Miracle-dz/UniFAR-FTUs huggingface dataset:
From Mouse to Man: Predictions of Human Pharmacokinetics of Orally Administered Docetaxel From Preclinical Studies

Intravenously administered docetaxel is approved for the treatment of various types of cancer. An oral regimen, in combination with ritonavir, is being evaluated in clinical trials. The pharmacokinetics of docetaxel are determined by the activity of the metabolizing enzyme cytochrome P450 3A (CYP3A) and the drug efflux transporter P‐glycoprotein (P‐gp). The effects of these proteins on the pharmacokinetics of docetaxel were investigated in different mouse models that lack 1 or both detoxifying systems. Docetaxel was given to these mice orally or intravenously with or without a strong CYP3A inhibitor, ritonavir. The data of these 2 preclinical studies were pooled and analyzed using nonlinear mixed‐effects modeling. The results of the preclinical studies could be integrated successfully, with only a small difference in residual error (33% and 26%, respectively). Subsequently, the model was used to predict human exposure using allometric scaling and this was compared with clinical trial data. This model led to adequate predictions of docetaxel exposure in humans.
Rapid prototyping of 3D DNA-origami shapes with caDNAno

DNA nanotechnology exploits the programmable specificity afforded by base-pairing to produce self-assembling macromolecular objects of custom shape. For building megadalton-scale DNA nanostructures, a long ‘scaffold’ strand can be employed to template the assembly of hundreds of oligonucleotide ‘staple’ strands into a planar antiparallel array of cross-linked helices. We recently adapted this ‘scaffolded DNA origami’ method to producing 3D shapes formed as pleated layers of double helices constrained to a honeycomb lattice. However, completing the required design steps can be cumbersome and time-consuming. Here we present caDNAno, an open-source software package with a graphical user interface that aids in the design of DNA sequences for folding 3D honeycomb-pleated shapes A series of rectangular-block motifs were designed, assembled, and analyzed to identify a well-behaved motif that could serve as a building block for future studies. The use of caDNAno significantly reduces the effort required to design 3D DNA-origami structures. The software is available at http://cadnano.org/, along with example designs and video tutorials demonstrating their construction. The source code is released under the MIT license.
Relationship between fatigue and nutritional status in patients with cancer undergoing radiotherapy.

PURPOSE The purpose of this study was to identify the relationship between fatigue and nutritional status in patients undergoing radiotherapy. DESIGN A correlational and crossectional study design was used. METHOD One-hundred-fifty-one subjects with cancer receiving radiotherapy were recruited from a university hospital in Chonan, Korea. Fatigue was measured using Piper's Fatigue Scale (PFS). The parameters for nutritional status included body weight, body mass index, hemoglobin, and lymphocyte counts. Cancer stage was controlled in analyzing the differences in fatigue, body weight and body mass index. RESULTS The patients who experienced most fatigue were in their fifties, employed, had head and neck cancer, received radiotherapy on the head and neck, and had concomitant chemotherapy. Disease-related characteristics such as cancer type, and treatment type were frequently related to poorer nutritional status. Patients who showed poorer nutritional status, such as those with lower body weight, lower body mass index and lower hemoglobin levels were more fatigued than those who did not exhibit such characteristics. Lymphocyte counts did not correlate with fatigue. CONCLUSION The findings can be used by nurses who are taking care of patients undergoing radiotherapy. Considering the relationship between fatigue and nutritional status, nurses can identify the risk group most vulnerable to fatigue and malnourishment in order to provide appropriate interventions for them.
Jointly Extracting Relations with Class Ties via Effective Deep Ranking

Connections between relations in relation extraction, which we call class ties, are common. In distantly supervised scenario, one entity tuple may have multiple relation facts. Exploiting class ties between relations of one entity tuple will be promising for distantly supervised relation extraction. However, previous models are not effective or ignore to model this property. In this work, to effectively leverage class ties, we propose to make joint relation extraction with a unified model that integrates convolutional neural network (CNN) with a general pairwise ranking framework, in which three novel ranking loss functions are introduced. Additionally, an effective method is presented to relieve the severe class imbalance problem from NR (not relation) for model training. Experiments on a widely used dataset show that leveraging class ties will enhance extraction and demonstrate the effectiveness of our model to learn class ties. Our model outperforms the baselines significantly, achieving state-of-the-art performance.
Characterization of neuronal responses to noxious visceral and somatic stimuli in the medial lumbosacral spinal cord of the rat.

The cutaneous receptive fields, long ascending projections, and responses to colorectal distension (20-100 mmHg) and tail movement of 252 neurons in spinal segments L6-S1 were characterized in pentobarbital- or halothane-N2O anesthetized, physiologically intact male rats. Seventeen additional neurons were studied in spinalized rats. Neurons studied were located within 0.5 mm of the midline at depths 0.2-1.4 mm from the spinal cord dorsum and included the area immediately dorsal and lateral to the central canal. Colorectal distension and/or antidromic invasion from the contralateral ventral quadrant of the cervical spinal cord were used as search stimuli. One hundred seventeen neurons responded to noxious colorectal distension; many had long ascending projections and convergent somatic input from deep joint receptors, ipsilateral perianal/scrotal cutaneous receptive fields, or both. Stimulus-response functions (SRFs) of 45 neurons to graded colorectal distension were linear, allowing extrapolation of threshold distending pressures to neuronal response. Neurons responsive to colorectal distension were subdivided into four classes based on their initial response colorectal distension (75-80 mmHg, 20 s). Short-latency abrupt (SL-A) neurons were excited at short latency by colorectal distension; activity abruptly returned to base line following termination of distension. Most SL-A neurons had long ascending projections, convergent somatic receptive fields, and 4/6 tested were excited by bradykinin administered intraarterially. The threshold distending pressure, estimated from the SRFs of 19 SL-A neurons, extrapolated to 2.7 mmHg. Short-latency sustained (SL-S) neurons were also excited at short latency by colorectal distension, but responses were sustained for 4-120 s following termination of distension. Most SL-S neurons had long ascending projections, convergent somatic receptive fields, and 18/20 tested were excited by intraarterial bradykinin. The threshold distending pressure, estimated from the SRFs of 20 SL-A neurons, extrapolated to 17.0 mmHg. Long-latency (LL) neurons were excited by colorectal distension at long latency following the onset of distension. No LL neurons had demonstrable long ascending projections, and few had convergent excitatory somatic fields. Three of five LL neurons were excited by intraarterial bradykinin. The threshold distending pressure, estimated from the SRFs of six LL neurons, extrapolated to 9.8 mmHg. Inhibited (INHIB) neurons were spontaneously active and were inhibited by colorectal distension. (ABSTRACT TRUNCATED AT 400 WORDS)
Multiplets, models, and the search for meaning: improving per-test fault diagnosis

The advantage to "one test at a time" fault diagnosis is its ability to implicate the components of complicated defect behaviors. The disadvantage is the large size and opacity of the diagnostic answer. In this paper, we address the problems of per-test diagnosis by improving the candidate matching, introducing scoring and ranking techniques, and by developing a method to translate the results into common defect scenarios. Our experimental results on simulated defects indicate that not only are the results improved on complex behaviors, but by considering passing test results we improve a common case where per-test algorithms can perform significantly worse than traditional diagnosis algorithms. Finally, our method of candidate analysis provides a way to bridge the per-test approach with traditional model-based fault diagnosis.
Cost‐Effectiveness of Therapeutic Drug Monitoring in Diagnosing Primary Aldosteronism in Patients With Resistant Hypertension

Primary aldosteronism (PA) is present in up to 20% of patients with treatment‐resistant hypertension (TRH). Investigation for PA in patients with TRH is recommended by current guidelines after medication nonadherence is excluded. Studies using therapeutic drug monitoring (TDM) have shown that >50% of patients with TRH are nonadherent to their prescribed antihypertensive medications. However, the relationship between the prevalence of PA and medication adherence as confirmed by TDM has not been previously assessed. A retrospective analysis from a hypertension referral clinic showed that prevalence of PA in adherent patients with TRH by TDM was significantly higher than in nonadherent patients (28% vs 8%, P<.05). Furthermore, cost analysis showed that TDM‐guided PA screening was $590.69 less expensive per patient, with minimal impact on the diagnostic accuracy. These data support a TDM‐guided PA screening approach as a cost‐saving strategy compared with routine PA screening for TRH.
Trust Based Content Distribution for Peer-To- Peer Overlay Networks

In peer-to-peer content distribution the lack of a central authority makes authentication difficult. Without authentication, adversary nodes can spoof identity and falsify messages in the overlay. This enables malicious nodes to launch man-in-the-middle or denial-of-service attacks. In this paper, we present a trust based content distribution for peer-to-peer overlay networks, which is built on the trust management scheme. The main concept is, before sending or accepting the traffic, the trust of the peer must be validated. Based on the success of data delivery and searching time, we calculate the trust index of a node. Then the aggregated trust index of the peers whose value is below the threshold value is considered as distrusted and the corresponding traffic is blocked. By simulation results we show that our proposed scheme achieves increased success ratio with reduced delay and drop.
Microsatellite loci for the Chinese bamboo rat Rhizomus sinensis

We describe 19 polymorphic microsatellite loci for the bamboo rat Rhizomus sinensis. When tested with 20 samples from a single population, these loci exhibited a mean of 4.5 alleles per locus and a mean expected heterozygosity of 0.612. All loci were in Hardy–Weinberg equilibrium and no evidence for linkage disequilibrium was detected between any loci. These loci will be useful for studying population genetic diversity and differentiation in the Chinese bamboo rat.
A refined deterministic linear program for the network revenue management problem with customer choice behavior

We present a new deterministic linear program for the network revenue management problem with customer choice behavior. The novel aspect of our linear program is that it naturally generates bid prices that depend on how much time is left until the time of departure. Similar to the earlier linear program used by van Ryzin and Liu (2004), the optimal objective value of our linear program provides an upper bound on the optimal total expected revenue over the planning horizon. In addition, the percent gap between the optimal objective value of our linear program and the optimal total expected revenue diminishes in an asymptotic regime where the leg capacities and the number of time periods in the planning horizon increase linearly with the same rate. Computational experiments indicate that when compared with the linear program that appears in the existing literature, our linear program can provide tighter upper bounds, and the control policies that are based on our linear program can obtain higher total expected revenues. © 2008 Wiley Periodicals, Inc. Naval Research Logistics, 2008
Alternating direction algorithms for $\ell_0$ regularization in compressed sensing.

In this paper we propose three iterative greedy algorithms for compressed sensing, called \emph{iterative alternating direction} (IAD), \emph{normalized iterative alternating direction} (NIAD) and \emph{alternating direction pursuit} (ADP), which stem from the iteration steps of alternating direction method of multiplier (ADMM) for $\ell_0$-regularized least squares ($\ell_0$-LS) and can be considered as the alternating direction versions of the well-known iterative hard thresholding (IHT), normalized iterative hard thresholding (NIHT) and hard thresholding pursuit (HTP) respectively. Firstly, relative to the general iteration steps of ADMM, the proposed algorithms have no splitting or dual variables in iterations and thus the dependence of the current approximation on past iterations is direct. Secondly, provable theoretical guarantees are provided in terms of restricted isometry property, which is the first theoretical guarantee of ADMM for $\ell_0$-LS to the best of our knowledge. Finally, they outperform the corresponding IHT, NIHT and HTP greatly when reconstructing both constant amplitude signals with random signs (CARS signals) and Gaussian signals.
Cross-media agent platform

We have developed a general purpose use and modular architecture of an embodied conversational agent (ECA). Our agent is able to communicate using verbal and nonverbal channels like gaze, facial expressions, and gestures. Our architecture follows the SAIBA framework that sets 3-step process and communication protocols. In our implementation of SAIBA architecture we focus on flexibility and we introduce different levels of the customization. In particular, our system is able to display the same communicative intention with different embodiments, be a virtual agent or a robot. Moreover our framework is independent of the animation player technology. Agent animations can be displayed across different medias, such as web browser, virtual or augmented reality. In this paper we present our agent architecture and its main features.
A novel seamless transfer method for a microgrid based on droop characteristic adjustment

In this paper, a novel seamless transfer method for a microgrid based on droop characteristic adjustment is proposed, the parallel operation of distributed generations is based on droop control to avoid critical communications. Linear integration method, which uses less communication and is more reliable, is proposed to adjust the microgrid voltage to synchronize it with the utility grid. Fault islanding is detected and the microgrid transfer to stand-alone mode. A flexible microgrid is obtained. The proposed method is verified by simulation and by the experiment in the laboratory
Sirolimus-eluting coronary stent.

PURPOSE The mechanism of action and pharmacokinetics of sirolimus when used as part of a drug-eluting stent (DES) and the efficacy and cost of using DESs versus bare-metal stents are discussed. SUMMARY The use of balloon angioplasty with or without coronary artery stenting is limited by the phenomenon of in-stent restenosis (ISR). Until very recently, most efforts to overcome ISR had been ineffective. The search to prevent or reduce the frequency of ISR has led to the recent development of novel coronary artery stents designed to deliver a drug that acts locally. The first DES was approved by FDA in April 2003. This stent releases sirolimus, an agent that inhibits vascular smooth-muscle-cell proliferation. To date, four major clinical trials have demonstrated the sirolimus-eluting stent to be safe and effective in preventing restenosis in de novo coronary artery lesions. CONCLUSION The sirolimus-eluting coronary stent is associated with less ISR than non-drug-containing stents, but further investigation is needed to determine its exact place in the treatment of coronary artery occlusion.
Clinical neuropathology practice guide 5-2013: markers of neuronal maturation

This review surveys immunocytochemical and histochemical markers of neuronal lineage for application to tissue sections of fetal and neonatal brain. They determine maturation of individual nerve cells as the tissue progresses to mature architecture. From a developmental perspective, neuronal markers are all about timing. These diverse cellular labels may be classified in two ways: 1) time of onset of expression (early; intermediate; late); 2) labeling of subcellular structures or metabolic functions (nucleoproteins; synaptic vesicle proteins; enolases; cytoskeletal elements; calcium-binding; nucleic acids; mitochondria). Apart from these positive markers of maturation, other negative markers are expressed in primitive neuroepithelial cells and early stages of neuroblast maturation, but no longer are demonstrated after initial stages of maturation. These examinations are relevant for studies of normal neuroembryology at the cellular level. In fetal and perinatal neuropathology they provide control criteria for application to malformations of the brain, inborn metabolic disorders and acquired fetal insults in which neuroblastic maturation may be altered. Disorders, in which cells differentiate abnormally, as in tuberous sclerosis and hemimegalencephaly, pose another yet aspect of mixed cellular lineage. The measurement in living patients, especially neonates, of serum and CSF levels of enolases, chromogranins and S-100 proteins as biomarkers of brain damage may potentially be correlated with their corresponding tissue markers at autopsy in infants who do not survive. The neuropathological markers here described can be performed in ordinary hospital laboratories, not just research facilities, and offer another dimension of diagnostic precision in interpreting abnormally developed fetal and postnatal brains.
Age and educational level effects on the performance of normal elderly on category verbal fluency tasks

Cognitive decline, particularly executive dysfunction, is observed in normal aging. In Brazil, the elderly population presents broad educational diversity. Category verbal fluency tests are frequently used to detect cognitive impairment, assessing executive function, language and semantic memory. Objective To investigate the effects of age and education on category animal fluency task (CAF) in healthy elderly. Methods We evaluated 319 healthy elderly from outpatient care units of two university reference centers of Rio de Janeiro and São Paulo. The sample was divided into two age, and five schooling subgroups. To be included participants had to demonstrate preservation of global cognitive functioning, independence for activities of daily living and not fulfill diagnostic criteria for dementia. All participants were submitted to neurological and neuropsychological evaluations. Results There was a correlation between age and CAF performance (r= –0.26, p<0.01), which was not confirmed when years of education were included as a covariant in univariate ANCOVA. Significant differences were found in CAF performance among the different educational level groups on correlation analysis (r=0.42, p<0.01) and ANCOVA analysis (F=18.8, p<0.05). Illiteracy was associated with worst CAF performance, while university level was associated with best performance. Conclusion The best CAF performance was found in the first years of schooling (literacy learning process) compared to illiteracy, and when finishing high school and starting university courses compared to all other educational levels. These stages are associated with significant gains in semantic memory and executive function which are critical for verbal fluency performance.
MEF‐2 function is modified by a novel co‐repressor, MITR

The MEF‐2 proteins are a family of transcriptional activators that have been detected in a wide variety of cell types. In skeletal muscle cells, MEF‐2 proteins interact with members of the MyoD family of transcriptional activators to synergistically activate gene expression. Similar interactions with tissue or lineage‐specific cofactors may also underlie MEF‐2 function in other cell types. In order to screen for such cofactors, we have used a transcriptionally inactive mutant of Xenopus MEF2D in a yeast two‐hybrid screen. This approach has identified a novel protein expressed in the early embryo that binds to XMEF2D and XMEF2A. The MEF‐2 interacting transcription repressor (MITR) protein binds to the N‐terminal MADS/MEF‐2 region of the MEF‐2 proteins but does not bind to the related Xenopus MADS protein serum response factor. In the early embryo, MITR expression commences at the neurula stage within the mature somites and is subsequently restricted to the myotomal muscle. In functional assays, MITR negatively regulates MEF‐2‐dependent transcription and we show that this repression is mediated by direct binding of MITR to the histone deacetylase HDAC1. Thus, we propose that MITR acts as a co‐repressor, recruiting a specific deacetylase to downregulate MEF‐2 activity.
History effects on network growth

Growth dynamic of real networks because of emerging complexities is an open and interesting question. Indeed it is not realistic to ignore history impact on the current events. The mystery behind that complexity could be in the role of history in some how. To regard this point, the average effect of history has been included by a kernel function in differential equation of Barabasi Albert (BA) model . This approach leads to a fractional order BA differential equation as a generalization of BA model. As opposed to unlimited growth for degree of nodes, our results show that over time the memory impact will cause a decay for degrees. This gives a higher chance to younger members for turning to a hub. In fact in a real network, there are two competitive processes. On one hand, based on preferential attachment mechanism nodes with higher degree are more likely to absorb links. On the other hand, node history through aging process prevents new connections. Our findings from simulating a network grown by considering these effects also from studying a real network of collaboration between Hollywood movie actors conforms the results and significant effects of history and time on dynamic.
Clarifying the role of distance in friendships on twitter: discovery of a double power-law relationship

This study analyzes friendships in online social networks involving geographic distance with a geo-referenced Twitter dataset, which provides the exact distance between corresponding users. We start by introducing a strong definition of "friend" on Twitter, requiring bidirectional communication. Next, by utilizing geo-tagged mentions delivered by users to determine their locations, we introduce a two-stage distance estimation algorithm. As our main contribution, our study provides the following newly-discovered friendship degree related to the issue of space: The number of friends according to distance follows a double power-law (i.e., a double Pareto law) distribution, indicating that the probability of befriending a particular Twitter user is significantly reduced beyond a certain geographic distance between users, termed the separation point. Our analysis provides much more fine-grained social ties in space, compared to the conventional results showing a homogeneous power-law with distance.