Miracle-dz/UniFAR-FTUs huggingface dataset:
Variability in spontaneous subcellular calcium release in guinea‐pig ileum smooth muscle cells

1 Spontaneous, localized transient increases in [Ca2+]i (‘Ca2+ sparks’) were observed in about 40 % of fluo‐3‐loaded myocytes examined using laser scanning confocal microscopy. Ca2+ sparks persisted after application of Cd2+ (200 μM), but were abolished by ryanodine (30 μM) or thapsigargin (0.1 μM), suggesting that they arise from the spontaneous activation of ryanodine receptors (RyR) in the sarcoplasmic reticulum (SR). 2 Ca2+ sparks occurred much more frequently at certain sites (or ‘frequent discharge sites’, FDSs) within any confocal plane of the cell and line‐scan imaging revealed a wide variation in their spatial size, amplitude and time course. Some spontaneous local transients were very similar to ‘Ca2+ sparks’ observed in heart, i.e. lasting ≈200 ms with a peak fluorescence ratio of 1.75 ± 0.23 (mean ± s.d., n= 33). Other events were faster and smaller, lasting only ≈40 ms with a peak normalized fluorescence of 1.36 ± 0.09 (mean ± s.d., n= 28). 3 Spontaneous Ca2+ waves with a wide range of propagation velocities (between 30 and 260 μm s−1) were also observed. In about 60 % of records (n= 33), Ca2+ sparks could be detected at the sites of wave initiation. Waves of elevated [Ca2+]i propagated with non‐constant velocity and in some cases terminated. These observations could be explained by heterogeneity in the distribution of subcellular release sites as well as variability in the contribution of each release site to the wave. 4 Spontaneous [Ca2+]i transients in single dispersed visceral smooth muscle cells have a wide spectrum of behaviour that is likely to be the result of spatio‐temporal recruitment of smaller local events, probably via a calcium‐induced calcium release (CICR) mechanism. The spatial non‐uniformity of SR and RyR distribution within the cell may account for the existence of ‘frequent discharge sites’ firing the majority of the smooth muscle Ca2+ sparks and the wide variation in the Ca2+ wave propagation velocities observed.
Nephrotoxicity testing in vitro--what we know and what we need to know.

The kidney is affected by many chemicals. Some of the chemicals may even contribute to end-stage renal disease and thus contribute considerably to health care costs. Because of the large functional reserve of the kidney, which masks signs of dysfunction, early diagnosis of renal disease is often difficult. Although numerous studies aimed at understanding the mechanisms underlying chemicals and drugs that target various renal cell types have delivered enough understanding for a reasonable risk assessment, there is still an urgent need to better understand the mechanisms leading to renal cell injury and organ dysfunction. The increasing use of in vitro techniques using isolated renal cells, nephron fragments, or cell cultures derived from specific renal cell types has improved our insight into the molecular mechanisms involved in nephrotoxicity. A short overview is given on the various in vitro systems currently used to clarify mechanistic aspects leading to sublethal or lethal injury of the functionally most important nephron epithelial cells derived from various species. Whereas freshly isolated cells and nephron fragments appear to represent a sufficient basis to study acute effects (hours) of nephrotoxins, e.g., on cell metabolism, primary cultures of these cells are more appropriate to study long-term effects. In contrast to isolated cells and fragments, however, primary cultures tend to first lose several of their in vivo metabolic properties during culture, and second to have only a limited life span (days to weeks). Moreover, establishing such primary cultures is a time-consuming and laborious procedure. For that reason many studies have been carried out on renal cell lines, which are easy to cultivate in large quantities and which have an unlimited life span. Unfortunately, none of the lines display a state of differentiation comparable to that of freshly isolated cells or their primary cultures. Most often they lack expression of key functions (e.g., gluconeogenesis or organic anion transport) of their in vivo correspondents. Therefore, the use of cell lines for assessment of nephrotoxic mechanisms will be limited to those functions the lines express. Upcoming molecular biology approaches such as the transduction of immortalizing genes into primary cultures and the utilization of cells from transgenic animals may in the near future result in the availability of highly differentiated renal cells with markedly extended life spans and near in vivo characteristics that may facilitate the use of renal cell culture for routine screening of nephrotoxins. ImagesFigure 1Figure 2
Predictors of cheating behavior at a university: A lesson from the psychology of work

The present study investigated students' behavior across academic departments to establish how personality, demographic, educational, attitudinal, and climate (both psychological and departmental) predicted self-reported cheating behavior at a university, Participants were 107 students from a variety of academic disciplines, The results explain 50.5% of the variability in self-reported cheating behavior in terms of demographic (male, school education qualifications), departmental climate, and individual differences (Lie and Neuroticism scales), We concluded that an expanded theoretical perspective (utilizing a wide range of person and situation variables) explained more variability than would otherwise be explained from any single perspective, and that findings from the literature of integrity at work generalize to educational settings. Finally, we discuss the limitations and implications of this research.
Benchmarks for Science Literacy: a review symposium∗

∗The book reviewed is Benchmarks for Scientific Literacy, American Association for the Advancement of Science, Project 2061, Oxford University Press, New York and Oxford (1993), pp. 448, $21‐95 (pbk), ISBN 0‐19‐508986‐3.
Retirement of Dutch Male Older Workers: The Role of Mid-Life Educational, Work, Health, and Family Experiences

Objectives: The life course perspective suggests that the retirement process cannot be understood thoroughly without paying attention to distal life experiences. In empirical studies on predictors of retirement, however, mid-life experiences often have remained implicit or have been neglected. This study aims to improve our understanding of retirement, by studying the impact of mid-life experiences in the educational, work, health, and family life spheres on retirement intentions and behavior. Methods: Using panel data of 1229 Dutch male older workers, we estimated linear regression models to explain retirement intentions and Cox proportional hazards regression models to explain retirement behavior. Results: Mid-life experiences in all studied life spheres were related to retirement intentions. For mid-life work experiences (dismissal and employer change) the relationships were explained by the perceived financial consequences of these experiences (pension shortcomings). The effects of most mid-life experiences in the educational, health, and family spheres remained significant after controlling for different aspects of the preretirement financial situation. Only some of the predictors of retirement intentions also predicted retirement behavior. Discussion: Given the de-standardization of life courses, information on distal life experiences might become even more important for understanding retirement in the future.
A study of caching proxy mechanisms realized on wide area distributed networks

The information retrieval systems on a wide area distributed network, such as the World-Wide Web (WWW), become popular among the extremely large number of users. The caching proxy has an important role in these systems for improving their accessibility and serviceability. The caching proxy mechanism is discussed in this paper. First, the role and structure of the caching proxy is explained, and two major problems of existing systems are pointed out. Our solution to overcome these problems is proposed next. Changing a file size by controlling a quality level of cached multimedia data is proposed as a measure to overcome one problem. As a solution to the other problem, making a cluster among neighboring caching proxies, using hyperlink information, is proposed. Finally, an improved caching proxy mechanism based upon these ideas is shown.
Populations of Ixodes scapularis (Acari: Ixodidae) Are Modulated by Drought at a Lyme Disease Focus in Illinois

Abstract From 1990 through 1997, Ixodes scapularis Say larvae and nymphs were sampled between May and October along a 400-m segment of a nature trail in a Lyme disease endemic site in northern Illinois. Ticks were removed from Peromyscus leucopus mice and collected via tick drags at ≈3-wk intervals. Mouse population estimates along the trail varied from 2, in the spring of 1996 following a year of drought, to >200 in 1993, the wettest year on record. During the 8-yr period, there were major droughts during the summers of 1991 and 1995. Cumulative degree-days were positively correlated with the number of ticks collected on drags in the same year and negatively correlated with larval tick populations for the following year (P < 0.05). Cumulative rainfall was positively correlated with larval tick abundance for the following year. This was most readily apparent by examination of the larval density on captured mice. In the year following each of two drought years, larval densities were significantly depressed compared with the 8-yr average at the site.
Crystal Structure of Human Protein N-Terminal Glutamine Amidohydrolase, an Initial Component of the N-End Rule Pathway

The N-end rule states that half-life of protein is determined by their N-terminal amino acid residue. N-terminal glutamine amidohydrolase (Ntaq) converts N-terminal glutamine to glutamate by eliminating the amine group and plays an essential role in the N-end rule pathway for protein degradation. Here, we report the crystal structure of human Ntaq1 bound with the N-terminus of a symmetry-related Ntaq1 molecule at 1.5 Å resolution. The structure reveals a monomeric globular protein with alpha-beta-alpha three-layer sandwich architecture. The catalytic triad located in the active site, Cys-His-Asp, is highly conserved among Ntaq family and transglutaminases from diverse organisms. The N-terminus of a symmetry-related Ntaq1 molecule bound in the substrate binding cleft and the active site suggest possible substrate binding mode of hNtaq1. Based on our crystal structure of hNtaq1 and docking study with all the tripeptides with N-terminal glutamine, we propose how the peptide backbone recognition patch of hNtaq1 forms nonspecific interactions with N-terminal peptides of substrate proteins. Upon binding of a substrate with N-terminal glutamine, active site catalytic triad mediates the deamination of the N-terminal residue to glutamate by a mechanism analogous to that of cysteine proteases.
A METHOD OF STAINING THIN SECTIONS WITH LEAD HYDROXIDE FOR PRECIPITATE-FREE SECTIONS

Staining of thin sections results in greater contrast which facilitates focusing and the observation of fine structure. Lead hydroxide, as suggested by Watson (1), has become increasingly popular as a stain for electron microscopy. However, when lead hydroxide is exposed to the carbon dioxide of air, lead carbonate forms and is deposited on the sections as fine, needle-like crystals, large amorphous or polygonal precipitates, or small granules. In order to prevent the stain from coming in contact with air, Peachey (2) used a plastic, air-free syringe as a receptacle for the stain and as a mechanism for staining sections. The cover of the syringe was filled with a carbon dioxide trap consisting of sodium hydroxide, anhydrous calcium chloride, and cotton. Parsons and Darden (3) designed a
300-kA Fast Linear Transformer Driver Stage

A modular linear transformer driver (LTD) is a novel fast-discharge high-pulsed power source for primarily stored energy. In LTDs, a large number of stages (or cavities) can be connected in series or in parallel conveniently to directly generate high power pulses of 50-200 ns with the required voltage or current. This paper introduces an LTD stage developed by us recently. This LTD stage consists of 14 bricks in parallel. Each brick contains two 40-nF capacitors and a compact multigap gas spark switch in series. The switch is a modification of our original version, and the diameter and the height of which have been reduced to 98 and 127 mm, respectively. The circuit model of this stage is established in PSPICE, and its output parameters are obtained through simulation. Driving a rough-matched resistive load of 0.27 Ω, its output current peak is 300 kA with an overall rise time of about 110 ns at a charged voltage of the capacitors of about ±90 kV, agreeing well with its simulation result.
Continuous monitoring of directional wave spectra and meteo-marine data aimed at the modeling of coastal erosion in the north eastern Adriatic Sea

The aim of this paper is to give an example of the application of the continuous monitoring of environmental data and numerical modeling in resolving the specific problem of coastal erosion. The example is part of a project in progress aimed at monitoring the coastline of the Lignano and Bibione beaches. Although these areas in the northern Adriatic Sea are not protected areas, they constitute the major natural resource of the local communities, and as such there is strong economic, social and political pressure to conserve them. Since 2001, a continuous monitoring of wave motion (DWR buoy) and of meteo-marine variables (MAMBO buoy) has been carried out in the Gulf of Trieste, to the south of the two beaches. This allows the application of a numerical model to obtain necessary information for the study of coastal erosion in the area. The evaluation of sediment transport using morphological data to compare several possible solutions aimed at reducing the phenomenon is currently being attempted. In this paper, some examples are given on the tidal numerical simulation in the Trieste Gulf, validated with the measured data and on the modeling of wave propagation in the same area. Since both, monitoring and the implementation of the models are in progress, the paper shows preliminary results.
The power system risk assessment under rainfall weather and subsequent geological disasters

The heavy rainfall weather often results in subsequent geological hazards and causes severe transmission line outage. In this paper, risk assessment model is established to evaluate related impacts against power grid. Specifically, transmission line failure probability is quantitatively modeled for risk evaluation based on precipitation and transmission tower deflection and non-sequential Monte Carlo simulation and optimal load shedding model. The interior point method and risk indicators are used for system risk calculation. The simulation examples of a Western China regional power grid show that the power system risk gradually increases with the expanded scope and increases severity of the hazards, which is in accordance with the real situation. The proposed methodology is very valuable in guiding transmission line construction and maintenance in tough weather and geological regions and is capable of substantial improvement of power supply quality.
Increased avidity for Dpp/BMP2 maintains the proliferation of eye progenitors in Drosophila

During normal organ development, the progenitor cell state is transient: it depends on specific combinations of transcription factors and extracellular signals, that cooperate to sustain the proliferative potential and undifferentiated status of organ progenitor cells. Not surprisingly, abnormal maintenance of progenitor transcription factors may lead to tissue overgrowth, and the concurrence of specific signals from the local environment is often critical to trigger this overgrowth. Therefore, the identification of the specific combinations of transcription factors and signals that promote or oppose proliferation in progenitor cells is essential to understand normal development and disease. We have investigated this issue by asking what signals may promote the proliferation of eye progenitors in Drosophila. Two transcription factors, the MEIS1 homologue homothorax (hth) and the Zn-finger teashirt (tsh) are transiently expressed in eye progenitors causing the expansion of the progenitor pool. However, if their co-expression is maintained experimentally, cell proliferation continues and differentiation is halted. Here we show that Hth+Tsh-induced tissue overgrowth requires the BMP2 ligand Dpp and the activation of its pathway. In Hth+Tsh cells, the Dpp pathway is abnormally hyperactivated. Rather than using autocrine Dpp expression, Hth+Tsh cells increase their avidity for Dpp, produced locally, by upregulating extracellular matrix components. During normal development, Dpp represses hth and tsh ensuring that the progenitor state is transient. However, cells in which Hth+Tsh expression is maintained use Dpp to enhance their proliferation. Summary Statement In Drosophila, homothorax, the Meis1 homologue, and teashirt jointly sustain the proliferation of eye progenitor cells by increasing their avidity for BMP produced by the local microenvironment.
Proteoglycan and collagen expression during human air conducting system development

The lung is formed from a bud that grows and divides in a dichotomous way. A bud is a new growth center which is determined by epithelial-mesenchymal interactions where proteins of the extracellular matrix (ECM) might be involved. To understand this protein participation during human lung development, we examined the expression and distribution of proteoglycans in relation to the different types of collagens during the period in which the air conducting system is installed. Using light microscopy and immunohistochemistry we evaluate the expression of collagens (I, III and VI) and proteoglycans (decorin, biglycan and lumican) between 8 to 10 weeks post fertilization and 11 to 14 weeks of gestational age of human embryo and fetus lungs. We show that decorin, lumican and all the collagen types investigated were expressed at the epithelium-mesenchymal interface, forming a sleeve around the bronchiolar ducts. In addition, biglycan was expressed in both the endothelial cells and the smooth muscle of the blood vessels. Thus, the similar distribution pattern of collagen and proteoglycans in the early developmental stages of the human lung may be closely related to the process of dichotomous division of the bronchial tree. This study provides a new insight concerning the participation of collagens and proteoglycans in the epithelial-mesenchymal interface during the period in which the air conducting system is installed in the human fetal lung.
A 3.1–7 GHz 40-nm CMOS digital polar transmitter with high data-rate and feed-forward operation

A 3.1-7 GHz fully integrated polar transmitter (TX) in 40-nm CMOS process with high data-rate and reconfigurable feed-forward operation is proposed. The real-time feed-forward operation is utilized to improve the power efficiency at back-off and saturated power levels in a wideband. With the wideband Marchand balun based open-loop digital phase modulator, the wide modulation-bandwidth and high data-rate are achieved. Operating from a 1.2-V supply, the TX delivers peak Psat of 21.8 dBm and 45.1% peak drain efficiency. Using the feed-forward operation, the measured drain efficiency has maximum 7.3% and 4.8% improvement at the saturated and 6-dB back-off power, respectively. The TX exhibits RMS-EVMs of 3.93% and 4.69% for 64-QAM signals with modulation bandwidths of 12.5 and 25 MHz at data-rates of 68 and 136 Mbps, respectively. To the best of our knowledge, this is the first reported digital polar TX with the data-rate more than 100 Mbps and EVM lower than 4.7%, simultaneously.
An analytical model to design and manage green access networks to CPE node

Across broadband access networks, significant opportunities to minimise energy consumption exist at the application and networks level but are not fully coordinated. For example, an application can tune its QoS in accordance with the available power levels of network systems. As a first step towards enabling energy efficiency, we study the interrelationship between energy consumption and application performance in a residential home-gateway. The study reveals the power and application performance trade-offs in broadband access networks and then employs an agent based approach that works together in accordance with a flexible set of power-performance objectives and determines the existence of a feasible coordinated operating point. The key elements of our approach include (a) a power-performance polygon-based methodology which automatically selects power management settings that keep the pathway from access network to home-gateway operating close to the optimal operating point (b) a multi-agent policy-based approach which adaptively manages performance and power consumption based on varying traffic load during peak/off-peak hours. Finally, the efficiency of the model is demonstrated by the initial results of the experiments.
The European Confederation of Medical Mycology (ECMM) survey of candidaemia in Italy: in vitro susceptibility of 375 Candida albicans isolates and biofilm production.

OBJECTIVES To investigate the in vitro antifungal susceptibility pattern of 375 Candida albicans bloodstream isolates recovered during the European Confederation of Medical Mycology survey of candidaemia performed in Lombardia, Italy and to test the ability to form biofilm. METHODS In vitro susceptibility to flucytosine, fluconazole, itraconazole, posaconazole, voriconazole and caspofungin was performed by broth microdilution following the NCCLS guidelines. Biofilm production was measured using the XTT reduction assay in 59 isolates selected as representative of different patterns of susceptibility to flucytosine and azoles. RESULTS MICs (mg/L) at which 90% of the strains were inhibited were < or =0.25 for flucytosine, 0.25 for caspofungin, 4 for fluconazole and 0.06 for itraconazole, voriconazole and posaconazole. Flucytosine resistance was detected in five isolates and was associated with serotype B in 2/29 and serotype A in 3/346. Resistance to fluconazole was detected in 10 isolates; nine of these exhibited reduced susceptibility to the other azoles. Among the 10 patients with fluconazole-resistant C. albicans bloodstream infection, only one, an AIDS patient, had been previously treated with fluconazole. Biofilm production was observed in 23 isolates (39%) and was significantly associated with serotype B. No relationship was detected with the pattern of antifungal susceptibility. CONCLUSIONS Resistance is uncommon in C. albicans isolates recovered from blood cultures, while biofilm production is a relatively frequent event. Periodic surveillance is warranted to monitor the incidence of in vitro antifungal resistance as well as of biofilm production.