cssi/SciSciGPT-SciSciNet huggingface dataset:
A Myosin Activator improves Actin Assembly and Sarcomere Function of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes with a Troponin T Point Mutation

We have investigated cardiac myocytes derived from human-induced pluripotent stem cells (iPSC-CMs) from two normal control and two family members expressing a mutant cardiac troponin T (cTnT-R173W) linked to dilated cardiomyopathy (DCM). cTnT is a regulatory protein of the sarcomeric thin filament. The loss of this basic charge, which is strategically located to control tension, has consequences leading to progressive DCM. iPSC-CMs serve as a valuable platform for understanding clinically relevant mutations in sarcomeric proteins; however, there are important questions to be addressed with regard to myocyte adaptation that we model here by plating iPSC-CMs on softer substrates (100 kPa) to create a more physiologic environment during recovery and maturation of iPSC-CMs after thawing from cryopreservation. During the first week of culture of the iPSC-CMs, we have determined structural and functional characteristics as well as actin assembly dynamics. Shortening, actin content, and actin assembly dynamics were depressed in CMs from the severely affected mutant at 1 wk of culture, but by 2 wk differences were less apparent. Sarcomeric troponin and myosin isoform composition were fetal/neonatal. Furthermore, the troponin complex, reconstituted with wild-type cTnT or recombinant cTnT-R173W, depressed the entry of cross-bridges into the force-generating state, which can be reversed by the myosin activator omecamtiv mecarbil. Therapeutic doses of this drug increased both contractility and the content of F-actin in the mutant iPSC-CMs. Collectively, our data suggest the use of a myosin activation reagent to restore function within patient-specific iPSC-CMs may aid in understanding and treating this familial DCM.
Detection of Minimal Residual bcr/abl Transcripts by a Modified Polymerase Chain Reaction

The Philadelphia (Ph1) chromosome in chronic myelogenous leukemia (CML) involves reciprocal translocation of the bcr gene and the c-abl oncogene. The fused bcr/abl gene is transcribed into two types of chimeric mRNA. By means of a combined method of S1 nuclease protection and polymerase chain reaction, we amplified sequences representative of the chimeric bcr/abl transcripts. Only 5 micrograms of total cellular RNA is needed and the chimeric bcr/abl message can be detected at a dilution of 1:100,000. We also detected residual chimeric bcr/abl transcripts in the remission samples from two Ph1-positive CML patients. This technique has the potential to identify a subpopulation of Ph1-positive CML patients in remission who are at high risk of relapse.
Does sodium dodecyl sulfate wash out of detergent-treated bovine pericardium at cytotoxic concentrations?

BACKGROUND AND AIM OF THE STUDY The ionic detergent sodium dodecyl sulfate (SDS) is a proposed treatment for the removal of antigenic proteins from unfixed biological scaffolds used in tissue engineering. However, questions remain about possible cytotoxic effects of SDS-treated tissues. The study aims were to: (i) develop a sensitive SDS assay for physiological solutions; (ii) measure SDS concentrations in the washing media of SDS-treated tissue; and (iii) determine cytotoxic SDS concentrations in cultured ovine vascular cells. METHODS An assay was developed to monitor SDS concentrations at microM levels, based on attenuated total reflectance infrared spectroscopy. Bovine pericardium was treated with SDS (1.0 to 0.01%) and washed for 96 h. The SDS concentration in the washing media was measured at 24-h intervals; data were expressed as microM/g tissue. Ovine vascular cells were cultured in DME media at 37 degrees C for 48 h in various SDS concentrations (10 to 1000 microM). The cells were then counted, and the percentage live cells expressed, based on trypan blue exclusion (n=5). RESULTS SDS concentrations > or =10 microM significantly reduced (p or =100 microM reduced (p < 0.05) the percentage live cells of ovine vascular cell cultures. SDS was present in the washing media of SDS-treated bovine pericardium. SDS leaching from bovine pericardium was found to depend on the SDS concentration used for the treatment, and diminished with time. CONCLUSION SDS leaches from SDS-treated bovine pericardium at concentrations that are potentially cytotoxic. An understanding of the dynamics of SDS washout, based on a sensitive SDS assay, may lead to the creation of protocols for the preparation of biological scaffolds that are free from cytotoxic leaching.
Pre-pregnancy BMI, delivery BMI, gestational weight gain and the risk of postpartum venous thrombosis.

Abstract Objective To characterize the risk of postpartum venous thromboembolism (VTE) associated with body-mass-index (BMI) in both pre-pregnancy and at delivery, and with gestational weight gain (GWG). Methods In a population-based, case-control study, we identified all women in Washington State with ICD-9 codes for VTE in the postpartum period between 2003 and 2011. Controls were women without VTE in the postpartum period, matched by delivery year to cases. Pre-pregnancy BMI, delivery BMI, and covariates were abstracted from birth certificates. Adjusted logistic regression models separately estimated postpartum VTE risk associated with categories of BMI in pre-pregnancy and at delivery. Results Cases ( n = 289) had a higher mean BMI than controls ( n = 4208) pre-pregnancy (29.9 kg/m 2 and 26.3 kg/m 2 , respectively) and at delivery (34.8 kg/m 2 vs. 31.4 kg/m 2 , respectively), with similar gestational weight gains. Compared with women with a normal pre-pregnancy BMI (18.5–24.9 kg/m 2 ), overweight (BMI 25–29.9 kg/m 2 ) and obese (BMI ≥ 30 kg/m 2 ) women were at a 1.5-fold and 1.8–4 fold greater risk of postpartum VTE, respectively, with greatest risks in women with class III obesity (BMI ≥ 40 kg/m 2 : OR 4.0, 95%CI 2.7–6.3). Observed associations of delivery BMI with postpartum VTE were less strong than those of pre-pregnancy BMI. Large weight gains during pregnancy (> 22 kg) also contributed to greater VTE risks (OR 1.5, 95%CI 1.0–2.2). Conclusion Maternal BMI is an important risk factor for postpartum VTE, grading from weak in overweight women to very strong in women with class III obesity. Care providers may prefer to use pre-pregnancy BMI, along gestational weight gain, when stratifying the risk of postpartum VTE at delivery.
Phylogeny of Paussus L. (Carabidae: Paussinae): unravelling morphological convergence associated with myrmecophilous life histories

. Ant nest beetles (Paussus L.) are ecologically fascinating and phenotypically bizarre. Obligate myrmecophiles, Paussus have undergone extreme adaptations for life with ants and their profound range of phenotypic diversity has been difficult to reconcile in a systematic framework. We conducted a detailed morphological study of Paussus utilizing novel techniques and character systems in order to discover anatomical apomorphies diagnostic of the major clades of Paussus strongly supported by molecular data. Bayesian inference (BI) of molecules alone, morphology alone and varying combinations of the two data types reveal that morphology is informative for placing Paussus species, despite the extreme phenotypic diversity and convergence prevalent in the group. We propose a new classification for Paussus based on this phylogeny. The genus Paussus is revised to include all genera, subgenera and species formerly classified as Paussus by Nagel (2003) in addition to Hylopaussus syn.n., Hylotorus syn.n. and Granulopaussus syn.n. The following species are transferred to Paussus: Paussus sebakuanus (Peringuey) comb.n., Paussus gracilis (Reichensperger) comb.n., Paussus bucephalus Gyllenhal, Paussus caroli (Reichensperger) comb.n., Paussus uelensis (Reichensperger) comb.n., Paussus hottentottus (Westwood) comb.n., Paussus blanchardi (Raffray) comb.n., Paussus basilewskyi (Luna de Carvalho) comb.n., Paussus granulatus Westwood, Paussus sankuruensis Reichensperger, Paussus leleupi (Reichensperger) comb.n., Paussus reichenspergeri (Luna de Carvalho) comb.n. We formally delineate and diagnose the following major subgroups of Paussus: Paussus I series, comprising the subgenera Bohemanipaussus Luna de Carvalho stat. rev. sensu n., Bathypaussus Wasmann stat. rev. sensu n., and Edaphopaussus Kolbe stat. rev. sensu n.; the Paussus II series comprising the subgenera Paussus L. stat. rev. sensu n., Klugipaussus Kolbe stat. rev. sensu n., Scaphipaussus Fowler stat. rev. sensu n., Hylotorus Dalman stat.n. sensu n., and Anapaussus Wasmann stat. rev. sensu n.; and the Paussus III series comprising the subgenera Lineatopaussus Kolbe stat. rev. sensu n. and Shuckardipaussus Kolbe stat. rev. sensu n.
The Cockroach DCMD Neurone: I. Lateral Inhibition and the Effects of Light- and Dark-adaptation

1.The responses of the cockroach descending contralateral movement detector (DCMD) neurone to moving light stimuli were studied under both light- and dark-adapted conditions. 2.With light-adaptation the response of the DCMD to two moving 2° (diam.) spots of white light is less than the response to a single spot when the two spots are separated by less than 10° (Fig. 2). 3. With light-adaptation the response of the DCMD to a single moving light spot is a sigmoidally shaped function of the logarithm of the light intensity (Fig. 3a). With dark-adaptation the response of a DCMD to a single moving light spot is a bell-shaped function of the logarithm of the stimulus intensity (Fig. 3b). The absolute intensity that evokes a threshold response is about one-and-a-half log units less in the dark-adapted eye than in the light-adapted eye. 4.The decrease in the DCMD9s response that occurs when two stimuli are closer than 10°, and when a single bright stimulus is made brighter, indicates that lateral inhibition operates among the afferents to the DCMD. 5.It is shown that this inhibition cannot be produced by a recurrent lateral inhibitory network. A model of the afferent path that contains a non-recurrent lateral inhibitory network can account for the response/intensity plots of the DCMD recorded under both light-adapted and dark-adapted conditions. 6.The threshold intensity of the DCMD is increased if a stationary pattern of light is present near the path of the moving spot stimulus. This is shown to be due to a peripheral tonic lateral inhibition that is distinct from the non-recurrent lateral inhibition described earlier. 7.It is suggested that the peripheral lateral inhibition acts to adjust the threshold of afferents to local background light levels, while the proximal non-recurrent network acts to enhance the acuity of the eye to small objects in the visual field, and to filter out whole-field stimuli.
Bullous, pseudobullous, & pustular dermatoses

Several dermatoses are typified by the formation of spaces (blisters; bullae) within or beneath the epidermis. These may be acellular or filled with particular species of inflammatory cells. Etiological categories include infectious, immune-mediated, genetic, drug-related, and idiopathic lesions. Examples of such disorders include impetigo, Herpes virus infections, pemphigus, bullous pemphigoid and pemphigoid gestationis, epidermolysis bullosa acquisita, IgA-related dermatoses, inherited epidermolysis bullosa variants, Hailey-Hailey disease, and porphyria cutanea tarda. Other conditions manifest microscopic acantholysis within the surface epithelium but are not associated with clinical bullae, such as Darier disease and Grover disease. Finally, both infectious and non-infectious causes exist for the development of neutrophilic pustules in the epidermis, as seen in pustular psoriasis, Sneddon-Wilkinson disease (subcorneal pustular dermatosis), and acute generalized exanthematous pustulosis. This review considers the clinical and histological features of all of these diseases.
Effector and Regulatory T Cell Subsets in Follicular Lymphoma Tumors: Implications for Pathogenesis and Prognosis.

Abstract 2718 Gene expression profiling of follicular lymphoma (FL) tumors showed that genes attributable to infiltrating T cells were associated with improved survival (Dave et al., NEJM 2004; 351: 2109). However, the precise nature of the protective T cell subsets is unknown. Recent studies suggest that master transcription factors (TFs) such as T-bet, GATA-3, RORgt, and Bcl6 regulate the differentiation of effector T cells (Teffs) into TH1/TC1, TH2/TC2, TH17/TC17, and follicular helper T cell (TFH) subsets, respectively. These dominant TFs along with other TFs imprint specific cytokine and chemokine receptor expression in both CD4+ and CD8+ T-cell subsets. Based on these studies, identification of TH1/TC1, TH2/TC2, TH17/TC17, and TFH subsets using chemokine receptor expression pattern has been described in normal donors (Duhen et al., Blood 2012; 119: 4430). To determine whether this chemokine receptor expression pattern could be used for identification of Teff subsets in FL tumors, we FACSorted T cells from single cell suspensions of FL tumors and performed real-time PCR for master TFs and subset-specific cytokines. We found that T cell subsets in FL tumors have similar chemokine receptor expression pattern as peripheral blood T cells from normal donors: TH1/TC1 are CXCR3+, TH17/TC17 are CXCR3-CCR6+CCR4+, and TFH are CXCR5hiPD-1hi. A similar profile was also observed in tonsils, widely accepted as suitable controls for FL. Recent studies also suggest that the TFs essential for Teff differentiation are also involved in polarization of Foxp3+ regulatory T cells (Tregs) into specialized subsets that regulate the corresponding Teff subsets. Moreover, these Treg subsets express identical chemokine receptors as their target Teffs. Using Foxp3 and chemokine receptor expression pattern we found two major subsets of Tregs in FL and tonsils: Foxp3+CXCR3+ Tregs that regulate TH1/TC1 and Foxp3+CXCR5hiPD-1hi follicular regulatory T cells (TFR) that regulate TFH. Next, using 10-color, 12-parameter flow cytometry we analyzed single cell suspensions of FL tumors (n=41) and normal tonsils (n=11) and determined the percentages of various Teff and Treg subsets, B cells, NK cells, and macrophages of total live cells. We found that NK cells and macrophages were not significantly different between the two but the percentage of B cells was significantly lower in FL vs tonsils (p Disclosures: No relevant conflicts of interest to declare.
ACR Appropriateness Criteria® Suspected Osteomyelitis, Septic Arthritis, or Soft Tissue Infection (Excluding Spine and Diabetic Foot)

Infection of the musculoskeletal system is a common clinical problem. Differentiating soft tissue from osseous infection often determines the appropriate clinical therapeutic course. Radiographs are the recommend initial imaging examination, and although often not diagnostic in acute osteomyelitis, can provide anatomic evaluation and alternative diagnoses influencing subsequent imaging selection and interpretation. MRI with contrast is the examination of choice for the evaluation of suspected osteomyelitis, and MRI, CT, and ultrasound can all be useful in the diagnosis of soft tissue infection. CT or a labeled leukocyte scan and sulfur colloid marrow scan combination are alternative options if MRI is contraindicated or extensive artifact from metal is present. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.
Horizontal Dip-Spin Casting of Aqueous Alumina-Polyvinylpyrrolidone Suspensions with Chopped Fiber

A novel ceramic processing method, called Horizontal Dip Spin Casting (HDSC), enabled fabrication of tubular ceramic parts with an aligned chopped fiber phase. HDSC was demonstrated using highly loaded aqueous alumina suspensions with >50 vol.% solids loading and ≤5 vol.% water-soluble polymer employed as a rheological modifier. Chopped carbon fibers were added to the suspensions to attain maximum loadings of 30 vol.%. During forming, cylindrical foam molds were dipped into the suspension while being rotated radially about the long axis. Simultaneously, a doctor blade was placed at a specified distance from the foam surface to facilitate the flow of the suspension to align the fiber and control the thickness of the material that accrued on the mold. Rheological study of alumina-PVP suspensions with and without chopped carbon fiber showed that the suspensions exhibited a yield-pseudoplastic flow behavior. The degree of alignment of the carbon fiber phase in the green bodies was characterized for various suspension formulations, carbon fiber contents and forming speeds. Stereological characterization of green body specimens confirmed the effectiveness of HDSC to attain the desired tubular geometry with considerable fiber alignment for a suspension composition containing ≤20 vol.% chopped fibers.
Structural and Anatomic Restoration of the Anterior Cruciate Ligament Is Associated With Less Cartilage Damage 1 Year After Surgery: Healing Ligament Properties Affect Cartilage Damage.

Background:Abnormal joint motion has been linked to joint arthrosis after anterior cruciate ligament (ACL) reconstruction. However, the relationships between the graft properties (ie, structural an...
The Politics of Recitation: Ideology, Interpellation, and Hegemony.

In this article, David I. Backer introduces the politics of recitation as a third realm for research on recitation pedagogy, in addition to process and product. Recitation is the pattern of classroom talk where a teacher asks a question, a student responds to the question, and the teacher evaluates the response. Research on classroom talk shows that this pattern is the dominant script in classrooms in the United States. Revisiting debates among critical theorists of schooling, particularly around the concept of hegemony, Backer argues that the politics of recitation is best understood in terms of interpellation, the concrete occurrence of ideological reproduction. He also maintains that recitation does not interpellate students into a particular category but instead teaches students to become interpellatable to any social category, independent of historical context. The article opens new possibilities for research into the connection between recitation and ideology and describes what liberatory pedagogy c...
Addressing the Social Determinants of Health: A Call to Action for School Nurses:

Social determinants of health (SDOH), the conditions in which children are born, grow, live, work or attend school, and age, impact child health and contribute to health disparities. School nurses must consider these factors as part of their clinical practice because they significantly and directly influence child well-being. We provide clinical guidance for addressing the SDOH when caring for children with three common health problems (obesity, insufficient sleep, and asthma). Given their unique role as school-based clinical experts, care coordinators, and student advocates, school nurses are well suited to serve as leaders in addressing SDOH.
The Comparative Efficacy of Traditional Systemic, Biologic, and Combination Therapies in the Treatment of Psoriasis: An Expansion Study:

BackgroundThere is a lack of comparative effectiveness research, particularly in the clinical setting, guiding psoriasis therapy.ObjectiveTo compare the efficacies of the traditional systemic, biol...
Crystal and defect chemistry of rare earth cations in BaTiO3

This study revisits the issue of rare earth cation substitutions into barium titanate. Analysis based upon crystal chemistry, defect chemistry and metastable states is presented to aid interpretation of experimental data. Recent detailed and highly precise X-ray powder diffraction and Electron Paramagnetic Resonance experiments performed on samples produced with different A/B ratios and fired under different oxygen partial pressure conditions give rise to new insights into the material. Specifically, the site occupancy and the valence states for the rare-earth dopants in barium titanate are considered. Earlier work is also reviewed and compared to the studies performed here. Collectively a classification of the various types of behavior observed for the rare-earth series in barium titanate is presented.
Biomechanics of Brain Injury: Looking to the Future

In this chapter, we review the state of the field in understanding how the cellular components of the brain and spinal cord respond to the biomechanical loading that occurs at the moment of traumatic injury. Several other recent reviews can be collected and reviewed in their own right for this purpose (Kumaria A, Tolias CM, Br J Neurosurg 22(2):200–206, 2008; Morrison B 3rd, Elkin BS, Dolle JP, Yarmush ML, Annu Rev Biomed Eng 13:91–126, 2011; Chen YC, Smith DH, Meaney DF, J Neurotrauma 26(6):861–876, 2009; LaPlaca MC, Simon CM, Prado GR, Cullen DK, Prog Brain Res 161:13–26, 2007). Rather, we intend to provide a broad overview of the basic principles that led to our current understanding of how cells in the nervous system respond to mechanical force. We also point out critical emerging areas in this discipline as we move from molecules, genes, and cells to circuit, behavior and degenerative disease. Our holistic objective is bringing a mechanistic understanding of how mechanotransmission in the CNS can shape the neurobehavioral response of the organism after traumatic CNS injury.
Doxycycline improves cage activity, but not exercised, supraspinatus tendon and muscle in a rat model

Abstract The objective of this study was to investigate the effects of doxycycline, a broad-spectrum MMP inhibitor, on cage activity and exercised supraspinatus tendon and muscle using a Sprague-Dawley rat model of non-injurious exercise. Because exercise may alter muscle and tendon MMP activity and matrix turnover, we hypothesized that doxycycline would abolish the beneficial adaptations found with exercise but have no effect on cage activity muscle and tendon properties. Rats were divided into acute or chronic exercise (EX) or cage activity (CA) groups, and half of the rats received doxycycline orally. Animals in acute EX groups were euthanized 24 h after a single bout of exercise (10 m/min, 1 h) on a flat treadmill. Animals in chronic EX groups walked on a flat treadmill and were euthanized at 2 or 8 week time points. Assays included supraspinatus tendon mechanics and histology and muscle fiber morphologic and type analysis. Doxycycline improved tendon mechanical properties and collagen organization in chronic cage activity groups, which was not consistently evident in exercised groups. Combined with exercise, doxycycline decreased average muscle fiber cross-sectional area. Results of this study suggest that administration of doxycycline at pharmaceutical doses induces beneficial supraspinatus tendon adaptations without negatively affecting the muscle in cage activity animals, supporting the use of doxycycline to combat degenerative processes associated with underuse; however, when combined with exercise, doxycycline does not consistently produce the same beneficial adaptations in rat supraspinatus tendons and reduces muscle fiber cross-sectional area, suggesting that doxycycline is not advantageous when combined with activity.
Real-Time Capacity Estimation of Lithium-Ion Batteries Utilizing Thermal Dynamics

Increasing longevity remains one of the open challenges for Lithium-ion (Li-ion) battery technology. We envision a health-conscious advanced battery management system, which implements monitoring and control algorithms that increase battery lifetime while maintaining performance. For such algorithms, real-time battery capacity estimates are crucial. In this paper, we present an online capacity estimation scheme for Li-ion batteries. The key novelty lies in: 1) leveraging thermal dynamics to estimate battery capacity and 2) developing a hierarchical estimation algorithm with provable convergence properties. The algorithm consists of two stages working in cascade. The first stage estimates battery core temperature and heat generation based on a two-state thermal model, and the second stage receives the core temperature and heat generation estimation to estimate state-of-charge and capacity. Results from numerical simulations and experimental data illustrate the performance of the proposed capacity estimation scheme.
A Framework for Adaptation of Training Task, Assistance and Feedback for Optimizing Motor (Re)-Learning With a Robotic Exoskeleton

Motor (re)-learning using a robotic exoskeleton can be improved by understanding what constitutes the optimal training environment for a subject that can maximize motor learning. We present a framework for motor (re)-learning using a robotic exoskeleton that provides subject-specific training by adapting one or more factors that constitute the training environment (training task, assistance, and feedback) based on the performance of the subject on the task. We present a torque-based task that requires subjects to dynamically regulate their joint torques for dexterous manipulation training and adapt the difficulty of the task based on their performance. We also present an adaptive impedance control for the robotic exoskeleton that transitions between error augmentation and haptic guidance training based on performance. Furthermore, we present an adaptive visual feedback approach that changes the transparency of the feedback based on performance. We conduct a study with ten healthy human subjects (five per training group) using a hand exoskeleton to evaluate if adaptations in task, assistance (assistive torque from the exoskeleton), and feedback (visual depiction of the torque trajectories) can modulate challenge and affect motor learning. Half of the participants were trained using an adaptive training paradigm (task, assistance, and feedback all adapted based on performance) and the other half with a nonadaptive training paradigm. A multiple comparison test showed that performance scores after adaptive training were significantly lower than nonadaptive training (MD: 62.6, 95% CI: 42.65–82.55, p $ 0.0001) demonstrating that adaptations in task, assistance, and feedback can modulate challenge and significantly affect motor learning.
ROSS PROCEDURE LEADING TO NEO-AORTIC INSUFFICIENCY

Ross procedure is used in young adults with congenital aortic stenosis. Over time, patients may develop autograft insufficiency and RV-PA homograft dysfunction. 42F with congenital aortic stenosis s/p aortic valvotomy followed by percutaneous valvuloplasty and Ross procedure presented with
SPECTROSCOPY OF HYDROTHERMAL REACTIONS. 5. DECARBOXYLATION KINETICS OF MALONIC ACID AND MONOSODIUM MALONATE

The kinetics of decarboxylation of 1.07 m malonic acid and monosodium malonate at 120−230 °C and 275 bar were determined directly in a combined microflow reactor and short-pathlength IR spectroscopy cell. Malonic acid and monosodium malonate decomposed in a single step to CO2 and acetic acid and CO2 and the acetate ion, respectively. The kinetics for malonic acid were modeled as an equilibrium between malonic acid and the monoanion with parallel decarboxylation of both species. The Arrhenius parameters are Ea = 120 ± 2 kJ/mol and ln A (s-1) = 29.4 ± 0.1 for the malonate monoanion and Ea = 126 ± 2 kJ/mol and ln A (s-1) = 31.4 ± 0.1 for malonic acid in a 316 stainless steel flow reactor at 120−210 °C. Decarboxylation of the monoanion is slower than that of malonic acid. The rates of decarboxylation of malonic acid are slower above 140 °C in a Pt/Ir alloy flow reactor with diamond windows than in a 316 stainless steel flow reactor with sapphire windows.
Auto-Sending Messages in an Intelligent Orchestration System: A Pilot Study

FACT (Formative Assessment with Computational Technology) is an intelligent orchestration system. That is, because it helps the teacher manage the workflow of a complicated set of activities in the classroom, it is an orchestration system. Because it conducts tasks-specific and domain-specific analyses of the students’ mathematical products and their group interactions, it is more intelligent than other orchestration systems. From analyzing videos of our iterative development trials, we realized that too many students needed help simultaneously, but the teacher could only visit one group at a time. Thus, we modified FACT to send a few messages to the students directly instead of sending all its advice to the teacher. This paper reports a successful pilot test of auto-sending.
The i3+3 design for phase I clinical trials.

3066Background: Other than the 3+3 design, new model-based statistical designs like the mTPI design (Ji and Wang, 2013, JCO) are alternative choices for oncology dose-finding trials, including immu...
Live imaging-assisted domain-specific CRISPR genome editing at single cell resolution in plants

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) technology has been widely used for genome engineering in a wide range of organisms, but much of the development of CRISPR-based genome editing has been aimed toward improving its efficiency and accuracy, so as to obtain genetic materials carrying known and stably heritable genome modifications. Precise spatiotemporal control over genome editing technology at cell type resolution is a key challenge for gene function studies. Some tissue-specific CRISPR genome editing methods relying on phenotypic characterization and fluorescent immune-staining techniques have been developed for biomedical research and gene therapy, they function by spatially controlling expression of Cas9. Recent work establishes the presence and location of mutational events at a single cell level in Arabidopsis roots and stomata. Here we present an efficient domain-specific CRISPR-Cas9 system combined with a high resolution live-imaging based screening strategy, applied in the shoot apical meristem of Arabidopsis thaliana. Using the system we investigate PIN-FORMED1 (PIN1) protein functions in tissue morphogenesis and PIN1 mechanical stress response in a cell layer-specific fashion. We find that reported failure to generate new primordia in epidermal PIN1 knockout SAMs is due to a reduction in mechanical stress differences in the sub-epidermal layer. The methods described are applicable to spatial-temporal gene manipulation in plants.
5 – Fluid Mechanics

Publisher Summary This chapter presents the application of dimensional analysis to several problems associated with the flow of fluids. Dimensional analysis related fluid properties, fluid statics, surface tension, pipe flow, hydrodynamic lubrication, and Bernoulli equation are discussed. Galileo's views concerning fluid statics is also presented in this chapter. Galileo pointed out that cause must precede effect, and the force holding the surfaces together cannot be due to the tendency for a vacuum to develop on separation of the surfaces. He also discovered that it is easy to find two bodies that fall with different speeds in water but with the same speed in air. This suggests that at least two effects are involved—buoyancy and drag. He also gave the concept of surface tension. In discussing the resistance (drag) of large and small bodies, Galileo concludes that the surface area and the surface roughness (rugosity) play important roles. Dimensional analysis also helped in solving the problem of Hagen–Poiseuille law for capillary flow.
Survival benefit of oophorectomy in stage IV gastric cancer patients with Krukenberg tumors.

e16566Background: The management of Krukenberg tumors from primary gastric cancer remains unclear and it is unknown if oophorectomy improves survival. The purpose of this study was to compare the o...
Primary care provider involvement in thyroid cancer survivorship care.

e14028Background: While prior research has examined how primary care providers (PCPs) can help care for breast and colon cancer survivors, little is known about the role of PCPs in thyroid cancer s...
Rate-Regularization and Generalization in VAEs

Variational autoencoders optimize an objective that combines a reconstruction loss (the distortion) and a KL term (the rate). The rate is an upper bound on the mutual information, which is often interpreted as a regularizer that controls the degree of compression. We here examine whether inclusion of the rate also acts as an inductive bias that improves generalization. We perform rate-distortion analyses that control the strength of the rate term, the network capacity, and the difficulty of the generalization problem. Decreasing the strength of the rate paradoxically improves generalization in most settings, and reducing the mutual information typically leads to underfitting. Moreover, we show that generalization continues to improve even after the mutual information saturates, indicating that the gap on the bound (i.e. the KL divergence relative to the inference marginal) affects generalization. This suggests that the standard Gaussian prior is not an inductive bias that typically aids generalization, prompting work to understand what choices of priors improve generalization in VAEs.
Open Pancreaticoduodenectomy for Peri-Ampullary Cancers

Pancreaticoduodenectomy is a technically challenging procedure composed of multiple individual steps, many of which have multiple variations. This chapter describes the procedure of open pancreaticoduodenectomy in a step-by-step fashion and discusses variations in technique and complex situations that may be encountered.
Duck Nest Detection Through Remote Sensing

Ducks are monitored extensively since they are an important game species and, as migratory birds, they are protected under the Migratory Bird Treaty Act. The prairies of North Dakota are part of the Prairie Pothole Region where more than 50% of ducks are produced in North American annually. To improve our ability to monitor annual populations of ducks, we assessed the feasibility of utilizing thermal imaging systems aboard Unmanned Aerial Systems (UASs) to automatically detect duck nests. With 24 flights across five days collecting 134 images of nests, we demonstrated a nest detection of 38% and 17% from flight altitudes of 40m and 80m, respectively. With higher resolution, via a different sensor or lower altitudes, this method of duck nest detection is feasible.
Free-Homomorphic Relations on Banach $$*$$ ∗ -Probability Spaces Generated by Semicircular Elements Induced by Natural Numbers

In this paper, we study how an arbitrary natural number, greater than 1, induces a finite free semicircular family, and the corresponding Banach $$*$$ -probability space. And then certain $$*$$ -homomorphisms acting on such Banach $$*$$ -probability spaces are considered. In particular, we are interested in cases where such $$*$$ -homomorphisms preserve free-distributional data among them.
Semiautomatic analysis of tumor proportion in colon cancer: Lessons from a validation study.

Abstract The tumor stroma ratio (TSR) is a promising histopathologic prognostic biomarker, which could allow for more accurate risk stratification and improved patient management in colorectal cancer. The purpose of our research was to validate the results of a previous study, which had suggested that not only a low but also a high tumor proportion (TP) might be an independent risk factor for occurrence of distant metastasis and worse overall survival using a semiautomatic image analysis approach with the open-source software ImageJ. We investigated 253 pT3 and pT4 adenocarcinomas of no special type. The previously established thresholds (PES-cut-offs) used to classify the patients (previous 3-tiered-classification) according to the tumor proportion (TP) in a highTP (TP ≥ 54%), a mediumTP (TP 15%) and a lowTP (TP ≤ 15%) group did not show a significant risk stratification. Even the adjustment of these threshold revealed no significant results. Therefore, a receiver-operating characteristic (ROC) analysis was performed to establish the cut-off with the most significant predictive power and a “new 2-tiered-classification” using this cut-off (40% at MinTP) showed a significantly shorter absence of metastasis for patients with a low TP (p = 0.007). These results confirm that a low TP is associated with an adverse prognosis. This study did not confirm the previous assumption that a high TP might also be a risk factor for occurrence of metastasis. Furthermore, it demonstrates that this semiautomatic technique is not superior to the established method, so that approaches to enhance prognostic techniques should continue.
SIRT2 Promotes Murine Melanoma Progression Through Natural Killer Cell Inhibition.

Purpose/Objective(s) SIRT2, an NAD+-dependent histone deacetylase, has been shown to play a pivotal role in various physiological processes, however, its role in cancer is currently controversial. In recent years, SIRT2 has been described as both a tumor suppressor and oncogene with divergent expression and function in various malignancies. With established roles in inflammation and glucose and iron metabolism, systemic and microenvironment SIRT2, rather than just intrinsic tumor cell expression, might have implications in tumor progression. Moreover, recent interest in the tumor immune microenvironment has further characterized immune cells involved in tumor suppression, including natural killer (NK) cells. Here, we sought to investigate the biological role of systemic SIRT2 in melanoma tumor progression and to evaluate its interaction with key tumor suppressive immune cells. Materials/Methods Murine models were employed to investigate the effect of systemic SIRT2 on melanoma tumor progression. Tumor progression was measured in terms of weight and volume for 20 days following subcutaneous inoculation of Sirt2-KI and WT mice with B16-F10 melanoma cells. Differences in tumor-infiltrating immune cell composition were determined by flow cytometry. Granzyme B and Ki-67 immunohistochemical staining was used to measure NK cell functional activity and proliferation in in vivo melanoma samples. NK cell function was further evaluated using in vitro and ex vivo mouse models as well as an in vitro human model. Antibody-mediated NK cell depletion established NK cells as an integral player in SIRT2-mediated tumor promotion. Finally, SIRT2 was pharmacologically inhibited by SirReal2, and the effect on melanoma progression and NK cell tumor infiltration was established. Results Increased systemic expression of SIRT2 promoted melanoma progression in mice, resulting in larger and heavier tumors. Mechanistically, systemic SIRT2 overexpression reduced the number of tumor-infiltrating NK cells and suppressed NK cell activation and proliferation within the tumor microenvironment. Furthermore, despite the effect of increased tumor growth rate and tumor volume in wild-type littermate mice, NK cell depletion did not affect that in SIRT2-overexpressing mice. Lastly, pharmacological inhibition of SIRT2 increased NK cell tumor infiltration and suppressed melanoma tumor growth. Conclusion Systemic SIRT2 and NK cell activity exhibit a dynamic functional interaction which promotes melanoma tumor progression. Given the recent renewed interest in NK-cell-mediated immunotherapy response, SIRT2 could represent a new opportunity to mediate immunotherapy response and resistance.
Quoting Lead Times and Prices to Customers

Firms in service and make-to-order manufacturing industries often quote lead times and prices to customers. We define uniform quotation mode (UQM) as the strategy where a firm offers a single lead time and price quotation, and differentiated quotation mode (DQM) is where a firm offers a menu of lead times and prices for customers to choose from. Both modes are followed in practice. Firms should determine which is more profitable. We classify customers into two groups: lead time sensitive (LS) and price sensitive (PS). LS customers value lead time reduction more than PS customers. We develop mathematical models of both quotation modes and analyze them to determine the most profitable mode under specified situations as well as the best lead time and price quotations within each mode. We find that DQM is dominated by UQM whenever PS customers have positive utilities from UQM or LS customers have positive utilities from DQM. Otherwise, which quotation mode is better depends on multiple factors, such as customer characteristics (including lead time reduction valuation and product valuation of a customer, and the proportion of LS customers) and production characteristics (including the desired service level and service or production cost).
Control of the Synthesis of T4 Phage Deoxynucleotide Kinase Messenger Ribonucleic Acid in Vivo

Abstract The regulation of the synthesis of messenger RNA of T4 phage-specific deoxynucleotide kinase has been studied in vivo by assay of mRNA for its capacity to direct the synthesis of deoxynucleotide kinase in vitro. The deoxynucleotide kinase mRNA first appears at 2 min after infection and increases in amount until 8 min. Thereafter the messenger activity decreases. The appearance of deoxynucleotide kinase mRNA is blocked when chloramphenicol is added before or immediately after infection. When added at 8 min the normal levels of kinase mRNA were observed at times later in the infection period. However, the addition of chloramphenicol at 3 min after infection results in the production of an exaggerated amount of deoxynucleotide kinase mRNA, which keeps increasing until at least 30 min after infection. The high level of mRNA formed in the presence of chloramphenicol could reflect the absence of an agent or agents required for the termination of the synthesis of this mRNA. This conclusion was reached from experiments with the inhibitor of RNA synthesis, rifampicin. When added to cultures at a time late in the infection period, rifampicin caused an immediate drop in the level of kinase mRNA. At this time the level of this mRNA is therefore a balance between synthesis and degradation. When similar experiments were carried out to study the level of mRNA for α-glucosyltransferase, cultures receiving chloramphenicol at 3 min after infection and rifampicin at 11 and 17 min did not show a drop in the level of mRNA for this enzyme. There is thus a difference in the stability of the two types of mRNA in regard to their degradation by bacterial nucleases when the infection was carried out with chloramphenicol added at 3 min. In the absence of chloramphenicol both kinds of mRNA underwent degradation. The overproduction and the delay of shutoff of the synthesis of deoxynucleotide kinase mRNA are also seen when nonpermissive Escherichia coli K-12 is infected with T4 DO mutants or when DNA synthesis is inhibited by fluorodeoxyuridine. The infection with an MD mutant does not result in the same effect as that observed with the DO mutants. We favor the hypothesis that both new T4 protein (or proteins) and continuous T4 DNA replication are necessary for the proper termination of synthesis of delayed-early T4 RNA.
Model Reference Adaptive Control for Systems with Time Varying Model Commands

Model reference adaptive control is applied to linear time invariant systems for the case of arbitrary time varying model commands. Asymptotic stability is guaranteed provided that the output stabilized transfer matrix is strictly positive real. Only output measurements are needed. Neither perfect model following nor explicit parameter identification is required. Simulations show the scheme to be capable of guaranteeing stability when the model inputs are time varying.
Collision avoidance and resolution multiple access (CARMA)

The collision avoidance and resolution multiple access (CARMA) protocol is presented and analyzed. CARMA uses a collision avoidance handshake in which the sender and receiver exchange a request to send (RTS) and a clear to send (CTS) before the sender transmits any data. CARMA is based on carrier sensing, together with collision resolution based on a deterministic tree-splitting algorithm. For analytical purposes, an upper bound is derived for the average number of steps required to resolve collisions of RTSs using the tree-splitting algorithm. This bound is then applied to the computation of the average channel utilization in a fully connected network with a large number of stations. Under light-load conditions, CARMA achieves the same average throughput as multiple access protocols based on RTS/CTS exchange and carrier sensing. It is also shown that, as the arrival rate of RTSs increases, the throughput achieved by CARMA is close to the maximum throughput that any protocol based on collision avoidance (i.e., RTS/CTS exchange) can achieve if the control packets used to acquire the floor are much smaller than the data packet trains sent by the stations. Simulation results validate the simplifying approximations made in the analytical model. Our analysis results indicate that collision resolution makes floor acquisition multiple access much more effective.
The interaction of connective tissue with aqueous urea: I. Reversible and irreversible effects

Abstract The interaction of dilute aqueous urea ( Concentrated urea (> 5 M) profoundly changes the isometric force. This can be described as Step 1, rapid force elevation that is followed by Step 2, a slow further increase in force which attains a maximum; finally, Step 3 reduces the force until the tendon ruptures. These three steps are considered to be a result of: (i) rapid diffusion of urea into flexible regions of collagen which results in their dehydration, (ii) slow melting of crystalline segments that are stabilized by hydrogen bonds, and (iii) creeping of the polypeptide chains that are liberated during Step 2.
Vitamin D in systemic lupus erythematosus: modest association with disease activity and the urine protein-to-creatinine ratio.

Objective We investigated whether an increase in vitamin D levels in patients with systemic lupus erythematosus was associated with improvement in disease activity.
Patterns in specific leaf area and the structure of a temperate heath community

Relationships between the distribution and specific leaf area (SLA: leaf area per unit dry mass) of six heath (Ericaceae) species were investigated along an environmental gradient between peat bogs and conifer forest in British Columbia, Canada. I asked whether patterns in SLA could help to identify the processes shaping plant distributional patterns. Specifically, I assessed whether (i) species’ distributions across the environmental gradient are correlated with SLA (ii) relationships between plant distributional patterns and SLA are similar among bogs with different shrub species (iii) intraspecific patterns in SLA parallel interspecific relationships between distributions and SLA, and (iv) intraspecific patterns are environmentally determined. Results showed that distributional patterns were often correlated with SLA; species with lower SLA were more abundant towards the centre of bogs, while species with higher SLA were more abundant in forest. Intraspecific patterns in SLA paralleled distributional patterns across the gradient; individuals located towards the centre of bogs had lower SLA than those growing in forest. A transplantation experiment showed that plants typically altered their SLA according to local environmental conditions. However, one bog showed no relationship between species’ distributions and SLA. This bog lacked the two species with lowest SLA, which typically occurred at the centre of other bogs. In their absence, species with higher SLA that typically occurred in forest increased in abundance towards the centre of the bog, where they obtained lower values of SLA. Therefore, while distributional patterns were often closely associated with SLA, plasticity in SLA was associated with increased breadth of species’ distributions across the gradient. Overall results indicate SLA may serve as a useful proxy for a range of life history traits to help elucidate the processes structuring plant communities.