cssi/SciSciGPT-SciSciNet huggingface dataset:
Voting strategy for artifact reduction in digital breast tomosynthesis.

Artifacts are observed in digital breast tomosynthesis (DBT) reconstructions due to the small number of projections and the narrow angular range that are typically employed in tomosynthesisimaging. In this work, we investigate the reconstruction artifacts that are caused by high-attenuation features in breast and develop several artifact reduction methods based on a “voting strategy.” The voting strategy identifies the projection(s) that would introduce artifacts to a voxel and rejects the projection(s) when reconstructing the voxel. Four approaches to the voting strategy were compared, including projection segmentation, maximum contribution deduction, one-step classification, and iterative classification. The projection segmentation method, based on segmentation of high-attenuation features from the projections, effectively reduces artifacts caused by metal and large calcifications that can be reliably detected and segmented from projections. The other three methods are based on the observation that contributions from artifact-inducing projections have higher value than those from normal projections. These methods attempt to identify the projection(s) that would cause artifacts by comparing contributions from different projections. Among the three methods, the iterative classification method provides the best artifact reduction; however, it can generate many false positive classifications that degrade the image quality. The maximum contribution deduction method and one-step classification method both reduce artifacts well from small calcifications, although the performance of artifact reduction is slightly better with the one-step classification. The combination of one-step classification and projection segmentation removes artifacts from both large and small calcifications.
The pulse wave arrival time (QKd interval) in normal children.

The interval between the onset of QRS of the electrocardiogram and the arrival of the pulse wave at the brachial artery, as detected by the appearance of Korotkoff sounds at diastolic pressure (QKd), provides a measure of a pulse wave arrival time, i.e., the sum of the pre-ejection period and a pulse transmission time. This measurement has proven useful in the evaluation of cardiovascular disease, thyroid and catecholamine status, and several other conditions in adults. In order to standardize this measurement in children, measurements were obtained on 63 normal children ranging in age from 7 months to 18 years. Because of the dependence of pulse transmission time on the distance of propagation, the QKd interval (in msec) is related to height (H in cm) by the equation: QKd = 56.6 + 0.797H. By use of this equation one can obtain a "height corrected QKd." Correction for pulse rate is not necessary for resting subjects. These normal ranges permit use of the QKd interval for clinical studies in children. These studies also permit measurement of the mean pulse wave velocity for a group of individuals. PWV (m/sec) increases with age according to the equation: PWV = 2.44 + 0.203 A, (A in years) with a correlation coefficient of r = 0.823. This implies progressive loss of functional elasticity of the major arteries throughout childhood.
Tips for Incorporating Quality Improvement Projects Into a Residency Program Curriculum

In February 2001, the ACGME endorsed systems-based practices as 1 of 6 competencies to form the basis of residency education [1,2]. In the proram requirements, the ACGME’s iagnostic Radiology Residency Reiew Committee states that residents ust “participate in identifying sysem errors and implementing potenial systems solutions” and be trained to analyze systemically the roblems, develop solutions, impleent solutions, and evaluate the efectiveness of the intervention” [3]. hus, residents need to be conductng and participating in quality imrovement projects as part of their esidencies. Engaging residents in a epartmental performance improveent initiative can provide them ith valuable experience in physician eadership, and the department gets a aluable asset in tackling problems. he real trick is incorporating these CGME requirements into an aleady overregulated and compressed esidency without it being the straw hat breaks the resident’s back [4]. The first step is to view this reuirement as a meaningful way to enich the residency program. On anther level and in a study of medical tudent education, schools that inorporated practice management raining into their programs found hat students were significantly more atisfied with their education than chools that did not [5]. Following re suggestions for incorporating a erformance improvement curricuum into your radiology residency rogram. Consider Quality Improvement as an “Antirotation”
Abandoning medical malpractice

(1984). Abandoning medical malpractice. Journal of Legal Medicine: Vol. 5, No. 4, pp. 549-594.
Toughness-curve behavior of an alumina-mullite composite

Toughness-curve (T- or R-curve) behavior of a composite of 30 vol%, polycrystalline, coarse-grained, spherical alumina agglomerates dispersed throughout a fine-grained, 50/50 vol% alumina-mullite matrix, and that of its microstructural end-members (100% matrix and 100% alumina), were studied using the indentation-strength-in-bending technique. T-curves were deconvoluted from indentation-strength data using an indentation fracture mechanics model. The monolithic matrix and alumina exhibited an invariant toughness and a moderate T-curve, respectively. In comparison, the composite exhibited a pronounced T-curve. The T-curve of the composite is best explained as deriving from the interaction of a propagating crack with the alumina agglomerates: crack propagation experiments revealing two possible toughening mechanisms-intra-agglomerate frictional grain bridging and elastic bridging ligaments in the matrix that appeared to be associated with alumina agglomerates. Rule-of-mixtures toughness calculations indicated that intra-agglomerate bridges could account for only a fraction of the toughening exhibited by the composite. It is suggested that the extra toughening arises from the elastic bridging ligaments.
Experiential Modes of Game Play

In order to gather empirical & qualitative data on game play across all genres, and at the same time addressing multiple research questions, a framework was established at the VX Lab at Indiana University to standardize methodology. This Experiential Mode Framework allows for the inclusion of player perceptions, experiences, and allows for coupling with game structures and functionality. Following a postpositivist methodology devised by Robert Yin, this paper describes the logic, strategies, and incorporation of the Experiential Mode Framework in Game Play Analysis.
Technology in Mathematics Education: Preparing Teachers for the Future

The preparation of preservice teachers to use technology is one of the most critical issues facing teacher education programs. In response to the growing need for technological literacy, the University of Northern Colorado created a second methods course, Tools and Technology of Secondary Mathematics. The goals of the course include (a) providing students with the opportunity to learn specific technological resources in mathematical contexts, (b) focusing student attention on how and when to use technology appropriately in mathematics classrooms, and (c) giving opportunities for students to apply their knowledge of technology and its uses in the teaching and learning of mathematics. Three example activities are presented to illustrate these instructional goals of the course.
Transcending the individual human mind—creating shared understanding through collaborative design

Complex design problems require more knowledge than any single person possesses because the knowledge relevant to a problem is usually distributed among stakeholders. Bringing different and often controversial points of view together to create a shared understanding among these stakeholders can lead to new insights, new ideas, and new artifacts. New media that allow owners of problems to contribute to framing and resolving complex design problems can extend the power of the individual human mind. Based on our past work and study of other approaches, systems, and collaborative and participatory processes, this article identifies challenges we see as the limiting factors for future collaborative human-computer systems. The Envisionment and Discovery Collaboratory (EDC) is introduced as an integrated physical, and computational environment addressing some of these challenges. The vision behind the EDC shifts future development away from the computer as the focal point, toward an emphasis that tries to improve our understanding of the human, social, and cultural system that creates the context for use. This work is based on new conceptual principles that include creating shared understanding among various stakeholders, contextualizing information to the task at hand, and creating objects to think with in collaborative design activities. Although the EDC framework is applicable to different domains; our initial effort has focused on the domain of urban planning (specifically transportation planning) and community development.
Catechol O-Methyltransferase Val158Met Polymorphism in Schizophrenia: Differential Effects of Val and Met Alleles on Cognitive Stability and Flexibility

OBJECTIVE: The catechol O-methyltransferase (COMT) Val158Met polymorphism has been associated with cognitive and behavioral phenotypes in schizophrenia. Whether COMT genotype is beneficial may depend on phenotype definition. The authors examined the effects of COMT genotype on a task that distinguishes imitation from reversal learning. They hypothesized that the Val and Met alleles would be associated with deficits in imitation learning and reversal learning, respectively. METHOD: Twenty-six patients with schizophrenia and schizoaffective disorder completed a task requiring alternation between imitation and reversal rules. RESULTS: Met homozygotes showed better acquisition of the imitation rule but greater deficit shifting from imitation to reversal. Val homozygotes had poorer imitation performance and slower reaction times. CONCLUSIONS: The Met allele, by increasing tonic dopamine, may promote cognitive stability but limit cognitive flexibility.
Dual equations and classical orthogonal polynomials

Abstract : Dual integral equations involving Bessel functions and dual series equations involving Jacobi polynomials occur in several branches of applied mathematics and large classes of these equations can now be solved. We show how many dual sequence equations involving Jacobi and Laguerre polynomials can be solved by similar methods. (Author)
The subjective effect of two-dimensional pictorial noise

A study has been made of the subjective effects of the class of independent additive rectangular low-pass Gaussian noises. Three original pictures, varying in the amount of detail, were used. The general shapes of the isopreference surfaces in - k_{1} - k_{2} space where a is the \sigma value, and k_{1} and k_{2} are the bandwidths of the noise in the horizontal and vertical directions, respectively, were found. If the objectionability of noise is a linear functional of the noise spectrum, then one may deduce that for the class of noises whose spectra are symmetrical with respect to both horizontal and vertical frequencies, the weighting function in the integral representing noise objectionability is similar in shape to these isopreference surfaces.
Endoscopic ultrasound-guided fine-needle aspiration

Thirty-eight consecutive patients underwent endoscopic ultrasound-guided fine-needle aspiration. Of 46 lesions, 34 were extraluminal (12 pancreatic masses, 8 periesophageal nodes, 6 celiac nodes, 2 pericolonic masses, 1 mediastinal mass, 1 perigastric mass, 1 liver, 1 periduodenal node, 1 perirectal mass, 1 perirectal node) and 12 were submucosal (8 gastric, 3 duodenal, 1 esophageal). One hundred sixty-three passes were made, with an average of 3.5 passes per lesion and 4.3 passes per patient (range, 1 to 8). Adequate specimens were obtained from 91% of targeted lesions. The overall diagnostic accuracy was 87%. In patients with malignant lesions, sensitivity was 91% and specificity 100%. Celiac nodes were successfully sampled and diagnostic in 5 of 6 (83%) patients. No complications occurred. Using this technique, an initial tissue diagnosis of malignancy was made in 66% of cancer patients without a previous diagnosis and the preoperative stage was changed in 44% of cancer patients. The additional information gained by this modality directly influenced the decision not to perform surgery in 26% of patients with a primary malignancy. Endoscopic ultrasound-guided fine-needle aspiration is feasible and can be safely used to evaluate submucosal and extraluminal lesions in both the upper and lower gastrointestinal tract with a high degree of diagnostic accuracy.
Multiple page size modeling and optimization

With the growing awareness that individual hardware cores will not continue to produce the same level of performance improvement, there is a need to develop an integrated approach to performance optimization. In this paper we present a paradigm for continuous program optimization (CPO), whereby automatic agents monitor and optimize application and system performance. The monitoring data is used to analyze and create models of application and system behavior. Using this analysis, we describe how CPO agents can improve the performance of both the application and the underlying system. Using the CPO paradigm, we implemented cooperating page size optimization agents that automatically optimize large page usage. An offline agent uses vertically integrated performance data to produce a page size benefit analysis for different categories of data structures within an application. We show how an online CPO agent can use the results of the predictive analysis to automatically improve application performance. We validate that the predictions made by the CPO agent reflect the actual performance gains of up to 60% across a range of scientific applications including the SPEC-cpu2000 floating point benchmarks and two large high performance computing (HPC) applications.
Rapid kinetics of endocytosis at rod photoreceptor synapses depends upon endocytic load and calcium.

Release from rods is triggered by the opening of L-type Ca2+ channels that lie beneath synaptic ribbons. After exocytosis, vesicles are retrieved by compensatory endocytosis. Previous work showed that endocytosis is dynamin-dependent in rods but dynamin-independent in cones. We hypothesized that fast endocytosis in rods may also differ from cones in its dependence upon the amount of Ca2+ influx and/or endocytic load. We measured exocytosis and endocytosis from membrane capacitance (Cm) changes evoked by depolarizing steps in voltage clamped rods from tiger salamander retinal slices. Similar to cones, the time constant for endocytosis in rods was quite fast, averaging <200 ms. We manipulated Ca2+ influx and the amount of vesicle release by altering the duration and voltage of depolarizing steps. Unlike cones, endocytosis kinetics in rods slowed after increasing Ca2+ channel activation with longer step durations or more strongly depolarized voltage steps. Endocytosis kinetics also slowed as Ca2+ buffering was decreased by replacing BAPTA (10 or 1 mM) with the slower Ca2+ buffer EGTA (5 or 0.5 mM) in the pipette solution. These data provide further evidence that endocytosis mechanisms differ in rods and cones and suggest that endocytosis in rods is regulated by both endocytic load and local Ca2+ levels.
Prenatal Ultrasonographic Detection of Bladder Rhabdomyosarcoma

Rhabdomyosarcomas are the most common sarcomas of childhood, comprising 5% to 15% of all childhood solid tumors and 4% to 8% of total childhood malignancies. Although primary lesions are most common in the head and neck, approximately 20% involve the genitourinary system. Most rhabdomyosarcomas present by age 10 years, and 2 age peaks are observed at ages 2 to 6 years and 15 to 19 years. However, neonatal rhabdomyosarcomas are extremely rare. Of 3,217 patients in Intergroup Rhabdomyosarcoma Study (IRS) groups I to IV only 14 (0.4%) were younger than 30 days at diagnosis.1 To our knowledge only 2 other cases of bladder rhabdomyosarcoma neonates have been reported.1, 2 CASE REPORT
ADULT PSYCHOPATHOLOGY ON THE MMPI AND DYSFUNCTIONAL FAMILIES OF ORIGIN

Adults who were raised in dysfunctional families demonstrate psychopathology on the MMPI. 396 (140 men, 256 women) adult clients (mean age = 35 yr.) from dysfunctional families who were seeking tre...
Selecting beam weight and wedge filter on the basis of dose gradient analysis

This study proposes an algorithm for selecting beam weight, wedge angle, and wedge orientation for three-dimensional radiation therapy treatment planning. According to dose gradient analysis, the necessary and sufficient condition for achieving a homogeneous dose over the target volume is that the total vector sum of the dose gradients of all beams be zero everywhere in the target volume. This study presents equations for calculating the beam weight, wedge angle, and collimator angle (because the collimator angle determines wedge orientation when beam direction is known) for treatment plans using two angled beams or three coplanar or noncoplanar beams. It also provides suggestions for calculations of treatment plans using more than three beams, for which many feasible solutions will be available. When tested using two clinical cases, this algorithm achieved homogeneous dose distributions over target volumes. With this algorithm, repeated manual adjustments are reduced, and the quality and efficiency of treatment planning are improved.
Impact of control structures on assimilative capacity of rivers and fish habitat

This research studies the impact of water level control structures on self-assimilative capacity of rivers and on fish habitat. Constructing a water level control structure in a river reach will alter its hydraulics as well as its water quality, thermal regime and fish habitat. A mathematical model is developed to simulate river hydraulics, water quality, temperature and fish habitat. Diurnal dissolved oxygen concentrations are investigated to show their impact on fish. A case of a Nile River reach was studied to investigate the impact of the existence of the Esna barrage on the water quality and fish in its upstream reach. The barrage has negative impacts on the upstream self-assimilative capacity of the rivers. The waste load that the river could absorb was only 54 % (at low flow) and 78 % (at high flow) of the entire load if no barrage was present. Including in the simulation of the effects of photosynthesis and respiration, the above mentioned percentages were raised to 54 % and 91 %, respectively. Although water level control structures have negative impacts on the upstream self-assimilative capacity of the rivers, they have positive effect on downstream dissolved oxygen concentrations due to reaeration that happens across them. Downstream dissolved oxygen concentration increased by 6 % from its upstream concentration value. The barrage has a positive effect on fish habitat in the upstream section. The weighted usable area of Tilapia fish is doubled in case of barrage existence. The barrage causes a slight decrease in water temperature that reaches an average of 0.13 degree in the month of June.
The Five-Factor Framing of Personality and Beyond: Some Ruminations

The five-factor conceptualization of personality has been presented as all-embracing in understanding personality and has even received authoritative recommendation for understanding early development. I raise various concerns regarding this popular model. More specifically, (a) the atheoretical nature of the five-factors, their cloudy measurement, and their inappropriateness for studying early childhood are discussed; (b) the method (and morass) of factor analysis as the exclusive paradigm for conceptualizing personality is questioned and the continuing nonconsensual understandings of the five-factors is noted; (c) various unrecognized but successful efforts to specify aspects of character not subsumed by the catholic five-factors are brought forward; and (d) transformational developments in regard to inventory assessment of personality are mentioned. I conclude by suggesting that repeatedly observed higher order factors hierarchically above the proclaimed five may promise deeper biological understanding...
Origins of manganese in air particulates in California.

The proportions of manganese to other metals in samples of airborne fine particles taken at some sites in California have increased greatly since the beginning of 1985. Here, data are presented which indicate that the addition of manganese to leaded gasoline is largely responsible for this increase. Concentrations of manganese, silicon, titanium, iron, lead and other elements in airborne particles were measured using energy-dispersive X-ray fluorescence analysis. Coefficients of correlation among levels of manganese, iron and lead measured at twenty sites in California were calculated. Levels of manganese and iron are generally highly correlated because of the presence of large amounts of these elements in the earth’s crust. Levels of airborne manganese and lead at sites In Southern California are often highly correlated, suggesting a vehicular source of manganese. Observed manganese concentrations are apportioned into two major sources: the earth’s crust and motor vehicles. The apportionment indicates th...
Effect of REM sleep on retroglossal cross-sectional area and compliance in normal subjects

It has been proposed that the upper airway compliance should be highest during rapid eye movement (REM) sleep. Evidence suggests that the increased compliance is secondary to an increased retroglos...
Radiation tolerance studies of long wavelength infrared InAs/GaSb detectors

In this work we investigated the effect of proton irradiation on the performance of long wavelength infrared (LWIR) InAs/GaSb photodiodes (λc = 10.2μm) based on the complementary barrier infrared detector (CBIRD) design. We found that irradiation with 68MeV protons up to the total ionizing dose TID = 200 kRad results in only small (about 15%) decrease of the Quantum Efficiency and does not increase the operational bias of the photodiodes. However, the irradiation causes a significant increase of the dark current from jd = 5x10-5 A/cm2 at Vb = 0.1V and T = 80K to jd = 6x10-3 A/cm2 at TID = 200 kRad. This change in the dark current mechanism can be attributed to the onset of surface leakage current, generated by the trap assisted tunneling processes in the proton displacement damage areas near the device sidewalls.
Extrathoracic axillary-iliac bypass substitution of a resected descending thoracic aorta

Resection of a dissecting aneurysm of the descending thoracic aorta (Type III) was accomplished in a uremic patient on hemodialysis with reconstruction of blood flow through extrathoracic bilateral axillary-subclavian-iliac Dacron grafts. Review of the literature revealed no similar operation reported before. Other potential uses for this operation, such as infected aortic grafts and resections of the arch and descending thoracic aorta in high-risk patients, are discussed. Despite complete rehabilitation of this patient 10 months after operation, the application of this procedure must await longer term follow-up. The operative procedure described thus far was applied only in one patient and should be considered only in special circumstances, as discussed.
BioNetGen 2.2: advances in rule-based modeling

Summary : BioNetGen is an open-source software package for rule-based modeling of complex biochemical systems. Version 2.2 of the software introduces numerous new features for both model specification and simulation. Here, we report on these additions, discussing how they facilitate the construction, simulation and analysis of larger and more complex models than previously possible. Availability and Implementation : Stable BioNetGen releases (Linux, Mac OS/X and Windows), with documentation, are available at http://bionetgen.org . Source code is available at http://github.com/RuleWorld/bionetgen . Contact: bionetgen.help@gmail.com Supplementary information: Supplementary data are available at Bioinformatics online.
POPULATION STRUCTURE OF A CLONAL GORGONIAN CORAL: THE INTERPLAY BETWEEN CLONAL REPRODUCTION AND DISTURBANCE.

Clonality is a common feature of plants and benthic marine organisms. In some cases clonal propagation results in a modest increase in population density, while in other cases dense populations may be generated by the propagation of only a few clones. We analyzed the population structure of the clonal gorgonian Plexaura kuna across several reef habitats with a range of disturbance regimes in the San Blas Islands, Panama, and the Florida Keys, U.S.A. Using multilocus DNA fingerprinting to distinguish clones, we estimated that clones ranged in size from single individuals to 500 colonies. The number of genotypes identified on nine reefs ranged from three to 25. Population density and clonal structure varied markedly among reefs with GO :GE ranging from 0.03 to 1.00. On some reefs vegetative reproduction transformed P. kuna from a rare species to the numerically most abundant gorgonian. The effect of clonal propagation on P. kuna population structure was dependent on interactions between fragmentation and the reef environment (disturbance regime, substratum). We present a generalized model relating population structure of clonal species to disturbance and the mode of vegetative propagation. Disturbance promotes colony propagation and skews the size-frequency distribution of clones among P. kuna and many species that propagate via fragmentation. Propagation of these species is promoted by disturbance (disturbance sensitive), and they tend to have clones that are dispersed across local sites. Species that fragment and have dispersed clones, have high genotypic diversity in habitats with low levels of disturbance. Genotypic diversity then decreases at intermediate disturbance and increases again at the highest disturbance levels. Clonal species that do not rely on disturbance for vegetative propagation (disturbance insensitive) generally do not disperse and form aggregated clones. Among these taxa disturbance has a greater affect on individual survival than on propagation. Genotypic diversity is directly related to the level of disturbance until very high levels of disturbance, at which time genotypic diversity declines.
A Single Genetic Locus Determines the Efficacy of Serum Therapy Against Murine Adenocarcinoma 755a

We have recently described a unique model system for immunotherapy where immunological management of a highly lethal tumor, the ascites form of the Adenocarcinoma 755 (AD755a), could be carried out reproducibly and with remarkable efficiency [7]. Some of the basic features of this model are summarized in Table 1. The studies to be described in this report will concern themselves primarily with a more in depth analysis of the phenomenon of strain variation in relation to the protective capacity of the serum, and were done in an effort to gain some insight into the mechanism by which the serum mediates its powerful effect.
A Clinical Study of the AutoAnalyzer Method for Prenatal Antibody Evaluation and Screening

Many variables influence sensitivity in automated hemagglutination. Standardization of antibody from different sources is limited by heterogeneity of antigen-antibody interaction. In this report, the AutoAnalyzer method for screening and quantitating Rh(D) antibody in the sera of 50 Rh negative mothers is compared to the manual indirect automated hemagglutination tube test. Although false-positive and false-negative results are not eliminated by the automated method, the authors conclude that the AutoAnalyzer method for screening and quantitating Rh(D) antibody is as reliable as the manual method. A modification of the AutoAnalyzer method for screening and quantitating antibodies of the Rh-system is described.
Broken Windows, Broken Promises Grief, Privilege, and Hope in the Mythical Post Racial, a Call and Response

We present our narrative as an exercise in Critical Performance Pedagogy: Culture Jamming. It is our contribution to the #BlackLivesMatter movement. Our collective voice, which is framed as a refle...
Determination of vitamin A in serum by High performance liquid chromatography with internal standard method

Objective:Vitamin A acetate as internal standard for determination of vitamin A in serum by high performance liquid chromatography method was studied.Methods: Serum sample and vitamin A acetate as internal standard were extracted by hexane,absolute alcohol was used for constant volume after volatilization of hexane,and inverse C18 column was employed for separation with methanol-water(98∶ 2) as mobile phase,finally the sample was detected by diode array detector.Results:When concentration of vitamin A was in the range of 0.11 μg/ml to 1.65 μg/ml,the peak area ratio and concentration showed a good linear relationship,the minimum detection limit of vitamin A was 0.020 μg/ml.The relative standard deviation was 3.1%~6.6%.The recovery was 90%~107.2%.In 240 serum samples,vitamin A content was 0.191 μg/ml~1.298 μg/ml,The average value was 0.559 μg/ml.Conclusion: The method is sensitive,accurate,simple,rapid,reproducible,which can be used for the determination of vitamin A content in serum.
Morphoproteomics and biomedical analytics confirm the mTORC2/Akt pathway as a resistance signature and activated ERK and STAT3 as concomitant prosurvival/antiapoptotic pathways in metastatic renal cell carcinoma (RCC) progressing on rapalogs: Pathogenesis and therapeutic options

// Robert E. Brown 1 , Jamie Buryanek 1 , Varaha S. Tammisetti 2 , Mary F. McGuire 1 , Keri Csencsits-Smith 1 1 Department of Pathology and Laboratory Medicine, The University of Texas Health Science Center at Houston McGovern Medical School, TX 77030, Houston, USA 2 Diagnostic and Interventional Imaging, The University of Texas Health Science Center at Houston McGovern Medical School, TX 77030, Houston, USA Correspondence to: Keri Csencsits-Smith, email: Keri.C.Smith@uth.tmc.edu Keywords: renal cell carcinoma, rapalog therapy, immunohistochemistry, MTORC2, resistance Received: November 11, 2015 Accepted: April 16, 2016 Published: May 20, 2016 ABSTRACT Background: It has been proposed that resistance to rapalog therapies in renal cell carcinoma (RCC) is due to adaptive switching from mammalian target of rapamycin complex 1 (mTORC1) to mTORC2. Objective: To combine phosphoprotein staining and applied biomedical analytics to investigate resistance signatures in patients with metastatic RCC progressing on rapalog therapies. Design: We applied morphoproteomic analysis to biopsy specimens from nine patients with metastatic RCC who continued to show clinical progression of their tumors while being treated with a rapalog. Results: In patients who were on temsirolimus or everolimus at the time of biopsy, a moderate to strong expression of phosphorylated (p)-mTOR (Ser 2448) in the nuclear compartment with concomitant expression of p-Akt (Ser 473) confirmed the mTORC2 pathway. Concomitant moderate to strong nuclear expression of p-ERK 1/2 (Thr202/Tyr204) and p-STAT3 (Tyr705) was confirmed. Histopathologic changes of hypoxic-type coagulative necrosis in 5 cases as well as identification of insulin-like growth factor-1 receptor (IGF-1R) expression and histone methyltransferase EZH2 in all tumors studied suggested that hypoxia also contributed to the resistance signature. Biomedical analytics provided insight into therapeutic options that could target such adaptive and pathogenetic mechanisms. Conclusions: Morphoproteomics and biomedical analytics confirm mTORC2/Akt as a resistance signature to rapalog therapy in metastatic RCC and demonstrate activation of the prosurvival ERK and STAT3 pathways and involvement of hypoxic pathways that contribute to pathogenesis of such adaptive resistance. These results highlight the need for a novel combinatorial therapeutic approach in metastatic RCC progressing on rapalogs.
Retrospective Analysis of an Interdisciplinary Ventilator Care Program Intervention on Survival of Infants with Ventilator-Dependent Bronchopulmonary Dysplasia

Background The clinical needs of infants with severe bronchopulmonary dysplasia (BPD) that remain ventilator-dependent are complex, and management strategies that optimize survival and long-term outcomes controversial. We hypothesized that an interdisciplinary ventilator care program (VCP), committed to the care of this population will improve survival through standardized approaches to cardiopulmonary care and related comorbidities, enhanced communication, and continuity of care. Methods Retrospective chart reviews were performed on patients at Children's Hospital Colorado's neonatal intensive care unit, who underwent tracheostomy placement between 2000 and 2013. Data were collected for two time periods: 2000 to 2005 and 2006 to 2013, before and after initiation of the VCP. Collected data on infants with ventilator-dependent BPD included: gestational age (GA), age at tracheostomy, respiratory severity score (RSS; mean airway pressure [MAP] × fraction of inspired oxygen [FiO 2 ]), comorbidities, medication use, and the age of death. Tracheostomy patients without severe BPD were excluded. Results Despite no difference in GA, birth weight, or cardiorespiratory comorbidities, survival to discharge increased from 50 to 85% after implementation of the VCP ( p Conclusion These findings suggest an interdisciplinary approach to the care of infants with ventilator-dependent BPD can improve survival.
Clinical Detection and Treatment of Thyroid Diseases

While thyroid cancer is relatively rare overall, accounting for less than 1% of all human malignancies, it is the most common endocrine malignancy, comprising nearly 90% of all endocrine cancers.1 The vast majority are well-differentiated cancers derived from follicular epithelium and most of these are papillary carcinomas (PTC). Prognosis is generally favorable, with only 1,500 thyroid cancer-related deaths per year,2 and a 10-year survival of greater than 90%. However, the incidence of PTC has been on the rise during recent years, perhaps due to increased rates of detection with the almost ubiquitous use of imaging studies with ever-increasing sensitivity.3,4
Recent Advances in Instrumentation

Our common interest is in nuclear radiation—its origin, its measurement, its uses. In order to review what is new in instrumentation, we might consider the sources of radiation, radiation detectors, electronic components which might be employed in these circuits, techniques for using the above, and systems designed for particular jobs.
Practical Strategies for Collaboration across Discipline-Based Education Research and the Learning Sciences

As the field of discipline-based education research continues to grow and enters into its “second generation,” this essay provides timely and useful advice for advancing life sciences education res...
Interior and Exterior Shape Representations Using the Screened Poisson Equation

Shape classification is a required task in many systems for image and video understanding. Implicit shape representations, such as the solutions to the Eikonal or Poisson equations defined on the shape, have been shown to be particularly effective for generating features that are useful for classification. The Poisson-based shape representation can be derived at each point inside the shape as the expected time for a particle undergoing Brownian motion to hit the shape boundary. This representation has no natural generalization when considering points outside of a shape, however, because the corresponding Brownian motion would have infinite expected hitting time. In this article, we modify the Brownian motion model by introducing an exponential lifetime for the particle, yielding a random variable whose expected value satisfies a screened Poisson equation that can be solved at points both interior and exterior to the shape. We then show how moments of this new random variable can be used to improve classification results on experiments with natural silhouettes and handwritten numerals.
The Clinical Phenotype of Myelofibrosis Encompasses a Chronic Inflammatory State That Is Favorably Altered by INCB018424, a Selective Inhibitor of JAK1/2

Background: Current evidence links some of the disease manifestations in myelofibrosis (MF) to abnormal cytokines, likely produced by clonally involved megakaryocytes and monocytes. Furthermore, the recent discovery of JAK2/MPL mutations in MF suggests the contribution of abnormal JAK-STAT signaling to both clonal myeloproliferation and cytokine-driven debility. In order to gain additional pathogenetic insight regarding cytokine-phenotype correlations in MF, we looked into the plasma cytokine profile of MF before and after treatment with INCB018424, a selective JAK1/2 inhibitor. Methods: The current study includes subjects with MF enrolled in an ongoing phase 1–2 study of oral INCB018424 (doses ranging from 25 mg/day to 50 mg BID). Plasma samples were obtained prior to treatment and at intervals of 2 weeks, 1 month and 2 months following INCB018424 dosing. Samples were submitted to Rules Based Medicine Human MAP multiplexed immunoassay system to obtain plasma levels on a range of protein analytes. Results: Plasma cytokine levels in MF patients (n=53) vs. normal healthy volunteers (n=15):Compared to normal controls, plasma levels of pro-inflammatory cytokines and markers of inflammation were significantly increased in MF patients (Table; mean +/− SD values). Furthermore, the observed inflammatory cytokine levels in MF were often higher than those seen in patients with rheumatoid arthritis or cancer-associated cachexia (data to be presented at the meeting). Correlation of plasma cytokine levels in MF withJAK2V617F mutational status, MF subtype and/or constitutional symptoms/cachexia:Comparison of JAK2V617F positive (n=40) and negative (n=13) MF cases suggested significantly (p Post-INCB018424 treatment cytokine levels: Treatment with INCB018424 induced a rapid decrease in MF-associated inflammatory cytokine levels, in parallel with the observed clinical benefit of both reduced splenomegaly and improvement in constitutional symptoms/cachexia (data to be presented at the meeting). Conclusion: The plasma cytokine profile of MF is reminiscent of a chronic inflammatory state with levels of pro-inflammatory cytokines that are possibly higher than those seen in other inflammatory/malignant conditions. Furthermore, the current study suggests a fundamental link between these cytokines and MF-associated constitutional symptoms/cachexia. Cytokine modulation through JAK-STAT inhibition appears to be a mechanism of action for INCB018424 in MF.
Impact of atrial fibrillation on the clinical course of apical hypertrophic cardiomyopathy

Background Apical hypertrophic cardiomyopathy (ApHCM) is considered a ‘benign’ form of hypertrophic cardiomyopathy, with limited data on the long-term outcome. However, the clinical impact of atrial fibrillation (AF) in ApHCM is largely unknown. The hypothesis was that AF is common and has a prognostic implication in ApHCM. Methods The occurrence of AF and outcome was assessed in 306 consecutive patients with ApHCM (68% male, 62±11 years). Results AF occurred in 77 patients with ApHCM (prevalence, 25.2%; annual incidence, 4.6%/year) and was independently predicted by old age and large left atrium (>45 mm). Among 70 AF patients indicated with anticoagulation, 53 patients (76%) received warfarin. During a follow-up of 5.5±2.0 years, the patients with AF had a higher incidence of all-cause death, cardiovascular death and strokes (11.7% vs 1.3%, 6.5% vs 0.9% and 19.5% vs 2.6%, respectively, all p Conclusion In patients with ApHCM, AF was common and was associated with a substantial risk for strokes and mortality suggesting that AF should be carefully managed in ApHCM.
Acute kidney injury risk associated with piperacillin/tazobactam compared with cefepime during vancomycin therapy in hospitalised patients: a cohort study stratified by baseline kidney function

Abstract Recent studies have found an association between piperacillin/tazobactam when added to vancomycin and acute kidney injury (AKI) risk. However, studies were limited by the small sample size and residual confounding. The aim of this study was to compare the risk of AKI with vancomycin plus piperacillin/tazobactam (VPT) versus vancomycin plus cefepime (VC) and to examine whether pre-existing renal impairment mediates the risk. This was a retrospective cohort study using electronic health records for patients admitted to two hospitals in 2012–2013. The outcome, AKI, was defined as an increase in serum creatinine level of ≥0.3 mg/dL or ≥50% from baseline. Patients were stratified by level of renal impairment as estimated by baseline creatinine clearance. Inverse probability of treatment weighting was used to balance baseline covariates between groups. Cox proportional hazards regression was used to evaluate VPT risk of AKI compared with VC. A total of 935 (17.53%) AKI cases were identified among 5335 patients receiving VPT or VC. VPT was associated with a higher risk of AKI relative to VC, with an adjusted hazard ratio (aHR) of 1.25 [95% confidence interval (CI) 1.11–1.42] in the total population and 1.70 (95% CI 1.44–2.02) in patients with normal baseline renal function. However, no elevated risk was found in patients with prior renal impairment (aHR = 0.81, 95% CI 0.65–1.01). VPT was associated with a higher risk of AKI relative to VC. The association was true in patients with normal renal function but not in those with pre-existing renal impairment.
Abstract 76: Toll-Like Receptor 4 Deficiency Protects C3H/HeJ Mice from Angiotensin-II Induced Renovascular Fibrosis

Toll-like receptor 4 (TLR4) is a molecule involved in innate immune response. Current evidence suggests that activation of TLR4 is associated with vascular and cardiac remodeling by a process which involves production of reactive oxygen species and inflammatory cytokines. Oxidative stress is well established in the development of renal fibrosis in chronic hypertension. In this study, we hypothesized that TLR4 deficiency in C3H/HeJ (C3H) mice protects the kidney from angiotensin induced renal remodeling by reducing mitochondrial oxidative stress. Wildtype (WT) and C3H mice were implanted with osmotic pumps loaded without or with Angiotensin-II (Ang-II) for delivery at 250 ng/kg/min for 4 weeks. Animal groups were 1) WT + Saline, 2) WT + Ang-II, 3) C3H + Saline, 4) C3H + Ang-II. Blood pressure was measured weekly and end-point laser Doppler flowmetry was done to assess renal cortical blood flow. Superoxide content was measured by dihydroethidium staining. Mitochondrial oxidative stress was measured by H 2 O 2 production, manganese superoxide dismutase (MnSOD) and catalase was measured by gel and assay method respectively. Ang-II administration induced higher blood pressure in WT mice than in C3H mice (135.8 ± 5.1 vs. 109.4 ± 5.6 mm of Hg). Ang-II decreased renal cortical flux to a greater degree in WT mice compared to C3H mice [1052.8 ± 67.8 vs. 1182.9 ± 24.7 perfusion units (PU)]. Superoxide content was increased in WT + Ang-II mice compared to C3H + Ang-II. The expression and activity of mitochondrial MnSOD was increased in C3H mice compared to WT mice receiving Ang-II. H 2 O 2 production was increased in C3H + Ang-II compared to WT mice receiving similar treatment. Collagen accumulation and wall-to-lumen ratio was increased in the cortical vessels of WT mice compared to C3H mice receiving Ang-II indicating fibrosis. C3H mice also exhibited lower levels of inflammatory cytokines TGF-β, TNF-α and IL-6 than WT mice receiving Ang-II. Our data suggests that in TLR4 deficiency (C3H mice), upregulation of mitochondrial MnSOD reduces reactive oxygen species production and inflammation and thus renovascular remodeling in Ang-II induced hypertension.
LMNA Sequences of 60,706 Unrelated Individuals Reveal 132 Novel Missense Variants in A-Type Lamins and Suggest a Link between Variant p.G602S and Type 2 Diabetes.

Mutations in LMNA, encoding nuclear intermediate filament proteins lamins A and C, cause multiple diseases (‘laminopathies’) including muscular dystrophy, dilated cardiomyopathy, familial partial lipodystrophy (FPLD2), insulin resistance syndrome and progeria. To assess the prevalence of LMNA missense mutations (‘variants’) in a broad, ethnically-diverse population, we compared missense alleles found among 60,706 unrelated individuals in the ExAC cohort to those identified in 1,404 individuals in the laminopathy database (UMD-LMNA). We identified 169 variants in the ExAC cohort, of which 37 (~22%) are disease-associated including p.I299V (allele frequency 0.0402%), p.G602S (allele frequency 0.0262%) and p.R644C (allele frequency 0.124%), suggesting certain LMNA mutations are more common than previously recognized. Independent analysis of LMNA variants via the type 2 diabetes (T2D) Knowledge Portal showed that variant p.G602S associated significantly with type 2 diabetes (p=0.02; odds ratio=4.58), and was more frequent in African Americans (allele frequency 0.297%). The FPLD2-associated variant I299V was most prevalent in Latinos (allele frequency 0.347%). The ExAC cohort also revealed 132 novel LMNA missense variants including p.K108E (limited to individuals with psychiatric disease; predicted to perturb coil-1B), p.R397C and p.R427C (predicted to perturb filament biogenesis), p.G638R and p.N660D (predicted to perturb prelamin A processing), and numerous Ig-fold variants predicted to perturb phenotypically-characteristic protein-protein interactions. Overall, this two-pronged strategy— mining a large database for missense variants in a single gene (LMNA), coupled to knowledge about the structure, biogenesis and functions of A-type lamins— revealed an unexpected number of LMNA variants, including novel variants predicted to perturb lamin assembly or function. Interestingly, this study also correlated novel variant K108E with psychiatric disease, identified known variant p.I299V as a potential risk factor for metabolic disease in Latinos, linked variant p.G602 with type 2 diabetes, and specifically identified p.G602S as a predictor of diabetes risk in African Americans.
Porous Polymeric Hollow Fibers As Bifunctional Catalysts for CO₂ Conversion to Cyclic Carbonates

Abstract In this study, development of cooperative catalyst is demonstrated whereby Lewis acid/base species and nucleophilic parts are immobilized in the pores of a polyamide-imide (PAI) hollow fiber support. The highly solvent-stable and porous Br/APS-grafted ZrO2-PAI hollow fiber (Br/APS/Zr-PAIHF) catalyst was created by crosslinking of bare ZrO2-PAIHF polymer with 3-aminopropyltrimethoxysilane (APS) followed by alkylation with 1,2-dibromoethane at 110 °C. This bifunctional catalyst consists of a porous ZrO2-PAIHF polymer crosslinked with APS that was further immobilized with nucleophilic bromide ions. Porous ZrO2-PAIHF provides a physical barrier to prevent cooperative Lewis acid/base species and nucleophilic parts movement, aggregation, and detachment from the support into the product stream. The performance of Br/APS/Zr-PAIHFs as heterogeneous catalyst was investigated for the reaction of carbon dioxide (CO2) with styrene oxide (SO) which leads to the formation of styrene carbonate (SC). The influence of various reaction parameters including reaction temperature, reaction time, solvents, and CO2 pressure were systematically investigated in detail. Our results indicated that the synergistic cooperative effect of nucleophilic bromide ion (Br−) and Lewis acid/base species on PAIHF supports leads to a maximum SC selectivity of 99.1%. Additionally, SO conversion of 100% and excellent SC selectivity of 98% were obtained over Br/APS/Zr-PAI-HF catalyst.