cssi/SciSciGPT-SciSciNet huggingface dataset:
Recent liquid lithium limiter experiments in CDX-U

Recent experiments in the Current Drive Experiment-Upgrade (CDX-U) provide a first-ever test of large area liquid lithium surfaces as a tokamak first wall to gain engineering experience with a liquid metal first wall and to investigate whether very low recycling plasma regimes can be accessed with lithium walls. The CDX-U is a compact (R = 34 cm, a = 22 cm, Btoroidal = 2 kG, IP = 100 kA, Te(0) ∼ 100 eV, ne(0) ∼ 5 × 10 19 m −3 ) spherical torus at the Princeton Plasma Physics Laboratory. A toroidal liquid lithium pool limiter with an area of 2000 cm 2 (half the total plasma limiting surface) has been installed in CDX-U. Tokamak discharges which used the liquid lithium pool limiter required a fourfold lower loop voltage to sustain the plasma current, and a factor of 5–8 increase in gas fuelling to achieve a comparable density, indicating that recycling is strongly reduced. Modelling of the discharges demonstrated that the lithium limited discharges are consistent with Zeffective < 1.2 (compared with 2.4 for the pre-lithium discharges), a broadened current channel and a 25% increase in the core electron temperature. Spectroscopic measurements indicate that edge oxygen and carbon radiation are strongly reduced.
Exploiting disruption aversion to control code bloat

The authors employ multiple crossovers as a novel natural extension to crossovers as a mixing operator. They use this as a framework to explore the ideas of code growth. Empirical support is given for popular theories for mechanisms of code growth. Three specific algorithms for multiple crossovers are compared with classic methods for performance in terms of fitness and genome size. The details of the performance of these algorithms is examined in detail for both practical value and theoretical implications. The authors conclude that multiple crossovers is a practical scheme for containing code growth without a significant loss of fitness.
Amenable Coverings of Complex Manifolds and Holomorphic Probability Measures

Let π : Y → X be a covering map between complex manifolds X and Y . For many holomorphic objects (such as functions or forms) one can define a pushforward operator π∗ carrying objects on Y to objects on X by summing over the fiber. The pushforward is efficient if there is little cancellation in the sum. To achieve efficiency, there must be coherence in phase on different sheets of the covering. In this paper we will demonstrate a direct connection between efficiency of the push-forward π∗ and amenability of the covering π. The latter is a purely combinatorial property of the pair of groups π1(Y ) ⊂ π1(X); the covering is amenable if there exists a π1(X)-invariant finitely additive probability measure on the coset space π1(X)/π1(Y ). Amenability is discussed in more detail in §3. The connection will be established by studying complex-valued measures on the fibers of the covering, varying holomorphically with respect to the base.
A Calculus of Multiparameter Martingales and its Applications

Let Wt be a standard one-parameter Wiener process, and let X be a process defined by $${X_t} = {X_0} + \int\limits_0^t {{\theta _s}d{W_s} + \int\limits_0^t {{b_s}ds} } $$ (1.1) where the first integral is an Ito stochastic integral. For a continuouly twice differentiate function f the celebrated Ito lemma [3] yields the representation $$f\left( {{X_t}} \right) = f\left( {{X_0} + \int\limits_0^t {f'\left( {{X_s}} \right)\left[ {{\theta _s}d{W_s} + {b_s}ds} \right] + \frac{1}{2}\int\limits_0^t {f''\left( {{X_s}} \right)\theta _s^2ds} } } \right)$$ (1.2) which shows that the representation (1.1) of a process as the sum of a stochastic integral plus an ordinary Lebesgue integral is unchanged under C2 transformations.
Historical demography of freshwater mussels (Bivalvia: Unionidae): genetic evidence for population expansion and contraction during the late Pleistocene and Holocene

Genetic variation was examined in two endangered mussel species, Epioblasma brevidens and Epioblasma capsaeformis, and in a non-listed species, Lampsilis fasciola, in the Clinch River, Tennessee, USA, by screening mitochondrial DNA (mtDNA) sequences and nuclear DNA microsatellites. Patterns of mtDNA polymorphism exhibited different trends in long-term population sizes for each species during the late Pleistocene and Holocene (∼20 000 ya to present); namely, E. brevidens has declined over time, E. capsaeformis has remained demographically stable, and L. fasciola has expanded. However, analyses using microsatellites did not exhibit similar trends, perhaps because homoplasy had eliminated long-term population signatures for the loci examined. For both marker types, long-term effective population size (Ne) was low in E. brevidens, intermediate in E. capsaeformis, and high in L. fasciola. Moderately diverged mtDNA lineages, perhaps indicative of secondary contact, were observed in E. brevidens and E. capsaeformis. Perhaps the most surprising result of this study was the high level of genetic variation observed at both mtDNA and microsatellite DNA markers for L. fasciola, variation seemingly contrary to the relatively small demes that currently reside in the Clinch River. However, the data are consistent with known demographic and life-history traits of these three mussel species and their fish hosts, namely that they each use hosts with different dispersal capabilities, ranging from low, moderate, and high, respectively. The low divergence of mtDNA sequence variation reported in this and other recent mussel studies indicates that considerable extant population genetic variation probably originated during the late Pleistocene and Holocene. © 2015 The Linnean Society of London, Biological Journal of the Linnean Society, 2015, 114, 376–397.
A virtual test bed for power electronic circuits and electric drive systems

Applications of the virtual test bed (VTB) to a power electronic circuit and an electric drive system are described. The VTB is a software environment that has been developed for design, analysis and virtual prototyping of large-scale multi-technical systems. It has the capability of integrating models, which have been created in a variety of languages such as SPICE, ACSL and SABER, into one simulation environment. It also provides advanced visualization of simulation results including full-motion animation of mechanical components. These two important features of the VTB are utilized in the modeling and simulation of a power electronic circuit and an electric drive system.
Structural and Mutational Analysis of a Conserved Gene (DGSI) from the Minimal DiGeorge Syndrome Critical Region

The majority of patients with DiGeorge syndrome (DGS), velocardiofacial syndrome (VCFS), conotruncal anomaly face syndrome (CTAFS) and some individuals with familial or sporadic conotruncal cardiac defects have hemizygous deletions of chromosome 22. Most patients with these disorders share a common large deletion, spanning > 1.5 Mb within 22q11.21-q11.23. Recently, the smallest region of deletion overlap has been narrowed to a 250 kb area, the minimal DGS critical region (MDGCR), which includes the locus D22S75 (N25). We have isolated and characterized a novel, highly conserved gene, DGSI, within the MDGCR. DGSI has 10 exons and nine introns encompassing 1702 bp of cDNA sequence and 11 kb of genomic DNA. The encoded protein has 476 amino acids with a predicted mol. wt of 52.6 kDa. The intron-exon boundaries have been analyzed and conform to the consensus GT/AG motif. The corresponding murine Dgsi has been isolated and localized to proximal mouse chromosome 16. The mouse gene contains the same number of exons and introns, and the predicted protein has 479 amino acids with 93.2% identity to that of the human DGSI gene. By database searching, both genes have significant homology to a Caenorhabditis elegans hypothetical protein, F42H10.7. Further, mutation analysis has been performed in 16 patients, who have no detectable 22q11.2 deletion and some of the characteristic clinical features of DGS/VCFS. We have detected eight sequence variants in DGSI. These occurred in the 5'-untranslated region, the coding region and the intronic regions adjacent to the intron-exon boundaries of the gene. Seven of the eight variants were also present in normal controls or unaffected family members, suggesting they may not be of etiologic significance.
Genetics of Essential Hypertension– Historical perspective and current concept

Essential hypertension was first recognized as morbid entity in 1911 and the word “essential” was substituted by “constitutional” in 1933. Diastolic hypertension may be constitutional or “symptomatic” if it belongs to the symptoms of a disease of specific organs (kidneys, endocrine, metabolic disease, cerebral or vascular disease). It is futile to search for such a diseased specific organ in constitutional hypertension (1933). Constitutional hypertension is a constitutional variant due to insufficient perfection of the homeostatic (feed-back) system maintaining the habitual blood pressure at a constant normal level. It is of multifactorial (polygenic) etiology (1960). It is a definite predisposition to actual diseases. It is a matter of semantics whether or not it should be called a disease of its own. The syntropy of constitutional hypertension and diabetes, obesity and arteriosclerosis is best explained by sharing various parts of polygenomes that are the common genetic basis of each of these morbid states.
Roles of Anthrax Toxin Receptor 2 in Anthrax Toxin Membrane Insertion and Pore Formation

Interaction between bacterial toxins and cellular surface receptors is an important component of the host-pathogen interaction. Anthrax toxin protective antigen (PA) binds to the cell surface receptor, enters the cell through receptor-mediated endocytosis, and forms a pore on the endosomal membrane that translocates toxin enzymes into the cytosol of the host cell. As the major receptor for anthrax toxin in vivo, anthrax toxin receptor 2 (ANTXR2) plays an essential role in anthrax toxin action by providing the toxin with a high-affinity binding anchor on the cell membrane and a path of entry into the host cell. ANTXR2 also acts as a molecular clamp by shifting the pH threshold of PA pore formation to a more acidic pH range, which prevents premature pore formation at neutral pH before the toxin reaches the designated intracellular location. Most recent studies have suggested that the disulfide bond in the immunoglobulin (Ig)-like domain of ANTXR2 plays an essential role in anthrax toxin action. Here we will review the roles of ANTXR2 in anthrax toxin action, with an emphasis on newly updated knowledge.
Cognitive-behavioral interventions in childhood anxiety disorders

Anxiety disorders are among the most common conditions affecting children and adolescents (Costello and Angold, 1995) with most modern epidemiological reports estimating the prevalence of significant anxiety disorders at greater than 10% worldwide (Pine, 1994) and from 12% to 20% in the USA (Kessler et al., 1994; Achenbach et al., 1995; Shaffer et al., 1996). Nevertheless, and in spite of the high prevalence, anxiety in childhood has not been as well studied as many other less common childhood disorders, possibly due to the incorrect perception that this problem is typically transient and innocuous (Benjamin et al., 1990). Over the last decade, however, our understanding of the phenomenology, prevalence, and treatment of childhood anxiety has increased dramatically. Although cognitive factors are presumed to play an important role in the expression and maintenance of childhood anxiety and most treatments contain at least some cognitive techniques specifically addressing these factors, only a handful of studies have been published investigating cognitive aspects of anxiety in children and adolescents. In addition to the epidemiological findings, recent studies suggest that anxiety disorders in childhood are highly comorbid, relatively stable over time, and associated with significant impairment both acutely and over the long term. Clinic and community studies suggest that 50–75% of anxious children demonstrate two or more anxiety diagnoses (Costello and Angold, 1995; Last et al., 1987), and that comorbidity with both mood and externalizing disorders is also common (Bernstein and Borchardt, 1991; Ollendick and King, 1994).
Substitution on Metallaboranes at Boron. Syntheses of closo-1-X-[2,3,4-(η5-C5Me5)3(μ-H)2Co3B2H], X = Cl and OH, and closo-1,5-Cl2-[2,3,4-(η5-C5Me5)3(μ-H)2Co3B2] from closo-[2,3,4-(η5-C5Me5)3(μ-H)2Co3B2H2]†

The reaction of closo-[2,3,4-(η5-C5Me5)3(μ-H)2Co3B2H2], 1, with metal chlorides results in the formation of either closo-1-Cl-[2,3,4-(η5-C5Me5)3(μ-H)2Co3B2H], 2, or closo-1,5-Cl2-[2,3,4-(η5-C5Me5)3...
P143 Single molecule analysis of the RIG-I-like receptor, LGP2

Introduction The RIG-I-like receptor (RLR) proteins, RIG-I, MDA5, and LGP2 are cytoplasmic DExD/H box proteins that function to specifically recognize molecular features of RNA species that discriminate the pathogen from the host. Both RIG-I and MDA5 are able to activate downstream antiviral signal transduction, while LGP2 has been linked to diverse effector functions both upstream and downstream of RIG-I and MDA5, leaving the overall function of LGP2 largely unresolved. All of the RLRs bind dsRNA with varying affinities and exhibit RNA-enhanced ATP hydrolysis activity. The RNA binding ability of these proteins is critical for antiviral responses, but the importance of ATP hydrolysis is poorly understood. Methods We have utilized biochemical methods and single molecule TIRF microscopy-based imaging to investigate the enzymatic and RNA binding activities of LGP2 and mutant variants. Results LGP2 was found to have a uniquely high level of basal ATP hydrolysis activity in the absence of dsRNA, in addition to the dsRNA-enhanced ATP hydrolysis activity. These two enzymatic activities are separable by specific point mutations to LGP2 that create defects in basal, but not dsRNA-stimulated, ATP hydrolysis. Single molecule analysis of LGP2-dsRNA interaction revealed no evidence for ATP-driven LGP2 translocation on dsRNA, as was reported for RIG-I. Instead, we observe that ATP hydrolysis activity enhances the ability of LGP2 to engage dsRNA. This ATP-enhancement of dsRNA binding requires basal ATP hydrolysis activity, and enables LGP2 to form more interactions with diverse dsRNA ligands that are intrinsically poor substrates. Conclusion These findings indicate LGP2 uses basal ATP hydrolysis to enable recognition of a broader range of target dsRNA ligands.
Preparation of the Hard Metals Containing Small Amounts of Cobalt by Mechanical Alloying Treatment

Hard metals containing small amounts of cobalt were prepared by mechanical alloying using a vibrational ball mill in Ar atmosphere under reduced pressure. The contamination in the hard metal during mechanical alloying was attributed to wear of vibrational balls and could be reduced by using hard metal balls. Although mechanical alloying treatment was effective for the hard metals containing less than 3 mass%Co, increasing in cobalt content resulted in the formation of η phase (Co3W3C).A mechanical alloyed WC-lmass%Co hard metal, sintered at 1773K for 1.2ks in a vacuum, showed finer structure and higher hardness than a mixed WC-1mass%Co one.
Social Workers and LGBT Policies: Attitude Predictors and Cultural Competence Course Outcomes

Lesbian, gay, bisexual, and transgender (LGBT) people are gaining ground in civil rights but still experience exclusion or discrimination through social policy, and policy advocacy on behalf of LGBT people is an ongoing need. Social work practice areas intersect with policies that are relevant to LGBT people’s civil rights. This study examined the effects of social work graduate students’ gender, political views, religious attendance, beliefs about sexual orientation and gender identity choice, active critical thinking, and empathy, in combination with a cultural competence course, on attitudes about LGBT military policy, marital equality, and LGBT discrimination. Men and more conservative students had less affirming attitudes about LGBT military policy. Men and students with more conservative political ideology, less empathy, and more active thinking held less affirming attitudes about marital policy. Students who believed that sexual orientation and gender identity are not a choice were more likely to report recognition of LGBT discrimination. Students changed significantly after the course in their acknowledgement of discrimination, and attitudes stayed the same (generally affirming) about military policy and marital laws. Implications for examining critical thinking and empathy and attitudes about military policy and measuring course interventions for social workers with regard to attitudes about LGBT discrimination and related policies are discussed, and recommendations are made for future research.
Preventive effect and mechanism of Salviae miltiorrhizae on fibroblast proliferation

Objective To investigate the inhibitive effect and mechanism of Salviae miltiorrhizae on fibroblast proliferation,and provide new medicine for the prevention of proliferative vitreoretinopathy.Methods Using 5-Fu,dexamethasone and hydrocortisone as contrast,the rabbit conjunctival fibroblast cultured in vitro was treated with Salviae miltiorrhizae.After 48 hours of incubation with medicine above,the proliferative alteration of fibroblast was detected by MTT.After different time points of incubation with Salviae miltiorrhizae with different concentrations,the apoptotic rate of fibroblast was detected by flow cytometry.After 48 hours of incubation with Salviae miltiorrhizae,the apoptosis of cultured conjunctival fibroblast was determined by TUNEL method.Results Salvia miltiorrhizae with certain concentrations(from 1.74 g·L-1 to 111.00 g·L-1) could inhibit the proliferation of in a dose-dependent manner.The apoptotic rate of Salviae miltiorrhizae with 3.47 g·L-1,27.75 g·L-1 and 111.00 g·L-1 on fibroblast at 6 hours were(8.67±0.97)%,(11.04±1.04)% and(20.83±1.74)%,which at 24 hours were(13.06±1.41)%,(25.68±1.21)% and(39.65±0.23)%,respectively;Compared with the contrast group(4.40±0.08)%,there were significant differences(all P0.01).After 48 hours of incubation with different concentrations of Salviae miltiorrhizae,the nucleus of fibroblast showed positive staining.Conclusion Salviae Miltiorrhizae inhibit the proliferation of fibroblast by inducing their apoptosis,and has the potential role in treating proliferative vitreoretinopathy.
Beyond the Nash Equilibrium Barrier.

Nash equilibrium analysis has become the de facto standard for judging the solution quality achieved in systems composed of selfish users. This mindset is so pervasive in computer science that even the few papers devoted to directly analyzing outcomes of dynamic processes in repeated games (e.g., best-response or no-regret learning dynamics) have focused on showing that the performance of these dynamics is comparable to that of Nash equilibria. By assuming that equilibria are representative of the outcomes of selfish behavior, do we ever reach qualitatively wrong conclusions about those outcomes? In this paper, we argue that there exist games whose equilibria represent unnatural outcomes that are hard to coordinate on, and that the solution quality achieved by selfish users in such games is more accurately reflected in the disequilibrium represented by dynamics such as those produced by natural families of on-line learning algorithms. We substantiate this viewpoint by studying a game with a unique Nash equilibrium, but where natural learning dynamics exhibit non-convergent cycling behavior rather than converging to this equilibrium. We show that the outcome of this learning process is optimal and has much better social welfare than the unique Nash equilibrium, dramatically illustrating that natural learning processes have the potential to significantly outperform equilibrium-based analysis.
Age Smile - Evolution of Firm Value

Pastor and Veronesi (2003) proposed a model in which as investors learn more about a firm’s future profitability and therefore as the profitability uncertainty declines, the firm value, in terms of market-to-book ratio will decline. In this study, I tried to extend their work by examining the evolution of firm value over a longer life span and found that the change of firm value over time exhibited a “U-shape”. For firms that were at their early stage of their life span, the decline in profitability uncertainty dominated the process of firm valuation and caused firm value to decline as the learning model predicts; while for firms that were at more mature stage of their life span, the decline in cost of equity dominated the process of firm valuation and caused firm value to increase. But paying dividends had a mixed impact on firm value: market-to-book ratio has a negative association with dividend dummy while paying dividend helps older firms to reduce their cost of equity which in turn helps to boost market-to-book ratio; furthermore, for older firms paying dividend also helps to smooth valuation fluctuations.
Prenatal Diagnosis of Congenital Diaphragmatic Hernia with Predictors of Mortality

Since the late 1970s, congenital diaphragmatic hernia (CDH) has been diagnosed antenatally by ultrasound. With improvements in ultrasound resolution, CDH is being diagnosed more frequently and at an earlier stage in gestation. This provides an opportunity to administer in utero therapy to the fetus. As 50% of babies born with CDH survive, it is imperative that accurate prognostic indicators are available to guide antenatal therapy. Antenatal diagnosis and prognostic indicators are discussed.
Transport Behavior of Dense Protons in a Slab

Absorbed hydrogen in a transition metal may be to a first order approximation regarded as a system of protons interacting pairwise via long-range forces. By limiting momentum transfers in proton-proton scattering to small wavevectors, the relaxation func­tion for a many-proton system is obtained analytically by a method of recurrence relations recently developed by Lee. Other dynamical quantities including diffusivity are also obtained analytically.
Indirect Effects of Attributional Style for Positive Events on Depressive Symptoms Through Self-Esteem During Early Adolescence

Research on adolescent depression has overwhelmingly focused on risk factors, such as stressful negative events and cognitive vulnerabilities, but much important information can be gained by focusing on protective factors. Thus, the current study aimed to broaden understanding on adolescent depression by considering the role of two positive elements as protective factors, attributional style for positive events and self-esteem, in a model of depression. The sample included 491 middle school students (52 % female; n = 249) with an age range from 12 to 15 years (M = 13.2, SD = .70). The sample was ethnically/racially diverse, with 55 % White, 22 % Hispanic, 10 % Asian American, 3 % African American, and 10 % Biracial/Other. Correlational analyses indicated significant cross-sectional and longitudinal associations between an enhancing attributional style (internal, stable, global attributions for positive events), self-esteem and depressive symptoms. Further, prospective analyses using bootstrapping methodology demonstrated significant indirect effects of an enhancing attributional style on decreases in depressive symptoms through its effects on self-esteem. These findings highlight the importance of considering attributional style for positive events as a protective factor in the developmental course of depressive symptoms during early adolescence.
Atypical pneumonia syndrome.

A variety of microbial agents can cause atypical pneumonia. Accurate diagnosis requires knowledge of the salient features specific for these infections and allows for appropriate initiation of antimicrobial therapy.
Patient-Specific Implants and Instruments Improved Outcomes of Total Knee Replacement

Introduction: Patient-specific cutting guides (PSCG) built from imaging of the extremity can improve the accuracy of bone cuts during total knee replacement (TKR). Some reports have suggested that PSCG offer only marginal improvement in the accuracy of alignment and component positioning in TKA. We compared outcomes between TKRs done with PSCG versus standard, intramedullary-based instrumentation. Methods: Blood loss, duration of surgery, alignment of the mechanical axis of the leg, and implant position on standing, long-leg, and standard lateral digital radiographs were compared between a CT-guided, custom-built TKA implant (n = 50; ConforMIS iTotal, Boston, MA) implanted with PSCG, versus an off-shelf posterior stabilized TKA implanted with standard instrumentation (n = 50; NKII total knee, Zimmer, Warsaw, IN). The fraction of outliers (>3 degrees) was calculated for the two groups. Results: The mean mechanical axis of iTotal was 181 degrees with a fraction of outliers of 0.2, versus 178 degrees for NKII with fraction of outliers of 0.7. For frontal plane positioning of femoral components, fraction of outliers for iTotal was 0.04, versus 0.6 for NKII. For tibial components, corresponding values were 0.1 and 0.6, respectively. Sagittal plane outliers were 0.2 and 0.9, respectively, for femoral components; and 0.2 and 0.6 for tibial components. Surgery duration was 5 minutes less and blood loss was 100 mL less for iTotal than for intramedullary-aligned NKII. Conclusion: Patient specific instrumentation and custom-built implants showed a trend toward improved accuracy of alignment, reduction in blood loss and operating time, when compared to standard, off-the-shelf TKA implants with intramedullary alignment, with fewer radiographic outliers. Larger, randomized trials are necessary to evaluate this technology further, but the initial outcomes appear favorable, with no cost disadvantage to the custom-built implant.
A Phase I/II Study of Escalating Doses of Bortezomib in Conjunction with High-Dose Melphalan as a Conditioning Regimen for Salvage Autologous Peripheral Blood Stem Cell Transplantation in Patients with Multiple Myeloma

Abstract Escalating doses of bortezomib with high-dose melphalan was evaluated as as a conditioning regimen for autologous stem cell transplantation (ASCT) in patients with relapsed or refractory multiple myeloma (MM). MM patients with less than a partial remission (PR) (or 50% reduction) compared to their pretransplantation paraprotein parameters after a prior ASCT with melphalan conditioning, or who were in relapse after a prior autologous transplantation, were eligible for study. Bortezomib was dose escalated in steps of 1, 1.3, and 1.6 mg/m2 (3 × 3 design) on days −4 and −1 before transplantation with melphalan 200 mg/m2 given on day −2. Thirty-two patients were enrolled: 12 in the phase I dose escalation phase and an additional 20 in phase II to gain additional experience with the regimen. Twenty-four (75%) patients were Durie Salmon stage III, and 12 (37.5%) had >2 prior lines of therapy. The overall response rate (≥PR) was 44% with 22% complete remission. Two-year overall survival and progression-free survival were 76% and 39%, respectively, with a median follow-up of 31.7 months. The most common grade 3 and 4 nonhematologic adverse events were neutropenic fever (25%), nausea (18.8%), and mucositis (9.4%). Serious adverse events included intensive care unit admission (9.4%), seizure (3.1%), prolonged diarrhea (3.1%), and Guillain-Barre syndrome (3.1%). Two patients (6%) died of sepsis. There was no emergent peripheral neuropathy nor increase in any pre-existing peripheral neuropathy. The addition of bortezomib to melphalan as conditioning for salvage ASCT was well tolerated. More importantly, it can provide durable remission for patients who have a suboptimal response to prior single-agent melphalan conditioning for ASCT, without requiring a reduction in the dose of melphalan. Larger randomized prospective studies to determine the effect of combination conditioning are being conducted.
Using multitemporal night-time lights data to compare regional development in Russia and China, 1992–2012

Multitemporal remotely sensed night-time lights data are often used as a proxy for population and economic growth, with China the most commonly researched area. Less is known about how lights respo...
Corrosion in the Human Body: Metallic Implants in the Complex Body Environment

Metals and alloys have been used in the human body as biomaterials to repair, replace, or augment tissues and structures for many decades. A principal concern in the use of metals in the body is th...
Biventricular differences in β-adrenergic receptor signaling following burn injury

Burn injury detrimentally affects the myocardium, primarily due to over-activation of β-adrenergic receptors (β-AR). Autopsy reports from our institution reveal that patients often suffer from right ventricle (RV) failure. Since burn injury affects β-AR signaling in the left ventricle (LV), we proposed that β-AR signaling may also be altered in the RV. A rodent model with a scald burn of 60% of the total body surface area was used to test this hypothesis. Ventricles were isolated 7 days post-burn. We examined the expression of β-ARs via Western blotting and the mRNA expression of downstream signaling proteins via qRT-PCR. Cyclic adenosine monophosphate (cAMP) production and protein kinase A (PKA) activity were measured in membrane and cytosolic fractions, respectively, using enzyme immunoassay kits. β1-AR protein expression was significantly increased in the RV following burn injury compared to non-burned RV but not in the LV (p = 0.0022). In contrast, β2-AR expression was unaltered among the groups while Gαi expression was significantly higher in the LV post-burn (p = 0.023). B-arrestin-1 and G-protein coupled receptor kinase-2 mRNA expression were significantly increased in the left ventricle post-burn (p = 0.001, p<0.0001, respectively). cAMP production and PKA activity were significantly lower in the LV post-burn (p = 0.0063, 0.0042, respectively). These data indicate that burn injury affects the β-AR signaling pathway in the RV independently of the LV. Additionally, non-canonical β-AR signaling may be activated in the RV as cAMP production and PKA activity were unchanged despite changes in β1-AR protein expression.
Multimodal Examination of Atrial Fibrillation Substrate: Correlation of Left Atrial Bipolar Voltage Using Multi-Electrode Fast Automated Mapping, Point-by-Point Mapping, and Magnetic Resonance Image Intensity Ratio.

Abstract Objectives The aim of this study was to examine atrial fibrillation (AF) substrate using different modalities (point-by-point [PBP], fast anatomic mapping [FAM], and late gadolinium enhancement [LGE] magnetic resonance imaging [MRI] mapping) in patients presenting for AF ablation. Background Bipolar voltage mapping, as part of AF ablation, is traditionally performed in a PBP approach using single-tip ablation catheters. Alternative techniques for fibrosis delineation include FAM with multi-electrode circular catheters and LGE MRI. The correlation between PBP, FAM, and LGE-MRI fibrosis assessment is unknown. Methods LGE MRI was performed pre-ablation in 26 patients (73% men, mean age 63 ± 8 years). Local image intensity ratio (IIR) was used to normalize myocardial intensities. PBP and FAM voltage maps were acquired, in sinus rhythm, prior to ablation and coregistered with LGE MRI. Results The mean bipolar voltage for all 19,087 FAM voltage points was 0.88 ± 1.27 mV, and the average IIR was 1.08 ± 0.18. In an adjusted mixed-effects model, each unit increase in local IIR was associated with a 57% decrease in bipolar voltage (p 0.74 corresponded to a bipolar voltage Conclusions LGE-MRI, FAM, and PBP mapping showed good correlation in delineating electroanatomic AF substrate. Each approach has fundamental technical characteristics, the awareness of which allows proper assessment of atrial fibrosis.
Characterization of flexible pH micro-sensors based on electrodeposited IrOx thin film

In this work, we report polyimide-based biocompatible and flexible pH micro-probes. The sensing electrodes were based on iridium oxide (IrOx) thin film, electrodeposited by a cyclic voltammetry process onto a base sputtered gold (Au) layer. Square electrode configurations with sizes of 1 mm2, 500 μm2, 300 μm2, and 200 μm2 were designed, fabricated and tested; these yielded sensitivities of ∼71 mV/pH, ∼62 mV/pH, ∼52 mV/pH and ∼51 mV/pH, as well as limit of detection (LOD) values of 0.04 pH, 0.047 pH, 0.065 pH and 0.075 pH, respectively. Reference electrodes (REs) were developed by applying AgCl paste onto Au electrodes, followed by a curing process; demonstrating a comparable performance to commercial REs. Our pH micro-sensors hold promise for various applications, from analyses of chemical processes, to in-vitro and in-vivo experiments, to environmental or food safety monitoring.
Structural Components as Markers of Differentiation and Neoplastic Progression in Mammary Epithelial Cells

One of the primary aims in breast cancer research has been the development of molecular markers that can a) distinguish among the different cell types (epithelial, myoepithelial, stem cell, stromal, etc.) present in normal and abnormal mammary tissues and in cultures derived from these tissues, and b) identify a cell as normal, hyperplastic/preneoplastic, or malignant. Components of the cell surface and the cytoskeleton are especially promising candidates for such markers. A variety of surface antigens, usually defined by monoclonal antibodies, have now been described and were the subject of a number of recent reviews (1–5). The focus of the present chapter will therefore be on the cytoskeleton and in particular on intermediate filaments and their constituent proteins.
Basic Issues for an Ontology of the Natural Sciences

In this chapter I would like to discuss some issues that are of vital importance for any ontology of the natural sciences. I shall discuss these issues from the hermeneutic phenomenological point of view outlined in Chapter 2.
Impact of diagnostic workup resulting from a positive low-dose molecular breast imaging scan in a screening environment

2301 Objectives Molecular Breast Imaging (MBI) has been shown to have a high sensitivity and specificity for the detection of breast cancer in women with dense breast tissue on their mammogram. MBI may demonstrate positive findings in patients with negative mammographic and ultrasonic findings, requiring final confirmation with another modality such as contrast enhanced breast MRI. The aim of this study was to ascertain the consequences of a positive MBI on the need for secondary diagnostic exams and breast biopsy. Methods A total of 373 patients with mammographically dense breasts presenting for a screening mammogram underwent low-dose MBI with 8 mCi Tc-99m sestamibi as part of a research protocol. Screening mammography was performed within 21 days of and interpreted in conjunction with the MBI. MBI studies were assigned an uptake score of 3 (probably benign), 4 (suspicious) or 5 (highly suspicious) which paralleled BIRADs assessments. Subsequent workup comprised of diagnostic mammography, ultrasound, MRI, and/or biopsy was performed as necessary to resolve MBI findings. An assessment was made of the percentage of patients returning for diagnostic workup. Results Of the 373 patients, a total of 33 (8.8%) were called back for additional work-up based on positive MBI findings. The findings in 16/33 patients (48%) were resolved by correlation with a diagnostic mammogram and ultrasound. Ultrasound alone provided resolution for 1/33 (3%) patients. Ultrasound-guided biopsy was necessary to resolve 11/33 (33%) cases. Findings in an additional 5/32 patients (15%) required diagnostic evaluation by MRI with 4/33 (12%) needing MRI guided biopsy to resolve findings. Conclusions In patients with positive MBI scans, 15% required MRI evaluation and 12% required MRI-guided biopsy, both of which are technically challenging and costly procedures. Hence the development of an MBI-guided biopsy device could clearly be beneficial in resolving positive MBI findings. Research Support Komen for a Cure and the Mayo Foundation
Amino Acid Analysis by Reverse-Phase High Performance Liquid Chromatography: Separation of Phenylthiocarbamyl Amino Acids by Spherisorb Octadecylsilane Columns

A liquid chromatographic approach to automatic amino acid analysis first became available to analytical laboratories in 19581. Automated ion-exchange chromatography as developed by Moore, Stein, and Spackman has undergone refinements in the design of narrower bore columns, more sensitive flow cells, smaller resin particle size, and greater electronic amplification of spectroscopic signals. Improvements in the instrumentation design have made it possible to increase the sensitivity in the subnanomole range and decrease the analysis time from days to minutes2.
Geriatric Assessment for the Oncologist

The incidence of cancer, particularly gynecologic malignancy, increases with advanced age. The geriatric population is a heterogeneous group, and a patient’s chronologic age does not always reflect their overall health status. Therefore, oncologists need to be adept at assessing physiologic and functional capacity in older patients. The comprehensive geriatric assessment is the gold standard for evaluation of the geriatric patient. The various components of the CGA have been shown to influence cancer-related therapy in a multitude of ways, as previously discussed. The combined data from the CGA can be used to stratify patients into risk categories to better predict their tolerance to treatment and risk for chemotherapy toxicity. However, the CGA is a comprehensive tool requiring significant time and training to perform. Therefore, a variety of screening tools have been developed which may be useful in the general oncology practice setting to identify patients that may benefit from further testing and intervention. Further research is still needed to evaluate whether these screening tools can predict cancer-related outcomes in older patients.
Porcine Reproductive and Respiratory Syndrome Virus: Diagnostic update and search for novel modified live vaccines

Porcine reproductive and respiratory syndrome virus continues to be a significant problem for pork producers. The aim of this body of work was to help stakeholders control and prevention infection with this virus. A literature review of currently available diagnostic tests and guidelines for their interpretation serves as a resource for producers, practitioners, and researchers. The research focus was to evaluate two novel methods to develop improved modified live vaccines. The efficacy of viral chimeras constructed from a commercially available vaccine and a virulent wild-type isolate and the ability to attenuate wild-type isolates with a unique cell passage process are reported. Both techniques proved to be capable of developing potential vaccine candidates.
Using the Theory of Demand Management to Prepare for the Impacts of Climate Change on Public Lands

The scientific and economic communities recognize that demand management is an effective climate change adaptation response because it uses future supply predictions to allocate present resource use. It has been incredibly effective in managing water demand and use in several major western cities, including Los Angeles, San Francisco, Seattle, and Denver, despite steady population growth. Given the certain impacts that climate change will have on the 245 million acres of western rangelands managed for livestock grazing, including changed precipitation patterns, decreased surface water supply, and increasing temperatures, it will be necessary for the United States Forest Service and the Bureau of Land Management to change their approach to managing the rangeland resource. This Article will discuss the relevant statutes, regulations, and administrative processes governing livestock grazing on Forest Service and BLM lands and highlight the loci in which demand management could be used to plan for climate change. It will also address the ways in which agencies can use demand management principles to accommodate the changed circumstances that climate change will present for the federal range, in the absence of statutory range reform, consistent with President Obama’s 2013 Executive Order on Climate Change Preparedness.
Single Vessel Double Anastomosis for Flow Augmentation - A Novel Technique for Direct Extracranial to Intracranial Bypass Surgery.

BACKGROUND A double anastomosis using a single superficial temporal artery (STA) donor branch for both a proximal side-to-side (S2S) and a distal end-to-side anastomosis is a novel direct bypass technique for use in selected patients necessitating flow augmentation. OBJECTIVE To describe the single-vessel double anastomosis (SVDA) technique, including its indications, advantages, and limitations, in addition to reporting our cases series of patients who underwent a SVDA bypass surgery. METHODS Patients undergoing a SVDA bypass at a single institution between January 2010 and February 2016 were retrospectively reviewed. Intraoperative flow data was collected, including STA cut-flow, bypass flows, and cut flow index (CFI). Bypass patency was assessed by cerebral angiography and quantitative magnetic resonance angiography with noninvasive optimal vessel analysis. Adverse events occurring during the hospital stay and clinical status at last follow up was recorded. RESULTS Seven patients underwent SVDA bypass. Mean follow-up was 14.5 mo. Initial CFI for the S2S bypasses averaged 0.56 ± 0.25 and CFI after the SVDA averaged 1.15 ± 0.24. There was a statistically significant average difference in CFI before and after the SVDA bypass (p < .013). Thirteen bypasses (93%) were patent postoperatively, and remained patent at last follow up. Four patients experienced various postoperative complications. None of the patients had a new stroke since hospital discharge. CONCLUSION SVDA is a novel technique that can be advantageous for selected cases of extracranial-to-intracranial bypass. Expertise in bypass procedures is a necessary prerequisite. Graft patency rates and complications appear comparable to other bypass techniques.
Introduction to a Special Issue on Entrepreneurship and Employment: Connecting Labor Market Institutions, Corporate Demography, and Human Resource Management Practices

With the growing attention to entrepreneurship as an engine of job creation and economic development, it is important for social scientists who are broadly interested in labor market and employment...
Single Cell Sequencing Analysis of Lizard Phagocytic Cell Populations and Their Role in Tail Regeneration.

Abstract Lizards are the closest relatives of mammals capable of tail regeneration, but the specific determinants of amniote regenerative capabilities are currently unknown. Macrophages are phagocytic immune cells that play a critical role in wound healing and tissue regeneration in a wide range of species. We hypothesize that macrophages regulate the process of lizard tail regeneration, and that comparisons with mammalian cell populations will yield insight into the role phagocytes play in determining an organism's regenerative potential. Single cell RNA sequencing (scRNAseq) was used to profile lizard immune cells and compare with mouse counterparts to contrast cell types between the two species. Treatment with clodronate liposomes effectively inhibited lizard tail stump tissue ablation and subsequent regeneration, and scRNAseq was used to profile changes in lizard immune cell populations resulting from tail amputation as well as identifying specific cell types affected by clodronate treatment. ScRNAseq analysis of lizard bone marrow, peripheral blood, and tissue-resident phagocyte cell populations was used to trace marker progression during macrophage differentiation and activation. These results indicated that lizard macrophages are recruited to tail amputation injuries faster than mouse populations and express high levels of matrix metalloproteinases (MMPs). In turn, treatment with MMP inhibitors inhibited lizard tail regeneration. These results provide single cell sequencing data sets for evaluating and comparing lizard and mammalian immune cell populations, and identifying macrophage populations that are critical regulators of lizard tail regrowth.
Single-molecule level structural dynamics of DNA unwinding by human mitochondrial Twinkle helicase

Knowledge of the molecular events in mitochondrial DNA (mtDNA) replication is crucial to understanding the origins of human disorders arising from mitochondrial dysfunction. Twinkle helicase is an essential component of mtDNA replication. Here, we employed atomic force microscopy imaging in air and liquids to visualize ring assembly, DNA binding, and unwinding activity of individual Twinkle hexamers at the single-molecule level. We observed that the Twinkle subunits self-assemble into hexamers and higher-order complexes that can switch between open and closed-ring configurations in the absence of DNA. Our analyses helped visualize Twinkle loading onto and unloading from DNA in an open-ringed configuration. They also revealed that closed-ring conformers bind and unwind several hundred base pairs of duplex DNA at an average rate of ∼240 bp/min. We found that the addition of mitochondrial single-stranded (ss) DNA–binding protein both influences the ways Twinkle loads onto defined DNA substrates and stabilizes the unwound ssDNA product, resulting in a ∼5-fold stimulation of the apparent DNA-unwinding rate. Mitochondrial ssDNA-binding protein also increased the estimated translocation processivity from 1750 to >9000 bp before helicase disassociation, suggesting that more than half of the mitochondrial genome could be unwound by Twinkle during a single DNA-binding event. The strategies used in this work provide a new platform to examine Twinkle disease variants and the core mtDNA replication machinery. They also offer an enhanced framework to investigate molecular mechanisms underlying deletion and depletion of the mitochondrial genome as observed in mitochondrial diseases.
Evidenced-Based Practice Among Trainees: A Survey on Facial Trauma Wound Management

Objective Assess whether facial trauma wound care and antibiotic use recommendations are guided by evidence-based practice (EBP) or practice patterns, and investigate strategies to improve EBP adoption among surgical trainees. Design We conducted a survey of all trainees who manage facial trauma (general surgery, emergency medicine, plastic surgery, otolaryngology) to assess clinical knowledge and sources of treatment recommendations. Clinical questions were based on Oxford Center for Evidence-Based Medicine Level 1 or 2 evidence. We measured internal validity of questions using Cronbach's α. Results were weight-adjusted for nonresponse and then analyzed using Welch t test and descriptive statistics. Study Setting Stanford Hospital and Clinics, a Level I trauma center. Results Response rate was 50.3% overall (78/155). For recommendations on facial trauma wound and antibiotic use, nonspecialty junior residents most frequently relied on their own senior or specialty residents (79.1%); nonspecialty senior residents relied on specialty residents (67.9%). Specialty junior residents most often relied on their own senior residents (51.0%), the majority of whom made recommendations based on their own knowledge (73.2%). Questions assessing EBP knowledge had Cronbach's α of 0.98; response accuracy was similar between specialty and nonspecialty residents (54.6% vs 55.5%, p = 0.96). When provided recommendations that conflict with EBP, both nonspecialty and specialty residents more frequently followed recommendations rather than EBP; junior residents reported doing so to avoid conflict with superiors. Total 92.6% of surveyed residents felt cross-departmental EBP guidelines would improve patient care. Conclusions Facial trauma wound care and antibiotic recommendations disseminate down seniority and from craniofacial specialty to nonspecialty residents, yet knowledge of EBP among senior specialty and nonspecialty residents was weak. EBP may be difficult to adopt in the absence of consensus society guidelines. To address this gap, we published a review of EBP for facial trauma and plan to update our trauma manual with cross-departmental guidelines to facilitate EBP adoption among trainees.