cssi/SciSciGPT-SciSciNet huggingface dataset:
Adult and Embryonic Gecko Cells in Vitro: Growth Characteristics, Infection by Rabies, Sindbis and Polyoma Viruses, and Transformation by SV40:

SummaryCell lines were established from trypsin-dispersed or minced and explanted tissues of whole embryo or adult tail tissues of the leopard gecko, Eublepharis macularis. Embryo cells grew more rapidly at early passage levels, but an adult cell line exhibited a growth rate similar to that of embryonic cells (mean cell population doubling time = ca. 3.5 days) after adaptation to in vitro growth for 12 passages (14 wk). Embryo-origin cells were predominantly epithelial-like, whereas adult tail-origin cell lines were fibroblast-like.Adult- and embryo-origin cell lines could not be distinguished on the basis of temperature optimum (29-31°), medium pH requirements (pH 6.9-7.7), karyotypic changes (all passage levels tested [to number 25] were euploid), or virus susceptibility. Adult and embryonic leopard gecko cells supported cytopathic infection by vaccinia, herpes simplex, frog polyhedral, Newcastle disease, Sindbis and vesicular stomatitis viruses. Single step growth curves of Sindbis virus were identical...
Integrating the evolving modern cockpit

This paper applies to Free Flight some lessons learned from ten years of investigation into computing in the modern cockpit. Early efforts concluded that Artificial Intelligence was better suited to Flight Management and Pilot Decision Support than to aircraft control. Later efforts produced an AI-based cockpit software decision system for inferring current flight operation without querying the pilot. That decision system was used to drive adaptive displays and a rulebased Pilot Advisor. This prior work implemented a state of the art fixed-base engineering flight simulator, whose software was favorably evaluated by a team of pilots. Currently, an innovative Flight Management System is being implemented, based on cooperating software agents. The technology focus is not just on hardware but on the software that can integrate new Free Flight functionality, in terms of increasing pilot situational awareness, while not increasing his workload. Software methods integrate data from multiple sources, dealing with weather, traffic, terrain, and route. Such data fusion results in an integrated, pilot-centered, smart guidance and display system.
Experimental Host Preferences of Monoctonus paulensis (Hymenoptera: Braconidae), including a Hypothetical Scheme of Host Selection

When offered a choice of 5 known dactynotine host species in cage experiments, the aphidiine parasite, Monoctonus paulensis (Ashmead), did not exhibit a distinct preference for a particular species, but parasitized them all with equal frequency. Further tests, utilizing Pyrex® tubes, exposed 2 pairs of aphid hosts to parasite attack, i.e., Acyrthosiphon pisum (Harris) and Therioaphis trifolii (Monell), and Sitobion fragariae (Walker) and Rhopalosiphum padi (L.). The 1st member of each pair was a known host in the Dactynotini, the other species belonged to a different aphid group and was not known to be an acceptable host. Female parasites did not display a preference for attacking S. fragariae in favor of R. padi in these tests, but did prefer A. pisum nymphs to those of T. trifolii . Nymphs of R. padi and T. trifolii were found to be physiologically unsuitable hosts. The results of these tests, combined with field data obtained in an earlier study, were used to depict the host-selection process of this parasite species as it probably occurs in the field.
Recent Development, The Role of Civil Society Organizations in the United States Recently-Concluded CERD Review

In recent years, American civil society organizations (CSOs) have taken on a more active role in monitoring and enforcing America’s compliance with a variety of its obligations under international law. CSOs have engaged in a human rights monitoring and enforcement strategy to pursue their missions. CSOs are interacting with a variety of global enforcement monitors to hold the United States’ feet to the fire — spotlighting areas where they believe the United States has fallen short of its responsibilities to protect and advance social justice. This Recent Development will examine the United States’ recently concluded Convention on the Elimination of all forms of Racial Discrimination periodic review to illustrate and explore both its mechanics and implications.
Moment and IV Selection Approaches: A Comparative Simulation Study

We compare three moment selection approaches, followed by post-selection estimation strategies. The first is adaptive least absolute shrinkage and selection operator (ALASSO) of Zou (2006), recently extended by Liao (2013) to possibly invalid moments in GMM. In this method, we select the valid instruments with ALASSO. The second method is based on the J test, as in Andrews and Lu (2001). The third one is using a Continuous Updating Objective (CUE) function. This last approach is based on Hong et al. (2003), who propose a penalized generalized empirical likelihood-based function to pick up valid moments. They use empirical likelihood, and exponential tilting in their simulations. However, the J-test-based approach of Andrews and Lu (2001) provides generally better moment selection results than the empirical likelihood and exponential tilting as can be seen in Hong et al. (2003). In this article, we examine penalized CUE as a third way of selecting valid moments.Following a determination of valid moments, w...
A new approach to predict fan failures with fan speed correlation

When aging fans in server chassis wear out, they slow down and circulate less air, eventually causing overheating condition and unexpected thermal shutdown. We propose a novel approach to predictive analysis of fan failures before the significant wear-out or slow-down by modeling the correlation of the speed measurements of multiple fans. We present the empirical result that the speed measurements of multiple fans in a server are highly correlated and exploit the observation to devise the use of data-driven anomaly detection methods in predictive fan failure analysis. A comparative study on several variants of the approach is performed on the simulated data sets demonstrating how certain heuristics substantially improve the performance.
Study on the Principles of Risk and Return

Two classics were reviewed: Portfolio Selection (Hary M.Markowitz) and Capital Asset Pricing Model (William F.Sharpe). Some misunderstanding among academic circles were clarified; The paper presented the principles of risk and return in a new way.
Inhibitory effects on Colletotrichum gloeosporioides and control efficacy against mango anthracnose by Bacillus subtilis 9A

【Objective】 Bacillus subtilis 9A was isolated from a lesion of powdery mildew on the leaves of Cucurbit. The study is to evaluate the biocontrol potential of 9A. 【Method】 The effects of culture filtrate of9A on mycelial growth, membrane permeability, conidial production, conidial germination, and appressorial formation of Colletotrichum gloeosporioides were tested in vitro, and the control efficacy of culture broth of 9A against mango anthracnose was estimated on detached leaves and in the field. 【Results】 The results showed that mycelial growth was inhibited on the plates containing culture filtrate of 9A at concentrations from 2% to 10%, with the inhibition rate up to 91.86% at the concentration of 10%, meanwhile,the production of conidium was stimulated with those concentrations; appressoria did not melanize when the concentration reached 1.5%, and conidia did not germinate when treated with the concentration of culture filtrate at 4%; membrane permeability was enhanced when treated with filtrate of 9A, but reduced back to steady after rising up to the top at 36 h; the control efficacy on detaced leaves and in the filed was respectively 0% and 40.55% when leaves were treated with culture broth of 9A at 24 h after inoculation,and the control efficacy on detaced leaves and in the filed was respectively 100% and 82.04% when the leaves were treated with culture broth of 9A at 24 h before inoculation.【Conclusion】 The results indicated that Bacillus subtilis 9A has potential for control of mango anthracnose.
Abstract PR06: Precision medicine for newly diagnosed and refractory/recurrent pediatric cancer patients: Lessons learned from “N=1” studies

Whole genome sequencing has rapidly emerged as the preferred method for unbiased genomic interrogation. Leveraging this technology, we have developed a precision medicine clinical research protocol for pediatric, adolescent, and young adult cancer patients. The primary objective of this study is to arrive at genome informed treatment recommendations for individual patients suffering from aggressive and/or worsening disease in a clinically relevant time frame. The second objective is to survey the genomic landscape of newly diagnosed and recurrent/refractory patients. To accomplish this, we have employed an interdisciplinary workflow including a customized bioinformatic analysis pipeline, contextual biological interpretation of the data, and case reviews during weekly molecular tumor board meetings. Here we report the results of having sequenced over 50 patients diagnosed with both common and rare malignancies. Factors affecting the successful identification of therapeutically actionable targets and subsequent intervention are varied. The most consistent findings are the increased mutation burden in patients who have received chemotherapy and/or radiation prior to tissue collection. Lastly, we highlight the realistic opportunities, challenges, and insight gained from an ongoing single institution experience. This abstract is also presented as Poster 27. Citation Format: Troy A. McEachron, Keri B. Zabokrtsky, Aaron F. Sassoon, Sara Nasser, Tyler Izatt, Chad P. Garner, David W. Craig, John D. Carpten, Leonard S. Sender. Precision medicine for newly diagnosed and refractory/recurrent pediatric cancer patients: Lessons learned from “N=1” studies. [abstract]. In: Proceedings of the AACR Precision Medicine Series: Integrating Clinical Genomics and Cancer Therapy; Jun 13-16, 2015; Salt Lake City, UT. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(1_Suppl):Abstract nr PR06.
Time delayed directional beam quadrifilar helix phased array antenna

The main objective of this project is to construct a phased array antenna with a steerable beam (manually if need be) having a center frequency of 2.45 GHz and a bandwidth in the range of 100 MHz. The phase shifting of the elements is accomplished using time-delayed feeds to the individual antennas via coaxial cables. This documentation depicts the design, simulation, fabrication and analysis of a two-dimensional planar phased array antenna using the quadrifilar helical antenna (QHA) as the element of choice.
Analysis of ASTM X-ray shrinkage rating for steel castings

This paper presents the results of two different studies that examined the ASTM x-ray shrinkage rating system for radiographs of steel castings. The first study evaluated the repeatability and repr...
Improving quality outcomes in head and neck free flap surgery with the use of a physician inpatient coordinator

Objectives/Hypothesis Head and neck free flap patients require complex postoperative care. The quality of care for these patients often depends on their management from the time they leave the operating room. The purpose of this study was to investigate the impact of a postoperative inpatient coordinator (IC) for head and free flap patients on quality outcomes: length of stay (LOS), 30-day unplanned return to the emergency department (30dRED), 30-day unplanned readmissions (30dUR), and complication rates. Study Design Retrospective cohort study. Methods One hundred eighty-eight consecutive patients who underwent head and neck free flap surgery between January 2012 and January 2016 were reviewed using a prospective database. Patients had an IC for their entire hospitalization (group 1) or for less than their entire hospitalization (group 2). Logistic regression analysis was performed to identify risk factors for quality outcomes. Results Mean LOS was 13.8 days and 17.3 days in groups 1 and 2, respectively (P = .002). The 30dRED rate was 12% and 22%, respectively (P = .04). Group 2 had an increased LOS by 4.1 days (P = .001) and a 2.4 fold increased 30dRED (P = .03). 30dUR and complications were not influenced by the IC (P > .05). Conclusions An IC may help decrease LOS and 30dRED in head and neck free flap patients. Level of Evidence 4 Laryngoscope, 2017
Metabolic and Biochemical Stressors in Diabetic Cardiomyopathy

Diabetic cardiomyopathy (DCM) or diabetes-induced cardiac dysfunction is a direct consequence of uncontrolled metabolic syndrome and is widespread in US population and worldwide. Despite of the heterogeneous and distinct features of DCM, the clinical relevance of DCM is now becoming established. DCM progresses to pathological cardiac remodeling with the higher risk of heart attack and subsequent heart failure in diabetic patients. In this review, we emphasize lipid substrate quality and the phenotypic, metabolic, and biochemical stressors of DCM in the rodent and human pathophysiology. We discuss lipoxygenase signaling in the inflammatory pathway with multiple contributing and confounding factors leading to DCM. Additionally, emerging biochemical pathways are emphasized to make progress toward therapeutic advancement to treat DCM.
Sobreimpresiones cartográficas y fugas textuales: políticas del espacio a partir del poema «Los Neochilenos» de Roberto Bolaño

espanolResumen El presente trabajo propone una lectura del poema «Los Neochilenos» de Roberto Bolano, que argumenta a favor de su papel central en la configuracion de los espacios disenados por el autor. Mediante un dialogo entre este poema y el resto de la obra de Bolano se sostiene que el autor ofrece una interpretacion de las fronteras como espacios de intercambio entre las zonas interiores y exteriores, resignificando el motivo del viaje como un transito que subvierte las fronteras politicas y tensiona el arraigo territorial de los diversos canones inscritos en los espacios nacionales. De esta forma, los desplazamientos realizados por los personajes de Bolano describirian trayectos que permiten articular espacios de confluencia entre el Mapa y la Biblioteca, discursos que confluyen en la configuracion de las identidades nacionales. EnglishAbstract This paper proposes a reading of the poem «Los Neochilenos» by Roberto Bolano, arguing for their central role in the configuration of the spaces designed by the author. Through a dialogue between this poem and the rest of the work of Bolano it is argued that this author offers an interpretation of borders as spaces of exchange between interior and exterior zones, giving a new meaning to the theme of travel as a transit that subverts political borders and it puts in dialogue the various registered canons in national spaces. Thus, the trips made by Bolano's characters describe paths which allow joint spaces of convergence between the Map and the Library as instances of power.
Low impedance arrays of coupled Cross-Sectional Lamé mode resonators with high figure of merit in excess of 100

We report on novel high electromechanical coupling coefficient (k t 2) and large input capacitance (C 0 ) Cross-Sectional Lame mode resonators (CLMRs). We show that, by coupling multiple 3-fingers CLMRs, it is possible to simultaneously achieve high Figure of Merit (FoM, namely the product between quality factor, Q, and k t 2) and large C 0 -values. The use of this design approach permits to evade the intrinsic reduction of FoM, occurring in traditional single-plate CLMRs at increasing C0-values. In addition, we report on the performance of a 3-finger 730 MHz CLMR, showing a FoM in excess of 147. Such a record high FoM is the highest reported in AlN resonators operating in the same frequency range.
Updating Austen: Catherine Hubback and Emily Eden

This chapter, considers how mid-Victorian domestic novels by Catherine Hubback and Emily Eden specifically engage with Austen’s work. Hubback and Eden update Jane Austen and her heroines by combining elements of her fiction with popular genres, such as the silver fork novel, and incorporating contemporary mid-Victorian social concerns into their texts. For these writers, Austen became useful for negotiating questions about the development of the novel, the changing literary marketplace, and the role of the woman writer in the nineteenth century.
Driving Rel-iant Tregs toward an Identity Crisis

Inhibiting Treg cell function in tumors is an attractive strategy to improve anti-cancer immunity. In a pair of papers in Immunity and Cell, Ghosh and colleagues show that the canonical NF-κB subunits p65 and c-Rel have non-redundant, critical roles in promoting Treg cell development and function (Oh et al., 2017). Targeting c-Rel blunts Treg cell immunosuppressive activity in the tumor microenvironment and enhances anti-tumor T cell responses (Grinberg-Bleyer et al., 2017).
A Systematic Review of the Demographic Characteristics of Participants in US-Based Randomized Controlled Trials of Mindfulness-Based Interventions

This systematic review examines the socio-economic and demographic characteristics of adults enrolled in US-based randomized controlled trials of mindfulness-based stress reduction (MBSR) and mindfulness-based cognitive therapy (MBCT). We conducted a literature search using Medline, PsycINFO, and CINAHL electronic databases from the earliest available until March 2017. We found 69 randomized controlled trials that met inclusion criteria. Only one study specifically aimed to test the mindfulness interventions in racial/ethnic minority or lower socio-economic status populations and none reported their effectiveness in these populations. For the 56 articles that reported the proportion of Caucasians in their samples, 79% of all individuals were identified as Caucasian. Out of the 45 studies that reported data on other races and ethnicities, 76% of the individuals were Caucasian, 11% were African-American, 4% were Asian-American, 4% were Hispanic/Latinx, < 1% were American Indian/Native American, and 5% were reported as “other” or multi-ethnic. The three most commonly reported socio-economic characteristics were educational attainment (n = 48), employment/professional status (n = 29), and income (n = 27). The proportion of college graduates in the study samples was higher than the national average in all but one of the studies that reported this data. Most of the studies that reported employment rates had more than half of their participants employed. Of the studies that reported average income, most had more than 50% of their participants making over $40,000 a year. This review highlights the need for increased diversity in randomized controlled trials of mindfulness-based interventions as these interventions have great promise to alleviate mental and physical health problems in underserved populations.
The Cost-effectiveness of Antimicrobial Lock Solutions for the Prevention of Central Line-Associated Bloodstream Infections.

Background Antimicrobial lock solutions are a low-cost strategy that can reduce the incidence of central line-associated bloodstream infection (CLABSI). The aim of this study was to evaluate the cost-effectiveness of antimicrobial locks for the prevention of CLABSI. Methods We constructed a decision-analytic model comparing antimicrobial lock solutions to heparin locks for the prevention of CLABSI in 3 settings: hemodialysis, cancer treatment, and home parenteral nutrition. Cost-effectiveness was determined by calculating CLABSIs prevented and incremental cost-effectiveness ratios. Uncertainty was addressed by plotting cost-effectiveness planes and acceptability curves for various willingness-to-pay thresholds. Results In probabilistic analysis, at a willingness to pay of $50000, antimicrobial lock solutions had a 96.24% chance of being cost-effective, compared with heparin locks in the hemodialysis setting, an 88.00% chance in the cancer treatment setting, and a 92.73% chance in the home parenteral nutrition setting. In base-case analysis, antimicrobial lock solutions resulted in savings of $68721.03 for the hemodialysis setting, $85061.41 for the cancer setting, and $78513.83 for the home parenteral nutrition setting per CLABSI episode prevented. Conclusions In 3 distinct and clinically important settings (hemodialysis, cancer treatment, and home parenteral nutrition), antimicrobial lock solutions are an effective strategy for the prevention of CLABSI, and their use can result in significant healthcare savings.
Convolutional Neural Network Based Breast Cancer Risk Stratification Using a Mammographic Dataset.

Rationale and Objectives We propose a novel convolutional neural network derived pixel-wise breast cancer risk model using mammographic dataset. Materials and Methods An institutional review board approved retrospective case-control study of 1474 mammographic images was performed in average risk women. First, 210 patients with new incidence of breast cancer were identified. Mammograms from these patients prior to developing breast cancer were identified and made up the case group [420 bilateral craniocaudal mammograms]. The control group consisted of 527 patients without breast cancer from the same time period. Prior mammograms from these patients made up the control group [1054 bilateral craniocaudal mammograms]. A convolutional neural network (CNN) architecture was designed for pixel-wise breast cancer risk prediction. Briefly, each mammogram was normalized as a map of z-scores and resized to an input image size of 256 × 256. Then a contracting and expanding fully convolutional CNN architecture was composed entirely of 3 × 3 convolutions, a total of four strided convolutions instead of pooling layers, and symmetric residual connections. L2 regularization and augmentation methods were implemented to prevent overfitting. Cases were separated into training (80%) and test sets (20%). A 5-fold cross validation was performed. Software code was written in Python using the TensorFlow module on a Linux workstation with NVIDIA GTX 1070 Pascal GPU. Results The average age of patients between the case and the control groups was not statistically different [case: 57.4years (SD, 10.4) and control: 58.2years (SD, 10.9), p = 0.33]. Breast Density (BD) was significantly higher in the case group [2.39 (SD, 0.7)] than the control group [1.98 (SD, 0.75), p Conclusion Novel pixel-wise mammographic breast evaluation using a CNN architecture can stratify breast cancer risk, independent of the BD. Larger dataset will likely improve our model.
Integration of speech information (or not) across electric and acoustic modes in hearing impaired listeners

Many people with hearing loss use two cochlear implants (bilateral CIs), or combine a CI and hearing aid (bimodal). While the addition of a second CI or acoustic input improves speech perception (particularly in noise), it is not well understood how listeners fuse these disparate inputs. We addressed this with a duplex perception experiment. Listeners heard the four cardinal vowels from six talkers. In the duplex condition, the first formant was presented to the CI, and the second to the other CI or hearing aid (and vice versa). In normal listeners (N = 14), accuracy under duplex presentation (across ears; M= 0.80) did not differ from combined presentation (both formants, both ears, M = 0.76, p = 0.14), but performance dropped to near chance with isolated formants (M = 0.40, p<0.001). CI users (Bilateral: N = 7; bimodal: N = 11; single-side-of-deafness [SSD]: N = 7) performed well in combined presentation (Bilateral: M = 0.72, Bimodal: M = 0.70, SSD: M = 0.83), and poorly for isolated formants (Bilateral: M = 0.42, Bimodal: M = 0.39, SSD: M = 0.41). Duplex presentation was significantly poorer than combined (Bilateral: M = 0.54, p = 0.0078; Bimodal: M = 0.55, p<0.001; SSD: Duplex: 0.48, p<0.001), though better than isolated formants (p<0.05). Thus, CI users may not fuse inputs well at an auditory level, and the benefits of acoustic + electric hearing may derive from central integration.Many people with hearing loss use two cochlear implants (bilateral CIs), or combine a CI and hearing aid (bimodal). While the addition of a second CI or acoustic input improves speech perception (particularly in noise), it is not well understood how listeners fuse these disparate inputs. We addressed this with a duplex perception experiment. Listeners heard the four cardinal vowels from six talkers. In the duplex condition, the first formant was presented to the CI, and the second to the other CI or hearing aid (and vice versa). In normal listeners (N = 14), accuracy under duplex presentation (across ears; M= 0.80) did not differ from combined presentation (both formants, both ears, M = 0.76, p = 0.14), but performance dropped to near chance with isolated formants (M = 0.40, p<0.001). CI users (Bilateral: N = 7; bimodal: N = 11; single-side-of-deafness [SSD]: N = 7) performed well in combined presentation (Bilateral: M = 0.72, Bimodal: M = 0.70, SSD: M = 0.83), and poorly for isolated formants (Bilateral:...
Multimodal action of ONECUT2 in driving neuroendocrine prostate cancer.

Prostate cancer (PC) is the second leading cause of cancer death in American men (behind lung cancer), being responsible for 29,430 deaths annually (per 2018 estimates of the American Cancer Society). The vast majority of PCs (>95%) arise as adenocarcinomas, which are frequently dependent (at least initially) on the androgen receptor (AR) axis for their growth and express AR target genes, such as KLK3 (PSA).
Changes in Physical Assault Among Adults Moving Into Permanent Supportive Housing

People experiencing homelessness experience high rates of physical assault. While this high risk for victimization is well established, there is no research that examines whether victimization rate...
Elevated neutrophil-lymphocyte ratio predicts mortality following elective endovascular aneurysm repair.

Abstract Objective The neutrophil-lymphocyte ratio (NLR) is an inexpensive and useful inflammatory marker that incorporates the balance of the innate (neutrophil) and adaptive (lymphocyte) immune responses. Data exist on the association between NLR and mortality in various coronary diseases and in cancer surgery, but there is a paucity of data on the impact of preoperative NLR on vascular surgical outcomes. The aim of this study was to evaluate the relationship between preoperative NLR and elective endovascular aortic aneurysm repair (EVAR) outcome. Methods A retrospective review of all patients who underwent elective EVAR at a single institution between 2010 and 2018 was conducted (n = 373). Only patients who had a preoperative complete blood count with differential within 30 days of their operation were included. The NLR was computed by dividing the absolute neutrophil count by the absolute lymphocyte count. A receiver operating characteristic curve was used to determine the optimal cutoff value of NLR with the strongest association with mortality. NLR was dichotomized so that patients with NLR above the threshold were at increased risk of mortality compared with those below it. Continuous variables were analyzed using Wilcoxon nonparametric signed-rank test and categorical variables with the Fisher exact test. A comparison of NLR and mortality was completed using Kaplan-Meier survival analysis. Cox regression analysis was used to evaluate factors associated with mortality through 5-year follow-up. Results Overall, 108 patients were included in this study. An NLR ≥ 4.0 was found to be associated with mortality (P Conclusions Patients with an elevated preoperative NLR, irrespective of other comorbidities, may represent a previously unrecognized subset of patients who are at heightened risk of mortality after elective EVAR. A complete blood count with differential is an inexpensive test that may be used as a prognostic indicator for outcome after EVAR. Further research is warranted to identify clinical, pathological, or anatomical factors associated with an elevated NLR and to determine modifiable factors, which may help improve long-term survival.
How to Succeed in Fellowship Acquisition: A Survey of Pathology Residents:

Medical school curricula limit students' exposure to pathology practice while pathology subspecialty training programs require residents to apply for fellowships as early as the end of their first year of training. Thus, limited exposure to pathology practice creates significant confusion and anxiety, often making the fellowship application process premature. Additionally, early focus on subspecialty training in order to acquire a fellowship adds to the initial lack of emphasis on general pathology training. We prepared a voluntary online survey with questions developed through focus groups and advice from an expert in survey design to determine which fellowships are desired and how successful residents are in their pursuit of these fellowships. The survey was distributed through the Pathology Residency Program Directors' (PRODS) listserv. Answers were solicited from pathology trainees throughout the entire training cycle. There were 141 (4.6% response rate) total respondents with each postgraduate year represented. One hundred twenty-two (95%) of 129 residents plan on completing 1 or 2 fellowships after residency training. Encouragingly, 94 (75%) of 126 pathology residents attained their desired specialty fellowship. However, 32 (32%) of 99 residents who acquired at least one fellowship chose a general surgical pathology fellowship. Furthermore, 33 (24%) respondents had already decided to pursue a specific specialty while still in medical school. An additional 32 (23%) came to their decision during postgraduate year 1. Therefore, although most residents are successful in attaining their desired fellowship, further research is needed to understand the effect of early commitment to a subspecialty and its impact on pathology education.
Varying co-factor requirements for MAML1-dependent transcription at different Notch-responsive target genes

Abstract Mastermind proteins are required for transcription of Notch target genes, yet the molecular basis for mastermind function remains incompletely understood. Previous work has shown that Notch can induce transcriptional responses by binding to promoters, but more often by binding to enhancers, with HES4 and DTX1 as representative mammalian examples of promoter and enhancer responsiveness, respectively. Here, we show that mastermind dependence of the Notch response at these loci is differentially encoded in Jurkat T-ALL cells. Knockout of Mastermind-like1 (MAML1) eliminates Notch responsive activation of both these genes, and reduced target gene expression is accompanied by a decrease in H3K27 acetylation, consistent with the importance of MAML1 for p300 activity. Add-back of defined MAML1 constructs in knockout cells identifies residues 151-350 of MAML1 as essential for expression of either Notch-responsive gene. Fusion of the Notch-binding region of MAML1 to the HAT domain of p300 rescues expression of HES4 but not DTX1, suggesting that an additional activity of MAML1 is needed for gene induction at a distance. Together, these studies establish the functional importance of the MAML1151-350 region for Notch-dependent transcriptional induction, and reveal differential requirements for MAML1-dependent recruitment activities at different Notch responsive loci, highlighting the molecular complexity of NTC-stimulated transcription.
Haptic Perception of Liquids Enclosed in Containers

Service robots will require several important manipulation skills, including the ability to accurately measure and pour liquids. Prior work on robotic liquid pouring has primarily focused on visual techniques for sensing liquids, but these techniques fall short when liquids are obscured by opaque or closed containers. This paper proposes a complementary method for liquid perception via haptic sensing. The robot moves a container through a series of tilting motions and observes the wrenches induced at the manipulator’s wrist by the liquid’s shifting center of mass. That data is then analyzed with a physics-based model to estimate the liquid’s mass and volume. In experiments, this method achieves error margins of less than lg and 2mL for an unknown liquid in a 600mL cylindrical container. The model can also predict the viscosity of fluids, which can be used for classifying water, oil, and honey with an accuracy of 98%. The estimated volume is used to precisely pour 100mL of water with less than 4% average error.
Dietary morphology of two island-endemic murid rodent clades is consistent with persistent, incumbent-imposed competitive interactions

A lineage colonizing a geographic region with no competitors may exhibit rapid diversification due to greater ecological opportunity. The resultant species diversity of this primary-colonizing (inc...
13.09 – Ion Channels*

Transport of ions across biological membranes through ion channels is a critical event that regulates signal transduction, ionic homeostasis, and other cellular physiological processes. Ion channels are integral pore-forming membrane proteins that are activated by changes in membrane voltage or by binding of specific ligands. Specific binding sites on ion channels are also modulatory targets for a variety of toxic compounds, which affect ion channel functions resulting in deleterious toxicological effects. Several toxins that generally target one group of ion channels or one specific subtype of ion channels have been isolated from a variety of plants, invertebrates, and vertebrates. The voltage-gated sodium channels are ubiquitously present in several types of cells and have several binding sites for toxins enabling classification of toxins based on their binding sites. Sodium channel physiology and toxicology has been extensively researched and the major types of toxins that modulate these channels include tetrodotoxin, saxitoxin, scorpion toxins, spider toxins, sea anemone toxins, and pyrethroids. The potassium channels show great variety in terms of their genetic diversity and channel properties. The major toxins that modulate potassium channels include scorpion toxins and dendrotoxins. The voltage-gated calcium channels are classified mainly on their voltage threshold for activation and channel properties and are affected by toxins such as ω-conotoxins, ω-agatoxins, huwenotoxins, and glycerotoxin. The chloride channels are inhibited by Georgia anion toxin and are different from the ligand-gated γ-aminobutyric acid (GABA) and glycine receptors. GABA receptors in particular are well characterized in terms of toxicology and are well-known targets of certain insecticides. The ionotropic glutamate receptors are one major class of ligand-gated receptors that are affected by heavy metal ions and toxins, both synthetic and natural. The other major types of receptors include acetylcholine receptors and serotonin receptors of which the former are targets of peptide toxins from venoms and the latter are targets of abused drugs of plant origin. The ion channel toxins, mainly the ones with high binding affinities, have served as valuable tools for elucidating the structure and function of various ion channels. In addition, the knowledge of the ion channel modulations by toxins serves as a basis for future development of effective therapies. This chapter provides an updated systematic review of ion channel toxicology, particularly of the voltage-gated ion channels, whereas the ligand-gated ion channels are reviewed in detail in Chapter 13.09.
Experimental study of a string-based counterflow wet electrostatic precipitator for collection of fine and ultrafine particles

Wet electrostatic precipitators (WESP) have been widely studied for collecting fine and ultrafine particles, such as diesel particulate matter (DPM), which have deleterious effects on human health. Here, we report an experimental and numerical simulation study on a novel string-based two-stage WESP. Our new design incorporates grounded vertically aligned polymer strings, along which thin films of water flow down. The water beads, generated by intrinsic flow instability, travel down the strings and collect charged particles in the counterflowing gas stream. We performed experiments using two different geometric configurations of WESP: rectangular and cylindrical. We examined the effects of the WESP electrode bias voltage, air stream velocity, and water flow rate on the number-based fractional collection efficiency for particles of diameters ranging from 10 nm to 2.5 μm. The collection efficiency improves with increasing bias voltages or decreasing airflow rates. At liquid-to-gas (L/G) as low as approximately 0.0066, our design delivers a collection efficiency over 70% even for fine and ultrafine particles. The rectangular and cylindrical configurations exhibit similar collection efficiencies under nominally identical experimental conditions. We also compare the water-to-air mass flow rate ratio, air flow rate per unit collector volume, and collection efficiency of our string-based design with those of previously reported WESPs. The present work demonstrates a promising design for a highly efficient, compact, and scalable two-stage WESPs with minimal water consumption.Implications: Wet Electrostatic Precipitators (WESPs) are highly effective for collecting fine particles in exhaust air streams from various sources such as diesel engines, power plants, and oil refineries. However, their large-scale adoption has been limited by high water usage and reduced collection efficiencies for ultrafine particles. We perform experimental and numerical investigation to characterize the collection efficiency and water flow rate-dependence of a new design of WESP. The string-based counterflow WESP reported in this study offers number-based collection efficiencies >70% at air flow rates per collector volume as high as 4.36 (m3/s)/m3 for particles of diameters ranging from 10 nm - 2.5 μm, while significantly reducing water usage. Our work provides a basis for the design of more compact and water-efficient WESPs.
Pharmacological suppression of the WNT signaling pathway attenuates age-dependent expression of the phenotype in a mouse model of arrhythmogenic cardiomyopathy

Introduction Arrhythmogenic cardiomyopathy (ACM) is a genetic disease of the myocardium, characterized by cardiac arrhythmias, dysfunction, and sudden cardiac death. The pathological hallmark of ACM is fibro-adipocytes replacing cardiac myocytes. The canonical WNT pathway is implicated in the pathogenesis of ACM. Aim The study aimed to determine the effects of the suppression of the WNT pathway on cardiac phenotype in a mouse model of ACM. Methods and results One copy of the Dsp gene, a known cause of ACM in humans, was deleted specifically in cardiac myocytes (Myh6-Cre-Dsp W/F). Three-month-old wild type and Myh6-Cre-Dsp W/F mice, without a discernible phenotype, were randomized to either untreated or daily administration of a vehicle (placebo), or WNT974, the latter an established inhibitor of the WNT pathway, for three months. The Myh6-Cre-Dsp W/F mice in the untreated or placebo-treated groups exhibited cardiac dilatation and dysfunction, increased myocardial fibrosis, and apoptosis upon completion of the study, which was verified by complementary methods. Daily administration of WNT974 prevented and/or attenuated evolving cardiac dilatation and dysfunction, normalized myocardial fibrosis, and reduced apoptosis, compared to the untreated or placebo-treated groups. However, administration of WNT974 increased the number of adipocytes only in the Myh6-Cre-Dsp W/F hearts. There were no differences in the incidence of cardiac arrhythmias and survival rates. Conclusion Suppression of the WNT pathway imparts salutary phenotypic effects by preventing or attenuating age-dependent expression of cardiac dilatation and dysfunction, myocardial fibrosis, and apoptosis in a mouse model of ACM. The findings set the stage for large-scale studies and studies in larger animal models to test the beneficial effects of the suppression of the WNT pathway in ACM. One sentence summary Suppression of the WNT signaling pathway has beneficial effects on cardiac dysfunction, myocardial apoptosis, and fibrosis in a mouse model of arrhythmogenic cardiomyopathy.
Genetic Signatures From RNA Sequencing of Pediatric Localized Scleroderma Skin

The purpose of this study was to explore the skin transcriptional profile in pediatric localized scleroderma (LS) to provide a better understanding of the altered immune and fibrotic pathways promoting disease. LS is a progressive disease of the skin and underlying tissue that causes significant functional disability and disfigurement, especially in developing children. RNA sequencing (RNAseq) technology allows for improved understanding of relevant cellular expression through transcriptome analysis of phases during LS disease progression (more active/inflammatory vs. inactive/fibrotic) and also permits the use of RNA extracted from existing paraffin-embedded skin tissue, which is important in pediatrics. A strong correlation was observed between the comparison of genes expressed between fresh (RNAlater) and paraffinized skin in healthy and LS subjects, supporting the use of paraffinized tissue. LS gene signatures compared to healthy controls showed a distinct expression of an inflammatory response gene signature (IRGS) composed of IFNγ-, IFNα-, and TNFα-associated genes. GSEA© enrichment analysis showed that the IRGS, including interferon-inducible chemokines such as CXCL9, CXCL10, CXCL11, and IFNγ itself, was more highly expressed in LS patients with more inflammatory lesions. The use of paraffinized skin for sequencing was proven to be an effective substitute for fresh skin by comparing gene expression profiles. The prevalence of the IFNγ signature in the lesion biopsies of active LS patients indicates that these genes reflect clinical activity parameters and may be the promoters of early, inflammatory disease.
Middle turbinate concha bullosa osteoma: A comprehensive review of all reported cases

Abstract Introduction Osteomas are benign, slow growing tumours of bone. Recently, a number of reports have emerged describing osteomas within concha bullosa of the middle turbinate (MT) as rhinogenic sources of headache. Objective Our objective was to summarize literature on presentation of osteomas within MT concha bullosa in order to inform management. Methods All reports with osteoma located within the MT concha bullosa on imaging were included in the review of English literature through September 2020. Results Eight documented cases of osteomas localized within MT concha bullosa were identified through the review along with our Case presentation. The majority of patients were female with a mean age of 43.0. Median size was 19.9 mm at presentation. In previous reports, headaches led to the discovery of the concha bullosa osteoma. However, our patient presented with ipsilateral nasal obstruction. If patients consented to surgery, all osteomas were approached endoscopically leading to resolution of presenting symptoms. Conclusion Our Case report adds to the current literature by demonstrating that concha bullosa osteomas can present in absence of headaches. Location within concha bullosa presents an opportunity for endoscopic resection. The size of the osteoma guided MT preservation.
How Do Programs Measure Resident Performance? A Multi-Institutional Inventory of General Surgery Assessments.

OBJECTIVE To perform an inventory of assessment tools in use at surgical residency programs and their alignment with the Milestone Competencies. DESIGN We conducted an inventory of all assessment tools from a sample of general surgery training programs participating in a multi-center study of resident operative development in the United States. Each instrument was categorized using a data extraction tool designed to identify criteria for effective assessment in competency based education and according to which Milestone Competency was being evaluated. Tabulations of each category were then analyzed using descriptive statistics. Interviews with program directors and assessment coordinators were conducted to understand each instrument's intended use within each program. SETTING Multi-institutional review of general surgery assessment programs. PARTICIPANTS We identified assessment tools used by 10 general surgery programs during the 2019 to 2020 academic year. Programs were selected from a cohort already participating in a separate research study of resident operative development in the United States. RESULTS We identified 42 unique assessment tools used. Each program used an average of 7.2 (range 4-13) unique assessment instruments to measure performance, of which only 5 (11.9%) were used by at least 1 other program in our sample. Of all assessments, 59.5% were used monthly or less frequently. The majority (66.7%) of instruments were retrospective global assessments, rather than discrete observed performances. There were 4 (9.5%) instruments with established reliability or validity evidence. Across programs there was also significant variation in the volume of assessment used to evaluate residents, with the median total number of evaluations/trainee across all Milestone Competencies being 217 (IQR 78) per year. Patient care was the most frequently evaluated Milestone Competency. CONCLUSIONS General surgical assessment systems predominantly employ non-standardized global assessment tools that lack reliability or validity evidence. This variability makes it challenging to interpret and compare competency standards across programs. A standardized assessment toolkit with established reliability and validity evidence would allow training programs to measure the competence of their trainees more uniformly and understand where improvements in our training system can be made.
Proton magnetic resonance study of lysine-binding to the kringle 4 domain of human plasminogen. The structure of the binding site.

Abstract The binding of l -Lys, d -Lys and e-aminocaproic acid (eACA) to the kringle 4 domain of human plasminogen has been investigated via one and two-dimensional 1H-nuclear magnetic resonance spectroscopy at 300 and 600 MHz. Ligand-kringle association constants (Ka) were determined assuming single site binding. At 295 K, pH∗ 7.2, d -Lys binds to kringle 4 much more weakly (Ka = 1.2m m −1) than does l -Lys (Ka = 24.4 m m −1). l -Lys binding to kringle 4 causes the appearance of ring current-shifted high-field resonances within the −1 ≲ δ ≲ 0 parts per million range. The ligand origin of these signals has been confirmed by examining the spectra of kringle 4 titrated with deuterated l -Lys. A systematic analysis of ligand-induced shifts on the aromatic resonances of kringle 4 has been carried out on the basis of 300 MHz two-dimensional chemical shift correlated (COSY) and double quantum correlated spectroscopies. Significant differences in the effect of l -Lys and d -Lys binding to kringle 4 have been observed in the aromatic COSY spectrum. In particular, the His31 H4 and Trp72 H2 singlets and the Phe64 multiplets appear to be the most sensitive to the particular enantiomers, indicating that these residues are in proximity to the ligand Cα center. In contrast, the rest of the indole spectrum of Trp72 and the aromatic resonances of Trp62 and Tyr74, which are affected by ligand presence, are insensitive to the optical nature of the ligand isomer. These results, together with two-dimensional proton Overhauser studies and ligand-kringle saturation transfer experiments reported previously, enabled us to generate a model of the kringle 4 ligand-binding site from the crystallographic co-ordinates of the prothrombin kringle 1. The latter, although lacking recognizable lysine-binding capability, is otherwise structurally homologous to the plasminogen kringles.