Miracle-dz/UniFAR-FTUs huggingface dataset:
Next Generation of Pancreatic Enzyme Replacement Therapy: Recombinant Microbial Enzymes and Finding the Perfect Lipase.

76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110 111 112 113 114 115 116 117 Ptients with almost complete loss of pancreatic exocrine function as occurs in cystic fibrosis, advanced chronic pancreatitis, or surgical resection of the pancreas. The loss of pancreatic digestive enzymes associated with PEI causes maldigestion of dietary fats, proteins, and starch. Untreated PEI causes malnutrition with poor linear growth in children, as well as loss of weight and muscle mass and deficiencies of fat-soluble vitamins and essential fatty acids at all ages. The mainstay therapy for PEI is pancreatic enzyme replacement therapy (PERT) with extracts of porcine pancreas. There are no other approved options for treatment, even though PERT rarely eliminates pancreatic steatorrhea, requires numerous capsules per meal, can cause allergic reactions, theoretically could transmit infectious agents to humans, and may not accepted by some patients who have religious objections to consuming pork. Consequently, there is considerable interest in developing recombinant digestive enzymes to treat patients with PEI. Because most of the nutritional issues in PEI are secondary to poor dietary fat digestion, many investigators have focused on identifying recombinant microbial lipases that can improve fat digestion in PEI. So far, none have been approved for treatment of patients creating a need for other options. In this issue of Gastroenterology, Aloulou et al provide evidence that a lipase from Yarrowia lipolytica may be an ideal candidate for recombinant therapy of fat maldigestion in PEI. There are several difficulties in finding a recombinant microbial lipase that is suitable for use in humans. First, dietary fat digestion is a multistep process requiring several different lipases, biliary secretion, and absorption of the released fatty acids by intestinal enterocytes (Figure 1). Lipolysis begins in the stomach where gastric lipase releases 15%–20% of fatty acids. The gastric contents enter the duodenum and mix with pancreatic and biliary secretions. Pancreatic fluid contains multiple lipases, pancreatic lipase, pancreatic lipase-related protein 2, carboxyl ester lipase, and phospholipase A2. Digestion of lipids occurs at the surface of large emulsion particles. As digestion products accumulate in the emulsion surface, they bud from the surface and, in the presence of bile salts, form mixed micelles. The digested fats are absorbed from mixed micelles by intestinal enterocytes.
Mechanisms of Population Structuring in Giant Australian Cuttlefish Sepia apama

While a suite of approaches have been developed to describe the scale, rate and spatial structure of exchange among populations, a lack of mechanistic understanding will invariably compromise predictions of population-level responses to ecosystem modification. In this study, we measured the energetics and sustained swimming capacity of giant Australian cuttlefish Sepia apama and combined these data with information on the life-history strategy, behaviour and circulation patterns experienced by the species to predict scales of connectivity throughout parts of their range. The swimming capacity of adult and juvenile S. apama was poor compared to most other cephalopods, with most individuals incapable of maintaining swimming above 15 cm s−1. Our estimate of optimal swimming speed (6–7 cm s−1) and dispersal potential were consistent with the observed fine-scale population structure of the species. By comparing observed and predicted population connectivity, we identified several mechanisms that are likely to have driven fine-scale population structure in this species, which will assist in the interpretation of future population declines.
Exploring Keyphrase Extraction and IPC Classification Vectors for Prior Art Search

In this paper we describe experiments conducted for CLEF- IP 2011 Prior Art Retrieval track. We examined the impact of 1) us- ing key phrase extraction to generate queries from input patent and 2) the use of citation network and (International Patent Classification) IPC class vector in ranking patents. Variations of a popular key phrase extrac- tion technique were explored for extracting and scoring terms of query patent. These terms are used as queries to retrieve similar patents. In the second approach, we use a two stage retrieval model to find similar patents. Each patent is represented as an IPC class vector. Citation net- work of patents is used to propagate these vectors from a node (patent) to its neighbors (cited patents). Similar patents are found by comparing query vector with vectors of patents in the corpus. Text based search is used to re-rank this solution set to improve precision. Two-stage sys- tem is used to retrieve and rank patents. Finally, we also extract and add citations present within the text of a query patent to the result set. Adding these citations (present in query patent text) to the results shows significant improvement in Mean Average Precision (MAP).
Quantification of the influence of cigarette smoking on rheumatoid arthritis: results from a population based case-control study, using incident cases

Objective: To quantify the influence of cigarette smoking on the risk of developing rheumatoid arthritis (RA). Methods: 679 cases and 847 controls included during May 1996–June 2000 in a case-control study, using incident cases, comprising the population aged 18–70 years of a defined area of Sweden, were investigated. A case was defined as a person from the study base who received for the first time a diagnosis of RA using the 1987 American College of Rheumatology criteria, and controls were randomly selected from the study base. Self reported smoking habits among cases and controls, and rheumatoid factor status among cases were registered. The incidence of RA in current smokers, ex-smokers, and ever-smokers, respectively, was compared with that of never-smokers. Results: Current smokers, ex-smokers, and ever-smokers of both sexes had an increased risk for seropositive RA (for ever-smokers the odds ratio was 1.7 (95% confidence interval (95% CI) 1.2 to 2.3) for women, and 1.9 (95% CI 1.0 to 3.5) for men), but not for seronegative RA. The increased risk was only apparent among subjects who had smoked ⩾20 years, was evident at an intensity of smoking of 6–9 cigarettes/day, and remained for up to 10–19 years after smoking cessation. The risk increased with increasing cumulative dose of smoking. Conclusion: Smokers of both sexes have an increased risk of developing seropositive, but not seronegative, RA. The increased risk occurs after a long duration, but merely a moderate intensity, of smoking and may remain for several years after smoking cessation.
Knowledge-based activities in industry: A decision-support approach

Due to global market and the emerging economies, industry is living its most difficult days ever. To survive in this new economic picture, they must find an organisational solution enabling them to cope with global business opportunities without suffering from limited resources or exposing themselves to the risk of direct investment. The inclusion of additional life-time services is, nowadays, one of the most important added-values from the consumer point of view. The ability resides in the appropriate and efficient use of the company's assets to make the best decision at several levels. These tasks can become highly critical due to the complexity in distributing, incorporating and using the knowledge. This paper proposes that an intelligent decision-support approach to the knowledge-based activities in industry is the basis to improve competitiveness of companies in a global market. Intelligent decision support tools can hugely facilitate the decision-making process, especially, if they are equipped with prediction and adaptation capabilities. The combination of these characteristics allows predicting the consequence of selecting an alternative based on the experience gained from past similar situations. The decision-making aspects being explored in the scope of three European projects are briefly discussed.
A hybrid feedback controller for robust global trajectory tracking of quadrotor-like vehicles with minimized attitude error

In this paper, we tackle the problem of trajectory tracking for a particular class of underactuated vehicles with full torque actuation and a single force direction (thrust) that is fixed relative to a body attached frame. Additionally, we consider that thrust reversal is not available. We present the design of a hybrid controller that, under some given assumptions, is able to globally asymptotically stabilize the vehicle to a reference position trajectory while minimizing the angle to the desired attitude trajectory. This objective is achieved robustly and globally, in the sense that small perturbations do not lead to instability and it is achieved regardless of the initial state of the vehicle. The algorithm is tested in a experimental setup, using a small scale quadrotor vehicle and the VICON motion capture system.
Integrative Systems Models of Cardiac Excitation–Contraction Coupling

Excitation–contraction coupling in the cardiac myocyte is mediated by a number of highly integrated mechanisms of intracellular Ca2+ transport. The complexity and integrative nature of heart cell electrophysiology and Ca2+ cycling has led to an evolution of computational models that have played a crucial role in shaping our understanding of heart function. An important emerging theme in systems biology is that the detailed nature of local signaling events, such as those that occur in the cardiac dyad, have important consequences at higher biological scales. Multiscale modeling techniques have revealed many mechanistic links between microscale events, such as Ca2+ binding to a channel protein, and macroscale phenomena, such as excitation–contraction coupling gain. Here, we review experimentally based multiscale computational models of excitation–contraction coupling and the insights that have been gained through their application.
Calmodulin is a subunit of nitric oxide synthase from macrophages

A central issue in nitric oxide (NO) research is to understand how NO can act in some settings as a servoregulator and in others as a cytotoxin. To answer this, we have sought a molecular basis for the differential regulation of the two known types of NO synthase (NOS). Constitutive NOS's in endothelium and neurons are activated by agonist- induced elevation of Ca2+ and resultant binding of calmodulin (CaM). In contrast, NOS in macrophages does not require added Ca2+ or CaM, but is regulated instead by transcription. We show here that macrophage NOS contains, as a tightly bound subunit, a molecule with the immunologic reactivity, high performance liquid chromatography retention time, tryptic map, partial amino acid sequence, and exact molecular mass of CaM. In contrast to most CaM-dependent enzymes, macrophage NOS binds CaM tightly without a requirement for elevated Ca2+. This may explain why NOS that is independent of Ca2+ and elevated CaM appears to be activated simply by being synthesized.
A Strategy Based on Cooperative Transmission for Minimizing Delivery Delay in WSN

To achieve the purpose of energy conservation, various sleep scheduling approaches, such as duty cycle, are applied in wireless sensor networks (WSN). However, the duty-cycle mechanism results in data delivery latency, which is critical to monitor applications. To minimize the delay caused by sleeping nodes in the transmission path, we propose to “hop over” the sleeping nodes based on the range extension of cooperative transmission (CT). The transmission delay models for the random duty-cycled WSN and optimized fixed duty-cycled WSN under cooperative operation are formulated, and an algorithm named (delay-tolerant cooperative transmission DTCT) is presented for the selection of transmission modes to avoid waiting for the sleeping nodes to wake up. The energy consumption model under direct transmission (DT) and CT mode is also presented. Theoretical analysis shows that sleep latency can be greatly reduced in the cooperative scheme, and it is validated by simulations that it outperforms the traditional store-and-forward (DT) mode in delivery latency. Especially, CT reduces 67% and 14.3% of the transmission delay in random and optimized fixed low duty-cycled WSN, respectively, and DTCT algorithm saves energy by 11.29% in random low duty-cycled WSN.
How much anonymity does network latency leak?

Low-latency anonymity systems such as Tor, AN.ON, Crowds, and Anonymizer.com aim to provide anonymous connections that are both untraceable by “local” adversaries who control only a few machines and have low enough delay to support anonymous use of network services like Web browsing and remote login. One consequence of these goals is that these services leak some information about the network latency between the sender and one or more nodes in the system. We present two attacks on low-latency anonymity schemes using this information. The first attack allows a pair of colluding Web sites to predict, based on local timing information and with no additional resources, whether two connections from the same Tor exit node are using the same circuit with high confidence. The second attack requires more resources but allows a malicious Web site to gain several bits of information about a client each time he visits the site. We evaluate both attacks against two low-latency anonymity protocols—the Tor network and the MultiProxy proxy aggregator service—and conclude that both are highly vulnerable to these attacks.
Estimation in hidden Markov models via efficient importance sampling

Given a sequence of observations from a discrete-time, finite-state hidden Markov model, we would like to estimate the sampling distribution of a statistic. The bootstrap method is employed to approximate the con fidence regions of a multi-dimensional parameter. We propose an importance sampling formula for efficient simulation in this context. Our approach consists of constructing a locally asymptotically normal (LAN) family of probability distributions around the default resampling rule and then minimizing the asymptotic variance within the LAN family. The solution of this minimization problem characterizes the asymptoti cally optimal resampling scheme, which is given by a tilting formula. The implementation of the tilting formula is facilitated by solving a Poisson equation. A few numerical examples are given to demonstrate the efficiency of the proposed importance sampling scheme.
Peptic peptides from the beta polypeptide chain of AII component of chicken hemoglobin.

The aminoethylated beta polypeptide chain in AII component from the hemoglobin of adult chicken was digested with trypsin [EC 3.4. 21.4] and the resulting peptides were separated and purified by ion exchange chromatography, paper chromatography, and gel filtration. Eighteen tryptic peptides, which were nonoverlapping, accounted for all of the amino acid residues in the beta polypeptide chain. The amino acid sequences of the tryptic peptides were established by a combination of enzymatic digestion and subtractive Edman degradation.
Doctors and Vampires in Sub-Saharan Africa: Ethical Challenges in Clinical Trial Research

Collecting blood samples from individuals recruited into clinical research projects in sub-Saharan Africa can be challenging. Strikingly, one of the reasons for participant reticence is the occurrence of local rumors surrounding “blood stealing” or “blood selling. ” Such fears can potentially have dire effects on the success of research projects—for example, high dropout rates that would invalidate the trial's results—and have ethical implications related to cultural sensitivity and informed consent. Though commonly considered as a manifestation of the local population's ignorance, these rumors represent a social diagnosis and a logical attempt to make sense of sickness and health. Born from historical antecedents, they reflect implicit contemporary structural inequalities and the social distance between communities and public health institutions. We aim at illustrating the underlying logic governing patients' fear and argue that the management of these beliefs should become an intrinsic component of clinical research.
Intravesical ALT-803 and BCG Treatment Reduces Tumor Burden in a Carcinogen Induced Bladder Cancer Rat Model; a Role for Cytokine Production and NK Cell Expansion

Intravesical Bacillus Calmette-Guérin (BCG) has been shown to induce a specific immunologic response (i.e., activation of IL-2 and effector T-cells), while preclinical studies using ALT-803 (mutated IL-15 analogue combined with IL-15Rα-Fc fusion) have shown promising results by prolonging the agent's half-life and stimulating CD8+ T-cells. Based on these results, we hypothesized that the intravesical administration of ALT-803 along with BCG will generate an immunologic response leading to significant bladder tumor burden reduction. Using a well-established carcinogen induced rat non-muscle invasive bladder cancer (NMIBC) model, we studied the effects of intravesical ALT-803 with and without BCG. Rat tissues were evaluated to document treatment response. Intravesical ALT-803 was safe and well tolerated alone and in combination with BCG. As a single treatment agent, ALT-803 reduced tumor burden by 35% compared to control whereas BCG alone only reduced tumor burden by 15%. However, the combination of ALT-803 plus BCG reduced tumor burden by 46% compared to control. Immune monitoring suggested that the antitumor response was linked to the production and secretion of IL-1α, IL-1β and RANTES, which in turn, induced the proliferation and activation of NK cells. Lastly, tumoral responses of the combinational treatment were associated with 76% reduction in angiogenesis, which is significantly higher than when assessed with either agent alone. The enhanced therapeutic index seen with this duplet provides justification for the development of this regimen for future clinical trials.
Genomic diversity of 2010 Haitian cholera outbreak strains

The millions of deaths from cholera during the past 200 y, coupled with the morbidity and mortality of cholera in Haiti since October 2010, are grim reminders that Vibrio cholerae, the etiologic agent of cholera, remains a scourge. We report the isolation of both V. cholerae O1 and non-O1/O139 early in the Haiti cholera epidemic from samples collected from victims in 18 towns across eight Arrondissements of Haiti. The results showed two distinct populations of V. cholerae coexisted in Haiti early in the epidemic. As non-O1/O139 V. cholerae was the sole pathogen isolated from 21% of the clinical specimens, its role in this epidemic, either alone or in concert with V. cholerae O1, cannot be dismissed. A genomic approach was used to examine similarities and differences among the Haitian V. cholerae O1 and V. cholerae non-O1/O139 strains. A total of 47 V. cholerae O1 and 29 V. cholerae non-O1/O139 isolates from patients and the environment were sequenced. Comparative genome analyses of the 76 genomes and eight reference strains of V. cholerae isolated in concurrent epidemics outside Haiti and 27 V. cholerae genomes available in the public database demonstrated substantial diversity of V. cholerae and ongoing flux within its genome.
The International Journal of Biostatistics A Note on Inferring Acyclic Network Structures Using Granger Causality Tests

Granger causality (GC) and its extension have been used widely to infer causal relationships from multivariate time series generated from biological systems. GC is ideally suited for causal inference in bivariate vector autoregressive process (VAR). A zero magnitude of the upper or lower off-diagonal element(s) in a bivariate VAR is indicative of lack of causal relationship in that direction resulting in true acyclic structures. However, in experimental settings, statistical tests, such as F-test that rely on the ratio of the mean-squared forecast errors, are used to infer significant GC relationships. The present study investigates acyclic approximations within the context of bi-directional two-gene network motifs modeled as bivariate VAR. The fine interplay between the model parameters in the bivariate VAR, namely: (i) transcriptional noise variance, (ii) autoregulatory feedback, and (iii) transcriptional coupling strength that can give rise to discrepancies in the ratio of the mean-squared forecast errors is investigated. Subsequently, their impact on statistical power is investigated using Monte Carlo simulations. More importantly, it is shown that one can arrive at acyclic approximations even for bi-directional networks for suitable choice of process parameters, significance level and sample size. While the results are discussed within the framework of transcriptional network, the analytical treatment provided is generic and likely to have significant impact across distinct paradigms.
Parallel Construction of Data Cubes on Multi-Core Multi-Disk Platforms

On-line Analytical Processing (OLAP) has become one of the most powerful and prominent technologies for knowledge discovery in VLDB (Very Large Database) environments. Central to the OLAP paradigm is the data cube, a multi dimensional hierarchy of aggregate values that provides a rich analytical model for decision support. Various sequential algorithms for the efficient generation of the data cube have appeared in the literature. However, given the size of contemporary data warehousing repositories, multi-processor solutions are crucial for the massive computational demands of current and future OLAP systems. In this paper we discuss the development of MCMD-CUBE, a new parallel data cube construction method for multi-core processors with multiple disks. We present experimental results for a Sandy Bridge multi-core processor with four parallel disks. Our experiments indicate that MCMD-CUBE achieves very close to linear speedup. A critical part of our MCMD-CUBE method is parallel sorting. We developed a new parallel sorting method termed MCMD-SORT for multi-core processors with multiple disks which outperforms other previous methods.
Is universal antifungal prophylaxis mandatory in lung transplant patients?

Purpose of review Lung transplantation remains the main therapy for patients with end-stage lung disease, yet survival remains limited by infection and chronic rejection. Invasive fungal infection, especially invasive aspergillosis, continues to cause a high rate of mortality after lung transplantation, and there is evidence that fungal colonization in itself may have a negative impact as well. This article reviews clinical trials in primary antifungal prophylaxis to determine whether antifungal prophylaxis after lung transplantation is indicated. Recent findings A variety of antifungal regimens have been tested after lung transplantation including itraconazole or voriconazole monotherapy, inhaled amphotericin B products, and combination therapy. Studies using a historical cohort that has not received antifungal prophylaxis show a decrease in the incidence of invasive fungal disease and/or invasive aspergillosis with antifungal prophylaxis, with relatively few safety concerns. Both systemic azoles and inhaled amphotericin B products appear to provide benefit. Summary Despite multiple reports of antifungal prophylaxis efficacy, a randomized, controlled, multicenter trial has yet to be performed. The optimal agent or agents for prophylaxis and length of therapy posttransplantation remain unknown. However, sufficient evidence exists for the utility of some type of antifungal prophylaxis posttransplantation for the majority of lung transplant recipients.