Miracle-dz/UniFAR-FTUs huggingface dataset:
Case study: lessons learned through digitizing the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research Collection.

The Indiana University Center for Bioethics (IUCB) and the Ruth Lilly Medical Library (RLML), Indiana University School of Medicine, joined forces in 2005 to augment online access to bioethics-related materials by developing the Bioethics Digital Library (BEDL) [1]. BEDL's goal is to acquire or borrow unique bioethics-related materials and special collections for digitization, to preserve the digitized materials, and to provide open access to these materials through a full-text indexed, Web-integrated database. To enhance discoverability of BEDL materials, content will be linked to citation records in the Kennedy Institute of Ethics National Reference Center for Bioethics Literature ETHX on the Web database [2] as well as other appropriate digital repositories, creating a network of bioethics resources with multiple access points. Interest in providing open access to digital scholarship is increasing as evidenced by the National Institutes of Health's Public Access Policy [3] and the introduction of the Federal Research Public Access Act of 2006 (FRPAA, S.2695) [4]. One way to contribute to the open access initiative is to convert historical materials found in disparate locations to digital formats that are discoverable and freely accessible on the Internet. This paper presents a digitization case study that illustrates the challenges of transforming a historical collection to a digital collection while attempting to retain the look and feel of the original historical materials.
Smooth relevance vector machines

Regression tasks belong to the set of core problems faced in statistics and machine learning and promising approaches can often be generalized to also deal with classification, interpolation or denoising problems. Whereas the most widely used classical statistical techniques place severe a priori constraints on the type of function that can be approximated (e.g. only lines, in the case of linear regression), the successes of sparse kernel learners, such as the SVM (support vector machine) demonstrate that good results may be obtained in a quite general framework by enforcing sparsity. Similarly, even very simple sparsity-based denoising techniques, such as classical wavelet shrinkage, can produce surprisingly good results on a wide variety of different signals, because, unlike noise, most signals of practical interest share vital characteristics (such as smoothness, or the ability to be well approximated by piece-wise linear polynomials of a low order) that allow a sparse representation in wavelet space. On the other hand results obtained from SVMs (and classical wavelet-shrinkage) suffer from a certain lack of interpretability, since one cannot straightforwardly attach probabilities to them. By contrast regression, and even more importantly classification, in a Bayesian context always entails a probabilistic measure of confidence in the results, which, provided the model assumptions are reasonably accurate, forms a basis for principled decision-making. The relevance vector machine (RVM) combines these strengths by explicitly encoding the criterion of model sparsity as a (Bayesian) prior over the model weights and offers a single, unified paradigm to efficiently deal with regression as well as classification tasks. However the lack of an explicit prior structure over the weight variances means that the degree of sparsity is to a large extent controlled by the choice of kernel (and kernel parameters). This can lead to severe overfitting or oversmoothing – possibly even both at the same time (e.g. for the multiscale Doppler data). This thesis details an efficient scheme to control sparsity in Bayesian regression by incorporating a flexible noise-dependent smoothness prior into the RVM. The resultant smooth RVM (sRVM) encompasses the original RVM as a special case, but empirical results with a variety of popular data sets show that it can surpass RVM performance in terms of goodness of fit and achieved sparsity as well as computational performance in many cases. As the smoothness prior effectively makes it possible to use (highly efficient) wavelet kernels in an RVM setting this work also unveils a strong connection between Bayesian wavelet shrinkage and RVM regression and effectively further extends the applicability of the RVM to denoising tasks for up to millions of datapoints. We further discuss its applicability to classification tasks.
Visualizing agent-based simulation dynamics in a CAVE — Issues and architectures

Displaying an agent-based simulation on an immersive virtual environment called CAVE (Cave Automatic Virtual Environment), a human expert is enabled to evaluate the simulation's dynamics from the same point of view as in real life — from a within perspective instead of a birds eye view. As this form of face validation is useful for many multiagent simulations, it should be possible to setup such a system with as little effort as possible. In this context, we systematically analyse the critical issues that a realization of such a system raises. Addressing these problems, we finally discuss design aspects of basic framework architectures.
Design and Construction of an Equibiaxial Cell Stretching System That Is Improved for Biochemical Analysis

We describe the design and validation of an equibiaxial stretching device in which cells are confined to regions of homogeneous strain. Using this device, we seek to overcome a significant limitation of existing equibiaxial stretching devices, in which strains are not homogeneous over the entire region of cell culture. We cast PDMS in a mold to produce a membrane with a cylindrical wall incorporated in the center, which was used to confine cell monolayers to the central membrane region subjected to homogeneous equibiaxial strain. We demonstrated that the presence of the wall to hold the culture medium did not affect strain homogeneity over the majority of the culture surface and also showed that cells adhered well onto the PDMS membranes. We used our device in cyclic strain experiments and demonstrated strain-dependent changes in extracellular signal-regulated kinase (ERK) and tyrosine phosphorylation upon cell stretching. Furthermore, we examined cell responses to very small magnitudes of strain ranging from 1% to 6% and were able to observe a graduated increase in ERK phosphorylation in response to these strains. Collectively, we were able to study cellular biochemical response with a high degree of accuracy and sensitivity to fine changes in substrate strain. Because we have designed our device along the lines of existing equibiaxial stretching technologies, we believe that our innovations can be incorporated into existing systems. This device would provide a useful addition to the set of tools applied for in vitro studies of cell mechanobiology.
Use of medications with anticholinergic effect predicts clinical severity of delirium symptoms in older medical inpatients.

BACKGROUND Use of anticholinergic (ACH) medications is a biologically plausible and potentially modifiable risk factor of delirium, but research findings are conflicting regarding its association with delirium. OBJECTIVES To evaluate the longitudinal association between use of ACH medications and severity of delirium symptoms and to determine whether this association is modified by the presence of dementia. PATIENTS AND METHODS A total of 278 medical inpatients 65 years and older with diagnosed incident or prevalent delirium were followed up with repeated assessments using the Delirium Index for up to 3 weeks. Exposure to ACH and other medications was measured daily. The association between change in medication exposure in the 24 hours preceding a Delirium Index assessment was assessed using a mixed linear regression model. RESULTS During follow-up (mean +/- SD, 12.3 +/- 7.0 days), 47 medications with potential ACH effect were used in the population (mean, 1.4 medications per patient per day). Increase in delirium severity was significantly associated with several measures of ACH medication exposure on the previous day, adjusting for dementia, baseline delirium severity, length of follow-up, and number of non-ACH medications taken. Dementia did not modify the association between ACH medication use and delirium severity. CONCLUSION Exposure to ACH medications is independently and specifically associated with a subsequent increase in delirium symptom severity in elderly medical inpatients with diagnosed delirium.
Interaction of tiagabine with valproate in the mouse pentylenetetrazole-induced seizure model: an isobolographic analysis for non-parallel dose-response relationship curves.

PURPOSE To characterize the interaction between tiagabine (TGB) and valproate (VPA)--two antiepileptic drugs in the mouse pentylenetetrazole (PTZ)-induced clonic seizure model, type I isobolographic analysis for non-parallel dose-response relationship curves (DRRCs) was used. MATERIAL AND METHODS Clonic seizures were evoked in albino Swiss mice by subcutaneous injection of PTZ at its CD97 (100 mg/ kg). To ascertain the nature of interaction between TGB and VPA administered in combination, total brain concentrations of TGB and VPA were estimated by using high-performance liquid chromatography (HPLC) and fluorescence polarization immunoassay (FPIA). RESULTS TGB and VPA produced clear-cut anticonvulsant effects against PTZ-induced clonic seizures in mice and their DRRCs were not parallel to one another. The type I isobolographic analysis for non-parallel DRRCs revealed that the combination of TGB with VPA at the fixed-ratio of 1:1 exerted additive interaction against PTZ-induced clonic seizures in mice. With FPIA, it was found that TGB did not affect total brain VPA concentrations in experimental animals. Moreover, VPA had no significant impact on total brain concentrations of TGB in mice, as measured with HPLC. CONCLUSION The additive interaction between TGB and VPA at the fixed-ratio of 1:1 in the mouse PTZ model was pharmacodynamic in nature.
CD44 expression in IgA nephropathy.

Immunoglobulin A (IgA) nephropathy is a frequent, chronic renal disease characterized by a broad spectrum of clinical presentations and pathologic findings. CD44, a family of type I transmembrane glycoproteins involved in cell-cell and cell-matrix interactions, may orchestrate partially the cascade of inflammation, accumulation of myofibroblasts, and fibrosis leading to end-stage renal disease. To clarify the possible role of CD44 in the progression of IgA nephropathy, the expression of CD44 in glomeruli and the tubulointerstitial compartment was analyzed in 25 renal biopsy specimens of patients with IgA nephropathy and was correlated to histopathologic, serologic, and urinary parameters. The expression of CD44 correlated significantly with the degree of glomerular and interstitial damage, even better than the accumulation of alpha-smooth muscle actin-positive myofibroblasts, which is recognized as a reliable marker for the progression of IgA nephropathy. A positive correlation also was found between proteinuria and the expression of CD44 in the tubulointerstitial compartment. The glomerular and tubulointerstitial expression of CD44 correlated with the degree of renal damage in IgA nephropathy and could be a reliable marker of the progression of IgA nephropathy. CD44 may have a pivotal role in the cascade of renal inflammation and fibrosis.
Cytokine Gene Expression by Peripheral Blood Leukocytes in Horses Experimentally Infected with Anaplasma phagocytophila

ABSTRACT Human granulocytic ehrlichiosis (HGE), a tick-borne zoonosis, is caused by an obligatory intragranulocytic bacterium, the HGE agent, a strain of Anaplasma phagocytophila. The equine model of HGE is considered valuable in understanding pathogenic and immune mechanisms of HGE. In the present study, cytokine mRNA expression by peripheral blood leukocytes (PBLs) in horses was examined during the course of infection by intravenous inoculation of A. phagocytophila or by allowing feeding by infected ticks. The p44 genes encoding the major outer membrane protein P44s of A. phagocytophila were detected by PCR in PBLs of all four horses from 4 to 20 days postexposure. During the 20-day infection period, interleukin-1β (IL-1β) and tumor necrosis factor alpha (TNF-α) mRNA expression was upregulated in PBLs of all four horses, and IL-8 mRNA expression was upregulated in three horses. Gamma interferon, IL-10, and IL-12 p35 mRNAs were weakly expressed in only one horse each. IL-2, IL-4, IL-6, and IL-12 p40 mRNA expression , however, could not be detected in the PBLs of any of the four horses. These results suggest that IL-1β, TNF-α, and IL-8 generation during A. phagocytophila infection has a primary role in HGE pathogenesis and immunomodulation.
Implications for Diagnostics in the Biochemistry and Physiology of Saliva

Abstract: Oral fluid mainly consists of a mixture of glandular salivas. In addition, it is contaminated by some crevicular fluid, containing serum constituents. The contribution of the various salivary glands shows a continuous variation, resulting in wide ranges of concentrations for all constituents of oral fluid. As a consequence, the collection of oral fluid for diagnostic purposes should be standardized. Oral fluid can be used to detect a number of diseases and recent use of illicit drugs. It can also be used to monitor therapeutic drug concentrations. The development of microchips for salivary components offers great possibilities to use oral fluid for point‐of‐care testing.
Presynaptic Calcium Stores Modulate Afferent Release in Vestibular Hair Cells

Hair cells, the mechanoreceptors of the acoustic and vestibular system, are presynaptic to primary afferent neurons of the eighth nerve and excite neural activity by the release of glutamate. In the present work, the role played by intracellular Ca2+ stores in afferent transmission was investigated, at the presynaptic level, by monitoring changes in the intracellular Ca2+ concentration ([Ca2+]i) in vestibular hair cells, and, at the postsynaptic level, by recording from single posterior canal afferent fibers. Application of 1-10 mm caffeine to hair cells potentiated Ca2+ responses evoked by depolarization at selected Ca2+ hot spots, and also induced a graded increase in cell membrane capacitance (ΔCm), signaling exocytosis of the transmitter. Ca2+ signals evoked by caffeine peaked in a region located ∼10 μm from the base of the hair cell. [Ca2+]i increases, similarly localized, were observed after 500 msec depolarizations, but not with 50 msec depolarizations, suggesting the occurrence of calcium-induced calcium release (CICR) from the same stores. Both Ca2+ and ΔCm responses were inhibited after incubation with ryanodine (40 μm) for 8-10 min. Consistent with these results, afferent transmission was potentiated by caffeine and inhibited by ryanodine both at the level of action potentials and of miniature EPSPs (mEPSPs). Neither caffeine nor ryanodine affected the shape and amplitude of mEPSPs, indicating that both drugs acted at the presynaptic level. These results strongly suggest that endogenous modulators of the CICR process will affect afferent activity elicited by mechanical stimuli in the physiological frequency range.
Mutations within the mepA Operator Affect Binding of the MepR Regulatory Protein and Its Induction by MepA Substrates in Staphylococcus aureus

ABSTRACT The expression of mepA, encoding the Staphylococcus aureus MepA multidrug efflux protein, is repressed by the MarR homologue MepR. Repression occurs through binding of two MepR dimers to an operator with two homologous and closely approximated pseudopalindromic binding sites (site 1 [S1] and site 2 [S2]). MepR binding is impeded in the presence of pentamidine, a MepA substrate. The effects of various mepA operator mutations on MepR binding were determined using electrophoretic mobility shift assays and isothermal titration calorimetry, and an in vivo confirmation of the effects observed was established for a fully palindromic operator mutant. Altering the S1-S2 spacing by 1 to 4 bp severely impaired S2 binding, likely due to a physical collision between adjacent MepR dimers. Extension of the spacing to 9 bp eliminated the S1 binding-mediated DNA allostery required for efficient S2 binding, consistent with positive cooperative binding of MepR dimers. Binding of a single dimer to S1 was maintained when S2 was disrupted, whereas disruption of S1 eliminated any significant binding to S2, also consistent with positive cooperativity. Palindromization of binding sites, especially S2, enhanced MepR affinity for the mepA operator and reduced MepA substrate-mediated MepR induction. As a result, the on-off equilibrium between MepR and its binding sites was shifted toward the on state, resulting in less free MepR being available for interaction with inducing ligand. The selective pressure(s) under which mepA expression is advantageous likely contributed to the accumulation of mutations in the mepA operator, resulting in the current sequence from which MepR is readily induced by MepA substrates.
Gouverner la reconversion industrielle dans le Haut-milanais : interrogations sur les processus de représentation et de défense des intérêts territoriaux

Aboutissement d’une enquete de communaute menee sur deux ans et demi dans le Haut-milanais (2008-2010), cette etude s’interesse a la maniere dont a ete gouvernee la reconversion industrielle dans cette region, en se concentrant tout particulierement sur la ville de Legnano. La premiere partie expose le cadre theorique mobilise pour cette etude, a savoir la political economy de la petite ville, qui s’interesse particulierement a l’articulation entre dimensions politiques et dimensions economiques. La partie suivante presente les donnees que nous avons collectees pour repondre a la question principale de l’enquete. Nous presentons notamment des donnees positionnelles et reputationnelles sur les elites qui ont joue un role majeur dans la reconversion de trois zones strategiques. Dans la derniere partie de cette etude, nous nous interrogeons sur les aspects politiques du gouvernement du territoire en distinguant les acteurs decisionnaires au niveau local de ceux qui sont en mesure de les representer a d’autres niveaux, afin de mobiliser des ressources grâce auxquelles il devient possible de mettre en œuvre ces decisions. Ainsi, les acteurs du gouvernement local sont-ils en mesure de s’eriger en tant qu’interlocuteurs face aux demandes sociales, de recueillir et de filtrer les requetes et les interets qui emanent du territoire, et de structurer les modalites de coordination entre autorites locales et principaux acteurs economiques. Pourtant, la representation de ces interets a des niveaux superieurs est deleguee a des groupes segmentaires a forte solidarite interne.
Distributed Localization Method Based on Loose Iterative MDS in Wireless Sensor Networks

The localization of sensor node is an important technology in wireless sensor networks. In this paper, a distributed localization method based on loose iterative MDS (multidimensional scaling) is proposed. This method can build global map by the combination of local maps, which are calculated by loose iterative MDS algorithm. The simulations show that the global map can be obtained quickly both in regularly-shaped and irregularly-shaped networks. Compared with the extant methods, the proposed method has the lower computing complexity in the case of the same accuracy of location error
Monocytes Are Highly Sensitive to Clostridium difficile Toxin A-Induced Apoptotic and Nonapoptotic Cell Death

ABSTRACT In this study we investigated the in vitro responses of peripheral blood mononuclear preparations and purified monocytes to Clostridium difficile toxin A. In contrast to the responses of T and B cells, exposure to toxin A led to a rapid loss of monocytes in a time- and dose-dependent fashion (the majority of cells were lost within 24 h of exposure to >100 ng of toxin per ml). Transmission electron microscopy, flow cytometry, and fluorescence microscopy after propidium iodide and Hoechst staining showed that cell death in purified preparations of monocytes following exposure to 100 and 1,000 ng of toxin A per ml occurred by apoptosis. Further studies showed that 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazole-carbocyanine iodide aggregates were retained within toxin A-exposed monocyte mitochondria, but cytochrome c was released, suggesting that the apoptotic cascade was triggered in the absence of mitochondrial permeability transition. There was also an increase in caspase-3 activity in toxin A-stimulated monocytes. Following exposure to very high concentrations of toxin A (30 μg/ml), monocyte cell death was predominantly of the necrotic type, with rapid extracellular release of lactate dehydrogenase. These studies demonstrated that C. difficile toxin A has a cell-specific effect, in which monocytes exhibit greater susceptibility than lymphocytes and their death is induced in a concentration-dependent manner.
A Lightweight Hat: Simple Type-Preserving Instrumentation for Self-Tracing Lazy Functional Programs

Existing methods for generating a detailed trace of a computation of a lazy functional program are complex. These complications limit the use of tracing in practice. However, such a detailed trace is desirable for understanding and debugging a lazy functional program. Here we present a lightweight method that instruments a program to generate such a trace, namely the augmented redex trail introduced by the Haskell tracer Hat. The new method is a major step towards an omniscient debugger for real-world Haskell programs.
Hand sanitisers for reducing illness absences in primary school children in New Zealand : a cluster randomised controlled trial study protocol

Background: New Zealand has relatively high rates of morbidity and mortality from infectious disease compared with other OECD countries, with infectious disease being more prevalent in children compared with others in the population. Consequences of infectious disease in children may have significant economic and social impact beyond the direct effects of the disease on the health of the child; including absence from school, transmission of infectious disease to other pupils, staff, and family members, and time off work for parents/guardians. Reduction of the transmission of infectious disease between children at schools could be an effective way of reducing the community incidence of infectious disease. Alcohol based no-rinse hand sanitisers provide an alternative hand cleaning technology, for which there is some evidence that they may be effective in achieving this. However, very few studies have investigated the effectiveness of hand sanitisers, and importantly, the potential wider economic implications of this intervention have not been established. Aims: The primary objective of this trial is to establish if the provision of hand sanitisers in primary schools in the South Island of New Zealand, in addition to an education session on hand hygiene, reduces the incidence rate of absence episodes due to illness in children. In addition, the trial will establish the cost-effectiveness and conduct a cost-benefit analysis of the intervention in this setting. Methods/Design: A cluster randomised controlled trial will be undertaken to establish the effectiveness and costeffectiveness of hand sanitisers. Sixty-eight primary schools will be recruited from three regions in the South Island of New Zealand. The schools will be randomised, within region, to receive hand sanitisers and an education session on hand hygiene, or an education session on hand hygiene alone. Fifty pupils from each school in years 1 to 6 (generally aged from 5 to 11 years) will be randomly selected for detailed follow-up about their illness absences, providing a total of 3400 pupils. In addition, absence information will be collected on all children from the school rolls. Investigators not involved in the running of the trial, outcome assessors, and the statistician will be blinded to the group allocation until the analysis is completed. Trial registration: ACTRN12609000478213