Miracle-dz/UniFAR-FTUs huggingface dataset:
Detection of stellate distortions in mammograms

Malignant densities in mammograms have an irregular appearance and frequently are surrounded by a radiating pattern of linear spicules. In this paper a method is described to detect such stellate patterns. This method is based on statistical analysis of a map of pixel orientations. If an increase of pixels pointing to a region is found, this region is marked as suspicious, especially if such an increase is found in many directions. Orientations of the image intensity map are determined at each pixel using a multiscale approach. At a given scale, accurate line-based orientation estimates are obtained from the output of three-directional, second-order, Gaussian derivative operators. The orientation at the scale at which these operators have maximum response is selected. If a line-like structure is present at a given site, this method provides an estimate of the orientation of this structure, whereas in other cases the image noise will generate a random orientation. The pixel orientation map is used to construct two operators which are sensitive to radial patterns of straight lines. Combination of the output of these operators using a classifier allows for detection of stellate patterns. Different classification methods have been compared and results obtained on a common database are presented. Around 90% of the malignant cases were detected at rate of one false positive (FP) per image.
Chronic kidney disease is associated with a risk of higher mortality following total knee arthroplasty in diabetic patients: a nationwide population-based study

Diabetes and chronic kidney disease (CKD) are associated with a higher rate of complications in patients undergoing total knee arthroplasty (TKA). The purpose of this study was to determine the effects of CKD and diabetes in patients after TKA. Diabetic patients who received unilateral primary TKA between January 2008 and December 2011 were enrolled. The follow-up period was more than 6 months. The primary outcome was a TKA-related infection and the secondary outcome was all-cause mortality. The study cohort included 13844 patients who were followed for a mean period of 2 years, of whom 1459 (10.5%) had CKD. The patients with CKD were older than those without CKD (71.6 versus 70.3 years, P<0.0001) and had higher rates of hypertension, gouty arthritis, ischemic heart disease, chronic pulmonary obstructive disease, pulmonary embolism and deep vein thrombosis (all P<0.0001). After adjustment of comorbidities, the CKD group had a higher incidence of urinary tract infections (OR: 1.61, 95% CI: 1.19-2.17). There were no significant differences in wound infections, pneumonia, pulmonary embolism or in-hospital death between the two groups. After adjustment of confounders, the CKD group had higher rates of myocardial infarction (HR: 2.06, 95% CI: 1.26–3.39) and mortality (HR: 1.99, 95% CI: 1.59–2.48). The risk of TKA-related infection during follow-up was comparable between the two groups (HR: 1.31, 95% CI: 0.94–1.82). In conclusion, CKD is associated with increased risks of urinary tract infections, myocardial infarction and all-cause mortality after TKA. Surgeons should be aware of this when evaluating TKA patients with renal disease.
New Insights into the Assembly of Bacterial Secretins

Background: Secretins are outer membrane dodecameric translocation channels in bacterial type II secretion systems (T2SS). Results: The basic assembly unit of XcpQ, the T2SS secretin of the human pathogen Pseudomonas aeruginosa, is a dimer. Conclusion: Functional secretin likely results from hexameric assembly of secretin subunit dimers. Significance: This work is a conceptual advancement in understanding the assembly principles and dynamic function of bacterial secretins. The type II secretion system is a multiprotein assembly spanning the inner and outer membranes in Gram-negative bacteria. It is found in almost all pathogenic bacteria where it contributes to virulence, host tissue colonization, and infection. The exoproteins are secreted across the outer membrane via a large translocation channel, the secretin, which typically adopts a dodecameric structure. These secretin channels have large periplasmic N-terminal domains that reach out into the periplasm for communication with the inner membrane platform and with a pseudopilus structure that spans the periplasm. Here we report the crystal structure of the N-terminal periplasmic domain of the secretin XcpQ from Pseudomonas aeruginosa, revealing a two-lobe dimeric assembly featuring parallel subunits engaging in well defined interactions at the tips of each lobe. We have employed structure-based engineering of disulfide bridges and native mass spectrometry to show that the periplasmic domain of XcpQ dimerizes in a concentration-dependent manner. Validation of these insights in the context of cellular full-length XcpQ and further evaluation of the functionality of disulfide-linked XcpQ establishes that the basic oligomerization unit of XcpQ is a dimer. This is consistent with the notion that the dodecameric secretin assembles as a hexamer of dimers to ensure correct projection of the N-terminal domains into the periplasm. Therefore, our studies provide a key conceptual advancement in understanding the assembly principles and dynamic function of type II secretion system secretins and challenge recent studies reporting monomers as the basic subunit of the secretin oligomer.
Systematic Quantification of GPCR/cAMP-Controlled Protein Kinase A Interactions

Abstract The diffusible second messenger cyclic AMP (cAMP) originates from multiple G protein-coupled receptor (GPCR) cascades activating the intracellular key effector protein kinase A (PKA). Spatially and temporally restricted cAMP-fluxes are directly sensed by macromolecular PKA complexes. The consequences are alterations of molecular interactions, which lead to activation of compartmentalized PKA phosphotransferase activities, regulating a vast array of cellular functions. To decode cell-type and cell-compartment specific PKA functions, the spatio-temporal dynamics of small molecule:protein interactions, protein:protein interactions (PPIs), cAMP-mobilization, and phosphotransferase activities need to be determined directly in the appropriate cellular context. A collection of cell-based reporters has been developed to either visualize or quantitatively measure kinase activities or PKA complex formation/dissociation. In this review, we list a collection of unimolecular and bimolecular PKA biosensors, followed by the specification of the modular design of a Renilla luciferase based protein-fragment complementation assay (PCA) platform for measuring PKA network interactions. We discuss the application spectrum of the PCA reporter to identify, quantify, and dissect dynamic and transient PKA complexes downstream of specific GPCR activities. We specify the implementation of a PCA PKA platform to systematically quantify the concurrent involvement of receptor-cAMP signaling, post-translational modifications, and kinase subunit mutations/perturbations in PKA activation. The systematic quantification of transient PKA network interactions will contribute to a better understanding how GPCR-recognized input signals are streamlined through the compartmentalized and cAMP-interacting PKA signalosome.
Retinoid-Induced Apoptosis in HL-60 Cells Is Associated with Nucleolin Down-Regulation and Destabilization of Bcl-2 mRNA

All-trans retinoic acid (ATRA) induces differentiation of promyelocytic leukemia cells, but the mechanisms by which cellular differentiation leads to apoptosis are not well understood. Studies were done to address the question whether ATRA-induced apoptosis is a consequence of destabilization of bcl-2 mRNA and decreased cellular levels of the anti-apoptotic protein, bcl-2. ATRA induced differentiation of HL-60 cells along the granulocytic pathway within 48 h. The half-lives of bcl-2 mRNA in HL-60 cells incubated with ATRA for 48 or 72 h were reduced to 39 and 7% of the corresponding untreated control values, respectively. Cellular differentiation was accompanied by down-regulation of the cytoplasmic levels of nucleolin, a bcl-2 mRNA-stabilizing protein. Binding of a bcl-2 mRNA instability element (AU-rich element-1) to nucleolin in S100 extracts from ATRA-treated cells was decreased to 15% of control within 72 h. The decay of 5′ capped, polyadenylated bcl-2 mRNA transcripts containing ARE-1 was more rapid in S100 extracts from ATRA-treated cells compared with untreated cells. However, when recombinant nucleolin was added to extracts of ATRA-treated cells, the rate of bcl-2 mRNA decay was similar to the rate in extracts of untreated cells. These results provide evidence that ATRA-induced apoptosis is a consequence of cellular differentiation, which leads to nucleolin down-regulation and bcl-2 mRNA instability.
A low noise current readout architecture for fluorescence detection in living subjects

Optical molecular imaging is emerging as a powerful preclinical research tool for investigating and quantifying molecular events in living subjects, with applications including earlier detection of disease, therapeutic monitoring and understanding fundamental biology [1]. For example, imaging the fluorescent molecular probe RGD-Cy5.5, which specifically binds to molecules (αvβ3 integrin receptors) that regulate new blood vessel growth in tumors, can be used to quantify this growth [2]. Capturing the fluorescent signal in living subjects with an implanted biosensor would enable continuous monitoring of tumors in freely moving subjects. Continuous monitoring in the setting of cancer would give valuable information on tumor progression, both in assessing drug efficacy and detecting recurrent tumor growth after treatment. Presently, fluorescence imaging in living subjects is performed with bulky instrumentation that does not permit continuous monitoring of freely moving subjects over long time periods. In order to make a fluorescence-detection system implantable, and portable, a laser excitation source, a photodetector and a readout circuit for measuring and digitizing photocurrents are integrated in a single package, and continuous fluorescence detection is demonstrated in live animals.
A dynamic courtship: The Salvation Army and the welfare state in the Netherlands (1887-1990)

The Salvation Army has been battling social problems in the Netherlands for more than 125 years. Over the course of this period, the Dutch Salvation Army has developed into a well-known faith-based organization as well as an important professional social service provider. These two characteristics: religious work and social work, are regarded by the Army as essential to its identity, and are considered distinct but in – separable. However, as this study shows, during much of the Army’s history this bilateral character created an inescapable field of tension. This became explicitly clear with the development of the Dutch social policy system during the twentieth century, when the evolving relationship between the Salvation Army and the Dutch government created certain problems for both actors. How would the government cooperate with a valued social service provider that had an explicit faith-based identity? And on the other hand, how did the Army cope with this relationship in relation to its identity? The work presented in this thesis was supported by the University of Applied Sciences Utrecht (HU) and the VU University Amsterdam.
Actin Depolymerization Factor/Cofilin Activation Regulates Actin Polymerization and Tension Development in Canine Tracheal Smooth Muscle*

The contractile activation of airway smooth muscle tissues stimulates actin polymerization, and the inhibition of actin polymerization inhibits tension development. Actin-depolymerizing factor (ADF) and cofilin are members of a family of actin-binding proteins that mediate the severing of F-actin when activated by dephosphorylation at serine 3. The role of ADF/cofilin activation in the regulation of actin dynamics and tension development during the contractile activation of smooth muscle was evaluated in intact canine tracheal smooth muscle tissues. Two-dimensional gel electrophoresis revealed that ADF and cofilin exist in similar proportions in the muscle tissues, and that ∼40% of the total ADF/cofilin in unstimulated tissues is phosphorylated. Phospho-ADF/cofilin decreased concurrently with tension development in response to stimulation with acetylcholine (ACh) or potassium depolarization indicating the activation of ADF/cofilin. Expression of an inactive phospho-cofilin mimetic (cofilin S3E) but not wild type cofilin in the smooth muscle tissues inhibited endogenous ADF/cofilin dephosphorylation and ACh-induced actin polymerization. Expression of cofilin S3E in the tissues depressed tension development in response to ACh, but it did not affect myosin light chain phosphorylation. The ACh-induced dephosphorylation of ADF/cofilin required the Ca2+-dependent activation of calcineurin (PP2B). The results indicate that the activation of ADF/cofilin is regulated by contractile stimulation in tracheal smooth muscle and that cofilin activation is required for actin polymerization and tension development in response to contractile stimulation.
Computer-aided detection and characterization of hyperparathyroidism in digital hand radiographs

A computer algorithm has been developed to detect and possibly stage subperiosteal resorption from digitized hand radiographs for patients with primary or secondary hyperparathyroidism. The method can quantify the severity of bony resorption by analyzing the roughness of the radial phalangeal margins as projected on the hand radiographs. This margin is detected by a model-guided boundary-tracking scheme and its roughness is quantified by the mean-square variation and the first moment of the power spectrum. The preliminary results indicate that the computer-aided diagnosis system if accurately trained, may assist radiologists in detection and staging of hyperparathyroidism by providing reproducible and consistent analysis of bony erosion. <<ETX>>
Lithospheric Thinning Beneath Rifted Regions of Southern California

Seismic imaging reveals the degree to which extensional forces can pull apart the lithosphere. The stretching and break-up of tectonic plates by rifting control the evolution of continents and oceans, but the processes by which lithosphere deforms and accommodates strain during rifting remain enigmatic. Using scattering of teleseismic shear waves beneath rifted zones and adjacent areas in Southern California, we resolve the lithosphere-asthenosphere boundary and lithospheric thickness variations to directly constrain this deformation. Substantial and laterally abrupt lithospheric thinning beneath rifted regions suggests efficient strain localization. In the Salton Trough, either the mantle lithosphere has experienced more thinning than the crust, or large volumes of new lithosphere have been created. Lack of a systematic offset between surface and deep lithospheric deformation rules out simple shear along throughgoing unidirectional shallow-dipping shear zones, but is consistent with symmetric extension of the lithosphere.
NCAM polysialylation during adherence transitions: Live cell monitoring using an antibody‐mimetic EGFP‐endosialidase and the viability dye DRAQ7

Polysialylation of neural cell adhesion molecule (NCAM) in small‐cell lung cancer (SCLC) is thought to regulate NCAM‐mediated cell–surface interactions, imparting antiadhesive properties to cells. However, SCLC cells in culture demonstrate anchorage‐independent growth and spontaneously generate adherent forms. Here, the ability of polySia‐NCAM to influence cell proliferation and adherence is unclear. We analyzed live SCLC cell polySia‐NCAM expression by flow cytometry, using the novel combination of a polySia antibody‐mimetic eGFP‐tagged endosialidase and the viability dye DRAQ7. Enrichment for adherence (<30 population doublings) in SCLC cell lines resolved populations with increased (SHP‐77 and COR‐L279) or negligible (NCI‐H69) polysialylation compared with nonadherent parent populations. Adherent forms retained NCAM expression as confirmed by immunofluorescence and immunoblotting. Initial transition to adherence and loss of polysialylation in NCI‐H69 was linked to a reduced proliferation rate with no increase in cell death. This reduced proliferation rate was reiterated in vivo as determined by the growth of noninvasive subcutaneous xenografts in mice. Continued selection for enhanced substrate adherence in NCI‐H69 (>150 population doublings) resolved cells with stable re‐expression of polySia and increased growth rates both in vitro and in vivo. Endoneuraminidase removal of polySia from re‐expressing cells showed that rapid adherence to extracellular matrix components was functionally independent of polySia. PolySia expression was not altered when isolated adherent forms underwent enforced cell–cell contact in three‐dimensional culture. Coculture of polySia expression variants modulated overall polySia expression profiles indicating an influence of SCLC microcommunity composition independent of substrate adherence potential. We conclude that an obligatory linkage between substrate adherence potential and polySia expression is rejected for SCLC cells. We suggest that a degree of homeostasis operates to regulate polysialylation within heterogeneous cell populations. The findings suggest a new model for SCLC progression while the application of live cell profiling of polysialylation could be used to assess polySia‐NCAM‐targeted therapies. © 2013 International Society for Advancement of Cytometry
Greasing or sanding the wheels? Effect of corruption on economic growth in sub-Saharan Africa

Corruption is a pervasive challenge confronting the world economy more especially countries in sub-Saharan Africa. This paper investigates the effect of corruption on economic growth in the sub-region using data spanning 1998 to 2011. By employing the pooled estimated generalised least squares (EGLS) and two stage least squares (2SLS), we find that corruption is inimical to economic growth through its indirect effect on gross fixed capital formation and labour force. The results are not only robust to controlling for endogeneity using regional blocs of the countries as instruments in the 2SLS estimations but identifies government expenditure as additional pass-through effect of corruption on growth. Our findings suggest that for countries within the sub-region to achieve sustained economic growth, control of corruption must take precedence over the design and implementation of any macroeconomic policy. Campaign against corruption does not only improve on institutional quality but is by far growth-enhancing.
When Talk Isn't Cheap: The Corporate Value of Political Rhetoric

Does political rhetoric matter for firms and investors? We conduct a textual analysis of all 388 gubernatorial “State of the state” speeches given between 2002 and 2010 across U.S. states, to examine this question. Political speeches may reduce policy uncertainty (Pastor and Veronesi, 2012), reflect the politician’s views regarding the economic future of the state, and contain new information regarding future policies that affect the business environment. Using data on 5,721 firms matched based on their location of their headquarters and main operations, we conduct an event study examining the market reaction to the tone of the State of the state addresses. To examine whether the information has a long-run impact on firms, we also consider changes in firms’ investment and employment decisions. Controlling for speech length, firm, and state-level characteristics, the results show a statistically significant and positive association between the level of optimism expressed in a Governor’s speech, and the abnormal returns of firms headquartered in that Governor’s state. We also find that a more optimistic speech is associated with a statistically significant increase in investment and employment, relative to firm size, whereas a more pessimistic speech is associated with a decline in investment and employment for firms located in that state. To identify the impact of the speech on firms, we show that the results are robust to identifying the geographic focus of firms’ operations, using a matched sample of firms located in neighboring states as a control group, and instrumental variables. To identify channels by which the content of the speech may have an impact, we show that firms that obtain state-government contracts, and those that are more dependent on skilled human capital and therefore education spending, significantly increase investments if the budget-related and education-related parts of the speech are more optimistic. We also find that political rhetoric is most informative during uncertain economic conditions, when government policy has had a greater impact. Lastly, we show that institutional characteristics, such as term limits and state-level transparency, affect the response of firms to the speech. * Art Durnev is at the Henry B. Tippie College of Business, University of Iowa, artem-durnev@uiowa.edu; Larry Fauver is at the University of Tennessee, lafauver@utk.edu, and Nandini Gupta is at the Kelley School of Business, Indiana University, nagupta@indiana.edu. We thank participants in the finance department seminars at Indiana and Iowa, IU Maurer School of Law, 2013 CICF Conference, Shanghai, 2013 CAF Conference at Indian School of Business, and the American Economic Association 2014 meetings.
Mobility and low contrast trip hazard avoidance using augmented depth

Objective. We evaluated a novel visual representation for current and near-term prosthetic vision. Augmented depth emphasizes ground obstacles and floor-wall boundaries in a depth-based visual representation. This is achieved by artificially increasing contrast between obstacles and the ground surface via a novel ground plane extraction algorithm specifically designed to preserve low-contrast ground-surface boundaries. Approach. The effectiveness of augmented depth was examined in human mobility trials compared against standard intensity-based (Intensity), depth-based (Depth) and random (Random) visual representations. Eight participants with normal vision used simulated prosthetic vision with 20 phosphenes and eight perceivable brightness levels to traverse a course with randomly placed small and low-contrast obstacles on the ground. Main results. The number of collisions was significantly reduced using augmented depth, compared with intensity, depth and random representations (48%, 44% and 72% less collisions, respectively). Significance. These results indicate that augmented depth may enable safe mobility in the presence of low-contrast obstacles with current and near-term implants. This is the first demonstration that an augmentation of the scene ensuring key objects are visible may provide better outcomes for prosthetic vision.
Risk taking behaviour and managerial ownership in the United States life insurance industry

This study examines the relation between risk and managerial ownership for a sample of life insurance companies in the United States. Evidence is found that the level of life insurance company risk is dependent on the level of managerial ownership. Specifically, as the level of managerial ownership increases, the level of risk increases supporting a wealth transfer hypothesis over a risk aversion hypothesis. These results are robust across several risk measures. The findings suggest that when compensation packages encourage higher levels of managerial ownership, manager and stockholder interest converge. With respect to regulation, the results suggest that regulators can control the risk taking activities of life insurers by requiring a separation between ownership and management.