cssi/SciSciGPT-SciSciNet huggingface dataset:
On the use of DXMS to produce more crystallizable proteins: Structures of the T. maritima proteins TM0160 and TM1171

The structure of two Thermotoga maritima proteins, a conserved hypothetical protein (TM0160) and a transcriptional regulator (TM1171), have now been determined at 1.9 A and 2.3 A resolution, respectively, as part of a large-scale structural genomics project. Our first efforts to crystallize full-length versions of these targets were unsuccessful. However, analysis of the recombinant purified proteins using the technique of enhanced amide hydrogen/deuterium exchange mass spectroscopy (DXMS) revealed substantial regions of rapid amide deuterium hydrogen exchange, consistent with flexible regions of the structures. Based on these exchange data, truncations were designed to selectively remove the disordered C-terminal regions, and the resulting daughter proteins showed greatly enhanced crystallizability. Comparative DXMS analysis of full-length protein versus truncated forms demonstrated complete and exact preservation of the exchange rate profiles in the retained sequence, indicative of conservation of the native folded structure. This study presents the first structures produced with the aid of the DXMS method for salvaging intractable crystallization targets. The structure of TM0160 represents a new fold and highlights the use of this approach where any prior structural knowledge is absent. The structure of TM1171 represents an example where the lack of a substrate/cofactor may impair crystallization. The details of both structures are presented and discussed.
Chemical Vapor Deposition of Chromium Carbide from Organometallic Precursors

Chemical vapor deposition from CpCr(CO)3H, Cr(CH2CMe3)4, and Cr(NPri 2)3 at low pressures yields chromium carbide films at temperatures as low as 330 °C. The films are mirror-bright and extremely smooth with no significant features observable by SEM. In general, films prepared at higher temperatures had lower resistivities, and were more likely to be crystalline than those prepared at lower temperatures. However, amorphous films deposited at 330 °C were much harder than the crystalline films. Chemical vapor deposition from Cr(NPri 2)3 resulted in carbide films with the most desirable properties.
Anthrax—Pasteur to the present

Abstract : Few microbial pathogens have had as great an impact on the early development of medical bacteriology and immunology as Bacillus anthracis. From studies on this etiologic agent of anthrax during the mid-1800s have stemmed many of the fundamental concepts of infection and immunity now generally accepted. Although anthrax has long been recognized as a disease primarily associated with herbivorous animals, it can occur in humans, usually as a result of incidental contact with infected animals or contaminated animal products. It was in response to the major epidemics of the mid-1800s, that the French Minister of Agriculture commissioned Pasteur to develop methods to control anthrax.
Traumatic cardiogenic shock due to massive air embolism. A possible role for cardiopulmonary bypass.

Systemic arterial embolism is a potentially lethal complication of bronchopulmonary venous fistula in trauma patients with blunt chest trauma or isolated penetrating lung injury on positive pressure ventilation. A high index of suspicion, early diagnosis and management in specialized centres are keys to a successful outcome.
Unequal access of chromosomal regions to each other in Salmonella: probing chromosome structure with phage λ integrase‐mediated long‐range rearrangements

Summary We have investigated the fluidity of the Salmonella chromosome architecture using the phage lambda site-specific recombination system as a probe. We determined how chromosome position affects the extent of integrase-mediated recombination between pairs of inversely oriented att sites at various loci. We also investigated the accessibility of each chromo- somal att site to an extrachromosomal partner carried on a low-copy plasmid. Recombination events were assayed by semi-quantitative polymerase chain reac- tion of the attP product. The extent of recombination between the chromosome and the plasmid was gen- erally higher than intrachromosomal recombination except for two loci, araA :: attL and galT :: attL , which gave no detectable recombination with any other locus. Based on 20 intervals, we found that chromo- somal locations are not equally accessible to each other. Although multiple factors probably affect accessibility, the most important is the specific com- bination of the end-points used. Neither the size of the intervals nor the accessibility of individual end- points to extrachromosomal sequences is as impor- tant. These results suggest that the chromosome is not completely fluid but rather organized in some way, with barriers that limit the movement of DNA within the cell. The nature of the barriers involved in chro- mosomal organization remains to be determined.
Evaluation of a new body composition phantom for quality control and cross-calibration of DXA devices

This study evaluated a new body composition phantom and its use for quality control and cross-calibration of dual-energy X-ray absorptiometry (DXA) instruments for measurements of body composition. We imaged the variable composition phantom (Lunar, Madison, WI) on eight different DXA devices. Deviations of up to 7% fat were observed when we compared the percent fat values measured by the different devices with the nominal values provided by the manufacturer. Absolute precision error of percent fat measurements for the phantom ranged from 0.6 to 0.8%. The phantom's percent fat values were also compared with whole body composition measurements from 130 female and male volunteers. The phantom detected differences in percent fat values that were similar to those found by comparing in vivo measurements with values from different DXA scanner models from the same manufacturer. When comparing different models of scanners from different manufacturers, such as the Hologic QDR-4500 and the Lunar DPX-IQ, the phantom showed a different relationship than was seen for patients. Therefore, corrections or comparisons based on the phantom data alone would be incorrect. In conclusion, the Lunar variable composition phantom is capable of accurately measuring the fat calibration of DXA devices and may be suitable for cross-sectional cross-calibration between scanners from the same manufacturer; however, for comparison of DXA scanners from different manufacturers, in vivo cross-calibration is still the only accurate method. The phantom may be used in longitudinal quality control to verify an instrument's temporal stability.
Acreage Response Under Farm Programs for Major Southeastern Field Crops

An expected utility model that includes output price and yield uncertainly was used to estimate cotton, corn, and soybean acreage response equations for the Southeast. The model appeared to fit the soybean and corn data well, resulting in own-price elasticity estimates of 0.317 for com and 0.727 for soybeans. When applied to cotton acreage, however, the model did not yield satisfactory results. When elasticity was allowed to changeover time, however, statistical results for the cotton equation improved, yielding an own-price elasticity of 0.915 at data means.
Internal model control of infinite dimensional systems

An internal model control (IMC) design method is proposed that is applicable to linear infinite-dimensional systems. An infinite-dimensional filter is coupled with the inverse of the irrational transfer function between the process input and output, to produce a physically realizable controller with a tuning parameter to trade off nominal performance with robustness. The proposed IMC design technique is applied to two boundary control problems for mass transport described by partial differential equations, in which the proposed method provides much better robust performance compared to regular IMC design applied to the finite-dimensional approximation of the transfer function.
Biomolecular analysis with microring resonators: applications in multiplexed diagnostics and interaction screening.

Microring optical resonators are a promising class of sensor whose value in bioanalytical applications has only begun to be explored. Utilized in the telecommunication industry for signal processing applications, microring resonators have more recently been re-tasked for biosensing because of their scalability, sensitivity, and versatility. Their sensing modality arises from light/matter interactions — light propagating through the microring and the resultant evanescent field extending beyond the structure is sensitive to the refractive index of the local environment, which modulates resonant wavelength of light supported by the cavity. This sensing capability has recently been utilized for the detection of numerous biological targets including proteins, nucleic acids, viruses, and small molecules. Herein we highlight some of the most exciting recent uses of this technology for biosensing applications, with an eye towards future developments in the field.
Evaluation of a Nurse-Managed Insulin Infusion Protocol

Abstract Background: The purpose of this study was to evaluate the performance of an insulin infusion protocol targeting a blood glucose (BG) level of 140–180 mg/dL and to characterize protocol adherence. Materials and Methods: This was a retrospective observational cohort study including patients for whom the protocol was ordered from January 2012 to May 2013. Performance metrics were assessed in all patients and in patients with an initial BG level of ≥200 mg/dL. Protocol adherence was assessed in a random subset of 50 patients without hypoglycemia and in all hypoglycemic patients. Results: In patients with an initial BG level of ≥200 mg/dL, the mean time to goal was 7.1 h. The rate of decline of BG level in the first 6 h was 16.4 mg/dL/h. Mean BG level was 167 mg/dL, with 43.9% of BG values within goal and 80.3% between 80 and 199 mg/dL. The rate of hypoglycemic events was 0.14 per 100 h. The mean protocol violation rate was higher in patients with hypoglycemia compared with those without (39.8 vs. 23....
Decrease in Scour Rate of Fresh Deposited Muds

This note comments on the observation that the decrease in the rate of scour of freshly deposited muds is attributed to a gradual development of a resistive bed roughness pattern. Since prolonged fluid stressing causes internal rearrangement of bed particles that results in pronounced defects in the bed surface, there is a brief period of increased scour in the early stages of bed consolidation. Experimental studies show this roughness pattern gradually reaches a certain limiting size beyond which the scour rate decreases and bed stability is enhanced.
Are attractive male crickets better able to pay the costs of an immune challenge

Reproduction and immunity are fitness-related traits that trade-off with each other. Parasite-mediated theories of sexual selection suggest, however, that higher-quality males should suffer smaller costs to reproduction-related traits and behaviours (e.g., sexual display) from an immune challenge because these males possess more resources with which to deal with the challenge. We used Gryllus texensis field crickets to test the prediction that attractive males should better maintain the performance of fitness-related traits (e.g., calling effort) in the face of an immune challenge compared with unattractive males. We found no support for our original predictions. However, that immune activation causes attractive males to significantly increase their calling effort compared with unattractive males suggests that these males might terminally invest in order to compensate for decreased future reproduction.
Avoiding Normative Canons in the Review of Administrative Interpretations of the Law: A Brand X Doctrine of Constitutional Avoidance

This Article explores the conflicting commands of modern constitutional avoidance (courts must construe ambiguous statutes not only to adopt a constitutional construction but to avoid constructions that raise constitutional questions) and Chevron deference (courts must defer to an agency’s reasonable interpretation of an ambiguous statute it administers). While courts and commentators have suggested that constitutional avoidance trumps Chevron deference (at either step one or two), this Article advocates that modern avoidance should play no role in the review of administrative interpretations of law. Once Congress has empowered an agency to interpret an ambiguous statutory provision, a court cannot simply invalidate the agency’s interpretation and replace it with one the court believes better avoids constitutional questions. Instead, if an agency’s reasonable interpretation raises constitutional questions, a court must determine whether the interpretation is indeed unconstitutional and thus an impermissible interpretation at Chevron step two. This approach constitutes a return to the classical doctrine of constitutional avoidance, and it finds support in the Supreme Court’s decision in National Cable & Telecommunications Ass’n v. Brand X Internet Services. As the Article illustrates in a variety of administrative contexts, this Brand X doctrine of constitutional avoidance is necessary to preserve a proper separation of powers between the courts, the Executive, and Congress. It is also justified under Dean Edward Rubin’s network theory of administrative law.
How does an amalgamated Ni cathode affect carbon nanotube growth? A density functional theory study

This is a Density Functional Theory (DFT) study on the influence of an alloying mixture of Ni–Zn catalysts on carbon nanotube, CNT, growth. The study is inspired by the one pot synthesis of carbon nanofibers during the electrolysis of Li2CO3. Unlike CVD, CNT growth initiates at the liquid/solid, rather than gas/solid interface in the above process. The electrodes are an amalgamated Zn cathode and with a pure Ni crucible as the anode, and both zinc and nickel (or other transition metals) are required for high yield production. The use of transition metals as the catalyst for CNT, CVD growth is well known. However, in this study we show how a mixture of the Zn–Ni alloy can act as the catalyst for the effective CNT growth. Ni and Zn are taken as an example of first row transition metals with a partially empty and completely filled d orbital respectively. The study shows that the π–d bonding between the nanotube and the metal results in strong bond formation at the interface of the nanotube growth. The study remains valid for other such metal alloys with partially and completely filled d orbitals.
Effect of fatigue on susceptibility of mice to poliomyelitis.

SummaryIn order to determine the effect of fatigue on susceptibility to experimental poliomyelitis, mice were forced to run in a revolving drum during the day preceding and for 8 hours each day subsequent to the intra cerebral injection of the Lansing strain of virus. Control animals inoculated at the same time with the same amount of virus were allowed to rest in their cages. In all 7 experiments, the incidence of the disease as measured both by paralysis and by death was greater in the exercised animals than in the resting controls.
Tyrosine kinase activities in the modulation of stimulated parietal cell acid secretion

The effects of protein tyrosine kinase (PTK) activities on the modulation of secretion were investigated in isolated rabbit parietal cells. Two classes of inhibitors, genistein (an inhibitor of both soluble and membrane-associated PTK activities) and an erbstatin analogue (an inhibitor of membrane-associated PTK activities), were tested against both secretagogue stimulation as well as transforming growth factor-alpha (TGF-alpha) inhibition. Pretreatment of rabbit parietal cells with 10(-7) M rat TGF-alpha resulted in inhibition of both histamine- and carbachol-stimulated [14C]-aminopyrine (AP) accumulation. TGF-alpha inhibition was totally reversed by simultaneous pretreatment of cells with 50 microM genistein or an erbstatin analogue, indicating that a receptor-associated PTK activity is likely involved in the inhibition of parietal cell secretion. Furthermore, genistein, but not the erbstatin analogue, potentiated histamine-stimulated AP accumulation with a change in EC50 from 1.9 to 0.5 microM. Similarly, genistein, but not the erbstatin analogue, potentiated the response to forskolin with a change in EC50 from 1.5 to 0.1 microM. Genistein had no effect on stimulation of AP uptake by either dibutyryladenosine 3',5'-cyclic monophosphate or carbachol. In addition, genistein failed to increase histamine or forskolin stimulation beyond the maximal level and had no significant effect on either cellular adenosine 3',5'-cyclic monophosphate production or intracellular Ca2+ concentration. These results suggest that a PTK-protein phosphotyrosine phosphatase system may be involved in the potentiation of the histamine signal by a mechanism independent of adenylate cyclase activation.
Bayesian nonparametric relational learning with the broken tree process

Recently, an increase in the availability and importance of relational datasets-such as social network data or protein interaction data-has lead to increased interest in modelling and learning from such data. Such data are often modelled as exchangeable arrays, yielding a particular representation due to Aldous and Hoover. We present a Bayesian nonparametric model based on this representation, which uses a novel process to generate a partition of the data. We present a Reversible Jump MCMC algorithm for inference in this model, and demonstrate the effectiveness of this approach on real-world data.
Scalable Algorithms at Genomic Resolution to fit LD Distributions

While the problem of reconstructing a population that matches a given LD (linkage disequilibrium) distribution is not straightforward, it is further compounded if the population must additionally match MAF (minimum allele frequency) distribution as well. Here we address the task of co-fitting the multiple distributions at genomic resolutions. The solution is based on incrementally scaling a fast, i.e., linear time, non-generative algorithm (SimBA). Non-generative implies that the algorithm does not generate the population through evolution-simulation. Instead it directly builds the genomes in terms of polymorphic alleles that mimic the the structure of the desired population. We present an incremental framework to scale up the algorithm that continues to be both accurate and efficient. We demonstrate the efficacy of the algorithm on a variety of data sets, both human as well as plant data. Such simulation of populations that match summary distributions play a critical role in in-silico hypothesis-testing and optimization. For instance in-silico breeding optimization in plants can model years or decades of experimentation to predict breeding outcomes in an incredibly short time of days, if not hours or minutes.
551. Longitudinal High Resolution 3-D Imaging of AAV Gene Expression In Vivo

Adeno-associated viral (AAV) are small non-integrating vectors that are being developed for a number of gene therapy applications. Different AAV serotypes, armed with constitutive or tissue specific promoters, capable of infecting various tissue types have been engineered to enable preferential transduction of the target tissues. In order to rapidly screen and evaluate the best AAV serotype and promoter for high levels of transgene expression in a specific organ, we have been developing the sodium iodide symporter (NIS) as a reporter gene for screening the biodistribution of AAV vectors. NIS is expressed endogenously in thyroid follicular cells where its role is to concentrate iodine for the synthesis of thyroid hormones. For more than 70 years, thyroidal NIS expression has been provided the basis for I-123 gamma camera or SPECT/CT imaging in thyroid disorders and for I-131 tumor ablation of metastatic thyroid cancer. Using NIS imaging, we would be able to longitudinally monitor gene expression in the same animal over time, from rodents, dogs, nonhuman primates and in human subjects. In this study, we have generated a panel of AAV vectors of serotype 1, 2, 5, 8, and 9 and administered the vectors via various routes of delivery. The mice and rats were imaged using SPECT (I-125 or Tc99m pertechnetate) isotopes on a high resolution microSPECT/CT scanner. Results indicate robust AAV gene expression by 2 weeks post vector administration. View Large Image | Download PowerPoint Slide[Figure 1: AAV mediated NIS gene expression in the liver and heart of mice post IV administration of vector]. For example, AAV9-CMV-NIS gave high levels of cardiac gene expression and interestingly, of subcutaneous brown fat (scapular region). In contrast AAV1-CMV-NIS resulted in highest gene expression in the subcutaneous brown fat only whereas AAV-LST-NIS (liver specific promoter) gave only NIS expression in the liver. When the regions of interests were quantitated, we found that AAV-NIS gene expression was maintained over 90 days in immunocompetent rats and over 200 days in immunocompromised mice. Using NIS as the reporter gene, we are able to use the same vector construct and perform similar noninvasive NIS imaging studies in large animal models using the same SPECT isotopes in combination with clinical SPECT/CT scanners. In contrast to traditional biodistribution studies utilizing PCR analysis or luciferase imaging, NIS imaging enables rapid identification of the organs supporting high levels of transgene expression.
Using Principal Component Scores to Enhance the Validity and Reliability of Big Five Personality Measures

Abstract. Varimax rotated principal component scores (VRPCS) have previously been offered as a possible solution to the non-orthogonality of scores for the Big Five factors. However, few researchers have examined the reliability and validity of VRPCS. To address this gap, we use a lab study and a field study to investigate whether using VRPCS increase orthogonality, reliability, and criterion-related validity. Compared to the traditional unit-weighting scoring method, the use of VRPCS enhanced the reliability and discriminant validity of the Big Five factors, although there was little improvement in criterion-related validity. Results are discussed in terms of the benefit of using VRPCS instead of traditional unit-weighted sum scores.
Preference for Averageness in Faces Does Not Generalize to Non-Human Primates.

Facial attractiveness is a long-standing topic of active study in both neuroscience and social science, motivated by its positive social consequences. Over the past few decades, it has been established that averageness is a major factor influencing judgments of facial attractiveness in humans. Non-human primates share similar social behaviors as well as neural mechanisms related to face processing with humans. However, it is unknown whether monkeys, like humans, also find particular faces attractive and, if so, which kind of facial traits they prefer. To address these questions, we investigated the effect of averageness on preferences for faces in monkeys. We tested three adult male rhesus macaques using a visual paired comparison task, in which they viewed pairs of faces (both individual faces, or one individual face and one average face); viewing time was used as a measure of preference. We did find that monkeys looked longer at certain individual faces than others. However, unlike humans, monkeys did not prefer the average face over individual faces. In fact, the more the individual face differed from the average face, the longer the monkeys looked at it, indicating that the average face likely plays a role in face recognition rather than in judgments of facial attractiveness: in models of face recognition, the average face operates as the norm against which individual faces are compared and recognized. Taken together, our study suggests that the preference for averageness in faces does not generalize to non-human primates.
Autobiographical Docudrama as Testimony: Jonas Carpignano's Mediterranea

Refugee life narrative occupies a complex and contentious discursive space because its most crucial manifestation, the asylum court, serves as the setting in which a migrant's fate is determined an...
The Master–Slave Dialectic

This chapter expounds Hegel’s “master-slave dialectic,” explaining why it provides a necessary framework for approaching Hegel’s views on empire. This dialectic reveals that the human self is born in social interaction, through a process—a struggle—for recognition. In order to understand Hegel’s views on Africa and slavery, and the “mastery” of Europe over the rest of the world, it is crucial to grasp how he conceptualizes mastery and slavery in general. The master-slave dialectic is not only essential to Hegel’s view of subjectivity, but also furnishes a framework for assessing Hegel’s views of the Other in relation to European identity. Moreover, it is a dialectic with which important postcolonial theorists have engaged in their critique of Hegel’s Eurocentric vision.
A role for corticotropin-releasing factor signaling in the lateral habenula and its modulation by early-life stress

Centrally released corticotropin-releasing factor or hormone (extrahypothalamic CRF or CRH) in the brain is involved in the behavioral and emotional responses to stress. The lateral habenula (LHb) is an epithalamic brain region involved in value-based decision-making and stress evasion. Through its inhibition of dopamine-mediated reward circuitry, the increased activity of the LHb is associated with addiction, depression, schizophrenia, and behavioral disorders. We found that extrahypothalamic CRF neurotransmission increased neuronal excitability in the LHb. Through its receptor CRFR1 and subsequently protein kinase A (PKA), CRF application increased the intrinsic excitability of LHb neurons by affecting changes in small-conductance SK-type and large-conductance BK-type K+ channels. CRF also reduced inhibitory γ-aminobutyric acid-containing (GABAergic) synaptic transmission onto LHb neurons through endocannabinoid-mediated retrograde signaling. Maternal deprivation is a severe early-life stress that alters CRF neural circuitry and is likewise associated with abnormal mental health later in life. LHb neurons from pups deprived of maternal care exhibited increased intrinsic excitability, reduced GABAergic transmission, decreased abundance of SK2 channel protein, and increased activity of PKA, without any substantial changes in Crh or Crhr1 expression. Furthermore, maternal deprivation blunted the response of LHb neurons to subsequent, acute CRF exposure. Activating SK channels or inhibiting postsynaptic PKA activity prevented the effects of both CRF and maternal deprivation on LHb intrinsic excitability, thus identifying potential pharmacological targets to reverse central CRF circuit dysregulation in patients with associated disorders.
Clinical efficacy of ruxolitinib and chemotherapy in a child with Philadelphia chromosome-like acute lymphoblastic leukemia with GOLGA5-JAK2 fusion and induction failure.

Patients with Philadelphia chromosome-like B-cell lymphoblastic leukemia (Ph-like or BCR-ABL1 -like BALL) experience high relapse rates and are difficult to cure with conventional chemotherapy.[1][1],[2][2] The Ph-like ALL subtype comprises 15-25% of B-ALL in older children and adolescents/young
Quality Assurance Measures for Environmental Data

An understanding of the occurrence, fate, effects, and pollution potential of suspected toxic substances requires a wide variety and large quantity of analytical data, obtained over extended time intervals, in diverse locations, and by independent investigators. Unfortunately, much of the data reported in the literature is often difficult to interpret and correlate because of lack of information on the reliability of sampling and measurement. This paper discusses general principles of quality control of both measurement and sampling and recommends minimum requirements for reporting environmental data. The use of generally accepted reference materials to intercalibrate measurement laboratories is emphasized.
Exercise Stage of Change and Self-Efficacy in Primary Care: Implications for Intervention

Multiple chronic diseases are caused or complicated by a sedentary lifestyle. Thus, an important and challenging application of psychology in clinical settings is changing the behavior of sedentary primary care patients. This study focused on exercise stage of change and self-efficacy in a sample of adult family practice patients recruited while waiting for their scheduled physician appointment. Regarding exercise stage of change, 15% of respondents were in the Precontemplation stage, 26% in the Contemplation stage, 50% in the Preparation stage, 7% in the Action stage, and 13% in the Maintenance stage. Mean self-efficacy scores for exercise were significantly higher among respondents in the Action and Maintenance stages of change. These cross-sectional data are consistent with the hypothesis that movement through the exercise stages of change could be encouraged by clinical interventions that increase exercise self-efficacy. The identification of multiple personal opportunities for increasing exercise self-efficacy may be clinically useful in this context. Recommendations for psychologists in primary care settings in their work with physicians are offered.
Nonparametric Estimation of Marginal Temporal Functionals in a Multi-State Model

Multi-state models are generalizations of traditional survival analysis and reliability studies. They are common in medical and engineering applications where a subject (say a patient or a machine) is moving through a succession of states (each representing a stage of disease progression or the condition of a machine) with time. In addition, several key questions in event history analysis and multi-variate survival analysis can be formulated in terms of a staged system making the use of multi-state models extremely broad. While the use of parametric and semiparametric models to various transitions are the most common approaches to study multi-state data, this overview paper deals entirely with nonparametric methods. In addition, we limit our exposition to estimation questions related to marginal models rather than conditional (e.g., regression) models. We review a number of methods from the recent past dealing with estimation of hazards, transition and state occupation probabilities, state entry, exit and waiting time distributions and also discuss some ongoing and future research problems on these topics. Various forms of censoring that occur in the collection of multi-state data are discussed including right and interval censoring.
Narrative Financial Therapy

This chapter provides an introduction to narrative financial therapy (NFT), which is an integrated theoretical approach to financial therapy that both mental health and financial planning professionals can utilize. The NFT approach integrates aspects of the six-step financial planning process with empirically supported narrative therapeutic techniques. This integration provides the underpinnings to a manualized approach. Concluding the chapter, a case study is presented to demonstrate the approach, explore potential ethical considerations, and introduce future considerations.
Strategies for optimizing hemoglobin response in cancer patients: focus on new epoetin alfa dosing regimens

Abstract As the prevalence and impact of anemia in patients with cancer have been recognized, clinical guidelines with recommendations for the use of both transfusions and recombinant human erythropoietin (rHuEPO; epoetin alfa) are continuing to evolve. The strength of recommendations varies depending on the availability of randomized, controlled clinical trial data for a given endpoint, which can include transfusion reduction, improvements in hemoglobin (Hb) levels, quality of life (QOL) improvement, or potential treatment outcome benefits. Clinical studies have shown that epoetin alfa, in doses of 150–300 IU/kg three times a week, consistently increases Hb levels by ∼1 g/dl at 4 weeks and ∼2 g/dl at 8 weeks. A prospective, community-based clinical trial has demonstrated that a once-weekly (QW) regimen of epoetin alfa (40 000–60 000 IU) increases Hb levels by 1.1 g/dl at week 4 and by 1.7 g/dl at week 8. Results from a second prospective, open-label, community-based trial are consistent with these findings. These increases are associated with statistically significant reductions in transfusion requirements and improvements in QOL. The question as to whether epoetin alfa should be given to patients with mild anemia is currently being evaluated in several early-intervention studies (i.e. in patients with mean Hb ∼12 g/dl). Preliminary results suggest that epoetin alfa, given QW at doses of 40 000–60 000 IU, prevents Hb decline and may ameliorate deterioration in QOL during chemotherapy in these patients. In addition to studies evaluating early intervention with epoetin alfa, several ongoing studies are examining new epoetin alfa dosages and administration schedules in an effort to optimize Hb correction. For example, investigators are evaluating whether regimens with high initial dosages (60 000–80 000 IU QW) of epoetin alfa, given for a short period of time, may improve hematologic response in patients with established anemia and whether less frequent maintenance dosing (i.e., 120 000 IU every 3 weeks) is sufficient to maintain the Hb response. If high initial epoetin alfa doses followed by infrequent maintenance dosing proves effective in larger clinical trials, a variety of more convenient dosing regimens may be available.
Genetic approaches to the study of disease resistance: with special emphasis on the use of recombinant inbred mice.

Central to studies of microbial pathogenesis is an identification of the protective mechanisms that defend the host against each pathogen. One way to do this is to identify genes of the host that affect the resistance to the pathogen and then determine their mechanisms of action. This approach automatically establishes the in vivo relevance of all mechanisms studied. the discovery of variant alleles affecting particular functions also serves to identify important protective mechanisms that might have otherwise remained unknown. The power of this type of approach is aptly illustrated by the major histocompatibility complex of mammals and birds, where much of our present knowledge has come from attempts to understand how a single genetic region could affect graft rejection, immunoresponsiveness, and disease susceptibility.
Neurobehavioral Complications of HIV Infection

It is estimated that 34.3 million people worldwide are now living with human immunodeficiency virus (HIV) infection (United Nations Programme on HIV/AIDS & World Health Organization, 2000), a retrovirus that causes acquired immunodeficiency syndrome (AIDS). Since the beginning of the HIV pandemic, almost 19 million individuals have died from AIDS (2.8 million of these in 1999). Despite significant medical advances in the treatment of the disease, the rate at which individuals are becoming infected continues to increase. Close to 6 million new individuals were infected in 1998, primarily in the developing world (see Table 1). Sub-Saharan African countries are the most profoundly impacted, with up to one quarter of young adults being HIV seropositive.
Quantifying the burden of pre-existing conditions in older trauma patients: A novel metric based on mortality risk

Abstract Introduction Pre-existing medical conditions (PEC) represent a unique domain of risk among older trauma patients. The study objective was to develop a metric to quantify PEC burden for trauma patients. Methods A cohort of 4526 non-severe blunt-injured trauma patients aged 55 years and older admitted to a Level I trauma center between January 2006 and December 2012 were divided into development (80%) and test (20%) sets. Cox regression was used to develop the model based on in-hospital and 90-day mortality. Regression coefficients were converted into a point-based PEC Risk Score. Performance of the PEC Risk Score was compared in the test set with two other PEC-based metrics and three injury-based metrics. An external cohort of 2284 trauma patients admitted in 2013 was used to evaluate combined metric performance. Results Total mortality was 9.4% and 9.1% in the development and test set, respectively. The final model included 12 PEC. In the test set, the PEC Risk Score (c-statistic: 79.7) was superior for predicting in-hospital and 90-day mortality compared with all other metrics. For in-hospital mortality alone, the PEC Risk Score similarly outperformed all other metrics. Combination of the PEC Risk Score and any injury-based metric significantly improved prediction compared with any injury-based metric alone. Conclusion Our 12-item PEC Risk Score performed well compared with other metrics, suggesting that the classification of trauma-related mortality risk may be improved through its use. Among non-severely injured older trauma patients, the utility of prognostic metrics may be enhanced through the incorporation of comorbidities.
Public Perception of Autism Treatments: The Role of Credibility and Evidence

We explored the influence of credibility and evidence on public perceptions of ASD treatments using survey methodology. Participants (N = 379) read texts about different ASD treatments. The text presentation was based on a 2 × 2 within-subjects factorial design with treatment status [evidence based practices (EBP) vs. non-EBP] and source credibility in the text (credible vs. non-credible) as the independent variables. An instructional manipulation condition served as a between subjects factor. Respondents were more familiar with non-EBPs than EBPs, but viewed EBPs as being more credible and were more likely to endorse them compared to pseudoscientific practices. Interactions between source credibility and instructional manipulation were found on ratings of credibility and recommendation of both EBP and non-EBP texts. Implications of these findings are discussed.
Phase-field modeling of fission gas bubble growth on grain boundaries and triple junctions in UO2 nuclear fuel

Abstract A phase-field model of fission gas bubble evolution was developed and applied to gain an improved understanding of the microstructure-level processes leading to fission gas release from nuclear fuel, and to inform engineering-scale fission gas release models. The phase-field model accounts for multiple fuel grains and fission gas bubbles and tracks the local concentration of vacancies and gas atoms. The model was used to simulate the growth of grain boundary and triple junction bubbles in a hexagonal periodic 3D grain structure. The fractional coverage of the triple junctions and the number of fully saturated triple junctions (that is, triple junctions fully covered by the gas phase) was calculated, and correlations were developed between these quantities and the grain boundary coverage. The effects of initial triple junction bubble density, vacancy source strength, and bubble semi-dihedral angle on triple junction coverage and saturation were evaluated. High initial triple junction coverage and high bubble semi-dihedral angle can lead to triple junction saturation well before grain boundary percolation. The implications of these findings for engineering-scale fuel performance modeling are discussed.
Reproduction Ability and Growth Effect of Pin Nematode, Paratylenchus nanus, With Selected Field Pea Cultivars.

Greenhouse experiments were conducted to determine the reproductive ability and effect of the pin nematode Paratylenchus nanus from North Dakota on field pea cultivars. Reproduction of P. nanus was...
Treating B Cell Lymphomas with Anti CD81 Antibodies

Abstract The tetraspanin CD81 associates with CD19 on B cells; this molecular complex functions as co-receptor to lower the threshold of BCR-initiated B cell activation. Recently we have shown the importance of CD81 in tumor growth and metastasis of solid tumors (Vences-Catalan et al., 2015). However, the role of CD81 in lymphoid malignancies has not been explored. Previous studies demonstrated anti-proliferative effects of anti-CD81 antibodies on human B cell lymphomas using in vitro assays (Oren et al., 1990). Here we tested the therapeutic effect of an anti-human CD81 antibody in vivo against Raji and SUP-B8 B cell lymphomas using a xenograft model in SCID mice. Our studies demonstrated that our anti-human CD81 antibody (mouse IgG1) had therapeutic effect comparable to Rituximab (human IgG1) (Figure 1A). Yet, the two antibodies differ in their ability to mediate antibody-dependent cell cytotoxicity (ADCC), Rituximab is known to be highly effective, whereas the mouse IgG1 anti-CD81 antibody is not expected to mediate ADCC. To enhance the anti-CD81-mediated ADCC, we class switched the hybridoma to mouse IgG2a; we also engineered a chimeric antibody containing human IgG1ADCC-HIGH Fc constant region. Indeed, mouse IgG2a and the chimeric human IgG1 anti-CD81 mAb showed a remarkable increase in NK cell-mediated ADCC as well as complement-dependent cytotoxicity (CDC) when compared to Rituximab in vitro (data not shown) and in vivo (Figure 1B). These results suggest that CD81 can be a potential therapeutic target on B cell lymphomas by virtue of both its direct cytotoxic effect and as a mediator of ADCC and CDC. The humanized IgG1 version is being developed as a therapeutic candidate. Download : Download high-res image (128KB) Download : Download full-size image Disclosures Levy: Kite Pharma: Consultancy; Five Prime Therapeutics: Consultancy; Innate Pharma: Consultancy; Beigene: Consultancy; Corvus: Consultancy; Dynavax: Research Funding; Pharmacyclics: Research Funding.
Management of Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis: a Review and Update

This review highlights current concepts in the management of Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). A new scoring system, the ABCD-10, was recently developed to better estimate mortality among SJS/TEN patients. Supportive care remains the mainstay of treatment, and includes wound care, fluid and electrolyte management, management of medical co-morbidities, and infection control. The value of adjuvant therapy remains unclear, but new recent retrospective studies suggest that the combination therapies may be efficacious. Recent prospective studies investigating cyclosporine and etanercept have shown promise in the treatment of SJS/TEN. SJS and TEN are severe mucocutaneous drug reactions associated with high morbidity and mortality. Supportive care is the most universally accepted therapy, although specific strategies may vary among institutions. Adjuvant therapies include corticosteroids, IVIG, cyclosporine, TNF alpha inhibitors, and plasmapheresis but prospective data is still lacking. Clinical trials that may better elucidate their efficacy are currently under way.
iMIRAGE: an R package to impute microRNA expression using protein-coding genes.

SUMMARY MicroRNAs (miRNAs) are critical post-transcriptional regulators of gene expression. Due to challenges in accurate profiling of small RNAs, a vast majority of public transcriptome datasets lack reliable miRNA profiles. However, the biological consequence of miRNA activity in the form of altered protein-coding gene (PCG) expression can be captured using machine-learning algorithms. Here, we present iMIRAGE (imputed miRNA activity from gene expression), a convenient tool to predict miRNA expression using PCG expression of the test datasets. The iMIRAGE package provides an integrated workflow for normalization and transformation of miRNA and PCG expression data, along with the option to utilize predicted miRNA targets to impute miRNA activity from independent test PCG datasets. AVAILABILITY AND IMPLEMENTATION The iMIRAGE package for R, along with package documentation and vignette, is available at https://aritronath.github.io/iMIRAGE/index.html. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
Learning dispatching rules for single machine scheduling with dynamic arrivals based on decision trees and feature construction

In this paper, we address the dynamic single-machine scheduling problem for minimisation of total weighted tardiness by learning of dispatching rules (DRs) from schedules. We propose a decision-tre...
Use of self-rated health to identify frailty and predict mortality in older adults with cancer. Results from the care study.

12046Background: Poor self-rated health (SRH) is a known predictor of mortality in the general adult population, but little is known about its use in older adults with cancer. The purpose of this s...
Thoracic Enhanced Recovery After Surgery: Single Academic Center Observations After Implementation

Background Enhanced recovery after surgery (ERAS) is an evidence-based, multidisciplinary perioperative care model shown to reduce complications and hospital length of stay (LOS). While some thoracic ERAS studies were inconclusive, others demonstrated that ERAS improves patient outcomes after lung resections and provides more cost-effective care. We aimed to investigate the effects of preliminary implementation of an ERAS protocol, in comparison with conventional care, on lung resection outcomes at a single academic institution. Methods In this observational study, adult patients undergoing lung resections during the pre-ERAS (April 2014 to September 2015) and post-ERAS (January 2016 to May 2017) periods were identified. Relevant demographic, preoperative, anesthesia, and surgical variables were collected. Pre-ERAS and post-ERAS cohorts were compared in terms of hospital LOS, postoperative complications, and 30-day outcomes. Results We identified 264 patients, half in each cohort. Pre-ERAS and post-ERAS groups were similar with respect to age, race, and comorbidities. There were no significant differences in LOS, complications, 30-day readmission and mortality rates, or patient-reported outcomes. Of the patients with prolonged LOS, 31% had pulmonary complications, almost half of which were prolonged air leaks. ERAS adherence rate was approximately 60%. Conclusions In the first year of implementation, median LOS, complications, and 30-day outcomes did not differ significantly between the pre-ERAS and post-ERAS groups. Prolonged air leaks commonly led to prolonged LOS; therefore, thoracic ERAS protocols could include interventions to reduce air leak and consideration for discharging patients with chest tubes placed to Heimlich valves. Buy-in and adherence to a new protocol are necessary for implementation to be effective.
Development of MW-Level, Narrow-Band, FIR Lasers for Plasma Diagnostics

Required MW-level, 30 MHz linewidth, 496 μm radiation for plasma diagnostics may be achieved in CH 3 F using an oscillator-pulse amplifier combination employing transverse optical pumping (TOP). It is estimated that an upper limit of 150 joules of CO 2 laser pump energy is required to produce 1 MW (.07 joules, 60 nsec) FIR pulses.
A1C Reduction in Patients Who Declined Pharmacist-Led Diabetes Management Services.

Introduction:The purpose of this research is to assess the mean change in A1C associated with patients who declined a pharmacy-led diabetes management program and to evaluate effects of predictor v...
A matrix trace inequality

Si A et B sont deux matrices definies positives n×n, alors I) tr(AB)>0 et II) [tr(AB)] 1/2 <(trA+trB)/2
Parental Race/Ethnicity and Children’s Summer Activities: A Critical Race Approach:

Using the Early Childhood Longitudinal Study, Kindergarten Class of 2010–2011 (N = 3,748), we examine how children’s summer activities vary across White, Black, Latino, and Asian American families,...