Miracle-dz/UniFAR-FTUs huggingface dataset:
Mixture Subclass Discriminant Analysis Link to Restricted Gaussian Model and Other Generalizations

In this paper, a theoretical link between mixture subclass discriminant analysis (MSDA) and a restricted Gaussian model is first presented. Then, two further discriminant analysis (DA) methods, i.e., fractional step MSDA (FSMSDA) and kernel MSDA (KMSDA) are proposed. Linking MSDA to an appropriate Gaussian model allows the derivation of a new DA method under the expectation maximization (EM) framework (EM-MSDA), which simultaneously derives the discriminant subspace and the maximum likelihood estimates. The two other proposed methods generalize MSDA in order to solve problems inherited from conventional DA. FSMSDA solves the subclass separation problem, that is, the situation in which the dimensionality of the discriminant subspace is strictly smaller than the rank of the inter-between-subclass scatter matrix. This is done by an appropriate weighting scheme and the utilization of an iterative algorithm for preserving useful discriminant directions. On the other hand, KMSDA uses the kernel trick to separate data with nonlinearly separable subclass structure. Extensive experimentation shows that the proposed methods outperform conventional MSDA and other linear discriminant analysis variants.
NADPH Oxidase Is Required for the Sensory Plasticity of the Carotid Body by Chronic Intermittent Hypoxia

Respiratory motoneuron response to hypoxia is reflex in nature and carotid body sensory receptor constitutes the afferent limb of this reflex. Recent studies showed that repetitive exposures to hypoxia evokes long term facilitation of sensory nerve discharge (sLTF) of the carotid body in rodents exposed to chronic intermittent hypoxia (CIH). Although studies with anti-oxidants suggested the involvement of reactive oxygen species (ROS)-mediated signaling in eliciting sLTF, the source of and the mechanisms associated with ROS generation have not yet been investigated. We tested the hypothesis that ROS generated by NADPH oxidase (NOX) mediate CIH-evoked sLTF. Experiments were performed on ex vivo carotid bodies from rats and mice exposed either to 10 d of CIH or normoxia. Acute repetitive hypoxia evoked a ∼12-fold increase in NOX activity in CIH but not in control carotid bodies, and this effect was associated with upregulation of NOX2 mRNA and protein, which was primarily localized to glomus cells of the carotid body. sLTF was prevented by NOX inhibitors and was absent in mice deficient in NOX2. NOX activation by CIH required 5-HT release and activation of 5-HT2 receptors coupled to PKC signaling. Studies with ROS scavengers revealed that H2O2 generated from O2·− contributes to sLTF. Priming with H2O2 elicited sLTF of carotid bodies from normoxic control rats and mice, similar to that seen in CIH-treated animals. These observations reveal a novel role for NOX-induced ROS signaling in mediating sensory plasticity of the carotid body.
Accelerated blood clearance and altered biodistribution of repeated injections of sterically stabilized liposomes.

Sterically stabilized liposomes are considered promising carriers of therapeutic agents because they can facilitate controlled release of the drugs, thereby reducing drug-related toxicity and/or targeted delivery of drugs. Herein, we studied the pharmacokinetics and biodistribution of repeated injections of radiolabeled polyethyleneglycol (PEG) liposomes. Weekly injections of (99m)Tc-PEG liposomes dramatically influenced the circulatory half-life in rats. Biodistribution 4 h after the second dose showed a significantly reduced blood content (from 52.6 +/- 3.7 to 0.6 +/- 0.1% injected dose (ID), P <. 01) accompanied by a highly increased uptake in the liver (from 8.1 +/- 0.8 to 46.2 +/- 9.8%ID, P <.01) and in the spleen (from 2.2 +/- 0.2 to 5.3 +/- 0.7%ID, P <.01). At subsequent injections the effect was less pronounced: after the fourth dose, the pharmacokinetics of the radiolabel had almost returned to normal. The same phenomenon was observed in a rhesus monkey, but not in mice. The enhanced blood clearance of the PEG liposomes also was observed in rats after transfusion of serum from rats that had received PEG liposomes 1 week earlier, indicating that the enhanced blood clearance was caused by a soluble serum factor. This serum factor was a heat-labile molecule that coeluted on a size exclusion column with a 150-kDa protein. In summary, i.v. administration of sterically stabilized PEG liposomes significantly altered the pharmacokinetic behavior of subsequently injected PEG liposomes in a time- and frequency-dependent manner. The observed phenomenon may have important implications for the repeated administration of sterically stabilized liposomes for targeted drug delivery.
Gcg-XTEN: An Improved Glucagon Capable of Preventing Hypoglycemia without Increasing Baseline Blood Glucose

Objective While the majority of current diabetes treatments focus on reducing blood glucose levels, hypoglycemia represents a significant risk associated with insulin treatment. Glucagon plays a major regulatory role in controlling hypoglycemia in vivo, but its short half-life and hyperglycemic effects prevent its therapeutic use for non-acute applications. The goal of this study was to identify a modified form of glucagon suitable for prophylactic treatment of hypoglycemia without increasing baseline blood glucose levels. Methodology/Principal Findings Through application of the XTEN technology, we report the construction of a glucagon fusion protein with an extended exposure profile (Gcg-XTEN). The in vivo half-life of the construct was tuned to support nightly dosing through design and testing in cynomolgus monkeys. Efficacy of the construct was assessed in beagle dogs using an insulin challenge to induce hypoglycemia. Dose ranging of Gcg-XTEN in fasted beagle dogs demonstrated that the compound was biologically active with a pharmacodynamic profile consistent with the designed half-life. Prophylactic administration of 0.6 nmol/kg Gcg-XTEN to dogs conferred resistance to a hypoglycemic challenge at 6 hours post-dose without affecting baseline blood glucose levels. Consistent with the designed pharmacokinetic profile, hypoglycemia resistance was not observed at 12 hours post-dose. Importantly, the solubility and stability of the glucagon peptide were also significantly improved by fusion to XTEN. Conclusions/Significance The data show that Gcg-XTEN is effective in preventing hypoglycemia without the associated hyperglycemia expected for unmodified glucagon. While the plasma clearance of this Gcg-XTEN has been optimized for overnight dosing, specifically for the treatment of nocturnal hypoglycemia, constructs with significantly longer exposure profiles are feasible. Such constructs may have multiple applications such as allowing for more aggressive insulin treatment regimens, treating hypoglycemia due to insulin-secreting tumors, providing synergistic efficacy in combination therapies with long-acting GLP1 analogs, and as an appetite suppressant for treatment of obesity. The improved physical properties of the Gcg-XTEN molecule may also allow for novel delivery systems not currently possible with native glucagon.
Integração financeira e autonomia de política monetária: investigando relações de causalidade para a economia brasileira, 1990 - 2005

Nos ultimos anos, aumentou a integracao financeira entre os paises e surgiram questoes acerca da autonomia da politica monetaria. A abordagem tradicional sustenta que, nesse contexto, a taxa de juros e determinada pela oferta e demanda de fundos emprestaveis e que, por isso, a autoridade monetaria nao tem autonomia para fixar taxas diferentes daquelas determinadas pelo mercado. Uma abordagem alternativa afirma que e possivel fixar autonomamente a taxa de juros domestica, especialmente pelo fato de que o sentido da causalidade vai da taxa de juros para o premio de risco e nao o contrario. A explicacao basica e que a reducao da taxa de juros melhora os fundamentos da economia, aumentando a atratividade dos titulos do governo no mercado financeiro internacional. Empregando tecnicas mais recentes de teste de raiz unitaria, o estudo investiga relacoes de causalidade para a economia brasileira. Os resultados fornecem evidencia em favor da abordagem alternativa. Abstract In the last two decades the financial integration between countries has arisen. In consequence questions on different degrees of autonomy of monetary policy of these countries appeared. The traditional sight is that the interest rate is determined by offer and demand of funds of loans and that the monetary authority has no autonomy to fix different rates from those ones of the market. But an alternative sight defends that is possible to define with autonomy the domestic interest rate, even in this context. This paper analyzes some consequences of financial integration for Brazilian real situation, applying new methodology to test unit root hypothesis and to investigate Granger causality relations. The results endorse the alternative approach. Therefore, it could be feasible that the monetary authority could reduce the interest rate to make a virtuous circle of greater growing and stability possible. Key words: Economic development. Financial integration. Monetary policy. Interest rate
Odorant-Evoked Nitric Oxide Signals in the Antennal Lobe of Manduca sexta

The gaseous signaling molecule nitric oxide (NO) can affect the activities of neurons and neural networks in many different systems. The strong expression of NO synthase (NOS) in the primary synaptic neuropil (the antennal lobe in insects and the olfactory bulb in vertebrates) of the olfactory system of most organisms, and the unique spheroidal geometry of olfactory glomeruli in those neuropils, have led to suggestions that NO signaling is important for processing olfactory information. No direct evidence exists, however, that NO signals are produced in olfactory glomeruli. We investigated the production of NO in the antennal lobe of the moth, Manduca sexta, by using immunocytochemistry and real-time optical imaging with a NO-sensitive fluorescent marker, diaminofluorescein diacetate. We confirmed that NOS was expressed in the axons of olfactory receptor neurons projecting to all glomeruli. Soluble guanylyl cyclase, the best characterized target of NO, was found in a subset of postsynaptic antennal lobe neurons that included projection neurons, a small number of GABA-immunoreactive neurons, and a serotonin-immunoreactive neuron. We found that odorant stimulation evoked NO signals that were reproducible and spatially focused. Different odorants evoked spatially distinct patterns of NO production. Increased concentrations of pheromone and plant odorants caused increases in peak signal intensity. Increased concentrations of plant odorants also evoked a dramatic increase in signal area. The results of these experiments show clearly that odorant stimulation can evoke NO production in the olfactory system. The NO signals produced are likely to play an important role in processing olfactory information.
Open Source Developer Download Tiers: A Survival Framework

The Developer Download Tier is a survival strategy framework that aims to guide the open source community, particularly to maximise developer download performance. The framework shows two tiers, displaying tier 1 as high surge software download by technical developer and non-developer and tier 2 as slow surge software download by technical developer and non-developer. Results show inconsistent download strategy between technical and non- technical developers, who apply criteria differently. Tier 1 technical developers targeted at appropriate license properties, non-windows operating system and C programming language whereas non-technical developers targeted appropriate license properties however non-windows operating systems and non C programming language. For Tier 2, technical developers targeted at appropriate license properties, operating system and programming language in different variations and non-technical developers targeted less appropriate license properties however operating systems and programming language on different variations.
An Ontology-Centric Approach for Flexible Configuration and Pricing of Product Families

The paper presents an approach to variability management in product family development using semantic technologies. There is a need for more flexible configuration management and pricing, explicitly representing domain knowledge and configuration rules. For this purpose, an ontology and rules are adopted. The paper discusses pros and cons of semantic technologies applied in this context. The project is done for DNV Software, a company offering solutions for maritime, offshore and process industries.
Expression of GDNF Family Receptor Components during Development: Implications in the Mechanisms of Interaction

Glial cell line-derived neurotrophic factor (GDNF) and a related factor, neurturin, promote survival of diverse groups of neurons. Both GDNF and neurturin signal via a two-component receptor complex that consists of a ligand-binding GDNF family receptor (GFRα-1 or GFRα-2) and the receptor protein tyrosine kinase Ret. Recently, a third receptor related to GFRα-1 and GFRα-2 has also been isolated and designated GFRα-3. Although much is known about the interaction among GDNF family factors, Ret, and the α-receptors in vitro, it remains unclear about their interactions in vivo. We show here by in situ hybridization that Ret and the α-receptors may be colocalized in the same tissues or expressed separately in projecting and target tissues, respectively, indicating that two distinct modes of interaction between Ret and the α-receptors exist in vivo. First, Ret may interact with the α-receptors expressed in the same cells (termed interaction “in cis”) in many tissues and cell populations that respond to GDNF and/or neurturin, such as the substantia nigra, dorsal root ganglia, spinal cord motoneurons, kidney, and intestine. Second, Ret may interact with the α-receptors localized in the target neurons (termed interaction “in trans”). In addition, we present evidence in vitro that GFRα-1 mediates Ret activation by GDNF in trans. These observations suggest that there are multiple mechanisms regulating the interaction between Ret and the α-receptors that mediates the effects of GDNF family trophic factors on the survival and differentiation of cells and on neuron–target interactions in the nervous system.
Authors’ Reply to “Comments on “On optimal control of spatially distributed systems””

We thank the author in [1] for careful reading of our paper and pointing out the errors. It is very unfortunate that both of us and the reviewers missed these errors. In [2], the notion of spatially-decaying (SD) matrices is introduced. These are classes of infinite matrices defined by the off-diagonal decay of their entries. Families of coupling characteristic functions (e.g. exponential and algebraic off-diagonal decay) are defined to quantify off-diagonal decay of matrices. The objective of [2] is to show that the unique solution of Lyapunov and Riccati equations with SD coefficients are SD. These results are reported in Theorems 5 and 6 in [2], respectively. The proofs of these theorems are mainly based on convergence properties of the corresponding differential Lyapunov and Riccati equations and the result of Corollary 1 in [2]. The statement of Corollary 1 in [2] asserts that if a sequence of operators in the Banach algebra of SD matrices is convergent in the sense of `p , then it is also convergent in the Banach algebra of SD matrices. As pointed in [1] Corollary 1 in [2] is not true in general, resulting in the collapse of the proofs of Theorems 5 and 6. Even though some of the proofs as appeared in [2] are wrong, the statements of Theorem 5 in [2] and a modified version of Theorem 6 still hold under some additional assumptions on the coupling characteristic functions and the distance function. We assume that the following assumptions hold: the GRS-condition (2) which essentially requires that the coupling characteristic function decays sub-exponentially, a weak growth condition (5) on the coupling characteristic function, a growth condition (6) on the volume of a ball in the index set, and A being self-adjoint. We provide a proof for Theorem 5 in [2] which does not rely on Corollary 1 in [2]. A modified and more restrictive version of Theorem 6 in [2] remains valid. Essentially, we prove that the solution of the operator Riccati differential equation is in the Banach algebra on finite time intervals. Whether the result is true for infinite time, remains to be seen.
Increased Wounding of Southern Right Whale (Eubalaena australis) Calves by Kelp Gulls (Larus dominicanus) at Península Valdés, Argentina

At least 626 southern right whale (Eubalaena australis) calves died at the Península Valdés calving ground, Argentina, between 2003 and 2014. Intense gull harassment may have contributed to these deaths. In the 1970s, Kelp Gulls (Larus dominicanus) began feeding on skin and blubber pecked from the backs of living right whales at Valdés. The frequency of gull attacks has increased dramatically over the last three decades and mother-calf pairs are the primary targets. Pairs attacked by gulls spend less time nursing, resting and playing than pairs not under attack. In successive attacks, gulls open new lesions on the whales’ backs or enlarge preexisting ones. Increased wounding could potentially lead to dehydration, impaired thermoregulation, and energy loss to wound healing. The presence, number and total area of gull-inflicted lesions were assessed using aerial survey photographs of living mother-calf pairs in 1974–2011 (n = 2680) and stranding photographs of dead calves (n = 192) in 2003–2011. The percentage of living mothers and calves with gull lesions increased from an average of 2% in the 1970s to 99% in the 2000s. In the 1980s and 1990s, mothers and calves had roughly equal numbers of lesions (one to five), but by the 2000s, calves had more lesions (nine or more) covering a greater area of their backs compared to their mothers. Living mother-calf pairs and dead calves in Golfo Nuevo had more lesions than those in Golfo San José in the 2000s. The number and area of lesions increased with calf age during the calving season. Intensified Kelp Gull harassment at Península Valdés could be compromising calf health and thereby contributing to the high average rate of calf mortality observed in recent years, but it cannot explain the large year-to-year variance in calf deaths since 2000.
Cross-sectional analysis of patient phone calls to an inflammatory bowel disease clinic

Background Patients with inflammatory bowel disease (IBD) require close follow up and frequently utilize healthcare services. We aimed to identify the main reasons that prompted patient calls to gastroenterology providers and further characterize the “frequent callers”. Methods This retrospective cross-sectional study included all phone calls registered in medical records of IBD patients during 2012. Predictive variables included demographics, psychiatric history, IBD phenotype, disease complications and medical therapies. Primary outcome was the reason for call (symptoms, medication refill, procedures and appointment issues). Secondary outcome was the frequency of changes in management prompted by the call. Results 209 patients participated in 526 calls. The mean number of calls per patient was 2.5 (range 0-27); 49 (23.4%) patients met the criterion of “frequent caller”. Frequent callers made or received 75.9% of all calls. Crohn’s disease, anxiety, extra-intestinal manifestations and high sedimentation rate were significantly associated with higher call volume. 85.7% of frequent callers had at least one call that prompted a therapeutic intervention, compared to 18.9% of non-frequent callers (P<0.001). The most common interventions were ordering laboratory or imaging studies (15.4%), dose adjustments (12.1%), changes in medication class (8.4%), and expediting clinic visits (8.4%). Conclusion Most phone calls originated from a minority of patients. Repeated calling by the same patient and new onset of gastrointestinal (GI) and non-GI symptoms were important factors predicting the order of diagnostic modalities or therapeutic changes in care. Triaging calls to IBD healthcare providers for patients more likely to require a change in management may improve healthcare delivery.
Distribution of Hepatitis C Virus Genotypes Among Patients With Hepatitis C Virus Infection in Hormozgan, Iran

Background More than 170 million people in the world are infected with Hepatitis C virus (HCV). Determination of HCV genotype before starting the treatment is required, because HCV genotype affects the course of treatment and drug dosage Objectives We aimed to evaluate HCV genotypes among patients with positive results for anti-HCV in Bandar Abbas from 2011 to 2012. Patients and Methods Five hundred and nine consecutive patients with established chronic HCV infection referred to Behavioral Diseases Consultation Center, Blood Transfusion and Center for Special Diseases from March 2011 to March 2012 were enrolled in this cross sectional study. Five mL of peripheral blood was taken from precipitants and viral RNA extracted after plasma separation. Hepatitis C virus RNA was detected by reverse transcriptase-nested polymerase chain reaction (RT-nested PCR) assay and then HCV genotypes analyzed using restriction fragment length polymorphism (RFLP) method. Results In overall, 509 patients enrolled to this study. The mean age of these patients was 38.87 ± 9.55 years ranging from 1 to 90 years. Routs of transmission were: 238 (46.7%) inject of substance, 149 (29.3%) unknown rout, 62 (12.2%) blood transfusion, 50 (9.8%) sexual contact, and 10 (2%) mother to child. Frequency of HCV genotypes were: 316 (62.1%) 1a, 117 (23%) 1b, and 76 (14.9%) 3a. there was no significant association between HCV genotypes and gender, educational degree, risk factor of Hepatitis C, job, monthly income, HIV infection, Hepatitis B virus (HBV) infection, Intravenous drug injection, and underlying disease (P > 0.05). Conclusions This results the same as many similar studies demonstrated that common HCV genotypes in Iranian patients were 1a, 3a and 1b, respectively. Patients with 1a and 1b genotypes have lower responses to interferon treatment, and it is reasonable to perform early screening to diagnose and determine HCV genotype for effective treatment and diagnose high-risk cases.
Xuebijing Injection Promotes M2 Polarization of Macrophages and Improves Survival Rate in Septic Mice

Xuebijing (XBJ) injection, a concoction of several Chinese herbs, has been widely used as an immunomodulator for the treatment of severe sepsis in China. However, the precise mechanisms responsible for its efficacy have not been fully elucidated. In our study, we determined the flow cytometry markers (F4/80, CD11c, and CD206), the levels of secreted cytokines (TNF-α, IL-6, and IL-10), and the expression of specific proteins of M2 (Ym1, Fizz1, and Arg1) to assess macrophage polarization. Treatment with XBJ lowered M1 associated cytokine levels and increased the level of M2 associated cytokine level. The percentage of M2 phenotype cells of XBJ group was much higher than that of the control group. Expressions of phosphorylated Janus kinase 1 (JAK1) and signal transducer and activator of transcription 6 (STAT6) were markedly enhanced after the administration of XBJ; on the other hand, the M2 associated cytokines and proteins were decreased following treatment with JAK1 or STAT6 inhibitor. In addition, the treatment of XBJ significantly improved the survival rate of septic mice. These studies demonstrate that XBJ can markedly promote M2 polarization and improve the survival rate of septic mice, thereby contributing to therapeutic effect in the treatment of septic complications.