Miracle-dz/UniFAR-FTUs huggingface dataset:
Assessing business-IT alignment in networked organizations

Concerns such as identifying ways to control costs, improve quality, increase effectiveness, and manage risk have become increasingly important for organizations as they face more and more pressure to gain and maintain their competitive edge. Business-IT alignment (B-ITa) is recognized as a solution to these concerns. Aligning IT with the business remains one of the top priorities for both business practitioners and researchers. Interest in B-ITa is stimulated by cases of organizations that have successfully aligned their IT to gain competitive advantage and to improve organizational performance. There is a considerable literature on B-ITa in single organizations. Within this broad scope of literature, a number of authors have stressed the importance of assessing B-ITa in order to plan B-ITa improvement actions. In support of this, these authors have developed maturity models (MMs). MMs describe the development of a speci_c domain over time. Based on maturity assessments, organizations know the extent to which processes in such domains are predictable. That is, organizations can be aware of whether a speci_c area is su_ciently re_ned and documented so that the activities in such area now have the potential to achieve their desired outcomes. However, B-ITa in collaborative networked organizations (CNOs) has hardly been studied. Yet, this is important because improved B-ITa entails a more ef- _cient use of IT in the CNO supporting the integration of information systems and processes across organizational boundaries. CNOs form the core of a new discipline that focuses on the structure, behavior, and dynamics of networks of independent organizations that collaborate using IT to better achieve common goals. Notwithstanding the e_ective application of current B-ITa MMs for single organizations, to the best of our knowledge at the time of writing this dissertation, there is no MM that speci_cally addresses the processes needed for achieving alignment between business and IT in CNOs. In response, this dissertation introduces the ICoNOs MM, a MM to assess B-ITa in CNOs. The ICoNOs MM presents a roll up of recommendations { e.g., coordination mechanisms, implementation strategies and organizational changes, in the form of process areas, speci_c goals and practices. Through its maturity levels, the ICoNOs MM provides improvement routes for those domains that are the most important for achieving alignment in CNOs. We believe that achieving B-ITa in CNOs is more complex than in single organizations because in collaborative settings, B-ITa is driven by goals of different independent organizations commonly with no centralized decision-making processes. Throughout this dissertation, we present the results of four literature surveys, one focus group, and six case studies. Based on these conceptual and empirical research activities, we designed and validated the components underlying the ICoNOs MM and the model itself.
Aldehyde Oxidase 1 (AOX1) in Human Liver Cytosols: Quantitative Characterization of AOX1 Expression Level and Activity Relationship

Aldehyde oxidase 1 (AOX1) is a cytosolic enzyme highly expressed in liver and plays a key role in metabolizing drugs containing aromatic azaheterocyclic substituents. Rapid metabolism catalyzed by AOX1 can cause a drug to exhibit high clearance, low exposure, and hence decreased efficacy or even increased toxicity (if AOX1 generated metabolites are toxic). There is a need to develop the correlation between AOX1 expression levels and AOX1-substrate clearance. A fast, sensitive, and robust liquid chromatography–tandem mass spectrometry (LC-MS/MS) method was developed to quantify AOX1 in human liver cytosol for the first time. This LC-MS/MS method includes a straightforward ultrafiltration fractionation step and gives great selectivity and wide dynamic range (5.2 pM to 20.7 nM). The AOX1 levels in human liver cytosols of 20 donors were quantified using this method to investigate individual differences in AOX1 expression. No significant individual or gender differences in AOX1 levels were observed, although male donors exhibited a broader distribution than female donors (0.74–2.30 pmol/mg versus 0.74–1.69 pmol/mg, respectively). The AOX1 protein levels measured by LC-MS/MS were consistent with those measured by an enzyme-linked immunosorbent assay. Several donors have a normal AOX1 protein level but low enzyme activity, which might be due to cofactor deficiency, single nucleotide polymorphism, or homodimer dissociation. Cytosols from donors with chronic alcohol consumption had low AOX1-catalyzed carbazeran oxidation activities (<51 µl/min per milligram compared with a median of 455 µl/min per milligram), but preserved similar AOX1 protein expression levels (approximately 15% less than the median value)
Assessing the Nature of Lipid Raft Membranes

The paradigm of biological membranes has recently gone through a major update. Instead of being fluid and homogeneous, recent studies suggest that membranes are characterized by transient domains with varying fluidity. In particular, a number of experimental studies have revealed the existence of highly ordered lateral domains rich in sphingomyelin and cholesterol (CHOL). These domains, called functional lipid rafts, have been suggested to take part in a variety of dynamic cellular processes such as membrane trafficking, signal transduction, and regulation of the activity of membrane proteins. However, despite the proposed importance of these domains, their properties, and even the precise nature of the lipid phases, have remained open issues mainly because the associated short time and length scales have posed a major challenge to experiments. In this work, we employ extensive atom-scale simulations to elucidate the properties of ternary raft mixtures with CHOL, palmitoylsphingomyelin (PSM), and palmitoyloleoylphosphatidylcholine. We simulate two bilayers of 1,024 lipids for 100 ns in the liquid-ordered phase and one system of the same size in the liquid-disordered phase. The studies provide evidence that the presence of PSM and CHOL in raft-like membranes leads to strongly packed and rigid bilayers. We also find that the simulated raft bilayers are characterized by nanoscale lateral heterogeneity, though the slow lateral diffusion renders the interpretation of the observed lateral heterogeneity more difficult. The findings reveal aspects of the role of favored (specific) lipid–lipid interactions within rafts and clarify the prominent role of CHOL in altering the properties of the membrane locally in its neighborhood. Also, we show that the presence of PSM and CHOL in rafts leads to intriguing lateral pressure profiles that are distinctly different from corresponding profiles in nonraft-like membranes. The results propose that the functioning of certain classes of membrane proteins is regulated by changes in the lateral pressure profile, which can be altered by a change in lipid content.
Patterns of Cascading Behavior in Large Blog Graphs

How do blogs cite and influence each other? How do such links evolve? Does the popularity of old blog posts drop exponentially with time? These are some of the questions that we address in this work. Blogs (weblogs) have become an important medium of information because of their timely publication, ease of use, and wide availability. In fact, they often make headlines, by discussing and discovering evidence about political events and facts. Often blogs link to one another, creating a publicly available record of how information and influence spreads through an underlying social network. Aggregating links from several blog posts creates a directed graph which we analyze to discover the patterns of information propagation in blogspace, and thereby understand the underlying social network. Here we report some surprising findings of the blog linking and information propagation structure, after we analyzed one of the largest available datasets, with 45, 000 blogs and ≈ 2.2 million blog-postings. Our analysis also sheds light on how rumors, viruses, and ideas propagate over social and computer networks.
Quantifying changes in the thiol redox proteome upon oxidative stress in vivo

Antimicrobial levels of reactive oxygen species (ROS) are produced by the mammalian host defense to kill invading bacteria and limit bacterial colonization. One main in vivo target of ROS is the thiol group of proteins. We have developed a quantitative thiol trapping technique termed OxICAT to identify physiologically important target proteins of hydrogen peroxide (H2O2) and hypochlorite (NaOCl) stress in vivo. OxICAT allows the precise quantification of oxidative thiol modifications in hundreds of different proteins in a single experiment. It also identifies the affected proteins and defines their redox-sensitive cysteine(s). Using this technique, we identified a group of Escherichia coli proteins with significantly (30–90%) oxidatively modified thiol groups, which appear to be specifically sensitive to either H2O2 or NaOCl stress. These results indicate that individual oxidants target distinct proteins in vivo. Conditionally essential E. coli genes encode one-third of redox-sensitive proteins, a finding that might explain the bacteriostatic effect of oxidative stress treatment. We identified a select group of redox-regulated proteins, which protect E. coli against oxidative stress conditions. These experiments illustrate that OxICAT, which can be used in a variety of different cell types and organisms, is a powerful tool to identify, quantify, and monitor oxidative thiol modifications in vivo.
Static and Buckling Analysis of Concrete Spherical Shells

A finite element analysis, including static and buckling analysis is presented for several notable concrete spherical shells around the world. Also, the structural optimization study of these shells was performed for thickness distribution and structure shape to reduce overall tensile stress, deflection and reinforcements. The finite element analysis using Sofistik software shows that a distributed concrete thickness reduces shell stresses, deflections and reinforcements. A geometrically non-linear analysis of these structures with and without imperfections was also performed. To take into account the possible plastification of the material an analysis with non-linear material was performed simultaneously with the geometrically non-linear analysis. This helps in developing an understanding of the structural behaviour and helps to identify all potential failure causes using failure analysis.
Identification of logically related heap regions

This paper introduces a novel set of heuristics for identifying logically related sections of the heap such as recursive data structures, objects that are part of the same multi-component structure, and related groups of objects stored in the same collection/array. When combined with lifetime properties of these structures, this information can be used to drive a range of program optimizations including pool allocation, object co-location, static deallocation, and region-based garbage collection. The technique outlined in this paper also improves the efficiency of the static analysis by providing a compact normal form for the abstract models (speeding the convergence of the static analysis). We focus on two techniques for grouping parts of the heap. The first is a technique for identifying recursive data structures in object-oriented programs based on connectivity and type information. The second technique is a method for grouping objects that make up the same composite structure and that allows us to partition the objects stored in a collection/array into groups based on a similarity relation. We provide a parametric component in the similarity relation to support specialized analysis applications (e.g. numeric analysis of object fields). Using the Em3d and Barnes-Hut benchmarks from the JOlden suite we show how these grouping methods can be used to identify various types of logical structures and enable the application of many region-based optimizations.
A Tabu Search approach for Multi Constrained Team Orienteering Problem and its application in touristic trip planning

The touristic trip planning problem can be considered as a Multi Constrained Team Orienteering Problem with Time Windows (MCTOPTW). The MCTOPTW is characterized with a set of points of interest (POI), each having a score, a time window and some attributes such as the type or entry fee. The maximum number of POIs of certain types that can be included into the itinerary is limited. A tourist can visit the POIs during their respective time windows. The objective is to visit the points that have the highest scores during specified periods of time. This paper proposes a Tabu Search approach for solving the MCTOPTW problem. To explore the neighborhood the moves Insert, Replace and Swap are applied. Additionally, the algorithm employs a tabu list, a perturbation and a diversification mechanism. The algorithm is evaluated on benchmark instances from the literature and its performance is compared to the state of the art results.
How the Cortex Gets Its Folds: An Inside-Out, Connectivity-Driven Model for the Scaling of Mammalian Cortical Folding

Larger mammalian cerebral cortices tend to have increasingly folded surfaces, often considered to result from the lateral expansion of the gray matter (GM), which, in a volume constrained by the cranium, causes mechanical compression that is relieved by inward folding of the white matter (WM), or to result from differential expansion of cortical layers. Across species, thinner cortices, presumably more pliable, would offer less resistance and hence become more folded than thicker cortices of a same size. However, such models do not acknowledge evidence in favor of a tension-based pull onto the GM from the inside, holding it in place even when the constraint imposed by the cranium is removed. Here we propose a testable, quantitative model of cortical folding driven by tension along the length of axons in the WM that assumes that connections through the WM are formed early in development, at the same time as the GM becomes folded, and considers that axonal connections through the WM generate tension that leads to inward folding of the WM surface, which pulls the GM surface inward. As an important necessary simplifying hypothesis, we assume that axons leaving or entering the WM do so approximately perpendicularly to the WM–GM interface. Cortical folding is thus driven by WM connectivity, and is a function of the fraction of cortical neurons connected through the WM, the average length, and the average cross-sectional area of the axons in the WM. Our model predicts that the different scaling of cortical folding across mammalian orders corresponds to different combinations of scaling of connectivity, axonal cross-sectional area, and tension along WM axons, instead of being a simple function of the number of GM neurons. Our model also explains variations in average cortical thickness as a result of the factors that lead to cortical folding, rather than as a determinant of folding; predicts that for a same tension, folding increases with connectivity through the WM and increased axonal cross-section; and that, for a same number of neurons, higher connectivity through the WM leads to a higher degree of folding as well as an on average thinner GM across species.
INRICH: interval-based enrichment analysis for genome-wide association studies

SUMMARY Here we present INRICH (INterval enRICHment analysis), a pathway-based genome-wide association analysis tool that tests for enriched association signals of predefined gene-sets across independent genomic intervals. INRICH has wide applicability, fast running time and, most importantly, robustness to potential genomic biases and confounding factors. Such factors, including varying gene size and single-nucleotide polymorphism density, linkage disequilibrium within and between genes and overlapping genes with similar annotations, are often not accounted for by existing gene-set enrichment methods. By using a genomic permutation procedure, we generate experiment-wide empirical significance values, corrected for the total number of sets tested, implicitly taking overlap of sets into account. By simulation we confirm a properly controlled type I error rate and reasonable power of INRICH under diverse parameter settings. As a proof of principle, we describe the application of INRICH on the NHGRI GWAS catalog. AVAILABILITY A standalone C++ program, user manual and datasets can be freely downloaded from: http://atgu.mgh. harvard.edu/inrich/.
Heterogeneous Information and Nominal Rigidities

This paper develops a model of slow macroeconomic adjustment to monetary shocks. I proceed in three steps. First, I develop a mechanism for price rigidities. My mechanism captures the notion that firms are reluctant to increase prices after an increase in demand or costs because it creates a disproportionate adverse reaction among consumers. These reactions arise endogenously for purely informational reasons. The key assumption is that some consumers are better informed than others about monetary shocks. If few consumers are informed, equilibria with nominal rigidity exist. In these equilibria firms do not change prices even though they are arbitrarily well informed, and have no menu costs. Moreover, if the proportion of informed consumers is low enough, these equilibria dominate equilibria with flexible prices. Second, I show that when firms do not change prices they inflict an informational externality on other firms. Consumers buy goods sequentially, one after the other, and change their beliefs about shocks when they see prices change. Therefore, when firms do not change prices, consumers do not learn. This hurts both firms and consumers. Third, I study the dynamic responses of output and inflation to shocks. Because learning is initially slow, the responses are delayed and hump-shaped. The responses are also asymmetric – prices increase faster than they decrease, and therefore negative shocks trigger larger output responses than positive shocks.
Leptin Directly Depolarizes Preproglucagon Neurons in the Nucleus Tractus Solitarius

OBJECTIVE Glucagon-like peptide (GLP)-1 inhibits food intake, acting both in the periphery and within the central nervous system. It is unclear if gut-derived GLP-1 can enter the brain, or whether GLP-1 from preproglucagon (PPG) cells in the lower brainstem is required to activate central GLP-1 receptors. Brainstem PPG neurons, however, have been poorly characterized, due to the difficulties in identifying these cells while viable. This study provides data on the electrical properties of brainstem PPG cells and their regulation by orexigenic and anorexigenic peptides. RESEARCH DESIGN AND METHODS Transgenic mice expressing Venus under control of the PPG promoter were used to identify PPG neurons in vitro in brainstem slice preparations for electrophysiological recordings. RESULTS The majority of PPG neurons were spontaneously active. Further electrical and molecular characterization revealed that GLP-1 receptor activation had no pre- or postsynaptic effect and that PPG neurons lack GLP-1 receptors. Similarly, they were unresponsive to PYY and ghrelin. In contrast, leptin rapidly and reversibly depolarized these neurons. Responses to electrical stimulation of the solitary tract suggest that PPG cells are mostly second-order neurons, receiving direct input from vagal afferent fibers. Both evoked and spontaneous excitatory postsynaptic currents were predominantly glutamatergic. CONCLUSIONS The study introduces PPG-promoter-Venus transgenic mice as a viable and important tool to study brainstem PPG cells. PPG neuron activity is directly modulated by leptin but was unaffected by other satiety or hunger peptides. Direct synaptic input from the solitary tract suggests that peripheral signals (including GLP-1) could modulate PPG cells via vagal afferents.
Meta-analysis of cell therapy trials for patients with heart failure.

RATIONALE Cell-based therapies are a promising intervention for the treatment of heart failure (HF) secondary to ischemic and nonischemic cardiomyopathy. However, the clinical efficacy of such new treatment requires further evaluation. OBJECTIVE To assess available clinical evidence on the safety and efficacy of cell-based therapies for HF. METHODS AND RESULTS Electronic databases (CENTRAL, DARE, NHSEED & HTA, PubMed, MEDLINE, EMBASE, CINAHL, LILACS, KoreaMed, PakMediNet, IndMed, and the Transfusion Evidence Library) were searched for relevant randomized controlled trials to June 2014. Trials of participants with HF and where the administration of any dose of autologous cells by any delivery route was compared with no intervention or placebo were eligible for inclusion. Primary outcomes were defined as mortality and rehospitalization as a result of HF. Secondary outcomes included performance status, quality of life, incidence of arrhythmias, brain natriuretic peptide levels, left ventricular ejection fraction, myocardial perfusion, and adverse events. Thirty-one independent trials (1521 participants) were included. The treatment significantly reduced the risk of mortality and rehospitalization caused by HF. There was a significant improvement in favor of stem cell treatment in performance status and exercise capacity, left ventricular ejection fraction, and quality of life. The treatment was also associated with a reduction of brain natriuretic peptide levels and no increase in the incidence of arrhythmias. However, there was considerable risk of performance, selection, and reporting bias among the included trials. CONCLUSIONS This study shows evidence that autologous cell therapy may be beneficial for patients having HF, but further evidence is required.
Lessons learned from unintended consequences about erasing the stigma of mental illness

Advocates and scientists have partnered to develop and evaluate programs meant to erase the egregious effects of the different forms of stigma. Enough evidence has been collected to yield lessons about approaches to stigma change. Some of the most insightful of these lessons emerge from unintended consequences of good intentioned approaches, and are the focus of this paper. They include the limited benefits of education especially when compared to contact, beating stigma is more than changing words, beware pity as a message, understand the competing agendas of stigma change, replace ideas of normalcy with solidarity, and avoid framing self‐stigma as the problem of people with mental illness and not of society. The paper ends with consideration of the back seat role that psychiatrists and other mental health providers should have in stigma change.
Comparison of DNA extraction kits and modification of DNA elution procedure for the quantitation of subdominant bacteria from piggery effluents with real-time PCR

Four commercial DNA extraction kits and a minor modification in the DNA elution procedure were evaluated for the quantitation of bacteria in pig manure samples. The PowerSoil®, PowerFecal®, NucleoSpin® Soil kits and QIAamp® DNA Stool Mini kit were tested on raw manure samples and on lagoon effluents for their ability to quantify total bacteria and a subdominant bacteria specific of pig manure contamination: Lactobacillus amylovorus. The NucleoSpin® Soil kit (NS kit), and to a lesser extent the PowerFecal® kit were the most efficient methods. Regardless of the kit utilized, the modified elution procedure increased DNA yield in the lagoon effluent by a factor of 1.4 to 1.8. When tested on 10 piggery effluent samples, compared to the QIAamp kit, the NS kit combined with the modified elution step, increased by a factor up to 1.7 log10 the values of the concentration of L. amylovorus. Regardless of the type of manure, the best DNA quality and the highest concentrations of bacteria were obtained using the NS kit combined with the modification of the elution procedure. The method recommended here significantly improved quantitation of subdominant bacteria in manure.