cssi/SciSciGPT-SciSciNet huggingface dataset:
Neutrinos from Pair Instability Supernovae

We present the first ever calculations of the neutrino signal from pair-instability supernovae (PISNe) using two hydrodynamical simulations which bracket the mass range of the stars which explode via this mechanism. We take into account both the time and energy dependence of the emission and the flavor oscillations, as well as investigating the equation-of-state dependence. We then process the computed neutrino fluxes at Earth through four different neutrino detectors. We show how the neutrino signal from PISNe possesses unique features that distinguish it from other supernovae, how the detectors we consider are capable of observing neutrinos from PISNe at the standard distance of 10 kpc, and how the proposed HyperKamiokande detector can even reach the Large Magellanic Cloud and the several very high mass stars known to exist there.
Birth and early developmental screening outcomes associated with cannabis exposure during pregnancy.

To compare birth and early developmental screening outcomes for infants with and without in utero cannabis exposures. Observational cohort of women receiving prenatal care within a large health system, live birth between October 1, 2015 and December 1, 2017, and at least one infant visit. Cannabis exposure was through routine urine toxicology screen. Preterm birth, small for gestational age (SGA) birth, birth defects, and early developmental screening outcomes were assessed from birth and electronic health record data. Of 3435 women, 283 (8.2%) had a positive urine toxicology screen. In utero cannabis exposure was associated with SGA birth, adjusted rate ratio (aRR) 1.69 (95% confidence interval [CI]: 1.22–2.34). Abnormal 12-month developmental screens occurred in 9.1% of infants with in utero cannabis exposure vs. 3.6% of those with negative maternal screens, aRR 1.90 (95% CI: 0.92–3.91). Additional birth outcomes were not associated with in utero cannabis exposure. Exposure to cannabis during pregnancy may adversely impact fetal growth.
Prime Time for Genome Editing

New Tool for Correcting Mutations Protein engineering has yielded a new, potent tool — in the form of a chimeric enzyme — for correcting genetic mutations. Proof of principle that this enzyme can c...
Low-spin cobalt(II) redox shuttle by isocyanide coordination

Coordination of the strong-field ligand 2,6-dimethylphenyl isocyanide (DMP-CN) to the Co(PY5Me2) framework, where PY5Me2 represents the pentadentate ligand 2,6-bis(1,1-bis(2-pyridyl)ethyl)pyridine, has resulted in a new low-spin Co(II) complex with a relatively low reorganization energy and fast electron-transfer kinetics compared to the prototypical cobalt tris-bipyridine redox shuttle, [Co(bpy)3]3+/2+, where bpy represents 2,2′-bipyridine. Despite nearly 160 mV reduced regeneration driving force, the [Co(PY5Me2)(DMP-CN)]3+/2+ redox shuttle displayed an increased regeneration efficiency relative to [Co(bpy)3]3+/2+, however recombination losses hinder the performance as evidenced by a reduced recombination resistance. Future directions point to low-spin Co(II) redox shuttles with more negative redox potentials to be paired with a dye or dye mixture that absorbs into the near infrared region.
Cooling of PEM Fuel Cell Stacks Using Open-Cell Metal Foam

For safe and efficient operation of the proton exchange membrane fuel cell (PEMFC), effective thermal management is needed. This study presents the use of aluminum foam in PEMFC’s thermal management using forced air. An analytical study was performed using a bipolar plate air-cooled channel to examine the effects of operating temperatures on fuel cells and to study heat transfer and temperature distribution in the stack. In the simulation, the heat transfer and fluid flow for a thin layer of metal foam inserted between two bipolar plates of fuel cell stack were simulated using ANSYS-Fluent 19.2, and both the local thermal equilibrium and the local thermal non-equilibrium assumptions were applied. The outcomes, such as pressure drop through porous medium per plate length and plate maximum temperatures, were calculated. The temperature profile distributions were drawn, and the comparison between two models was investigated. Based on this simulation, a new design was provided to improve the thermal design of an air-cooled fuel cell by using metal foam.
The Most Complete Political Machine Ever Known: The North's Union Leagues and the American Civil Wa

Review of: “The Most Complete Political Machine Ever Known”: The North’s Union Leagues and the American Civil War, by Paul Taylor
Murine interfollicular epidermal differentiation is gradualistic with GRHL3 controlling progression from stem to transition cell states

The interfollicular epidermis (IFE) forms a water-tight barrier that is often disrupted in inflammatory skin diseases. During homeostasis, the IFE is replenished by stem cells in the basal layer that differentiate as they migrate toward the skin surface. Conventionally, IFE differentiation is thought to be stepwise as reflected in sharp boundaries between its basal, spinous, granular and cornified layers. The transcription factor GRHL3 regulates IFE differentiation by transcriptionally activating terminal differentiation genes. Here we use single cell RNA-seq to show that murine IFE differentiation is best described as a single step gradualistic process with a large number of transition cells between the basal and spinous layer. RNA-velocity analysis identifies a commitment point that separates the plastic basal and transition cell state from unidirectionally differentiating cells. We also show that in addition to promoting IFE terminal differentiation, GRHL3 is essential for suppressing epidermal stem cell expansion and the emergence of an abnormal stem cell state by suppressing Wnt signaling in stem cells.
Risk of ventricular arrhythmia in cardiac resynchronization therapy responders and super-responders: a systematic review and meta-analysis.

AIMS Response to cardiac resynchronization therapy (CRT) is associated with improved survival, and reduction in heart failure hospitalization, and ventricular arrhythmia (VA) risk. However, the impact of CRT super-response [CRT-SR, increase in left ventricular ejection fraction (LVEF) to ≥ 50%] on VA remains unclear. METHODS AND RESULTS We undertook a meta-analysis aimed at determining the impact of CRT response and CRT-SR on risk of VA and all-cause mortality. Systematic search of PubMed, EMBASE, and Cochrane databases, identifying all relevant English articles published until 31 December 2019. A total of 34 studies (7605 patients for VA and 5874 patients for all-cause mortality) were retained for the meta-analysis. The pooled cumulative incidence of appropriate implantable cardioverter-defibrillator therapy for VA was significantly lower at 13.0% (4.5% per annum) in CRT-responders, vs. 29.0% (annualized rate of 10.0%) in CRT non-responders, relative risk (RR) 0.47 [95% confidence interval (CI) 0.39-0.56, P < 0.0001]; all-cause mortality 3.5% vs. 9.1% per annum, RR of 0.38 (95% CI 0.30-0.49, P < 0.0001). The pooled incidence of VA was significantly lower in CRT-SR compared with CRT non-super-responders (non-responders + responders) at 0.9% vs. 3.8% per annum, respectively, RR 0.22 (95% CI 0.12-0.40, P < 0.0001); as well as all-cause mortality at 2.0% vs. 4.3%, respectively, RR 0.47 (95% CI 0.33-0.66, P < 0.0001). CONCLUSIONS Cardiac resynchronization therapy super-responders have low absolute risk of VA and all-cause mortality. However, there remains a non-trivial residual absolute risk of these adverse outcomes in CRT responders. These findings suggest that among CRT responders, there may be a continued clinical benefit of defibrillators.
iProMix: A decomposition model for studying the function of ACE2 based on bulk proteogenomic data for coronavirus pathogenesis

Both SARS-CoV and SARS-CoV-2 use ACE2 receptors to enter epithelial cells in lung and many other tissues to cause human diseases. Genes and pathways that regulate ACE2 may facilitate/inhibit viral entry and replication, and genes and pathways that are controlled by ACE2 may be perturbed during infection, both affecting disease severity and outcomes. It is critical to understand how genes and pathways are associated with ACE2 in epithelial cells by leveraging proteomic data, but an accurate large-scale proteomic profiling at cellular resolution is not feasible at current stage. Therefore, we propose iProMix, a novel framework that decomposes bulk tissue proteomic data to identify epithelial cell component specific associations between ACE2 and other proteins. Unlike existing decomposition based association analyses, iProMix allows both predictors and outcomes to be impacted by cell type composition of the tissue and accounts for the impacts of decomposition variations and errors on hypothesis tests. It also builds in the functions to improve cell type estimation if estimates from existing literature are unsatisfactory. Simulations demonstrated that iProMix has well-controlled false discovery rate and large power in non-asymptotic settings with both correctly and mis-specified cell-type composition. We applied iProMix to the 110 adjacent normal tissue samples of patients with lung adenocarcinoma from Clinical Proteomic Tumor Analysis Consortium, and identified that interferon α and γ pathways were most significantly associated with ACE2 protein abundances in epithelial cells. Interestingly, the associations were sex-specific that the positive associations were only observed in men, while in women the associations were negative.
Acquired antithrombin deficiency is a risk factor for venous thromboembolism after major trauma.

Abstract Background Up to 30% of severely injured patients on prophylactic anticoagulation experience venous thromboembolism (VTE). Our previous work shows that acquired antithrombin (AT) deficiency [AT Methods A secondary analysis of the Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) clinical trial was performed. Patients who died within 24 h of hemorrhage were excluded from analysis. Demographics, mechanism and severity of injury, transfusions volumes, and outcomes were compared between patients who did and did not develop VTE. Non-parametric statistical tests were used to compare patients with and without VTE. Logistic regression analyses were performed to identify predictors of VTE risk, controlling for AT deficiency (over first 72 h), age, gender, race, body mass index, study site, randomization group and injury severity. A Cox proportional hazards model was used to assess the contribution of AT deficiency to the risk of VTE, while censoring for early deaths. Results Of the 680 patients enrolled in PROPPR, 101 died of hemorrhage. Of the remaining 579 patients, 86 (14.9%) developed VTE. The median time to VTE was 6 days (IQR 3, 13). No differences in demographics, injuries, or transfusion volumes were identified between VTE cases and controls. AT deficiency at 72 h post-admission was independently associated with VTE. Patients who experienced AT deficiency at 72 h had a 3.3 fold increased risk of VTE [p Conclusions Acquired AT deficiency (AT
Perspective on model-informed drug development

Model-informed drug development (MIDD) is a process intended to expedite drug development, enhance regulatory science, and produce benefits for patients. Quantitative modeling and simulation-principally by population pharmacokinetics (PK), exposure-response, and physiologically based pharmacokinetic (PBPK) analysis-is the technology that provides the capability to deploy MIDD across a range of applications. MIDD was codified in the 2017 Prescription Drug User Fee Act Reauthorization 1 (PDUFA VI, 2018-2022) and a performance goal was a MIDD pilot program to hold 2 to 4 industry-U.S. Food and Drug Administration (FDA) paired meetings quarterly through 2022.
Sex differences in 3,4-methylenedioxypyrovalerone (MDPV)-induced taste avoidance and place preferences☆

Abstract Synthetic cathinones, otherwise known as “bath salts”, have gained significant attention in the last few years as a result of increased use and abuse. One such compound, 3,4-methylenedioxypyrovalerone (MDPV), is pharmacologically and behaviorally similar to cocaine and has been shown to possess both aversive and rewarding effects. For a host of other drugs, each of these effects (and their relative balance) can be influenced by a variety of factors, including sex, which in turn impacts drug taking behavior. In this context, the present assessment sought to determine whether males and females differed in MDPV-induced CTA and CPP. Both male and female Sprague–Dawley rats underwent a combined CTA/CPP procedure, in which an injection of one of three doses of MDPV (1.0, 1.8 or 3.2 mg/kg) was paired with both a novel saccharin solution and a novel environment and changes in preferences for these stimuli were examined. Taste avoidance was evident in both sexes, although this avoidance was weaker in females compared to males. MDPV also produced place preferences in all drug-treated animals, but these preferences did not vary as a function of sex. The fact that females showed a weaker avoidance response compared to males (despite comparable preferences) suggests that females may have a heightened susceptibility to use and abuse of MDPV, paralleling results seen with cocaine and other stimulants. The present findings extend the behavioral characterization of MDPV and the factors that may alter its aversive and rewarding effects.
A Career in Soviet Studies

The right combination of mentors, happy accidents, experiences, and choices can lead to a rewarding career.
A novel Lyn-protein kinase Cδ/ε-protein kinase D axis is activated in B cells by signalosome-independent alternate pathway BCR signaling.

BCR signaling initiates multiple activities critical for B-cell function. Recently, we identified an alternate BCR signaling pathway, induced by IL-4, that is signalosome-independent, unlike the classical signalosome-dependent pathway, and that leads to activation of the MAP kinase, ERK. Here we questioned whether alternate pathway signaling extends to other key downstream events, especially protein kinase D (PKD) activation. We found that in murine spleen-derived B cells the IL-4-induced alternate pathway for BCR signaling results in PKD and PKD substrate phosphorylation, and that alternate pathway phosphorylation of HDAC5/7 and other key substrates requires PKD. Furthermore, we found that tyrosine phosphorylation of PKCδ/e occurs as a result of alternate but not classical pathway signaling and is required for phosphorylation of PKD and PKD substrates. This result identifies PKCδ/e tyrosine phosphorylation as a unique outcome of the alternate pathway. The alternate pathway is mediated by Lyn that is not required for classical pathway signaling and we found that Lyn associates directly with PKCδ/e and is required for phosphorylation of PKCδ/e and of PKD. These findings indicate that IL-4 influences B-cell activation by inducing a novel signaling pathway from BCR to Lyn to PKCδ/e to PKD.
Identity-based strong multi-designated verifiers signatures

Designated verifier signatures are privacy-oriented signatures that provide message authenticity only to a specified verifier but nobody else. We consider strong multi-designated verifiers such that knowledge of either one of designated verifiers’ private keys is required to verify the signature. We propose the first identity-based construction.
Speeding up SAT solver by exploring CNF symmetries : Revisited

Boolean Satisfiability solvers have gone through dramatic improvements in their performances and scalability over the last few years by considering symmetries. It has been shown that by using graph symmetries and generating symmetry breaking predicates (SBPs) it is possible to break symmetries in Conjunctive Normal Form (CNF). The SBPs cut down the search space to the nonsymmetric regions of the space without affecting the satisfiability of the CNF formula. The symmetry breaking predicates are created by representing the formula as a graph, finding the graph symmetries and using some symmetry extraction mechanism (Crawford et al.). Here in this paper we take one non-trivial CNF and explore its symmetries. Finally, we generate the SBPs and adding it to CNF we show how it helps to prune the search tree, so that SAT solver would take short time. Here we present the pruning procedure of the search tree from scratch, starting from the CNF and its graph representation. As we explore the whole mechanism by a non-trivial example, it would be easily comprehendible. Also we have given a new idea of generating symmetry breaking predicates for breaking symmetry in CNF, not derived from Crawford's conditions. At last we propose a backtrack SAT solver with inbuilt SBP generator.
Survivin expression and its clinical significance in pancreatic cancer

Survivin, an inhibitor of apoptosis is expressed in several human cancers. Its expression is known to be associated with poor clinical outcome, but not widely studied in pancreatic cancer. We performed this study to determine the survivin expression in pancreatic cancer and its clinical significance as a prognostic factor. We performed immunohistochemical staining for survivin, p53, and Bax in formalin-fixed, paraffin-embedded block from forty-nine pancreatic tissues. To determine the association with clinical course, we reviewed the patients' clinical record. Of the 49 cases of pancreatic cancer, 46 cases (93.9%) were positive for survivin expression. There was no significant association between survivin expression and p53 or bax. For clinicopathological parameters, perineural invasion was more common in survivin positive and venous invasion was more common in survivin negative (p = 0.041 and 0.040, respectively). Responsiveness to chemotherapy appeared to be slightly better in patients with low survivin expression. Survivin expression may be associated with venous or perineural invasion, indicating metastatic route, and seems to have a potential as a predictive marker for chemotherapy. Further study of large scale is required to determine the clinical significance of survivin expression in pancreatic cancer.
Are Experienced Analysts More Accurate

We examine the relationship between analyst experience and the accuracy of annual earnings forecasts using a 20-year sample (1983-2002) from the Thomson Financial First Call I/B/E/S database. We test for this relationship using three different measures of forecast accuracy employed by prior researchers, which are regressed against measures of general experience and specific experience, along with five other controls, for four independent 5-year subperiods, as well as for the full 20-year period. We find that general experience levels are positively associated with forecast accuracy (negatively associated with forecast error) in most subperiods for two of the three measures of forecast accuracy. We also find, in contrast with the extant literature, that for two of the three measures of forecast accuracy and for most subperiods, specific experience does not have an association with forecast accuracy beyond that provided by the general experience measure. Our results suggest that the relationship between forecast accuracy and analyst experience (as well as some other commonly examined analyst characteristics) is dependent on the measure of accuracy employed and the time period studied.
Structure-activity studies on hallucinogenic amphetamines using model interaction calculations☆

Abstract In summary, we can briefly describe the model as developed at this time. We view the amphetamine receptor as possessing two principal features: one site provides anchoring for the onium group, whereas the other feature interacts with the phenyl ring and substitutents. In addition, there is implied the presence of a feature associated with the 3,4 region of the phenyl ring. The best model for the phenyl ring receptor is the methylindole molecule with the two rings, one directly above the other at a separation distance of 4·5 A. The correlation from these results [equation (2)] is better than that reported for any other SAR study to date, accounting for 74 % of the variation in the data. Further inclusion of a term relating to distribution or absorption improves the correlation so that 82Y. of the variation is accounted for. This provisional model can now be tested against data for other amphetamines, mescalines, tryptamines and other hallucinogenic agents.
Fluvial sedimentation in response to postglacial uplift and environmental change, Missisquoi River, Vermont

Three lithologically distinct alluvial units of Holocene age can be distinguished along trenched cross sections of the Missisquoi valley bottom. The oldest is of early Holocene age, and the associated floodplain had aggraded to nearly its present level by 8000 14C yr B.P. At that time, early Archaic projectile points were deposited in a fire hearth 50 cm below the surface. Abandonment of this floodplain was followed by the development of an A-E-Bt soil profile. Accumulation of a younger floodplain had begun by 6400 14C yr B.P. and local sedimentation persisted to ca. 500 14C yr B.P., as indicated by radiocarbon dates of buried woody debris (including large logs) and of charcoal. Alluvium of the modern floodplain began accreting after A.D. 1860 and contains machine-cut square nails, whiteware ceramics, and coal clinker. Previous locations of the river channel can be reconstructed from relict surfaces marked by paleosols, the preserved depositional stratigraphy, and the radiocarbon samples. Immediately after regression of the Champlain Sea from this part of the valley, and before 8000 14C yr B.P., the river incised late Fleistocene marine silts and clays at an average rate of at least 1 m/100 yr. After the interval of downcutting, episodic lateral migration became the dominant process, with the rate varying between 0 and 4 m/100 yr. The early Holocene incision was most likely a lagged response to postglacial crustal rebound, whereas strong soil development and floodplain stability between 8000 and 6400 14C yr B.P. may reflect an independently documented warmer, and perhaps drier, climate in New England at this time. Finally, the post-A.D. 1860 period of active floodplain sedimentation may have been a response to timber clear-cutting, row crop agriculture, and cattle and sheep grazing in the watershed.
Practice patterns and anesthesia‐related costs for liver transplantation

C osts at the clinical end of medicine are driven by practice patterns. In our corner of medicine, those practice patterns are driven by hepatologists, surgeons, anesthesiologists, intensivists, medical consultants, nurses, etc. Unfortunately, patterns of practice are by no means uniformly standardized, primarily because of the lack of solid clinical evidence to clearly call one form of care superior to another, whether it is more or less expensive. Our intraoperative care of transplant recipients is driven by the needs of surgeons and by our own requirements. Such needs are driven by preferences, experience, science, and occasionally whim. Objective data regarding the risks and benefits of using or avoiding various technologies is limited and sometimes conflicting.
Cardiac atrophy in the heterotopically transplanted rat heart: in vitro protein synthesis.

Heterotopic cardiac isografts are vasculary perfused organs that maintain structural and functional integrity. We have used this model to study the time course of change in total heart and left ventricular size which results from mechanical unloading of the myocardium. When compared to the in situ (working) heart there is a 19% decrease in the size of the heterotopic (non-working) heart (P < 0.01) as early as 3 days post-transplantation. By 14 days there is 50% decrease in the size of the transplanted heart which is maintained at this atrophic size when measured after 4 weeks. Left ventricular protein synthesis was assayed by the simultaneous in vitro perfusion of the host and transplanted hearts under identical hemodynamic conditions. The hourly incorporation of 14C-lysine into total left ventricular protein was 21 nmol in the transplant compared to 50 nmol in the in situ heart (P < 0.01). This incorporation remained significantly lower throughout the period of study. In contrast, both the total (μmol lysine/g protein nitrogen/h) and fractional rates of protein synthesis which were lower in the transplanted left ventricle at days 3 and 7 returned to control values by day 28. The present studies demonstrate that heterotopic cardiac transplantation leads to a prompt and reproducible decline in cardiac mass and in total protein synthesis. These studies further support the role of cardiac work as an important determinant in the regulation of cardiac protein synthesis.
Progress in Postoperative ICU Management

The clinical case presented in this article illustrates how many of the more recent advances in the management of critically ill patients apply to current clinical practice. Simple cost-effective general measures (eg, optimal sterile precautions during procedures; hand washing; early goal-directed resuscitation with appropriate fluids, inotropes, and antibiotics; and surgical source control of infected foci) still should form the basis of clinical practice, however. There has been renewed interest in blood transfusion therapy and its associated risks. Lower tidal volume ventilation now is practiced almost universally in patients with ARDS, and several new selective pulmonary vasodilators have extended the armamentarium when taking care of these patients. High-frequency oscillatory ventilation and ECMO remain challenging options in patients with refractory hypoxemia. Appropriate patient selection is important when corticosteroid therapy is considered. Tight blood glucose control and monitoring improve outcome and should be part of ICU care of septic patients. The role of the PAC is controversial. Other techniques to measure cardiac output, hemodynamics, and perfusion are available and should be considered. Sedation and analgesia form an integral part of critical care. Because of its immediate and long-term risks, neuromuscular blockade should be used sparingly and only when all other options have been exhausted. Ongoing education regarding sedation protocols and the effect of sedation on outcome is needed among physicians and nurses caring for these patients.
Low threshold, compressively-strained InAsP/InGaAsP and strain-compensated InAsP/InGaP 1.3 [micro sign]m lasers grown by gas source molecular beam epitaxy

1.3 /spl mu/m wavelength strain-compensated InAsP/InGaP/InGaAsP/InP and compressively-strained InAsP/InGaAsP/InP separate confinement heterostructure multiquantum well lasers grown by gas source molecular beam epitaxy are demonstrated for the first time. Record low threshold current densities of 210 A/cm/sup 2/ for 2 mm long broad-area compressively-strained lasers were obtained.
Hegel and Schleiermacher at Berlin: A Many-Sided Debate

Anyone who wishes to understand the debate between Hegel and Schleiermacher is forced to confront not only the staggering complexity of their thought but also the disparate nature of the key texts which are available and the fact that many philosophers and theologians approach Hegel and Schleiermacher with misleading preconceptions. This article attempts to illuminate the conflict between the two thinkers by exploring the biographical and historical context in which it arose. The author argues that, while neither thinker depended upon the other in forming his own position, each man kept the other's position constantly in view as a foil for his own. After a consideration of some early indications of conflict, the debate between Hegel and Schleiermacher is traced through a series of events which begins with Hegel's call to Berlin. While Schleiermacher was apparently quite willing to have Hegel come to Berlin, differences in political philosophy soon led to conflict, with the student movement providing a concrete focus for their disagreement. Schleiermacher's role in excluding Hegel from the Berlin Academy of Sciences is shown to have heightened the tensions. The article concludes with an exploration of Hegel's critique of Schleiermacher's dogmatics. It is argued that the intellectual core of the conflict between the two men centers upon the problem of immediate knowledge. Richard Crouter (Th.D., Union) is Professor of Religion at Carleton College. Currently he is working on a book about Hegel and Schleiermacher on religion. This content downloaded from 157.55.39.124 on Mon, 16 Jan 2017 18:11:42 UTC All use subject to http://about.jstor.org/terms
IMPLEMENTATION OF A TRUST REGION MODEL MANAGEMENT STRATEGY IN THE DAKOTA OPTIMIZATION TOOLKIT

A trust region-based optimization method has been incorporated into the DAKOTA optimization software toolkit. This trust region approach is designed to manage surrogate models of the objective and constraint functions during the optimization process. In this method, the surrogate functions are employed in a sequence of optimization steps, where the original expensive objective and constraint functions are used to update the surrogates during the optimization process. This sequential approximate optimization (SAO) strategy is demonstrated on two test cases, with comparisons to optimization results obtained with a quasi-Newton method. For both test cases the SAO strategy exhibits desirable convergence trends. In the first test case involving a smooth function, the SAO strategy converges to a slightly better minimum than the quasi-Newton method, although it uses twice as many function evaluations. In the second test case involving a function with many local minima, the SAO strategy generally finds better local minima than does the quasi-Newton method. The performance of the SAO strategy on this second test case demonstrates the utility of using this optimization method on engineering optimization problems, many of which contain multiple local optima.
Associations Between Vitamin D Status and Pain in Older Adults: The Invecchiare in Chianti Study

Musculoskeletal pain is a well-documented cause of functional decline and progressive disability in older adults.1,2 With the expectation that the older population will increase 75% over the next 25 years,3 there will inevitably be an increase in prevalence of chronic pain and its associated societal costs. Thus, clinicians and researchers need to gain a better understanding of underlying pain mechanisms that are potentially mutable to develop effective intervention strategies. Vitamin D deficiency has been linked to multiple poor outcomes in older adults, such as greater fracture risk,4 impaired lower extremity function,5 osteomalacia, and pain.6–9 Vitamin D is known to be critically important for the maintenance of bone and muscle health through its role in calcium homeostasis.10 The role of vitamin D in development of pain syndromes is less well known. It has been proposed that hypovitaminosis D-induced pain is due to a lack of calcium phosphate available to mineralize the collagen matrix of bone, with the matrix expanding under the innervated periosteum, leading to diffuse pain.11 Although multiple studies have suggested a link between vitamin D status and pain, particularly back pain,6,7,9,12,13 there have been several studies that have found no relationship between vitamin D status and pain.14–16 The relationship between vitamin D status and pain needs to be further explored. No large-scale study in older adults has examined the association between 25-hydroxyvitamin D (25(OH)D) concentrations and pain in ambulatory older persons. The objective of this study was to examine cross-sectional associations between vitamin D status and musculoskeletal pain using data from the Invecchiare in Chianti (InCHIANTI) Study. The hypothesis was that lower levels of 25(OH)D would be associated with the presence of significant pain in older adults. Because chronic pain is more prevalent in older women,17 whether these relationships would differ according to sex was also examined.
Choosing Motherhood: Matilda Robbins’ Story

Sometime in 1918, after years of adhering to the principle that “intelligent women had no right to bring children into a social chaos,” Matilda Robbins experienced “an overwhelming, unconquerable d...
Modalities for model checking: branching time logic strikes back

Abstract We consider automatic verification of finite state concurrent programs. The global state graph of such a program can be viewed as a finite (Kripke) structure, and a model checking algorithm can be given for determining if a given structure is a model of a specification expressed in a propositional temporal logic. In this paper, we present a unified approach for efficient model checking under a broad class of generalized fairness constraints in a branching time framework extending that of Clarke et al. (1983). Our method applies to any type of fairness expressed in a certain canonical form. Almost all ‘practical’ types of fairness from the literature, including the fundamental notions of impartiality, weak fairness, and strong fairness, can be succintly written in our canonical form. Moreover, our branching time approach can easily be adapted to handle types of fairness (such as fair reachability of a predicate) which cannot even be expressed in a linear temporal logic. We go on to argue that branching time logic is always better than linear time logic for model checking. We show that given any model checking algorithm for any system of linear time logic (in particular, for the usual system of linear time logic) there is a model checking algorithm of the same order of complexity (in both the structure and formula size) for the corresponding full branching time logic which trivially subsumes the linear time logic in expressive power (in particular, for the system of full branching time logic CTL * ). We also consider an application of our work to the theory of finite automata on infinite strings.
Vitronectin: a possible determinant of adenovirus type 19 tropism for human corneal epithelium.

Purpose Adenoviruses typically demonstrate specific tissue tropisms, as in the association of Ad19 with epidemic keratoconjunctivitis. We sought to determine factors that might influence the apparent tropism of Ad19 for the cornea. Design Laboratory investigation. Methods Adenovirus serotypes Ad2, 5, 9, 10, 11, 13, and 19 were compared for their capacity to replicate in human corneal epithelial cells (HCECs) in culture. Organotypically cultured human corneas were infected with Ad19 or Ad2, and viral titers were compared after 7 days. Replication of both viruses was compared in HCECs cultured on various extracellular matrices. Western blot analysis and immunohistochemistry were applied to human donor corneas and HCECs. Results One week after infection of HCEC monolayer cultures, Ad2 titers were significantly higher than any of the other viruses tested ( P P = .0003). Ad2 replication in HCECs equaled or exceeded that of Ad19 on all extracellular matrices except vitronectin, where Ad2 replication was reduced and Ad19 replication enhanced ( P v integrin expression and greater tyrosine kinase phosphorylation in HCECs cultured on vitronectin were demonstrated by Western blot analysis. Conclusions In vitro, vitronectin enhances growth of Ad19, possibly by up-regulation of receptor α v integrins and increased activity of tyrosine kinases necessary for adenoviral internalization. We hypothesize that differential tissue tropisms for adenoviruses may derive in part from tissue-specific extracellular matrix expression.
Two-photon absorption in liquid xenon.

Excitation spectra of two-photon excited xenon near the triple point have been obtained in order to study exciton structure near the band edge. While the band gap is suppressed in the low-temperature liquid, absorption due to even-parity exciton states is presented and discussed. The even-parity ${\mathrm{\ensuremath{\Gamma}}}_{3/2}$,n=2 Wannier excitons observed in the liquid are shifted approximately 0.12 eV to higher energies relative to the energy of odd-parity excitons observed in the liquid by Beaglehole. The absorption linewidths (full width at half maximum) are measured to be 0.15 eV. Comparisons are made to one-photon absorption spectra in xenon.
Averaging using elliptic functions: approximation of limit cycles

We apply the method of averaging to first order in the small parameter e to the autonomous system $$x'' + \alpha x + \beta x^3 + \varepsilon g\left( {x, x'} \right) = 0$$ where we do not consider β as small. This involves perturbing off of Jacobian elliptic functions, rather than off of trigonometric functions as is usually done. The resulting equations involve integrals of elliptic functions which are evaluated using a program written in the computer algebra system MACSYMA. The results are applied to the problem of approximating limit cycles in the above differential equation.
THERMODYNAMICS OF THE UNFOLDING AND SPECTROSCOPIC PROPERTIES OF THE V66W MUTANT OF STAPHYLOCOCCAL NUCLEASE AND ITS 1-136 FRAGMENT

Spectroscopic studies have been performed to characterize the solution structure of the V66W mutant of Staphylococcal nuclease and the corresponding 1−136 fragment, referred to as V66W‘. Whereas wi...
A protective function for noncoding, or secondary DNA

The genome of many eukaryotic organisms contains a large amount of noncoding, or secondary DNA. I propose that secondary DNA functions as a sink for the integration of viral and nonviral inserting elements, thereby protecting coding sequences from insertional damage.
Visualizing F-Actin Structure in Developing Zebrafish Zygotes to Supplement Viscoelastic Measurements

The cell has developed an elaborate cytoskeleton that can undergo dramatic rearrangements in order to grow, divide, or move. In the one-cell stage of the zebrafish embryo, the cytoskeleton completely reorganizes to form the cellular compartment. We want to understand the link between the morphological structure of the cell's cytoskeleton and the mechanical properties of the cell. That is, we want to find out if rearrangements of filamentous cytoskeletal proteins like F-actin and microtubules lead to changes in cellular viscosity or elasticity. To do this, we need to correlate images of cytoskeletal structures with mechanical measurements. In this part of our project, we imaged the rearrangement of the F-actin network during cytoskeletal formation in the one-cell stage of the zebrafish embryo. These images will complement microrheology measurements of the viscoelasticity of the cell. To take images, we fixed the embryo and labeled the cellular F-actin with the dye phalloidin. We then imaged the mounted embryos on a confocal microscope to see the F-actin organization. Our images show that just before cellular cleavage, the F-actin has collected at the cellular periphery, similar to previous work.
Hypoglycemia in Prader–Willi syndrome

Although mouse models of Prader-Willi syndrome (PWS) suggest that hypoglycemia may be part of this syndrome, review of the literature shows little evidence that it is an issue in humans with PWS. Both adrenal and growth hormone deficiency can be seen in PWS, and both of these hormone deficiencies are associated with increased risk for hypoglycemia. We reviewed medical records for patients with PWS seen at the University of Florida Prader-Willi Program. Children were 2 months to 5 years of age. We recorded the presence, degree, and persistence of hypoglycemia, age of first occurrence, genetic diagnosis, and gestational age. Repeated hypoglycemia was determined if individuals had multiple blood glucose (BG) values <50 mg/dl before 1 month old, or BG levels <50 mg/dl once and additional BG values <70 mg/dl after 1 year of age. Of 95 patient charts reviewed, 12 (12.6%) had recorded hypoglycemia. Six of 12 patients with hypoglycemia had documented BG levels <40 mg/dl. Seven had their first episode of hypoglycemia within the first day of life. Of these seven individuals, five had BG <40 mg/dl. Repeated hypoglycemia was noted in 10 patients (83% of all patients with hypoglycemia). Only two with hypoglycemia had documented adrenal insufficiency. Our study suggests that infants with PWS may be predisposed to hypoglycemia from birth. Additional investigation is necessary to confirm our findings and define the cause of hypoglycemia. If the presence of hypoglycemia is confirmed, early detection and treatment may result in improved neurocognitive outcomes.
Larval hindgut of Manduca sexta (L.) (Lepidoptera: Sphingidae)☆

Abstract A detailed study of the hindgut of 5th-instar larvae of the tobacco horn-worm, Manduca sexta (L.), revealed a unique muscle-nerve complex that consists of a network of innervated muscle extensions derived from the underlying, supercontracting circular muscles of the ileum and colon. The extensions are innervated by axons from the proctodaeal nerve, that appear to originate from 2 giant multinucleated cells positioned on the dorsal branch of the proctodaeal nerve over the rectal valve region. This neuromuscular complex is used to move a fully formed fecal pellet from the ileum to the rectum. A sensory neuron is positioned at the anterior end of the ileum, and its axon merges with the proctodaeal nerve. Dendrites from this neuron are associated with the anterior surface of the ileum, and the neuron appears to function as a stretch receptor regulating the muscular activity of the pylorus by sensing the dilation of the ileum.
How to measure CMB polarization power spectra without losing information

We present a method for measuring CMB polarization power spectra given incomplete sky coverage and test it with simulated examples such as Boomerang 2001 and MAP. By augmenting the quadratic estimator method with an additional step, we find that the E and B power spectra can be effectively disentangled on angular scales substantially smaller than the width of the sky patch in the narrowest direction. We find that the basic quadratic and maximum-likelihood methods display an unneccesary sensitivity to systematic errors when $T\ensuremath{-}E$ cross-correlation is involved, and show how this problem can be eliminated at negligible cost in increased error bars. We also test numerically the widely used approximation that sample variance scales inversely with sky coverage, and find it to be an excellent approximation on scales substantially smaller than the sky patch.
Early feeding after cesarean: a randomized clinical trial

Abstract Objective: To determine if early introduction of solid food decreases postoperative pain and improves patient satisfaction. Methods: We performed a randomized clinical trial on low-risk, consenting women after cesarean delivery. Fifty-four patients were randomly assigned to receive either a traditional diet (nothing by mouth the day of surgery, liquids day 1, and solid food after flatus) or early feeding (solid food begun 6 hours after surgery). Charts were abstracted for number of complaints (nausea, vomiting, gas pain) and number of requests for analgesics. At discharge, patients were interviewed regarding their pain severity, pain control, and diet satisfaction. Results: Our sample size could detect a 25% difference in analgesic request. The groups were similar regarding demographic and intraoperative characteristics. Objective complaints and subjective responses are shown below. Conclusions: Compared with traditional diet management, early feeding after cesarean does not decrease objective or subjective indices of postoperative pain. Other than a modest increase in subjective pain severity, early feeding was not associated with significant complications and, thus, is an acceptable alternative to the traditional regimen. Traditional (N = 28) Early (N = 26) P value Patient complaints Analgesic requests (N) 11 ± 5 12 ± 7 0.70 Gas pain (N) 1.3 ± 1.8 2.0 ± 1.9 0.12 Nausea (N) 0.30 ± 0.6 0.04 ± 0.2 0.06 Vomiting (N) 0.07 ± 0.4 0.04 ± 0.2 1.0 Questionnaire (1 = least to 5 = most) Pain severity 1.6 ± 0.8 2.0 ± 0.6 0.04 Pain control 4.5 ± 0.6 4.2 ± 0.6 0.05 Satisfaction 4.2 ± 0.9 4.5 ± 0.7 0.25
Simvastatin and ROCK inhibition in Th0 and Th17 systems

Purpose The deregulation of the Def6-ROCK2-IRF4 axis in murine models results in both lupus-like and rheumatoid arthritis-like disease characterized by increased IL-17 and IL-21 production that is ameliorated by ROCK inhibition. A known beneficial pleiotropic effect of statins is inhibition of ROCK activation via their effect on RhoA activation. Statins have also been reported to decrease IL-17 and IL-21 production in T cells. Whether statins exert their inhibitory effects by interfering with the ROCK2-IRF-4 interaction in CD4+ T cells is unknown. The aim of the present study is to investigate whether statins can inhibit the ROCK pathway in CD4+ T cells and inhibit IL-17 and IL-21 production.
The effect of iso-thermal aging on vibrational performance of SAC 105 and 305 alloys

Ball grid array (BGA) packages have rapidly become the popular choice of manufacturers in the semiconductor industry over the past decade. The characteristics of BGA packages in a vibration environment have a deleterious effect after long term isothermal aging. The effectiveness of this characteristics was demonstrated with promising results through vibration testing of SAC 105 and 305 alloys. This experiment focuses on the vibration fatigue life of 10 mm, 15 mm and 19 mm BGA solder-joints at aging temperatures of 55°C for 6, 12 and 24 months. The deleterious effect of the on the characteristic fatigue lifetime is reported. The results show that the aging time has a direct impact on the total time to failure. The results show that the Time-To-Failure (TTF) of the solder joint decreases with aging. A step stress test approach was taken in selecting a vibration profile for the study in order to reduce the duration of the test with most failures and as to record the failure more precisely over aging across 6,12 and 24 months. The paper concludes with discussion of the deterioration intensity aging has on SAC alloys and the change in reliability over time. The results obtained in this work show that there is a significant deleterious effect on the mechanical strength of SAC alloy solder balls during elevated temperature aging. The data demonstrate that the low-silver-content alloy (SAC105) is more sensitive to elevated temperature aging.
Infection of monocytes or immature dendritic cells (DCs) with an attenuated rabies virus results in DC maturation and a strong activation of the NFκB signaling pathway

To assess the potential role of dendritic cells (DCs) or monocytes in the development of a protective immune response, we infected human immature DCs or monocytes with a live rabies virus (RV) vaccine strain (SPBNGAS-GAS) and a pathogenic RV (DOG4). Both cell types were infected with SPBNGAS-GAS and DOG4 and both RVs were similarly potent in inducing maturation of immature DCs or monocytes. However, in contrast to DOG4, SPBNGAS-GAS induced very high levels of IFN-alpha1 mRNA in monocytes and DCs. Furthermore, at least 26 other genes related to the NFkappaB signaling pathway were strongly upregulated in SPBNGAS-GAS-infected DCs, but only somewhat increased in DOG4-infected cells. Thus, the extent of upregulation of NFkappaB pathway-related genes in DCs infected with the live RV vaccine strain might explain the strong protective activity of SPBNGAS-GAS.
Reduction of odometry errors in over-constrained mobile robots

This paper presents an analysis of odometry errors in over-constrained mobile robots, that is, vehicles that have more independent motors than degrees of freedom. Based on our analysis we developed and examined three novel error-reducing methods. One method, called “Fewest Pulses” method, makes use of the observation that most terrain irregularities, as well as wheel slip, result in an erroneous over-count of encoder pulses. A second method, called “Cross-coupled Control,” optimizes the motor control algorithm of the robot to reduce synchronization errors that would otherwise result in wheel slip with conventional controllers. The third method is based on so-called Expert Rules. With this method readings from redundant encoders are compared and utilized in different ways, according to predefined rules. In the work described here we implemented our three error reducing methods on a modified Pioneer AT skid-steer platform and compared their odometric accuracy. The results in this paper point to clear advantages of the Expert Rule-based method over the other tested methods.