and many other control problems there is a single bound that needs to be satisfied. Frequently, the implication this has on a robust stability formulation is that it becomes a robust stability requirement of a single feedback system or polynomial family. We have seen several examples of this in Chapters 4 and 8.
POPE: pipeline of parentally-biased expression

While one might expect the phenotypes of progeny to be an additive combination of the parents, Mendelian analysis reveals that this is not always the case. Deviations from additive expectation are observable even at the level of gene expression, and identifying such instances is a prerequisite to the understanding of gene regulation and networks. Many biological studies employ mRNA-seq to identify instances where the overall and allelic expression in hybrids deviates from expectation. We describe a pipeline, POPE (Pipeline of Parentally-biased Expression), that is capable of detecting these instances, building off of a linear model of gene expression in terms of regulatory sequence strength and concentration of synergistic transcriptional regulators. We illustrate the performance of POPE on an existing mRNA-seq data set. POPE is implemented entirely in shell, python, and R, and it is designed for unix-based platforms. The code can be found at http://www.cs.ucdavis. edu/~filkov/POPE/ .
Electron-transfer and charge-transfer clastic binding hypotheses for drug-receptor interactions

The origins and development of clastic binding hypotheses for interaction of morphines with the opiate receptor and various hallucinogens with their putative receptors are reviewed. Possible alternative explanations of the facts which led to the clastic binding hypotheses are offered. Possible integration of the clastic binding processes into other, better-recognized processes at the receptors is considered.
Venous Stenosis and Hemorrhage After Radiosurgery for Cerebral Arteriovenous Malformations

Background The risk of hemorrhage remains after radiosurgery for patients with arteriovenous malformations (AVMs), especially during the latency period. The effect of venous outflow stenosis on postradiosurgery AVM hemorrhage has been understudied. The present study sought to clarify the effect of venous stenosis on postradiation hemorrhage. Methods We retrospectively reviewed the records of patients with AVM seen at our institution from 1990 to 2015. Patients who had undergone radiosurgery were included, and those without sufficient data were excluded. We performed multivariable Cox regression to evaluate the predictors of postradiosurgery hemorrhage, with specific emphasis on venous stenosis. Patients were censored from the first radiosurgery to hemorrhage or the last follow-up visit. The baseline and angiographic characteristics were compared between those with venous stenosis and those without to address potential confounders. Results The present study included 240 patients, of whom 29 (12.1%) had venous stenosis. The venous stenosis cohort included more patients with venous varices (P = 0.009) and fewer with deep venous drainage (P = 0.048) compared with those without venous stenosis. Most patients had grade III or higher AVMs (63.2%), with an obliteration rate of 32.9%. In an all-inclusive multivariable Cox regression, hemorrhage risk was associated with venous stenosis (hazard ratio [HR], 3.70; P = 0.034), age (HR, 1.05; P = 0.002), AVM volume (HR, 1.04; P = 0.004), and hemorrhage before treatment (HR, 4.11; P = 0.014). Male gender was protective (HR, 0.31; P = 0.036) against hemorrhage. Conclusions We identified statistically significant risk factors for postradiosurgery AVM hemorrhage, which included advanced age, female gender, the presence of venous stenosis, a larger AVM volume, and previous hemorrhage. We recommend cautious selection of patients for radiosurgery with close follow-up after treatment, especially for patients with these risk factors.
Preemptive Treatment of Phantom and Residual Limb Pain with Targeted Muscle Reinnervation at the Time of Major Limb Amputation.

Background A majority of the nearly 2 million Americans living with limb loss suffer from chronic pain in the form of neuroma-related residual limb and phantom limb pain (PLP). Targeted muscle reinnervation (TMR) surgically transfers amputated nerves to nearby motor nerves for prevention of neuroma. The objective of this study was to determine whether TMR at the time of major limb amputation decreases the incidence and severity of PLP and residual limb pain. Study Design A multi-institutional cohort study was conducted between 2012 and 2018. Fifty-one patients undergoing major limb amputation with immediate TMR were compared with 438 unselected major limb amputees. Primary outcomes included an 11-point Numerical Rating Scale (NRS) and Patient-Reported Outcomes Measurement Information System (PROMIS) pain intensity, behavior, and interference. Results Patients who underwent TMR had less PLP and residual limb pain compared with untreated amputee controls, across all subgroups and by all measures. Median "worst pain in the past 24 hours" for the TMR cohort was 1 out of 10 compared to 5 (PLP) and 4 (residual) out of 10 in the control population (p = 0.003 and p Conclusions Preemptive surgical intervention of amputated nerves with TMR at the time of limb loss should be strongly considered to reduce pathologic phantom limb pain and symptomatic neuroma-related residual limb pain.
Abstract 168: Response Gene to Complement 32 Suppresses Adipose Tissue Thermogenic Genes through Inhibiting Beta3 Adrenergic Receptor mTORC1 Signaling

Our previous study have shown that response gene to complement 32 (RGC-32) deficiency (Rgc32-/-) protects mice from diet-induced obesity and increases thermogenic gene expression in adipose tissues...