cssi/SciSciGPT-SciSciNet huggingface dataset:
The RtcB RNA ligase is an essential component of the metazoan unfolded protein response

RNA ligation can regulate RNA function by altering RNA sequence, structure and coding potential. For example, the function of XBP1 in mediating the unfolded protein response requires RNA ligation, as does the maturation of some tRNAs. Here, we describe a novel in vivo model in Caenorhabditis elegans for the conserved RNA ligase RtcB and show that RtcB ligates the xbp-1 mRNA during the IRE-1 branch of the unfolded protein response. Without RtcB, protein stress results in the accumulation of unligated xbp-1 mRNA fragments, defects in the unfolded protein response, and decreased lifespan. RtcB also ligates endogenous pre-tRNA halves, and RtcB mutants have defects in growth and lifespan that can be bypassed by expression of pre-spliced tRNAs. In addition, animals that lack RtcB have defects that are independent of tRNA maturation and the unfolded protein response. Thus, RNA ligation by RtcB is required for the function of multiple endogenous target RNAs including both xbp-1 and tRNAs. RtcB is uniquely capable of performing these ligation functions, and RNA ligation by RtcB mediates multiple essential processes in vivo.
Hyperbaric oxygenation treatment alleviates CCI-induced neuropathic pain and decreases spinal apoptosis.

Background Increased apoptotic changes in the spinal cord may be responsible for the development of chronic constriction injury (CCI)-induced neuropathic pain. We previously reported the beneficial effect of hyperbaric oxygen (HBO) in the treatment of CCI-induced neuropathic pain. In this study, we tested our hypotheses that HBO may achieve its beneficial effect by inhibiting CCI-induced proapoptosis gene expression and apoptosis in the spinal cord. Methods Male rats were randomized into: SHAM, CCI and CCI + HBO groups. Mechanical hyperalgesia was tested daily following surgery. CCI + HBO rats were treated with HBO for 1 h daily. At 3 days post-CCI, the expression of tumour necrosis factor (TNF)-α and caspase-3 genes was detected. At 7 days post-CCI, apoptotic cells in the spinal cord were detected. Results Three days post-CCI, mechanical allodynia had developed in the ipsilateral paw compared with SHAM animals. HBO significantly alleviated CCI-induced mechanical allodynia. In comparison with SHAM, CCI-induced neuropathic pain was associated with higher mRNA levels of TNF-α and caspase-3. HBO significantly decreased CCI-induced mRNA levels of TNF-α and caspase-3. CCI-induced neuropathic pain was also associated with more apoptotic cells in the spinal cord 7 days post-CCI. HBO significantly reduced CCI-induced apoptosis to the level of SHAM animals. Conclusions Overly expressed proapoptosis genes, and subsequent increase in spinal apoptotic cells, seem to contribute to the development of CCI-induced neuropathic pain. The inhibitory role of HBO on spinal proapoptosis genes and apoptotic changes may contribute to its beneficial effect on CCI-induced neuropathic pain.
Surgery Is Preferred for the Diabetic With Multivessel Disease

When angioplasty was first introduced by Andreas Gruentzig in 1977, it was envisioned as a treatment for angina pectoris refractory to medical therapy but applicable to patients who might otherwise have undergone bypass surgery. Assessment of patients before the intervention included exercise stress testing documenting ischemia, and the lesions selected for treatment were those that could be attempted using the primitive balloon angioplasty equipment that was available at that time. As the equipment for percutaneous coronary interventions (PCIs) improved, the technique was expanded to encompass a larger population of patients who otherwise would have been referred for bypass surgery. By 1990, the frequency of coronary angioplasty had increased to equal that of coronary bypass surgery. By the end of the decade, almost twice as many percutaneous interventions were being performed as were coronary bypass surgical procedures.1 As angioplasty began to infringe on the domain of bypass surgery, there was a call for randomized control trials testing the comparative value of angioplasty in traditionally surgical applications. Andreas Gruentzig proposed such a trial when angioplasty had reached a degree of maturity 6 years after the first procedure was performed. National Heart, Lung, and Blood Institute (NHLBI) funding for the first comparison of bypass surgery and angioplasty was finally obtained, and the Emory Angioplasty versus Surgery Trial (EAST) was begun in 1987, 2 years after Gruentzig’s tragic death.2 A second multicenter randomized trial, the Bypass Angioplasty Revascularization Investigation (BARI), was also approved by the NHLBI and was begun 1 year after the initiation of the EAST trial. The outcomes of these trials confirmed the overall equivalence of angioplasty and bypass surgery for patients suitable for angioplasty and were consistent with other trials initiated in Europe and South America.3 However, when the 5-year outcome of the BARI trial was reported in …
On the state-space design of optimal controllers for distributed systems with finite communication speed

We consider the problem of designing optimal distributed controllers whose impulse response has limited propagation speed. We introduce a state-space framework in which such controllers can be described. We show that the optimal control problem is not convex with respect to certain state-space design parameters, and demonstrate a reasonable relaxation that renders the problem convex. This relaxation is associated with an iterative numerical scheme known as the Steiglitz-McBride (SM) algorithm. We improve the SM algorithm by using the algebraic Lyapunov equation to relieve time integration, thus significantly reducing computational costs.
Science, the Sea, and Marine Resource Management: Researching the International Council for the Exploration of the Sea

The International Council for the Exploration of the Sea (ICES) has since its founding in 1902 provided a forum for many branches of marine science and embraced a practical mission, to promote fisheries. ICES commissioned a history for its centenary. This paper reflects on how researching ICES history melded public history with environmental history and history of science. All three traditions were essential to understand its institutional development as well as the impact it had on North Atlantic marine resource utilization. More broadly, marine environmental history, to date a virtually nonexistent field, also demands the concert of these three traditions, as well as the international approach that naturally accompanied ICES history.
Overexpression of 17β-hydroxysteroid dehydrogenase type 10 increases pheochromocytoma cell growth and resistance to cell death

Background 17β-hydroxysteroid dehydrogenase type 10 (HSD10) has been shown to play a protective role in cells undergoing stress. Upregulation of HSD10 under nutrient-limiting conditions leads to recovery of a homeostatic state. Across disease states, increased HSD10 levels can have a profound and varied impact, such as beneficial in Parkinson’s disease and harmful in Alzheimer’s disease. Recently, HSD10 overexpression has been observed in some prostate and bone cancers, consistently correlating with poor patient prognosis. As the role of HSD10 in cancer remains underexplored, we propose that cancer cells utilize this enzyme to promote cancer cell survival under cell death conditions.
Abortion and human nature

According to the future of value argument for the immorality of abortion, the best explanation for the presumptive serious wrongness of killing innocent post-natal children and adults is that killing them deprives them of all of the goods of life that they would have experienced had they not been killed. These future goods can be called their “futures of value”. Fetuses have futures (very much!) like ours. Therefore, given some assumptions, ending their lives is seriously presumptively wrong, or so the argument goes.1i The future of value argument has two parts. (1) It is an account of what is sufficient to make killing presumptively seriously wrong in the cases of all those individuals whom, we all agree, it is wrong to kill. (2) It endorses the implication that it is presumptively seriously wrong to end the life of a fetus. In the first part of this essay I briefly shall discuss the virtues of the future of value account of the wrongness of killing. In the second part I shall discuss how this theory of the wrongness of killing is one aspect of a larger plausible portion of morality. Finally, I shall discuss how, when the future of value account is placed within this larger bit of morality, the relation of the future of value account to some other issues in bioethics can be illuminated. Although I may, with some justification, be accused of bias in this matter, I believe that the future of value account of the wrongness of killing has a number of virtues. 1. The future of value view is one aspect of a more general understanding of why premature death, whether caused by a human agent or caused by something else, is a misfortune. It reflects why persons who are facing premature death from …
Novel cluster-based probability model for texture synthesis, classification, and compression

We present a new probabilistic modeling technique for high-dimensional vector sources, and consider its application to the problems of texture synthesis, classification, and compression. Our model combines kernel estimation with clustering, to obtain a semiparametric probability mass function estimate which summarizes -- rather than contains -- the training data. Because the model is cluster based, it is inferable from a limited set of training data, despite the model's high dimensionality. Moreover, its functional form allows recursive implementation that avoids exponential growth in required memory as the number of dimensions increases. Experimental results are presented for each of the three applications considered.© (1993) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.
To proliferate or not to proliferate.

This editorial refers to ‘Cardiomyocyte cell cycle control and growth estimation in vivo —an analysis based on cardiomyocyte nuclei’ by S. Walsh et al ., pp. 365–373, this issue. Cardiomyocytes in mammalian hearts undergo significant reduction in their cell proliferation capacity soon after birth, which is not disputed. However, it remains uncertain whether the adult heart contains a limited capacity for cell proliferation. Through the use of immunohistochemical staining methods, it has been reported that adult mouse cardiomyocytes can re-enter the cell cycle and duplicate.1,2 However, the origin of the cell-cycle-positive cells was not determined. Others reported permanent inhibition of cell-cycle progression in adult cardiomyocytes in mice.3 With advances in lineage tracing technology, a recent genetic labelling study demonstrated that stem or precursor cells did not contribute significantly to the formation of cardiomyocytes during normal ageing up to 1 year in the mouse. In contrast, precursor cells may participate in the formation of new cardiomyocytes after cardiac injury.4 In humans, high myocyte proliferation rates that could result in the exchange of all cardiomyocytes within 5 years have been reported by employing immunostaining technology on sections of human patients who died of acute myocardial infarction.5 In contrast, using 14C dating analyses in humans, Bergmann et al .6 reported that cardiomyocytes are renewed with a gradual decrease from …
FeedClean: feedback-driven clean utilization management to improve real-time data services in dynamic environments

Real-time data services can significantly increase, e.g., the profit of online trades by processing transactions within their deadlines. However, supporting the transaction timeliness in dynamic environments such as the WWW is challenging, since transactions may arrive in a bursty manner and execute longer than expected. As a result, the degree of data/resource contention may vary, causing deadline misses. To address this problem, we refine real-time data service performance metrics and develop a novel feedback-based scheme to manage the clean CPU utilization, which is the difference between the aggregate utilization and wasted utilization due to data conflicts and deadline misses, in main memory real-time databases. According to the control signal computed in the feedback loop, the QoS of relatively large transactions, which usually incur more data/resource contention, can be degraded under high contention. Admission control can also be applied to incoming transactions, if necessary, to improve the real-time database performance under severe overload. By carefully managing the clean utilization, we can substantially improve the success ratio, i.e., the fraction of the submitted transactions that have been admitted and finished within their deadlines. In a simulation study, which models bursty arrivals of long-running transactions with timing constraints, our approach improves the success ratio by up to an order of magnitude compared to existing approaches.
Thermal Inertia of Conductivity Cells: Observations with a Sea-Bird Cell

Abstract We have examined the magnitude and relaxation time of the thermal anomaly of the fluid flowing through the conductivity cell manufactured by Sea-Bird Electronics (SBE) that is induced by the heat stored in the wall of this cell using oceanic data collected in a thermohaline staircase. The relaxation is 9 to 10 s, about twice the value predicted by Lueck, while the initial magnitude of the conductivity error is 2.8%, about 35% smaller than predicted. The error in the measured conductivity is significant and long-lived and results in density errors detectable for 45 s after the sensor enters an isopycnal layer. An efficient numerical algorithm removes the anomaly from the measured conductivity signal and clears the resulting error from the computed salinity and density.
Foucault’s On the Government of the Living

In The Government of the Living , Foucault demonstrates elegantly and convincingly the emergence of a new idea and practice of penitence within the early Church, one that traced its origins to the Bible but in fact represented a departure from earlier Christian beliefs. This shift occurred largely under the influence of monastic and ascetic tendencies that came to play an increasingly powerful role in the second and third centuries after Christ. I suggest that this is the fundamental contribution of the lectures, rather than the framing narrative concerning truth and power. In my comments, I focus on the ideas of conversion, change of heart, remorse, and repentance, and show how the classical Greek and Latin terms for a change of mind ( metanoia , paenitentia ) assume meanings as widely different as “conversion” and “penitence.” This semantic slide or instability mirrors and enables the reinterpretation of Biblical faith as penitence. I also discuss the relationship between self-disclosure, as the classical writers understood it, and confession, and relate this to a new conception of the inviolable self.
Reversible Modification of Blood-Brain Barrier Permeability to Proteins

Entry of proteins into the central nervous system (CNS) is severely restricted by the blood-brain barrier (BBB), which is interposed between brain and cerebrospinal fluid (CSF) on the one hand, and blood on the other. The BBB has been demonstrated at three separate sites: the cerebrovascular endothelium, the epithelium of the choroid plexus, and the arachnoid membrane that separates the subdural from the subarachnoid space (reviewed by Rapoport, 1976). Each of these sites restricts protein and ion exchange because it contains a continuous layer of cells connected by tight junctions, or close intercellular adhesions. These make the cell layer have the approximate permeability properties of an extended cell membrane and limit passive protein and ion diffusion into the brain (Fig. 1). In addition, cerebrovascular endothelial cells have very little vesicular transport activity as compared to peripheral vascular endothelia, further limiting transport of protein across cerebral blood vessels (Reese and Karnovsky, 1967; Crone, 1965).
The Transformation of Partisan Rhetoric in Presidential Campaigns, 1952-2012: Partisan Polarization and the Rise of Bipartisan Posturing Among Democratic Candidates

What are the dynamics of partisan rhetoric in presidential campaigns? (How) has presidential candidate partisanship changed over time? Analyzing a comprehensive dataset of party-related statements in presidential campaign speeches over the 1952-2012 period, we show that Democratic and Republican candidates have taken distinctive approaches to partisanship. Overall, Democratic candidates have been partisans, while Republicans have largely refrained from partisan rhetoric on the campaign trail. However, this difference has narrowed substantially over time, due to a dramatic decline in the partisanship of Democratic presidential candidates. We argue that Democratic and Republican candidates have adopted different campaign strategies that reflect both enduring party differences and changing political contexts. Though naturally inclined to partisanship, Democratic candidates have adopted more conciliatory strategies primarily in response to growing public antipathy toward partisan rancor. In contrast, Republicans’ tendency toward more conciliatory rhetoric has been reinforced by political developments discouraging partisan campaigning.
Abstract 287: Tcf7l2 Expression By Insulin And High Glucose

Backgrounds: Genetic variations of TCF7L2, a nuclear transcriptional factor in canonical Wnt signaling are associated with increased risks of Diabetes Mellitus. How TCF7L2 is regulated by diabetic conditions in the heart is poorly understood. Methods: TCF7L2 expression was investigated by Western blotting in HL-1 cells treated with 14 mM mannitol (M), 25 mM glucose (G), 10 nM insulin (I), and G plus I (G+I). In addition, TCF7L2 levels were examined by Western blotting in the heart of B6.Cg-m Leprdb/+ +/J (db) and C57Bl/6J (C57) mice 4 hours after intraperitoneal injections of 1.5 IU/kg insulin. Result: The expression of TCF7L2 was higher in db than C57 hearts. Insulin treatment decreased TCF7L2 in C57 hearts. Paradoxically, TCF7L2 was further increased by insulin in db hearts. In HL-l cells, TCF7L2 started to decrease at one hour and remained lower up to 24 hours after insulin treatment compared to untreated controls. In contrast, G increased TCF7L2 expression at 1, 6 and 24 hours after treatment relative to M. Insulin could decrease TCF7L2 at 1 and 6 hours, but failed to do so at 24 hours in G+I. At 48 hours, no difference in TCF7L2 expression was observed among different treatment groups. Conclusion: Insulin regulation of TCF7L2 is interfered by high glucose in vitro and misregulation of TCF7L2 in the heart of diabetic mice may contribute to the pathogenesis of diabetic cardiomyopathy.
Substantiating the need for primary care-based sexual health promotion interventions for ethnic minority adolescent women experiencing health disparities.

PURPOSE: Assess the context of psychological distress, violence, and substance use among African- and Mexican-American adolescent women with a history of STI, violence, or high sexual risk behavior. These adolescents experience multiple health disparities, limited access to care, and are at particularly high risk of adverse sexual health outcomes. The results will inform sexual health promotion interventions provided by advanced practice nurses in primary care-based settings for women experiencing these disparities. METHODS: Analysis of self-report data obtained at study entry from African- and Mexican-American adolescent women (n = 559) enrolled in a randomized trial of a behavioral intervention for sexual risk reduction. CONCLUSIONS: High levels of psychological distress, sexual risk behavior, sexually transmitted infection (STI), personal and friend/peer substance use, alcohol use, and violence were reported by women at study entry. Analyses found that STI, physical violence, and substance-using friends were twice as likely associated with personal substance use. Alcohol users were five times more likely to use other substances. Mexican Americans were three times more likely than African Americans to use substances. IMPLICATIONS FOR PRACTICE: Recommendation is made for integration of multicomponent sexual health promotion interventions as advanced practice nurse provider services addressing these health disparities within primary care-based settings. Language: en
A Distributable and Computation-flexible Assignment Algorithm: From Local Task Swapping to Global Optimality.

The assignment problem arises in multi-robot taskallocation scenarios. This paper introduces an algorithm for solving the assignment problem with several appealing features for online, distributed robotics applications. The method can start with any initial matching and incrementally improve the solution to reach the global optimum, producing valid assignments at any intermediate point. It is an any-time algorithm with an attractive performance profile (quality improves linearly) that, additionally, is comparatively straightforward to implement and is efficient both theoretically (O(n lgn) complexity is better than widely used solvers) and practically (comparable to the fastest implementation, for up to hundreds of robots/tasks). We present a centralized version and two decentralized variants that trade between computational and communication complexity. Inspired by techniques that employ task exchanges between robots, our algorithm guarantees global optimality while using generalized “swap” primitives. The centralized version turns out to be a computational improvement and reinterpretation of the little-known method of Balinski-Gomory, proposed half a century ago. Deeper understanding of the relationship between approximate swap-based techniques —developed by roboticists— and combinatorial optimization techniques, e.g., the Hungarian and Auction algorithms —developed by operations researchers but used extensively by roboticists— is uncovered.
Striking Effect of Intra- versus Intermolecular Hydrogen Bonding on Zwitterions: Physical and Electronic Properties.

We report the synthesis, characterization, and application of novel zwitterions. The zwitterionic structures consist of a positively charged cyanine and negatively charged dienolate moieties, confirmed by experimental observations and theoretical calculations. Single crystal X-ray studies revealed that BIT-(NPh)2 is a coplanar molecule that forms 1-D chains via π–π interactions. In contrast, BIT-(NHexyl)2 is a twisted molecule with a dihedral angle of 78° between the charged planes. In charge transport studies, thin films of the flat zwitterion show semiconducting properties, with a hole mobility of 2.1 × 10–4 cm2 V–1 s–1 while the twisted zwitterion is a high resistivity insulator.
Marijuana Use and Breastfeeding

Marijuana is one of the most widely used recreational substances in the United States, with high rates of use during peak childbearing years. Medical marijuana use is also becoming more widely accepted in the United States, with legalization in 17 states and the District of Columbia. The available literature suggests that maternal marijuana use during breastfeeding is associated with potentially negative outcomes for infants and children. Adverse effects can include feeding difficulty, lethargy, and delayed cognitive and motor development. Mothers considered heavy or chronic users of marijuana are advised to not breastfeed infants. The aim of this article is to examine the prevalence of marijuana use, the potential effects on breastfed infants, and current recommendations from lactation experts.
Effects of Ductile Phase Additions on the Fracture Behavior and Toughness of DRA Composites

Discontinuously reinforced aluminum (DRA) composites have been processed to contain discrete regions of unreinforced aluminum with the objective of enhancing the damage tolerance. The effects of changes in the ductile phase size, shape and strength as well as the SiCp reinforcement distribution on the toughness were studied. The incorporation of the ductile phase can increase the crack growth resistance of the DRA composite. In such cases, stable crack propagation (i.e. R curve behavior) is observed in contrast to the behavior of the conventional DRA composite which fails catastrophically under the conditions tested. The level of toughening is affected by the size and mechanical properties of the ductile phase as well as the orientation and shape of the ductile regions with respect to the test geometry (i.e. crack arrestor vs crack divider).
Healthy Lifestyle and Risk of Heart Failure: An Ounce of Prevention Well Worth the Effort.

Despite the well-publicized decline in incidence of coronary heart disease and stroke in the United States over the past half century, prevalence and incidence of heart failure (HF) have not experienced a parallel decline. Approximately 5.5 million Americans currently have chronic HF, which represents the most common reason for hospitalization among Medicare recipients.1 Annual heathcare costs for HF are estimated at $40 billion. Although major advances in medical and device therapy have modestly improved survival for the subset of HF patients with reduced left ventricular ejection fraction, 5-year survival remains lower than many cancers. From a public health perspective, therefore, the primary prevention of HF is of tremendous importance to reduce the medical and societal costs of this disorder. See Article by Larsson et al Several epidemiological studies in the last decade have demonstrated an association between lifestyle variables and HF risk in the general population. In these studies, a healthy lifestyle, defined by maintaining regular physical activity, a healthy dietary pattern, a normal body mass index, and not smoking resulted in 45% to 81% reductions in HF incidence.2–4 Furthermore, these studies have shown a graded reduction in HF risk in parallel to the number of healthy lifestyle practices followed. With this background, the study by Larsson et al in this issue of Circulation: Heart Failure provides additional strong epidemiological evidence of a consistent and graded relationship between a healthy lifestyle and a lower risk of HF in 2 large Swedish cohorts over a 13-year follow-up.5 In 33 966 men from the Cohort of Swedish Men and 30 713 women …
I Don't Always Have Positive Attitudes, but When I Do It Is Usually About a Robot: Development of the Robot Perception Scale.

The increasing use of robots and their role in society has important implications for research and development in human-robot interactions (HRIs). The purpose of the present study was to develop a new measure to assess attitudes toward robots in HRIs. Measures of attitudes humans have “about” robots are relatively uncommon. Those that exist have potential problems limiting utilization in research evaluating the human element in HRIs. The Robot Perception Scale (RPS) was developed to redress this gap by examining a new set of factors in unique ways. The RPS consists of two subscales in which participants rate their agreement with statements concerning general attitudes toward robots and attitudes toward human-robot similarity and attractiveness. Findings provide preliminary support for a robotic perception scale that can be used to further our understanding of robots engaged in a variety of HRI settings.
Ileal Conduit Urinary Diversion in Children

In the evaluation of the morbidity associated with ileal conduit urinary diversion in children, a retrospective analysis of the complications in 125 such children was done. When retroperitoneal Penrose drainage was used or when additional surgical procedures were performed, a significantly increased number of early postoperative complications were found. Conversely, when peristomal skin preconditioning was accomplished or when a single layer ureteroileal anastomosis was constructed, postoperative morbidity was markedly reduced. Ileal conduit urinary diversion remains the most satisfactory method of permanent urinary diversion in children.
Implicit prioritization in life cycle assessment: text mining and detecting metapatterns in the literature

Life cycle assessment aims to evaluate multiple kinds of environmental impact associated with a product or process across its life cycle. Objective evaluation is a common goal, though the community recognizes that implicit valuations of diverse impacts resulting from analytical choices and choice of subject matter are present. This research evaluates whether these implicit valuations lead to detectable priority shifts in the published English language academic LCA literature over time. A near-comprehensive investigation of the LCA literature is undertaken by applying a text mining technique known as topic modeling to over 8200 environment-related LCA journal article titles and abstracts published between 1995 and 2014. Topic modeling using MALLET software and manual validation shows that over time, the LCA literature reflects a dramatic proportional increase in attention to climate change and a corresponding decline in attention to human and ecosystem health impacts, accentuated by rapid growth of the LCA literature. This result indicates an implicit prioritization of climate over other impact categories, a field-scale trend that appears to originate mostly in the broader environmental community rather than the LCA methodological community. Reasons for proportionally increasing publication of climate-related LCA might include the relative robustness of greenhouse gas emissions as an environmental impact indicator, a correlation with funding priorities, researcher interest in supporting active policy debates, or a revealed priority on climate versus other environmental impacts in the scholarly community. As LCA becomes more widespread, recognizing and addressing the fact that analyses are not objective becomes correspondingly more important. Given the emergence of implicit prioritizations in the LCA literature, such as the impact prioritization of climate identified here with the use of computational tools, this work recommends the development and use of techniques that make impact prioritization explicit and enable consistent analysis of result sensitivity to value judgments. Explicit prioritization can improve transparency while enabling more systematic investigation of the effects of value choices on how LCA results are used.
New Treatments for Systemic Lupus Erythematosus

The treatment of systemic lupus erythematosus (SLE) currently depends heavily on nonspecific immunosuppressives. Belimumab was the first biologic to be approved for the use of nonrenal SLE. Currently, several biologics and small molecules are being evaluated for the treatment of both lupus nephritis and nonrenal SLE. Two molecules—epratruzumab, an anti-CD22 antibody and sifalizumab, an anti-interferon-α antibody—have shown promising results in phase II trials. We also discuss biologics and small molecules that target cytokines, the complement, co-stimulatory, and surface molecules and are at earlier phases of development.
Auger Electron Spectroscopy: Metallurgical Applications

A relatively new tool in the field of metallurgy, namely Auger electron spectroscopy, has several potentially valuable uses for metallurgists. Areas of interest in which Auger electron spectroscopy studies are useful are corrosion, alloy formation, nucleation, diffusion, catalysis, epitaxy, thin film growth, and fractography. The actual experimental methods associated with the use of this technique are discussed in some detail. And where they are available, specific examples are given to illustrate usages in the above areas.
Properties of cellulose–soy protein blend biofibers regenerated from an amine/salt solvent system

Blend biofibers with relatively high protein content were fabricated from cellulose and soy protein isolate (SPI) using an ethylenediamine–potassium thiocyanate solvent system. Due to the decrease in solution viscosity, the SPI loading was limited to a maximum of 40 %, considering the 100 % draw down ratio applied during fiber coagulation. The results obtained from chemical and X-ray analyses support the formation of interaction through mainly secondary bonding. Increasing the protein content resulted in fibers with slightly improved thermal stability. Electron microscopy images of the fibers revealed a homogeneous dispersion of protein without clear phase separation. The percent crystallinity and the tensile data revealed that the best compatibility was obtained for 20 % SPI ratio and that the fiber exhibited the same birefringence as control fiber. In addition, blending cellulose with protein resulted in fibers with faster biodegradation.
The Salvador Option: The United States in El Salvador, 1977-1992

El Salvador's civil war between the Salvadoran government and Marxist guerrillas erupted into full force in early 1981 and endured for eleven bloody years. Unwilling to tolerate an advance of Soviet and Cuban-backed communism in its geopolitical backyard, the US provided over six billion dollars in military and economic aid to the Salvadoran government. El Salvador was a deeply controversial issue in American society and divided Congress and the public into left and right. Relying on thousands of archival documents as well as interviews with participants on both sides of the war, The Salvador Option offers a thorough and fair-minded interpretation of the available evidence. If success is defined narrowly, there is little question that the Salvador Option achieved its Cold War strategic objectives of checking communism. Much more difficult, however, is to determine what human price this 'success' entailed - a toll suffered almost entirely by Salvadorans in this brutal civil war.
Activation of the P38 MAPK Pathway Results in Ubiquitin-Proteasome Degradation of the PML Tumor Suppressor Protein.

Abstract The promyelocytic leukemia gene (PML) is involved in the t(15;17) chromosomal translocation of acute promyelocytic leukemia (APL). PML is a tumor suppressor whose inactivation is causal in leukemogenesis. PML exerts its function by interacting with several tumor suppressor proteins such as p53, pRb, Smad2, Smad3 and CBP/p300. We have recently demonstrated that PML protein is frequently lost in a large portion of hematologic and solid tumors. In these tumors, PML gene sequence and RNA expression were wild type. These findings suggest that PML protein loss is mediated by a post-translational mechanism. We investigated whether PML protein loss is due to degradation via the ubiquitin/proteasome system. Several tumor cell lines have absent or reduced levels of PML protein when compared to untransformed primary cells. We found that in these cases, PML protein half-life is reduced as a result of increased protein degradation. In addition, PML ubiquitinylation is markedly increased in tumor derived cell lines. Incubation of PML negative tumor cell lines with proteasome inhibitors restored wild type PML protein levels. We also defined the minimal PML sequence that is required for ubiquitinylation. This region is in the immediate proximity to p38 mitogen-activated protein kinase consensus sites (p38 MAPK). The p38 MAPK kinase responds to cellular stress, such as osmotic shock, increased free radicals and hypoxia. Notably, p38 MAPK activation has been associated with poor prognosis in breast cancer and follicular lymphoma (Esteva et al. Cancer, 2003. Elenitoba-Johnson et al. Proc Natl Acad Sci U S A. 2003). We therefore, tested whether PML and p38 MAPK functionally interact. Activation of p38 MAPK signaling resulted in dramatic PML degradation due to increased ubiquitinylation. Furthermore, activation of P38 MAPK resulted in increased PML phosphorylation and sumoylation. Treatment with specific inhibitors of p38 MAPK or expression of a p38 dominant negative mutant also inhibited p38 induced PML degradation. In addition, we demonstrated that PML is a direct target of p38 MAPK activity. Bacterially expressed PML is a direct substrate of p38 MAPK in an in vitro kinase assay. The p38 MAPK phosphorylation sites present in the PML protein were mapped. Alanine to serine substitutions of predicted p38 MAPK sites abolished PML phosphorylation by p38 MAPK in vitro and abrogated p38 MAPK dependent PML degradation within the cell. In addition, co-immunoprecipitation experiments clearly demonstrated that PML binds to the active form of p38 MAPK. Confocal immunofluorescence analysis revealed that both activated p38 MAPK colocalize with PML in the nuclear body. These data indicate that the p38 MAPK signaling pathway results in ubiquitin/proteasome mediated PML degradation and imply that MAPK signaling pathways may contribute to oncogenesis by inducing the degradation of the PML tumor suppressor protein. Pharmacological manipulation of this pathway may prove useful for the treatment of tumors that lose PML protein.
Theoretical Modeling of Internal Ionic Resistance Due to SEI Layer Formation in Li/S Batteries

Li/S batteries have received too much attention due to their considerable theoretical energy density suitable for high energy applications. Here, we study the consequences of the SEI layer on internal resistance of the single battery cell due to polysulfide (PS) shuttling. The growth in resistance is related to the capacity fading of the cell. Using a model of series resistors, the total internal ionic resistance over cycling performance is expressed and compared for various nanostructured cathodes at different rates. It has been shown that SEI layer is the most significant factor in increasing of ionic resistance at the beginning of the battery aging, while electrode degradation and other phenomena are dominating resistance rise over higher cycles. We also demonstrate that cathodes with smaller equivalent porosity represent an excellent performance in preventing internal resistance enhancement.
Pope Innocent III and the Annulment of Magna Carta

Historians have offered a variety of explanations for Pope Innocent III's release of King John from the promise that he made to observe the clauses of Magna Carta. None has won general acceptance. This article proposes an alternative by examining the tenets of the canon law as it was understood in 1215. That examination shows that the law of oaths (De iureiurando) played a central role in canonistic thought of the time. It contained the juristic resources that made it possible for Innocent to release John from the oath that he had taken at Runnymeade.
Using Cosmogenic Radionuclides for the Determination of Effective Surface Exposure Age and Time-Averaged Erosion Rates

We discuss the cosmogenic method of determining exposure ages and erosion rates of exposed surfaces. This method is recognized to date as the only reliable method of quantifying important processes in geochronology, provided the exposure history of the surfaces can be successfully characterized using two or more cosmogenic nuclides produced in situ in the surfaces of interest. The success of the cosmogenic technique is based on two important characteristics of the secondary cosmic ray beam interacting with the exposed surfaces: (1) cosmic ray labeling is sensitively dependent on the geometry of exposure of the solid, and (2) the mean distance characterizing the absorption of cosmic ray beam in typical rocks is only about 50 cm. These facts make it possible to determine the past exposure history of the exposed surfaces; this task can be put on much firmer ground if information on the exposure history can be constrained based on geological information.
The relational push-pull model: a generative model for relational data clustering

Relational data clustering is a form of relational learning that clusters data using the relational structure of data sets to guide the clustering. Many approaches for relational clustering have been proposed recently. The common assumption in much of this research is that relations have a binding tendency (Neville, Adler, & Jensen 2003; Bhattacharya & Getoor 2007; Taskar, Segal, & Koller 2001; Neville & Jensen 2006). That is, edges are assumed to appear more frequently within clusters than between clusters. This binding quality may be too strong an assumption. Bhattacharya & Getoor (2007) acknowledge that it is possible for a relation to provide “negative evidence,” where the presence of a relation between two objects implies that the objects belong in different clusters. If most of the edges in a relational set provide negative evidence, then this set should be considered to have a separating, rather than a binding, tendency. Consider a social network of university students containing both men and women. If the social network is partitioned by gender, edges for a dating relation will appear most frequently between the clusters. This can be visualized as an approximately bipartite structure between the two clusters that “pushes” them apart. Edges for a roommate relation, on the other hand, will appear most frequently within the clusters. This binding relation can be visualized as a net that “pulls” the objects in a cluster closer together, hence the name “Relational Push-Pull Model.” The prevailing approach to clustering when the relational tendency is not known a priori is stochastic block modeling. Nowicki & Snijders (2001) presented a method for automated learning of stochastic block models in which only object-object relations are observed. Recently, researchers (Handcock, Rafferty, & Tantrum 2007; Tallberg 2005; Anthony & desJardins 2007) have acknowledged that Nowicki & Snijders’ approach ignores a valuable source of information: the attributes associated with the data objects in the relational data set. I propose an extension to Nowicki & Snijders’s model in which relations exist probabilistically as a function of the connected objects’ features. My research has taken a generative approach to the clustering problem: I assume that each object and each relation
The Research of Matrix Converter Space Vector Modulation

For the problems of matrix converter in practical application, firstly this paper analyzes the working principle of matrix converter and the space vector modulation control strategy, then uses matlab/simulink to model and simulate for matrix converter, analyze the key problems of space vector modulation control strategy between the simulation: the sector partition and the nine-segment symmetric modulation, the theory of Matrix Converter space vector modulation is correct through the simulation test, realize the advantages of Matrix Converter: the input power factor, high efficiency, two-way flow of energy and good output voltage waveform and so on. It is the foundation of matrix converter in the application of doubly-fed wind power generation system.
Who's the Boss? Autonomics and New-Fangled Security Gizmos with Minds of Their Own.

Faithfully does what humans might May waste or duplicate effortneglect (backups?)Could result in huge efficiency gains Could violate unstated constraintsCan’t handle completely newproblemsHandles known errors wellMay mask human activity (or serveas an excuse)Anticipates user action (e.g., webprefetching)Can handle tasks previously only Doesn’t know when to ask for helphumans could doFails to account for interactionsbetween systems (story time)Accomplishes individual tasks wellSaves system administrator labor Hides information
Predicting the Incidence of Pressure Ulcers in the Intensive Care Unit Using Machine Learning

Background: Reducing hospital-acquired pressure ulcers (PUs) in intensive care units (ICUs) has emerged as an important quality metric for health systems internationally. Limited work has been done to characterize the profile of PUs in the ICU using observational data from the electronic health record (EHR). Consequently, there are limited EHR-based prognostic tools for determining a patient’s risk of PU development, with most institutions relying on nurse-calculated risk scores such as the Braden score to identify high-risk patients. Methods and Results: Using EHR data from 50,851 admissions in a tertiary ICU (MIMIC-III), we show that the prevalence of PUs at stage 2 or above is 7.8 percent. For the 1,690 admissions where a PU was recorded on day 2 or beyond, we evaluated the prognostic value of the Braden score measured within the first 24 hours. A high-risk Braden score ( Conclusion: We demonstrate that an EHR-based model can outperform the Braden score as a screening tool for PUs. This may be a useful tool for automatic risk stratification early in an admission, helping to guide quality protocols in the ICU, including the allocation and timing of prophylactic interventions.
Xylose assimilation enhances the production of isobutanol in engineered Saccharomyces cerevisiae.

Bioconversion of xylose-the second most abundant sugar in nature-into high-value fuels and chemicals by engineered Saccharomyces cerevisiae has been a long-term goal of the metabolic engineering community. Although most efforts have heavily focused on the production of ethanol by engineered S. cerevisiae, yields and productivities of ethanol produced from xylose have remained inferior as compared with ethanol produced from glucose. However, this entrenched focus on ethanol has concealed the fact that many aspects of xylose metabolism favor the production of nonethanol products. Through reduced overall metabolic flux, a more respiratory nature of consumption, and evading glucose signaling pathways, the bioconversion of xylose can be more amenable to redirecting flux away from ethanol towards the desired target product. In this report, we show that coupling xylose consumption via the oxidoreductive pathway with a mitochondrially-targeted isobutanol biosynthesis pathway leads to enhanced product yields and titers as compared to cultures utilizing glucose or galactose as a carbon source. Through the optimization of culture conditions, we achieve 2.6 g/L of isobutanol in the fed-batch flask and bioreactor fermentations. These results suggest that there may be synergistic benefits of coupling xylose assimilation with the production of nonethanol value-added products.
Victim of Your (Customer's) Own Success

Under the context of digital health, I explore the potential opportunity costs associated with giving customers a sense of success. Using large-scale data from a popular mobile fitness application, I show that many users who enjoy certain past successes need not necessarily upgrade to the premium version, or even continue using the app. These observed dynamics motivate a structural model of self-reputation, where users learn about their own ability at maintaining healthy behavior. The model estimates reveal that improvements in perceived ability do not necessarily increase their desire to upgrade, and in some cases, may even increase the incentives of quitting. Furthermore, I show that the observed heterogeneity in their prior beliefs about true ability matches patterns found in past research on self-confidence. Finally, counterfactual simulations reveal that improvements in the salience of personal performance metrics, while helpful for the user's learning process, would at the same time decrease the number of upgrades to the paid version.
Near Abroad: Putin, the West and the Contest Over Ukraine and the Caucasus

Gearoid O Tuathail (Gerard Toal) the esteemed Irish political geographer has delivered a tour-de-force in Near Abroad: Putin, the West and the Contest Over Ukraine and the Caucasus. The book certai...