Miracle-dz/UniFAR-FTUs huggingface dataset:
Investigating the design space of smartwatches combining physical rotary inputs

Watches benefit from a long design history. Designers and engineers have successfully built devices using rotary physical inputs such as crowns, bezels, and wheels, separately or combined. Smart watch designers have explored the use of some of these inputs for interactions. However, a systematic exploration of their combinations has yet to be done. We investigate the design space of interactions with multiple rotary inputs through a three stages exploration. (1) We build upon observations of a collection of 113 traditional or electronic watches to propose a typology of physical rotary inputs for watches. (2) We conduct two focus groups to explore combination of physical rotary inputs. (3) We then build upon the output of these focus groups to design a low fidelity prototype, and further discuss the potential and challenges of rotary inputs combinations during a third focus group.
Pirfenidone suppresses TGF-β1-induced human intestinal fibroblasts activities by regulating proliferation and apoptosis via the inhibition of the Smad and PI3K/AKT signaling pathway

Intestinal fibroblasts, the main effector cells of intestinal fibrosis, are considered to be a good target for anti-fibrotic therapy. The aim of the present study was to examine the effects of pirfenidone (PFD) on human intestinal fibroblasts (HIFs) stimulated by transforming growth factor (TGF)-β1 and to explore the potential mechanism. Prior to stimulation with TGF-β1 (10 ng/ml), HIFs were treated with or without PFD (1 mg/ml). Cell proliferation was determined by Cell Counting Kit (CCK)-8 and colony formation assays, and cell apoptosis was assessed using flow cytometry and a TUNEL assay. Reverse transcription-quantitative polymerase chain reaction and western blotting were performed to evaluate the mRNA and protein expressions of α-smooth muscle actin (α-SMA), collagen I and fibronectin. The protein expression of TGF-β1/mothers against decapentaplegic homolog (Smad) and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathways was evaluated by western blotting. CCK-8 and colony formation assays demonstrated that PFD significantly inhibited cell proliferation in HIFs stimulated with TGF-β1. Flow cytometry and TUNEL assays revealed that PFD treatment significantly enhanced apoptosis in TGF-β1-stimulated HIFs. In addition, PFD markedly reduced TGF-β1-induced HIF activities, such as myofibroblast differentiation (α-SMA), and collagen production (collagen I and fibronectin). These effects of PFD were mediated by the inhibition of the TGF-β1/Smad and PI3K/AKT signaling pathways. Therefore, the present study demonstrated that PFD reduced TGF-β1-induced fibrogenic activities of HIFs, suggesting that PFD may be a potential therapeutic agent for intestinal fibrosis.
Essentials of Aquaphotomics and Its Chemometrics Approaches

Aquaphotomics is a novel scientific discipline involving the study of water and aqueous systems. Using light-water interaction, it aims to extract information about the structure of water, composed of many different water molecular conformations using their absorbance bands. In aquaphotomics analysis, specific water structures (presented as water absorbance patterns) are related to their resulting functions in the aqueous systems studied, thereby building an aquaphotome—a database of water absorbance bands and patterns correlating specific water structures to their specific functions. Light-water interaction spectroscopic methods produce complex multidimensional spectral data, which require data processing and analysis to extract hidden information about the structure of water presented by its absorbance bands. The process of extracting information from water spectra in aquaphotomics requires a field–specific approach. It starts with an appropriate experimental design and execution to ensure high-quality spectral signals, followed by a multitude of spectral analysis, preprocessing and chemometrics methods to remove unwanted influences and extract water absorbance spectral pattern related to the perturbation of interest through the identification of activated water absorbance bands found among the common, consistently repeating and highly influential variables in all analytical models. The objective of this paper is to introduce the field of aquaphotomics and describe aquaphotomics multivariate analysis methodology developed during the last decade. Through a worked-out example of analysis of potassium chloride solutions supported by similar approaches from the existing aquaphotomics literature, the provided instruction should give enough information about aquaphotomics analysis i.e. to design and perform the experiment and data analysis as well as to represent water absorbance spectral pattern using various forms of aquagrams—specifically designed aquaphotomics graphs. The explained methodology is derived from analysis of near infrared spectral data of aqueous systems and will offer a useful and new tool for extracting data from informationally rich water spectra in any region. It is the hope of the authors that with this new tool at the disposal of scientists and chemometricians, pharmaceutical and biomedical spectroscopy will substantially progress beyond its state-of-the-art applications.
Target searching in unknown environment of multi-robot system using a hybrid particle swarm optimization

Target searching in unknown environment using multi-robot search systems has received increasing attention in recent years. Particle Swarm Optimization (PSO) has applied successfully on multi-robot target searching system. However, this algorithm suffer from premature convergence problem and cannot escape from the local optima. It is, therefore, important to have an efficient method to escape from the local optima and create and efficient balance between exploitation and exploration. In this study, we propose a new method based on PSO algorithm (ATREL-PSO) to find the target in unknown environment using multi-robot system within a limited time. This novel algorithm is demonstrated to escape from the local optima and create an efficient balance between exploration and exploitation to reach the target faster. The concept of attraction, repulsion and the combination of repulsion and attraction enhancing the search exploration, and when the robot get closer to the target it should forget the PSO concept and apply the local search method to reach the target faster. Experimental results obtained in a simulated environment show that biological and sociological inspiration could be useful to meet the challenges of robotic applications that can be described as optimization problems.
Deep-Learning Ensembles for Skin-Lesion Segmentation, Analysis, Classification: RECOD Titans at ISIC Challenge 2018

This extended abstract describes the participation of RECOD Titans in parts 1 to 3 of the ISIC Challenge 2018 "Skin Lesion Analysis Towards Melanoma Detection" (MICCAI 2018). Although our team has a long experience with melanoma classification and moderate experience with lesion segmentation, the ISIC Challenge 2018 was the very first time we worked on lesion attribute detection. For each task we submitted 3 different ensemble approaches, varying combinations of models and datasets. Our best results on the official testing set, regarding the official metric of each task, were: 0.728 (segmentation), 0.344 (attribute detection) and 0.803 (classification). Those submissions reached, respectively, the 56th, 14th and 9th places.
Regression Adjustments for Estimating the Global Treatment Effect in Experiments with Interference

Abstract Standard estimators of the global average treatment effect can be biased in the presence of interference. This paper proposes regression adjustment estimators for removing bias due to interference in Bernoulli randomized experiments. We use a fitted model to predict the counterfactual outcomes of global control and global treatment. Our work differs from standard regression adjustments in that the adjustment variables are constructed from functions of the treatment assignment vector, and that we allow the researcher to use a collection of any functions correlated with the response, turning the problem of detecting interference into a feature engineering problem. We characterize the distribution of the proposed estimator in a linear model setting and connect the results to the standard theory of regression adjustments under SUTVA. We then propose an estimator that allows for flexible machine learning estimators to be used for fitting a nonlinear interference functional form. We propose conducting statistical inference via bootstrap and resampling methods, which allow us to sidestep the complicated dependences implied by interference and instead rely on empirical covariance structures. Such variance estimation relies on an exogeneity assumption akin to the standard unconfoundedness assumption invoked in observational studies. In simulation experiments, our methods are better at debiasing estimates than existing inverse propensity weighted estimators based on neighborhood exposure modeling. We use our method to reanalyze an experiment concerning weather insurance adoption conducted on a collection of villages in rural China.
Mechanism of BDNF Modulation in GABAergic Synaptic Transmission in Healthy and Disease Brains

In the mature healthy mammalian neuronal networks, γ-aminobutyric acid (GABA) mediates synaptic inhibition by acting on GABAA and GABAB receptors (GABAAR, GABABR). In immature networks and during numerous pathological conditions the strength of GABAergic synaptic inhibition is much less pronounced. In these neurons the activation of GABAAR produces paradoxical depolarizing action that favors neuronal network excitation. The depolarizing action of GABAAR is a consequence of deregulated chloride ion homeostasis. In addition to depolarizing action of GABAAR, the GABABR mediated inhibition is also less efficient. One of the key molecules regulating the GABAergic synaptic transmission is the brain derived neurotrophic factor (BDNF). BDNF and its precursor proBDNF, can be released in an activity-dependent manner. Mature BDNF operates via its cognate receptors tropomyosin related kinase B (TrkB) whereas proBDNF binds the p75 neurotrophin receptor (p75NTR). In this review article, we discuss recent finding illuminating how mBDNF-TrkB and proBDNF-p75NTR signaling pathways regulate GABA related neurotransmission under physiological conditions and during epilepsy.
Protein evolution speed depends on its stability and abundance and on chaperone concentrations

Significance Some biological evolution is slow (millions of years), and some is fast (months to years). The speed at which a protein evolves depends on how stable a protein’s folded structure is, how well it avoids aggregation, and how well-chaperoned it is. What are the mechanisms? We compute fitness landscapes by combining a model of protein-folding equilibria with sequence-change dynamics. We find that adapting to a new environment is fastest for proteins that are least stably folded, because those sit on steep downhill parts of fitness potentials. The modeling shows that cells should adapt to warmer environments faster than to colder ones, explains why increasing a protein’s abundance slows cell evolution, and explains how chaperones accelerate evolution by mitigating this effect. Proteins evolve at different rates. What drives the speed of protein sequence changes? Two main factors are a protein’s folding stability and aggregation propensity. By combining the hydrophobic–polar (HP) model with the Zwanzig–Szabo–Bagchi rate theory, we find that: (i) Adaptation is strongly accelerated by selection pressure, explaining the broad variation from days to thousands of years over which organisms adapt to new environments. (ii) The proteins that adapt fastest are those that are not very stably folded, because their fitness landscapes are steepest. And because heating destabilizes folded proteins, we predict that cells should adapt faster when put into warmer rather than cooler environments. (iii) Increasing protein abundance slows down evolution (the substitution rate of the sequence) because a typical protein is not perfectly fit, so increasing its number of copies reduces the cell’s fitness. (iv) However, chaperones can mitigate this abundance effect and accelerate evolution (also called evolutionary capacitance) by effectively enhancing protein stability. This model explains key observations about protein evolution rates.
Renal phosphorus excretion in adult healthy cats after the intake of high phosphorus diets with either calcium monophosphate or sodium monophosphate

Renal and faecal phosphorus excretion of adult healthy European shorthaired cats after the intake of high phosphorus diets (meat/rice based) with either calcium monophosphate (HP-CaP) or sodium monophosphate (HP-NaP) as main phosphorus source was compared. The control diets (CON-CaP and CON-NaP, respectively) did not contain any added phosphorus. Calcium/phosphorus ratio was adjusted to 1.3/1 by adding calcium carbonate. Twenty-three cats were available for the trials. All cats were fed the control diets for 29 days; then, the HP diets were tested for 29 days against controls in a crossover design. Faeces and urine were collected in the last 10 days of each trial. Phosphorus in food, faeces and urine was measured by photometry after wet digestion. Phosphorus intake amounted to 84 ± 10 mg/kg body weight (BW) in CON-NaP (n = 13) and to 74 ± 7 in CON-CaP (n = 12). In the HP groups, the intake was 255 ± 34 mg/kg BW (HP-NaP; n = 13) and 216 ± 20 mg/kg BW (HP-CaP; n = 12). The sodium monophosphate in group HP-NaP led to a higher renal phosphorus excretion (83 ± 15 mg/kg BW) than the calcium monophosphate (25 ± 5 mg/kg BW; p < 0.05), even though the apparent phosphorus digestibility was higher in HP-CaP than in HP-NaP (p < 0.05). Faecal calcium excretion was strictly correlated to faecal phosphorus excretion (r2 = 0.98). The same was true for calcium and phosphorus balance (r2 = 0.89). In group HP-NaP, seven of 13 cats showed glucosuria. By contrast, in HP-CaP glucosuria was not observed. Highly water-soluble inorganic phosphorus sources such as sodium phosphate are likely to lead to phosphaturia and may present a risk for renal health of cats.
Discovery and Identification of Pyrazolopyramidine Analogs as Novel Potent Androgen Receptor Antagonists

Androgen receptor (AR), an important target in the current androgen derivation therapy, plays a critical role in the development and progress of prostate cancer (PCa). Nonsteroidal antiandrogens, such as enzalutamide and bicalutamide, are commonly used in clinic to treat PCa. Though they are very effective at the beginning, drug resistance problem appears after about 18 months. One of the reasons is that these antiandrogens share similar structure skeleton. Therefore, it is urgent to discover novel antiandrogens with different skeletons for resistance problem. Herein, we combined structure- and ligand-based methodologies for virtual screening chemical databases to identify potent AR antagonists. Then the cytotoxic activities of the screened hit samples were evaluated by using LNCaP prostate cancer cells. Virtual screening and biological evaluation assay results suggest that several chemicals with novel pyrazolopyrimidine skeleton can inhibit the proliferation of prostate cancer cells with similar, or even higher, bioactivities to bicalutamide. AR reporter gene assay experiments proved that Compound III showed potential antagonistic effects. In addition, molecular dynamics simulations results proved that Compound III can properly bind to AR and prevent helix 12 (H12) from closing to distort the formation of activation function 2 (AF2) site, resulting in the invalid transcription. Hence, pyrazolopyrimidine was discovered as a novel, potent and promising antiandrogen skeleton deserved to be further studied.
Effects of a Brief Hypnosis Relaxation Induction on Subjective Psychological States, Cardiac Vagal Activity, and Breathing Frequency

Abstract This study investigated the effects of a brief hypnosis including relaxation suggestions on physiological markers of relaxation, cardiac vagal activity, and breathing frequency. Forty participants were tested in a within-subjects design. Participants listened to a recorded hypnosis session and to a nonhypnotic recording. No differences were found regarding cardiac vagal activity. Participants breathed significantly faster during the audio conditions (hypnosis and nonhypnotic recording) in comparison to resting measures. After hypnosis, subjective arousal was significantly lower and emotional valence was significantly more positive than after the nonhypnotic recording condition. The relaxing effects of hypnosis that includes relaxation suggestions appear to be located at the subjective level but not at the peripheral physiological level.
“Green Medicine”: The Past, Present, and Future of Botanicals

Botanicals are plant‐derived products that have been consumed by humans for centuries. Today, the marketing and use of botanicals for health and wellness benefits continues to thrive worldwide, with consumers projected to spend more than $140 billion globally by 2024 (Global Analysis, Inc). However, research on the quality and safety of these products has lagged behind sales. Because of this divergence, opportunities abound for collaborations amongst scientists from industry, academia, and government to address these unmet public health needs. Clinical pharmacologists and toxicologists from all of these sectors play critical roles in developing harmonized approaches to achieve the common goal of ensuring botanical products with superior quality and safety.
RKIP: A Key Regulator in Tumor Metastasis Initiation and Resistance to Apoptosis: Therapeutic Targeting and Impact

RAF-kinase inhibitor protein (RKIP) is a well-established tumor suppressor that is frequently downregulated in a plethora of solid and hematological malignancies. RKIP exerts antimetastatic and pro-apoptotic properties in cancer cells, via modulation of signaling pathways and gene products involved in tumor survival and spread. Here we review the contribution of RKIP in the regulation of early metastatic steps such as epithelial–mesenchymal transition (EMT), migration, and invasion, as well as in tumor sensitivity to conventional therapeutics and immuno-mediated cytotoxicity. We further provide updated justification for targeting RKIP as a strategy to overcome tumor chemo/immuno-resistance and suppress metastasis, through the use of agents able to modulate RKIP expression in cancer cells.
Interferon-γ and Interleukin-10 Responses during Clinical Malaria Episodes in Infants Aged 0–2 Years Prenatally Exposed to Plasmodium falciparum: Tanzanian Birth Cohort

Background Infants born to mothers with placental malaria are prenatally exposed to Plasmodium falciparum antigens. However, the effect of that exposure to subsequent immune responses has not been fully elucidated. This study aimed at determining the effect of prenatal exposure to P. falciparum on Interleukin-10 and Interferon-γ responses during clinical malaria episodes in the first 24 months of life. Methods This prospective cohort study involved 215 infants aged 0-2 years born to mothers with or without placental malaria. Enzyme-linked immunosorbent assay (ELISA) was used to determine levels of IL-10 and IFN-γ in infants and detect IgM in cord blood. Data were analyzed using SPSS version 20. Findings Geometric mean for IFN-γ in exposed infants was 557.9 pg/ml (95% CI: 511.6-604.1) and in unexposed infants it was 634.4 pg/ml (95% CI: 618.2-668.5) (P=0.02). Mean IL-10 was 22.4 pg/ml (95% CI: 19.4-28.4) and 15.1 pg/ml (95%CI: 12.4-17.6), respectively (P=0.01). Conclusions Prenatal exposure to P. falciparum antigens significantly affects IL-10 and IFN-γ responses during clinical malaria episodes in the first two years of life.
The Complexity of Learning Acyclic Conditional Preference Networks

Learning of user preferences, as represented by, for example, Conditional Preference Networks (CP-nets), has become a core issue in AI research. Recent studies investigate learning of CP-nets from randomly chosen examples or from membership and equivalence queries. To assess the optimality of learning algorithms as well as to better understand the combinatorial structure of classes of CP-nets, it is helpful to calculate certain learning-theoretic information complexity parameters. This article focuses on the frequently studied case of learning from so-called swap examples, which express preferences among objects that differ in only one attribute. It presents bounds on or exact values of some well-studied information complexity parameters, namely the VC dimension, the teaching dimension, and the recursive teaching dimension, for classes of acyclic CP-nets. We further provide algorithms that learn tree-structured and general acyclic CP-nets from membership queries. Using our results on complexity parameters, we assess the optimality of our algorithms as well as that of another query learning algorithm for acyclic CP-nets presented in the literature. Our algorithms are near-optimal, and can, under certain assumptions, be adapted to the case when the membership oracle is faulty.
Neoadjuvant PET and MRI-based intensity modulated radiotherapy leads to less toxicity and improved pathologic response rates in locally advanced rectal cancer.

Background Neoadjuvant chemoradiation (NeoCRT) is standard of care for the treatment of locally advanced rectal cancer (LARC). Contemporary radiation techniques and pre-treatment imaging may impact toxicities and pathologic response (PR). Herein we compare intensity modulated radiotherapy (IMRT) and advanced pre-treatment imaging in the neoadjuvant treatment of LARC and resulting impact on toxicities and pathologic outcomes relative to 3 dimensional conformal radiotherapy (3DCRT). Methods LARC patients treated at 4 large academic centers in the US from 2007-2016 were reviewed. Patients received 5-FU-based NeoCRT concurrently with IMRT or 3DCRT. PR was recorded as none, partial, or complete. Common terminology for adverse events version 4 was used to grade toxicities. Toxicity rates were compared using Chi-square analysis. Multivariable models were fit adjusting for age, gender, pre-tx CT to identify independent predictors of PR and toxicity. Results A total of 128 patients were analyzed: 60.1% male and 39.8% female, median age 57.7 years (range, 31-85 years). Clinical characteristics were similar across RT groups. The outcome of partial and complete PR was similar for IMRT and 3DCRT (48.1%, 23.1% vs. 31.7%, 23.3%), respectively. After adjusting for gender, age, and pre-RT chemotherapy type, IMRT and pretreatment PET and/or MRI imaging was significantly associated with increased odds for complete and partial response (OR =2.95, 95% CI: 1.21-7.25, P=0.018; OR =14.70, 95% CI: 3.69-58.78, P<0.0001). Additionally, IMRT was associated with reduced rates of dehydration, dermatitis, rectal pain, rectal bleeding, and diverting ostomy (P<0.05). Overall rates of grade 2 and higher toxicities were significantly reduced in IMRT vs. 3DCRT after adjusting for confounders (OR =0.27, 95% CI: 0.08-0.87). Conclusions NeoCRT IMRT with pretreatment PET and/or MRI for LARC leads to reduced acute toxicities and improved PR compared to 3DCRT. Given the challenges associated with prospective validation of these data, IMRT with pretreatment PET and/or MRI should be considered standard treatment for LARC.