Miracle-dz/UniFAR-FTUs huggingface dataset:
Chloroaluminum phthalocyanine tetrasulfonate delivered via acid‐labile diplasmenylcholine‐folate liposomes: Intracellular localization and synergistic phototoxicity

Folate‐diplasmenylcholine (1,2‐di‐O‐(Z‐1′‐hexadecenyl)‐sn‐glycero‐3‐phosphocholine; DPPlsC) liposomes have been shown to greatly enhance the potency of water‐soluble antitumor agents via a selective folate‐mediated uptake and acid‐catalyzed endosomal escape mechanism (Rui et al. J. Am. Chem. Soc., 1998; 120:11213–18). This study describes an adaptation of this strategy for the delivery of chloroaluminum phthalocyanine tetrasulfonate (AlPcS44−), a water‐soluble sensitizer used in photodynamic therapy, in a binary targeting scheme designed to enhance both its tumor selectivity and phototoxicity. AlPcS44−/DPPlsC:folate liposomes (9.8 μM bulk concentration, 2.5 mM intraliposomal concentration) were substantially more phototoxic to folate‐deficient KB cells than 12.5 μM free AlPcS44− after a 30 min irradiation (630–910 nm). Considerable differences in phototoxicity were observed, however, between the commercially‐available AlPcS44− and an HPLC purified sample of AlPcS44− due to an increased tendency for the latter to aggregate. Experiments with AlPcS44−/DPPC:folate and folate‐free AlPcS44−/DPPlsC liposomes (acid‐insensitive and non‐targeted controls, respectively) showed significantly reduced phototoxicities under the same illumination conditions. Our results imply that higher concentrations of water‐soluble sensitizers can be delivered to target cells using the folate receptor‐mediated pathway, which can change both the biodistribution and intracellular localization of the sensitizer when acid‐labile DPPlsC liposomes are used as the delivery vehicle. Potential advantages of this approach include the use of lower bulk AlPcS44− concentrations, rapid plasma clearance of free AlPcS44−, and better phototoxic responses, due to higher intracellular AlPcS44− concentrations combined with reduced collateral photodamage arising from misguided sensitizer accumulation, thereby enhancing the selective phototoxicity of PDT treatments. © 2001 Wiley‐Liss, Inc.
On the dependence of P300 latency on stimulus evaluation processes.

McCarthy and Donchin (1981) found that the latency of a late positive component of the event-related potential (ERP) was influenced by the presence of noise in a stimulus matrix but not by the compatibility between the stimulus presented and the response required. They concluded that this component is a P300 and that its latency was influenced by stimulus evaluation but not by response selection processes. The present experiments were designed to confirm that the component identified by McCarthy and Donchin was indeed a P300 and to determine if its latency varies systematically with increases in stimulus evaluation time produced by graded changes in noise level. In Experiment 1, subjects performed a standard oddball task in which they were required to count the rarer of two stimuli (the words RIGHT or LEFT) which were, or were not, embedded in a noise matrix (characters from the alphabet). The positive component of the ERP, whose amplitude was larger for rare target stimuli, was labeled a P300, and the latency of this component was longer when the stimuli were embedded in noise. In Experiment 2, subjects performed a choice reaction time task. Following the procedures used by McCarthy and Donchin, stimulus words RIGHT and LEFT required right or left hand responses depending on the presence of a cue word SAME or OPPOSITE which preceded the stimulus. Stimulus words were presented in four different degrees of noise, the levels of which were manipulated by varying the set size of the alphabetic characters which could surround the stimulus words. Reaction time increased both with noise (by 325 ms) and as a function of stimulus-response incompatibility (by 127 ms). In contrast, P300 latency increased substantially with noise (by 200 ms) but, to a much lesser extent (by 14 ms), with response incompatibility. These results indicate that the P300 is sensitive to the ease with which a target stimulus can be discriminated from noise. They confirm that P300 latency can be used as a measure of the timing of stimulus evaluation processes that is relatively independent of response selection and execution.
Interactive effects of nutrient and mechanical stresses on plant morphology.

BACKGROUND AND AIMS Plant species frequently encounter multiple stresses under natural conditions, and the way they cope with these stresses is a major determinant of their ecological breadth. The way mechanical (e.g. wind, current) and resource stresses act simultaneously on plant morphological traits has been poorly addressed, even if both stresses often interact. This paper aims to assess whether hydraulic stress affects plant morphology in the same way at different nutrient levels. METHODS An examination was made of morphological variations of an aquatic plant species growing under four hydraulic stress (flow velocity) gradients located in four habitats distributed along a nutrient gradient. Morphological traits covering plant size, dry mass allocation, organ water content and foliage architecture were measured. KEY RESULTS Significant interactive effects of flow velocity and nutrient level were observed for all morphological traits. In particular, increased flow velocity resulted in size reductions under low nutrient conditions, suggesting an adaptive response to flow stress (escape strategy). On the other hand, moderate increases in flow velocity resulted in increased size under high nutrient conditions, possibly related to an inevitable growth response to a higher nutrient supply induced by water renewal at the plant surface. For some traits (e.g. dry mass allocation), a consistent sense of variation as a result of increasing flow velocity was observed, but the amount of variation was either reduced or amplified under nutrient-rich compared with nutrient-poor conditions, depending on the traits considered. CONCLUSIONS These results suggest that, for a given species, a stress factor may result, in contrasting patterns and hence strategies, depending on a second stress factor. Such results emphasize the relevance of studies on plant responses to multiple stresses for understanding the actual ecological breadth of species.
Silencing of Monocarboxylate Transporters via Small Interfering Ribonucleic Acid Inhibits Glycolysis and Induces Cell Death in Malignant Glioma: An in Vitro Study

OBJECTIVE:Dependence on glycolysis is a hallmark of malignant tumors. As a consequence, these tumors generate more lactate, which is effluxed from cells by monocarboxylate transporters (MCTs). We hypothesized that 1) MCT expression in malignant tumors may differ from normal tissue in quantity, isoform, or both; and 2) silencing MCT expression would induce intracellular acidification, resulting in decreased proliferation and/or increased cell death. METHODS:We quantified expression of MCT isoforms in human glioblastoma multiforme and glioma-derived cells lines by Western blot analysis. MCTs that were abundant or specific to glioma then were targeted in the model U-87 MG glioma cell line via small interfering ribonucleic acid-mediated gene silencing and tested for inhibition of lactate efflux, intracellular pH changes, reduced proliferation, and/or induction of cell death. RESULTS:MCT 1 and 2 were the primary isoforms expressed in human glioblastoma multiforme and glioma-derived cell lines. In contrast, MCT 3 was the predominantly expressed isoform in normal brain. Small interfering ribonucleic acid specific for MCT 1 and 2 reduced expression of these isoforms in U-87 MG cells to barely detectable levels and reduced lactate efflux by 30% individually and 85% in combination, with a concomitant decrease of intracellular pH by 0.6 units (a fourfold increase in intracellular H+). Prolonged silencing of both MCTs reduced viability by 75% individually and 92% in combination, as measured by both phenotypic and flow cytometric analyses. CONCLUSION:MCT targeting significantly reduced the viability of U-87 MG cells mediated by both apoptosis and necrosis. This indicates that the strategy may be a useful therapeutic avenue for treatment of patients with malignant glioma.
Iontophoretic Enhancement of Timolol across Human Dermatomed Skin In Vitro

The objective of this study was to assess the in vitro the iontophoretic delivery of Timolol across human dermatomed skin in order to determine whether therapeutic doses of this drug can be delivered. Anodal iontophoresis of Timolol was performed by manipulating the donor vehicle and the current density. It was observed that by reducing simultaneously the competitive ions (NaCl) from 8 to 4 g/l and the pH from 7.4 to 4.7, the iontophoretic flux was significantly increased by a factor of 1.5 (669±81 μg/cm2 h). In order to simulate the situation in a transdermal patch, the iontophoretic delivery of Timolol was also studied after adding an artificial porous membrane placed between the Timolol formulation and the human dermatomed skin. No significant difference was observed in the steady state flux across the skin when an artificial membrane was added. Furthermore, a linear relationship was found between current density and steady state flux. These results indicate that the iontophoretic delivery of Timolol can be accurately controlled by the applied current. Assuming a one to one in vitro/in vivo correlation the Timolol transport in vitro results in therapeutic plasma concentrations in humans with very low current densities limiting possible skin irritation.
Spiritual Interventions Provided by Mental Health Nurses

This descriptive qualitative study explored the spiritual nursing interventions provided by mental health nurses. Fifty mental health nurses responded to open-ended interrogative statements to report on nursing interventions in three situations that supported the spiritual needs of patients and families. Their responses were grouped into four categories, nurses being with the client, doing for the client, encouraging the client to look inward, and encouraging the client to look outward. Being with was demonstrated through the presence of the nurse. Doing for included interventions performed on the clients behalf and included the nurse using time, people, and space to provide care. Clients were encouraged to look inward for strength and look outward for people and objects that could be resources for them. A serendipitous finding was that mental health nurses were able to describe the ideal spiritual interventions but reportedfewer instances of actually having intervened.
Efficacy of voluntary nasogastric tube feeding in female inpatients with anorexia nervosa.

BACKGROUND This investigation assesses the efficacy of a voluntary nasogastric tube feeding protocol on the weight gain of patients with anorexia nervosa, tube feeding's effect on recovery from the psychologic aspects of anorexia, patient satisfaction with treatment, and medical complications. METHODS The study included a nonrandomized retrospective review of 381 female inpatients with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of anorexia nervosa, both subtypes. A total of 155 patients received tube feeding and oral refeeding; 226 received oral refeeding alone. Recovery from the psychologic aspects of anorexia was measured by the change in Eating Disorder Inventory-2 scores between admission and discharge. Patient satisfaction with treatment was measured with a patient satisfaction questionnaire completed at discharge. Repeated measures and multivariate analyses were performed. RESULTS When severity-of-illness and caloric intake differences between patients with and without tube feeding were controlled, patients who received tube feeding gained significantly more weight per treatment week than those who received oral kilocalories alone. Patients who received tube feeding for at least one-half their length of stay gained 1 kg/week versus 0.77 kg/week for patients receiving oral refeeding alone. Tube-fed patients evidenced no differences in recovery from anorexia's psychologic aspects, satisfaction with treatment, or medical complication frequency. CONCLUSIONS In residential psychiatric treatment settings in which intensive therapeutic interventions and appropriate medical monitoring can manage potential psychologic and medical risks, tube feeding's weight gain benefits may be a viable and safe option in treating anorexia.
An inherently-robust 300°C MEMS temperature sensor for wireless health monitoring of ball and rolling element bearings

Presented is an inherently-robust wireless capacitive MEMS temperature sensor capable of operating to 300°C. The heart of the sensor is an array of bimorph (metal-dielectric) cantilevers whose deflections are sensed by an array of appropriatelyplaced electrodes. The key advantages of this configuration are the following. First, its dielectric layer is SiO2 thermally-grown at 1,100°C as opposed to conventional low-temperature PECVD or sputtered films. Second, the lack of a sensing surface directly beneath the movable structures renders stiction nearly impossible. Third, the fringing-field sensing results in constant sensitivity throughout the entire temperature range. Fourth, the employed passive approach is immune to high-temperature reliability issues faced by active devices. Furthermore, the fabrication yield is over 99%, even in an academic cleanroom (Birck Nanotechnology Center at Purdue University). When configured with an inductor and wirelessly interrogated, the measured resonant frequency has a linear shift from 206 MHz at room temperature to 199 MHz at 300°C.
D . 1 HOT TOWERS FORMATION – A SIMPLE PLUME RISE MODEL

Hurricane intensification has been studied by scientists for decades and one phenomenon that appears to always accompany the intensification is the presence of hot towers of cumulous clouds that stretches to 15 km high, touching the top of the troposphere (Figure 1a &b). The hypothesis of Hot towers was first proposed in 1958 by Riehl and Malkus (Anthes, 1999), who wrote in conclusion from their observations that
Essential Role of A-kinase Anchor Protein 121 for cAMP Signaling to Mitochondria*

A-Kinase anchor proteins (AKAPs) immobilize and concentrate protein kinase A (PKA) isoforms at specific subcellular compartments. Intracellular targeting of PKA holoenzyme elicits rapid and efficient phosphorylation of target proteins, thereby increasing sensitivity of downstream effectors to cAMP action. AKAP121 targets PKA to the cytoplasmic surface of mitochondria. Here we show that conditional expression of AKAP121 in PC12 cells selectively enhances cAMP·PKA signaling to mitochondria. AKAP121 induction stimulates PKA-dependent phosphorylation of the proapoptotic protein BAD at Ser155, inhibits release of cytochrome c from mitochondria, and protects cells from apoptosis. An AKAP121 derivative mutant that localizes on mitochondria but does not bind PKA down-regulates PKA signaling to the mitochondria and promotes apoptosis. These findings indicate that PKA anchored by AKAP121 transduces cAMP signals to the mitochondria, and it may play an important role in mitochondrial physiology.
Vortex Search Topology Control Algorithm for Wireless Sensor Networks

Wireless sensor networks (WSNs) is composed of a huge number of sensor nodes that are densely deployed in a target environment. One of the major fundamental challenges in WSNs is the Topology control (TC). TC algorithms try to reduction the average of nodes transition radius without reduction of the network connectivity. This paper has proposed a metaheuristic algorithm for TC based on the vortex search (VS) algorithm for WSNs termed VSTC. VSTC algorithm dynamically adjusts transition radius of nodes, so the proper transition radius can be obtained using VS algorithm, so the position of each node is to calculate and represented in a binary format to enhance the coverage area and reduce the number of active nodes. Furthermore, the proposed algorithm is under a less average number of neighbours and the energy consumption compared with the present algorithms. In addition, the proposed algorithm is simulated with the A1 topology algorithm (A1), A3 topology algorithm (A3), and topology control scheme based on particle swarm optimization algorithm (PSOTCS) algorithm, the experimental results have been provided the highest in terms of the high residual energy by 34% and the number of active nodes was decreased
Acetylcholine and the sympathetic innervation of the spleen

This paper is concerned with the role of acetylcholine-like substances in the sympathetic innervation of the spleen. The presence of cholinergic fibres in the sympathetic nerve supply to the cat's spleen was deduced by Burn & Rand (1960c) from observations on the response of the spleen of reserpine-treated cats to splenic nerve stimulation. Stimulation of the splenic nerve in a normal cat releases noradrenaline (Peart, 1949) and causes contraction of the spleen. But when the spleen is depleted of noradrenaline by reserpine (Burn & Rand, 1959 a), splenic nerve stimulation produces either a smaller contraction than usual or a relaxation which is enhanced by eserine and abolished by atropine. The innervation of the cat's spleen has been studied by Utterback (1944), who concluded that there was no parasympathetic innervation and that there were no ganglion cells in the spleen. Sympathetic denervation leads to a decrease in the noradrenaline content of the spleen (von Euler & Purkhold, 1951; Burn & Rand, 1959a), and von Euler (1956) concluded that the loss of noradrenaline on denervation could be explained if it were normally contained in the nerves. However, in another sympathetically innervated structure, the vessels of the rabbit's ear, denervation has been shown to cause a fall in acetylcholine content (Armin, Grant, Thompson & Tickner, 1953). It is well known that the spleen contains acetylcholine. This was first observed by Dale & Dudley (1929), although as yet no explanation has been given for its presence. In order to investigate the possibility that the acetylcholine might be associated with the splenic nerves, we have studied the effect of sympathetic denervation on the acetylcholine content of the cat's spleen. Acetylcholine has been detected in the venous effluents after the stimulation of the sympathetic nerves to a number of structures: the sweat glands (Dale & Feldberg, 1934), the blood vessels of the dog's hind legs
Agile Methods: Fast-Paced, but How Fast?

What are the roles of time and time pressures in design and performance of agile processes for software development? How do we plan our rapid development activities given the constraints of due dates? What does it mean to be on ‘internet time’? Agile methods are meant to be fast-paced, but are they fast in an effective way? How do time-pressures influence the productivity of a project team and how do they impact the motivations of developers? This paper considers the time issues in agile approaches to managing software projects and posits research propositions to guide further study of this area.
A Cellular RNA-Binding Protein Enhances Internal Ribosomal Entry Site-Dependent Translation through an Interaction Downstream of the Hepatitis C Virus Polyprotein Initiation Codon

ABSTRACT Translational initiation of hepatitis C virus (HCV) mRNA occurs by internal entry of ribosomes into an internal ribosomal entry site (IRES) at the 5′ nontranslated region. A region encoding the N-terminal part of the HCV polyprotein has been shown to augment the translation of HCV mRNA. Here we show that a cellular protein, NS1-associated protein 1 (NSAP1), augments HCV mRNA translation through a specific interaction with an adenosine-rich protein-coding region within the HCV mRNA. The overexpression of NSAP1 specifically enhanced HCV IRES-dependent translation, and knockdown of NSAP1 by use of a small interfering RNA specifically inhibited the translation of HCV mRNA. An HCV replicon RNA capable of mimicking the HCV proliferation process in host cells was further used to confirm that NSAP1 enhances the translation of HCV mRNA. These results suggest the existence of a novel mechanism of translational enhancement that acts through the interaction of an RNA-binding protein with a protein coding sequence.
Activation of MEK‐1 and SEK‐1 by Tpl‐2 proto‐oncoprotein, a novel MAP kinase kinase kinase.

The Tpl‐2 protein serine/threonine kinase was originally identified, in a C‐terminally deleted form, as the product of an oncogene associated with the progression of Moloney murine leukemia virus‐induced T cell lymphomas in rats. The kinase domain of Tpl‐2 is homologous to the Saccharomyces cerevisiae gene product, STE11, which encodes a MAP kinase kinase kinase. This suggested that Tpl‐2 might have a similar activity. Consistent with this hypothesis, immunoprecipitated Tpl‐2 and Tpl‐2deltaC (a C‐terminally truncated mutant) phosphorylated and activated recombinant fusion proteins of the mammalian MAP kinase kinases, MEK‐1 and SEK‐1, in vitro. Furthermore, transfection of Tpl‐2 into COS‐1 cells or Jurkat T cells. markedly activated the MAP kinases, ERK‐1 and SAP kinase (JNK), which are substrates for MEK‐1 and SEK‐1, respectively. Tpl‐2, therefore, is a MAP kinase kinase kinase which can activate two MAP kinase pathways. After Raf and Mos, Tpl‐2 is the third serine/threonine oncoprotein kinase that has been shown to function as a direct activator of MEK‐1.
Photoplethysmography sampling frequency: pilot assessment of how low can we go to analyze pulse rate variability with reliability?

Pulse rate variability (PRV) analysis appears as the first alternative to heart rate variability analysis for wearable devices; however, there is a constraint on computational load and energy consumption for the limited system resources available to the devices. Considering that adjustment of the sampling frequency is one of the strategies for reducing computational load and power consumption, this study aimed to investigate the influence of sampling frequency (fs) on PRV analysis and to find the minimum sampling frequency while maintaining reliability. We generated 5000, 2500, 1000, 500, 250, 100, 50, 25, 20, 15, 10, 5 Hz down-sampled photoplethysmograms from 10 kHz-sampled PPGs and derived time- and frequency-domain variables of the PRV. These included AVNN, SDNN, SDSD, RMSSD, NN50, pNN50, total power, VLF, LF, HF, LF/HF, nLF and nHF for each down-sampled signal. Derived variables were compared with heart rate variability of the 10 kHz-sampled electrocardiograms, and then statistically investigated using one-way ANOVA test and Bland–Altman analysis. As a result, significant differences (P < 0.05) were found for SDNN, SDSD, RMSSD, NN50, pNN50, TP, HF, LF/HF, nLF and nHF, but not for AVNN, VLF and LF. Based on the post hoc tests, it was found that the NN50 and pNN50, SDSD and RMSSD, LF/HF and nHF, SDNN, TP and nLF analysis had significant differences at fs ⩽ 20 Hz, fs ⩽ 15 Hz, fs ⩽10 Hz; fs = 5 Hz, respectively. In other words, a significant difference was not seen for any variable if the fs was greater than 25 Hz. Consequently, our pilot study suggests that analysis of variability in the time and frequency domain from pulse rate obtained through PPG may be potentially as reliable as that derived from the analysis of the electrocardiogram, provided that fs ⩾25 Hz sampling frequency is used.