Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular characterization of neuroendocrine prostate cancer (NEPC) and identification of new drug targets.

4536 Background: NEPC is an aggressive variant of prostate cancer that can arise de novo or from existing prostate adenocarcinoma (PCA), and is promoted by the use of hormonal therapy. We sought to better understand the molecular transformation of NEPC and identify new drug targets. METHODS Using Next Generation RNA sequencing and oligonucleotide arrays, we profiled 7 NEPC, 30 PCA, and 5 benign prostate (BEN), and validated findings on tumors from a large cohort of patients (30 NEPC, 118 PCA, 30 BEN) using IHC and FISH. Functional studies were performed using NCI-H660 (NEPC), VCaP and LNCaP (PCA), RWPE (BEN). RESULTS ERG rearrangement was present in 47% of NEPC, but ERG protein expression was absent and corresponded with lack of AR. There were significant molecular differences between NEPC and PCA, with 936/25932 genes differentially expressed (P<0.001). Aurora kinase A (AURKA) and N-myc (MYCN) were overexpressed in NEPC vs PCA (P<0.001), and both genes were amplified in 35% of NEPC, 5% of PCA, and none of BEN. Transfection of MYCN induced AURKA expression and kinase activity in vitro, and AURKA induced MYCN. Either MYCN or AURKA induced expression of neuroendocrine markers (SYP, NSE) in RWPE and LNCaP, and N-myc directly binds promoters of NSE, SYP, and AR to regulate their expression (and downstream androgen regulated genes). After validating NCI-H660 as model of NEPC, we observed enhanced in vitro and in vivo sensitivity to the Aurora kinase inhibitor PHA-739358 compared to LNCaP and VCaP, with > 50% tumor shrinkage in NEPC and minimal to no effect in PCA. Phospho-H3, a downstream marker of Aurora kinase activity, was inhibited in the treated NCI-H660 and not in PCA. Notably, NE marker expression was suppressed in the treated NCI-H660 xenografts, again supporting a role of Aurora kinase in modulating the NE phenotype. CONCLUSIONS There is likely clonal origin of NEPC from PCA (with ERG fusion in both), but ERG expression limited to PCA and driven by AR signaling. We discovered significant overexpression and amplification of AURKA and MYCN in NEPC and a small subset of PCA, and evidence that that they cooperate and induce a NE phenotype in prostate cells. In vitro and in vivo data confirms that these are novel drug targets for NEPC.
Understanding IT-Culture Conflicts to Drive Successful Technochange Projects - a Case Study

The introduction of new information systems oftentimes requires organizational changes to realize improvements in a company’s performance. Still, many attempts to bring such technology driven organizational change (i.e., technochange) into practice fail. In this regard, cultural misfits are described to be a decisive cause for organizations’ resistance to change. With this paper, we outline our case study approach of investigating culture caused misfits in technochange projects using the theory of IT-culture conflicts. By ascribing cultural values to IT, we will identify potential cultural misfits concerning IT in a comprehensive and theory guided way. Based on insights we gain from a case study conducted during a Customer Relationship Management system integration in the energy sector, we will provide guidance on how to overcome cultural misfits in technochange projects as a practical contribution. As a theoretical contribution, we contribute to the exploration of culture and its influence on organizational outcomes in technochange.
Interaction design for public spaces

In this abstract I describe the doctorial research project "Interaction Design for Public Spaces". The objective of the project is to explore and design interaction contexts in culture related public spaces such as museums, experience centres and festivals. As a perspective on this domain, I will focus on the usage of the body as an interaction device. Furthermore, the project will involve a dramaturgic take on communication and design of interactive systems in the pursuit of new ways to stage the interactive contexts. The outcome of the project will be guidelines and conceptual frameworks which will help interaction designers when designing for bodily movement, and communicating and staging interactive content in public spaces.
Confusing the Crowd: Task Instruction Quality on Amazon Mechanical Turk

Task instruction quality is widely presumed to affect outcomes, such as accuracy, throughput, trust, and worker satisfaction. Best practices guides written by experienced requesters share their advice about how to craft task interfaces. However, there is little evidence of how specific task design attributes affect actual outcomes. This paper presents a set of studies that expose the relationship between three sets of measures: (a) workers’ perceptions of task quality, (b) adherence to popular best practices, and (c) actual outcomes when tasks are posted (including accuracy, throughput, trust, and worker satisfaction). These were investigated using collected task interfaces, along with a model task that we systematically mutated to test the effects of specific task design guidelines.
Dose-normalization for exposure to mycophenolic acid and the early clinical outcome in patients taking tacrolimus after heart transplantation.

BACKGROUND The early phase of MPA exposure has rarely been investigated after solid organ transplantation, especially in heart transplantation patients. We evaluated the association between exposure to mycophenolic acid (MPA), a main metabolite of mycophenolate mofetil (MMF), and clinical events within 3 months after heart transplantation. MATERIAL AND METHODS Trough (C0) and area under the curve (AUC)0-12h levels of MPA and its metabolite, mycophenolic acid glucuronide (MPAG), were determined using high-performance liquid chromatography. Corresponding clinical endpoints included acute rejection or MMF-related adverse events (gastrointestinal symptoms, leucopenia, and anemia). AUC measurements (n=77) were collected from 21 patients. Dose-normalized C0 and AUC0-12h levels were used to evaluate the association between MPA or MPAG exposure and MMF-related adverse events. RESULTS No acute rejection or mortality occurred during the follow-up period. Twelve patients (57%) developed 13 MMF-related adverse events. The MMF dose was tapered from 2.50 g/day on D1 to 1.55±0.54 g/day on D90. Significantly higher levels of dose-normalized MPA C0 and AUC0-12h were associated with the events than with the absence of the events (C0: 1.04±0.42 vs. 0.84±0.85 µg/mL/g [p=0.047]; AUC0-12h: 20.37±3.21 vs. 14.97±1.13 µg × h/mL/g; [p=0.038]). Conclusions Dose-normalized MPA exposure may protect against MMF toxicity in the early stage after heart transplantation. The MMF dose can be decreased to near 1.5 g/day 3 months post-transplantation without jeopardizing patient safety; a well-planned, tapered MMF regimen should also be considered.
Analysis of interactive packing of secondary structural elements in α/β units in proteins

An α‐helix and a β‐strand are said to be interactively packed if at least one residue in each of the secondary structural elements loses 10% of its solvent accessible contact area on association with the other secondary structural element.An analysis of all such 5,975 nonidentical α/β units in protein structures, defined at 2. 5Å resolution, shows that the interaxial distance between the α‐helix and theβ‐strand is linearly correlated with the residue‐dependent function, log[(V/nda)/n‐int], where V is the volume of amino acid residues in the packing interface,nda is the normalized difference in solventaccessible contact area of the residues in packed and unpacked secondary structural elements, and n‐int is the number of residues in the packing interface. The β‐sheet unit (βu), defined as a pair of adjacent parallel or antiparallel hydrogen‐bonded β‐strands, packing with an α‐helix shows a better correlation between the interaxial distance and log (V/nda) for the residues in the packing interface.This packing relationship is shown to be useful in the prediction of interaxial distances inα/β units using the interacting residue information of equivalentα/β units of homologous proteins.It is, therefore, of value in comparative modeling of protein structures.
Disrupted bonds – parental perceptions of regionalised transfer of very preterm infants: a small-scale study

Background: Routine regionalised transfer of preterm infants occurs throughout Westernised countries. Transfer to lower acuity units occurs once infants are ready for convalescence and signals an infant’s improving health. However, many parents find transfer traumatic. Aims: To investigate parents’ perceptions of preterm infants’ transfer; to provide neonatal clinicians with insights to facilitate optimal service provision. Methods: Participants had experienced their baby born at less than 29 weeks gestation, and subsequent transfer. Six parents were interviewed. Design: Data were analysed using a general inductive approach. Findings: Three themes were interpreted through data analysis: NICU - incomparable haven; abandonment; and parental expertise side-lined. These themes represent a journey of interrupted identity that parents undergo when their baby is transferred to another unit. Conclusion: Despite studies recommending more family-centred transfer planning, gaps persist. Nursing care might be enhanced by incorporating insight into parental experiences and promotion of collaborative changes within and between units.
Establishment of the role of IL‐6 and TNF receptor 1 using gene knockout mice

Cytokines are known to be key players in host response to infection, immunological disorders, and tissue injury in the attempt of an organism to overcome the insult and restore homeostasis. Another important aspect of cytokines, however, is their normal physiological role during development in the unchallenged organism. The most elegant way to analyze both of these functions is to introduce targeted mutations in embryonic stem cells in order to create new mouse strains deficient for a given cytokine and identify the functions that are consequently impaired or lost, This review summarizes the mutant phenotypes of mice carrying a null mutation in the cytokine IL‐6 gene or the tumor necrosis factor receptor 1 (Tnfr1) gene. Results for interferon– and interferon‐γ receptor‐deficient mice are included for comparison. J. Leukoc. Biol. 56: 565–570; 1994.
Mistaken identity: Purified basophils likely contaminated with dendritic cells

IMMUNITY to large extracellular parasites such as helminths involves mounting an effective T helper (Th) 2 response. Initiating primary Th2 responses requires antigen recognition through pattern recognition receptors (PRR), antigen processing through endosomes and lysosomes, and antigen presentation via major histocompatiblity complex (MHC) Class II. Na€ıve T cells also require costimulation via CD80/CD86 in the presence of Th2 cytokines to proliferate and develop into Th2 cells. Activation and expansion of Th2 cells in secondary lymphoid tissues result in interleukin (IL-) 4, IL-5, IL-10, and IL-13 production. Th2 responses support B cell clonal expansion and isotype class switching in response to cognate antigen. However, inappropriate Th2 responses also result in priming of allergic reactions through B cell production of IgE. Cells expressing FceRI, such as basophils and mast cells will bind IgE–antigen complexes and release granules containing histamine, proteases, leukotrienes, and cytokines that attack parasites or cause prototypic allergic reactions. Although dendritic cells (DC) are identified as the best antigen-presenting cell for stimulating na€ıve CD4 T cell responses, the source of cytokines necessary to drive Th2 subset choice (namely IL-4) has been a mystery. Therefore, it was hypothesized that accessory cells such as basophils, mast cells, and/or Group 2 innate lymphoid cells (ILC2) are required for Th2 development as a source of IL-4. These candidate accessory cells have been reported to share functional characteristics, including Th2 cytokine production and MHC Class II expression, in response to helminths and allergens. A series of Nature Immunology papers in 2009 characterized basophils with antigen presentation potential in mice (1–3). Circulating basophils in humans do not possess antigen presentation potential (4), but basophils in human secondary lymphoid tissues have not been studied for antigen presentation potential to our knowledge. Basophils are circulating granulocytes, but have been shown to home to secondary lymphoid tissue in response to certain antigens (1,2). Importantly, these papers provided evidence that murine basophils were capable of antigen uptake and antigen presentation to stimulate Th2 responses (1,2). In addition, Sokol et al., demonstrated gene expression of MHC Class II and MHC Class II promoters in bone marrowderived basophils (2). However, the expression of MHC Class II was significantly less than DC and equivalent to macrophages. It is generally accepted that DC are the best antigen presenting cell for na€ıve T cells, while macrophages are actually poor antigen presenting cells. Four weaknesses existed in these early papers reporting murine basophil antigen-presenting capabilities. First, much of the in vivo work performed in this series of papers was done very late during the course of the immune response (14– 21 days post-infection). Initial antigen presentation generally
Offshoring: Big Deal, or Business as Usual?

I would like to thank, without implicating, Gene Grossman and Helmut Wagner for helpful comments on an earlier draft, Lael Brainard and Alan Krueger for valuable references, and Princeton's Center for Economic Policy Studies for financial support. I am also grateful for many useful comments from colleagues on several earlier papers on this subject.
Kidney Stiffness Measured in an Animal Model of Unilateral Renal Arterial Stenosis Using 2D MR Elastography

Results: Fig. 1 demonstrates the smaller stenotic right kidney and larger contralateral kidney in one of the experimental animals. Dashed lines indicate representative slices used in the 2-D GRE MRE acquisition. Shear stiffness was calculated from 2-D GRE MRE acquisitions, as shown in Fig. 2. The red stars indicate the stenotic kidney with RAS. The mean shear stiffness for the normal and RAS kidneys is shown in Fig.3. The shear stiffness was similar in normal kidneys between the cortex and medulla. The stenotic cortex and medulla of pigs with hemodynamically significant RAS ( 75%) showed lower shear stiffness levels vs those in the contralateral kidney (4.9±0.6 and 5.3±0.4 kPa) compared to (6.0±0.7 and 6.5±0.6 kPa, p<0.05). Discussion: The kidney is a richly perfused organ, receiving 25% of cardiac output. RAS diminishes renal blood flow and perfusion pressure, and threaten the viability of the kidney by leading to irreversible tissue fibrosis and ultimately kidney failure. Using an experimental model of renovascular hypertension and a 2-D MRE technique to quantitatively assess the mechanical properties of renal tissue in vivo, we observed that the shear stiffness was higher in the contralateral compared to the stenotic kidney. This is despite histological evidence that indicates the presence of renal fibrosis in RAS [5]. However, in addition to induction of fibrosis, vascular occlusive diseases lower renal blood flow and perfusion pressure to the affected kidney. This may be sufficient to counterbalance the stiffness due to fibrosis. Conclusion: Our preliminary evidence suggests that after 10 weeks of experimental RAS, tissue stiffness is reduced in stenotic kidneys. This may suggest that the effect of decreased blood flow and pressure in the stenotic kidney to diminish renal stiffness at least initially overrides the development of fibrosis, and overall reduces renal turgor and increases its elasticity. Future studies will need to monitor renal elasticity in kidneys with greater levels of fibrosis, such as those after more prolonged RAS or in the presence of co-existing renal disease. Our preliminary results encourage further evaluation of renal hemodynamics, the presence of fibrosis, and techniques that may be employed to assess tissue stiffness in RAS.
A Nonvolatile Memory With Resistively Switching Methyl-Silsesquioxane

Crossbar structures with integrated methyl-silsesquioxane (MSQ) were fabricated by UV nanoimprint lithography. The sandwiched MSQ film was used for the planarization of the bottom electrodes' interface as well as for the realization of functional resistively switching crosspoint junctions. With our process, future nonvolatile crossbar memories with stacking and, thus, high integration density potential can be realized. Using MSQ as functional material additionally indicates an attractive opportunity because it is highly CMOS compatible. By programming word registers with different bit patterns, we demonstrate the potential of this crossbar architecture for future memory and logic applications.
An Exploratory Analysis of Individual Taxpayers' Compliance Behaviour in Nigeria: a Study of Demographic Differences and Impact

Tax noncompliance is a phenomenon, which has attracted attention of policy makers as well as researchers over the years. In an attempt to reverse this phenomenon, researchers had identified demographic factors as most important factors having effect on tax compliance behaviour. However, most of these researchers conducted their studies in the developed economies. To further the understanding of tax noncompliance phenomenon in the developing economies, this study analyses the differences in individual taxpayers’ compliance behaviour across demographic variables using the data extracted through a survey of individual taxpayers in Nigeria. The data were statistically treated using ANOVA technique. The results indicate statistically significant differences in taxpayers’ compliance behaviour across demographic variables of age grouping, income level, employment status and ethnicity. This finding suggests that these demographic factors significantly affect taxpayers’ compliance behaviour in Nigeria. Accordingly, policy makers must pay attention to these demographic factors in reversing the phenomenon and reawaking the spirit of compliance among individual taxpayers in Nigeria.
Admission Control in the Cloud: Algorithms for SLA-Based Service Model

Cloud computing is a paradigm that allows the flexible and on-demand provisioning of computing resources. For this reason, many institutions and enterprises have moved their data centers to the Cloud and, in particular, to public infrastructures. Unfortunately, an increase in the demand for Cloud results in resource shortages affecting both providers and consumers. With this factor in mind, Cloud service providers need Admission Control algorithms in order to make a good business decision on the types of requests to be fulfilled. Cloud providers have a desire to maximize the net income derived from provisioning the accepted service requests and minimize the impact of unprovisioned resources. This chapter introduces and compares Admission Control algorithms and proposes a service model that allows the definition of Service Level Agreements for the Cloud.
A comprehensive polarisation model for surface orientation recovery

In this paper a polarisation model which predicts surface reflection as a function of refractive index and angle of incidence is introduced. We present the underlying physics of polarisation which is based on the Fresnel theory and Malus' law. The proposed model can be used to recover the shape of the objects for images taken under polarised light. The traditional way of shape recovery using diffuse polarisation is inaccurate due to noise in the degree of polarisation (DOP) measurements, computed from images captured under unpolarised light, which are small at most locations on the surface. The proposed model improves results as the DOP values are relatively larger in polarised light, we present a number of experimental results to demonstrate.
Using job analysis to identify core and specific competencies: implications for selection and recruitment

Objective Modern postgraduate medical training requires both accurate and reliable selection procedures. An essential first step is to conduct detailed job analysis studies. This paper reports data on a series of job analyses to develop a competency model for three secondary care specialties (anaesthesia, obstetrics and gynaecology, and paediatrics).
Concerning the function of the fetal zone of the human adrenal gland.

THE unusually large size of the adrenal glands of the human fetus (Figs. 1, 2) and their rapid partial involution have been the subject of numerous reports and investigations. Lanman (1953) contributed an admirable summary of all known details concerning the development and probable function of this gland in the developing human fetus and added a valuable comparative anatomic study of the adrenals in other animals. While a wealth of contributions to the literature is cited by Lanman (19.53), his conclusion is that little definite is known regarding the actual physiology of the adrenal in the unborn human fetus. In this communication the authors have attempted to summarize the. more important literature pertaining to the human fetal adrenal. In addition, a histologic correlation with the chemical data of the preceding paper is presented. On the basis of this material and evidence derived from the literature the endocrine relations are discussed which are of probable significance in the maintenance and func.
Subcellular localization and topology of the K88 usher FaeD in Escherichia coli

The subcellular localization of the K88 usher FaeD was studied in Escherichia coli whole ceils by using iso‐pycnic sucrose density gradient centrifugation of isolated membranes, the detergents Triton X‐100 and sodium lauryl sarcosinate and immunoblotting with a specific FaeD antiserum. Cells containing the complete K88 operon, as well as cells containing the sub‐cloned faeD gene in various expression vectors, were used. Most of the FaeD was present in the outer membranes in a detergent‐resistant form. Agglutination experiments with E coli cells expressing FaeD confirmed an outer membrane localization and indicated the presence of FaeD at the cell surface. Automated Edman degradation indicated that the mature FaeD contained 777 amino acid residues and confirmed that FaeD is synthesized with a rather long signal sequence of 35 amino acid residues. Twelve different FaeD–PhoA fusion proteins were prepared and characterized by nucleotide sequencing and immuno‐blotting. Most of these fusion sites were located in the amino‐terminal and carboxyl‐terminal regions of FaeD. Six amino‐terminal fusion proteins were soluble proteins in the peripiasm, whereas the other fusion proteins were associated with the outer membrane. The protease accessibility of FaeD and of the six outer membrane‐bound FaeD–PhoA fusion proteins was studied using whole cells, cells with permeabilized outer membranes, and isolated membranes. Collagenase H, kallikrein, trypsin and proteinase K were used. Based on the results of these experiments and computer predictions, a model for the membrane topology of FaeD was developed in which FaeD contains a large central domain containing 24 membrane‐spanning segments and two relatively large periplasmic regions, at the amino‐terminal and carboxyl‐terminal end of the protein, respectively.