Miracle-dz/UniFAR-FTUs huggingface dataset:
11 Acute-Phase Proteins : Alpha-1-Acid Glycoprotein

Acute-phase proteins are proteins whose plasma concentrations increase in response to inflammation. The variability in protein plasma levels, and following impact on drug binding extent, cause modifications in the mode of drug action, distribution, disposition and elimination. One of the most important acute phase proteins is a1-acid glycoprotein (AAG or AGP), principal binding protein for basic drugs. Although plasma concentration of AAG is much lower than that of albumin, AAG can become the major drug binding macromolecule in plasma with significant clinical implications. Moreover AAG is involved in drug-drug interactions, especially in the displacement of drugs and endogenous substances from their binding sites, with important pharmacokinetic and clinical consequences. AAG is an acidic glycoprotein of about 41 kDa , a single chain of 183 amino acids, the tertiary structure of which partially resembles those of cellular beta 2-agonist receptors. The carbohydrate content (glycans) represents 45% of its molecular weight. The biological function of AGP remains unknown; however, a number of activities of possible physiological significance, such as various immunomodulating effects, have been described. The immunomodulatory as well as the binding activities of AGP have been shown to be mostly dependent on its carbohydrate composition. AAG is one of the plasma acute phase proteins synthesized by the liver and is mainly secreted by hepatocytes and its serum concentration increases in response to systemic tissue injury, inflammation, infection or cancer. Human alpha1-acid glycoprotein displays genetic polymorphism. AGP of most individuals exists as a mixture of two or three main genetic variants (i.e. A variant and F1 and/or S variants). Concerning native human AGP composition, the relative occurrence of the three main phenotypes in the population was found to be about 50% for F1+S+A, 35% for F1+A and 15% for S+A. Different drug binding properties of the two main genetic products (F1-S and A variants) have been demonstrated. Various drug molecules have different selectivity in binding affinities for the genetic variants, ranging from the lack of selectivity to the total preference of one of the variants. In binding competition experiments performed by dialysis, radioactive imipramine and warfarin were chosen as high-affinity selective marker ligands for the A variant and the F1-S
Net2Text: Query-Guided Summarization of Network Forwarding Behaviors

Today network operators spend a significant amount of time struggling to understand how their network forwards traffic. Even simple questions such as “How is my network handling Google traffic? ” often require operators to manually bridge large semantic gaps between lowlevel forwarding rules distributed across many routers and the corresponding high-level insights. We introduce Net2Text, a system which assists network operators in reasoning about network-wide forwarding behaviors. Out of the raw forwarding state and a query expressed in natural language, Net2Text automatically produces succinct summaries, also in natural language, which efficiently capture network-wide semantics. Our key insight is to pose the problem of summarizing (“captioning”) the network forwarding state as an optimization problem that aims to balance coverage, by describing as many paths as possible, and explainability, by maximizing the information provided. As this problem is NP-hard, we also propose an approximation algorithm which generates summaries based on a sample of the forwarding state, with marginal loss of quality. We implemented Net2Text and demonstrated its practicality and scalability. We show that Net2Text generates high-quality interpretable summaries of the entire forwarding state of hundreds of routers with full routing tables, in few seconds only.
Exceptional potency and structural basis of a T1249-derived lipopeptide fusion inhibitor against HIV-1, HIV-2, and simian immunodeficiency virus

Enfuvirtide (T20) is the only viral fusion inhibitor approved for clinical use, but it has relatively weak anti-HIV activity and easily induces drug resistance. In succession to T20, T1249 has been designed as a 39-mer peptide composed of amino acid sequences derived from HIV-1, HIV-2, and simian immunodeficiency virus (SIV); however, its development has been suspended due to formulation difficulties. We recently developed a T20-based lipopeptide (LP-40) showing greatly improved pharmaceutical properties. Here, we generated a T1249-based lipopeptide, termed LP-46, by replacing its C-terminal tryptophan-rich sequence with fatty acid. As compared with T20, T1249, and LP-40, the truncated LP-46 (31-mer) had dramatically increased activities in inhibiting a large panel of HIV-1 subtypes, with IC50 values approaching low picomolar concentrations. Also, LP-46 was an exceptionally potent inhibitor against HIV-2, SIV, and T20-resistant variants, and it displayed obvious synergistic effects with LP-40. Furthermore, we showed that LP-46 had increased helical stability and binding affinity with the target site. The crystal structure of LP-46 in complex with a target surrogate revealed its critical binding motifs underlying the mechanism of action. Interestingly, it was found that the introduced pocket-binding domain in LP-46 did not interact with the gp41 pocket as expected; instead, it adopted a mode similar to that of LP-40. Therefore, our studies have provided an exceptionally potent and broad fusion inhibitor for developing new anti-HIV drugs, which can also serve as a tool to exploit the mechanisms of viral fusion and inhibition.
Speckle Suppression Based on Sparse Representation with Non-Local Priors

As speckle seriously restricts the applications of remote sensing images in many fields, the ability to efficiently and effectively suppress speckle in a coherent imaging system is indispensable. In order to overcome the over-smoothing problem caused by the speckle suppression algorithm based on classical sparse representation, we propose a non-local speckle suppression algorithm that combines the non-local prior knowledge of the image into the sparse representation. The proposed algorithm first applies shearlet to sparsely represent the input image. We then incorporate the non-local priors as constraints into the image sparse representation de-noising problem. The denoised image is obtained by utilizing an alternating minimization algorithm to solve the corresponding constrained de-noising problem. The experimental results show that the proposed algorithm can not only significantly remove speckle noise, but also improve the visual effect and retain the texture information of the image better.
Chronic AT1 blockade improves glucose homeostasis in obese OLETF rats.

Obesity is associated with the inappropriate activation of the renin-angiotensin system (RAS), which increases arterial pressure, impairs insulin secretion and decreases peripheral tissue insulin sensitivity. RAS blockade reverses these detriments; however, it is not clear whether the disease state of the organism and treatment duration determine the beneficial effects of RAS inhibition on insulin secretion and insulin sensitivity. Therefore, the objective of this study was to compare the benefits of acute vs chronic angiotensin receptor type 1 (AT1) blockade started after the onset of obesity, hyperglycemia and hypertension on pancreatic function and peripheral insulin resistance. We assessed adipocyte morphology, glucose intolerance, pancreatic redox balance and insulin secretion after 2 and 11 weeks of AT1 blockade in the following groups of rats: (1) untreated Long-Evans Tokushima Otsuka (lean control; n = 10), (2) untreated Otsuka Long-Evans Tokushima Fatty (OLETF; n = 12) and (3) OLETF + ARB (ARB; 10 mg olmesartan/kg/day by oral gavage; n = 12). Regardless of treatment duration, AT1 blockade decreased systolic blood pressure and fasting plasma triglycerides, whereas chronic AT1 blockade decreased fasting plasma glucose, glucose intolerance and the relative abundance of large adipocytes by 22, 36 and 70%, respectively. AT1 blockade, however, did not improve pancreatic oxidative stress or reverse impaired insulin secretion. Collectively, these data show that AT1 blockade after the onset of obesity, hyperglycemia and hypertension improves peripheral tissue insulin sensitivity, but cannot completely reverse the metabolic derangement characterized by impaired insulin secretion once it has been compromised.
Acyclovir Liposomes for Intranasal Systemic Delivery: Development and Pharmacokinetics Evaluation

Intranasal route is one of the most attractive routes for distributing drugs to systemic circulation. Liposomes are used as biocompatible carriers to improve delivery properties across nasal mucosa. The objective of the present study was to formulate acyclovir liposomes and partition into poly-N-vinyl-2-pyrrolidone. Entrapment efficiency showed that multilamellar and unilamellar liposomes were 43.2% ± 0.83 and 21% ± 1.01, respectively. The bioavailability of acyclovir from nasal mucoadhesive gel was 60.72% compared with intravenous route. The use of liposomes acyclovir and mucoadhesive gel not only promoted the prolonged contact between the drug and the absorptive sites in the nasal cavity, but also facilitated direct absorption through the nasal mucosa.
Bite Forces and Their Measurement in Dogs and Cats

Bite force is generated by the interaction of the masticatory muscles, the mandibles and maxillae, the temporomandibular joints (TMJs), and the teeth. Several methods to measure bite forces in dogs and cats have been described. Direct in vivo measurement of a bite in dogs has been done; however, bite forces were highly variable due to animal volition, situation, or specific measurement technique. Bite force has been measured in vivo from anesthetized dogs by electrical stimulation of jaw adductor muscles, but this may not be reflective of volitional bite force during natural activity. In vitro bite forces have been estimated by calculation of the force produced using mechanical equations representing the jaw adductor muscles and of the mandible and skull structure Bite force can be estimated in silico using finite element analysis (FEA) of the computed model of the anatomical structures. FEA can estimate bite force in extinct species; however, estimates may be lower than the measurements in live animals and would have to be validated specifically in domestic dogs and cats to be reliable. The main factors affecting the bite forces in dogs and cats are body weight and the skull’s morphology and size. Other factors such as oral pain, TMJ disorders, masticatory muscle atrophy, and malocclusion may also affect bite force. Knowledge of bite forces in dogs and cats is essential for various clinical and research fields such as the development of implants, materials, and surgical techniques as well as for forensic medicine. This paper is a summary of current knowledge of bite forces in dogs and cats, including the effect of measurement methods and of other factors.
On the Dimensions Preschoolers Use to Interpret Facial Expressions of Emotion

Dimensions of the meaning attributed to facial expressions of emotion were studied in preschoolers (nineteen 4-year-olds, twenty-one 3-year-olds, and thirty-eight 2-year-olds) plus thirty adults. Subjects indicated the similarity or dissimilarity between different emotions by placing photographs of emotional facial expressions into preordained numbers of groups. For each age group, multidimensional scaling of the pairwise similarities yielded a two-dimensiona l structure in which the expressions fell in a roughly similar circular order. Its dimensions could be interpreted as degree of pleasure and degree of arousal. Four-year-olds and adults also produced a third dimension, tentatively interpreted as assertiveness versus taken aback. As adults, we are highly skilled at reading facial expressions of emotion. We can interpret expressions in terms of such basic categories as anger, fear, happiness, surprise, and the like. We can also interpret expressions in terms of such basic bipolar dimensions as pleasure-displeasure and arousal-sleepiness. But in what terms do children at various ages interpret facial expressions? Does the message derived from a particular expression vary with age? Knowing how children of different ages interpret facial expressions should give us an important clue about the development of the skills involved in the interpretation of emotion in general. In this article, we examine one aspect of this issue: whether 2-, 3-, and 4-year-olds interpret facial expressions in terms of dimensions of pleasure and arousal. Degree of pleasure and degree of arousal are clearly the major dimensions (although not the only dimensions) underlying the way in which adults interpret emotions—their own and those of others. Research from several domains supports this conclusion (see Dittman, 1972). One source of evidence is multidimensionalscaling studies of the similarity perceived between emotions expressed in the face (Abelson & Sermat, 1962; Royal & Hays,
BOND BEHAVIOR BETWEEN FIBER-REINFORCED POLYMER LAMINATES AND CONCRETE

This paper studies the bond behavior between fiber-reinforced polymer laminates and concrete. In order to obtain the local bond stress (LBS) vs. slippage relationship, a double-face shear type bond test was conducted. Primary test variables were the types of fiber and concrete. Test results show that fiber stiffness influences both bond strength and shape of stress distribution. However, the LBS-slip relationships are not influenced by the type of fiber. Only the maximum LBS increases as concrete compressive strength also increases. A new model representing the LBS vs. slippage relationship is offered using Popovic's formula, which has been adapted to present the concrete compressive stress-strain relationship. A numerical analysis was performed to confirm the model, and experimental results are presented. The analytical results show good agreement with the bond strength and strain distribution found in the experimental results.
Physics-based simulations of aerial attacks by peregrine falcons reveal that stooping at high speed maximizes catch success against agile prey

The peregrine falcon Falco peregrinus is renowned for attacking its prey from high altitude in a fast controlled dive called a stoop. Many other raptors employ a similar mode of attack, but the functional benefits of stooping remain obscure. Here we investigate whether, when, and why stooping promotes catch success, using a three-dimensional, agent-based modeling approach to simulate attacks of falcons on aerial prey. We simulate avian flapping and gliding flight using an analytical quasi-steady model of the aerodynamic forces and moments, parametrized by empirical measurements of flight morphology. The model-birds’ flight control inputs are commanded by their guidance system, comprising a phenomenological model of its vision, guidance, and control. To intercept its prey, model-falcons use the same guidance law as missiles (pure proportional navigation); this assumption is corroborated by empirical data on peregrine falcons hunting lures. We parametrically vary the falcon’s starting position relative to its prey, together with the feedback gain of its guidance loop, under differing assumptions regarding its errors and delay in vision and control, and for three different patterns of prey motion. We find that, when the prey maneuvers erratically, high-altitude stoops increase catch success compared to low-altitude attacks, but only if the falcon’s guidance law is appropriately tuned, and only given a high degree of precision in vision and control. Remarkably, the optimal tuning of the guidance law in our simulations coincides closely with what has been observed empirically in peregrines. High-altitude stoops are shown to be beneficial because their high airspeed enables production of higher aerodynamic forces for maneuvering, and facilitates higher roll agility as the wings are tucked, each of which is essential to catching maneuvering prey at realistic response delays.
Cross-Talk between Staphylococcus aureus and Other Staphylococcal Species via the agr Quorum Sensing System

Staphylococci are associated with both humans and animals. While most are non-pathogenic colonizers, Staphylococcus aureus is an opportunistic pathogen capable of causing severe infections. S. aureus virulence is controlled by the agr quorum sensing system responding to secreted auto-inducing peptides (AIPs) sensed by AgrC, a two component histidine kinase. agr loci are found also in other staphylococcal species and for Staphylococcus epidermidis, the encoded AIP represses expression of agr regulated virulence genes in S. aureus. In this study we aimed to better understand the interaction between staphylococci and S. aureus, and show that this interaction may eventually lead to the identification of new anti-virulence candidates to target S. aureus infections. Here we show that culture supernatants of 37 out of 52 staphylococcal isolates representing 17 different species inhibit S. aureus agr. The dog pathogen, Staphylococcus schleiferi, expressed the most potent inhibitory activity and was active against all four agr classes found in S. aureus. By employing a S. aureus strain encoding a constitutively active AIP receptor we show that the activity is mediated via agr. Subsequent cloning and heterologous expression of the S. schleiferi AIP in S. aureus demonstrated that this molecule was likely responsible for the inhibitory activity, and further proof was provided when pure synthetic S. schleiferi AIP was able to completely abolish agr induction of an S. aureus reporter strain. To assess impact on S. aureus virulence, we co-inoculated S. aureus and S. schleiferi in vivo in the Galleria mellonella wax moth larva, and found that expression of key S. aureus virulence factors was abrogated. Our data show that the S. aureus agr locus is highly responsive to other staphylococcal species suggesting that agr is an inter-species communication system. Based on these results we speculate that interactions between S. aureus and other colonizing staphylococci will significantly influence the ability of S. aureus to cause infection, and we propose that other staphylococci are potential sources of compounds that can be applied as anti-virulence therapy for combating S. aureus infections.
A New Hybrid Model For Borefield Heat Exchangers Performance Evaluation

HEADING Ground coupled heat pump systems are gaining importance for heating and cooling of buildings. To assess their performance, detailed simulation models are required with both short-term (to calculate the instantaneous coefficient of performance of the heat pump) and long-term (to calculate the ground temperature evolution) accuracy. A step response is calculated using a combination of a short-term response model which takes into account the transient heat transfer in the heat carrier fluid, the grout and the immediately surrounding ground, and a long-term response model which calculates the boreholes interactions. The state-of-the-art of both models has been chosen from an extensive literature review. Moreover, an aggregation method is implemented to speed up the calculations. Validation shows good results and very high computational efficiency.
Higher Collagen VI Formation Is Associated With All-Cause Mortality in Patients With Type 2 Diabetes and Microalbuminuria

OBJECTIVE Type 2 diabetes is a common risk factor for the development of chronic kidney disease (CKD). Enhanced de novo collagen type VI (COL VI) formation has been associated with renal fibrosis and CKD. We investigated the hypothesis that PRO-C6, a product specifically generated during COL VI formation, is prognostic for adverse outcomes in patients with type 2 diabetes and microalbuminuria. RESEARCH DESIGN AND METHODS In a prospective, observational study, we measured PRO-C6 in the serum (S-PRO-C6) and urine (U-PRO-C6) of 198 patients with type 2 diabetes and microalbuminuria without symptoms of coronary artery disease. Patients were followed for a median of 6.5 years, and end points were a composite of cardiovascular events (n = 38), all-cause mortality (n = 26), and reduction of estimated glomerular filtration rate (eGFR) of >30% (disease progression [n = 42]). Cox models were unadjusted and adjusted for the conventional risk factors of sex, age, BMI, systolic blood pressure, LDL cholesterol, smoking, HbA1c, plasma creatinine, and urinary albumin excretion rate. RESULTS Doubling of S-PRO-C6 increased hazards for cardiovascular events (hazard ratio 3.06 [95% CI 1.31–7.14]), all-cause mortality (6.91 [2.96–16.11]), and disease progression (4.81 [1.92–12.01]). Addition of S-PRO-C6 to a model containing conventional risk factors improved relative integrated discrimination by 22.5% for cardiovascular events (P = 0.02), 76.8% for all-cause mortality (P = 0.002), and 53.3% for disease progression (P = 0.004). U-PRO-C6 was not significantly associated with any of the outcomes. CONCLUSIONS S-PRO-C6 generated during COL VI formation predicts cardiovascular events, all-cause mortality, and disease progression in patients with type 2 diabetes and microalbuminuria.
Annual carbon balance of a peatland 10 yr following restoration

Undisturbed peatlands represent long-term net sinks of carbon; however, peat extraction converts these systems into large and persistent sources of greenhouse gases. Although rewetting and restoration following peat extraction have taken place over the last several decades, very few studies have investigated the longer term impact of this restoration on peatland carbon balance. We determined the annual carbon balance of a former horticulturally-extracted peatland restored 10 yr prior to the study and compared these values to the carbon balance measured at neighboring unrestored and natural sites. Carbon dioxide (CO 2 ) and methane (CH 4 ) fluxes were measured using the chamber technique biweekly during the growing season from May to October 2010 and three times over the winter period. Dissolved organic carbon (DOC) export was measured from remnant ditches in the unrestored and restored sites. During the growing season the restored site had greater uptake of CO 2 than the natural site when photon flux density was greater than 1000 μmol m −2 s −1 , while the unrestored site remained a source of CO 2 . Ecosystem respiration was similar between natural and restored sites, which were both significantly lower than the unrestored site. Methane flux remained low at the restored site except from open water pools, created as part of restoration, and remnant ditches. Export of DOC during the growing season was 5.0 and 28.8 g m −2 from the restored and unrestored sites, respectively. Due to dry conditions during the study year all sites acted as net carbon sources with annual balance of the natural, restored and unrestored sites of 250.7, 148.0 and 546.6 g C m −2 , respectively. Although hydrological conditions and vegetation community at the restored site remained intermediate between natural and unrestored conditions, peatland restoration resulted in a large reduction in annual carbon loss from the system resulting in a carbon balance more similar to a natural peatland.