Miracle-dz/UniFAR-FTUs huggingface dataset:
Octaarginine- and Octalysine-modified Nanoparticles Have Different Modes of Endosomal Escape*

The present study examines the role of surface modification with an octaarginine peptide (R8) in liposomal escape from endocytic vesicles, using octalysine (K8) as a control cationic peptide; the mechanism of endosomal escape of liposomes was also investigated. Gene expression of condensed plasmid DNA encapsulated in R8-modified nanoparticles was more than 1 order of magnitude higher than that of K8-modified nanoparticles, and 2 orders of magnitude higher than gene expression using unmodified nanoparticles. The difference in gene expression could not be attributed to differences in uptake, as R8- and K8-modified liposomes were taken up primarily via macropinocytosis with comparable efficiency. The extent of R8-nanoparticle escape to the cytosol was double that of K8-nanoparticles. Suppression of endosome acidification inhibited R8-nanoparticle endosomal escape, but enhanced that of K8-nanoparticles. Using spectral imaging in live cells, we showed that R8- and K8-liposomes escaped from endocytic vesicles via fusion between the liposomes and the endosomal membrane. R8-liposomes fused efficiently at both acidic and neutral pH, whereas K8-liposomes fused only at neutral pH. Similar behavior was observed during in vitro lipid mixing and calcein-release experiments. Co-incubation of cells with distinctly labeled K8- and R8-modified nanoparticles confirmed a common uptake pathway and different rates of endosomal escape particularly at longer time intervals. Therefore, it was concluded that R8 on the liposome surface stimulates efficient escape from endocytic vesicles via a fusion mechanism that works at both neutral and acidic pH; in contrast, K8 mediates escape mainly at neutral pH.
Production, purification, and properties of a lipase from a bacterium (Pseudomonas aeruginosa YS-7) capable of growing in water-restricted environments

An extracellular lipase from the low-water-tolerant bacterium P. aeruginosa YS-7 was produced, purified, and characterized with respect to its functional properties in aqueous solutions and organic solvents. The enzyme was partially released from the cells during fermentation in defined medium with 5% (wt/vol) soybean oil. Approximately one-half of the total culture activity remained in solution after removal of cells. More than 95% of the activity was found in culture supernatant after mild detergent treatment (10 mM sodium deoxycholate) or after shifting the carbon source during the fermentation from triglyceride to a free fatty acid. The enzyme was recovered from an acetone precipitate of the whole culture and purified by hydrophobic interaction chromatography, yielding a preparation having a specific activity of about 1,300 mumol of fatty acid mg-1 h-1. The lipase (molecular size, approximately 40 kDa) hydrolyzes a variety of fatty acid esters and has an optimum pH of about 7. The enzyme retained its full activity at 20 to 55 degrees C, even after prolonged exposure (more than 30 days) to different concentrations of water-miscible organic solvents such as alcohols, glycols, pyridine, acetonitrile, dimethyl formamide, and dimethyl sulfoxide. The hydrolysis of 4-nitrophenyl laurate ester and of triglyceride emulsified in water was slightly accelerated with increasing concentrations of alcohols and glycols up to about 20% but was abolished with a further increase in alcohol concentration or in the presence of acetonitrile. In contrast, the rate of hydrolysis of these substrates in concentrated solutions of dimethyl formamide or dimethyl sulfoxide was markedly increased, by more than twofold and more than fivefold, respectively. (ABSTRACT TRUNCATED AT 250 WORDS)
Development and Application of an Oral Challenge Mouse Model for Studying Clostridium perfringens Type D Infection

ABSTRACT Clostridium perfringens type D isolates cause enterotoxemia in sheep, goats, and probably cattle. While the major disease signs and lesions of type D animal disease are usually attributed to epsilon toxin, a class B select agent, these bacteria typically produce several lethal toxins. Understanding of disease pathogenesis and development of improved vaccines are hindered by the lack of a small-animal model mimicking natural disease caused by type D isolates. Addressing this need, we developed an oral challenge mouse model of C. perfringens type D enterotoxemia. When BALB/c mice with a sealed anus were inoculated by intragastric gavage with type D isolates, 7 of 10 type D isolates were lethal, as defined by spontaneous death or severe clinical signs necessitating euthanasia. The lethalities of the seven type D isolates varied between 14 and 100%. Clinical signs in the lethally challenged mice included seizures, convulsions, hyperexcitability, and/or depression. Mild intestinal gas distention and brain edema were observed at necropsy in a few mice, while histology showed multifocal acute tubular necrosis of the kidney and edema in the lungs of most challenged mice that developed a clinical response. When the lethality of type D isolates in this model was compared with in vitro toxin production, only a limited correlation was observed. However, mice could be protected against lethality by intravenous passive immunization with an epsilon toxin antibody prior to oral challenge. This study provides an economical new model for studying the pathogenesis of C. perfringens type D infections.
Nox1 downstream of 12‐lipoxygenase controls cell proliferation but not cell spreading of colon cancer cells

The catalytic subunit of the NADPH oxidase complex, Nox1 (homologue of gp91phox/Nox2), expressed mainly in intestinal epithelial and vascular smooth muscle cells, functions in innate immune defense and cell proliferation. The molecular mechanisms underlying these functions, however, are not completely understood. We measured Nox1‐dependent O 2− production during cell spreading on Collagen IV (Coll IV) in colon carcinoma cell lines. Knocking down Nox1 by shRNA, we showed that Nox1‐dependent O 2− production is activated during cell spreading after 4 hr of adhesion on Collagen IV. Nox1 activation during cell spreading relies on Rac1 activation and arachidonic metabolism. Our results showed that manoalide (a secreted phospholipase A2 inhibitor) and cinnamyl‐3,4‐dihydroxy‐α‐cyanocinnamate (a 12‐lipoxygenase inhibitor) inhibit O 2− production, cell spreading and cell proliferation in these colonic epithelial cells. 12‐Lipoxygenase inhibition of ROS production and cell spreading can be reversed by adding 12‐HETE, a 12‐lipoxygenase product, supporting the specific effect observed with cinnamyl‐3,4‐dihydroxy‐α‐cyanocinnamate. In contrast, Nox1 shRNA and DPI (NADPH oxidase inhibitor) weakly affect cell spreading while inhibiting O 2− production and cell proliferation. These results suggest that the 12‐lipoxygenase pathway is upstream of Nox1 activation and controls cell spreading and proliferation, while Nox1 specifically affects cell proliferation. © 2007 Wiley‐Liss, Inc.
Film data reduction from Taylor impact tests

Abstract A high-speed photographic film record of a Taylor impact experiment was analysed to determine the strain, strain rate and stress. The stress was calculated on the basis of an interpretive analysis by Taylor involving the motion of a plastic wave in the material. The data on drawn OFE copper produced stresses from 300 to 400 MPa, for strains between 0 and 45 per cent. The strain rate approximation produced a peak value of 11 000 s−1. The strain rate data showed a wide range of values in the plastically deforming region.
Impact of Community-Based Larviciding on the Prevalence of Malaria Infection in Dar es Salaam, Tanzania

Background The use of larval source management is not prioritized by contemporary malaria control programs in sub-Saharan Africa despite historical success. Larviciding, in particular, could be effective in urban areas where transmission is focal and accessibility to Anopheles breeding habitats is generally easier than in rural settings. The objective of this study is to assess the effectiveness of a community-based microbial larviciding intervention to reduce the prevalence of malaria infection in Dar es Salaam, United Republic of Tanzania. Methods and Findings Larviciding was implemented in 3 out of 15 targeted wards of Dar es Salaam in 2006 after two years of baseline data collection. This intervention was subsequently scaled up to 9 wards a year later, and to all 15 targeted wards in 2008. Continuous randomized cluster sampling of malaria prevalence and socio-demographic characteristics was carried out during 6 survey rounds (2004–2008), which included both cross-sectional and longitudinal data (N = 64,537). Bayesian random effects logistic regression models were used to quantify the effect of the intervention on malaria prevalence at the individual level. Effect size estimates suggest a significant protective effect of the larviciding intervention. After adjustment for confounders, the odds of individuals living in areas treated with larviciding being infected with malaria were 21% lower (Odds Ratio = 0.79; 95% Credible Intervals: 0.66–0.93) than those who lived in areas not treated. The larviciding intervention was most effective during dry seasons and had synergistic effects with other protective measures such as use of insecticide-treated bed nets and house proofing (i.e., complete ceiling or window screens). Conclusion A large-scale community-based larviciding intervention significantly reduced the prevalence of malaria infection in urban Dar es Salaam.
Security challenges for peer-to-peer SIP

Recent research activities have proposed using a peer-to-peer network for user registration and user location in session initiation protocol (SIP)-based voice-over-IP (VoIP) networks. The main motivation for peer-to-peer (P2P) SIP is higher robustness as well as easy configuration and maintenance (compared to client-server SIP). However, these advantages come at the price of security. In this article the security challenges of using a P2P network as a substrate for SIP communication are explored. After a short introduction to SIP and structured P2P networks, the different approaches that have been proposed for using P2P technology in conjunction with SIP are compared. We focus on design issues that affect security in order to identify the security implications of using a structured overlay network for SIP registration and location lookup. Finally, possible solutions for securing P2P SIP are examined and explicit suggestions on how to improve the security of P2P SIP are given
Are the Disabled Less Loss Averse? Evidence from a Natural Policy Experiment

Research findings show that disabled persons often develop physical and psychological mechanisms to compensate for disabilities. Coping mechanisms may not be limited to the psychophysiological domain and may extend to cognitive bias and loss aversion. In this study, we apply unique microdata from a natural policy experiment to assess the role of loss aversion in home purchase among nondisabled and disabled households. Results of survival analysis indicate that the physically disabled are substantially less loss averse in home purchase. Furthermore, loss aversion varies with other population characteristics and attenuates with degree of disability. Findings provide new evidence of diminished cognitive bias and more rational economic decision‐making among the physically disabled.
Oxidative Stress Contributes to Sex Differences in Blood Pressure in Adult Growth-Restricted Offspring

Numerous experimental studies suggest that oxidative stress contributes to the pathophysiology of hypertension and, importantly, that oxidative stress plays a more definitive role in mediating hypertension in males than in females. Intrauterine growth restriction induced by reduced uterine perfusion initiated at day 14 of gestation in the rat programs hypertension in adult male growth-restricted offspring; yet, female growth-restricted offspring are normotensive. The mechanisms mediating sex differences in blood pressure in adult growth-restricted offspring are not clear. Thus, this study tested the hypothesis that sex-specific differences in renal oxidative stress contribute to the regulation of blood pressure in adult growth-restricted offspring. A significant increase in blood pressure measured by telemetry in male growth-restricted offspring (P<0.05) was associated with a marked increase in renal markers of oxidative stress (P<0.05). Chronic treatment with the antioxidant Tempol had no effect on blood pressure in male control offspring, but it normalized blood pressure (P<0.05) and renal markers of oxidative stress (P<0.05) in male growth-restricted offspring relative to male control offspring. Renal markers of oxidative stress were not elevated in female growth-restricted offspring; however, renal activity of the antioxidant catalase was significantly elevated relative to female control offspring (P<0.05). Chronic treatment with Tempol did not significantly alter oxidative stress or blood pressure measured by telemetry in female offspring. Thus, these data suggest that sex differences in renal oxidative stress and antioxidant activity are present in adult growth-restricted offspring and that oxidative stress may play a more important role in modulating blood pressure in male but not female growth-restricted offspring.
Phonological Reduction in Swedish

In this paper, the importance of pronunciation varia- tion modelling is discussed. As a first step in devel- oping a model of Swedish pronunciation variation due to speaking style and speech rate, a tentative reduc- tion rule system has been developed. An assessment experiment testing the impact of phonological reduc- tion, as defined by this system, on the perceived natu- ralness of speech synthesis was conducted. Canonical and reduced synthetic speech stimuli with three differ- ent speech rates were presented to na¨ ive subjects. The reduced pronunciations were significantly more often perceived as more natural than the canonical pronun- ciations at the higher speech rates, while there was no significant general difference in perceived naturalness depending on reduction level for the lowest rate. The dependence on speech rate for perceived naturalness was significant. A possible cause for some observed differences in perceived naturalness depending on the nature of specific stimuli is discussed. For a general description of speaking style dependent pronunciation variation in Swedish, both phonological and phonetic level rules will have to be developed. For this purpose, data-driven methods will be used on an- notated spontaneous speech corpora. The focus will be on general aspects of pronunciation variation, rather than on variation due to dialect or individual factors. As a starting point, a tentative knowledge-based phonological level rule system has been developed. The purpose of this rule system is to form a base from which a more elaborate rule system can be built. The rule system has some empirical grounds, since it is based partly on empirical results reported by Garding (1). The result of applying the rule system to canonical (maximally detailed) transcriptions can be compared to what can be observed in spontaneous speech cor- pora and the rules updated, if systematic deviations are found. The phonological rules can also serve as a skeleton to which more detailed phonetic rules can be added. In this paper, an assessment experiment testing the impact on the perceived naturalness of speech synthesis of the tentative rule system is reported. The specific questions asked are: 1) What is the impact on the perceived naturalness of synthesis output of applying the rule system to the input transcriptions, 2) What is the correlation between the perceived naturalness of the rule-processed stimuli and synthesis speech rate and 3) Are there differences in perceived naturalness depending on the rules applied and, if so, how can these differences be explained? 1.1 BACKGROUND
Hypoxia-Induced Post-Translational Changes in Red Blood Cell Protein Map of Newborns

Tyrosine (Tyr) phosphorylation is implicated in the modification of several erythrocyte functions, such as metabolic pathways and membrane transport, as well as in signal transduction systems. Here we describe the map of Tyr-phosphorylated soluble proteins of newborn red blood cells (RBC) using an in vitro model simulating RBC reoxygenation at birth after an intrauterine hypoxic event. We tested the hypothesis that a hypoxic environment and subsequent reoxygenation promote post-translational changes in the RBC protein map of newborns, in addition to desferrioxamine (DFO)-chelatable iron (DCI) release and methemoglobin (MetHb) formation. Umbilical cord blood RBC were incubated under hypoxic conditions for 16 h at 37°C, and subsequently for 8 h under aerobic conditions. Control erythrocytes were incubated under aerobic conditions at 37°C for the period of the experiment, i.e. for 24 h. Tyr-phosphorylation proteins were assessed using advanced high-resolution two-dimensional electrophoresis, 2-D immunoblot analysis with anti-phosphotyrosine (anti-pTyr) antibodies, and computer-aided electrophoretogram analysis. Higher DCI release and MetHb formation were observed in newborn RBC incubated under hypoxic conditions than in those incubated aerobically. Different immunoreactivity patterns with anti-pTyr antibodies were also observed between newborn RBC incubated under hypoxic conditions and controls. A hypoxic environment is a factor promoting DCI release, a well-known condition of oxidative stress. This is the first map of Tyr-phosphorylated soluble proteins of newborn RBC obtained using an in vitro model simulating RBC reoxygenation at birth after an intrauterine hypoxic event. Our results suggest that hypoxia increases Tyr-phosphorylation of antioxidant proteins, protecting RBC against oxidative stress.
The 12 kDa FK506-binding protein, FKBP12, modulates the Ca2+-flux properties of the type-3 ryanodine receptor

We have characterised the functional regulation of the type-3 ryanodine receptor by the 12 kDa FK506-binding protein. Wild-type type-3 ryanodine receptor and mutant type-3 ryanodine receptor in which the critical valine at position 2322 in the central 12 kDa FK506-binding protein binding site was substituted by aspartate, were stably expressed in human embryonic kidney cells. In contrast to the wild-type receptor, the mutant receptor was strongly impaired in binding to immobilised glutathione S-transferase 12 kDa FK506-binding protein. Caffeine-induced 45Ca2+-efflux was markedly increased in cells expressing mutant type-3 ryanodine receptor whereas the maximal-releasable Ca2+ was not affected. Confocal Ca2+ imaging provided clear evidence for a much higher sensitivity of the mutant receptor, which showed global Ca2+ release at about 20-fold lower caffeine concentrations than the wild-type receptor. Spontaneous Ca2+ sparks were observed in both wild-type- and mutant-expressing cells but the number of sparking cells was about 1.5-fold higher in the mutant group, suggesting that the degree of FK506 binding controls the stability of the closed state of ryanodine receptor channels. Furthermore, overexpression of 12 kDa FK506-binding protein decreased the number of sparking cells in the wild-type-expressing cells whereas it did not affect the number of sparking cells in cells expressing the mutant receptor. Concerning spark properties, the amplitude and duration of Ca2+ sparks mediated by mutant channels were significantly reduced in comparison to wild-type channels. This suggests that functional coupling between different mutant type-3 ryanodine receptor channels in a cluster is impaired. Our findings show for the first time that the central binding site for the 12 kDa FK506-binding protein of type-3 ryanodine receptor, encompassing the critical valine proline motif, plays a crucial role in the modulation of the Ca2+ release properties of the type-3 ryanodine receptor channel, including the regulation of both global Ca2+ responses and spontaneous Ca2+ sparks.
Trust in social Q&A: The impact of text and photo cues of expertise

Users increasingly rely on social Q&A sites to answer questions that are important to their everyday lives. Social Q&A differs significantly from library-based reference services in that there is no guarantee that the individuals answering questions have relevant expertise or are relying on authoritative sources. This raises an important research question: what factors influence users' trust in social Q&A? This paper seeks to determine the role that text and photo cues of expertise have on users' trust in answers in social Q&A. The results of an experiment with 241 subjects indicate that expertise cues in text lead to significantly higher trust among both experts and non-experts. However, expertise cues in photos increase trust among non-experts but do not increase trust among experts. These results indicate that both the expertise of the user and the expertise cues provided in the answer affect user trust in social Q&A.
A Smart Sensor for Image Processing: Towards a System on Chip

One of the solutions to reduce the computational complexity of image processing is to perform some low-level computations on the sensor focal plane. This paper presents a vision system based on a smart sensor. PARISl (programmable analog retina-like image sensor) is the first prototype used to evaluate the architecture of an on-chip vision system based on such a sensor and a digital processor. The sensor integrates analog and digital computing units. This architecture makes the vision system more compact and increases the performances reducing the data flow exchanges with the digital processor. A system has been implemented as a proof-of-concept. This has enabled us to evaluate the performance needed for a possible implementation of a digital processor on the same chip. The approach is compared to two architectures implementing CMOS sensors and interfaced to the same processor. The comparison is related to image processing computation time, processing reliability, programmability, precision, bandwidth and subsequent stages of computations
Epileptiform spike detection via convolutional neural networks

The EEG of epileptic patients often contains sharp waveforms called "spikes", occurring between seizures. Detecting such spikes is crucial for diagnosing epilepsy. In this paper, we develop a convolutional neural network (CNN) for detecting spikes in EEG of epileptic patients in an automated fashion. The CNN has a convolutional architecture with filters of various sizes applied to the input layer, leaky ReLUs as activation functions, and a sigmoid output layer. Balanced mini-batches were applied to handle the imbalance in the data set. Leave-one-patient-out cross-validation was carried out to test the CNN and benchmark models on EEG data of five epilepsy patients. We achieved 0.947 AUC for the CNN, while the best performing benchmark model, Support Vector Machines with Gaussian kernel, achieved an AUC of 0.912.
Construction and capacity analysis of high-rank line-of-sight MIMO channels

This paper describes a technique for realizing a high rank channel matrix in a line-of-sight (LOS) multiple-input-multiple-output (MIMO) transmission scenario. This is beneficial for systems which can not make use of the originally derived MIMO gain given by independent and identically distributed (i.i.d.) flat Rayleigh fading channels. Typical applications are fixed wireless access and radio relay systems. The technique is based on optimization of antenna placement in a uniform linear array. By introducing a new and more general geometrical model than that applied in earlier works, additional insight into the optimal design parameters is gained. A novel analysis of the sensitivity of the optimal design parameters is performed. The LOS transmission matrix is used in a Rician fading channel model, and performance is evaluated with respect to ergodic capacity, outage capacity, and effective degrees of freedom. The results show that even with some deviation from optimal design, the LOS MIMO case outperforms the i.i. d. Rayleigh case in terms of Shannon capacity.