cssi/SciSciGPT-SciSciNet huggingface dataset:
Clinical implications of basic research in hepatocellular carcinoma

A 58-year old Caucasian female has compensated hepatitis C related cirrhosis. Her surveillance ultrasound showed hypodense liver nodules and subsequent triple phase CT scan showed five tumor nodules with diameters ranging from 3-5cms involving both hepatic lobes. The nodules showed characteristic radiologic findings on the CT scan and she was diagnosed with hepatocellular carcinoma (HCC) based on non-invasive criteria. There was also associated right portal vein tumor thrombosis. Her functional capacity at diagnosis was slightly limited, but she was capable of performing all activities of daily living and self-care. Her laboratory tests at diagnosis were as follows: sodium 129mmol/L, potassium 3.6mmol/L, blood urea nitrogen 22mg/dL, creatinine 1.0mg/dL, albumin 2.9g/dl, bilirubin 1.8mg/dl, alanine aminotransferase 87U/L, aspartate aminotransferase 68U/L, alkaline phosphatase 139U/L, white blood cell 3.5x10(9)/L, hemoglobin 10.4, platelet count 73x10(9)/L, international normalized ratio 1.9 and alpha-fetoprotein 5200ng/ml. An upper endoscopy was negative for esophageal or gastric varices. Based on the tumor burden, presence of macrovascular invasion, ECOG performance status of 1 and Child-Pugh class A she was classified to have BCLC stage C HCC. She was started on sorafenib therapy at 400mg oral twice daily but unfortunately this had to be discontinued since she experienced severe diarrhea and skin rash. She now returns for follow-up and requests information on the available therapeutic options. This particular case scenario is not uncommon and does raise several clinically relevant questions: This review provides a comprehensive overview of the current state of HCC management and also examines the clinical implications of recent basic research in HCC.
Congenital absence of the vagina

Abstract Of 175 patients with congenital absence of the vagina treated at the Mayo Clinic from 1920 through June, 1966, 156 were followed from 1 to 37 years. In 123 patients undergoing primary construction of the vagina with a split-thickness skin graft (McIndoe operation), there were 7 major complications but no deaths. Ten patients required a second reconstruction of the vaginal canal. Of 113 traced patients, 24 had some vaginal contraction and 24 had stenosis (total of 42 percent). Yet of 93 reporting on sexual function, 84 (90 per cent ) said function was good. Of 100 patients followed 10 or more years, 71 had skin graft operation and 36 had some contracture or stenosis, but 56 of 60 (93 percent ) said sexual function was good. A vaginal mold was necessary for an average of about 2 years. In only 2 of 24 divorces among 156 traced patients was the surgical result a divorce factor, and 5 divorcees remarried. Bowel transplants also seemed to function well as an artificial vagina and the patient report satisfactory sexual function.
For Better or Worse? Change in Service Use by Children Investigated by Child Welfare Over a Decade.

Abstract Background Children, particularly minority children, referred to child welfare because of suspected maltreatment are vulnerable and need many services. We sought to assess whether service use has improved over the past decade and whether racial-ethnic disparities in service use have decreased. Methods We used 2 national data sets (the National Survey of Child and Adolescent Well-Being [NSCAW] I and II) collected a decade apart to assess changes over time in health, education, mental health (MH), and dental services and overall service use. Results In NSCAW II more children were young, had lower Child Behavior Checklist (CBCL) scores, and were Hispanic. We found significant increases in dental services, a decrease in special education services, and a decrease in MH services on the bivariate level (all P Conclusions These data showed no change in MH services over time for children referred for child welfare evaluation, but improvement in dental services was noted. Racial and ethnic disparities persist. Decrease in MH services occurred predominantly among children whose MH symptoms were below the clinical range.
Can VEBAs Alleviate Retiree Health Care Problems

The 2007 negotiations between the United Auto Workers (UAW) and Detroit automakers have focused national attention on a potentially innovative response to the long-term decline in retiree health insurance in the United States. The union agreed that an independent trust called a Voluntary Employees' Beneficiary Association (VEBA) will assume responsibility for UAW retiree medical care at the three automakers. Other unionized employers now are looking at these so-called defeasance VEBAs as a way to free themselves of burdensome health-care legacy costs. An analysis of the largest one, at GM, suggests that the concept is a second-best option for unions able to retain employer-paid retiree coverage. However, it may be a viable alternative for those unable to fend off unilateral elimination by an employer. Both private- and public-sector unions and employers can draw important lessons from the defeasance VEBA agreed to by the UAW and GM, which will deploy innovative tactics to distribute cost and risk amongst the company, workers, and retirees. More broadly, the new VEBAs illuminate a gaping hole in the federal tax code, which offers few incentives for employees to save for postemployment medical needs even as employers have shifted the responsibility on them to do so. A VEBA is a flexible vehicle that could provide the most tax-efficient savings method for workers whose employer doesn't offer retiree coverage. However, changes in federal law likely would be required for the concept to become widespread.
Metachronous T-Lymphoblastic Lymphoma and Burkitt Lymphoma in a Child With Constitutional Mismatch Repair Deficiency Syndrome.

Constitutional mismatch repair deficiency (CMMRD) is a cancer predisposition syndrome associated with a high risk of developing early-onset malignancies of the blood, brain, and intestinal tract. We present the case of a patient with T-lymphoblastic lymphoma at the age of 3 years, followed by Burkitt lymphoma 10 years later. This patient also exhibited numerous nonmalignant findings including cafe au lait spots, lipomas, bilateral renal nodules, a nonossifying fibroma, multiple colonic adenomas, and a rapidly enlarging pilomatrixoma. The spectrum of malignant and nonmalignant neoplasms in this patient highlights the remarkable diversity, and early onset, of lesions seen in children with CMMRD.
What Is, and What Is Not, A Capitalist Empire

ABSTRACTThis study argues that a historical materialist theory of what a capitalist empire is has yet to be fully articulated. It proceeds to lay out such a theory. The paper outlines a theory of capitalist empire situated in relation to a historical materialist conceptualization of how capitalism operates. In this I distinguish state and imperialism as aspects of capitalist empires, but empire itself as something related to, but larger than these historical processes. I also locate capitalist empires in relation to the logic of capitalism and its crises tendencies, and the way the logic of capital plays out over uneven development and the exploitation of a variety of labor forms. Additionally, the paper examines the racialized, gendered, and ecological aspects of capitalist empires in an attempt to begin to explain the political economy of capitalist empires as total social wholes.
Complementary levels of description in applied mathematics-III

Models of city equilibrium and growth developed by Amson in an urban studies context are summarized, and used to illustrate the philosophy and methodology of mathematical modelling, by identifying procedures and levels of description which are inherent in such models.
Auto-adjusting positive airway pressure treatment for sleep apnea diagnosed by home sleep testing.

Study Objectives:Compare auto-adjusting positive airway pressure (APAP) treatment with positive airway pressure (PAP) titration by polysomnography (PSG) followed by CPAP treatment in patients diagn...
Analysis of the epidemiological characteristics of 61 cases of severe hand-foot-mouth disease in Shenzhen

Objective To investigate the epidemiological characteristics and clinical features of hand-foot-mouth disease(HFMD) of Shenzhen.Method Epidemiological investigation was carried out on 61 cases of severe HFMD of Shenzhen in 2010 by collecting information and case survey.Results May was the epidemical season for HFMD.In 61 HFMD patients,the proportion of male and female was 1.77:1,and 80.33% of the cases were diagnosed before the age of 3 years old.The clinical manifestation was mainly fever,rash,vomiting and sleepiness.88.10% was caused by EV71.The interval from first symptom to diagnosis was 1.98 days.Conclusion HFMD of Shenzhen is a seasonal disease,and it always transmit in scattered living children under age 3.High risk groups should undergo intensive intervention in epidemic seasons.
Lysosomal sulphate transport is dependent upon sulphydryl groups

Using thiol blocking agents, we examined the role of sulphydryl groups for function of the lysosomal sulphate transport system. Monothiol binding reagents, p-hydroxymercuribenzoic acid (p-HMB) and p-chloromercuribenzene sulphonic acid (p-CMBS), dithiol binding reagents such as CuCl2, the alkylating agent, N-ethylmaleimide (NEM), and NADH all inhibited lysosomal sulphate transport. The inhibitory effects of NEM and Cu2+ were not additive, suggesting that they both act upon the same critical sulphydryl group(s). Unlike the case for NEM, the inhibitory effects of Cu2+ were reversed by the reducing agent, dithiothreitol. Exposure to NEM resulted in a seven-fold increase in Km to 867 microM versus a control value of 126 microM and a modest decrease in Vmax to 99 pmolperunit beta-hexosaminidase per 30 s versus a control value of 129 pmolperunit beta-hexosaminidase per 30 s. Similar although somewhat less dramatic results were obtained using Cu2+ with an increase of Km to 448 microM and a Vmax of 77 pmolperunit beta-hexosaminidase per 30 s. The sulphate transport activity of detergent solubilized lysosomal membranes could be bound to a p-chloromercuribenzoic acid (p-CMB)-Sepharose sulphydryl affinity resin and eluted with mercaptoethanol. Sulphydryl groups thus appear to play a role in sulphate transport through effects on substrate affinity. Sulphydryl-binding appears to be a strategy that may be useful for purification of the transporter.
A Randomized Controlled Trial of Patient-Controlled Valve Catheter and Indwelling Foley Catheter for Short-term Bladder Drainage.

OBJECTIVE The purpose of this study was to compare catheter-related pain and quality-of-life scores between 2 catheters used after failed voiding trials following urogynecologic surgery. METHODS Women failing an inpatient voiding trial requiring short-term catheterization after urogynecologic surgery were randomized to receive either a standard FC or a patient-controlled VC. Subjects completed a 6-item, visual analog scale-based postoperative questionnaire (POQ) and an outpatient voiding trial 3 to 7 days after surgery. Baseline demographic, surgical data, and results of the outpatient voiding trial were recorded. The primary outcome was the difference in mean score for catheter-related pain on the POQ, based on intent to treat. Secondary outcomes included between-group differences in means for individual POQ items and a calculated composite satisfaction score. The statistician was blinded to group assignment. RESULTS Forty-nine subjects were randomized to FC (n = 24) and VC (n = 25). Two subjects, one in each group, were excluded from the primary analysis because of missing data. Mean age was 60.6 (SD, 12.5) years. Baseline characteristics were similar. Valve catheter users had a lower median catheter-related pain score (1.25 vs 2.3), but not significantly (P = 0.153). Valve catheter users had significantly lower median scores for frustration (1.2 vs 3.8; P = 0.018) and limitation on social activities (0 vs 7.6; P < 0.001). Mean composite satisfaction score was statistically significantly lower for the VC group (2.23 [SD, 1.83] vs 3.62 [SD, 1.95]; P < 0.01), suggesting greater satisfaction. CONCLUSIONS Valve catheter and FC users report similar catheter-related pain. Valve catheter users scored better in overall satisfaction, frustration, and limitations on social activities.
Human Sexuality: Confluent Teaching Methods

AbstractThis paper is a description of a teaching methodology for persons who are involved in sex education. The teaching style combines an experiential group process approach with a didactic theme approach The various stages of group development are intertwined with the topic of human sexuality. The method is useful for psychologists, teachers, counselors and mental health workers who have a background in group dynamics and sex education.
Neighbours in Borysław. Jewish Perceptions of Collaboration and Rescue in Eastern Galicia

The present chapter offers a close reading of several Jewish testimonies given in the aftermath of the Holocaust. These testimonies come from survivors’ early attempts to document their experiences during World War II, from Jewish testimonies given in Polish courts, and from accounts written and recorded several decades later. While distinct times, contexts and languages in which these documents were produced have methodological implications for interpreting them, this chapter does not differentiate between diaries, memoirs, court statements and testimonies. The chapter examines what elsewhere I have called ‘intimate violence’ and does so in the local setting of a single community. I analyse the ways in which the survivors tackled the questions of local collaboration and local assistance and tried to make sense of their strained encounters with people they had known before the war. Not only do the testimonies undermine clear-cut categorizations of ‘victims’ and ‘perpetrators’, they also render ‘bystanders’ virtually non-existent. Last but not least, I address the question of individual and communal memory: how did people look back at a time of extreme crisis that broke a tenuous coexistence among a mixed population and turned former neighbours against one another?
Regulation of Chemerin Bioactivity by Plasma Carboxypeptidase N, Carboxypeptidase B (TAFIa) and Platelets.

Chemerin is a potent chemoattractant for cells that express the serpentine receptor CMKLR1 (chemokine-like receptor 1), such as plasmacytoid dendritic cells and tissue macrophages. Chemerin circulates in the blood in a relatively inactive form (prochemerin). Its chemotactic activity is unleashed following proteolytic cleavage of carboxyl-terminal amino acids by serine proteases including plasmin, factor XIIa and VIIa. Recruitment of plasmacytoid dendritic cells and macrophages by chemerin may play a role in local tissue immune and inflammatory responses. The shortest bioactive chemerin peptide NH2-YFPGQFAFS-COOH (9mer) is present in the carboxyl-terminal domain. In this work, we show that plasma carboxypeptidase N (CPN) and B (CPB or activated thrombin-activatable fibrinolysis inhibitor (TAFIa)) (30 nM) remove the C-terminal lysine (K) from YFPGQFAFSK (10mer) (200nM) and enhance the migration of CMKLR1-transfected cells by ∼16-fold. To investigate if sequential proteolysis by plasmin and carboxypeptidases can modulate the activity of chemerin peptides, we generated the carboxyl-terminal 15mer of prochemerin, NH2-YFPGQFAFSKALPRS-COOH. Plasmin cleavage (1 μM) generated a 10mer, which was further processed to 9mer by CPN or CPB (30 nM) cleavage. These sequential cleavages were paralleled by corresponding increases in chemotactic activity. At concentrations as high as 1 μM the 15 mer did not induce chemotaxis; after plasmin cleavage and conversion to 10mer, however, significant chemotactic activity was demonstrated. Treatment with CPN or CPB further enhanced this chemotactic activity. We observed a similar enhancement in bioactivity following sequential plasmin/CPN-or-CPB cleavage of full-length prochemerin. Endogenous plasma CPN supports the activation (∼2.5 fold increase in bioactivity) of plasmin-cleaved prochemerin (0.2 nM). This activation was blocked by incubating plasma with MGTA (DL-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid), a specific CPN inhibitor. In addition, we show that platelets are a rich source of chemerin (20–30 ng of chemerin/5x10 8 platelets). Chemerin released from activated platelets triggers CMKLR1-transfectant chemotaxis, which was blocked by anti-chemerin antibodies. Thus, the circulating humoral factors reported here (platelets, serine proteases, and carboxypeptidases) may contribute to the regulation of chemerin bioactivity in vivo and therefore play a critical role in CMKLR1-mediated immune responses.
Prevalence of psychiatric disorders in a southern Baffin Island Eskimo settlement.

The only evidence we have that mental disorders occurred in the Eskimo population prior to Euro-Canadian contact is the reports by the early explorers of the “pibloktoq” syndrome and the reminiscen...
The Contribution Of Ultrahigh Vacuum Science To Catalysis

Ultrahigh vacuum surface analysis techniques are used to study the steps in catalytic reactions one at a time on well characterized, single crystal surfaces. As well, the residues left after high pressure reactions can be analysed. In some cases, the reaction rates are very similar on low area crystals and on highly dispersed, supported catalysts. These techniques lead to a better understanding of catalytic processes.
Combining sparse coding and time-domain features for heart sound classification

Objective: This paper builds upon work submitted as part of the 2016 PhysioNet/CinC Challenge, which used sparse coding as a feature extraction tool on audio PCG data for heart sound classification. Approach: In sparse coding, preprocessed data is decomposed into a dictionary matrix and a sparse coefficient matrix. The dictionary matrix represents statistically important features of the audio segments. The sparse coefficient matrix is a mapping that represents which features are used by each segment. Working in the sparse domain, we train support vector machines (SVMs) for each audio segment (S1, systole, S2, diastole) and the full cardiac cycle. We train a sixth SVM to combine the results from the preliminary SVMs into a single binary label for the entire PCG recording. In addition to classifying heart sounds using sparse coding, this paper presents two novel modifications. The first uses a matrix norm in the dictionary update step of sparse coding to encourage the dictionary to learn discriminating features from the abnormal heart recordings. The second combines the sparse coding features with time-domain features in the final SVM stage. Main results: The original algorithm submitted to the challenge achieved a cross-validated mean accuracy (MAcc) score of 0.8652 (Se = 0.8669 and Sp = 0.8634). After incorporating the modifications new to this paper, we report an improved cross-validated MAcc of 0.8926 (Se = 0.9007 and Sp = 0.8845). Significance: Our results show that sparse coding is an effective way to define spectral features of the cardiac cycle and its sub-cycles for the purpose of classification. In addition, we demonstrate that sparse coding can be combined with additional feature extraction methods to improve classification accuracy.
Synthetic microbial consortia enable rapid assembly of pure translation machinery

Assembly of recombinant multiprotein systems requires multiple culturing and purification steps that scale linearly with the number of constituent proteins. This problem is particularly pronounced in the preparation of the 34 proteins involved in transcription and translation systems, which are fundamental biochemistry tools for reconstitution of cellular pathways ex vivo. Here, we engineer synthetic microbial consortia consisting of between 15 and 34 Escherichia coli strains to assemble the 34 proteins in a single culturing, lysis, and purification procedure. The expression of these proteins is controlled by synthetic genetic modules to produce the proteins at the correct ratios. We show that the pure multiprotein system is functional and reproducible, and has low protein contaminants. We also demonstrate its application in the screening of synthetic promoters and protease inhibitors. Our work establishes a novel strategy for producing pure translation machinery, which may be extended to the production of other multiprotein systems.
Enlisting friends to reduce sexual victimization risk: there's an app for that… but nobody uses it

OBJECTIVE The Circle of Six (Co6) phone application (app), winner of the White House's Apps Against Abuse Challenge, seeks to incorporate friends into sexual victimization risk reduction. Despite its growing presence on college campuses, the feasibility/acceptability of the app to college women is unknown. This mixed methods study sought to fill this gap. PARTICIPANTS College women (n = 44) participated in summer/fall 2015. METHODS Participants completed questionnaires, used the Co6 app for 2 months, and returned to report their experiences. RESULTS Consistent with the app's aim, women reported greater intentions to help friends versus strangers in sexually aggressive situations. However, app use was low over follow-up. Reasons women gave for not using the app included redundancy with existing smart phone features and discomfort with group messaging. Some saw the app as an emergency only resource. CONCLUSIONS The Co6 app may not meet the real world needs of college women.
Taking Stock of Federalism in the United States

Federalism is not the least of interests shared by Canada and the United States. The elements of likeness and unlikeness exist in a balance that makes comparison profitable, although such comparison is allowed to remain implicit in the following survey of trends in the United States. To discuss in Canada the federalism of another country, of course, is to carry to Newcastle the ashes of its own coals, so greatly are all federal systems in debt to the monumental inquiry of the Royal Commission on Dominion-Provincial Relations. No similar focus yet enlightens the analysis of federal problems in the United States. The temper of the United States is incorrigibly one of contrivance. The brevity of the constitution leaves it essentially unwritten. Of the obstacles of the formal amending process, of course, it can no longer quite be said, as Frank J. Goodnow put the matter in 1911, that “the constitution of the United States is, on account of the complicated procedure and the large majorities required, very difficult, if not impossible, of amendment under ordinary conditions.” After forty-three years without an amendment, six have been ratified since 1913. But the habit of relying on adjustment by interpretation is deep. The Supreme Court controversy in 1937 would have found the country at a loss to suggest just how it would amend the Constitution if the discussion as a practical matter had taken that turn. Students of government are sometimes irked by the atmosphere that takes for granted the necessity of advance by accommodation; mostly, however, their lives are spent on detailed inquiries that merely deepen the assumption. In recent years the impact of events abroad has challenged them to identify and to reaffirm the fundamentals of popular government. But the effect of these events has been to throw the United States back upon its constitutional tradition. The mood will last, it is admitted, only so long as there is movement and vigour. Never has the constitutional system of the United States been more fluent. Paradoxically, this condition encourages the survival of the old reliance on piecemeal adaptation.
Cannibalism of Egg and Neonate Larvae by Late Stage Conspecifics of Anopheles gambiae (Diptera: Culicidae): Implications for Ovipositional Studies

Laboratory experiments intended to test the effects of a purported ovipositional deterrent pheromone of Anopheles gambiae Giles sensu stricto (Diptera: Culicidae) led instead to the finding that egg cannibalism by fourth-instar larvae explained the 'deterrent effect' rather than chemical signals from larvae. Virtually no eggs were counted from cups containing fourth-instar larvae, after oviposition. Numbers of eggs from cups containing younger, conspecific larvae, or pupae did not differ significantly from water only control. Video recording of larval behavior revealed that fourth-instar larvae consumed entire eggs in one continuous ingestive bout. Egg output in the presence of fourth-instar larvae with their mouthparts sealed was similar to the larvae-absent treatment, but nearly 100-fold greater than that counted in the presence of fourth-instar larvae that could eat freely. Thus, the huge egg reduction in eggs counted in the presence of fourth-instar larvae was due to egg cannibalism, not because presence of these larvae deterred oviposition as has been reported in previous studies. Third and especially fourth-instar larvae also cannibalized newly hatched first-instar larvae. Artificial food availability did not eliminate but did reduce cannibalism during first several hours of exposure. The rate at which fourth-instar larvae consumed conspecifics rose significantly and linearly with prey density, generating a non-plateauing, type I functional response curve. These results clearly show that care must be taken such that mosquito ovipositional experiments are not confounded by presence of cannibalizing larvae.
Commentary: Simulation-Aided Inference in Cosmology

Higdon’s use of Gaussian Process (GP) emulation to analyze SDSS data using simulated power spectra from N-body simulations supplies a textbook case study of a set of techniques that are likely to become a standard part of the astrostatistics toolbox. The problems addressed by these techniques models based on expensive computer simulations that run on high-performance computing (HPC) platforms, which can only sparsely sample a large-dimensional input parameter space are likely to be of interest to a growing community of computational astrophysicists wishing to compare models to data, as this style of computing becomes “democratized” by the increasing availability of HPC platforms in University research settings. We comment here on the computational challenges of Gaussian Process modeling, the fidelity of model hierarchies, and strategies for the adaptive design of numerical experiments.
The Knowers in Charge

Epistemic Authority: A Theory of Trust, Authority, and Autonomy in Belief. By Linda Trinkaus Zagzebski. New York: Oxford University Press, 2012. Pp. xiii +279. ISBN 978–0–19–993647–2.
Development of a Medical Education Journal Club

Journal clubs offers a chance for professionals to keep up to date and engage in evidence-based medical education through a critical appraisal of literature offerings. After an attempt at monthly meetings in the New York area, the journal club moved on-line. Connected through a listserv, participants discuss the designated articles via e-mail. This provides the opportunity for national and even international collaboration and permits a flexible schedule for participation. However, it also requires overcoming some of the hurdles presented by asynchronous distance communications (e.g., response lags). The need for motivation and time to read can be a major obstacle in either format.
The effect of baseline complex ovarian cysts on in vitro fertilization outcome

Study Objective To determine the effect of baseline complex ovarian cysts on controlled ovarian hyperstimulation and in vitro fertilization (IVF) outcome. Design Retrospective analysis with stratification by stimulation regimen and the presence or absence of surgically documented endometriosis. Patients Two hundred sixty-one women undergoing IVF from May 1, 1989 to December 31, 1990. Main Outcome Measures The outcome measures assessed were the maximum estradiol (E 2 ) concentrations on day of human chorionic gonadotropin (hCG) administration, number of follicles with maximum diameter ≥15mm, number of follicles with maximum diameter ≥12mm, number of days to hCG administration, number of ampules of human menopausal gonadotropin (hMG) used, number of oocytes retrieved and fertilized, number of embryos transferred, and pregnancy and cycle cancellation rates. Results There were no statistical differences between cyst and noncyst groups in any of the above parameters of IVF performance. In a single subgroup, patients with endometriosis stimulated with hMG and patients with cysts had significantly lower E 2 concentrations than patients without cysts. Conclusion The presence of a complex cyst on a baseline ultrasound does not appear to adversely affect IVF cycle outcomes.
Integration of Drosophila and Human Genetics to Understand Notch Signaling Related Diseases

Notch signaling research dates back to more than one hundred years, beginning with the identification of the Notch mutant in the fruit fly Drosophila melanogaster. Since then, research on Notch and related genes in flies has laid the foundation of what we now know as the Notch signaling pathway. In the 1990s, basic biological and biochemical studies of Notch signaling components in mammalian systems, as well as identification of rare mutations in Notch signaling pathway genes in human patients with rare Mendelian diseases or cancer, increased the significance of this pathway in human biology and medicine. In the 21st century, Drosophila and other genetic model organisms continue to play a leading role in understanding basic Notch biology. Furthermore, these model organisms can be used in a translational manner to study underlying mechanisms of Notch-related human diseases and to investigate the function of novel disease associated genes and variants. In this chapter, we first briefly review the major contributions of Drosophila to Notch signaling research, discussing the similarities and differences between the fly and human pathways. Next, we introduce several biological contexts in Drosophila in which Notch signaling has been extensively characterized. Finally, we discuss a number of genetic diseases caused by mutations in genes in the Notch signaling pathway in humans and we expand on how Drosophila can be used to study rare genetic variants associated with these and novel disorders. By combining modern genomics and state-of-the art technologies, Drosophila research is continuing to reveal exciting biology that sheds light onto mechanisms of disease.
Abstract B36: A biomarker-guided approach to combining PARP inhibitors with radiotherapy in pediatric sarcomas

Background: Ewing sarcoma (EWS) expresses high levels of Schlafen-11 (SLFN11). SLFN11 disrupts checkpoint maintenance and may serve as a biomarker to assess sensitivity to Poly (ADP-ribose) polymerase 1 and 2 inhibitors (PARPi). The goal of this study is to evaluate SLFN11 protein expression in a panel of pediatric solid tumors and correlate levels of protein with sensitivity to PARP inhibition combined with ionizing radiation (IR), a component of therapy for many pediatric sarcomas and a potent inducer of DNA damage. Methods: SLFN11 mRNA and protein levels were assessed by quantitative RT-PCR, and immunohistochemistry, Western blot, and immunofluorescence microscopy, respectively. PARPi included talazoparib (TAL), niraparib (NIR), veliparib (VEL), and olaparib (OLA). Approximately 30 minutes after addition of systemic therapy, graded doses of radiation were delivered and viability across a panel of pediatric solid tumor cell lines was measured using the ATP-based Cell TiterGlo assay and confirmed with the colony formation assay. Results: We found that SLFN11 mRNA and protein is expressed at high levels in EWS, and SLFN11 is also variably present in a subset of other pediatric sarcomas, including desmoplastic small round cell tumor, osteosarcoma, and rhabdomyosarcoma. In all tumor cells with detectable SLFN11 expression, viability was reduced by greater than 90% when exposed to 2 Gy IR and 1-10 nM TAL, whereas cells with undetectable levels of SLFN11 were 5-10 times less sensitive. Intriguingly, variation in the potentiation between specific PARPi and IR correlated with the ability to form drug-induced PARP-DNA adducts, with the strong PARP trapper TAL showing ~10-fold higher potency compared to the moderate trapper NIR, and ~300-fold more potency relative to the weak trapper VEL. Consistent with our PARPi findings, the toposiomerase 1 inhibitor irinotecan, which also forms DNA adducts, potentiated with IR similarly to TAL at concentrations Conclusion: SLFN11 is present in select pediatric sarcomas and may induce a DNA repair defect that is best exploited by combining low doses of TAL and irinotecan with IR. Citation Format: Anang A. Shelat, Christopher L. Tinkle, Elizabeth Stewart, Sara Michele Federico, Brandon Bianski, Marcia Mellado-Lagarde. A biomarker-guided approach to combining PARP inhibitors with radiotherapy in pediatric sarcomas [abstract]. In: Proceedings of the AACR Conference on Advances in Sarcomas: From Basic Science to Clinical Translation; May 16-19, 2017; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(2_Suppl):Abstract nr B36.
An Analysis of Cabin Ozone Regulations

Exposure to elevated levels of ozone have been reported to be associated with complaints of discomfort such as dry mouth, eye irritation and dryness, nasal irritation coughing, and headaches. The Federal Aviation Administration (FAA) established regulatory requirements in 1980 to limit cabin ozone levels to no more than 0.25 parts per million (ppm) at any time or 0.1 ppm averaged over a 3-hour interval for any flight over four hours in length. The FAA also published an Advisory Circular (AC), AC 120-38, to provide guidance to air carriers on how to comply with these then new ozone regulations. Methods of compliance include the use of catalytic converters, or ozone filters, designed to remove ozone, utilizing statistical methods to prove that ozone concentrations will not exceed limits for the carrier’s route structure and flight planning to avoid areas of reported high concentrations of ozone. The calculations used to determine cabin ozone concentration from manufacturer’s filter efficiency data and ozone levels are to be based on published ozonesonde data found in the AC 120-38 or an equivalent data set. Unfortunately, the published ozonesonde data in the AC 120-38 are outdated and the AC does not point to any other data source that is acceptable to the FAA to conduct the required statistical analysis. In addition, once compliance is shown, no follow-up measurements are required to ensure that ozone levels remain below these required levels. Actual ozone concentrations have been measured in the aircraft by several researchers that exceed these regulatory levels. Finally, FAA ozone regulations and AC 120-38 do not address cumulative effects of ozone exposure to crewmembers over multiple flights and do not offer any protection against ozone exposure for crewmembers on non-passenger carrying flights. A revision of federal regulations to afford protection to all crewmembers, account for cumulative effects, and updated compliance methods that rely on current ozonesonde data and periodic ozone monitoring should be accomplished to ensure crewmembers are not subjected to ozone levels that could potentially result in serious health concerns.
A Composite Neoclassical Toroidal Viscosity Model Incorporating Torques from both Axisymmetric and Nonaxisymmetric Tokamak Magnetic Fields

AbstractThis paper combines the older neoclassical gyroviscous model for toroidal viscosity in the plasma core, which is based on an axisymmetric magnetic field and obtains reasonable agreement with experiment for toroidal rotation in the plasma core but not in edge plasma, with recent models for neoclassical toroidal viscosity (NTV) based on nonaxisymmetric “perturbation” magnetic field components present primarily in the edge plasma to obtain a composite toroidal viscosity model for toroidal velocity calculations in the tokamak core and edge plasma. This combination is facilitated by the fact that the same form of “drag frequency” representation of the viscous torque used in many of the new (NTV) torque models arising from toroidally nonaxisymmetric perturbation magnetic fields that are present mostly in the plasma edge can also be used to represent the old neoclassical toroidal viscous torques arising from toroidally axisymmetric magnetic fields.
Using Statistics to Assess Lethal Violence in Civil and Inter-State War

What role can statistics play in assessing the patterns of lethal violence in conflict? This article highlights the evolution of statistical applications in assessing lethal violence, from the pres...
The client-binding domain of the cochaperone SGTA/Sgt2 has a helical-hand structure that binds a short hydrophobic helix

The correct targeting and insertion of tail-anchored (TA) integral membrane proteins (IMP) is critical for cellular homeostasis. The mammalian protein SGTA, and its fungal homolog Sgt2 (Sgt2/A), binds hydrophobic clients and is the entry point for targeting of ER-bound TA IMPs. Here we reveal molecular details that underlie the mechanism of Sgt2/A binding to TA clients. We establish that the Sgt2/A C-terminal region is conserved but flexible, sufficient for client binding, and has functional and structural similarity to the DP domains of Sti1. A molecular model for Sgt2/A-C reveals a helical hand forming a hydrophobic groove, consistent with a higher affinity for TA clients with hydrophobic faces and a minimal length of 11 residues. Finally, we show that a hydrophobic face metric improves the predictions for TA localization in vivo. The structure and binding mechanism positions Sgt2/A into a broader class of helical-hand domains that reversibly bind hydrophobic clients.
Functional mapping reveals mechanistic clusters for OER catalysis across (Cu–Mn–Ta–Co–Sn–Fe)Ox composition and pH space

Identification of stable electrocatalysts for the oxygen evolution reaction (OER) remains a primary challenge in materials for energy. pH-Dependent activity is known for very few catalysts, prompting our exploration of a broad range of catalysts using high throughput experiments and data science. This approach enables the largest screening of OER activity and operational stability to date, as illustrated through investigation of the (Cu–Mn–Ta–Co–Sn–Fe)Ox composition space as 15 unique quaternary composition spaces. In total 2121 compositions are tested between pH 3 and 13, creating an extensive dataset whose interpretation requires development and application of data science to provide insights that are both beyond the standard composition–activity relationships and beyond human interpretation due to the dimensionality of the dataset. Three distinct classes of OER catalysts are identified with respect to pH-dependent activity and stability. The large-scale screening reveals a new class of Co-rich OER catalysts that can be compositionally tailored to a specified pH and perform on par with state-of-the-art acid OER catalysts.
Volubility, Consonant Emergence, and Syllabic Structure in Infants and Toddlers Later Diagnosed With Childhood Apraxia of Speech, Speech Sound Disorder, and Typical Development: A Retrospective Video Analysis.

Purpose Studies of infants' early vocalizations have proven helpful in describing the developmental characteristics of various communication disorders. However, few studies have addressed the early...
Incentives to Pander

Policies targeting individual companies for economic development incentives, such as tax holidays and abatements, are generally seen as inefficient, economically costly, and distortionary. Despite this evidence, politicians still choose to use these policies to claim credit for attracting investment. Thus, while fiscal incentives are economically inefficient, they pose an effective pandering strategy for politicians. Using original surveys of voters in the United States, Canada and the United Kingdom, as well as data on incentive use by politicians in the US, Vietnam and Russia, this book provides compelling evidence for the use of fiscal incentives for political gain and shows how such pandering appears to be associated with growing economic inequality. As national and subnational governments surrender valuable tax revenue to attract businesses in the vain hope of long-term economic growth, they are left with fiscal shortfalls that have been filled through regressive sales taxes, police fines and penalties, and cuts to public education.
Toward a clinical text encoder: pretraining for clinical natural language processing with applications to substance misuse.

OBJECTIVE Our objective is to develop algorithms for encoding clinical text into representations that can be used for a variety of phenotyping tasks. MATERIALS AND METHODS Obtaining large datasets to take advantage of highly expressive deep learning methods is difficult in clinical natural language processing (NLP). We address this difficulty by pretraining a clinical text encoder on billing code data, which is typically available in abundance. We explore several neural encoder architectures and deploy the text representations obtained from these encoders in the context of clinical text classification tasks. While our ultimate goal is learning a universal clinical text encoder, we also experiment with training a phenotype-specific encoder. A universal encoder would be more practical, but a phenotype-specific encoder could perform better for a specific task. RESULTS We successfully train several clinical text encoders, establish a new state-of-the-art on comorbidity data, and observe good performance gains on substance misuse data. DISCUSSION We find that pretraining using billing codes is a promising research direction. The representations generated by this type of pretraining have universal properties, as they are highly beneficial for many phenotyping tasks. Phenotype-specific pretraining is a viable route for trading the generality of the pretrained encoder for better performance on a specific phenotyping task. CONCLUSIONS We successfully applied our approach to many phenotyping tasks. We conclude by discussing potential limitations of our approach.
Microfluidic quantification and separation of yeast based on surface adhesion

Fungal adhesion is fundamental to processes ranging from infections to food production to bioengineering. Yet, robust, population-scale quantification methods for yeast surface adhesion are lacking. We developed a microfluidic assay to discriminate and separate genetically-related yeast strains based on adhesion strength, and to quantify effects of ionic strength and substrate hydrophobicity on adhesion. This approach will enable the rapid screening and fractionation of yeast based on adhesive properties for genetic protein engineering, anti-fouling surfaces, and a host of other applications.
Utilization of Power Module Baseplate Capacitance for Common-Mode EMI Filter Reduction

Interest in the electromagnetic compatibility of power electronic systems continues to accelerate due to continued advancement in application and technological drivers such as electrified transportation and maturation of wide-bandgap semiconductors, respectively. A parasitic coupling that is known to play a significant role in the generation of conducted emissions in power electronic systems is the capacitance between the power switches and their heat sink. This paper explores the use of this parasitic capacitance to reduce the CM filtering burden in a notional dc-fed machine-drive application. Specifically, a set of EMI filter designs is produced to reduce CM emissions below the MIL-STD-461 CE-102 limit: a traditional CM EMI filter, a low-capacitance variant, and a low-inductance variant. The low-capacitance/inductance versions are designed through a model-based approach, in which the antiresonance formed between the ac-side parasitic capacitance of the inverter switch modules and the inductive (machine) load is used to advantage. The antiresonance is employed to notch the worst-offending component of the CM noise source. Thereby the required cutoff frequency of the EMI filter at the input is relaxed and the overall CM filtering burden is significantly reduced.
A personalized behavioral intervention implementing mHealth technologies for older adults: A pilot feasibility study

Abstract Sedentary behavior has been associated with adverse health outcomes such as disturbed sleep in older adults. We conducted a single-group pretest and posttest study to evaluate the feasibility of a personalized behavioral intervention program using mobile health technology in improving physical activity and sleep in older adults. The four-week intervention included: personalized physical activity training, real-time physical activity self-monitoring, interactive prompts and feedback with a smartwatch, phone consultation with an exercise trainer and research team members, and weekly financial incentives for achieving weekly physical activity goals. Eight cognitively intact older adults were recruited and completed the study. Findings suggested that the intervention was feasible in this sample of older adults and provided favorable changes in levels of physical activity during the intervention and at post-intervention. Future studies will include a fully powered trial to evaluate the efficacy of this intervention in sedentary older adults.
Labour Demand and the Source of Adjustment Costs

To examine the importance of the two sources of costs of adjusting labor demand, net costs (of adjusting employment) and gross costs (of hiring and firing), the author collects new sets of short monthly time series from a medium-size hospital and three manufacturing plants. Models with quadratic costs and with lumpy costs are developed and yield lower bounds on the fraction of adjustment costs that are gross. The estimates demonstrate that both types of costs affect dynamic labor demand but that gross adjustment costs especially, and the turnover that generates them, deserve much more attention. Copyright 1995 by Royal Economic Society.
Fantastical pretense's effects on executive function in a diverse sample of preschoolers

Abstract Growing evidence supports pretense as a positive predictor of executive function (EF) in early childhood. However, there is a need for well controlled, experimental studies examining the effects of various styles of pretense on EF development in diverse populations. The present study included 179 preschoolers (ages 2–5; 38% low-income, in Head Start), randomly assigned to one of four conditions: Fantastical Pretense, Realistic Pretense, Non-Imaginative Play, or Business-as-Usual Control, with no pre-test group differences. After 5 weeks of daily intervention, data suggest that fantastical pretense, but not other styles of pretense/play, facilitates EF development among non-Head Start, middle-class children. Head Start children did not benefit, perhaps due to lower levels of engagement as well as lower initial EF levels and propensities towards pretense. These data highlight the value of engaging in fantastical pretend play among middle-class populations and emphasize the need to further investigate the role of pretense in at-risk samples.
#Amamantar: Representations of breastfeeding targeting Hispanic/Latinx populations on social media

Abstract Health organizations advocate breastfeeding as the optimal feeding for most infants worldwide, and health messaging increasingly takes place through social media. This study analyzes representations of breastfeeding targeting Hispanic/Latin American populations in 926 original posts to Instagram using the hashtag #amamantar (English translation: breastfeeding). Results reveal three main categories: maternal love, breastfeeding education, and public breastfeeding. Maternal love images displayed both mother and child, emphasizing emotional attachment developed through breastfeeding. Breastfeeding educational images focused only on the child, presenting the breast as a vessel, and reporting the properties of breastmilk. Public breastfeeding images showed women breastfeeding in public spaces and at work, normalizing breastfeeding in public. Analysis also revealed race and class biases, whereby most mothers and babies represented are white and mothers are depicted in professional occupations. These findings demonstrate that, although social media has been theorized as a potentially liberating forum, these images reproduce current power arrangements.