cssi/SciSciGPT-SciSciNet huggingface dataset:
Identification of a new transmembrane adaptor protein that constitutively binds Grb2 in B cells.

Transmembrane adaptor proteins cou- ple antigen receptor engagement to downstream signaling cascades in lymphocytes. One example of these proteins is linker for activation of T cells (LAT), which plays an indispensable role in T cell activation and development. Here, we report iden- tification of a new transmembrane adaptor mole- cule, namely growth factor receptor-bound protein 2 (Grb2)-binding adaptor protein, transmembrane (GAPT), which is expressed in B cells and myeloid cells. Similar to LAT, GAPT has an extracellular domain, a transmembrane domain, and a cytoplas- mic tail with multiple Grb2-binding motifs. In con- trast to other transmembrane adaptor proteins, GAPT is not phosphorylated upon BCR ligation but associates with Grb2 constitutively through its pro- line-rich region. Targeted disruption of the gapt gene in mice affects neither B cell development nor a nitrophenylacetyl-specific antibody response. However, in the absence of GAPT, B cell prolifer- ation after BCR cross-linking is enhanced. In aged GAPT / mice, the number of marginal zone (MZ) B cells is increased, and other B cell subsets are normal. The serum concentrations of IgM, IgG2b, and IgG3 are also elevated in these mice. These data indicate that GAPT might play an important role in control of B cell activation and proper maintenance of MZ B cells. J. Leukoc. Biol. 84: 000-000; 2008.
High-Throughput Screening for Novel Anti-Infectives Using a C. elegans Pathogenesis Model

In recent history, the nematode Caenorhabditis elegans has provided a compelling platform for the discovery of novel antimicrobial drugs. In this protocol, we present an automated, high-throughput C. elegans pathogenesis assay, which can be used to screen for anti-infective compounds that prevent nematodes from dying due to Pseudomonas aeruginosa. New antibiotics identified from such screens would be promising candidates for treatment of human infections, and also can be used as probe compounds to identify novel targets in microbial pathogenesis or host immunity.
Association of Cervical Cytology and HPV DNA Status During Pregnancy With Placental Abnormalities and Preterm Birth

The clinical implications of abnormal cervical cytology during pregnancy are unclear. Therefore, we performed the present study to determine the role of cervical cytologic screening during pregnancy in association with placental abnormalities and preterm birth. A review of 2,480 cases during 11 years revealed significant correlation of reactive, infectious, atypical, and dysplastic cytologic changes during pregnancy with abnormal placental findings. Also, all but dysplastic cytologic changes were significantly associated with preterm birth. Furthermore, we observed significant association of the presence of high-risk human papillomavirus (HPV) DNA with preterm birth and placental abnormalities. These findings indicate that cervical infection of HPV is a risk factor for preterm birth and that cervical cytology is an effective tool for screening women for infection and inflammation during pregnancy and predicting pregnancy outcome.
Body-composition alterations consistent with cachexia in children and young adults with Crohn disease

BACKGROUND Crohn disease (CD) in children is associated with low body mass index (BMI), poor growth, and delayed maturation; alterations in lean and fat mass, however, are poorly characterized. OBJECTIVE The objective was to quantify lean and fat mass in children and young adults with CD and in healthy control subjects, relative to height and pubertal maturation. DESIGN This cross-sectional study assessed whole-body lean and fat mass by using dual-energy X-ray absorptiometry in 104 subjects with CD and in 233 healthy control subjects aged 4-25 y. Linear regression was used to determine the effect of CD on body composition and to generate sex-specific SD scores (z scores) for lean and fat mass relative to height. RESULTS Subjects with CD had lower height-for-age and BMI-for-age z scores (P < 0.001 for both) than did control subjects. CD was associated with significant deficits in lean mass after adjustment for height, age, race, and Tanner stage (P = 0.003); deficits in fat mass were not observed. The mean (+/-SD) lean mass-for-height and fat mass-for-height z scores in the subjects with CD were -0.61 +/- 0.92 and -0.04 +/- 0.86, respectively. Within the control group, fat mass-for-height was positively correlated with lean mass-for height (r = 0.41, P < 0.0001); this association was absent in the subjects with CD. CONCLUSIONS Children and young adults with CD had significant deficits in lean mass but preserved fat mass, which is consistent with cachexia. Further research is needed to identify physical activity, nutritional, and antiinflammatory interventions to improve body composition in persons with CD.
Role-based integrated access control and data provenance for SOA based net-centric systems

Service-oriented architecture (SOA) has been widely adopted in the development of many net-centric application systems. In SOA, services potentially from different domains are composed together to accomplish critical tasks. In these systems, security and trustworthiness are the major concerns that have not been well addressed. Many access control models have been developed to ensure proper accesses to critical resources from local as well as external domains. Also, many data provenance schemes have been proposed in recent years to support data quality assessment and enhancement, data reproduction, etc. However, none of the existing mechanisms consider both access control and data provenance in a unified model. In this paper, we propose an integrated role-based access control and data provenance model to secure the cross-domain interactions. We develop a role-based data provenance scheme which tracks the roles of the data originators and contributors and uses this information to help evaluate data trustworthiness. We also make use of the data provenance information and the derived data quality attributes to assist with role-based access control. In this integrated model, the secure usage of a data resource must also consider the quality and trustworthiness of the data. To realize this concept, we develop an extended access control model in which access permissions are specified with constraints over the provenance attributes. Also, to assure confidentiality, we record the access constraints from the data originators and contributors to help decide how the data should be further disseminated.
A proposed benchmark model for wind energy transmission systems

The results of developing a transient stability benchmark model are presented. This benchmark model represents the effects of areas with large wind generation. The proposed benchmark system is based on the transmission network in the south-central region of the US. The model is first derived based on transmission interconnections, conventional and wind generation and the associated geographical information. Generating station and transmission geographical results were determined from the U.S. Energy Information Administration maps features (EIA). Steady-state power flow analysis is performed to check the reasonableness of the results in terms of the impact on the surrounding 345 kV transmission grid. The power flow analysis is also used to establish the initial conditions for subsequent transient stability analysis. Fault conditions were evaluated under large wind generation conditions using small-signal (eigenvalue) analysis. The results suggest that the model captures the principle effects of wind generation related transients and power flows. This method of model development results in a benchmark system that allows system planners to evaluate the impacts on power system reliability associated with wind energy transmission networks. The results suggest that the model is realistic and somewhat accurate. This is one of the first benchmark systems for wind energy transmission networks. The use of a realistic wind energy benchmark system is of utmost importance as wind energy systems have certain characteristics that need to be accounted for when developing new technologies for such systems.
A practical approach to dynamic load balancing

This paper presents a cohesive, practical load balancing framework that improves upon existing strategies. These techniques are portable to a broad range of prevalent architectures, including massively parallel machines, such as the Cray T3D/E and Intel Paragon, shared memory systems, such as the Silicon Graphics PowerChallenge, and networks of workstations. As part of the work, an adaptive heat diffusion scheme is presented, as well as a task selection mechanism that can preserve or improve communication locality. Unlike many previous efforts in this arena, the techniques have been applied to two large-scale industrial applications on a variety of multicomputers. In the process, this work exposes a serious deficiency in current load balancing strategies, motivating further work in this area.
Fracnet: stochastic simulation of fractures in layered systems

A new approach to stochastic simulation of fracture networks has been developed and the al- gorithm is presented here. The simulation procedure mimics fracture propagation. Fractures are grown following geomechanical rules of propagation inferred for each specific host geological environment. The algorithm developed is a hybrid pixel/object approach where fractures are constructed as objects which are themselves sets of connected pixels rather than parametric objects. Working on a pixel grid gives flexibility for modeling and the fractures are not required to take any pre-specified shape. In ad- dition, an incremental growth of the fractures, pixel by pixel, allows generating curvilinear or undulat- ing fractures. It also allows the fractures to be stopped in their propagation e.g. when they encounter previously simulated open fractures or shale laminae. # 1998 Elsevier Science Ltd. All rights reserved Code available at http://www.iamg.org/CGEditor/index.htm
Stress-Induced Seismic Velocity Anisotropy And Physical Properties In The Safod Pilot Hole In Parkfield, Ca.

[1] A comprehensive suite of geophysical logs was collected in the SAFOD Pilot Hole from a depth of 775 m to 2150 m in highly fractured Salinian granite. The Pilot Hole intersected numerous macroscopic fractures and faults with extremely varied orientations. Despite the highly variable orientation of the fractures and faults, the fast polarization direction of the shear waves is very consistent with the direction of maximum horizontal compression determined from wellbore breakouts and drilling induced tensile fractures. At least three major shear zones were intersected by the borehole that are characterized by anomalously low velocity and resistivity, anomalously high shear velocity anisotropy and an absence of stress-induced wellbore breakouts (which suggests anomalously low differential stress). We argue that the physical mechanism responsible for the seismic velocity anisotropy observed in the Pilot Hole is the preferential closure of fractures in response to an anisotropic stress state.
Distance functions and their application to robot path planning in the presence of obstacles

An approach to robotic path planning, which allows optimization of useful performance indices in the presence of obstacles, is given. The main idea is to express obstacle avoidance in terms of the distances between potentially colliding parts. Mathematical properties of the distance functions are studied and it is seen that various types of derivatives of the distance functions are easily characterized. The results lead to the formulation of path planning problems as problems in optimal control and suggest numerical procedures for their solution. A simple numerical example involving a three-degree-of-freedom Cartesian manipulator is described.
Variables That Can Enhance and Complicate Sibling Caregiving of Individuals With Intellectual and Developmental Disabilities

The increasing longevity of adults with intellectual and developmental disabilities (I/DD) has raised new issues for families. Individuals with I/DD who face difficulties in achieving full independence might remain dependent on family members such as aging parents, who may be unable to provide continued support. Therefore, reliance on siblings for the future care can be an adaptive action for many families. Sibling caregiving is a universal phenomenon and requires rigorous examination and exploration. Like other carers, siblings require support and services to fulfill their role's expectations. Nonetheless, the degree and kind of support and services needed by them remains undetermined owing to the lack of research. The author reviewed variables that can enhance and complicate sibling caregiving of individuals with I/DD through the application of the Push-Pull model. The Push-Pull model can help in understanding that the role and interaction of multiple influences can have methodological and pedagogical implications for sibling caregiving research, support programs, social law, and policy change. The author notes that the review can provide a foundation for future studies, and she recommends inclusion of siblings in family policies.
A novel telemammography scheme across ad hoc networks

One of the goals of the National Cancer Institute (NCI) cancer control program to reach more than 80% of the eligible women in mammography screening by the year 2000 yet remains as a challenge. That is primarily due to 1) the fact that examination process is a complex and lengthy one and 2) it is not available to the majority of women who live in remote and urban sites. This problem can be solved using ad hoc-networking technologies and signal processing algorithms. Software modules can help detect true negatives (TN), while marking true positives (TP) for further investigation. This reduces the load on network and radiologists by a tremendous amount. Ad hoc networking equipment make clinic-lab connection more accessible and image enhancement algorithms readily available to the radiologists. In this research automatic robust computer assisted diagnostic (CAD) methods for mass detection in breast cancer have been associated with region of interest (ROI) compression for efficient transmission over ad hoc networks. This telemammography system for remote computer-aided breast cancer detection and diagnosis has the advantage of better reach of women for cancer screening and at the same time provides the diagnosis with higher efficiency, better accuracy, and lower cost.
Dynamic stability analysis of a one‐link force‐controlled flexible manipulator

This study analyzes the effects of link flexibility on the dynamic stability of a force-controlled flexible manipulator. The closed-loop dynamic equation for a l-link manipulator is first derived explicitly using the modal representation technique. Stability analysis is then carried out by computing the system eigenvalues. Results show that the link flexibility is one of the causes of dynamic instability of motion of the flexible robotic arm.
The influence of I-region width modulation on PIN diode attenuator design

This paper discusses the effects of I-region width modulation on PIN diode attenuator performance. The work shows that the I-region thickness becomes thinner as the dc bias current decreases, and that overestimates of PIN diode forward resistance can be the result. >
Children's conceptual structures of science categories and the design of Web directories

Eleven middle school children constructed hierarchical maps for two science categories selected from two Web directories, Yahooligans! and KidsClick! For each category, children constructed a pair of maps: one without links and one with links. Forty-four maps were analyzed to identify similarities and differences. The structures of the maps were compared to the structures employed by the directories. Children were able to construct hierarchical maps and articulate the relationships among the concepts. At the global level (whole map), children's maps were not alike and did not match the structures of the Web directories. At the local levels (superordinate and subordinate), however, children shared similarities in the conceptual configurations, especially for the concrete concepts. For these concepts, substantial overlap was found between the children's structures and those employed in the directories. For the abstract concepts the configurations were diverse and did not match those in the directories. The findings of this study have implications for design of systems that are more supportive of children's conceptual structures.
Talking (fe)male: examining the gendered discourses of preservice teachers

Through the use of feminist poststructural discourse analysis (Baxter 2003), the author examines the gendered discourses created and reified by a group of preservice secondary social studies teachers (n = 25). Because gender is socially constructed, it is important for future teachers to examine their own gendered identities in order for them to be able to see how they contribute to the greater society. Findings reveal discourses of ‘having it all', ‘being a superwoman', ‘female struggle', and ‘gender not playing a key role in culture’ being advanced by both male and female identified individuals. Intersections of race and social class with gender added to the complexity of the different discourses. Implications for teacher education are discussed.
A Market-Based Solution to the Multiple Depots, Multiple Traveling Salesmen Problem with Profits

The Multiple Depots, Multiple Traveling Salesmen Problem extends the well-known Traveling Salesman Problem (TSP) to cases where there are several traveling salesmen originating from various initial locations (depots). We are interested in a variant of this problem, in which there is no constraint on visiting all the cities, but rather each city offers a benefit value associated with visiting it, and the goal is to maximize the profit by the team of salesmen. We propose a solution based on economic markets, and show that it is capable of producing near-optimal results at a much faster runtime relative to a solution based on Binary Programming.
Glucose-Functionalized, Serum-Stable Polymeric Micelles from the Combination of Anionic and RAFT Polymerizations

Poly(ethylene-alt-propylene)–poly[(N,N-dimethylacrylamide)-grad-(2-methacrylamido glucopyranose)] (PEP–poly(DMA-grad-MAG), or PG) diblock terpolymers were synthesized by combining anionic and reversible addition–fragmentation chain transfer (RAFT) polymerizations. An ω-trithiocarbonate-functionalized PEP homopolymer served as the macromolecular chain transfer agent (macroCTA), and RAFT copolymerizations of DMA and a trimethylsilyl-protected MAG (TMS-MAG) monomer gave a family of PG diblock terpolymers after hydrolysis. The terpolymers had similar degrees of polymerization, and the MAG content ranged from 3.5 to 39 mol % in the hydrophilic block. At 70 °C, the reactivity ratios of DMA (1) and TMS-MAG (2) were determined to be r1 = 1.86 ± 0.07 and r2 = 0.16 ± 0.01, and thus the poly(meth)acrylamide blocks in the PG diblock terpolymers were likely to be gradient copolymers. Micellar dispersions from PG diblock polymers in water were examined by cryogenic transmission electron microscopy (cryo-TEM) and dynami...
New press curable Class F ground insulation system for AC machines

To achieve improved efficiency and higher output in both AC motors and generators, an insulation system must be capable of withstanding high volts per mil stress and high operating temperatures. To obtain such performance the development of a new B-staged epoxy resin rich press curable mica paper tape must address several key elements. This paper presents definitions for establishing a Class F resin rich tape system; proposes a new laboratory procedure for producing test specimens; and presents test data on both laboratory specimens and production coils which verify the successful development of a new press curable mica paper tape insulation system for AC motor and generator coils and bar windings.
A negative arterial-portal venous glucose gradient decreases skeletal muscle glucose uptake

The effect of a negative arterial-portal venous (a-pv) glucose gradient on skeletal muscle and whole body nonhepatic glucose uptake was studied in 12 42-h-fasted conscious dogs. Each study consiste...
Gender Influences on Parent-Child Science Problem-Solving Behaviors

ABSTRACTGender is a critical social factor influencing how children view the world from very early childhood. Additionally, during the early elementary years, parents can have a significant influence on their child’s behaviors and dispositions in fields such as science. This study examined the influence of parent gender and child gender on 2nd- and 4th-grade children’s strategies for solving science problems with their parents, as well as their attitudes about science. The behaviors of 13 parent-child dyads as they solved hands-on science problems together in an informal setting were examined. A child interview and a parent questionnaire were used to elicit information about their attitudes toward life science compared to physical science. Quantitative and qualitative analyses of the parent-child interactions revealed differences in the amount of encouragement offered to boys versus girls. Additionally, there were differences in questioning behaviors by parents as a function of parent gender and child gen...
Remarks on Determinism, Deducing Macro Laws from Micro Facts and Other Issues in the Philosophy of Model Building in Marketing

Marketing scientists do not have answers for many pragmatic marketing problems because they are usually more interested in asking questions than in selling product. However, the practioner can also benefit by asking "scholarly" questions. For example, be suspicious if your consultant offers to do "the definitive segmentation study", "provide predictions which are 99% accurate" or "measure attitudes as precisely as you measure profits."
The use of auditory evoked responses recorded from newborn infants to predict later language skills.

Over the past two decades, an increasing number of investigations reported that various behavioral and medical measures are useful in characterizing the development of normal infants as well as those infants who may be at risk for a variety of learning disabilities (see V. Molfese, 1989, for a review and evaluation of the effectiveness of these measures). Although such research reports appear promising, the correlations reported and the percentage of variance accounted for are typically low. At best, 50% of the variance has been accounted for in predictive studies utilizing birth measures as predictors of outcomes in the preschool period (Molfese & Molfese, 1985). In an effort to predict more accurately later developmental outcomes, researchers have been turning toward other measures such as the brain stem evoked response and the long latency evoked potential response that might converge with these traditional behavioral assessment measures in order to build better predictive models. Studies utilizing such evoked brain responses have for some time been viewed as providing new information concerning the structural integrity of the brain, insights into brain functioning, and the development of hemispheric involvement in cognitive and language abilities (Callaway, Tueting, & Koslow, 1978).
Decolonization of the Self

In this chapter, the author reflects on immigration experiences during her journey through academia and on how exposure to critical pedagogy and autoethnography contributed to her personal perspectives and overall worldview. Through vignettes and theoretical discussion, she explores the symbolic violence inherent in the process of personal decolonization.
Surreal Time and Ultratasks

This paper suggests that time could have a much richer mathematical structure than that of the real numbers. Clark & Read (1984) argue that a hypertask (uncountably many tasks done in a finite length of time) cannot be performed. Assuming that time takes values in the real numbers, we give a trivial proof of this. If we instead take the surreal numbers as a model of time, then not only are hypertasks possible but so is an ultratask (a sequence which includes one task done for each ordinal number—thus a proper class of them). We argue that the surreal numbers are in some respects a better model of the temporal continuum than the real numbers as defined in mainstream mathematics, and that surreal time and hypertasks are mathematically possible.
Being and Becoming A College Student: Pedagogy as Rite of Passage

In ShortThe college years are meant to be transformative for traditional-aged students who come into university as adolescents and leave as emerging adults.Pedagogy can play an active role in movin...
The Self-Revising Muse: On the Spirit of the Unborn Creator in A Room of One’s Own

O’Hara tracks Woolf’s revelation of female genius beginning with the imagined narrator Mary Beton and Shakespeare’s fictional sister. A Nietzschean aphorism is used to establish a conception of sincere irony, which is further demonstrated in Wallace Stevens’s “Earthy Anecdote,” to show the sincere irony of the modernist period arises from the dialectic of imagination and reality. O’Hara explains that through her looking-glass theory, Woolf embraces and reverses the gender hierarchy by regrounding the proposition in the materiality of physical life. The incandescent imagination and the integrity of the author combined with the “inner light” of the reader enable the conditions for genius. O’Hara argues that Woolf expands Coleridge’s notion of the androgynous genius to a mutual and self-revising position of both sexes.
Consideration of patient and disease characteristics in selecting radiation regimens for treatment of bone metastases

Abstract Purpose Radiation therapy is one of the mainstays of treatment for painful bone metastases; however, the optimal fractionation and dosing of radiation for a given patient and disease characteristics are still subject to debate. Methods and materials We retrospectively examined 475 patients who received radiation for bone metastases at our institution from 2009 through 2014 and evaluated survival outcomes based on parameters of their first treatment course and patient demographics. Kaplan-Meier analysis was used to analyze factors associated with overall survival (OS). A recursive partition analysis (RPA) was used to generate a decision tree of patient characteristics resulting in significant differences in survival. A Cox model was used to verify the RPA and evaluate the significance of biologically equivalent dose (BED) along with other factors. Results In our cohort, median age was 62 years and median Karnofsky performance status (KPS) was 70. Survival time by primary tumor type: breast (median, 35.9 months), prostate (12.8 months), other (median, 11.0 months), lung (median, 5.3 months), and gastrointestinal (median, 4.0 months) ( P P = .72) or BED ( P = .14). Conclusion Our data demonstrate that selection of radiation fractionation schedules should take into account primary tumor type, KPS, and age, and we have generated an RPA model including these factors to help guide decision making. We also found that shorter fractionation schedules are as effective as longer fractionation schedules for pain control, regardless of primary tumor type.
Age-Related Changes in Axonal and Mitochondrial Ultrastructure and Function in White Matter.

The impact of aging on CNS white matter (WM) is of general interest because the global effects of aging on myelinated nerve fibers are more complex and profound than those in cortical gray matter. It is important to distinguish between axonal changes created by normal aging and those caused by neurodegenerative diseases, including multiple sclerosis, stroke, glaucoma, Alzheimer9s disease, and traumatic brain injury. Using three-dimensional electron microscopy, we show that in mouse optic nerve, which is a pure and fully myelinated WM tract, aging axons are larger, have thicker myelin, and are characterized by longer and thicker mitochondria, which are associated with altered levels of mitochondrial shaping proteins. These structural alterations in aging mitochondria correlate with lower ATP levels and increased generation of nitric oxide, protein nitration, and lipid peroxidation. Moreover, mitochondria–smooth endoplasmic reticulum interactions are compromised due to decreased associations and decreased levels of calnexin and calreticulin, suggesting a disruption in Ca2+ homeostasis and defective unfolded protein responses in aging axons. Despite these age-related modifications, axon function is sustained in aging WM, which suggests that age-dependent changes do not lead to irreversible functional decline under normal conditions, as is observed in neurodegenerative diseases. SIGNIFICANCE STATEMENT Aging is a common risk factor for a number of neurodegenerative diseases, including stroke. Mitochondrial dysfunction and oxidative damage with age are hypothesized to increase risk for stroke. We compared axon–myelin–node–mitochondrion–smooth endoplasmic reticulum (SER) interactions in white matter obtained at 1 and 12 months. We show that aging axons have enlarged volume, thicker myelin, and elongated and thicker mitochondria. Furthermore, there are reduced SER connections to mitochondria that correlate with lower calnexin and calreticulin levels. Despite a prominent decrease in number, elongated aging mitochondria produce excessive stress markers with reduced ATP production. Because axons maintain function under these conditions, our study suggests that it is important to understand the process of normal brain aging to identify neurodegenerative changes.
Utilization and Other Resource Management in Clinical Chemistry

The clinical chemistry laboratory within typically has the largest volume of testing, the most analytical equipment, highest budget for expenses, and largest numbers of personnel performing tests. Therefore, a program for the effective management of laboratory resources from within the chemistry laboratory division has the potential to have more of a significant impact on the clinical laboratory with regard to costs for delivering services than in other divisions. Utilization management can take one of two forms: eliminating unnecessary tests or decreasing the unit cost of tests that are performed by implementing process improvements. The most optimal strategy should incorporate both of these approaches to achieve the greatest overall impact on cost, efficiency, and clinical service.
Utilization of fatigued and non-fatigued isolated guinea-pig papillary muscles and ventricular myocytes on the comparison of inotropic, chronotropic and intracellular calcium changes induced by monensin and digoxin

We investigated four different concentrations of digoxin (0.3,1,3 and 10 junol/1) and three different concentrations of monensin (2,7 and 12 |amol/l) on the contraction force of guinea-pig papillary muscles. The highest increase in contraction force was obtained by using 3 |imol/l digoxin or 7 ^mol/1 monensin. These concentrations were chosen for subsequent experiments to study the effects of these drugs on contraction force (CF), initial contraction velocity (ICV), averse contraction velocity (ACV), initial relaxation velocity (IRV) and stimulus to response time (ST) change in fatigued (defined as the level at which papillary muscle contraction had lost 30% of its original contraction force with the elapse of time) and non-fatigued guinea-pig papillary muscles. The five hours of measurement in Experiment 3 were divided into five periods (TO was equilibration, Tl, T2, T3, and T4 were respectively one, two, three, and four hours after drug administration). We found that both monensin and digoxin increased the CF and ACV at Tl and increased the IRV at T2. Digoxin lost its effect with the elapse of time while monensin did not Digoxin also
The Status of Career and Technical Education Undergraduate and Graduate Programs in the United States

The purpose of this study was to examine undergraduate and graduate student enrollments, course delivery modes, and curricular trends and issues of CTE programs. Based on findings from 139 program/department coordinators, results emphasized that although CTE programs within institutions of higher education have declined in number (Fletcher, Gordon, Asunda, & Zirkle, 2015), student enrollments within those programs have remained steady compared to prior studies (Bruening et al., 2001; Lynch, 1990). Even so, CTE program/department administrators have articulated that declining student enrollment is a major challenge within their programs. Additionally, the development of online courses and the impact of state/national educational reform initiatives were identified as major curricular trends for CTE programs. Recommendations include the need for CTE faculty to embrace online instruction, and for programs to use broader nomenclature of CTE/Workforce Education, instead of names of more traditional subdisciplin...
Targeting intracellular protein–protein interactions with cell-permeable cyclic peptides

Intracellular protein-protein interactions (PPIs) are challenging targets for conventional drug modalities, because small molecules generally do not bind to their large, flat binding sites with high affinity, whereas monoclonal antibodies cannot cross the cell membrane to reach the targets. Cyclic peptides in the 700-2000 molecular-weight range have the sufficient size and a balanced conformational flexibility/rigidity for binding to flat PPI interfaces with antibody-like affinity and specificity. Several powerful cyclic peptide library technologies were developed over the past decade to rapidly discover potent, specific cyclic peptide ligands against proteins of interest including those involved in PPIs. Methods are also being developed to enhance the membrane permeability of cyclic peptides through both passive diffusion and active transport mechanisms. Integration of the permeability-enhancing elements into cyclic peptide design has led to an increasing number of cell-permeable and biologically active cyclic peptides against intracellular PPIs. In this account, we review the recent developments in the design and synthesis of cell-permeable cyclic peptides.
Intraoperative spatial frequency domain diffuse optical tomography with indo-cyanine green (ICG) fluorescence contrast (Conference Presentation)

Surgical resection is the most effective treatment strategy for solid tumors, but complete removal of the tumor is critical for post-surgical recovery/long-term survival and is dependent on correct identification of the tumor margin and accurate excision of microscopic residual tumor in the surgical field. Fluorescence image guided surgery is an emerging technique that has shown promise for intraoperative location of tumors and tumor margins. Current versions of such intraoperative fluorescence imaging, however, are generally limited to 2D near-surface images, i.e., without information about tumor depth. Here we present an intraoperative fluorescence imaging system for 3D volumetric imaging of tumors; the system uses spatial frequency domain diffuse optical tomography with an analytic inversion reconstruction method. The new instrument can derive depth-sensitive 3D tumor images at depths up to 1 cm, and it employs compact epi-imaging and illumination suitable for the operating room, with quasi-real-time image reconstruction for surgical visualization. We present experimental results with FDA-approved Indocynanine Green using an extensive array of tissue phantoms and in a pilot in-vivo study.
Programmed Innovation in New Product Development

(1969). Programmed Innovation in New Product Development. Research Management: Vol. 12, No. 4, pp. 279-287.
Sclerostin Antibody Treatment Stimulates Bone Formation to Normalize Bone Mass in Male Down Syndrome Mice.

Down syndrome (DS), characterized by trisomy of human chromosome 21, is associated with a variety of endocrine disorders as well as profound skeletal abnormalities. The low bone mass phenotype in DS is defined by low bone turnover due to decreased osteoclast and osteoblast activity, decreasing the utility of antiresorptive agents in people with DS. Sclerostin antibody (SclAb) is a therapeutic candidate currently being evaluated as a bone anabolic agent. Scl, the product of the sclerostin gene (SOST), inhibits bone formation through its inhibition of Wnt signaling. SclAb increases bone mass by suppressing the action of the endogenous inhibitor of bone formation, Scl. To examine the effects of SclAb on the DS bone phenotype, 8‐week‐old male wild‐type (WT) andTs65Dn DS mice were treated with 4 weekly iv injections of 100 mg/kg SclAb. Dual‐energy X‐ray absorptiometry (DXA), microCT, and dynamic histomorphometry analyses revealed that SclAb had a significant anabolic effect on both age‐matched WT littermate controls and Ts65Dn DS mice that was osteoblast mediated, without significant changes in osteoclast parameters. SclAb treatment significantly increased both cortical and trabecular bone mass at multiple sites; SclAb treatment resulted in the normalization of Ts65Dn bone mineral density (BMD) to WT levels in the proximal tibia, distal femur, and whole body. Ex vivo bone marrow cultures demonstrated that SclAb increased the recruitment of the mesenchymal progenitors into the osteoblast lineage, as indicated by increased alkaline phosphatase–positive colonies, with no effect on osteoclast differentiation. Together, in the setting of a murine model of DS and decreased bone turnover, SclAb had a potent anabolic effect. SclAb stimulated bone formation and increased osteoblastogenesis without affecting osteoclastogenesis or bone resorption. These data suggest that SclAb is a promising new therapy to improve bone mass and reduce fracture risk in the face of the low bone mass and turnover prevalent in the DS population. © 2017 The Authors JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
Trends in Knee Articular Cartilage Treatments: An American Board of Orthopaedic Surgery Database Study.

This study aims to evaluate the trends in treatment of knee articular cartilage lesions over the past decade using data obtained from the American Board of Orthopaedic Surgery (ABOS) Part II database. The ABOS Part II database was queried from 2004 to 2013 for chondroplasty, microfracture, and osteochondral grafting procedures. All cases were analyzed for patient age and operating surgeon's fellowship training status. Univariate analysis including chi-square test for categorical variables and Student's t-test for continuous variables was performed to determine if any significant changes in practice patterns were present. Linear regression analyses were utilized to examine temporal trends in procedures performed and fellowship training status. From 2004 to 2013, 25,938 procedures addressing articular cartilage lesions from 3,586 surgeons were identified in the ABOS database. 46.8% of these orthopaedic surgeons had completed a 1-year sports medicine fellowship. Sixty-six percent of cartilage surgeries were performed by sports medicine-trained surgeons. The articular cartilage surgical volume decreased from 3,126 cases in 2004 to 1,690 cases in 2013. The most common procedure coded overall was chondroplasty (80.23%) followed by microfracture (21.37%) and osteochondral grafting (2.1%). The mean age of patients undergoing chondroplasty was 46.9 years; this was significantly higher than microfracture (mean age 40.5 years) or osteochondral grafting procedures (mean age 31.6 years), p
Comparison of seasonal distribution patterns of Discostella stelligera and Lindavia bodanica in a boreal lake during two years with differing ice-off timing

Widespread changes in the relative abundances of Cyclotella sensu lato taxa have occurred in lakes of the Northern Hemisphere over the last ∼150 years, with these changes often attributed to climate-driven physical changes in lakes. While the links between Cyclotella ecology and lake thermal structure have been investigated extensively now, the role of the timing of ice-off in driving these diatom patterns remains unclear. We compared the seasonal distribution patterns of Cyclotella taxa in a boreal lake with high water transparency during two years with differing timing of ice-off. Vertical distributions of taxa in Jordan Pond (Maine, USA) were assessed every 5–24 days from early May to late October during an early ice-off year (19 March 2012) and a late ice-off year (29 April 2015). Seasonal succession patterns differed over the two years. During the early ice-off year, Lindavia bodanica cell densities were higher and peaked in the hypolimnion from July to October. The abundance of this taxon during the...
Nomenclature in heart failure: a call for objective, reproducible, and biologically-driven terminology

Contemporary clinical trials in heart failure (HF) enroll patients largely based on acuity of presentation, left ventricular ejection fraction (EF), and functional status. These trial programs variably employ certain enrichment criteria such as prior hospitalization for HF or elevated natriuretic peptide levels to reaffirm the HF diagnosis and identify patients at higher risk of clinical events. This approach has yielded heterogenous patient cohorts with distinct biological substrates and varying levels of clinical risk. Indeed, patients with HF have variable clinical trajectories that often depend on comorbidities, congestion, hemodynamics, and underlying etiology. In the past decade, progress has been made in identifying imaging- and biomarker-based signatures of HF and the development of risk scores for prognosis. Although these parameters have advanced the promise of precision-based therapeutic approaches, such tools have been variably incorporated alongside traditional eligibility criteria in contemporary trial design. Over the past 3 decades, since the initial publication of the CONSENSUS (Cooperative North Scandinavian Enalapril Survival Study) trial in 1987 (1), enrollment criteria have remained relatively stagnant and have not evolved in parallel with progress in defining HF as an entity. Similarly, patients early or late in their HF journey are loosely defined and have variable approaches to care. We explore complexities in the interpretation and application of traditional HF-related nomenclature in clinical practice and in clinical trials (Table 1). Table 1. Complexities with Current HF Nomenclature
Abstract 32: BCL11A is necessary for the expression of extracellular matrix genes and metastatic progression of triple-negative breast cancer

Cancer stem cells (CSC) contribute to the high incidence of metastatic recurrence in triple-negative breast cancer (TNBC) and elucidating the mechanisms controlling CSC properties should provide novel targets for therapeutic development that improves patient outcomes. The transcription factor BCL11A is highly differentially expressed in TNBC versus all other subtypes and controls breast CSC phenotypes such as marker expression and tumor initiation. However, the genes that BCL11A targets to control CSC biology and whether BCL11A promotes metastatic progression are unknown. To address these questions, we assessed the impact of transiently silencing the expression of BCL11A in TNBC cells using siRNA transfections. Reducing BCL11A expression did not impact TNBC cell viability or in vitro migratory capacity. However, silencing BCL11A significantly decreased invasion of TNBC cell lines, in vitro. Furthermore, stable shRNA-mediated silencing of BCL11A in the highly metastatic MDA-MB-231 cell line reduced metastatic outgrowth when xenografted into immunocompromised mice, suggesting that BCL11A is critical for metastatic progression of TNBC. To identify the BCL11A-regulated transcriptome in TNBC, we performed RNA-seq analysis of cells transiently transfected with non-targeting or BCL11A-targeted siRNAs in the MDA-MB-231 cell line. Consistent with the impact of BCL11A on invasion, numerous genes involved in adhesion and extracellular matrix were reduced with BCL11A silencing. The gene encoding the matrix metalloproteinase, MMP1, was the most significantly differentially expressed gene, with a 10-fold decrease in RNA expression following BCL11A suppression. We confirmed this down-regulation by both qRT-PCR and western blots of independent samples, as well as in the HCC1143 TNBC cell line. Current studies are assessing the functional impact of MMP1 regulation by BCL11A on invasion and metastatic progression of TNBC. Citation Format: Darcie D. Seachrist, Natasha N. Ingles, Molly M. Hannigan, Donny D. Licatalosi, Ruth A. Keri. BCL11A is necessary for the expression of extracellular matrix genes and metastatic progression of triple-negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 32.
Preoperative Evaluation: Indications and Risk Analysis

A thorough preoperative evaluation is paramount in performing successful TAVRs. All supporting literature in TAVR was done following careful risk stratification. This chapter addresses not only indications and contraindications but also special scenarios such as bicuspid aortic valve and bioprosthetic valve degeneration.
Intellectual Property at the Edge: Legal but unacceptable: Pallin v. Singer and physician patenting norms

In intellectual property discourse, the edge tends to be defined by disputes between producers and consumers or between upstream and downstream innovators. This Chapter tells a different kind of story, about the edge between the patent-based innovation system and a user innovator community governed by norms of reputation and sharing. In this story, a cataract surgeon’s attempt to enforce his surgical method patent in the early 1990s brought forth a surprisingly strong response from the medical profession. The incident generated a reaffirmation of the norm in the AMA’s ethical principles and a political movement that led to Congress’s passage of Section 287(c) of the Patent Act, exempting medical professionals from patent remedies in many cases. The Chapter argues that these events are fruitfully understood in light of the rejection of patenting by many user innovator companies in favor of norms-based systems of free revealing and sharing accompanied by reputational rewards.
A More Principled Approach to Criminalizing Carelessness: A Prescription for the Legislature

American society increasingly relies on technology and a faster pace to accomplish more tasks more quickly. However, these benefits are realized at some cost. The potential for increased societal harm generated by the combination of technological reliance and an up-tempo lifestyle poses a challenge to the law, particularly given the negligent nature of today's society. The criminal law traditionally has focused its sanctions on harmful activity produced intentionally or recklessly, relieving those who engage in ordinary negligent harm from criminal sanction. The modern technological revolution requires legislators and policymakers to reevaluate the traditional reluctance of criminal law to punish ordinary negligence and to broaden the scope of punishable conduct to include ordinary negligent conduct when such punishment will deter others. This article draws the conclusion that criminal law will not unfairly punish individuals and will provide prosecutors with enhanced tools to respond to dangerously careless conduct that could have been anticipated and averted.