Miracle-dz/UniFAR-FTUs huggingface dataset:
Macromolecular Crowding as a Suppressor of Human IAPP Fibril Formation and Cytotoxicity

The biological cell is known to exhibit a highly crowded milieu, which significantly influences protein aggregation and association processes. As several cell degenerative diseases are related to the self-association and fibrillation of amyloidogenic peptides, understanding of the impact of macromolecular crowding on these processes is of high biomedical importance. It is further of particular relevance as most in vitro studies on amyloid aggregation have been performed in diluted solution which does not reflect the complexity of their cellular surrounding. The study presented here focuses on the self-association of the type-2 diabetes mellitus related human islet amyloid polypeptide (hIAPP) in various crowded environments including network-forming macromolecular crowding reagents and protein crowders. It was possible to identify two competing processes: a crowder concentration and type dependent stabilization of globular off-pathway species and a – consequently - retarded or even inhibited hIAPP fibrillation reaction. The cause of these crowding effects was revealed to be mainly excluded volume in the polymeric crowders, whereas non-specific interactions seem to be most dominant in protein crowded environments. Specific hIAPP cytotoxicity assays on pancreatic β-cells reveal non-toxicity for the stabilized globular species, in contrast to the high cytotoxicity imposed by the normal fibrillation pathway. From these findings it can be concluded that cellular crowding is able to effectively stabilize the monomeric conformation of hIAPP, hence enabling the conduction of its normal physiological function and prevent this highly amyloidogenic peptide from cytotoxic aggregation and fibrillation.
A survey on context-aware systems

Context-aware systems offer entirely new opportunities for application developers and for end users by gathering context data and adapting systems behaviour accordingly. Especially in combination with mobile devices, these mechanisms are of high value and are used to increase usability tremendously. In this paper, we present common architecture principles of context-aware systems and derive a layered conceptual design framework to explain the different elements common to most context-aware architectures. Based on these design principles, we introduce various existing context-aware systems focusing on context-aware middleware and frameworks, which ease the development of context-aware applications. We discuss various approaches and analyse important aspects in context-aware computing on the basis of the presented systems.
Notch signaling coordinates the patterning of striatal compartments

Numerous lines of evidence suggest that Notch signaling plays a pivotal role in controlling the production of neurons from progenitor cells. However, most experiments have relied on gain-of-function approaches because perturbation of Notch signaling results in death prior to the onset of neurogenesis. Here, we examine the requirement for Notch signaling in the development of the striatum through the analysis of different single and compound Notch1 conditional and Notch3 null mutants. We find that normal development of the striatum depends on the presence of appropriate Notch signals in progenitors during a critical window of embryonic development. Early removal of Notch1 prior to neurogenesis alters early-born patch neurons but not late-born matrix neurons in the striatum. We further show that the late-born striatal neurons in these mutants are spared as a result of functional compensation by Notch3. Notably, however, the removal of Notch signaling subsequent to cells leaving the germinal zone has no obvious effect on striatal organization and patterning. These results indicate that Notch signaling is required in neural progenitor cells to control cell fate in the striatum, but is dispensable during subsequent phases of neuronal migration and differentiation.
Analyzing Tensor Power Method Dynamics in Overcomplete Regime

We present a novel analysis of the dynamics of tensor power iterations in the overcomplete regime where the tensor CP rank is larger than the input dimension. Finding the CP decomposition of an overcomplete tensor is NP-hard in general. We consider the case where the tensor components are randomly drawn, and show that the simple power iteration recovers the components with bounded error under mild initialization conditions. We apply our analysis to unsupervised learning of latent variable models, such as multiview mixture models and spherical Gaussian mixtures. Given the third order moment tensor, we learn the parameters using tensor power iterations. We prove it can correctly learn the model parameters when the number of hidden components k is much larger than the data dimension d, up to k = o(d1.5). We initialize the power iterations with data samples and prove its success under mild conditions on the signal-to-noise ratio of the samples. Our analysis significantly expands the class of latent variable models where spectral methods are applicable. Our analysis also deals with noise in the input tensor leading to sample complexity result in the application to learning latent variable models.
New Developments in the Methodology of Expert- and Argument-Based Probabilistic Population Forecasting

All population projections are based in one form or another on expert judgement about likely future trends, structural continuity, etc. Although experts are clearly superior to lay people in their field of expertise, when it comes to forecasting they may make serious errors and can be as ignorant as anybody. In the context of expert-based probabilistic population projections, this issue is receiving even more attention. In this paper we argue that information about the future cannot be true for the reason that it is being presented by an acknowledged authority (institution or person), nor is it acceptable to resolve scientific issues on the ground of voting or concert. As an alternative we propose the concept of argument-based expert opinion. Under this approach any structural and trend assumption needs to be based on explicit argumentation rather than implicit judgement.
Risk factors in patients with AFB smear-positive sputum who receive inappropriate antituberculous treatment

Background Acid-fast bacilli (AFB) smear-positive sputum is usually an initial clue in the diagnosis of pulmonary tuberculosis (TB); however, the test is not disease-specific. Nontuberculous mycobacterium-related colonization or lung disease often has AFB smear-positive sputum results, and physicians may prescribe unnecessary antituberculous drugs for these patients. The aim of this study was to analyze the clinical characteristics of patients with AFB smear-positive sputum who received unnecessary anti-TB treatment. Methods and patients From January 2008 to July 2011, we retrospectively enrolled 97 patients with AFB smear-positive sputum who did not have pulmonary TB according to mycobacterial cultures and clinical judgment. We analyzed the clinical and radiographic features of the patients who received inappropriate and unnecessary anti-TB treatment. Preliminary analyses of chisquare and Fisher’s exact tests were applied to determine factors unlikely to be associated with the independent variables. The relationship between independent covariates was then analyzed using multivariate logistic regression. Results Of the 97 enrolled patients, 25 (25.8%) were diagnosed with pulmonary TB and prescribed anti-TB drugs (mostly a combination of isoniazid, rifampicin, ethambutol, and pyrazinamide). The other 72 (74.2%) patients were not initially diagnosed with pulmonary TB and were classified as the control group. Compared to the control group, the patients who received inappropriate anti-TB treatment had more chronic cough as presentation symptom and heavy AFB Ziehl–Neelsen staining in sputum (>10/100 fields, grading 2+ to 4+). There were no significant differences in the radiographic analysis between the two groups. Conclusion Among the patients with AFB smear-positive sputum that did not have pulmonary TB, chronic cough and heavy AFB staining (2+ to 4+) were risk factors for the inappropriate administration of unnecessary anti-TB treatment.
One size fits all?

In this article, I would like to pick up an issue which has been around since the first commercialization efforts in microfluidics: standards and standardization. The discussion of this issue will not surprise many of you, as you will understand that the economic success of a large number of products or even complete industries can be attributed to a high degree of standardization. It is obvious that, at least in theory, standardization helps in increasing production volumes of products and thus, through learning curve and economy-of-scale effects, leads to reduced manufacturing cost which, in turn, increases market size and competitiveness of the technology. One of the exemplary industrial sectors which is frequently quoted to support this line of argument is the microelectronics industry. This example is used for historical reasons as many of the early works in microfluidics which formed the first images of this technology utilized classical fabrication methods directly borrowed from the microelectronics industry, namely methods to structure silicon using photolithography and wet chemical etching. It was assumed that these methods would play an important role in the commercialization of microfluidic devices. To quote from the conclusions of one of the earliest reviews of the field: ‘‘The possibility of mass fabricating devices using integrated circuit and micromachining technologies may lead to low cost systems. ’’. The second reason for using the microelectronics analogy lies in the fact that in both cases, miniaturization is seen as a common denominator for technological advances pushing the performance and lowering the cost of a new technology. The existence of Moore’s Law in microelectronics has, in the past, raised hopes of a similar development in the information creation in
Molecular and Cellular Functions Distinguish Superior Therapeutic Efficiency of Bone Marrow CD45 Cells Over Mesenchymal Stem Cells in Liver Cirrhosis

Liver fibrosis is strongly associated with chronic inflammation. As an alternative to conventional treatments for fibrosis, mesenchymal stem cells (MSCs) therapy is found to be attractive due to its immunomodulatory functions. However, low survival rate and profibrogenic properties of MSCs remain the major concerns, leading to skepticism in many investigators. Here, we have asked the question whether bone marrow (BM)‐derived CD45 cells is the better candidate than MSCs to treat fibrosis, if so, what are the molecular mechanisms that make such distinction. Using CCl4‐induced liver fibrosis mouse model of a Metavir fibrosis score 3, we showed that BM‐CD45 cells have better antifibrotic effect than adipose‐derived (AD)‐MSCs. In fact, our study revealed that antifibrotic potential of CD45 cells are compromised by the presence of MSCs. This difference was apparently due to significantly high level expressions of matrix metalloproteinases‐9 and 13, and the suppression of hepatic stellate cells' (HpSCs) activation in the CD45 cells transplantation group. Mechanism dissection studied in vitro supported the above opposing results and revealed that CD45 cell‐secreted FasL induced apoptotic death of activated HpSCs. Further analyses suggest that MSC‐secreted transforming growth factor β and insulin‐like growth factor‐1 promoted myofibroblastic differentiation of HpSCs and their proliferation. Additionally, the transplantation of CD45 cells led to functional improvement of the liver through repair and regeneration. Thus, BM‐derived CD45 cells appear as a superior candidate for the treatment of liver fibrosis due to structural and functional improvement of CCl4‐induced fibrotic liver, which were much lower in case of AD‐MSC therapy. Stem Cells 2016;34:135–147
Extraction, isolation and evaluation Trigonella foenum-graecum as mucoadhesive agent for nasal gel drug delivery

The purpose of the study is to formulate and evaluate a new, cheap and effective natural mucoadhesive agent that can be used as an effective alternative for traditional mucoadhesive agent. The study procedure involved extraction of mucoadhesive agent from the Trigonellafoenumgraecum (fenugreek) seeds, solubility testing of the mucilage obtained, phytochemical testing, determination of swelling index, preparation of nasal gel, measurement of viscosity, The study showed that the extraction of fenugreek seeds had 36% w/w of mucoadhesive agent. The natural mucoadhesive agent was soluble in hot water and cold water.The swelling index was found to be 160%. Fenugreek seeds produce high viscosity mucilage at low concentration levels.
64Cu-CTS: A Promising Radiopharmaceutical for the Identification of Low-Grade Cardiac Hypoxia by PET

The subtle hypoxia underlying chronic cardiovascular disease is an attractive target for PET imaging, but the lead hypoxia imaging agents 64Cu-2,3-butanedione bis(N4-methylthiosemicarbazone) (ATSM) and 18F-fluoromisonidazole are trapped only at extreme levels of hypoxia and hence are insufficiently sensitive for this purpose. We have therefore sought an analog of 64Cu-ATSM better suited to identify compromised but salvageable myocardium, and we validated it using parallel biomarkers of cardiac energetics comparable to those observed in chronic cardiac ischemic syndromes. Methods: Rat hearts were perfused with aerobic buffer for 20 min, followed by a range of hypoxic buffers (using a computer-controlled gas mixer) for 45 min. Contractility was monitored by intraventricular balloon, energetics by 31P nuclear MR spectroscopy, lactate and creatine kinase release spectrophotometrically, and hypoxia-inducible factor 1-α by Western blotting. Results: We identified a key hypoxia threshold at a 30% buffer O2 saturation that induces a stable and potentially survivable functional and energetic compromise: left ventricular developed pressure was depressed by 20%, and cardiac phosphocreatine was depleted by 65.5% ± 14% (P < 0.05 vs. control), but adenosine triphosphate levels were maintained. Lactate release was elevated (0.21 ± 0.067 mmol/L/min vs. 0.056 ± 0.01 mmol/L/min, P < 0.05) but not maximal (0.46 ± 0.117 mmol/L/min), indicating residual oxidative metabolic capacity. Hypoxia-inducible factor 1-α was elevated but not maximal. At this key threshold, 64Cu-2,3-pentanedione bis(thiosemicarbazone) (CTS) selectively deposited significantly more 64Cu than any other tracer we examined (61.8% ± 9.6% injected dose vs. 29.4% ± 9.5% for 64Cu-ATSM, P < 0.05). Conclusion: The hypoxic threshold that induced survivable metabolic and functional compromise was 30% O2. At this threshold, only 64Cu-CTS delivered a hypoxic-to-normoxic contrast of 3:1, and it therefore warrants in vivo evaluation for imaging chronic cardiac ischemic syndromes.
The interaction between monoamine oxidase A and punitive discipline in the development of antisocial behavior: Mediation by maladaptive social information processing

Abstract Previous studies demonstrate that boys' monoamine oxidase A (MAOA) genotype interacts with adverse rearing environments in early childhood, including punitive discipline, to predict later antisocial behavior. Yet the mechanisms by which MAOA and punitive parenting interact during childhood to amplify risk for antisocial behavior are not well understood. In the present study, hostile attributional bias and aggressive response generation during middle childhood, salient aspects of maladaptive social information processing, were tested as possible mediators of this relation in a sample of 187 low-income men followed prospectively from infancy into early adulthood. Given racial–ethnic variation in MAOA allele frequencies, analyses were conducted separately by race. In both African American and Caucasian men, those with the low-activity MAOA allele who experienced more punitive discipline at age 1.5 generated more aggressive responses to perceived threat at age 10 relative to men with the high-activity variant. In the African American subsample only, formal mediation analyses indicated a marginally significant indirect effect of maternal punitiveness on adult arrest records via aggressive response generation in middle childhood. The findings suggest that maladaptive social information processing may be an important mechanism underlying the association between MAOA × Parenting interactions and antisocial behavior in early adulthood. The present study extends previous work in the field by demonstrating that MAOA and harsh parenting assessed in early childhood interact to not only predict antisocial behavior in early adulthood, but also predict social information processing, a well-established social–cognitive correlate of antisocial behavior.
Minimal Wireless Broadcast Schedules for Multiobjective Pursuits

Mobile wireless devices can now act as push-based data broadcasters, disseminating information in crowded places. While assuming this role, a device must take into account various factors such as the mean service time, energy expenditure, or copyright costs. Apart from adhering to multiobjective optimality, a broadcast schedule must also be as small as possible in size to be producible and cacheable on a mobile device. This paper analytically proves the existence of optimal schedules that are finite and minimal in size. Furthermore, the optimality of the schedule is allowed to refer to an unlimited number of criteria. The analysis shows that multiobjective optimality can be met precisely by extremely small schedules, enabling their use in mobile devices. Simulations indicate perfect efficiency of the minimal schedules in realistic application scenarios.
Survey of Sedation and Analgesia Practice Among Canadian Pediatric Critical Care Physicians*

Background: Despite the fact that almost all critically ill children experience some degree of pain or anxiety, there is a lack of high-quality evidence to inform preferred approaches to sedation, analgesia, and comfort measures in this environment. We conducted this survey to better understand current comfort and sedation practices among Canadian pediatric intensivists. Methods: The survey was conducted after a literature review and initial focus groups. The survey was then pretested and validated. The final survey was distributed by email to 134 intensivists from 17 PICUs across Canada using the Research Electronic Data Capture system. Results: The response rate was 73% (98/134). The most commonly used sedation scores are Face, Legs, Activity, Cry, and Consolability (42%) and COMFORT (41%). Withdrawal scores are commonly used (65%). In contrast, delirium scores are used by only 16% of the respondents. Only 36% of respondents have routinely used sedation protocols. The majority (66%) do not use noise reduction methods, whereas only 23% of respondents have a protocol to promote day/night cycles. Comfort measures including music, swaddling, soother, television, and sucrose solutions are frequently used. The drugs most commonly used to provide analgesia are morphine and acetaminophen. Midazolam and chloral hydrate were the most frequent sedatives. Conclusion: Our survey demonstrates great variation in practice in the management of pain and anxiety in Canadian PICUs. Standardized strategies for sedation, delirium and withdrawal, and sleep promotion are lacking. There is a need for research in this field and the development of evidence-based, pediatric sedation and analgesia guidelines.
An integrated proteomic approach to identifying circulating biomarkers in high‐risk neuroblastoma and their potential in relapse monitoring

Purpose: Despite intensive treatment regimens, overall survival for high‐risk neuroblastoma (HRNB) is still poor. This is in part due to an inability to cure the disease once a patient has reached clinical relapse. Identifying plasma biomarkers of active disease may provide a way of relapse monitoring in HRNB.
Lymphoproliferative diseases of the ocular adnexa in Korea.

OBJECTIVES To evaluate the clinical features, treatments, and outcomes of patients with ocular lymphoproliferative disease classified according to the World Health Organization classification and to determine prognostic factors of this disease in South Korea. METHODS Between March 1, 1995, and December 31, 2005, 128 cases of patients with ocular lymphoid tumors treated at the Samsung Medical Center were retrospectively reviewed. RESULTS The mean patient age was 46.3 years (range, 1-87 years). The major histopathologic subtypes were mucosa-associated lymphoid tissue (MALT) lymphoma in 96 patients (75.0%), lymphoid hyperplasia in 11 (8.6%), diffuse large B-cell lymphoma in 6 (4.7%), and mantle cell lymphoma in 4 (3.1%). Ocular lymphoproliferative lesions were located in the conjunctiva (53 patients), the eyelid (33 patients), and the orbit (42 patients). Twenty patients had tumor relapses (15.6%), and 9 died of lymphoma during follow-up (7.0%). Regarding the analysis of prognostic factors, most patients with MALT lymphoma evidenced local disease, required local treatment, and exhibited a superior prognosis. CONCLUSIONS Lymphomas of the MALT type constitute most ocular adnexal lymphoproliferative diseases and occur more frequently in South Korea than in Western countries. Patients with MALT lymphoma have favorable outcomes compared with patients with other types of lymphoma.
Biochar application increases soil available nitrogen and plant-to-soil carbon input

Biochar has strong potential to promote soil carbon (C) sequestration and crop performance, but its effects on agricultural systems may vary over time. We applied pine wood chip biochar at 10 and 30 t ha-1 (B10, B30) in a macadamia orchard and measured soil properties, photosynthesis and leaf properties over 2 years (2012–2014). Biochar treatments initially reduced soil available nitrogen (N) (NH4+-N+NO3--N), probably due to its absorption effect, and this appeared to be responsible for the reduction of macadamia leaf photosynthetic capacity following biochar application. However, the effect of biochar on soil available N reversed in 12 months and biochar treatments (especially B30) generally displayed higher soil available N than the control during the second year. This is mainly caused by the increment of soil NO3--N in biochar treatments, probably attributable to accelerated nitrification rate and reduced NO3- leaching. The effect of biochar on soil available N matched with leaf δ15N signature: macadamia leaves were more 15N depleted in biochar treatments, suggesting better preservation of soil available N. Biochar application also led to higher soil total C and C:N ratio, and the gap between biochar treatments (especially B30) and the control increased over time. This pattern indicates that biochar increased soil C not only by instantaneous addition of recalcitrant C to soil, but also by promoting plant-to-soil C input in longer term, and this was supported by the observation of higher leaf photosynthetic capacity in B30 (than the control) by the end of the experiment. Our results suggest that the influence of biochar on soil and crop could have significant temporal effect and some benefits may exhibit with considerable time lag. This highlights the imperative need of long term studies for more complete understanding of the agronomic and climate mitigation benefits of biochar soil application.
Use of tumor dynamics to clarify the observed variability among biochemical recurrence nomograms for prostate cancer

Nomograms for biochemical recurrence (BCR) of prostate cancer (PC) after radical prostatectomy can yield very different prognoses for individual patients. Since the nomograms are optimized on different cohorts, the variations may be due to differences in patient risk‐factor distributions. In addition, the nomograms assign different relative scores to the same PC risk factors and rarely stratify for tumor growth rate.