cssi/SciSciGPT-SciSciNet huggingface dataset:
Plasma membrane localization of the Toll protein in the syncytial Drosophila embryo: importance of transmembrane signaling for dorsal-ventral pattern formation

Formation of the Drosophila embryo9s dorsal-ventral pattern requires the maternal product of the Toll gene. DNA sequence and genetic analyses together suggested that the Toll gene product is a transmembrane protein which communicates information from an extracytoplasmic compartment to the cytoplasm. Using antibodies as probes, we show that the Toll protein is a 135 × 10(3) Mr glycoprotein which is tightly associated with embryonic membranes. During the syncytial stage when dorsal-ventral polarity is established, the maternal Toll protein is associated with the plasma membrane around the entire embryo. During later embryonic stages, the Toll protein is expressed zygotically on many cell surfaces, possibly to promote cell adhesion. The plasma membrane localization of the Toll protein in the syncytial embryo suggests that transmembrane signaling from the extracellular perivitelline space to the cytoplasm is required for establishment of the embryonic dorsal-ventral pattern.
Experimental and Analytical Study of Micro-Serrations on Surgical Blades

This paper reports on a study and application of laser ablation for machining of micro-serrations on surgical blades. The proposed concept is inspired by nature and mimics a mosquito’s maxilla, which is characterized by a number of serrations along its edge in order to painlessly penetrate human skin and tissue. The focus of this study is to investigate the maxilla’s penetration mechanisms and its application to commercial surgical blades. The fundamental objective is to understand the friction and cutting behavior between a serrated hard surface and soft materials, as well as to identify serration patterns that would minimize the cutting force and the friction of the blade during tissue cutting. Micro-serrations characterized by different patterns and sizes ranging from 200 μm to 400 μm were designed and manufactured on surgical blades. As supported by finite element methods (FEM), a reduction of 20∼30% in the force during blade cutting has been achieved, which encourages further studies and their applications to biomedical devices.Copyright © 2015 by ASME
Sum of Independent Gamma Live Loads Model

The purpose of this note is to derive an expression for the addition of arbitrary, independent gamma-distributed variables and compare the result in a typical case to simplified procedure.
Non)Vanishing results on local cohomology of valuation rings

Abstract We examine local cohomology in the setting of valuation rings. The novelty of this investigation stems from the fact that valuation rings are usually non-Noetherian, whereas local cohomology has been extensively developed mostly in a Noetherian setting. Various vanishing results on local cohomology for valuation rings of finite Krull dimension are obtained, and a uniform bound on the global dimension of such rings is established. Our investigation reveals differences in the sheaf theoretic definition of local cohomology, and the algebraic definition in terms of a limit of certain Ext functors.
Amygdala lesions in rhesus macaques decrease attention to threat

Evidence from animal and human studies has suggested that the amygdala plays a role in detecting threat and in directing attention to the eyes. Nevertheless, there has been no systematic investigation of whether the amygdala specifically facilitates attention to the eyes or whether other features can also drive attention via amygdala processing. The goal of the present study was to examine the effects of amygdala lesions in rhesus monkeys on attentional capture by specific facial features, as well as gaze patterns and changes in pupil dilation during free viewing. Here we show reduced attentional capture by threat stimuli, specifically the mouth, and reduced exploration of the eyes in free viewing in monkeys with amygdala lesions. Our findings support a role for the amygdala in detecting threat signals and in directing attention to the eye region of faces when freely viewing different expressions. The amygdala in the medial temporal lobe of the human and non-human primate brain is known to process salient social stimuli and to mediate threat discrimination. Here, Dal Monte et al.show that rhesus monkeys with amygdala lesions have deficits in detecting threat signals and directing attention to the eye region of a conspecific's face.
SITE-DIRECTED MUTAGENESIS OF PREDICTED ACTIVE SITE RESIDUES IN GLUTAMATE CARBOXYPEPTIDASE II

Glutamate carboxypeptidase II (GCP II) catalyzes the extracellular hydrolysis of the neuromodulator N-acetyl-aspartylglutamate to N-acetyl-aspartate and glutamate. GCP II also hydrolyzes gamma-glutamyl bonds in folylpolyglutamate. The predicted amino acid sequence of GCP II displays similarities to aminopeptidases from Streptomyces griseus and Vibrio proteolyticus, whose crystal structures have been determined. These aminopeptidases are cocatalytic zinc metallopeptidases belonging to the peptidase family M28. Specific zinc and substrate ligands have been proposed in GCP II based on the amino acid sequence alignment to these M28 family members. In the present study, site-directed mutagenesis has been used to test the assignment of these putative ligands in human GCP II. Substitutions to the five putative zinc ligands resulted in severely reduced enzyme activity, although mutant protein was expressed as demonstrated by immunoblot analysis. In addition, substitutions of amino acids near the putative zinc ligands have identified other specific residues important for enzyme structure and/or function. Substitutions to putative substrate ligands were less perturbing, and increases in Km were observed for substitutions that introduced a large charge perturbation (e.g., Lys to Glu). The results from substitutions at the proposed zinc and substrate ligands are consistent with the assignment of these residues and suggest that GCP II has a three-dimensional structure similar to other members of the peptidase family M28.
Determination of serum calcium by means of orthocresolphthalein complexone.

The use of orthocresolphthalein complexone (OCPC) as a reagent for the determination of calcium was introduced by Anderegg and associates and Schwarzenbach. Pollard and Martin and Stern and Lewis soon thereafter described manual spectrophotometric procedures using this dye. The procedure of Pollard and Martin is not applicable to the analysis of biologic materials. The method described by Stern and Lewis deals with the analysis of blood serum. Calcium is precipitated as the oxalate from 0.1 ml. of serum. The precipitate is washed and the oxalate ion, which in this procedure interferes with subsequent color development, is destroyed by heat (500 C. for 30 min). The calcium carbonate residue is dissolved in 0.1 ml. of N HC1, all traces of which must be removed by drying and heating before and residue is treated with a pH 8.5 borate-buffered OCPC color reagent. The absorbance is measured at 575 mju. Kessler and Wolfman have recently described an automated procedure adapted to the Autotechnicon. Our paper presents a greatly improved manual spectrophotometric method based upon release of the bound calcium by means of protein precipitation and the complete masking of the response of the dye to magnesium by means of 8-quinolinol (direct method). As a reference method, the calcium is precipitated as the oxalate. Without being washed, this is dissolved in 0.2 N HC1, an aliquot of which is reacted with the OCPC color reagent (alternate procedure).
Comparative Effectiveness of Gallery-injected Insecticides and Fumigants to Control Carpenterworms (Lepidoptera: Cossidae) and Oak Clearwing Borers (Lepidoptera: Sesiidae)

Gallery injections with six insecticides and three fumigants were tested for comparative effectiveness in controlling two hardwood borers, the carpenterworm, Prionoxystus robiniae (Peck), and an oak clearwing borer, Paranthrene simulans (Grote). The insecticides were injected to treat both the phloem-cambium mine and gallery entrance; the fumigants were injected only into the gallery entrance, which was then plugged. Diazinon, chlorpyrifos, and carbaryl gave good to excellent control of both borers. Lindane and endosulfan were effective only at comparatively high rates. Bacillus thuringiensis was ineffective even at very high rates. The three fumigants (carbon disulfide, Serafume, and paradichlorobenzene) provided complete control. The gallery injection technique was deemed feasible for use against borers in high-value trees. Gallery injection has advantages over bark sprays because it can give satisfactory control of borers already established in galleries and limits chemical application to a few galleries instead of entire trees or stands of trees.
Epithelial NF-κB signaling promotes EGFR-driven lung carcinogenesis via macrophage recruitment

ABSTRACTSeveral studies have demonstrated that NF-κB activation is common in lung cancer; however, the mechanistic links between NF-κB signaling and tumorigenesis remain to be fully elucidated. We investigated the function of NF-κB signaling in epidermal growth factor receptor (EGFR)-mutant lung tumors using a transgenic mouse model with doxycycline (dox)-inducible expression of oncogenic EGFR in the lung epithelium with or without a dominant inhibitor of NF-κB signaling. NF-κB inhibition resulted in a significant reduction in tumor burden in both EGFR tyrosine kinase inhibitor (TKI)-sensitive and resistant tumors. However, NF-κB inhibition did not alter epithelial cell survival in vitro or in vivo, and no changes were detected in activation of EGFR downstream signaling pathways. Instead, we observed an influx of inflammatory cells (macrophages and neutrophils) in the lungs of mice with oncogenic EGFR expression that was blocked in the setting of NF-κB inhibition. To investigate whether inflammatory cells...
META-ANALYSIS OF RANDOMIZED CONTROL TRIALS (RCTS) COMPARING PERCUTANEOUS LEFT ATRIAL APPENDAGE (WATCHMAN DEVICE) CLOSURE VERSUS ADJUSTED DOSE WARFARIN FOR STROKE PROPHYLAXIS IN NON-VALVULAR ATRIAL FIBRILLATION

Recent RCTs indicate non-inferiority of percutaneous left atrial appendage (LAA) closure compared to warfarin for stroke prevention. The use of percutaneous devices remains controversial due to concerns for complications. We sought to pool the published data to compare LAA closure vs warfarin.
Synthesis of Metalated Pseudorotaxane Polymers with Full Control over the Average Linear Density of Threaded Macrocycles

Here we report the synthesis of metalated main-chain polypseudorotaxanes via ring-opening olefin metathesis copolymerization of macrocycles and metalated [2]catenanes. By varying the feed ratio of the macrocycle and the [2]catenate comonomers, we prepared metalated pseudorotaxane polymers with selected, predictable average linear densities of threaded macrocycles that ranged from 0% to 100%, thus allowing, for the first time, both full and fine control over this key parameter.
Effects of a Wide-area Application of ULV Malathion on Leafhoppers in Alfalfa

Beginning in 1968, a 16 (4×4) mi2 area of Dawson County, Nebr., was sprayed in August for 3 consecutive years with ULV malathion. Leafhoppers in alfalfa were monitored as nontarget organisms. Scaphytopius acutus (Say) was suppressed from one growing season into the next. All other major species, Aceratogallia uhleri (Van Duzee), Balclutha neglecta (DeLong and Davidson). Empoasca fabae (Harris), and Macrosteles fascifrons (Stal) recovered within 2–4 wk following treatment.
Mammalian histone acetyltransferase complexes.

Over the last decade, great progress has been made in elucidating how the human genome op- erates in the chromatin context. This paper describes our work on two human acetyltransferases, PCAF and TIP60, and their interaction partners. This study provides new clues on the function of these en- zymes. In a striking parallel with the general transcription factor TFIID, PCAF complex contains proteins that have histone-like domains. We speculate that these subunits can presumably form a nucleosome-like struc- ture on DNA, which would allow PCAF to contribute to the maintenance of an active state of chromatin. On the other hand, TIP60 complex contains two eukaryotic homologs of bacterial RuvB helicase/ATPse, involved in recombination and repair. Accordingly, expression of a dominant negative mutant of TIP60 in living cells inter- feres with their ability to repair DNA damage, which points out, for the first time, a role for a histone acetyltransferase in a process other than transcription. We also have evidence implicating TIP60 in the apoptotic response to DNA damage. Given that human genome operates in the context of chromatin, study of the machinery and activities that modify chromatin can greatly help in understanding how the hu- man genome works. Eventually, it can lead to the devel- opment of new ways to prevent and treat human health disorders, such as cancer, for example. First part of this paper reviews an approach used in our work to study a subset of the chromatin modifying activities, namely, his- tone acetyltransferases. it is based on identification of in- teraction partners of the proteins under study, which can greatly help in figuring out what is the function of a particu- lar protein. Our work on PCAF complex and the model of its function, based on the features of the PCAF complex components, will be described. The second part of the paper reviews new results obtained for TIP60 complex. These results implicate TIP60 acetyltransferase in DNA
Coherent Control of Population Transfer via Linear Chirp in Liquid Solution: The Role of Motional Narrowing

The conditions under which linear chirp can be used to control population transfer between the electronic states of a chromophore dissolved in liquid solution are investigated. To this end, we model the chromophore as a two-state system with shifted electronic potential energy surfaces and a fluctuating electronic transition frequency. The fluctuations are described as an exponentially correlated Gaussian stochastic process, which can be characterized by the average fluctuation amplitude, σ, and correlation time, τc. The time-dependent Schrodinger equation is solved numerically for an ensemble of stochastic histories, at different values of σ and τc, and under a wide range of pulse intensities and linear chirp coefficients. In the limit τc → ∞, we find that control diminishes rapidly as soon as σ exceeds the bandwidth of the pulse. However, we also find that control can be regained by reducing τc. We attribute this trend to motional narrowing, whereby decreasing τc narrows down the effective bandwidth of ...
Freeze Preservation of Squirrel Monkey Sperm for Use in Timed Fertilization Studies

These investigations were concerned with the response of squirrel monkey sperm to freezing. A procedure involving preincubation at 37° C, progressive cooling combined with a two-step dilution, and freezing on Dry Ice was applied to semen samples collected by electroejaculation from two animals. Sperm concentrations in these samples were 321.8×10 6 /ml (±204.1 SD) and 532.8×10 6 ml (±117.1 SD), respectively. Sperm motility prior to freezing was 68.1% (±15.9 SD) and 63.6% (±14.8 SD). Following freezing and thawing, motilities of 53.8% (±17.1 SD) and 51.8% (±22.9 SD) were observed. The freezing procedure increased sperm motility in approximately 30% of samples from both animals. Changes in the motile behavior of sperm were not observed after freezing. Serum testosterone measurements, the first made in the squirrel monkey, gave values similar to those obtained for other primates. A progressive decline in testosterone concentration, seen in both animals during the course of these investigations, did not affect semen characteristics or the response of sperm to freezing.
Effect of partly purified gastrone on acid secretion, body temperature, and leukocyte count in the dog.

Partly purified gastrone (fraction 7), extracted from human achlorhydric gastric juice was assayed in dogs with vagally denervated or vagally innervated gastric pouches. Assays with histamine, administered either as a single, subcutaneous injection repeated at three 1-hr intervals, or by continuous intravenous infusion, showed that the degree of inhibition of HC1 secretion by gastrone was dose-related. The dose of gastrone which inhibited secretion by 50% (inhibited dose 50) was between 55 and 100 μg. Assays with a standard 100-cal meat meal were performed in the dogs with vagally innervated pouches: doseresponsive inhibition of secretion was observed, with an inhibited dose 50 of 10 to 30 μg. Pyrexia was induced by gastrone in 60 of 64 assays. The rectal temperature increased significantly during the 1st hr, reached a peak at 2 hr, and then decreased. Inhibition of secretion followed a parallel course, but lagged 1 hr behind pyrexia. In four of the meat meal assays, using low doses of gastrone, significant inhibition of secretion occurred without a rise of temperature. Gastrone induced an initial leukopenia, followed by a leukocytosis. The pooled achlorhydric gastric juice from which the gastrone was prepared contained a mixed group of oral commensal bacteria. Gastrone and bacterial endotoxins produce similar effects on gastric acid secretion, body temperature, and leukocyte levels and the time course of these effects is also similar. The preparation of purified gastrone that does not have these biological actions of bacterial endotoxins (fever, leukocytosis) has not yet been reported.
Hot Corrosion of Alumina Matrix-Composites

The effects of sodium sulfate-induced hot corrosion on the room temperature strength of an alumina and three alumina-matrix composites were examined in this study. The strength of the alumina was unaffected by the corrosion. On the other hand, the strength of the composites decreased, to various degrees, with exposure to sodium sulfate.
Formation and Reactivity of Silicon Carbide Cluster Cations

Direct laser vaporization of a mixture of silicon and graphite powders produced silicon carbide cluster cations containing 1–3 silicon atoms and 1–12 carbon atoms. Gas-phase ion-molecule reactions with acetylene and other gases were studied in the FTMS. With C2H2 the cations with 1 silicon atom behave very similarly to the carbon cluster cations, indicating a linear structure for these ions. The cations with 2 silicon atoms exhibit unusual reactivity. The initial reaction to add CH2 is very slow. With increasing time, the reaction becomes faster and forms the adduct. 13C labelling studies revealed a process of carbon exchange, which may be linked to the “activation” process just described. A structural or electronic state isomerization is believed to be the cause. Cleavage of carbon-carbon multiple bonds, dehydrogenation, deoxygenation and dehalogenation reactions of Si2C2 + are also reported. Charge transfer reactions of the initial Si2C2 + ion population were used to bracket the ionization potential of the corresponding neutral.
Methods of Detection of Antitumour Immunity

It is well known that a too high challenge dose can overcome immunity so that it is impossible to find any difference between the control and immunized groups. Hence the so-called minimal dose must be determined for each tumour, i. e. the amount of viable tumour cells capable of growing in 100% of the control animals using a standard method of inoculation. This minimal dose shows great variations for different tumours and is influenced not only by the antigenicity of the tumour used, but also by its general biological properties. The degree of immunity achieved for different tumours is therefore best determined not by comparing the absolute number of cells overcoming immunity, but by the number of the minimal doses.
Minimally-Invasive Repair of Bilateral Calcaneal Fractures with Unilateral External Fixation: A Case Report

INTRODUCTION AND OBJECTIVES: Calcaneal fractures are a serious injury with significant associated morbidity. Bilateral calcaneal fractures complicate issues even further, due to the physical disability that the patient is left with. One of the major issues with any calcaneal fracture is the risk of soft tissue compromise caused by the traumatic nature of the injury. A percutaneous approach allows the soft tissue envelope to remain viable, while still fixating the fractures. The purpose of this presentation is to highlight the use of percutaneous repair, the role of external fixation in calcaneal fractures, and lastly discuss the outcome for this particular patient. METHODS: A 26 year-old male presented to the office with bilateral calcaneal fractures, approximately 1 week after sustaining a fall from a height of 12 feet. The patient was brought to the operating room after spending approximately 2 weeks in bilateral posterior splints with Jones compressive dressings. The right calcaneal fracture was fixate...
Proteomic Analysis of Waldenstrom Macroglobulinemia (WM) and IgM Monoclonal Gammopathy of Undetermined Significance (IgM-MGUS) Identifies Potential Targets for Drug Therapy.

Abstract The objective of this study was to analyze molecular changes that occur at the protein level in WM and IgM-MGUS in order to identify proteins dysregulated at disease progression and design new therapies. We employed antibody protein microarrays (BD Clonetech, CA) to measure changes in the patterns of protein expression between WM, IgM-MGUS and normal lymphoplasmacytic cells as control. The antibody array is a novel technique that assays protein differences directly by hybridizing fluorescently labeled protein mixtures from cell extracts onto a glass slide spotted with 512 different monoclonal antibodies specific for human proteins. CD 19+ and CD138+ purified lymphoplasmacytic cells were obtained from cryopreserved bone marrow samples of 5 newly diagnosed patients with WM and 5 patients with IgM-MGUS. Control plasma cells were obtained from 3 pooled CD19+ and CD138+ purified normal donor bone marrow cells. To assess differential expression, the mean of the ratios of Cy5/Cy3 for each sample were analyzed using the Clontech software to calculate an internally normalized ratio. The normalized data were analyzed by the Genespring software and changes of protein expression ≥2 fold in 60% of the samples as compared to normal control were identified in both WM and MGUS groups. There were 20 proteins upregulated in WM and 21 proteins in MGUS as compared to normal control cells These included proteins from the small GTPases such as the Ras, Rho and Ran families (Rab 4, MONA, RCC1, and CDC42GAP), Kinases/signaling proteins (ROK alpha, p62 dok, JAK, 14-3-3e), cyclin dependent kinase (CDK2), fatty acid synthase (HDAC3), NFkB pathway (IKKalpha, IKBe), and histone deacetylase. The WM and IgM MGUS differed in only 3 proteins using the 2-fold threshold. The WM samples showed overexpression of the heat shock protein Hsp90, the Ras family protein CDC25C, and the chemotaxis protein p43/EMAPII as compared to the MGUS samples. This is the first proteomic study of WM and MGUS patients. It identifies novel proteins dysregulated in WM that may serve in future clinical trials as targets for therapy such as Hsp90, NFkB, HDAC and fatty acid synthase. In addition, it identifies 3 proteins that identify disease progression from MGUS to WM, which could be useful for monitoring MGUS patients and designing targeted therapies to prevent progression to WM.
Outage Probability Study in a NOMA Relay System

In this paper two different non-orthogonal multiple access (NOMA) relay schemes are analyzed, namely NOMA cooperative scheme and NOMA TDMA scheme. Both schemes apply NOMA in the first stage by sending NOMA superimposed signals to relays. Relays then forward the messages to two UEs in the second stage. In the second stage of NOMA cooperative scheme, two relays form a cooperative pair to simultaneously transmit the decoded signals to their respective recipients. Dirty paper coding is used as precoding to cancel out inter-user interference. The second stage of NOMA TDMA scheme uses TDMA to send to two users in two separate time slots. The outage probability is analyzed for both schemes and the impact of error propagation in the NOMA successive interference cancellation is analyzed and evaluated. Performance study shows that the theoretical analysis matches the simulation results very well. NOMA cooperative scheme achieves an overall better outage performance than NOMA TDMA scheme.
Dopaminergic modulation of basal ganglia output through coupled excitation–inhibition

Learning and maintenance of skilled movements require exploration of motor space and selection of appropriate actions. Vocal learning and social context-dependent plasticity in songbirds depend on a basal ganglia circuit, which actively generates vocal variability. Dopamine in the basal ganglia reduces trial-to-trial neural variability when the bird engages in courtship song. Here, we present evidence for a unique, tonically active, excitatory interneuron in the songbird basal ganglia that makes strong synaptic connections onto output pallidal neurons, often linked in time with inhibitory events. Dopamine receptor activity modulates the coupling of these excitatory and inhibitory events in vitro, which results in a dynamic change in the synchrony of a modeled population of basal ganglia output neurons receiving excitatory and inhibitory inputs. The excitatory interneuron thus serves as one biophysical mechanism for the introduction or modulation of neural variability in this circuit.
Exploring Within-Rater Category Ordering: A Simulation Study Using Adjacent-Categories Mokken Scale Analysis:

The interpretation of ratings from educational performance assessments assumes that rating scale categories are ordered as expected (i.e., higher ratings correspond to higher levels of judged stude...
Comparative analysis of the Pocillopora damicornis genome highlights role of immune system in coral evolution

Comparative analysis of the expanding genomic resources for scleractinian corals may provide insights into the evolution of these organisms, with implications for their continued persistence under global climate change. Here, we sequenced and annotated the genome of Pocillopora damicornis, one of the most abundant and widespread corals in the world. We compared this genome, based on protein-coding gene orthology, with other publicly available coral genomes (Cnidaria, Anthozoa, Scleractinia), as well as genomes from other anthozoan groups (Actiniaria, Corallimorpharia), and two basal metazoan outgroup phlya (Porifera, Ctenophora). We found that 46.6% of P. damicornis genes had orthologs in all other scleractinians, defining a coral ‘core’ genome enriched in basic housekeeping functions. Of these core genes, 3.7% were unique to scleractinians and were enriched in immune functionality, suggesting an important role of the immune system in coral evolution. Genes occurring only in P. damicornis were enriched in cellular signaling and stress response pathways, and we found similar immune-related gene family expansions in each coral species, indicating that immune system diversification may be a prominent feature of scleractinian coral evolution at multiple taxonomic levels. Diversification of the immune gene repertoire may underlie scleractinian adaptations to symbiosis, pathogen interactions, and environmental stress.
A rapid and non-pathogenic assay for association of Mycobacterium tuberculosis gyrBA mutations and fluoroquinolone resistance using recombinant Mycobacterium smegmatis

We developed a method involving recombinant Mycobacterium bovis bacillus Calmette-Guerin (BCG) and recombinant Mycobacterium smegmatis to determine which mutations in Mycobacterium tuberculosis (Mtb) gyrBA are associated with fluoroquinolone (FQ) resistance. The minimal inhibitory concentration (MIC) for FQ for recombinant strains with wild-type Mtb gyrBA was equivalent to that for strains with intrinsic gyrBA. Among 27 gyrBA mutations, the fold-changes in FQ MIC for M. smegmatis and M. bovis BCG backgrounds were comparable and were in part equivalent to those previously reported for recombinant Mtb strains. Mutations at position 90 or 94 of gyrA conferred strong and synergistic FQ resistance, which may be associated with the clinical observation that isolates carrying these mutations are the most or second most frequent. Sitafloxacin hydrate had the lowest MIC among the FQs tested in this study, which is similar to findings from a previous in vivo animal study. Most gyrBA mutations detected in clinical Mtb isolates could confer FQ resistance, but several mutations reduced bacterial growth rates. Overall, recombinant M. smegmatis appears to be a beneficial surrogate system to evaluate FQ susceptibility of virulent mycobacteria.
Identifying lupus patients in electronic health records: Development and validation of machine learning algorithms and application of rule-based algorithms.

Abstract Objective To utilize electronic health records (EHRs) to study SLE, algorithms are needed to accurately identify these patients. We used machine learning to generate data-driven SLE EHR algorithms and assessed performance of existing rule-based algorithms. Methods We randomly selected subjects with ≥ 1 SLE ICD-9/10 codes from our EHR and identified gold standard definite and probable SLE cases by chart review, based on 1997 ACR or 2012 SLICC Classification Criteria. From a training set, we extracted coded and narrative concepts using natural language processing and generated algorithms using penalized logistic regression to classify definite or definite/probable SLE. We assessed predictive characteristics in internal and external cohort validations. We also tested performance characteristics of published rule-based algorithms with pre-specified permutations of ICD-9 codes, laboratory tests and medications in our EHR. Results At a specificity of 97%, our machine learning coded algorithm for definite SLE had 90% positive predictive value (PPV) and 64% sensitivity and for definite/probable SLE, 92% PPV and 47% sensitivity. In the external validation, at 97% specificity, the definite/probable algorithm had 94% PPV and 60% sensitivity. Adding NLP concepts did not improve performance metrics. The PPVs of published rule-based algorithms ranged from 45–79% in our EHR. Conclusion Our machine learning SLE algorithms performed well in internal and external validation. Rule-based SLE algorithms did not transport as well to our EHR. Unique EHR characteristics, clinical practices and research goals regarding the desired sensitivity and specificity of the case definition must be considered when applying algorithms to identify SLE patients.
Youth Depression Screening with Parent and Self-Reports: Assessing Current and Prospective Depression Risk.

Few studies have examined the incremental validity of multi-informant depression screening approaches. In response, we examined how recommendations for using a multi-informant approach may vary for identifying concurrent or prospective depressive episodes. Participants included 663 youth (AgeM = 11.83; AgeSD = 2.40) and their caregiver who independently completed youth depression questionnaires, and clinical diagnostic interviews, every 6 months for 3 years. Receiver operating characteristic (ROC) analyses showed that youth-report best predicted concurrent episodes, and that both youth and parent-report were necessary to adequately forecast prospective episodes. More specifically, youth-reported negative mood symptoms and parent-reported anhedonic symptoms incrementally predicted future depressive episodes. Findings were invariant to youth’s sex and age, and results from person and variable-centered analyses suggested that discrepancies between informants were not clinically meaningful. Implications for future research and evidence-based decision making for depression screening initiatives are discussed.
Generation of Stressmarks for Early Stage Soft-Error Modeling

Early-stage Soft-Error Rate (SER) vulnerability modeling and estimation is essential for all types of processing platforms, ranging from embedded/IoT processors to server-class systems, to ensure reliable and deterministic operation. The objective of such modeling is to provide inputs to designers on the addition of protection features, such as latch hardening, parity protection, ECC and redundancy techniques, for achieving RAS targets without significantly impacting the overall processor area and power. This calls for a systematic methodology, starting from the latch level and moving up to the micro-architecture and architecture level of abstraction. In this paper, we present a methodology that characterizes processor vulnerability and define a metric to effectively quantify this vulnerability. Based on these characterizations, we propose techniques to generate synthetic stressmarks that maximize SER vulnerability for a given processor configuration. We carry out an exploration of these stressmarks across different operating corners for a state-of-the-art POWERTM ISA-based server-class processor. In comparison to single instruction microbenchmarks as well as real workloads from the SPEC-2017 benchmark suite, our stressmarks demonstrate up to 16X increase in vulnerability in terms of our proposed metric.
In-beam γ-ray spectroscopy in the vicinity of 100Sn

In recent years, in-beam γ-ray experiments supplied a vast amount of data on high-spin states in nuclei in the vicinity of 100Sn. The present contribution reviews spectroscopic information obtained recently for N⩾50 nuclei around 100Sn, with emphasis on isomer studies, and discusses selected results in the frame of the shell model.
A combined analog and digital workflow for retrofitting a monolithic ceramic crown to an existing removable partial denture

Abstract A clinical and laboratory workflow for fabricating and retrofitting a monolithic ceramic crown to an existing removable partial denture (RPD) is described. A conventional polyvinyl siloxane impression was made of the prepared tooth with the RPD in place. A stone cast was poured and, after die sectioning, scanned with a tabletop scanner. The ceramic crown was designed and fabricated by using a digital workflow to fit the RPD clasp assembly, providing an adequate undercut for the clasp. The crown was then delivered and the RPD evaluated for adequate fit.
Employing design thinking methods in nursing to improve patient outcomes

Nurses are in a key position between the patient, provider, and the health care system. This position provides them with valuable insight into problems and potential solutions in health care, yet there is little recorded involvement of nurses in product or service development. A five-step process called design thinking has proven successful across multiple settings to generate meaningful solutions that provide value to those directly impacted by a problem. The purpose of this study is to describe the process of design thinking and review how it can be used by nurses for the creation of products and services that will benefit health care systems and improve nursing practice and patient care.
Genetic map and heritability of Aspergillus flavus.

Abstract The carcinogenic aflatoxins are a human health concern as well as an economic burden to corn, peanut and other crops grown within the United States and globally. Aflatoxins are produced by fungi species in Aspergillus section Flavi, primarily Aspergillus flavus. Though previously thought of as only asexual, A. flavus has recently been found to undergo sexual reproduction both in laboratory crosses and in the field. To elucidate the consequences of genetic exchange through a single generation of the sexual cycle within A. flavus, we constructed genetic maps based on three mapping populations, each composed of the parental strains and approximately 70 F1 progeny. Genome-wide data using double digest Restriction Associated DNA sequencing identified 496, 811, and 576 significant polymorphisms differentiating parents across eight linkage groups; these polymorphisms served as markers. Average spacing between marker loci was 3.1, 2.1, and 3.5 map units and overall map length was 1504.4, 1669.2, and 2001.3 cM. Recombination was non-randomly distributed across chromosomes with an average rate of recombination of about 46.81 cM per Mbp. We showed inheritance of mitochondrial loci from the sclerotial (female) parent in crosses, whereas nuclear loci showed a 1:1 segregation ratio from both parents. The linkage map will be useful in QTL analyses to identify traits that increase sexual fertility in A. flavus and modulate aflatoxin production, both of which have significant implications for sustainable reduction of aflatoxin contamination using biological control agents.
Decoding DMD transcriptional networks using single-nucleus RNA sequencing.

Duchenne muscular dystrophy (DMD) is an X chromosome-linked disease, and it is the most common form of muscular dystrophy caused by genetic mutations in the Dmd gene (1). The Dmd gene contains 79 exons, spans 2.4 Mb, and is the single largest gene in the human genome (2). This gene encodes for dystrophin, which is a component of the dystrophin–glycoprotein complex that provides structural stability to the cell membrane (by connecting the cytoskeleton and the extracellular matrix), and a dysfunctional or absent dystrophin protein leads to progressive muscle wasting with cycles of muscle degeneration and regeneration that ultimately fail (3, 4). Young boys with DMD lose their ability to ambulate, become wheelchair bound, and die prematurely (1, 5). This disease affects skeletal muscle, which is the single largest organ in the body, and it normally has a remarkable capacity for regeneration (6). In response to a severe injury caused by genetic disorders, trauma, or exposure to toxins that destroys over 90% of the muscle, the cytoarchitecture of the injured tissue is completely restored and is indistinguishable compared to uninjured muscle within a 2- to 4-wk period. This regenerative capacity is due to the myogenic stem cell population (i.e., satellite cells) that is resident in adult skeletal muscle, and with repeated DMD-mediated degeneration and regeneration this regenerative process ultimately is exhausted (6). While a number of studies have enhanced our understanding of the myogenic stem cell population, new insights are needed regarding the factors that govern muscle regeneration and potentially serve as therapies for diseases like DMD. In PNAS, Chemello et al. (7) use emerging technologies to provide a discovery science platform. First, they engineered a mouse model by deleting exon 51 of the Dmd gene. This gene-edited mouse (ΔEx51) was viable, lacked dystrophin in skeletal muscle and heart, … [↵][1]1To whom correspondence may be addressed. Email: garry{at}umn.edu. [1]: #xref-corresp-1-1
Formulation and Statistical Analysis of the Mixed, Continuous/Discrete Dependent Variable Model in Classical Production Theory

Data ste which contain jointly endogeneous discrete and continuous variables often occur in practice. This paper presents a model of the economic and stochastic processes generating such data as well as methods of estimation. A maximum likelihood estimator is examined and found to exhibit the usual optimality but it is computationally burdensome. A simpler estimator, the QREG, which is a simple weighted average of separate probits (or logits) and regression estimates is suggested as an alternative. The QREG is also found to be optimal but only when a certain covariance restriction is found to hold. Thus a test of the restriction based on the joint distribution of separate probit ans regression estimates is proposed.
Comparison of Two Illumina Whole Transcriptome RNA Sequencing Library Preparation Methods Using Human FFPE Specimens

Abstract RNA extraction and library preparation from formalin-fixed, paraffin-embedded (FFPE) samples are crucial pre-analytical steps towards achieving optimal downstream RNA Sequencing (RNASeq) results. We assessed the Illumina TruSeq Stranded Total RNA library preparation method and the Illumina TruSeq RNA Access library preparation method for RNA-Seq analysis using 25 FFPE samples from human cancer indications (NSCLC, CRC, RC, BC and HCC) at two independent vendors. These FFPE samples covered a wide range of sample storage durations (3-25 years-old), sample qualities, and specimen types (resection vs. core needle biopsy). Our data showed that TruSeq RNA Access libraries yield over 80% exonic reads across different quality samples, indicating higher selectivity of the exome pull down by the capture approach compared to the random priming of the TruSeq Stranded Total kit. The overall QC data for FFPE RNA extraction, library preparation, and sequencing generated by the two vendors are comparable, and downstream gene expression quantification results show high concordance as well. With the TruSeq Stranded Total kit, the average Spearman correlation between vendors was 0.87 and the average Pearson correlation was 0.76. With the TruSeq RNA Access kit, the average Spearman correlation between vendors was 0.89 and the average Pearson correlation was 0.73. Interestingly, examination of the crossvendor correlations compared to various common QC statistics suggested that library concentration is better correlated with consistency between vendors than is the RNA quantity. Our analyses provide evidence to guide selection of sequencing methods for FFPE samples in which the sample quality may be severely compromised.
From Bench to Bedside: The Role of a Multidisciplinary Approach to Treating Patients with Lymphedema.

Background: Lymphedema is a condition characterized by dysfunction of the lymphatic system resulting in chronic, progressive soft tissue edema that can negatively impact individuals' function, self-image, and quality of life. Understanding of the disease process has evolved significantly in the past two decades with advances in diagnostic modalities and surgical techniques revolutionizing prior treatment algorithms. Methods and Results: We reviewed our current approach at the University of Southern California to improving outcomes in lymphedema treatment. Given the complexity of this medical condition, patients are best served by a multidisciplinary approach. At our institution, this involves a collaborative effort between bench researchers, lymphatic therapists, medical physicians, and lymphedema surgeons. Basic science and translational research provide further understanding into the underlying mechanisms of lymphangiogenesis and the possibility for potential therapeutic interventions. Our surgical algorithms require patients to undergo a thorough diagnostic evaluation and consultation with certified lymphatic therapists prior to undergoing either physiologic or debulking operations. Patients are followed clinically following any interventions. Further community outreach and education is carried out in order to improve upon early diagnosis and symptom recognition. Conclusions: Optimizing lymphedema care requires a collaborative interplay between researchers, physicians, and therapists. Additionally, patient and provider education on early disease recognition and treatment options is an equally critical aspect of improving patient outcomes.
Neighborhood-Level Redlining and Lending Bias Are Associated with Breast Cancer Mortality in a Large and Diverse Metropolitan Area-Letter.

Collin and colleagues recently published their findings characterizing how redlining and lending bias (e.g., mortgages) impacted breast cancer mortality among patients in Georgia ([1][1]). This retrospective analysis builds upon their prior work that identified how institutional racism and bias
Confidence Intervals for Seroprevalence

This paper concerns the construction of confidence intervals in standard seroprevalence surveys. In particular, we discuss methods for constructing confidence intervals for the proportion of individuals in a population infected with a disease using a sample of antibody test results and measurements of the test's false positive and false negative rates. We begin by documenting erratic behavior in the coverage probabilities of standard Wald and percentile bootstrap intervals when applied to this problem. We then consider two alternative sets of intervals constructed with test inversion. The first set of intervals are approximate, using either asymptotic or bootstrap approximation to the finite-sample distribution of a chosen test statistic. We consider several choices of test statistic, including maximum likelihood estimators and generalized likelihood ratio statistics. We show with simulation that, at empirically relevant parameter values and sample sizes, the coverage probabilities for these intervals are close to their nominal level and are approximately equi-tailed. The second set of intervals are shown to contain the true parameter value with probability at least equal to the nominal level, but can be conservative in finite samples.
Targeted stellate decentralization: Implications for sympathetic control of ventricular electrophysiology

Background Selective bilateral cervicothoracic sympathectomy has proven to be effective for managing ventricular arrhythmias in the setting of structural heart disease. In the procedure currently used, the caudal portions of both stellate ganglia along with thoracic chain ganglia down to T4 ganglia are removed. Objective The purpose of this study was to define the relative contributions of the T1–T2 and T3–T4 paravertebral ganglia in modulating ventricular electrical function. Methods In anesthetized vagotomized porcine subjects (n = 8), the heart was exposed via sternotomy along with right and left paravertebral sympathetic ganglia to the T4 level. A 56-electrode epicardial sock was placed over both ventricles to assess epicardial activation–recovery intervals (ARIs) in response to individually stimulating right and left stellate vs T3 paravertebral ganglia. Responses to T3 stimuli were repeated after surgical removal of the caudal portions of stellate ganglia and T2 bilaterally. Results In intact preparations, stellate ganglion vs T3 stimuli (4 Hz, 4-ms duration) were titrated to produce equivalent decreases in global ventricular ARIs (right side: 85 ± 6 ms vs 55 ± 10 ms; left side: 24 ± 3 ms vs 17 ± 7 ms). Threshold of stimulus intensity applied to T3 ganglia to achieve threshold was 3 times that of T1 threshold. ARIs in unstimulated states were unaffected by bilateral stellate–T2 ganglion removal. After acute decentralization, T3 stimulation failed to change ARIs. Conclusion Preganglionic sympathetic efferents arising from the T1–T4 spinal cord that project to the heart transit through stellate ganglia via the paravertebral chain. Thus, T1–T2 surgical excision is sufficient to functionally interrupt central control of peripheral sympathetic efferent activity.