cssi/SciSciGPT-SciSciNet huggingface dataset:
Infection of macrophages in culture by leptomonads of Leishmania donovani.

SYNOPSIS. Peritoneal macrophages from hamsters were monolayered on coverslips in Leighton tubes. Twenty-four hours later these were transferred to a perfusion chamber. Leptomonads were added with fresh medium and the infection process observed with the aid of phase contrast. In the perfusion chamber free-swimming leptomonads attached to the macrophage by the tip of their flagella. Shortly after this initial attachment the macrophage extended a narrow pseudopodium around the flagellum which eventually reached and enveloped the body of the parasite. Upon complete envelopment the pseudopod containing the leptomonad was retracted into the central body of the macrophage. When first seen in the granular endoplasm of the macrophage, most of the leptomonads appeared to be surrounded by vacuoles. In most cases these vacuoles disappeared in a few minutes making it difficult to distinguish the parasite from the host cell cytoplasm. Leptomonads also were added directly to Leighton tube cultures, and the coverslips with the adherent macrophages and parasites were removed, fixed and stained periodically during the infection process. In these preparations most of the parasites were in clumps in the vicinity of macrophages. Details of the ingestion of the clumps could not be seen, but occasionally a single organism was seen with its flagellum and part of its body enclosed by an extended pseudopod. Most of the intracellular leptomonads were in large vacuoles. Forms intermediate between elongate leptomonads and LD bodies were surrounded by smaller vacuole-like spaces. The halo-like vacuoles most frequently seen around LD bodies may have been fixation artifacts. Under favorable conditions the leptomonads transformed to LD bodies in 1–4 hours, but it was 48 hours before a population increase could be found.
Performance Evaluation of Diversity Schemes over Space-Polarization MIMO Channels

We compare the performance of orthogonal space-time block code (OSTBC) diversity schemes for co-polarized (CP) MIMO architectures and for space-polarization MIMO (SP-MIMO) architectures. This latter architecture employs a dual-polarized antenna in place of the co-polarized antennas to provides twice the number of antenna ports without substantially increasing the form factor of the antenna system. However, SP-MIMO systems exhibit power asymmetries in the MIMO sub channel gains due to the use of orthogonally-polarized antennas. We derive an approximate outage capacity formulation for a SP-MIMO 1-path narrowband MIMO model and provide finite-SNR diversity-multiplexing trade off of OSTBC schemes over such SP-MIMO channels. We show that SP-MIMO systems outperform CP-MIMO. Also, the so called "diversity order" definition used in literature for Rician MIMO channel is shown not be a valid benchmark to compare performance of SP-MIMO and CP-MIMO under the considered channel normalization approach.
Embryonic Development of the Bicuspid Aortic Valve.

Bicuspid aortic valve (BAV) is the most common congenital valvular heart defect with an overall frequency of 0.5%–1.2%. BAVs result from abnormal aortic cusp formation during valvulogenesis, whereby adjacent cusps fuse into a single large cusp resulting in two, instead of the normal three, aortic cusps. Individuals with BAV are at increased risk for ascending aortic disease, aortic stenosis and coarctation of the aorta. The frequent occurrence of BAV and its anatomically discrete but frequent co-existing diseases leads us to suspect a common cellular origin. Although autosomal-dominant transmission of BAV has been observed in a few pedigrees, notably involving the gene NOTCH1, no single-gene model clearly explains BAV inheritance, implying a complex genetic model involving interacting genes. Several sequencing studies in patients with BAV have identified rare and uncommon mutations in genes of cardiac embryogenesis. But the extensive cell-cell signaling and multiple cellular origins involved in cardiac embryogenesis preclude simplistic explanations of this disease. In this review, we examine the series of events from cellular and transcriptional embryogenesis of the heart, to development of the aortic valve.
Real-time collaborative coding in a web IDE

This paper describes Collabode, a web-based Java integrated development environment designed to support close, synchronous collaboration between programmers. We examine the problem of collaborative coding in the face of program compilation errors introduced by other users which make collaboration more difficult, and describe an algorithm for error-mediated integration of program code. Concurrent editors see the text of changes made by collaborators, but the errors reported in their view are based only on their own changes. Editors may run the program at any time, using only error-free edits supplied so far, and ignoring incomplete or otherwise error-generating changes. We evaluate this algorithm and interface on recorded data from previous pilot experiments with Collabode, and via a user study with student and professional programmers. We conclude that it offers appreciable benefits over naive continuous synchronization without regard to errors and over manual version control.
Cardiac Rhabdomyoma in an Adult Patient Presenting With Ventricular Arrhythmia

Cardiac rhabdomyomasare extremely uncommon in the adult patient. We describe a previouslyhealthy man who presented with ventricular arrhythmias resulting from aright ventricular, cardiac rhabdomyoma. Echocardiography, CT scanning, and MRI are recognized as useful diagnostic modalities for intracardiaclesions. Cardiac catheterization in our patient demonstrated thepresence of a tumor blush. This has not previously been reported withcardiac rhabdomyomas. Although lesions may spontaneously regress, surgery is of ten necessary and frequently resolves the underlyingarrhythmia.
ORL: an object retrieval language interface to an object algebra

The authors present the design of ORL, an object retrieval language interface to the EQUAL object algebra. ORL has an extended SQL syntax and is implemented on top of the ONTOS object-oriented database system. The complete system provides an interactive query facility as an alternative to the programatic OSQL interface provided by ONTOS. In general, ORL provides a more concise, user-friendly approach to the expression of queries over objects than the object algebra on which it is based. The translation of ORL queries to their equivalent object algebra expressions is described. >
Community Radio Stations as Community Technology Centers: An Evaluation of the Development Impact of Technological Hybridization on Stakeholder Communities in South Africa

This study investigated the impact of using community radio stations to extend information and communication technology (ICT) benefits to poor communities in South Africa. Six community radio stations in six rural South African communities were studied, using face-to-face interviews, community conversations, and observation method. The study found these radio stations have ICT presence, but because of a lack of resources they are only able to allow their stakeholder communities' indirect access to these technologies. It concludes that for these stations to realize their full development potential of extending ICTs to poor rural communities in South Africa, collaborative innovative strategies will have to be instituted. The author thanks Andy Alali and several anonymous reviewers for their assistance and suggestions. An earlier version of this work was presented as a top research paper to the Human Information Technology Division at the 97th annual meeting of the Eastern Communication Association in Philad...
Building a New Paradigm: Analysis of a Case Study in Organizational Change in Collection Management Using Bolman's and Deal's Four-Frame Model

In 2010, the Oregon State University Libraries implemented changes to its organizational structure to align itself better with the university and respond to the ongoing fiscal crisis. The Collections & Resource Sharing Department was created at that time. This case study describes and analyzes changes in collection management using the four frames in Bolman's and Deal's model: structural, human resources, political, and symbolic. The article concludes with a discussion of ongoing challenges that are likely to require greater use of the political and symbolic frames for planning and implementing further changes.
Bertrand competition with capacity constraints: mergers among parking lots

To analyze the e1ects of mergers among 2rms facing capacity constraints, we develop a numerical model of price-setting behavior among multi-product 2rms di1erentiated by location and capacity. We perform a number of computational experiments designed to inform merger policy, with speci2c reference to the Central Parking–Allright merger of 1999. The experiments show that capacity constraints on merging 2rms attenuate merger e1ects by much more than capacity constraints on non-merging 2rms amplify them. The experiments also highlight the dependence of merger welfare e1ects on parking demand. In preparation for further industry consolidation, we propose estimators of parking demand to more precisely estimate the costs and bene2ts of future mergers. c 2002 Elsevier Science B.V. All rights reserved. JEL classi)cation: L41; C63; C35
Renormalization of the thermoelectric power due to the electron-electron interaction.

The quantum kinetic equation is used to study the renormalization of the thermoelectric power (TEP) of an impure normal metal by the electromagnetic electron-electron interaction. We consider processes with large momentum {ital q} and transfer {ital ql}{much gt}1, where {ital l}={ital v}{sub {ital F}}{tau} is the electron mean free path and {tau} is the electron momentum relaxation time due to electron-impurity scattering. It is shown that the Coulomb electron-electron interaction (interaction of electrons with longitudinal photons) leads to the normal renormalization of the TEP, while the relativistic electron-electron interaction (interaction of electrons with transverse photons) leads to an unusual logarithmic renormalization, indicating a deviation from Fermi-liquid theory at low temperatures.
Computer-generated double-phase holograms

A method of computer generating binary holograms based on the decomposition of a complex value into two phase quantities is described. Each Fourier transform cell is divided into subcells, and phase quantities are encoded by the detour phase technique. Noise due to the displacement of the subcells and the phase coding is discussed. Methods of suppressing this noise are also included.
Distal Biceps Tendon Injuries: Treatment of Partial and Complete Tears

Most distal bicep tendon ruptures occur in middle-aged men (fourth decade). The most common mechanism of distal biceps tears is sudden eccentric loading of an actively contracting biceps (lifting or pushing heavy load) resulting in tendon failure usually at the tendon-bone junction. The indications for surgical reconstruction, type of surgical approach, and the fixation techniques for the distal biceps tendon are areas of ongoing debate. Nonoperative treatment results in modest loss of elbow strength in supination. Primary repair of a complete distal biceps tear in acute stages results in a predictable recovery of elbow supination and flexion strength but carries a risk of heterotopic ossification and neurologic injury. Heterotopic ossification is more commonly described with a 2-incision technique. Nerve palsy is common with single-incision approach and is usually transient and self-limiting. Primary repair in a chronic distal biceps tear is difficult and often requires augmentation with an autograft or allograft. Biomechanical cadaveric studies demonstrate that cortical button provides a consistent higher load to failure compared with other techniques for fixation of distal biceps. Our preferred method for the repair of acute distal biceps tendon tear is a single anterior skin incision technique with hybrid fixation, which combines a cortical button using a tension slide technique and interference screw fixation. Improvement in fixation techniques of the torn tendon to bone allows for early active range of motion and is our preferred mode of rehabilitation.
Cognitive screening of psychiatric patients

The goal of the present study was to explore characteristic cognitive profiles which distinguish between psychiatric patients with and without organic mental disorder (OMD), using Neurobehavioral Cognitive Status Examination (NCSE), a brief screening battery. A mild degree of cognitive deficits was found to be common in the Non-OMD psychiatric group. The deficit was especially pronounced in the Memory domain. Patients in the OMD group demonstrated a higher frequency of moderate and severe impairment. The best discriminator was the scale assessing visuospatial constructional ability and visual memory. Verbal memory deficit in OMD patients was more severe than in Non-OMD patients. Implications for improving diagnostic sensitivity of cognitive screening are discussed.
A comparison of methods for modeling electrically thin dielectric and conducting sheets in the finite-difference time-domain (FDTD) method

A comparison is made between several different methods that have recently been proposed for efficiently modeling electrically thin material sheets in the finite-difference-time-domain (FDTD) method. The test problems used in the comparison are parallel-plate waveguides loaded with electrically thin dielectric (lossless) and conducting sheets for which exact solutions are available. The accuracy of the methods is illustrated by comparison with analytical results for model problems that have exact solutions. >
Truncated MultiGaussian Fields and Effective Conductance of Binary Media

Truncated Gaussian fields provide a flexible model for defining binary media with dispersed (as opposed to layered) inclusions. General properties of excursion sets on these truncated fields are coupled with a distance-based upscaling algorithm and approximations of point process theory to develop an estimation approach for effective conductivity in two-dimensions. Estimation of effective conductivity is derived directly from knowledge of the kernel size used to create the multiGaussian field, defined as the full-width at half maximum (FWHM), the truncation threshold and conductance values of the two modes. Therefore, instantiation of the multiGaussian field is not necessary for estimation of the effective conductance. The critical component of the effective medium approximation developed here is the mean distance between high conductivity inclusions. This mean distance is characterized as a function of the FWHM, the truncation threshold and the ratio of the two modal conductivities. Sensitivity of the resulting effective conductivity to this mean distance is examined for two levels of contrast in the modal conductances and different FWHM sizes. Results demonstrate that the FWHM is a robust measure of mean travel distance in the background medium. The resulting effective conductivities are accurate when compared to numerical results and results obtained from effective media theory, distance-based upscaling and numerical simulation.
Package crack resolution through low stress dambar punch design: A six sigma DMAIC approach

Package micro-crack has been a stern problem in ON Semiconductors Philippines Inc (OSPI) Trim and Form (T&F) process. That despite numerous studies to eliminate the problem it still persist. Package micro-crack was of concern as it has a high chance to escape assembly inspection control and electrical test. And potentially will contribute to the product failure upon application of stress.
Exploratory meta-analysis on dose-related efficacy and morbidity of bone morphogenetic protein in spinal arthrodesis surgery.

OBJECT Bone morphogenetic protein (BMP) is frequently used for spinal arthrodesis procedures in an “off-label” fashion. Whereas complications related to BMP usage are well recognized, the role of dosage is less clear. The objective of this meta-analysis was to assess dose-dependent effectiveness (i.e., bone fusion) and morbidity of BMP used in common spinal arthrodesis procedures. A quantitative exploratory meta-analysis was conducted on studies reporting fusion and complication rates following anterior cervical discectomy and fusion (ACDF), posterior cervical fusion (PCF), anterior lumbar interbody fusion (ALIF), transforaminal lumbar interbody fusion (TLIF), posterior lumbar interbody fusion (PLIF), and posterolateral lumbar fusion (PLF) supplemented with BMP. METHODS A literature search was performed to identify studies on BMP in spinal fusion procedures reporting fusion and/or complication rates. From the included studies, a database for each spinal fusion procedure, including patient demographic info...
Introduction to Biophysics Week: What is Biophysics?

Biophysics is a thriving discipline, as is evident by the breadth and depth of the science that is being presented at the Biophysical Society Annual Meetings and published in Biophysical Journal. Yet, biophysics also has an identity problem—due to the wide range of research topics that properly fall under the general rubric of biophysics—and biophysicists often find themselves challenged when asked to describe what the term actually represents.
Expression and Characterization of Recombinant Anti-Rh(D) Antibodies on Filamentous Phage: A Model System for Isolating Human Red Blood Cell Antibodies by Repertoire Cloning

The production of human anti-red blood cell (RBC) Igs in vitro from immunized individuals would greatly facilitate the genetic analysis of the human immune response to RBC antigens and also provide useful serologic reagents. Technical difficulties inherent in human B-cell immortalization have led to the development of molecular approaches that bypass the need for cell transformation. By cloning human Ig gene segments into bacterial expression vectors, libraries are created of filamentous phage particles displaying Fab fragments on their surfaces. Libraries have been screened with purified, soluble antigen and selected clones genetically manipulated in Escherichia coli to produce soluble Fab fragments. Our goal has been to adapt this technique to the study of RBC autoantibodies and alloantibodies that have specificities against unpurifiable membrane-bound antigens. To test the feasibility of this approach, two sets of phage were created, one set expressing a human anti-Rh(D) Ig and the other expressing a human antitetanus toxoid Ig. After verifying the presence of functional phage-displayed Fabs through biochemical, flow cytometric, and electron microscopic analyses, a model library was constructed comprising one anti-Rh(D)- expressing phage per 10(4) antitetanus toxoid-expressing phage. A method was developed for screening the library with intact Rh(D)- positive RBCs. After four rounds of panning, anti-Rh(D) specificity was enriched more than 10,000-fold to a final frequency of approximately 100%. Plasmid DNA derived from anti-Rh(D) phage was used to produce milligram quantities of soluble recombinant anti-Rh(D) Fabs purified by nitrogen cavitation and nickel-chelation affinity chromatography. The authenticity of the Fabs was confirmed by sodium dodecyl sulfate- polyacrylamide gel electrophoresis and immunoblotting, which showed bands with molecular weights of approximately 50 kD and 26 kD under nonreducing and reducing conditions, respectively. Binding of recombinant anti-Rh(D) Fabs to Rh(D)-positive RBCs was demonstrated by flow cytometry and by an agglutination assay. Our results suggest that repertoire cloning by cell-surface enrichment may have broad application to the study of the human immune response to erythroid antigens in addition to membrane-bound antigens present on other hematopoietic cells.
Vasodilatory Cascade: ICP Response to CPP Level and Reduction Rate

Previous work has suggested that CSF pressure waves are in large part the result of an unstable blood pressure acting upon a more or less intact autoregulating cerebral vascular bed in the face of pathologically increased ICP and/or increased brain stiffness. The “vasodilatory cascade” model for CSF pressure wave generation was subsequently developed. This model suggests decrements in CPP will stimulate vasodilatation which will tend to increase cerebral blood volume (CBV). The increase will increase ICP which will further reduce CPP. Unless there is a response in the systemic arterial blood pressure (SABP) side of the CPP equation, the cycle will continue leading to more vasodilatation, increased CBV and a further increase in ICP which will further reduce CPP until vasodilatation is maximal. We have undertaken a series of experiments to further validate this ICP wave model.
Abstract 1363: Associations between fatalistic beliefs, modesty concerns and breast cancer screening in the American Muslim community.

Background: Research on breast cancer screening among American Muslims is limited. The handful of studies conducted in the Muslim community, and research of South Asian and Arab Americans, a proportion of which are Muslim, consistently demonstrate rates of mammography screening markedly lower than the 81% Healthy 2020 target. Our prior work suggests that American Muslim health behaviors are strongly influenced by shared religious concepts such as the concern for modesty. We sought to assess mammography screening rates among a diverse sample of Muslims in Greater Chicago, and assess the relationships between religiosity, modesty concerns, fatalism and breast cancer screening in this group. Methods: We used a community-engaged research design partnering with the Council of Islamic Organizations of Greater Chicago to survey a diverse sample of Muslim women frequenting mosques and community sites. The survey incorporated several measures of fatalism adapted to the Muslim context, a measure of discrimination, several measures of Islamic Religiosity and a pilot measure of Islamic modesty concern. Results: 254 women participated with 56 African Americans (24%), 70 Arab Americans (30%), and 84 South Asians (36%). 76% of participants had insurance, while 84% had access to a primary care physician and 78% reported high levels of modesty concern. 75% of the sample reported ever having a mammogram while 44% had a mammogram within the past 1-2 years. There was not a significant relationship between racial and ethnic status and mammography rates. On multivariate analysis adjusting for socioeconomic factors high ratings of religiosity were associated with increased odds of ever having a mammogram (OR=1.08, p Conclusions: Contrary to our hypotheses modesty concerns and fatalistic beliefs were not significantly associated with mammography rates. Yet, on one hand higher intrinsic religiosity was positively associated with ever having a mammogram while positive religious coping was negatively associated with getting a mammogram every two years. Shared religious concepts appear to influence breast cancer screening behaviors among American Muslims across race and ethnicity, and research teasing out how religiosity impacts decisions to pursue breast cancer screening is needed. Citation Format: Aasim I. Padela, Sohad Murrar, Brigid Adviento, Farr Curlin, Olufunmilayo Olopade. Associations between fatalistic beliefs, modesty concerns and breast cancer screening in the American Muslim community. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1363. doi:10.1158/1538-7445.AM2013-1363
Candidate Reputations and Issue Agendas

How do campaigns decide what issues to emphasize for voters? According to most studies, campaigns rely on factors outside of their control—issue salience, party issue ownership, and district ideology. In this article, I argue that campaign messages are designed primarily based on the candidate. I examine the issue content of campaign advertisements from U.S. House and Senate campaigns from 2000 to 2004 and develop a measure that determines if candidates have developed a reputation on a particular issue. When candidates have developed such a reputation, their campaign is more likely to highlight that issue to voters than campaigns whose candidate has not developed such a reputation. This relationship is consistent across most issues and across two different measures of a campaign’s issue agenda.
The Treloar-Kearsley problem for elastomeric materials undergoing time-dependent microstructural evolution: Branching of extensional creep histories

Treloar carried out experiments on square rubber sheets that were loaded by equal in-plane forces along their edges. Kearsley observed from Treloar’s data that the deformations were equal biaxial extensions for smaller forces, but became unequal biaxial extensions beyond a larger force. By means of a simple non-linear elasticity problem, Kearsley showed that the governing equations had multiple solutions that allowed for bifurcation from an equal biaxial to an unequal biaxial deformation.The present work considers this bifurcation phenomenon if Treloar’s experiments were to be carried out in the temperature range, say, of 100–150°C. Tobolsky showed that rubber in this temperature range undergoes microstructural evolution attributed to a chemical process of scission and crosslinking of macromolecular junctions. When loaded by equal in-plane forces along its edges, the rubber sheet can be expected to undergo equal biaxial extensional creep. The possibility is considered that there may be a time when the equ...
Regulation of nonmuscle myosin II by tropomyosin

The actin cytoskeleton carries out cellular functions, including division, migration, adhesion, and intracellular transport, that require a variety of actin binding proteins, including myosins. Our focus here is on class II nonmuscle myosin isoforms, NMIIA, NMIIB, and NMIIC, and their regulation by the actin binding protein, tropomyosin. NMII myosins are localized to different populations of stress fibers and the contractile ring, structures involved in force generation required for cell migration, adhesion, and cytokinesis. The stress fibers and contractile ring that contain NMII myosins also contain tropomyosin. Four mammalian genes encode more than 40 tropomyosins. Tropomyosins inhibit or activate actomyosin MgATPase and motility depending on the myosin and tropomyosin isoform. In vivo, tropomyosins play a role in cell migration, adhesion, cytokinesis, and NMII isoform localization in an isoform-specific manner. We postulate that the isoform-specific tropomyosin localization and effect on NMII isoform localization reflect modulation of NMII actomyosin kinetics and motile function. In this study, we compare the ability of different tropomyosin isoforms to support actin filament motility with NMIIA, NMIIB, and NMIIC as well as skeletal muscle myosin. Tropomyosins activated, inhibited, or had no effect on motility depending on the myosin, indicating that the myosin isoform is the primary determinant of the isoform-specific effect of tropomyosin on actomyosin regulation. Activation of motility of nonmuscle tropomyosin–actin filaments by NMII myosin correlates with an increased Vmax of the myosin MgATPase, implying a direct effect on the myosin MgATPase, in contrast to the skeletal tropomyosin–actin filament that has no effect on the Vmax or maximal filament velocity.
“The Wisdom of Age”: Perspectives on Aging and Growth among Lesbian Older Adults

ABSTRACTOlder lesbian-identified women are a health disparate yet resilient population about whom knowledge is limited and emerging. Among the areas in need of research are older lesbians’ experiences of later life and stress-related growth. This article presents the findings from a qualitative study that investigated older lesbians’ experiences of adversity and adaptation as they age. In-depth, exploratory interviews were conducted with 12 lesbian-identified women who were between the ages of 65–80. This study applied grounded theory methodology to identify respondents sources of stress and fear, their strengths and coping strategies and how those relate to each other and to their growth in later life. We advance a model of adaptive change that shows how spirituality, social support, and resistance to cultural norms help older lesbian adults cope with loss, illness, and discrimination and develop wisdom in later life. Knowledgeable practitioners can help older lesbian women identify and maintain sources ...
Long-term follow-up of renal transplantation for Wegener's disease

Eight patients with end-stage renal failure due to Wegener's granulomatosis underwent renal transplantation at the University of Minnesota. Seven patients were alive with a functioning graft 40 to 128 months posttransplant (mean follow-up: 91 months). One patient died 126 months posttransplant with a well-functioning graft. Posttransplant immunosuppression controlled primary disease in all but 1 patient, who presented with perisinusitis. Recurrent disease was not noted in any of the transplanted organs. We conclude that transplantation is an excellent treatment for renal failure secondary to Wegener's disease.
An atomic orbital based real-time time-dependent density functional theory for computing electronic circular dichroism band spectra

One of the challenges of interpreting electronic circular dichroism (ECD) band spectra is that different states may have different rotatory strength signs, determined by their absolute configuration. If the states are closely spaced and opposite in sign, observed transitions may be washed out by nearby states, unlike absorption spectra where transitions are always positive additive. To accurately compute ECD bands, it is necessary to compute a large number of excited states, which may be prohibitively costly if one uses the linear-response time-dependent density functional theory (TDDFT) framework. Here we implement a real-time, atomic-orbital based TDDFT method for computing the entire ECD spectrum simultaneously. The method is advantageous for large systems with a high density of states. In contrast to previous implementations based on real-space grids, the method is variational, independent of nuclear orientation, and does not rely on pseudopotential approximations, making it suitable for computation of chiroptical properties well into the X-ray regime.
Re-interpreting Blackstone’s Commentaries: a seminal text in national and international contexts

Abraham Lincoln once recalled that as a young man he had ‘never read anything which so profoundly interested and thrilled me’ as did Sir William Blackstone’s Commentaries on the Laws of England (17...
Abstract 1310: Targetingprolactin signaling to suppress pancreatic cancer stem cells

Background: Pancreatic cancer (PCa) is a major cause of cancer related mortality in United States with Methods: PCa cells (MiaPaCa-2 and PanC-1) were grown to 70-80% of confluency and treated with and without prolactin (PRL) and JAK2, STAT3 and ERK phosphorylation in presence and absence of antipsychotic compound were evaluated by western blot. Growth of PCa lines (MiaPaCa-2, PanC-1, BxPC-3, AsPC-1) and normal ductal epithelial cells (HPNE) was measured by hexosaminidase and clonogenicity, respectively. Pancosphere formation was used to identify effects on stem cells. Results: We have recently identified that the receptor for the pituitary hormone prolactin is overexpressed in pancreatic cancers, and in pancreatic cancer cell lines. When prolactin (PRL) binds its cognate receptor (PRLR), it induces various downstream events including the JAK-STAT and ERK MAPK pathways. In pancreatic cancer cell lines, we observe that PRL treatment induced dose- and time-dependent JAK2, STAT3, and ERK1/2 phosphorylation. Furthermore, there was an increase in the expression of cancer stem cell (CSC) markers DCLK1 (doublecortin calmodulin like kinase 1) and CD44. In addition, PRL-induced pancosphere formation further suggesting that PRL affects stem cells. Based on these data, we conclude that PRL signaling enhances stemness in pancreatic cancers, and therefore we decided to target it for therapeutic intervention. For this, we developed a homology model for the C-terminal intracellular region of the receptor and performed a virtual screening in silico with FDA approved drugs. One compound, a first generation antipsychotic drug diphenylbutylpiperidine, also called Penfluridol was found to interact with the region of the receptor that also binds site for JAK2. The compound has a long half-life, and is used in the treatment of chronic schizophrenia and similar psychotic disorders. We have further determined that Penfluridol inhibits PRL-induced STAT3 and ERK phosphorylation. In addition, the compound reduced proliferation, colony formation, and spheroid formation. Moreover, it induced cells to undergo autophagy by activating LC3B and increasing expression of autophagy-related genes ATG5, 7 and 12. Conclusions: PRL signaling through its cognate PRLR receptor is critical for aggressive pancreatic cancer behavior, and therefore may be an effective therapeutic strategy. Citation Format: Prasad Dandawate, Gaurav Kaushik, Dharmalingam Subramaniam, Prabhu Ramamoorthy, Scott J. Weir, Roy A. Jensen, Shrikant Anant. Targetingprolactin signaling to suppress pancreatic cancer stem cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1310.
DuoSkin: rapidly prototyping on-skin user interfaces using skin-friendly materials

Miniature devices have become wearable beyond the form factor of watches or rings---functional devices can now directly affix to the user's skin, unlocking a much wider canvas for electronics. However, building such small and skin-friendly devices currently requires expensive materials and equipment that is mostly found in the medical domain. We present DuoSkin, a fabrication process that affords rapidly prototyping functional devices directly on the user's skin using gold leaf as the key material, a commodity material that is skin-friendly, robust for everyday wear, and user-friendly in fabrication. We demonstrate how gold leaf enables three types of interaction modalities on DuoSkin devices: sensing touch input, displaying output, and communicating wirelessly with other devices. Importantly, DuoSkin incorporates aesthetic customizations found on body decoration, giving form to exposed interfaces that so far have mostly been concealed by covers. Our technical evaluation confirmed that gold leaf was more durable and preferable when affixed to skin than current commodity materials during everyday wear. This makes gold leaf a viable material for users to build functional and compelling on-skin devices. In our workshop evaluation, participants were able to customize their own on-skin music controllers that reflected personal aesthetics.
Symptomatic and Incidental Thromboses Are Both Associated with Mortality In Pancreatic Cancer

Abstract Abstract 3167 Background: Incidentally diagnosed venous thromboembolism (VTE) is a growing clinical problem. Although pancreatic cancer is well-known to be associated with VTE, contemporary rates of incidental and symptomatic VTE events and their association with mortality are incompletely understood. Methods: We conducted a retrospective cohort study of consecutive pancreatic adenocarcinoma patients seen at the University of Rochester from 2006–2009. Radiologic reports were reviewed for presence of pulmonary embolism (PE), deep venous thrombosis (DVT), and visceral vein thrombosis. Multiple clinical variables and mortality outcomes were collected. Data were analyzed using a multivariate Cox proportional hazards model. Results: A total of 1151 radiologic exams for 135 patients were included. Forty-seven patients (34.8%) experienced at least one VTE event. There were 12 PEs (n=12 patients, 8.9%), 34 DVTs (n=17 patients, 12.6%), 47 visceral vein (n=31 patients, 22.9%) and 2 arterial (n=2 patients, 1.5%) events. Twenty-one patients (15.5%) experienced more than one event. Incidental events comprised 33.3% (n=4) of PEs, 17.6% (n=6) of DVTs and 100% (n=47) of visceral VTE. Median survival for the study population was 237 (95% CI 199–277) days. Patients with VTE had significantly reduced survival (73 vs. 233 days at 3 months post-diagnosis; 66 vs. 245 days at 6 months post-diagnosis). There was no significant difference between asymptomatic and symptomatic events in terms of conditional median survival at 3 months-, 6 months- or 1 year-post diagnosis. In multivariate analysis, occurrence of either DVT (HR 7.4 95% CI 3.8–14.6, P Conclusions: VTE occurs in over one-third of pancreatic cancer patients, including a significant proportion with incidentally discovered events. Patients with visceral vein events are generally not anticoagulated but these findings suggest a similar association with mortality as symptomatic DVT. Our findings require reconsideration of prognosis and anticoagulation options in pancreatic cancer patients with both incidental and symptomatic VTE. Disclosures: No relevant conflicts of interest to declare.
Focal Segmental Glomerulosclerosis

Focal segmental glomerulosclerosis (FSGS) is a leading cause of kidney disease worldwide. The presumed etiology of primary FSGS is a plasma factor with responsiveness to immunosuppressive therapy and a risk of recurrence after kidney transplant–important disease characteristics. In contrast, adaptive FSGS is associated with excessive nephron workload due to increased body size, reduced nephron capacity, or single glomerular hyperfiltration associated with certain diseases. Additional etiologies are now recognized as drivers of FSGS: high-penetrance genetic FSGS due to mutations in one of nearly 40 genes, virus-associated FSGS, and medication-associated FSGS. Emerging data support the identification of a sixth category: APOL1 risk allele–associated FSGS in individuals with sub-Saharan ancestry. The classification of a particular patient with FSGS relies on integration of findings from clinical history, laboratory testing, kidney biopsy, and in some patients, genetic testing. The kidney biopsy can be helpful, with clues provided by features on light microscopy (e.g., glomerular size, histologic variant of FSGS, microcystic tubular changes, and tubular hypertrophy), immunofluorescence (e.g., to rule out other primary glomerulopathies), and electron microscopy (e.g., extent of podocyte foot process effacement, podocyte microvillous transformation, and tubuloreticular inclusions). A complete assessment of renal histology is important for establishing the parenchymal setting of segmental glomerulosclerosis, distinguishing FSGS associated with one of many other glomerular diseases from the clinical-pathologic syndrome of FSGS. Genetic testing is beneficial in particular clinical settings. Identifying the etiology of FSGS guides selection of therapy and provides prognostic insight. Much progress has been made in our understanding of FSGS, but important outstanding issues remain, including the identity of the plasma factor believed to be responsible for primary FSGS, the value of routine implementation of genetic testing, and the identification of more effective and less toxic therapeutic interventions for FSGS.
Thin-film evaporation from micropillar wicks in ambient environment

We characterize thin-film evaporation of water from well-defined silicon micropillar arrays under ambient conditions (≈24 °C and ≈100 kPa). We compare the dryout heat fluxes from these experiments with the corresponding heat fluxes for experiments conducted at saturated conditions for water (≈24 °C and ≈3 kPa). Dryout heat fluxes for the experiments at 100 kPa were higher (τ2×) when compared to the corresponding values at 3 kPa. The dryout heat fluxes were found to be in good agreement with a semi-analytical thermal-fluidic model which accounts for the favorable change in the figure of merit of water when the vapor pressure changes from ≈3 kPa to ≈100 kPa. The experimental results show that self-regulated capillary-fed fluidic transport is vital for delaying nucleate boiling and achieving higher heat fluxes.
Decoding brain cognitive activity across subjects using multimodal M/EEG neuroimaging

Brain decoding is essential in understanding where and how information is encoded inside the brain. Existing literature has shown that a good classification accuracy is achievable in decoding for single subjects, but multi-subject classification has proven difficult due to the inter-subject variability. In this paper, multi-modal neuroimaging was used to improve two-class multi-subject classification accuracy in a cognitive task of differentiating between a face and a scrambled face. In this transfer learning problem, a feature space based on special-form covariance matrices manipulated with riemannian geometry are used. A supervised two-layer hierarchical model was trained iteratively for estimating classification accuracies. Results are reported on a publically available multi-subject, multi-modal human neuroimaging dataset from MRC Cognition and Brain Sciences Unit, University of Cambridge. The dataset contains simultaneous recordings of electroencephalography (EEG) and magnetoencephalography (MEG). Our model attained, using leave-one-subject-out cross-validation, a classification accuracy of 70.82% for single modal EEG, 81.55% for single modal MEG and 84.98% for multi-modal M/EEG.
Lewis Acid Activation of the Ferrous Heme–NO Fragment toward the N–N Coupling Reaction with NO To Generate N2O

Bacterial NO reductase (bacNOR) enzymes utilize a heme/non-heme active site to couple two NO molecules to N2O. We show that BF3 coordination to the nitrosyl O-atom in (OEP)Fe(NO) activates it toward N–N bond formation with NO to generate N2O. 15N-isotopic labeling reveals a reversible nitrosyl exchange reaction and follow-up N–O bond cleavage in the N2O formation step. Other Lewis acids (B(C6F5)3 and K+) also promote the NO coupling reaction with (OEP)Fe(NO). These results, complemented by DFT calculations, provide experimental support for the cis:b3 pathway in bacNOR.
Surface background suppression in liquid argon dark matter detectors using a newly discovered time component of tetraphenyl-butadiene scintillation

Decays of radioisotopes on inner detector surfaces can pose a major background concern for the direct detection of dark matter. While these backgrounds are conventionally mitigated with position cuts, these cuts reduce the exposure of the detector by decreasing the sensitive mass, and uncertainty in position determination may make it impossible to adequately remove such events in certain detectors. In this paper, we provide a new technique for substantially reducing these surface backgrounds in liquid argon (LAr) detectors, independent of position cuts. These detectors typically use a coating of tetraphenyl-butadiene (TPB) on the inner surfaces as a wavelength shifter to convert vacuum ultraviolet (VUV) LAr scintillation light to the visible spectrum. We find that TPB scintillation contains a component with a previously unreported exceptionally long lifetime ($\ensuremath{\sim}\mathrm{ms}$). We discovered that this component differs significantly in magnitude between alpha, beta, and VUV excitation, which enables the use of pulse shape discrimination to suppress surface backgrounds by more than a factor of $1{0}^{3}$ with negligible loss of dark matter sensitivity. We also discuss how this technique can be extended beyond just LAr experiments.
System reliability of floating offshore wind farms with multiline anchors

Abstract This research assesses the reliability of floating offshore windfarms utilizing two different anchor configurations: a conventional single-line system in which each anchor is loaded by a single mooring line and a multiline system in which each anchor is loaded by three mooring lines. While there are advantages to adopting a multiline system for floating offshore wind farms, the interconnectedness of this concept introduces disadvantages, such as reduction of system reliability and the potential for cascading failures among multiple structures. The reduction in system reliability is investigated here by running Monte-Carlo simulations in which mooring line and anchor demands and capacities are sampled from probability distributions. Demand distributions are generated through dynamic simulations with environmental conditions corresponding to the 500-year storm. Failure of mooring lines or anchors are initiated when their capacity is exceeded by their demand. The results of this research show that the reliability of the multiline system degrades significantly when progressive failures are taken into consideration. This research also shows that design considerations, such as the sizing of mooring lines and anchors and designing for single-line or multiline loads, significantly influence the system reliability of a floating offshore wind farm.
A high-sucrose diet does not enhance spontaneous metastasis of Lewis lung carcinoma in mice

A high energy intake contributes to obesity, a risk factor for cancer. We previously reported that an excessive intake of dietary fat enhances malignant spread in mice. This study tested the hypothesis that consumption of a diet with an excessive amount of sucrose enhances metastasis. In a spontaneous metastasis model of Lewis lung carcinoma (LLC), male C57BL/6 mice were maintained on an AIN93G, a high-fat, or a high-sucrose diet for the duration of the study. Pulmonary metastases from a primary tumor, established by a subcutaneous injection of LLC cells, were quantified. There were no differences in energy intake among the 3 groups. The percent body fat mass of the high-sucrose group, while higher than that of the AIN93G group, was lower than that of the high-fat group. The number and size of lung metastases were significantly higher in the high-fat group than in the AIN93G group; these measurements in the high-sucrose group remained similar to those in the AIN93G group. Hepatic concentrations of triacylglycerols and plasma concentrations of insulin, proinflammatory cytokines (leptin, plasminogen activator inhibitor-1, and monocyte chemotactic protein-1) and angiogenic factors (vascular endothelial growth factor and tissue inhibitor of metalloproteinase-1) in the high-sucrose group were significantly lower than those in the high-fat group. In conclusion, the high-sucrose diet does not enhance spontaneous metastasis of LLC. This null effect may be due to the inadequate production of tumorigenic proinflammatory cytokines and angiogenic factors by the high-sucrose diet compared to the high-fat diet.
New Conception of Relining in the Endovascular Aneurysm Sealing Era: A Monocentric Case Series Study

Over 20 years from the first endovascular aortic repair, endoleaks still represent a common problem, even with newer endograft generation. Numerous procedures can be adopted to manage these complications; relining of the endoprosthesis is a rational technique to treat type III and IV endoleaks. The absence of dedicated materials for these procedures forces the vascular surgeon to perform complex hybrid or endovascular interventions. In this case report, we aimed to evaluate our relining experience using the Nellix device in 5 consecutive cases.
AN INCIDENTAL FINDING OF ABRUPT BASAL SEPTAL DYSKINESIS IDENTIFIED BY SPECKLE TRACKING IMAGING: THINK WOLFF-PARKINSON-WHITE

The localization of accessory pathways in Wolf-Parkinson-White (WPW) syndrome patients is usually through an invasive electrophysiology (EP) study with no rule for 2-D echocardiography in current practice. A 31-year-old female with no significant history presented with 3 day history of fever and