cssi/SciSciGPT-SciSciNet huggingface dataset:
Protein Kinase A Regulation of P2X4 Receptors: Requirement for a Specific Motif in the C-terminus

Abstract The P2X purinergic receptor sub-family of ligand-gated ion channels are subject to protein kinase modulation. We have previously demonstrated that P2X 4 R signaling can be positively regulated by increasing intracellular cAMP levels. The molecular mechanism underlying this effect was, however, unknown. The present study initially addressed whether protein kinase A (PKA) activation was required. Subsequently a mutational approach was utilized to determine which region of the receptor was required for this potentiation. In both DT-40 3KO and HEK-293 cells transiently expressing P2X 4 R, forskolin treatment enhanced ATP-mediated signaling. Specific PKA inhibitors prevented the forskolin-induced enhancement of ATP-mediated inward currents in P2X 4 R expressing HEK-293 cells. To define which region of the P2X 4 R was required for the potentiation, mutations were generated in the cytoplasmic C-terminal tail. It was determined that a limited region of the C-terminus, consisting of a non-canonical tyrosine based sorting motif, was required for the effects of PKA. Of note, this region does not harbor any recognizable PKA phosphorylation motifs, and no direct phosphorylation of P2X 4 R was detected, suggesting that PKA phosphorylation of an accessory protein interacts with the endocytosis motif in the C-terminus of the P2X 4 R. In support of this notion, using Total Internal Reflection Fluorescence Microscopy (TIRF)\ P2X 4 -EGFP was shown to accumulate at/near the plasma membrane following forskolin treatment. In addition, disrupting the endocytosis machinery using a dominant-negative dynamin construct also prevented the PKA-mediated enhancement of ATP-stimulated Ca 2+ signals. Our results are consistent with a novel mechanism of P2XR regulation, whereby PKA activity, without directly phosphorylating P2X 4 R, markedly enhances ATP-stimulated P2X 4 R currents and hence cytosolic Ca 2+ signals. This may occur at least in part, by altering the trafficking of a population of P2X 4 R present at the plasma membrane.
Paxillin-Y118 phosphorylation contributes to the control of Src-induced anchorage-independent growth by FAK and adhesion

Focal adhesion kinase (FAK) and Src are protein tyrosine kinases that physically and functionally interact to facilitate cancer progression by regulating oncogenic processes such as cell motility, survival, proliferation, invasiveness, and angiogenesis. To understand how FAK affects oncogenesis through the phosphorylation of cellular substrates of Src, we analyzed the phosphorylation profile of a panel of Src substrates in parental and v-Src-expressing FAK+/+ and FAK-/- mouse embryo fibroblasts, under conditions of anchorage-dependent (adherent) and -independent (suspension) growth. Total Src-induced cellular tyrosine phosphorylation as well as the number of phosphotyrosyl substrates was higher in suspension versus adherent cultures. Although the total level of Src-induced cellular phosphorylation was similar in FAK+/+ and FAK-/- backgrounds, the phosphorylation of some substrates was influenced by FAK depending on adherence state. Specifically, in the absence of FAK, Src induced higher phosphorylation of p190RhoGAP, paxillin (poY118) and Crk irrespective of adhesion state, PKC-δ (poY311), connexin-43 (poY265) and Sam68 only under adherent conditions, and p56Dok-2 (poY351) and p120catenin (poY228) only under suspension conditions. In contrast, FAK enhanced the Src-induced phosphorylation of vinculin (poY100 and poY1065) and p130CAS (poY410) irrespective of adherence state, p56Dok-2 (poY351) and p120catenin (poY228) only under adherent conditions, and connexin-43 (poY265), cortactin (poY421) and paxillin (poY31) only under suspension conditions. The Src-induced phosphorylation of Eps8, PLC-γ1 and Shc (poY239/poY240) were not affected by either FAK or adherence status. The enhanced anchorage-independent growth of FAK-/-[v-Src] cells was selectively decreased by expression of paxillinY118F, but not by WT-paxillin, p120cateninY228F or ShcY239/240F, identifying for the first time a role for paxillinpoY118 in Src-induced anchorage-independent growth. Knockdown of FAK by siRNA in the human colon cancer lines HT-25 and RKO, resulted in increased paxillinpoY118 levels under suspension conditions as well as increased anchorage-independent growth, supporting the notion that FAK attenuates anchorage-independent growth by suppressing adhesion-dependent phosphorylation of paxillinY118. These data suggest that phosphorylation of Src substrates is a dynamic process, influenced temporally and spatially by factors such as FAK and adhesion.
On the norm of equality

Perceiving discrimination and unequal treatment as a problem implies an underlying value of human equality. Argues that such prescriptive equality is more powerful and more persuasive to the extent that it is built on a presumption of descriptive human equality. Explores the philosophical prerequisites for holding the presumption of actual equality. In the last part, surveys critically the general stance of economics regarding an affirmation of descriptive equality.
The gp91phox Component of NADPH Oxidase Is Not a Voltage-gated Proton Channel

During the “respiratory burst” in phagocytes, NADPH oxidase helps kill microbes by producing superoxide anion, O2−. As illustrated in the cartoon in [Fig. 1][1] , the NADPH oxidase complex has several components. In unstimulated cells, four components (p67 phox , p40 phox , p47 phox , and a G
The Equity Effects of Public Land Speculation in Iowa: Large versus Small Speculators

The economic impact of American public land policies in the nineteenth century can be assessed either in terms of their efficiency or equity effects, that is, their impact on national growth rates or on income distribution. Robert W. Fogel and Jack Rutner recently explored the growth question and discovered that federal land policy had a positive but minimal effect on economic growth in the mid-nineteenth century. This suggests that the equity question is perhaps more important than the efficiency issue, a point made several years earlier by Douglass C. North.
Adenosine 3',5'-monophosphate and thyroid hormone control of uncoupling protein messenger ribonucleic acid in freshly dispersed brown adipocytes.

We intend to develop in vitro model systems to study the hormonal regulation of uncoupling protein (UCP) and its role in brown adipose tissue (BAT) thermogenesis. We report here that UCP mRNA responses to adrenergic and thyroid hormone manipulations in freshly dispersed, mature brown adipocytes mimic in vivo observations. Studies were performed in brown adipocytes obtained from interscapular brown fat of euthyroid or hypothyroid rats. The tissue was dispersed with collagenase, and cells were isolated by floatation over 4% BSA. UCP mRNA in these cells is 2-3 times more abundant than that in the whole tissue, indicating a selection of cells expressing the gene. In cells from euthyroid rats, UCP mRNA is maximally elevated within 2 h of exposure to 1 microM forskolin and 50 ng T3/ml (77 nM total, 0.43 nM free). T3 significantly enhances the effect of forskolin. In the absence of stimulation, UCP mRNA rapidly disappears from euthyroid brown adipocytes, and this can be prevented with the addition of T3 by a mec...
Presurgical cognitive deficits in patients receiving coronary artery bypass graft surgery.

Coronary artery bypass graft (CABG) surgery with cardiopulmonary bypass (CPB) can produce a higher incidence of neuropsychological complications than other types of highly invasive noncardiac vascular surgery. Cognitive complications most likely arise from either embolization or hypoxia. An alternative surgical procedure has been developed that allows CABG to be performed without stopping the heart (“off-pump” CABG, or OPCABG). This study examined the neuropsychological performance of patients undergoing OPCABG, hypothesizing that patients undergoing OPCABG would show fewer cognitive deficits than patients whose hearts were stopped. A 1-hr neuropsychological battery was administered preoperatively to 43 patients before prospective randomization to either CPB CABG or OPCABG, and again to 34 of those patients 2 to 3 months postoperatively by an examiner blind to surgical condition. Neuropsychological status did not change 2.5 months postsurgically in either OPCABG or CABG groups. However, both groups showed dramatic presurgical cognitive deficits in multiple domains, particularly verbal memory and psychomotor speed. This corroborates previous research suggesting that patients requiring CABG surgery may evidence significant presurgical cognitive deficits as a result of existing vascular disease. ( JINS, 2003, 9, 913‐924.)
Class Struggle in Post-Revolutionary Iran

Classes are objective positions defined by the social relations of production. These positions broadly determine, among other things, the occupants' political and ideological orientations and their potential to participate in revolutionary movements. The conflict between and the contradictory nature of these positions are the underlying mechanisms for the generation and reproduction of class struggle. Nevertheless, a simple structural analysis is insufficient for analyzing the role of classes in a revolutionary movement. Classes are not static entities fixed once and for all, nor are they completely determined by “objective” economic “facts” such as the social relations of production.1 To understand the success of the dominated classes in a revolutionary movement, one must analyze their level of class formation—namely, the capacity of the members of a class to realize their interests. Class capacity is contingent, among other things, on the level of organization and mobilization of the members of the class. Rather than deriving automatically from the structural positions, class capacity is “rooted in traditional culture and communities.”2 Class boundaries, interests, and mobilization are always shifting: interests change, coalitions are formed and break up, positions in the economy are created or destroyed, and demobilization occurs.3 Classes are continually organized, disorganized, and reorganized.4 The methodological strategy adopted in this article to demonstrate the importance of class in shaping the economic policy of the Islamic Republic is based on the analysis of the significant and controversial issues that appeared in the post-revolutionary period. It will be argued that these issues were a manifestation of class struggle and that the way they were finally resolved reflected the balance of class forces.5
Crisis planning and preparedness in the United States tourism industry.

An empirical exploration of disaster planning and preparedness for the industry finds a reasonably high level of planning, with noteworthy weaknesses. Based on 155 telephone interviews with tourism leaders from three industry segments (namely, lodging, attractions, and promotions), the majority of organizations surveyed had a written crisis preparedness plan which was updated regularly—often annually. Most organizations had direct communication arrangements with local emergency preparedness agencies, but connections with national agencies, notably the Federal Emergency Management Agency, were less frequent. Given that many respondents were in destinations with many visitors (in this case, Florida), perhaps most troublesome finding was the relatively low percentage of written plans addressing procedures for visitors—mentioned by barely half of the respondents—and the relatively low participation in central relocation systems—again, just half of respondents. Overall, resource allocation had a greater impact...
Risk for immune-mediated graft dysfunction in liver transplant recipients with recurrent HCV infection treated with pegylated interferon.

Background & Aims Patients with recurrent hepatitis C virus infection treated with pegylated interferon (PEG) after liver transplantation can develop severe immune-mediated graft dysfunction (IGD) characterized by plasma cell hepatitis or rejection. Methods We conducted a multicenter case-control study of 52 liver transplant recipients with hepatitis C to assess the incidence of, risk factors for, and outcomes of PEG-IGD. Data from each patient were compared with those from 2 matched patients who did not develop PEG-IGD (n = 104). We performed a multivariate analysis of risk factors and analyzed treatment and outcomes of graft dysfunction subtypes. Results Overall incidence of PEG-IGD during a 10-year study period was 7.2%. Risk factors included no prior PEG therapy (odds ratio=5.3; P P = .03), and immune features (mainly plasma cell hepatitis) on pre-PEG therapy liver biopsies (odds ratio=3.9; P = .005). The PEG-IGD group had lower long-term patient (61.5% vs 91.3% of controls) and graft (38.5% vs 85.6% of controls) survival and higher rates of retransplantation (34.6% vs 6.7% of controls) (all, P P = .002), a high level of alkaline phosphatase at PEG initiation (HR = 1.003; P = .005), and lack of a sustained virologic response (HR = 3.3; P = .04). Variables associated with graft failure included a high level of alkaline phosphatase at PEG initiation (HR = 1.002; P = .04) and lack of a sustained virologic response (HR = 2.1; P = .04). Conclusions PEG-IGD has high morbidity and mortality and is not associated with increased rates of virologic response. It is important to avoid PEG therapy in liver transplant recipients with specific clinical, biochemical, and histologic risk factors for PEG-IGD.
Histopathological characterization of cholecystectomy specimens in patients with inflammatory bowel disease

Background and aims: Inflammatory bowel disease is associated with increased risk of cholelithiasis. However, the histologic patterns in gallbladders have not been extensively studied. This study is designed to characterize the histopathologic features of cholecystectomy specimens in inflammatory bowel disease patients, compared to a control group. Methods: Cholecystectomy specimens in 78 Crohn's disease patients and 50 ulcerative colitis patients were reviewed. These were compared with 93 cholecystomies from noninflammatory bowel disease patients of approximate age and sex. The pattern and extent of inflammation was noted. Results: Markedchroniccholecystitiswaspresentin12%ofulcerativecolitispatients(Pb0.05)and 10.3% of Crohn's disease patients (PN0.05), compared to 4.3% of the noninflammatory bowel disease control group. Eight percent of ulcerative colitis patients (Pb0.05) and 2.6% ofCrohn's disease patients (PN0.05) had acute serositis, compared to 0% of the noninflammatory bowel disease control. The third inflammatory pattern, nodular lymphoid aggregates, was significantly increased in Crohn's disease patients after adjusting for the effect of cholelithiasis. Nodular lymphoid aggregates were found in 21.2% ofCrohn's disease patients and 9.7% of ulcerative colitis patients without cholelithiasis, compared to 5% of noninflammatory bowel disease controls without cholelithiasis, a statistically significant difference between the Crohn's disease and control groups (Pb0.05). Conclusions: Inflammatoryboweldiseasepatientsshow similarinflammatorypatternsincholecystectomy specimens comparedto thegeneral population. However, twoinflammatory patterns that
Pediatric Lingual and Other Intraoral Lesions

This article explores pediatric lingual and other intraoral lesions. First the embryology and anatomy of the oral anatomy is outlined. Then the article discusses infections and inflammatory diseases, congenital malformations, benign neoplasms, and malignant tumors.
Symptomatic middle cerebral artery stenosis.

The clinical course of 16 consecutive patients with stenosis of the middle cerebral artery angiographically diagonosed between 1970 and 1977 was reviewed. All were managed nonsurgically with medical treatment including anticoagulation. Prior to therapy, transient ischemic attacks had occurred in 15 and cerebral infarction in 11. Initially, none exhibited more than a minor neurological deficit. Follow-up from one month to six years showed a benign course in 14 patients: 13 experienced no subsequent transient attacks or new stroke; 1 had repeated transient attacks for two years but not in the following four years. Two of the 16 developed a severe stroke early in the course, before medical therapy was started. No distinctive clinical or radiographic features were identified that permitted prediction of the outcome. This small series supports the need for a randomized study of bypass efficacy in these patients.
Search for peptide sequences involved in human antisperm antibody-mediated male immunoinfertility by using phage display technology.

The aim of the present study was to delineate peptide sequences against which anti- sperm antibodies (ASA) are raised in immunoinfertile men. Using the phage display technology, seven unique and novel dodecamer amino acid sequences were identified that reacted with the sera of immu- noinfertile men. The peptides were synthesized based upon these amino acid sequences and examined for their immunoreactivity with sera from ASA-positive immunofertile men (n ¼ 15) and ASA-negative fertile men (n ¼ 18) for IgM, IgG, and IgA class of antibody in the enzyme-linked immunosorbent assay (ELISA). All the seven synthetic peptides showed a significantly (P 2S D units) with 27%-40% of immunoinfertile sera com- pared to fertile controls. These peptide sequences may find applications in the specific diagnosis and treat- ment of immunoinfertility and in contraceptive vaccine development. The phage display technique provides an exciting and novel technology to delineate sperm epitopes involved in immunoinfertility. Mol. Reprod. Dev. 72: 25-30, 2005. 2005 Wiley-Liss, Inc.
Abnormal motor phenotype in the SMNΔ7 mouse model of spinal muscular atrophy

Spinal muscular atrophy (SMA) is a recessive motor neuron disease that affects motor neurons in the anterior horn of the spinal cord. SMA results from the reduction of SMN (survival motor neuron) protein. Even though SMN is ubiquitously expressed, motor neurons are more sensitive to the reduction in SMN than other cell types. We have previously generated mouse models of SMA with varying degrees of clinical severity. So as to more clearly understand the pathogenesis of motor neuron degeneration in SMA, we have characterized the phenotype of the SMNDelta7 SMA mouse which normally lives for 13.6+/-0.7 days. These mice are smaller than their non-SMA littermates and begin to lose body mass at 10.4+/-0.4 days. SMNDelta7 SMA mice exhibit impaired responses to surface righting, negative geotaxis and cliff aversion but not to tactile stimulation. Spontaneous motor activity and grip strength are also significantly impaired in SMNDelta7 SMA mice. In summary, we have demonstrated an impairment of neonatal motor responses in SMNDelta7 SMA mice. This phenotype characterization could be used to assess the effectiveness of potential therapies for SMA.
Beware the Air!: Why Particulate Matter Matters

See related article, pages 716 – 726 The “Six Cities Study,” as it is affectionately known by epidemiologists, was published in 1993. This landmark study laid the groundwork for an association between ambient air particulate matter (ie, fine particulate matter [PM] or PM2.5 [particulate matter of 2.5 μm aerodynamic diameter or less]) and the risk of all cause mortality in the United States.1 Simply put, the message of the study was: “Air pollution kills.” Since then, a steady stream of studies has grown into a river of reports that collectively have swelled the banks of this initial association and have further specified that ischemic heart disease (cardiovascular disease [CVD]) is the single-most abundant cause of morbidity and mortality in this association.2,–,4 Analysis of more than 100 studies (>100 million people in 119 cities in the United States and Europe) show that for each 10 μg/m3 acute or chronic increase in PM2.5, there is a significant increase in relative risk of cardiovascular mortality (chronic relative risk, 1.06 to 1.76), indicating that PM, even at ambient levels, has negative health consequences.4 Moreover, chronic exposure to each 10 μg/m3 PM2.5 increase is associated with a 4 to 6% increase in CVD deaths, which translates to 800 000 deaths annually in the world (according to the World Health Organization), making PM exposure the 13th leading cause of CVD deaths4 and, thus, deserving of urgent scientific and social attention. Currently, researchers in the field of environmental cardiology5 are addressing at least 1 of 2 major unanswered questions regarding this association: (1) What constituent of inhaled PM2.5 is responsible for the association?; and (2) What is the mechanism by which inhaled PM2.5 can specifically affect cardiovascular disease risk? In …
Analysis of Limb Morphogenesis in a Model System

Abstract A method for analysis of chicken limb morphogenesis was devised. This method consisted of grafting a limb ectodermal jacket containing dissociated and pelleted mesenchymal cellular components to the host somites. Different cellular components stuffed into the ectoderm could be mixed in varied ratios. After 7 days the grafts were analyzed for outgrowth. Stage 19 mesoblast cells alone when treated as above gave limblike outgrowths with good digits, toes, and claws in all cases. However, mesoblasts from the proximal half of older limbs (stages 24, 25 and chondrocytes) gave no outgrowths, and those from stage 23 gave outgrowths in 9% of the cases. In mixtures of 5% stage 19 cells with 95% chondrocytes, consistent morphogenesis (i.e., in 65% of grafts) occurred. The amount of morphogenesis (size of graft and perfection of digits) was directly proportional to the amount of stage 19 cells. However, these cells mixed with proximal cells of stages 23, 24, or 25 required higher proportions for equivalent morphogenesis. To obtain morphogenesis equivalent to the 5% mixture with chondrocytes, 10% stage 19 cells were needed when mixed with proximal stage 23, 25% with proximal stage 24 and 7% with proximal stage 25. Mixtures of stage 19 cells added to nonlimb (flank, stage 19) mesoderm, formed large tumorous mounds of tissue with no limblike features.
Crucified by God: Kazantzakis and the Last Anfechtung of Christ

Christ's struggles in Nikos Kazantzakis's The Last Temptation against temptations of the flesh and trials of the spirit can be read as a post/modern analogy of the differentiation—as formulated by Martin Luther and reaffirmed by Soren Kierkegaard—between earthly ‘temptation’ [Versuchung] and divinely instigated spiritual trial [Anfechtung]. Moreover, Kazantzakis's novel enriches previous literature on Anfechtung by vividly and appositely illustrating how Anfechtung and temptation may coexist antagonistically within the same trial of Christ. Through this Kierkegaardian-Lutheran lens, Kazantzakis's novel may thus be read as evocatively transcribing a humanistic rendition of the angefochtene Christus which implicitly collapses the ‘infinite qualitative difference’ between humanity and divinity so essential to Kierkegaard's own modern rehabilitation of the archaic notion of Anfechtung.‘God himself is crucifying him!’ 1
When to use a compilation service

Modern handheld computers are certainly capable of running general purpose applications, such as Java virtual machines. However, short battery life rather than computational capability often limits the usefulness of handheld computers. This paper considers how to reduce the energy consumption of Java applications.Broadly speaking, there are three interleaved steps in running Java programs in a compiled environment: downloading the bytecodes, compiling and possibly optimizing the bytecodes, and running the compiled code. Optimized code typically runs faster than non-optimized code but the optimization process itself may consume significant energy. We consider the possibility of moving compilation (optimizing or non-optimizing) to a tethered server. We demonstrate that there is a significant benefit to moving compilation to a server (up to 67% reduction in energy for a realistic handheld configuration). We also demonstrate that there is no single best compilation strategy for all methods.
Lack of synergy between phagocytes and antimicrobials against Nocardia asteroides

Previous observations suggested that synergy between antimicrobials and phagocytes may occur during Nocardia asteroides infection. We incubated N. asteroides with seven antimicrobials, and then exposed the nocardiae to phagocytes. Neutrophils and monocytes killed about half the nocardiae whether or not the nocardiae had been preincubated with antimicrobials. We also determined whether exposure to neutrophils led to increased susceptibility of nocardiae to antimicrobials, and it did not. We found no evidence for synergy between antimicrobials and phagocytes in host defence against this bacterium.
Load-sensitive transmission loss pricing considering wind energy

Although deregulation of power systems in most of the cases is considered as a worthy progress, however, for the operation and maintenance of this brand new environment, the associated new issues have to be clarified and solved. In this paper, a new method for pricing the transmission loss is proposed. The proposed method is fundamentally based on zero cash balance of the market. The idea of this paper for the loss allocation process is to consider and integrate the time of consumption into the cost of allocated losses to one party. That means the price of loss would not be the same as the price of power at same interval. This price of loss is a function of both market clearing price and the time of transmitting power. The method has been implemented and tested on several types of markets and two samples are summarized in the paper. The results show that the method has an acceptable performance in various situations.
CONFLUENT POSSIBILITY DISTRIBUTIONS AND THEIR REPRESENTATIONS

Abstract Possibilistic distributions admit both measures of uncertainty and (metric) distances defining their information closeness. For general pairs of distributions these measures and metrics were first introduced in the form of integral expressions. Particularly important are pairs of distributions p and q which have consonant ordering—for any two events x and y in the domain of discourse p(x)l p(y) if and only if q(x) l q(y). We call such distributions confluent and study their information distances. This paper presents discrete sum form of uncertainty measures of arbitrary distributions, and uses it to obtain similar representations of metrics on the space of confluent distributions. Using these representations, a number of properties like additivity. monotonicity and a form of distributivity are proven. Finally, a branching property is introduced, which will serve (in a separate paper) to characterize axiomatically possibilistic information distances.
Scanning electron microscopy of human spermatozoa after incubation with the spermicide nonoxynol-9

Scanning electron microscopy was used to assess the extent of membrane damage due to the direct action of nonoxynol-9 during an incubation period of 5 minutes. Nonoxynol-9 is the most frequently utilized spermicide in vaginal contraceptives. Nonoxynol-9 disrupted sperm membranes in all regions except the postacrosomal region and tail. It caused loosening and detachment of acrosomal neck and midpiece membranes of all sperm even at the lowest concentration tested (0.05%). Damage to all membranes was 1st evident as vesiculations then membranes became loose and detached. The severity of membrane alterations observed in any of these regions would render sperm immotile and unable to penetrate the ovum. A dose-response relationship was not apparent and there was no variation in response among sperm donors. The fact that these alterations are produced within 5 minutes confirms the effectiveness of nonoxynol-9 as a vaginal contraceptive. Scanning electron microscopy proved to be well suited for evaluating the extent of damage caused by nonoxynol-9 and provided more information than transmission electron microscopy.
DHBP Block of Ryanodine Receptor Channels

1,1′-diheptyl-4,4′-bipyridinium dibromide (DHBP), a divalent organic cation, was reported to inhibit muscle contraction, which was attributed to inhibition of ryanodine receptor (RyR) mediated Ca2+ release from the sarcoplasmic reticulum (SR). Still, single RyR channel studies are lacking and the mechanism by which DHBP blocks RyRs is unknown. We reconstituted RyRs from skeletal muscle and heart SR microsomes into planar bilayers. We observed with DHBP addition to the cytosolic surface of RyRs (clamped at Vm = 0 mV) decreased channel conductance (IC50 ∼ 1 mM). The percentage block in channel conductance elicited by DHBP was invariable in the range −30 to +30 mV. DHBP did not affect RyR gating characteristics, which was measured under Ca2+ conditions that produced low, moderate or high Po and in the presence/absence of physiological modulators (ATP, Mg2+). DHBP added to luminal and cytosolic sides of the RyRs, resulted in additive effects on channel conductance. DHBP also induced inhibition of RyR-mediated SR Ca2+ release from skeletal SR microsomes. A similar block of RyRs conductance was observed with other bipyridinum derivatives, none of which affected SERCA ATPase activity. Previous reports in the literature indicated block of RyRs by DHBP in cells required lower drug concentrations, suggesting a possible cellular mechanism of DHBP accumulation. In summary, DHBP blocks RyRs Ca2+ conductance resembling the action of polyamines and organic cations. DHBP properties make it an attractive experimental probe for understanding the role of RyR conductance in Ca2+ release from intracellular Ca2+ stores (Supported by American Heart Association and Eskridge Foundation).
Limited Trabecular Bone Density Heterogeneity in the Human Skeleton.

There is evidence for variation in trabecular bone density and volume within an individual skeleton, albeit in a few anatomical sites, which is partly dependent on mechanical loading. However, little is known regarding the basic variation in trabecular bone density throughout the skeleton in healthy human adults. This is because research on bone density has been confined to a few skeletal elements, which can be readily measured using available imaging technology particularly in clinical settings. This study comprehensively investigates the distribution of trabecular bone density within the human skeleton in nine skeletal sites (femur, proximal and distal tibia, third metatarsal, humerus, ulna, radius, third metacarpal, and axis) in a sample of individuals (11 males and 9 females). pQCT results showed that the proximal ulna (mean = 231.3 mg/cm3) and axis vertebra (mean = 234.3 mg/cm3) displayed significantly greater () trabecular bone density than other elements, whereas there was no significant variation among the rest of the elements (). The homogeneity of the majority of elements suggests that these sites are potentially responsive to site-specific genetic factors. Secondly, the lack of correlation between elements () suggests that density measurements of one anatomical region are not necessarily accurate measures of other anatomical regions.
"Plug-and-go" strategy to manipulate streptavidin valencies.

The streptavidin–biotin set is one of the most widely utilized conjugation pairs in biotechnological applications. The tetravalent nature of streptavidin and its homologues, however, tends to result in such undesirable complications as cross-linking or ill-defined stoichiometry. Here, we describe a mutagenesis-free strategy to manipulate the valencies of wild-type streptavidin that only requires commercially available reagents. The basic idea is simple: one obtains the desired streptavidin valency by blocking off unwanted binding sites using ancillary biotin (“plug”); this way, the extraordinary fM-biotin-binding affinity is fully retained for the remaining sites in streptavidin. In the present implementation, the ancillary biotin is attached to an auxiliary separation handle, negatively charged DNA or His-tagged protein, via a photochemically or enzymatically cleavable linker. Mixing streptavidin with the ancillary biotin construct produces a distribution of streptavidin valencies. The subsequent chromat...
Is There an Optimal Size of Fiscal Reserves for Local Governments

This chapter examines the topic of the optimal size of fiscal reserves. The fundamental question of whether there is an optimal level of reserves is considered, along with the elements of a model of the optimal reserve size. We examine existing research on the topic, and then build a model of reserves using a forecast simulation approach. We first develop a forecast model using data from a local government. The forecast model consists of two time-series systems equations. The first equation contains economic variables, producing a forecast of the local economy. Those forecasts then enter the second equation as predictors of revenues and expenditures. We then simulate the equations going forward to produce estimates of revenues and expenditures for the government, thus leading us to the level of fiscal reserves that should be required to cover potential shortfalls.
The dark double: the American media perception of Russia as a neo-Soviet autocracy, 2008–2014

This article combines quantitative and textual analysis of editorials in leading American newspapers devoted to Russia’s internal politics from 2008 to 2014. Despite rapprochement under President D...
Presurgical Dentofacial Orthopedic Management of the Cleft Patient

Over the last decade, presurgical orthopedic molding for the patient with cleft lip and palate has become much more common; it is even reasonable to assume it may be the standard of care for those wide unilateral and bilateral clefts with substantial dentofacial deformities. In 2013, there was a comparative study of nasoalveolar molding methods, comparing the Grayson-NAM device and DynaCleft. The results showed the 2 to be equivocal with both methods significantly reducing the cleft width and improving the nasal asymmetry.
Tweeting to Health: A Novel mHealth Intervention Using Fitbits and Twitter to Foster Healthy Lifestyles.

We developed and pilot tested a mHealth intervention, “Tweeting to Health,” which used Fitbits, Twitter, and gamification to facilitate support for healthy lifestyle changes in overweight/obese (OW) and healthy weight (HW) young adults. Participants tracked activity and diet using Fitbits and used Twitter for messaging for 2 months. Physical activity, dietary intake, and Tweets were tracked and participants completed surveys at enrollment, 1 month, and 2 months. Descriptive statistics were used to examine steps/day, physical activity intensity, lifestyle changes, and total Tweets. Participants were on average 19 to 20 years old and had familiarity with Twitter. OW participants had on average 11 222 daily steps versus 11 686 (HW). One-day challenges were successful in increasing steps. Participants increased fruit/vegetable intake (92%) and decreased their sugar-sweetened beverage intake (67%). Compliance with daily Fitbit wear (99% of all days OW vs 73% HW) and daily dietary logging (82% OW vs 73% HW) and...
The contribution of maternal psychological functioning to infant length of stay in the Neonatal Intensive Care Unit

Objective Assess maternal psychological functioning within the Neonatal Intensive Care Unit (NICU) and its contribution to neonate length of stay (LOS) in the NICU. Study design Mothers of infants admitted to the NICU (n=111) were assessed regarding postpartum depression, postpartum social support, postpartum NICU stress, and maternal anxiety at 2 weeks postpartum. Illness severity was assessed with the Clinical Risk Index for Babies (CRIB). Results Postpartum depression was not significantly correlated with LOS, but was significantly correlated with trait anxiety (r=0.620), which was significantly correlated with LOS (r=0.227). Among mothers with previous mental health history, substance abuse history and CRIB score were the best predictors of LOS. For mothers without a prior mental health issues, delivery type, stress associated with infant appearance, and CRIB scores were the best predictors of LOS. In this group, LOS was found to increase on average by 7.06 days per one unit increase in stress associated with infant appearance among mothers with the same delivery type and CRIB score. Conclusion Significant correlations of trait anxiety, stress associated with infant appearance, and parental role with LOS support the tenet that postpartum psychological functioning can be associated with NICU LOS.
Environments Conducive to Latin American Arms Production

Chapter 6 discussed several factors associated with arms production and arms imports. One of the major findings of that chapter was the apparent association between resource constraints, arms production, and arms imports. In general, it appeared that arms producers1 tend to be countries that have sufficient foreign exchange2 to support a continuing stream of imported components and support for their military industries. On the other hand it appeared that non-producers were relatively constrained in terms of available foreign exchange.3
Microstructure and mechanical properties of titanium aluminum carbides neutron irradiated at 400–700°C

Abstract This work reports the first mechanical properties of Ti 3 AlC 2 -Ti 5 Al 2 C 3 materials neutron irradiated at ∼400, 630 and 700 °C at a fluence of 2 × 10 25 n m −2 (E > 0.1 MeV) or a displacement dose of ∼2 dpa. After irradiation at ∼400 °C, anisotropic swelling and loss of 90% flexural strength was observed. After irradiation at ∼630–700 °C, properties were unchanged. Microcracking and kinking-delamination had occurred during irradiation at ∼630–700 °C. Further examination showed no cavities in Ti 3 AlC 2 after irradiation at ∼630 °C, and MX and A lamellae were preserved. However, disturbance of (0004) reflections corresponding to M-A layers was observed, and the number density of line/planar defects was ∼10 23 m −3 of size 5–10 nm. HAADF identified these defects as antisite Ti Al atoms. Ti 3 AlC 2 -Ti 5 Al 2 C 3 shows abrupt dynamic recovery of A-layers from ∼630 °C, but a higher temperature appears necessary for full recovery.
Sco2 deficient mice develop increased adiposity and insulin resistance

Cytochrome c oxidase (COX) is an essential transmembrane protein complex (Complex IV) in the mitochondrial respiratory electron chain. Mutations in genes responsible for the assembly of COX are associated with Leigh syndrome, cardiomyopathy, spinal muscular atrophy and other fatal metabolic disorders in humans. Previous studies have shown that mice lacking the COX assembly protein Surf1 (Surf1-/- mice) paradoxically show a number of beneficial metabolic phenotypes including increased insulin sensitivity, upregulation of mitochondrial biogenesis, induction of stress response pathways and increased lifespan. To determine whether these effects are specific to the Surf1 mutation or a more general effect of reduced COX activity, we asked whether a different mutation causing reduced COX activity would have similar molecular and physiologic changes. Sco2 knock-in/knock-out (KI/KO) mice in which one allele of the Sco2 gene that encodes a copper chaperone required for COX activity is deleted and the second allele is mutated, have previously been shown to be viable despite a 30-60% reduction in COX activity. In contrast to the Surf1-/- mice, we show that Sco2 KI/KO mice have increased fat mass, associated with reduced β-oxidation and increased adipogenesis markers, reduced insulin receptor beta (IR-β levels in adipose tissue, reduced muscle glucose transporter 4 (Glut4) levels and a impaired response to the insulin tolerance test consistent with insulin resistance. COX activity and protein are reduced approximately 50% in adipose tissue from the Sco2 KI/KO mice. Consistent with the increase in adipose tissue mass, the Sco2 KI/KO mice also show increased hepatosteatosis, elevated serum and liver triglyceride and increased serum cholesterol levels compared to wild-type controls. In contrast to the Surf1-/- mice, which show increased mitochondrial number, upregulation of the mitochondrial unfolded protein response (UPRMT) pathway and no significant change in mitochondrial respiration in several tissues, Sco2 KI/KO mice do not upregulate the UPRMT, and tissue oxygen consumption and levels of several proteins involved in mitochondrial function are reduced in adipose tissue compared to wild type mice. Thus, the metabolic effects of the Sco2 and Surf1-/- mutations are opposite, despite comparable changes in COX activity, illuminating the complex impact of mitochondrial dysfunction on physiology and pointing to an important role for complex IV in regulating metabolism.
Which Matters: Demand of Bond or Supply of Bond?

This paper provides a basic quantitative description of a compendium of macro economic variables based on their ability to predict bond returns and stock returns. We use three methods (asymptotic PCA ,LASSO, and SVM) to construct factors out of 133 monthly time series of economic activity spanning a period from 1996:1 to 2015:12 and classify these factors into two groups: bond demand factors and bond supply factors. In PCA regression, we find both demand factors and supply factors are unspanned by bond yields and have strong predictability power for future bond excess returns beyond CP factors. This predictability finding is con firmed and enhanced by machine learning technique LASSO and SVM. More interestingly, LASSO can be used to identify 15 most important economic variables and give direct economic meanings to both demand factors and supply factors. Regarding to stock predictability, we find both demand and supply factors are priced by the cross-section of stock returns. In particular, portfolios with highest exposure to aggregate supply factor outperform portfolios with lowest exposure to aggregate supply factor 1.8% per month while portfolios with lowest exposure to aggregate demand factor outperform portfolios with highest exposure to aggregate demand factor 2.1% per month. This finding is consistent with "fly to safety" explanation. Furthermore, variance decomposition from VAR shows that demand factors are much more important than supply factors in explaining asset returns. Finally, we incorporate demand factors and supply factors into macro-finance affine-term structure (MTSMs) to estimate market price of risk of factors and find that demand factors affect level risk and supply factors affect slope risk. Moreover, MTSMs enable us to decompose bond yields into expectation component and yield risk premium component and we find MTSMs without macro factors under-estimate yield risk premium.
The fibularis digiti quinti tendon: A cadaveric study with anthropological and clinical considerations

In addition to the fibularis longus and brevis muscles, a number of anomalous muscles or tendons can arise from the lateral compartment of the leg. The authors describe a bilateral and robust fibularis digiti quinti (FDQ) tendon present in the foot of a 99-year-old female cadaver, present the incidence of this tendon in a cohort of 26 cadavers dissected by podiatric-medical students for a lower-extremity anatomy course, and discuss the anthropological and clinical significance of the findings. In these specimen, the FDQ tendon arose from the fibularis brevis tendon proximal to the lateral malleolus, but did not separate completely from the fibularis brevis tendon until passing through the inferior fibular retinaculum. On the lateral dorsum of the foot, the FDQ passed through a third fibular retinaculum formed by the fibularis tertius tendon, and inserted onto the extensor sling of the fifth digit. This case specimen is designated as an example of the fully present category. Of the 52 limbs dissected, 17 limbs (33%) showed a fully present FDQ, while 20 limbs (38%) exhibited an FDQ in a rudimentary form. Thus, 71% of the limbs showed some presence of the FDQ. Because human bipedality requires less dexterity than that of nonhuman primates in the routine use of their hindlimbs, the authors interpret the high variability of the FDQ, including its absence in many feet, as a relaxation of natural selection maintaining this trait since the divergence of humans from African apes.
Siete símbolos-clave para perderse alegremente en los laberintos de Borges

En la literatura de Jorge Luis Borges hay simbolos que reaparecen una y otra vez. Cuando comprenden esos simbolos, a los lectores se les da permiso para ingresar en el terreno de la obra y de la mente laberintica de Borges. Los simbolos son: el laberinto, el libro, el espejo, el tigre, el coraje de la ironia, las palabras que tambien son musica, y el amigo. Los cuatro primeros simbolos son instrumentos que el autor utiliza para causar en el lector un sentimiento de desorientacion (el laberinto), una curiosidad que nunca queda satisfecha (el libro), la conciencia de un yo multiple (el espejo), y la anticipacion de la muerte (el tigre). Los tres simbolos restantes proveen, en cierto modo, un paliativo frente al pesimismo melancolico surgido desde los tres primeros simbolos. El coraje de la ironia y las palabras que son musica hacen posible cierta alegria individual dentro del universo borgesiano. Y, finalmente, para quienes anhelan escapar del aislamiento, el amigo permite dibujar una apertura metafisica posible hacia regiones de intimidad con otros seres humanos.
Extended cardiac ambulatory rhythm monitoring in adults with congenital heart disease: Arrhythmia detection and impact of extended monitoring.

Background Arrhythmias are a leading cause of death in adults with congenital heart disease (ACHD). While 24-48-hour monitors are often used to assess arrhythmia burden, extended continuous ambulatory rhythm monitors (ECAM) can record 2 weeks of data. The utility of this device and the arrhythmia burden identified beyond 48-hour monitoring have not been evaluated in the ACHD population. Additionally, the impact of ECAM has not been studied to determine management recommendations. Objective To address the preliminary question, we hypothesized that clinically significant arrhythmias would be detected on ECAM beyond 48 hours and this would lead to clinical management changes. Methods A single center retrospective cohort study of ACHD patients undergoing ECAM from June 2013 to May 2016 was performed. The number and type of arrhythmias detected within and beyond the first 48 hours of monitoring were compared using Kaplan-Meier curves and Cox proportional hazard models. Results Three hundred fourteen patients had monitors performed [median age 31 (IQR 25-41) years, 61% female). Significant arrhythmias were identified in 156 patients (50%), of which 46% were noted within 48 hours. A management change based on an arrhythmia was made in 49 patients (16%). Conclusions ECAM detects more clinically significant arrhythmias than standard 48-hour monitoring in ACHD patients. Management changes, including medication changes, further testing or imaging, and procedures, were made based on results of ECAM. Recommendations and guidelines have been made based on arrhythmias on 48-hour monitoring; the predictive ability and clinical consequence of arrhythmias found on ECAM are not yet known.
Vegetation response to wildfire and climate forcing in a Rocky Mountain lodgepole pine forest over the past 2500 years

Wildfire is a ubiquitous disturbance agent in subalpine forests in western North America. Lodgepole pine (Pinus contorta var. latifolia), a dominant tree species in these forests, is largely resili...
Elastic fields in superconductors caused by moving vortices

Strains in superconductors due to moving vortices and vortex lattices are discussed. It is shown that the energy stored in elastic strains increases with vortex velocity. For moving vortex lattices, the elastic energy depends on velocity orientation relative to the lattice having minimum for the velocity directed along one of the unit cell vectors of the moving lattice. It is shown that for supersonic motion, the vortex-induced stress field has a shape similar to supersonic shock waves.