Miracle-dz/UniFAR-FTUs huggingface dataset:
Screen for ISG15-crossreactive Deubiquitinases

Background The family of ubiquitin-like molecules (UbLs) comprises several members, each of which has sequence, structural, or functional similarity to ubiquitin. ISG15 is a homolog of ubiquitin in vertebrates and is strongly upregulated following induction by type I interferon. ISG15 can be covalently attached to proteins, analogous to ubiquitination and with actual support of ubiquitin conjugating factors. Specific proteases are able to reverse modification with ubiquitin or UbLs by hydrolyzing the covalent bond between their C-termini and substrate proteins. The tail regions of ubiquitin and ISG15 are identical and we therefore hypothesized that promiscuous deubiquitinating proteases (DUBs) might exist, capable of recognizing both ubiquitin and ISG15. Results We have cloned and expressed 22 human DUBs, representing the major clades of the USP protease family. Utilizing suicide inhibitors based on ubiquitin and ISG15, we have identified USP2, USP5 (IsoT1), USP13 (IsoT3), and USP14 as ISG15-reactive proteases, in addition to the bona fide ISG15-specific protease USP18 (UBP43). USP14 is a proteasome-associated DUB, and its ISG15 isopeptidase activity increases when complexed with the proteasome. Conclusions By evolutionary standards, ISG15 is a newcomer among the UbLs and it apparently not only utilizes the conjugating but also the deconjugating machinery of its more established relative ubiquitin. Functional overlap between these two posttranslational modifiers might therefore be more extensive than previously appreciated and explain the rather innocuous phenotype of ISG15 null mice.
Calcineurin transgenic mice have mitochondrial dysfunction and elevated superoxide production.

Introduction of the constitutively active calcineurin gene into neonatal rat cardiomyocytes by adenovirus resulted in decreased mitochondrial membrane potential (P < 0.05). Infection of H9c2 cells with calcineurin adenovirus resulted in increased superoxide production (P < 0.001). Transgenic mice with cardiac-specific expression of a constitutively active calcineurin cDNA (CalTG mice) exhibit a two- to threefold increase in heart size that progresses to heart failure. We prepared mitochondria enriched for the subsarcolemmal population from the hearts of CalTG mice and transgene negative littermates (control). Intact, well-coupled mitochondria prepared from one to two mouse hearts at a time yielded sufficient material for functional studies. Mitochondrial oxygen consumption was measured with a Clark-type oxygen electrode with substrates for mitochondrial complex II (succinate) and complex IV [tetramethylpentadecane (TMPD)/ascorbate]. CalTG mice exhibited a maximal rate of electron transfer in heart mitochondria that was reduced by approximately 50% (P < 0.002) without a loss of respiratory control. Mitochondrial respiration was unaffected in tropomodulin-overexpressing transgenic mice, another model of cardiomyopathy. Western blotting for mitochondrial electron transfer subunits from mitochondria of CalTG mice revealed a 20-30% reduction in subunit 3 of complex I (ND3) and subunits I and IV of cytochrome oxidase (CO-I, CO-IV) when normalized to total mitochondrial protein or to the adenine nucleotide transporter (ANT) and compared with littermate controls (P < 0.002). Impaired mitochondrial electron transport was associated with high levels of superoxide production in the CalTG mice. Taken together, these data indicate that calcineurin signaling affects mitochondrial energetics and superoxide production. The excessive production of superoxide may contribute to the development of cardiac failure.
Aesthetic Alteration of the Chin

Abstract Genioplasty, the alteration of the chin through either osseous manipulation or implant augmentation, is an integral component of aesthetic surgery of the face. When performed with proper preoperative assessment and technical execution, the results can harmonize and restore balance between skeletal, soft tissue, and dental components of the lower face. To this end, proper understanding of the underlying anatomy and the changes associated with movement of the chin, alone or in conjunction with formal orthognathic surgery, is paramount. The author presents pertinent points on proper assessment, treatment planning, and a description of the surgical technique, and discusses complications and outcomes to optimize outcome.
The Genome of Polymorphonuclear Neutrophils Maintains Normal Coding Sequences

Genetic studies often use genomic DNA from whole blood cells, of which the majority are the polymorphonuclear myeloid cells. Those cells undergo dramatic change of nuclear morphology following cellular differentiation. It remains elusive if the nuclear morphological change accompanies sequence alternations from the intact genome. If such event exists, it will cause a serious problem in using such type of genomic DNA for genetic study as the sequences will not represent the intact genome in the host individuals. Using exome sequencing, we compared the coding regions between neutrophil, which is the major type of polymorphonuclear cells, and CD4+ T cell, which has an intact genome, from the same individual. The results show that exon sequences between the two cell types are essentially the same. The minor differences represented by the missed exons and base changes between the two cell types were validated to be mainly caused by experimental errors. Our study concludes that genomic DNA from whole blood cells can be safely used for genetic studies.
Ginkgo Biloba Extract Reduces Endothelial Progenitor-Cell Senescence Through Augmentation of Telomerase Activity

Our previous studies have shown that Ginkgo biloba extract increased endothelial progenitor-cell (EPC) numbers and functional activity. However, the mechanisms remain to be determined. Recent studies have demonstrated that increased EPC numbers and activity were associated with the inhibition of EPC senescence, which involved activation of telomerase. Therefore, we investigated whether Ginkgo biloba extract inhibited the onset of EPC senescence through telomerase activation, leading to potentiation of cellular activity. After ex vivo cultivation, EPCs became senescent as determined by acidic ß-galactosidase staining. Ginkgo biloba extract dose-dependently prevented the onset of EPC senescence in culture. Moreover, Ginkgo biloba extract increased proliferation of EPCs as assessed by MTT assay and colony-forming capacity. To get further insights into the underlying mechanisms of these effects, we measured telomerase activity and determined the phosphorylation of Akt by Western blotting. Ginkgo biloba extract significantly increased telomerase activity and phosphorylation of the serine/threonine protein kinase Akt, a downstream effector of phosphoinositide 3-kinase (PI3K). Moreover, pretreatment with PI3K inhibitor, LY294002, significantly attenuated the Ginkgo biloba extract-induced telomerase activity. Taken together, the results indicated that Ginkgo biloba extract delayed the onset of EPC senescence, which may be related to activation of telomerase through the PI3k/Akt signaling pathway. The inhibition of EPC senescence by Ginkgo biloba extract in vitro may improve the functional activity of EPCs in a way that is important for potential cell therapy.
Choline Starvation Induces the Gene licD2 in Streptococcus pneumoniae

ABSTRACT Mutant strains of Streptococcus pneumoniae were constructed to monitor the regulation of three dispersed genes known or predicted to act in choline metabolism. One gene (licD2) was regulated in response to choline deprivation over a 30-fold range. The other two (SP1860 and licC) responded little if at all to the same challenge.
A Score Regression Approach to Assess Calibration of Continuous Probabilistic Predictions

Summary Calibration, the statistical consistency of forecast distributions and the observations, is a central requirement for probabilistic predictions. Calibration of continuous forecasts is typically assessed using the probability integral transform histogram. In this article, we propose significance tests based on scoring rules to assess calibration of continuous predictive distributions. For an ideal normal forecast we derive the first two moments of two commonly used scoring rules: the logarithmic and the continuous ranked probability score. This naturally leads to the construction of two unconditional tests for normal predictions. More generally, we propose a novel score regression approach, where the individual scores are regressed on suitable functions of the predictive variance. This conditional approach is applicable even for certain nonnormal predictions based on the Dawid–Sebastiani score. Two case studies illustrate that the score regression approach has typically more power in detecting miscalibrated forecasts than the other approaches considered, including a recently proposed technique based on conditional exceedance probability curves.
Flow-Based Service Selection forWeb Service Composition Supporting Multiple QoS Classes

In the service oriented paradigm applications are created as a composition of independently developed Web services. Since the same service may be offered by different providers with different non-functional Quality of Service (QoS) attributes, a selection process is needed to identify the constituent services for a given composite service that best meet the users QoS requirements. In this paper, we consider a broker that offers a composite service with multiple QoS classes to several users each generating a flow of requests over time. We propose a service selection scheme which optimizes the end-to-end aggregated QoS of all incoming flows of requests by means of a simple linear programming problem which scales as the number of users, request volumes and/or services grows. This approach differs from most of the current proposals which may not scale well since: a) requests, even from the same user, are handled independently from one another; and b) the selection process often requires the solution of an NP-hard problem.
Uniform Kernelization Complexity of Hitting Forbidden Minors

The F-Minor-Free Deletion problem asks, for a fixed set F and an input consisting of a graph G and integer k, whether k vertices can be removed from G such that the resulting graph does not contain any member of F as a minor. At FOCS 2012, Fomin et al. showed that the special case when F contains at least one planar graph has a kernel of size f(F) ċ kg(F) for some functions f and g. They left open whether this Planar F-Minor-Free Deletion problem has kernels whose size is uniformly polynomial, of the form f(F) ċ kc for some universal constant c. We prove that some Planar F-Minor-Free Deletion problems do not have uniformly polynomial kernels (unless NP ⊆ coNP/poly), not even when parameterized by the vertex cover number. On the positive side, we consider the problem of determining whether k vertices can be removed to obtain a graph of treedepth at most η. We prove that this problem admits uniformly polynomial kernels with O(k6) vertices for every fixed η.
Learning Recurrent Waveforms Within EEGs

Goal: We demonstrate an algorithm to automatically learn the time-limited waveforms associated with phasic events that repeatedly appear throughout an electroencephalogram. Methods: To learn the phasic event waveforms we propose a multiscale modeling process that is based on existing shift-invariant dictionary learning algorithms. For each channel, waveforms at different temporal scales are learned based on the assumption that only a few waveforms occur in any window of the time-series, but the same waveforms reoccur throughout the signal. Once the waveforms are learned, the timing and amplitude of the phasic event occurrences are estimated using matching pursuit. To summarize the waveforms learned across multiple channels and subjects, we analyze their frequency content, their similarity to Gabor-Morlet wavelets, and perform shift-invariant k-means to cluster the waveforms. A prototype waveform from each cluster is then tested for differential spatial patterns between different motor imagery conditions. Results: On multiple human EEG datasets, the learned waveforms capture key characteristics of signals they were trained to represent, with a consistency in waveform morphology and frequency content across multiple training sections and initializations. On multichannel datasets, the spatial amplitude patterns of the waveforms are also consistent and can be used to distinguish different modalities of motor imagery. Conclusion: We explored a methodology that can be used for modeling the recurrent waveforms in EEG traces. Significance: The methodology automatically identifies the most frequent phasic event waveforms in EEG, which could then be used as features for automatic evaluation and comparison of EEG during sleep, pathology, or mentally engaging tasks.
Title Learning Latent Subevents in Activity Videos Using Temporal Attention Filters

In this paper, we newly introduce the concept of temporal attention filters, and describe how they can be used for human activity recognition from videos. Many high-level activities are often composed of multiple temporal parts (e.g., sub-events) with different duration/speed, and our objective is to make the model explicitly learn such temporal structure using multiple attention filters and benefit from them. Our temporal filters are designed to be fully differentiable, allowing end-of-end training of the temporal filters together with the underlying frame-based or segment-based convolutional neural network architectures. This paper presents an approach of learning a set of optimal static temporal attention filters to be shared across different videos, and extends this approach to dynamically adjust attention filters per testing video using recurrent long short-term memory networks (LSTMs). This allows our temporal attention filters to learn latent sub-events specific to each activity. We experimentally confirm that the proposed concept of temporal attention filters benefits the activity recognition, and we visualize the learned latent sub-events.
Early-onset type 2 diabetes: metabolic and genetic characterization in the mexican population.

The objective of this study was to investigate possible defects in the insulin sensitivity and/or the acute insulin response in a group of Mexican patients displaying early-onset type 2 diabetes and to evaluate the contribution of mutations in three of the genes linked to maturity-onset diabetes of the young. We studied 40 Mexican patients with an age of diagnosis between 20 and 40 yr in which the insulin sensitivity as well as the insulin secretory response were measured using the minimal model approach. A partial screening for possible mutations in 3 of the 5 genes linked to maturity-onset diabetes of the young was carried out by PCR-single strand conformation polymorphism analysis. A low insulin secretory capacity (AIRg = 68.5 +/- 5 muU/mL.min) and a near-normal insulin sensitivity (3.43 +/- 0.2 min/muU.mL x 10(4)) were found in these patients. Among this group we found two individuals carrying missense mutations in exon 4 of the hepatocyte nuclear factor-1alpha (HNF-4alpha) gene (Asp(126)-->His/Tyr and Arg(154)-->Gln, respectively) and one carrying a nonsense mutation in exon 7 of the HNF-1alpha gene (Gln(486)-->stop codon); 7.5% had positive titers for glutamic acid decarboxylase antibodies. Thirty-five percent of cases had insulin resistance; these subjects had the lipid abnormalities seen in the metabolic syndrome. A defect in insulin secretion is the hallmark in Mexican diabetic patients diagnosed between 20 and 40 yr of age. Mutations in either the HNF-1alpha or the HNF-4alpha genes are present among the individuals who develop early-onset diabetes in our population. These particular sequence changes have not been previously reported and therefore represent putative new mutations. Even in the absence of endogenous hyperinsulinemia, insulin resistance is associated with an adverse lipid profile.
FinGAR: combination of electrical and mechanical stimulation for high-fidelity tactile presentation

It is known that our touch sensation is a result of activities of four types of mechanoreceptors, each of which responds to different types of skin deformation; pressure, low frequency vibration, high frequency vibration, and shear stretch. If we could selectively activate these receptors, we could combine and present any types of tactile sensation. This approach has been studied but not fully achieved. In our study, we developed FinGAR (Finger Glove for Augmented Reality), in which we combined electrical and mechanical stimulation to selectively stimulate these four channels and thus to achieve high-fidelity tactile sensation. The electrical stimulation with array of electrodes presents pressure and low frequency vibration with high spatial resolution, while the mechanical stimulation with DC motor presents high frequency vibration and shear deformation of the whole finger. Furthermore, FinGAR is lightweight, simple in mechanism, easy to wear, and does not disturb the natural movement of the finger, all of which are necessary for general-purpose virtual reality system.
Recommendation Method Using Bicluster Network Method

— In recent years, recommendation technology that predicts and proposes products and information matching user preferences has been gaining attention and is now widely used, particularly by online stores. The collaborative filtering method is the most popular form of recommendation technology. However, collaborative filtering often recommends similar items or items that the user already knows. Our objective is to improve the collaborative filtering method by developing a method that makes a recommendation after performing a wider and more relevant search of items that match the user's preferences in a database. This study proposes a method that expresses the transitivity of preferences between groups of users who like similar items as bicluster networks and recommends items on the basis of these bicluster networks. We performed a simulation experiment using film rating data to compare recommendation accuracy of the proposed method with that of an existing method on the basis of biclusters. The results demonstrate that the proposed method is far superior to existing methods in terms of the recall rate showing the degree of coverage of items that should be recommended.
Akaike's Information Criterion in Generalized Estimating Equations

Summary. Correlated response data are common in biomedical studies. Regression analysis based on the generalized estimating equations (GEE) is an increasingly important method for such data. However, there seem to be few model‐selection criteria available in GEE. The well‐known Akaike Information Criterion (AIC) cannot be directly applied since AIC is based on maximum likelihood estimation while GEE is nonlikelihood based. We propose a modification to AIC, where the likelihood is replaced by the quasi‐likelihood and a proper adjustment is made for the penalty term. Its performance is investigated through simulation studies. For illustration, the method is applied to a real data set.
Speci cation of Pre-Processing Operators Requirements

In this workpackage a speci cation of the pre-processing operations needed in order to analyse the available data warehouses is described. The collection of pre-processing requirements will serve as the unifying and organizing basis for all other workpackages, which shall provide methods for satisfying each of them. Based on partners' previous experience, those aspects of data selection and preparation that have proved to be most critical to the success in previous data mining activities have been identi ed, as well as the application context in which they arose.
Interference Aware Positioning of Aerial Relays for Cell Overload and Outage Compensation

Compensating temporary overload or site outage in cellular mobile networks is still an unsolved problem in order to avoid situations where services are unavailable. For this objective, we propose to use a swarm of Unmanned Aerial Vehicles (UAVs) equipped with cellular technology to temporarily offload traffic into neighbouring cells in LTE/4G networks. We discuss relay placement, amount of relays and relay transmit power for overload and outage compensation and provide an analytical model for evaluating system performance in the downlink. We assume that the spatial separation between the aerial service provider, users, and offload eNodeB is beneficial for temporarily increasing spectral efficiency. Our results give evidence, that aerial network provisioning can be used for optimizing mobile networks in overload and outage scenarios.
Longitudinal Assessment of Intellectual Achievement in Patients With Classical Galactosemia

OBJECTIVE: To conduct a longitudinal assessment of long-term cognitive outcome in patients with classical galactosemia. METHODS: Inclusion criteria were (1) previous assessment of IQ dating back >10 years with tests being comparable with the recent German tests HAWIK-III and HAWIE-R, (2) absence of illnesses other than galactosemia, (3) absence of foreign language problems, (4) enzymatic-metabolic proof of classical galactosemia, (5) compliance with dietary therapy, and (6) written informed consent. Twenty-three patients who fulfilled these criteria were found. They underwent the first IQ test at a mean age of 11 ± 5 years and the second 13.6 to 15.5 years later at a mean age of 26 ± 5 years. Results were corrected for the obsolescence of test norms (Flynn effect). RESULTS: Mean total IQ scores on the first and second tests were 78 ± 14 and 73 ± 15, respectively, and not significantly different. IQ scores in the average range were observed for 7 patients on the first test and for 5 patients on the second test. For 17 patients, the intraindividual IQ scores remained essentially unchanged. Five patients showed a decrease and 1 an increase of the IQ score over time. No consistent pattern of change was found with respect to performance or verbal IQ subscores or in achievements in the individual subtest. CONCLUSIONS: The results confirm the presence of reduced cognitive ability in classical galactosemia and present evidence for an absence of substantial galactosemia-induced aggravation of this impairment with increasing age, at least in patients from 4 to 40 years of age. It remains to be clarified whether a reduction of cognitive function in galactosemia may be initiated by an in utero toxicity of endogenously formed galactose and which role such a process may play in the development of intellectual deficiencies that are later maintained throughout life.