Miracle-dz/UniFAR-FTUs huggingface dataset:
Persistence-sensitive simplication of functions on surfaces in linear time

Persistence provides a way of grading the importance of homological features in the sublevel sets of a real-valued function. Following the definition given by Edelsbrunner, Morozov and Pascucci, an e-simplication of a function f is a function g in which the homological noise of persistence less than e has been removed. In this paper, we give an algorithm for constructing an e-simplication of a function defined on a triangulated surface in linear time. Our algorithm is very simple, easy to implement and follows directly from the study of the e-simplication of a function on a tree. We also show that the computation of persistence defined on a graph can be performed in linear time in a RAM model. This gives an overall algorithm in linear time for both computing and simplifying the homological noise of a function f on a surface.
Effects of chronic hypoxia on Ca2+ mobilization and Ca2+ sensitivity of myofilaments in uterine arteries.

The effect of chronic hypoxia on free intracellular Ca2+ concentration ([Ca2+]i) and Ca2+ sensitivity of myofilaments during agonist stimulation was examined in uterine arteries obtained from normoxic and chronically hypoxic pregnant sheep maintained at high altitude (3,820 m) for ∼110 days. Smooth muscle [Ca2+]iwas measured simultaneously with muscle contraction in the same intact tissue. Whereas both KCl and 5-HT increased [Ca2+]iand tension simultaneously in the uterine artery, 5-HT produced significantly greater contractile tension (in g) than KCl at a given amount of [Ca2+]ias indicated by the ratio of fura 2 fluorescence intensity induced by excitation at 340 nm to that induced at 380 nm (29.8 ± 6.9 vs. 16.9 ± 4.0, P < 0.05). Chronic hypoxia did not change KCl-induced contractions, nor did it affect KCl-mediated increases in [Ca2+]i. In contrast, chronic hypoxia significantly inhibited 5-HT-induced contractions and decreased the 5-HT-stimulated increase in [Ca2+]i(pD2 7.46 ± 0.18 → 6.86 ± 0.11, P < 0.05, where pD2 is -log half-maximal effective concentration) in uterine arteries. In addition, the slope (g tension/nM [Ca2+]i) of the 5-HT-mediated [Ca2+]i-tension relationship was significantly decreased in chronically hypoxic arteries (0.024 ± 0.002 → 0.013 ± 0.001, P < 0.01). The results suggest that chronic hypoxia suppresses agonist-mediated Ca2+ homeostasis in uterine arteries by inhibiting Ca2+mobilization and the agonist-enhanced Ca2+ sensitivity of myofilaments.
People detection and tracking from aerial thermal views

Detection and tracking of people in visible-light images has been subject to extensive research in the past decades with applications ranging from surveillance to search-and-rescue. Following the growing availability of thermal cameras and the distinctive thermal signature of humans, research effort has been focusing on developing people detection and tracking methodologies applicable to this sensing modality. However, a plethora of challenges arise on the transition from visible-light to thermal images, especially with the recent trend of employing thermal cameras onboard aerial platforms (e.g. in search-and-rescue research) capturing oblique views of the scenery. This paper presents a new, publicly available dataset of annotated thermal image sequences, posing a multitude of challenges for people detection and tracking. Moreover, we propose a new particle filter based framework for tracking people in aerial thermal images. Finally, we evaluate the performance of this pipeline on our dataset, incorporating a selection of relevant, state-of-the-art methods and present a comprehensive discussion of the merits spawning from our study.
System identification of closed-loop cardiovascular control mechanisms : diabetic autonomic neuropathy

Mukkamala, Ramakrishna, Joanne M. Mathias, Thomas J. Mullen, Richard J. Cohen, and Roy Freeman. System identification of closed-loop cardiovascular control mechanisms: diabetic autonomic neuropathy. Am. J. Physiol. 276 (Regulatory Integrative Comp. Physiol. 45): R905–R912, 1999. —We applied cardiovascular system identification (CSI) to characterize closed-loop cardiovascular regulation in patients with diabetic autonomic neuropathy (DAN). The CSI method quantitatively analyzes beat-to-beat fluctuations in noninvasively measured heart rate, arterial blood pressure (ABP), and instantaneous lung volume (ILV) to characterize four physiological coupling mechanisms, two of which are autonomically mediated (the heart rate baroreflex and the coupling of respiration, measured in terms of ILV, to heart rate) and two of which are mechanically mediated (the coupling of ventricular contraction to the generation of the ABP wavelet and the coupling of respiration to ABP). We studied 37 control and 60 diabetic subjects who were classified as having minimal, moderate, or severe DAN on the basis of standard autonomic tests. The autonomically mediated couplings progressively decreased with increasing severity of DAN, whereas the mechanically mediated couplings were essentially unchanged. CSI identified differences between the minimal DAN and control groups, which were indistinguishable based on the standard autonomic tests. CSI may provide a powerful tool for assessing DAN.
Effects of biologic disease-modifying anti-rheumatic drugs on the radiographic progression of rheumatoid arthritis: a systematic literature review.

OBJECTIVES To evaluate the effect of biologic disease-modifying anti-rheumatic drugs (bDMARDs) on radiographic progression in patients with rheumatoid arthritis (RA). METHODS A systematic review of electronic databases and conference proceedings was conducted through January 2015, to identify randomised controlled trials (RCTs) and observational studies that assessed the impact of bDMARDs [± conventional synthetic DMARDs (csDMARDs), mainly methotrexate (MTX)], versus csDMARDs alone, on radiographic progression in patients with RA. RESULTS Following screening of >5000 records, 104 publications covering 63 studies were included. Of 34 RCTs in patients with early, active (n=13) or established RA (n=21) [abatacept (1, 2); adalimumab (4, 2); certolizumab pegol (1, 4); etanercept (3, 3); golimumab (1, 4); infliximab (1, 1); rituximab (1, 1); tocilizumab (1, 5)], combination therapy with a bDMARD and MTX had a significantly greater effect than placebo or MTX alone, in inhibiting radiographic progression. This included patients previously unresponsive, or who responded incompletely, to MTX treatment alone, and was supported by data from observational studies. Findings from a smaller subset of these and other RCTs supported superiority of combination therapy over bDMARD monotherapy, and bDMARD monotherapy over MTX, in slowing radiographic progression. CONCLUSIONS There is evidence from RCTs with a range of bDMARDs that improvement in radiographic outcomes for patients with early or established RA, when used in combination with MTX and to a lesser extent as monotherapy, are significantly greater than MTX alone. There was no evidence of a difference between bDMARDs on inhibition of radiographic progression.
Engineering the Salt-Inducible Ectoine Promoter Region of Halomonas elongata for Protein Expression in a Unique Stabilizing Environment

It has been firmly established that organic osmolytes (compatible solutes) of halophilic Bacteria and Archaea have positive effects on conformation and activity of proteins, and may therefore improve their functional production. In particular, the amino acid derivative ectoine is known for its conformational stabilization, aggregation suppression, and radical protection properties. The natural producer and industrial production strain Halomonas elongata accumulates ectoine in the cytoplasm, and as a result offers a unique stabilizing environment for recombinant proteins. For the construction of broad hoast range vector systems with fluorescent reporter proteins, we chose the salt-inducible promoter region of the ectoine gene cluster (promA). A closer inspection of the genetic background revealed that its combination of sigma 38 (σ38) and sigma 70 (σ70) promoters was followed by a weak ribosomal binding site (RBS). This inspired a systematic approach for the construction of a promA-based vector series with a synthetic RBS region using the RBS Calculator v2.0, which resulted in a greatly improved salt-dependent expression—even in a deletion construct lacking the σ38 promoter. To expand the application range of this expression system, we looked further into the possible export of recombinant proteins into the periplasm. Both sec and tat leader sequences from H. elongata proved to be suitable for directed periplasmic transport into an extreme environment of freely selectable ionic strength.
Myostatin expression in porcine tissues: tissue specificity and developmental and postnatal regulation.

The objective of this study was to establish the developmental pattern and tissue specificity of porcine myostatin expression and to evaluate expression in skeletal muscle during circumstances in which muscle growth was altered. Northern blot analysis revealed two transcripts (1.5 and 0.8 kb). Myostatin mRNA was detected in whole fetuses at 21 and 35 days and was markedly increased ( P < 0.05) by 49 days. At birth, mRNA abundance in longissimus muscle had declined significantly ( P < 0.05) from that at day 105 of gestation and continued to decrease ( P < 0.05) to its lowest level 2 wk postnatally (4 kg body wt). Myostatin expression was higher ( P < 0.05) at 55, 107, and 162 kg body wt than at 4 kg body wt. Postnatally, myostatin mRNA was detected in skeletal muscle and mammary gland. Expression at birth was 65% higher ( P < 0.04) in longissimus muscle of low-birth-weight piglets (0.57 ± 0.052 kg body wt) vs. normal (1.37 ± 0.077 kg body wt) littermates, irrespective of gender. However, suppression of longissimus muscle growth by food deprivation (3 days) did not alter ( P > 0.15) myostatin expression in either 4- or 7-wk-old piglets. Additionally, myostatin mRNA abundance was not changed by porcine growth hormone administration in growing animals. These data indicate that myostatin expression in skeletal muscle peaks prenatally and that greater expression is associated with low birth weight. Expression in mammary gland indicates a possible role for myostatin in mammary gland development and/or lactation.
Effect of chronic bradykinin administration on insulin action in an animal model of insulin resistance.

The nonapeptide bradykinin (BK) has been implicated as the mediator of the beneficial effect of angiotensin-converting enzyme inhibitors on insulin-stimulated glucose transport in insulin-resistant skeletal muscle. In the present study, the effects of chronic in vivo BK treatment of obese Zucker ( fa/ fa) rats, a model of glucose intolerance and severe insulin resistance, on whole body glucose tolerance and skeletal muscle glucose transport activity stimulated by insulin or contractions were investigated. BK was administered subcutaneously (twice daily at 40 μg/kg body wt) for 14 consecutive days. Compared with a saline-treated obese group, the BK-treated obese animals had significantly ( P < 0.05) lower fasting plasma levels of insulin (20%) and free fatty acids (26%), whereas plasma glucose was not different. During a 1 g/kg body wt oral glucose tolerance test, the glucose and insulin responses [incremental areas under the curve (AUC)] were 21 and 29% lower, respectively, in the BK-treated obese group. The glucose-insulin index, the product of the glucose and insulin AUCs and an indirect index of in vivo insulin action, was 52% lower in the BK-treated obese group compared with the obese control group. Moreover, 2-deoxyglucose uptake in the isolated epitrochlearis muscle stimulated by a maximally effective dose of insulin (2 mU/ml) was 52% greater in the BK-treated obese group. Contraction-stimulated (10 tetani) 2-deoxyglucose uptake was also enhanced by 35% as a result of the BK treatment. In conclusion, these findings indicate that in the severely insulin-resistant obese Zucker rat, chronic in vivo treatment with BK can significantly improve whole body glucose tolerance, possibly as a result of the enhanced insulin-stimulated skeletal muscle glucose transport activity observed in these animals.
Galacto-Oligosaccharide/Polidextrose Enriched Formula Protects against Respiratory Infections in Infants at High Risk of Atopy: A Randomized Clinical Trial

Background: Early nutrition affects the risk of atopy and infections through modifications of intestinal microbiota. The Prebiotics in the Prevention of Atopy (PIPA) study was a 24-month randomised, double-blind, placebo-controlled trial. It aimed to evaluate the effects of a galacto-oligosaccharide/polydextrose (GOS/PDX)-formula (PF) on atopic dermatitis (AD) and common infections in infants who were born to atopic parents and to investigate the relationship among early nutrition, gut microbiota and clinical outcomes. Methods: A total of 201 and 199 infants were randomized to receive a PF and standard formula (SF), respectively; 140 infants remained on exclusive breastfeeding (BF). Results: The cumulative incidence of AD and its intensity and duration were not statistically different among the three groups. The number of infants with at least one episode of respiratory infection (RI) and the mean number of episodes until 48 weeks of age were significantly lower in the PF group than in the SF group. The number of patients with recurrent RIs and incidence of wheezing lower RIs until 96 weeks were lower in the PF group than the SF group, but similar to the BF group. Bifidobacteria and Clostridium cluster I colonization increased over time in the PF group but decreased in the SF and BF groups. Bifidobacteria had a protective role in RIs, whereas Clostridium cluster I was associated with atopy protection. Conclusion: The early administration of PF protects against RIs and mediates a species-specific modulation of the intestinal microbiota. Trial registration: clinicaltrial.gov Identifier: NCT02116452.
Capsaicin sensitivity and voltage-gated sodium currents in colon sensory neurons from rat dorsal root ganglia.

DiI-labeled colon sensory neurons were acutely dissociated from S1 rat dorsal root ganglia (DRG) and studied using perforated whole cell patch-clamp techniques. Forty-six percent (54/116) of labeled sensory neurons responded to capsaicin (10-8- 10-5M) with an increase in inward current, which was a nonspecific cation conductance. Responses to capsaicin applied by puffer ejection were dependent on dose, with a half-maximal response at 4.9 × 10-7 M; bath application was characterized by marked desensitization. Voltage-gated Na+currents in 23 of 30 DRG cells exhibited both TTX-sensitive and TTX-resistant components. In these cells, capsaicin induced an inward current in 11 of 17 cells tested. Of the cells containing only a TTX-sensitive component, none of six cells tested was sensitive to capsaicin. In all cells that responded to capsaicin with an increase in inward current, capsaicin abolished voltage-gated Na+currents ( n = 21). Capsazepine (10-6 M) significantly attenuated both the increase in inward current and the reduction in Na+currents. Na+ currents were not significantly altered by adenosine, bradykinin, histamine, PGE2, or serotonin at 10-6 M and 10-5 M. These findings may have important implications for understanding both the irritant and analgesic properties of capsaicin.
Activation of neuronal adenosine A1 receptors suppresses secretory reflexes in the guinea pig colon.

The role of adenosine A1 receptors (A1R) in reflex-evoked short-circuit current ( I sc) indicative of chloride secretion was studied in the guinea pig colon. The A1R antagonist 8-cyclopentyltheophylline (CPT) enhanced reflex-evoked I sc. Adenosine deaminase and the nucleoside transport inhibitor S-(4-nitrobenzyl)-6-thioinosine enhanced and reduced reflex-induced I sc, respectively. The A1R agonist 2-chloro- N 6-cyclopentyladenosine (CCPA) inhibited reflex-evoked I sc at nanomolar concentrations, and its action was antagonized by CPT. In the presence of either N-acetyl-5-hydroxytryptophyl-5-hydroxytryptophan amide to block the 5-hydroxytryptamine (5-HT)-mediated pathway or piroxicam to block the prostaglandin-mediated pathway, CCPA reduced the residual reflex-evoked I sc. CCPA reduced the response to a 5-HT pulse without affecting the tetrodotoxin-insensitive I sc responses to carbachol or forskolin. Immunoreactivity for A1R was detected in the membrane (10% of neurons) and cytoplasm (90% of neurons) of neural protein gene product 9.5-immunoreactive (or S-100-negative) submucosal neurons, in glia, and in the muscularis mucosa. A1R immunoreactivity in a majority of neurons remained elevated in the cytoplasm despite preincubation with adenosine deaminase or CPT. A1R immunoreactivity colocalized in synaptophysin-immunoreactive presynaptic varicose nerve terminals. The results indicate that endogenous adenosine binding to high-affinity A1R on submucosal neurons acts as a physiological brake to suppress reflex-evoked I scindicative of chloride secretion.
TNF-α and IL-1α induce heme oxygenase-1 via protein kinase C, Ca2+, and phospholipase A2 in endothelial cells.

Heme oxygenase-1 (HO-1), an enzyme important in protection against oxidant stress, is induced in human vascular endothelial cells by the cytokines tumor necrosis factor-α (TNF-α) and interleukin-1α (IL-1α). However, the signaling mediators that regulate the induction are not known. This study examined the involvement of protein kinase C (PKC), phospholipase A2(PLA2), calcium, and oxidants in cytokine induction of HO-1. Acute exposure to the PKC activator phorbol 12-myristate 13-acetate (PMA) stimulated HO-1 mRNA. However, prolonged exposure, which downregulates most PKC isoforms, blocked induction of HO-1 mRNA by IL-1α and TNF-α. Additionally, the phosphatase inhibitors okadaic acid and calyculin enhanced cytokine induction of HO-1. Mepacrine, a PLA2 inhibitor, prevented HO-1 induction by cytokine, suggesting a role for arachidonate, the product of PLA2hydrolysis of phospholipids, in HO-1 expression. The intracellular calcium chelator 1,2-bis(2-aminophenoxy)ethane- N, N, N', N'-tetraacetic acid acetoxymethyl ester (BAPTA-AM) blocked cytokine induction of HO-1. Paradoxically, the calcium ionophore A-23187 prevented HO-1 induction by cytokine but not by PMA. Finally, the oxidant scavenger N-acetylcysteine inhibited HO-1 induction by cytokines. These results demonstrate that TNF-α and IL-1α induction of HO-1 requires PKC-mediated phosphorylation and PLA2 activation as well as oxidant generation.
A Semi-Analytical Extraction Method for Interface and Bulk Density of States in Metal Oxide Thin-Film Transistors

A semi-analytical extraction method of interface and bulk density of states (DOS) is proposed by using the low-frequency capacitance–voltage characteristics and current–voltage characteristics of indium zinc oxide thin-film transistors (IZO TFTs). In this work, an exponential potential distribution along the depth direction of the active layer is assumed and confirmed by numerical solution of Poisson’s equation followed by device simulation. The interface DOS is obtained as a superposition of constant deep states and exponential tail states. Moreover, it is shown that the bulk DOS may be represented by the superposition of exponential deep states and exponential tail states. The extracted values of bulk DOS and interface DOS are further verified by comparing the measured transfer and output characteristics of IZO TFTs with the simulation results by a 2D device simulator ATLAS (Silvaco). As a result, the proposed extraction method may be useful for diagnosing and characterising metal oxide TFTs since it is fast to extract interface and bulk density of states (DOS) simultaneously.
Formulation of Poloxamers for Drug Delivery

Poloxamers, also known as Pluronics®, are block copolymers of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO), which have an amphiphilic character and useful association and adsorption properties emanating from this. Poloxamers find use in many applications that require solubilization or stabilization of compounds and also have notable physiological properties, including low toxicity. Accordingly, poloxamers serve well as excipients for pharmaceuticals. Current challenges facing nanomedicine revolve around the transport of typically water-insoluble drugs throughout the body, followed by targeted delivery. Judicious design of drug delivery systems leads to improved bioavailability, patient compliance and therapeutic outcomes. The rich phase behavior (micelles, hydrogels, lyotropic liquid crystals, etc.) of poloxamers makes them amenable to multiple types of processing and various product forms. In this review, we first present the general solution behavior of poloxamers, focusing on their self-assembly properties. This is followed by a discussion of how the self-assembly properties of poloxamers can be leveraged to encapsulate drugs using an array of processing techniques including direct solubilization, solvent displacement methods, emulsification and preparation of kinetically-frozen nanoparticles. Finally, we conclude with a summary and perspective.
Observed smoking and tobacco pack display in Australian outdoor cafés 2 years after implementation of plain packaging

Background Implementation of tobacco plain packaging (PP) in Australia in December 2012 was associated with significant reductions in the percentage of patrons at outdoor cafés observed to be displaying tobacco packs and actively smoking, immediately post-implementation and 1 year later. This study examines whether these positive effects were sustained through to 2 years post-PP. Methods An observational study conducted at cafés, restaurants and bars with outdoor seating in Melbourne, Australia documented the number of: patrons; patrons actively smoking; tobacco packs on display; orientation and type of displayed packs and whether or not children were present. Data were collected pre-PP (2012), early post-PP (2013), 1 year post-PP (2014) and 2 years post-PP (2015). Multilevel Poisson regressions analyzed changes in each outcome, adjusting for important covariates. Results Overall, positive effects of PP implementation on tobacco pack display and active smoking were not fully sustained through to 2 years post-PP for the total sample. Interactions between phase and the presence of children indicated that pack display and active smoking were lower in all post-implementation phases (compared with pre-PP) at venues where children were present but not at venues where children were not present. Conclusions Children at outdoor cafés were still being exposed to less tobacco packaging and active smoking, 2 years after implementation of the packaging changes. More regular refreshment of graphic health warnings is likely to be required to sustain these effects, and to reduce pack display behaviour at venues with no children.