Miracle-dz/UniFAR-FTUs huggingface dataset:
A Novel Phosphatidylinositol-3,4,5-trisphosphate 5-Phosphatase Associates with the Interleukin-3 Receptor*

To gain insight into the intracellular signaling cascades that are activated by the binding of interleukin-3 (IL-3) to its target cells, we have embarked on the identification of proteins that are associated with the IL-3 receptor (IL-3R). In a previous study we reported that a 110-kDa serine/threonine protein kinase is constitutively associated with the IL-3R and activated following IL-3 stimulation. We now report that a phosphatidylinositol-3,4,5-trisphosphate (PtdIns-3,4,5-P3) 5-phosphatase (5-ptase) is also constitutively associated with the IL-3R. This 5-ptase is magnesium-dependent and removes the 5-position phosphate from PtdIns-3,4,5-P3 but does not metabolize PtdIns-4,5-P2, inositol (Ins)-1,3,4,5-P4, or Ins-1,4,5-P3. This substrate specificity distinguishes it from any previously characterized 5-ptase. Interestingly, it may be bound indirectly via phosphatidylinositol 3-kinase (PI 3-kinase), another enzyme that is constitutively bound to the IL-3R. However, unlike PI 3-kinase which becomes activated following IL-3 stimulation, this receptor-associated 5-ptase activity does not increase following IL-3 stimulation, and its primary function may be to keep the principal in vivo product of PI 3-kinase, PtdIns-3,4,5-P3, at low levels in unstimulated cells, to terminate the PI 3-kinase signal following IL-3 stimulation or to metabolize PtdIns-3,4,5-P3 to a metabolically active second messenger, i.e. PtdIns-3,4-P2.
Automated ancillary cancer history classification for mesothelioma patients from free-text clinical reports

Background: Clinical records are often unstructured, free-text documents that create information extraction challenges and costs. Healthcare delivery and research organizations, such as the National Mesothelioma Virtual Bank, require the aggregation of both structured and unstructured data types. Natural language processing offers techniques for automatically extracting information from unstructured, free-text documents. Methods: Five hundred and eight history and physical reports from mesothelioma patients were split into development (208) and test sets (300). A reference standard was developed and each report was annotated by experts with regard to the patient′s personal history of ancillary cancer and family history of any cancer. The Hx application was developed to process reports, extract relevant features, perform reference resolution and classify them with regard to cancer history. Two methods, Dynamic-Window and ConText, for extracting information were evaluated. Hx′s classification responses using each of the two methods were measured against the reference standard. The average Cohen′s weighted kappa served as the human benchmark in evaluating the system. Results: Hx had a high overall accuracy, with each method, scoring 96.2%. F-measures using the Dynamic-Window and ConText methods were 91.8% and 91.6%, which were comparable to the human benchmark of 92.8%. For the personal history classification, Dynamic-Window scored highest with 89.2% and for the family history classification, ConText scored highest with 97.6%, in which both methods were comparable to the human benchmark of 88.3% and 97.2%, respectively. Conclusion: We evaluated an automated application′s performance in classifying a mesothelioma patient′s personal and family history of cancer from clinical reports. To do so, the Hx application must process reports, identify cancer concepts, distinguish the known mesothelioma from ancillary cancers, recognize negation, perform reference resolution and determine the experiencer. Results indicated that both information extraction methods tested were dependant on the domain-specific lexicon and negation extraction. We showed that the more general method, ConText, performed as well as our task-specific method. Although Dynamic-Window could be modified to retrieve other concepts, ConText is more robust and performs better on inconclusive concepts. Hx could greatly improve and expedite the process of extracting data from free-text, clinical records for a variety of research or healthcare delivery organizations.
Dust grains in astrophysics

Eleven years ago, it was fairly clear that dust grains were a state of solid state matter involved in a cycle producing and reprocessing the solid bodies in the Universe mainly from evolved stars, and that this cycle progressively enriched the galactic media with heavier and heavier “metallic” components. The main reecent progresses in the field was that chemistry and dynamics are strongly or weakly coupled depending on the surrounding gas density. First approaches of models including this coupling were built, though a lot of problems already known by people investigating separately dynamics and chemistry appeared still more complicated due to the variety of scales to be considered in self consistent models. However, models matched more or less well up to observations. Now due to the exponentially increasing power of computers and the refinement of observations, a lot of new approaches of grain nucleation and evolution processes on the one side and observations on the other side, and also the subsequent derivations of optical properties at many wavelengths suggest that ways of coupling dynamics to chemistry may be still more complex than expected, all the more since grains have been detected in media very far from any thermo-dynamical equilibrium, in which radiation is a phenomenon also strongly involved. The conclusion is that there is no available general solution and that dominant processes and most important scales must be, at the present time, carefully determined before any computation in order to built reasonable models in each case. If the production of dust by evolved stars is not questioned, other sources may be efficient. New species of “hens” and “eggs” should be taken under consideration.
Ensemble learning of inverse probability weights for marginal structural modeling in large observational datasets

Inverse probability weights used to fit marginal structural models are typically estimated using logistic regression. However, a data‐adaptive procedure may be able to better exploit information available in measured covariates. By combining predictions from multiple algorithms, ensemble learning offers an alternative to logistic regression modeling to further reduce bias in estimated marginal structural model parameters. We describe the application of two ensemble learning approaches to estimating stabilized weights: super learning (SL), an ensemble machine learning approach that relies on V‐fold cross validation, and an ensemble learner (EL) that creates a single partition of the data into training and validation sets. Longitudinal data from two multicenter cohort studies in Spain (CoRIS and CoRIS‐MD) were analyzed to estimate the mortality hazard ratio for initiation versus no initiation of combined antiretroviral therapy among HIV positive subjects. Both ensemble approaches produced hazard ratio estimates further away from the null, and with tighter confidence intervals, than logistic regression modeling. Computation time for EL was less than half that of SL. We conclude that ensemble learning using a library of diverse candidate algorithms offers an alternative to parametric modeling of inverse probability weights when fitting marginal structural models. With large datasets, EL provides a rich search over the solution space in less time than SL with comparable results. Copyright © 2014 John Wiley & Sons, Ltd.
Long‐Term Reduction in the Number of C‐Fibre Nociceptors Following Capsaicin Treatment of a Cutaneous Nerve in Adult Rats

The structure and function of C‐ and A‐fibres have been studied 3–12 months following a single 30 min exposure of the saphenous nerve of adult rats to 1% capsaicin. Examination of nerve cross‐sections showed that the number of C‐fibres was reduced by 36%, but A‐fibres were unaffected. The remaining C‐fibres included many that were unusually small in size. The changes were not restricted to the treatment site but were found over at least a further 10 mm proximal and distal to it. In treated nerves, the C‐fibre component of the compound action potential was reduced in size relative to the Aαβ component. Single unit studies revealed that an unusually high proportion of C‐fibres had no cutaneous receptive field (54%, compared with 28% in controls). There was no such change for A‐fibres. The conduction velocity range for C‐fibre units in treated nerves was almost normal, but this sample contained an unusually low proportion of polymodal nociceptors. Allowing for the fall in total numbers and the reduction in units with cutaneous receptive fields, it was calculated that overall the numbers of C‐polymodal nociceptor units had fallen by 74%. No significant changes in number had occurred in the other classes of C‐afferents. The reduction in the numbers of nociceptive C‐fibres is likely to be the direct cause of the reduction in pain responses and in neurogenic inflammation that several groups have reported following treatment of adult rats with capsaicin. Reduction in the numbers of C‐fibre is also likely to be the reason for reduced neuropeptide levels seen in tissues innervated by treated nerves.
Comparison of the AMICA and the InfoMax algorithm for the reduction of electromyogenic artifacts in EEG data

Electromyogenic or muscle artifacts constitute a major problem in studies involving electroencephalography (EEG) measurements. This is because the rather low signal activity of the brain is overlaid by comparably high signal activity of muscles, especially neck muscles. Hence, recording an artifact-free EEG signal during movement or physical exercise is not, to the best knowledge of the authors, feasible at the moment. Nevertheless, EEG measurements are used in a variety of different fields like diagnosing epilepsy and other brain related diseases or in biofeedback for athletes. Muscle artifacts can be recorded using electromyography (EMG). Various computational methods for the reduction of muscle artifacts in EEG data exist like the ICA algorithm InfoMax and the AMICA algorithm. However, there exists no objective measure to compare different algorithms concerning their performance on EEG data. We defined a test protocol with specific neck and body movements and measured EEG and EMG simultaneously to compare the InfoMax algorithm and the AMICA algorithm. A novel objective measure enabled to compare both algorithms according to their performance. Results showed that the AMICA algorithm outperformed the InfoMax algorithm. In further research, we will continue using the established objective measure to test the performance of other algorithms for the reduction of artifacts.
The prevalence of chronic lower‐limb ulceration has been underestimated: Results of a validated population questionnaire

A validated population questionnaire was used to survey 12 000 randomly selected inhabitants, aged 50–89 years, in two defined regions of Sweden. The sample included 7 per cent of the total population in the age interval. Overall response rate was 91 per cent. Open ulcers were reported by 306 subjects and 143 (47 per cent) agreed to be examined. The false‐positive response rate was high (43 per cent). The observed point prevalence of open leg ulcers was 0.63 (95 per cent confidence interval 054–0.72) per cent of the total population. The overall prevalence of leg ulcer history (open plus healed) in the population was estimated to be around 2 per cent and the ratio of open: previous ulcers was 1:2. This study shows a point prevalence more than double that expected, indicating a high rate of self treatment. Assessments of leg ulcer prevalence through the health care system, without knowledge of the rate of self care, measure only the workload of health care professionals. The problem of leg ulcers has generally been underestimated.
Est1 Protects Telomeres and Inhibits Subtelomeric Y′-Element Recombination

ABSTRACT In the budding yeast Saccharomyces cerevisiae, the structure and function of telomeres are maintained by binding proteins, such as Cdc13-Stn1-Ten1 (CST), Yku, and the telomerase complex. Like CST and Yku, telomerase also plays a role in telomere protection or capping. Unlike CST and Yku, however, the underlying molecular mechanism of telomerase-mediated telomere protection remains unclear. In this study, we employed both the CDC13-EST1 fusion gene and the separation-of-function allele est1-D514A to elucidate that Est1 provided a telomere protection pathway that was independent of both the CST and Yku pathways. Est1's ability to convert single-stranded telomeric DNA into a G quadruplex was required for telomerase-mediated telomere protection function. Additionally, Est1 maintained the integrity of telomeres by suppressing the recombination of subtelomeric Y′ elements. Our results demonstrate that one major functional role that Est1 brings to the telomerase complex is the capping or protection of telomeres.
Mechanisms of the inhibition by neostigmine of tetanic contraction in the mouse diaphragm

1 Neostigmine (0.5–2 μm) caused fade of tetanic contractions (Wedensky inhibition) evoked by repetitive nerve stimulation. The mechanism underlying this action was studied in intact and cut isolated phrenic nerve‐diaphragm preparations of mice. 2 The fade was brought about by failure to elicit muscle action potentials. During fade, the muscle was unable to conduct directly evoked action potentials across the central endplate zone. Recovery of excitability occurred in 5 s with continued stimulation. 3 In the presence of neostigmine, the resting membrane potential at endplate areas during repetitive stimulation decreased from − 80 mV to less than − 50 mV within the first 10 pulses at 75–200 Hz and thereafter recovered gradually to about − 60 mV in the following 5 s during continuous stimulation. 4 The quantal content of endplate potentials evoked by single stimulation was not reduced by neostigmine whereas that evoked by high frequency stimuli (75 Hz) was reduced to about 1/3 in 10 pulses. 5 It is concluded that the fade of tetanic contraction caused by inhibition of acetylcholinesterase is induced by the inactivation of sodium channels in the area surrounding the endplates and that the sustained fade is due to a decrease of transmitter release. Both effects are the result of acetylcholine accumulation.
Application of MIMO theory to the analysis of broadband fixed wireless access diversity systems above 10GHz

In this paper, a novel approach to the analysis of BFWA diversity systems has been presented which is quite different and more communications-oriented than the traditional propagation-based ones. In particular, it is shown that a double CSD BFWA system operating at frequencies above 10 GHz and under rain fades can be seen as a special case of a 2times2 MIMO system. After pointing out the differences and establishing the exact relationship between the two systems, well-known results available in the MIMO literature were applied for the performance analysis of BFWA diversity systems. This paper particularly looked at the single-user capacity of such a system in both cases that the channel is known and unknown to the transmitter. An interesting outcome of the analysis is that there is no significant capacity gain due to feedback, which further implies that no additional complexity in terms of feedback links is useful to a BFWA diversity system. This can be ascribed to the high correlation of rainfall medium. Furthermore, simulation results have shown that, in case of unbalanced BFWA diversity systems, exclusive power allocation is the optimal choice at low SNR, whereas at high SNR, equal power allocation is the optimal one. This paper hopes that this relationship between the two systems can be used to obtain additional useful insights into the design and analysis of BFWA diversity systems by drawing on the vast body of MIMO literature that is currently available
Induced Pluripotent Stem Cells: Advances in the Quest for Genetic Stability during Reprogramming Process

Evaluation of the extent and nature of induced pluripotent stem cell (iPSC) genetic instability is important for both basic research and future clinical use. As previously demonstrated regarding embryonic stem cells, such DNA aberrations might affect the differentiation capacity of the cells and increase their tumorigenicity. Here, we first focus on the contribution of multiple DNA damage response pathways during cellular reprogramming. We then discuss the origin and mechanisms responsible for the modification of genetic material in iPSCs (pre-existing variations in somatic cells, mutations induced by reprogramming factors, and mutations induced by culture expansion) and deepen the possible functional consequences of genetic variations in these cells. Lastly, we present some recent improvements of iPSC generation methods aimed at obtaining cells with fewer genetic variations.
Primal-Dual π Learning: Sample Complexity and Sublinear Run Time for Ergodic Markov Decision Problems

Consider the problem of approximating the optimal policy of a Markov decision process (MDP) by sampling state transitions. In contrast to existing reinforcement learning methods that are based on successive approximations to the nonlinear Bellman equation, we propose a Primal-Dual $\pi$ Learning method in light of the linear duality between the value and policy. The $\pi$ learning method is model-free and makes primal-dual updates to the policy and value vectors as new data are revealed. For infinite-horizon undiscounted Markov decision process with finite state space $S$ and finite action space $A$, the $\pi$ learning method finds an $\epsilon$-optimal policy using the following number of sample transitions $$ \tilde{O}( \frac{(\tau\cdot t^*_{mix})^2 |S| |A| }{\epsilon^2} ),$$ where $t^*_{mix}$ is an upper bound of mixing times across all policies and $\tau$ is a parameter characterizing the range of stationary distributions across policies. The $\pi$ learning method also applies to the computational problem of MDP where the transition probabilities and rewards are explicitly given as the input. In the case where each state transition can be sampled in $\tilde{O}(1)$ time, the $\pi$ learning method gives a sublinear-time algorithm for solving the averaged-reward MDP.
Endoscopic bile duct brushing of malignant pancreatic biliary strictures: Retrospective study with comparison of conventional smear and ThinPrep® techniques

Endoscopic bile duct brushing (EBDB) is carried out to differentiate benign from malignant biliary strictures in patients who have pancreaticobiliary disease. The sensitivity of this method for the diagnosis of malignancy is relatively low. The aim of this study is to analyze the cytomorphologic features that are helpful in increasing the sensitivity of detecting these lesions on cytologic samples. These features are compared with slides prepared with the ThinPrep® technique. The study included 142 patients with bile duct obstruction or pancreatic mass who underwent EBDB and follow‐up surgery or biopsy between 1997 to 2000. Twenty‐five (18%) of these cases were positive for malignancy in both EBDB and follow‐up surgical biopsy; 20 of these cases were used as positive controls (PC). Sixty‐one (43%) were negative in both EBDB and follow‐up surgical biopsy specimens, and 21 of those cases were used as negative controls (NC). Fifty‐six (39%) cases were negative/atypical in EBDB cytology but were suspicious or positive in the surgical or biopsy specimens (false‐negative). We identified the cytologic criteria that were helpful in differentiating our positive and negative control groups and applied these criteria to our false‐negative group to see whether our sensitivity could be increased, using well‐defined cytologic criteria alone. Of the 56 false‐negative cases, 9 (16%) were upgraded to suspicious/positive based on the presence of the following features: three‐dimensional (3D) micropapillae (95% PC vs 19% NC, P < 0.0001), anisonucleosis (90% PC vs 5% NC, P < 0.0001), high nuclear‐to‐cytoplasmic (N/C) ratio (95% PC vs 9% NC, P < 0.0001), nuclear contour irregularity (65% PC vs 24% NC, P = 0.0079), and prominent nucleoli (70% PC vs 38% NC, P = 0.0406). Cytomorphologic features which were not helpful in distinguishing positive and negative cases were: single naked nuclei (50% PC vs 28% NC, P = 0.1597), chromatin granularity (50% PC vs 62% NC, P = 0.54), and necrosis (10% PC vs 5% NC, P = 0.5197). Improvement in diagnostic sensitivity for carcinoma of pancreaticobiliary tract in EBDB samples may be achieved by identifying the key malignant cytomorphologic features: 3D micropapillae, anisonucleosis, nuclear contour irregularity, prominent nucleoli, and high N/C ratio. The sensitivity in detecting malignant biliary strictures increased from 31% to 42% based on these criteria in our current study. Diagn. Cytopathol. 2003;28:196–204. © 2003 Wiley‐Liss, Inc.
Genetic diversity of Bartonella quintana in macaques suggests zoonotic origin of trench fever

Bartonella quintana is a bacterium that causes a broad spectrum of diseases in humans including trench fever. Humans were previously considered to be the primary, if not the only, reservoir hosts for B. quintana. To identify the animal reservoir and extend our understanding of the ecological and evolutionary history of B. quintana, we examined blood samples from macaques and performed multilocus sequence typing (MLST) analysis. We demonstrated the prevalence of B. quintana infection was common in macaques from main primate centres in mainland China. Overall, 18.0% (59/328) of rhesus macaques and 12.7% (39/308) of cynomolgus macaques were found to be infected with B. quintana by blood culture and/or polymerase chain reaction. The infection was more frequently identified in juvenile and young monkeys compared with adult animals. In contrast with the relatively low level of sequence divergence of B. quintana reported in humans, our investigation revealed much higher genetic diversity in nonhuman primates. We identified 44 new nucleotide variable sites and 14 novel sequence types (STs) among the B. quintana isolates by MLST analysis. Some STs were found only in cynomolgus macaques, while some others were detected only in rhesus macaques, suggesting evidence of host‐cospeciation, which were further confirmed by phylogenetic analysis and Splits decomposition analysis. Our findings suggest that trench fever may primarily be a zoonotic disease with macaques as the natural hosts.
Cooperación institucional para la integración: actividades de sensibilización social sobre discapacidad visual en la Universidad de Las Palmas de Gran Canaria

Se presenta la experiencia de colaboracion entre la Universidad de Las Palmas de Gran Canaria y la Organizacion Nacional de Ciegos Espanoles, en el marco del convenio suscrito en 1999. Se describen los cursos de formacion y sensibilizacion sobre discapacidad visual, y se refieren los resultados positivos de la evaluacion de satisfaccion de los participantes, que valoran principalmente los aspectos mas practicos. Se concluye que las actividades formativas deben ser un elemento esencial en los planes y acuerdos de colaboracion institucional para mejorar la atencion a las personas con discapacidad visual en el ambito universitario.