Miracle-dz/UniFAR-FTUs huggingface dataset:
Endoplasmic Reticulum Quality Control and Pharmacological Chaperones

In cells, the quality of newly synthesized proteins is monitored with endoplasmic reticulum quality control (ERQC) in regard to proper folding and correct assembly in the early secretory pathway. Sequential checkpoints are distributed along the early secretory pathway, allowing efficiency and fidelity in protein secretion. Recently, ERQC has been mathematically modeled by breaking it into three subpathways; termed the Endoplasmic Reticulum Associated (ERA) Degradation (ERAD), ERA-Folding (ERAF) and ERA-Transport pathways. The major aim of ERQC is to assure that only properly folded and assembled proteins in the endoplasmic reticulum (ER) are transported for furher maturation and secretion. Disturbances in the ERQC have been linked with the pathophysiology of many human diseases; diabetes mellitus, alzheimer, parkinson, lysosomal storage diseases etc. Enzyme enhancement therapy, which uses pharmacological chaperones, is an emerging therapeutic approach that has the potential to treat many genetic diseases, associated with a mutant protein having difficulty in folding and/or assembling into active oligomers in the ER. This review focuses on the ERQC and its pathways, unfolded protein response in the ER, pharmacological chaperones and their action mechanisms.
Advances in oral delivery of anti-cancer prodrugs

ABSTRACT Introduction: Most anticancer drugs have poor aqueous solubility and low permeability across the gastrointestinal tract. Furthermore, extensive efflux by P-glycoproteins (P-gp) in the small intestine also limits the efficient delivery of anticancer drugs via oral route. Area covered: This review explores the prodrug strategy for oral delivery of anticancer drugs. Different categories of oral anticancer prodrugs along with recent clinical studies have been comprehensively reviewed here. Furthermore, novel anticancer prodrugs such as polymer-prodrugs and lipid-prodrugs have been discussed in detail. Finally, various nanocarrier-based approaches employed for oral delivery of anticancer prodrugs have also been discussed. Expert opinion: Premature degradation of anticancer prodrugs in the gastrointestinal tract could lead to variable pharmacokinetics and undesired toxicity. Despite their increased aqueous solubility, the oral bioavailability of several anticancer prodrugs are limited by their poor permeability across the gastrointestinal tract. These limitations can be overcome by the use of functional excipients (polymers, lipids, amino acids/dipeptides), which are specifically absorbed via transporters and receptor-mediated endocytosis. Oral delivery of anticancer prodrugs using nanocarrier-based drug delivery system is a recent development; however it should be justified based on the comparative advantages of encapsulating prodrug in a nanocarrier versus the use of anticancer prodrug molecule itself.
Modular multipulse voltage source inverters with integrating coupled reactors

A novel approach to the voltage source inverters (VSI) construction is presented in the paper. The invented inverter structures allow to operate several DC/AC converters in parallel resulting in lower voltage distortions at extremely low switching frequency. The research presented in the paper describes such a parallel operation of the VSI's which is possible thanks to the use of coupled inductors. The eighteen-pulse and twenty-four-pulse three-level converter was validated by the simulation and the prototype tests and the results of the examination are presented in the paper.
Mitochondrial Bound Hexokinase Activity as a Preventive Antioxidant Defense

Brain hexokinase is associated with the outer membrane of mitochondria, and its activity has been implicated in the regulation of ATP synthesis and apoptosis. Reactive oxygen species (ROS) are by-products of the electron transport chain in mitochondria. Here we show that the ADP produced by hexokinase activity in rat brain mitochondria (mt-hexokinase) controls both membrane potential (Δψm) and ROS generation. Exposing control mitochondria to glucose increased the rate of oxygen consumption and reduced the rate of hydrogen peroxide generation. Mitochondrial associated hexokinase activity also regulated Δψm, because glucose stabilized low Δψm values in state 3. Interestingly, the addition of glucose 6-phosphate significantly reduced the time of state 3 persistence, leading to an increase in the Δψm and in H2O2 generation. The glucose analogue 2-deoxyglucose completely impaired H2O2 formation in state 3-state 4 transition. In sharp contrast, the mt-hexokinase-depleted mitochondria were, in all the above mentioned experiments, insensitive to glucose addition, indicating that the mt-hexokinase activity is pivotal in the homeostasis of the physiological functions of mitochondria. When mt-hexokinase-depleted mitochondria were incubated with exogenous yeast hexokinase, which is not able to bind to mitochondria, the rate of H2O2 generation reached levels similar to those exhibited by control mitochondria only when an excess of 10-fold more enzyme activity was supplemented. Hyperglycemia induced in embryonic rat brain cortical neurons increased ROS production due to a rise in the intracellular glucose 6-phosphate levels, which were decreased by the inclusion of 2-deoxyglucose, N-acetyl cysteine, or carbonyl cyanide p-trifluoromethoxyphenylhydrazone. Taken together, the results presented here indicate for the first time that mt-hexokinase activity performed a key role as a preventive antioxidant against oxidative stress, reducing mitochondrial ROS generation through an ADP-recycling mechanism.
Prolactin and Deficient Luteal Function

The possibility of prolactin-dependent subfertility was investigated in a group of 8 women, with luteal insufficiency, exhibiting moderately elevated plasma prolactin (PRL) levels and/or galactorrhea. Another group of 10 normal women volunteers served as the control group. A “luteal index” was elaborated by integration of the area below the curve of plasma progesterone (P) values recorded throughout the postovulatory period. The calculated index for normal women was 177 ± 35 (SD) expressed as [(ng/ml) X time], and the value of 107 (—2 SD) was adopted as the lower limit of normality (97.5% confidence limit). All 8 patients had luteal indexes (range 20-105) below the established limit. Therapy with bromocriptine (CB 154), 5 mg/ day, suppressed PRL to normal levels and prolonged the poslovulatory hyperthermic phase in 6 out of 8 women. This was accompanied by an improvement in the luteal index, and 5 women conceived. It is concluded that prolactin may interfere with normal progesterone synthesis by the corpus lutcum, as demonstrated by the prompt restoration of fertility by bromocriptine treatment in women with regular cycles and inadequate luteal function.
Dimensions of buccal bone and mucosa at immediately placed implants after 7 years: a clinical and cone beam computed tomography study.

OBJECTIVE The objective of this study was to evaluate the dimensions of buccal bone and soft tissue at immediately placed implants over a 7-year period. MATERIAL AND METHODS Twenty-four patients, that participated in a clinical prospective study and received implants immediately placed into extraction socket, were enrolled for this study. Residual bone defects were grafted with xenogenic bone substitute and covered by means of collagen membrane. Baseline examination included measurements of full-mouth plaque and bleeding scores, width of keratinized mucosa, and dimensions of residual bone defects at the buccal aspect. Seven years after implant placement, full-mouth plaque score, full-mouth bleeding score, width of keratinized mucosa, and probing pocket depth were assessed and cone beam computed tomography images acquired. Dimensions of buccal bone and soft tissue were evaluated on the cross-sectional cone beam computed tomography reconstructions. Differences between two time-points were tested using the two-sided t-test. Correlation analysis was used to investigate the influence of baseline bone defect dimensions on the bone dimensions measured at the 7-year follow-up. RESULTS AND CONCLUSIONS Fourteen patients attended the follow-up examination. In five implants almost no buccal bone was detected, whereas in the remaining nine implants the buccal bone was found covering the rough implant surface. No correlation was found between initial bone defects and bone dimensions at the follow-up examination. The sites without radiographically detectable buccal bone at the 7-year control presented with 1 mm more apical mucosal level in comparison to implants with intact buccal bone.
Sex as Regulator of Triglyceride Metabolism in the Mosquito

The female mosquito, in contrast to the male mosquito or the male and female house fly, synthesizes triglycerides when maintained on glucose; after 7 days, the amount of triglycerides in the female may be 50 times that in the male. Polyunsaturated fatty acids are absent from the newly synthesized triglycerides.
Fumonisins in plant-origin food and fodder – a review

Fumonisins are mycotoxins produced by the Fusarium group of fungi commonly found on crops, mainly on maize. Some data suggest that as much as 25% of world crops may be lost because of mycotoxin contamination. Therefore, researchers in many countries (particularly in those in which relatively large amounts of maize are directly consumed by humans) are concerned with fumonisin levels in plant-origin foodstuffs and feeds available in their local markets. There is no doubt the levels are strongly correlated with the climate conditions prevailing in the region in which the maize was cultivated: the hotter the climate, the more serious the problem. Negative consequences of consumption of fumonisin-contaminated food by humans include an increased risk of oesophagus cancer and decreased body mass growth. In recent years some trials have been undertaken to reduce fumonisin levels in food and feed by the application of isothiocyanates naturally occurring in plants or peptidoglycans isolated from lactic acid bacteria (LAB). The results of these studies suggested that some reduction in contamination levels might be achieved. Additionally, some recent studies indicate that Sphingopyxis sp. bacteria produce enzymes that are able to break down the fumonisin molecule. Some fumonisins present in food may be bound/coupled with other compounds, and therefore difficult to detect. Such complexes in which the toxins are masked or hidden may even be at higher levels than the not-bound (free) molecules. The problem of how to evaluate effectively and efficiently the concentration of fumonisins in various foodstuffs is therefore a real-life challenge for scientists.
The same factors influence job turnover and long spells of sick leave--a 3-year follow-up of Swedish nurses.

BACKGROUND In many countries, a general shortage of nurses is a public health problem, and retention of nurses in active work is a challenge. The aim of this study was to ascertain whether the same individual factors, working conditions and health problems had led to increased probability of both leaving jobs and prolonged sickness absence in a cohort of Swedish nurses over a period of 3 years. METHODS A baseline questionnaire was answered by 2293 nurses, representing a response rate of 86%. Exposed and unexposed nurses were compared with regard to two outcomes. During the 3-year follow-up, exposed and unexposed nurses were compared with regard to two outcomes: resigning and having at least one sick leave spell that lasted 28 days or longer. RESULTS We found that 18% of the nurses left their employment, and 16% had sick leave spells > or =28 days. Work in geriatric care, being socially excluded by superiors and/or workmates, negative effects of organizational changes and poor self-rated general health were factors that increased the likelihood of both leaving jobs and long-term sick leave. CONCLUSIONS The present results underline the importance of improving working conditions and supporting sustainable health in order to prevent high turnover and prolonged sick leave among nurses. Resigning and moving to another institution can be interpreted as a way to actively cope with an unhealthy work environment.
Dopaminergic modulation of ganglion‐cell photoreceptors in rat

A novel class of photoreceptors, the intrinsically photosensitive retinal ganglion cells (ipRGCs), express the photopigment melanopsin and drive non‐image‐forming responses to light such as circadian photoentrainment, the pupillary light reflex and suppression of nocturnal melatonin production in the pineal. Because dendrites from one subclass of these cells – the M1‐type ipRGCs – make presumptive synaptic contacts at sites of dopamine release from dopaminergic amacrine cells, they are prime targets for modulation by dopamine, a neuromodulator implicated in retinal circadian rhythms and light adaptation. In patch‐clamp recordings from ipRGCs in intact rat retinas, dopamine attenuated the melanopsin‐based photocurrent. We confirmed that this was the result of direct action on ipRGCs by replicating the effect in dissociated ipRGCs that were isolated from influences of other retinal neurons. In these recordings, the D1‐family dopamine receptor agonist SKF38393 attenuated the photocurrent, caused a modest depolarization, and reduced the input resistance of ipRGCs. The D2‐family agonist quinpirole had no effect on the photocurrent. Single‐cell reverse‐transcriptase polymerase chain reaction revealed that the majority of ipRGCs tested expressed drd1a, the gene coding for the D1a dopamine receptor. This finding was supported by immunohistochemical localization of D1a receptor protein in melanopsin‐expressing ganglion cells. Finally, the adenylate cyclase activator forskolin, applied in combination with the phosphodiesterase inhibitor IBMX (isobutylmethylxanthine), mimicked the effects of SKF38393 on the ipRGC photocurrent, membrane potential and input resistance, consistent with a D1‐receptor signaling pathway. These data suggest that dopamine, acting via D1‐family receptors, alters the responses of ipRGCs and thus of non‐image‐forming vision.
Cerebellar LTD and Learning-Dependent Timing of Conditioned Eyelid Responses

Mammals can be trained to make a conditioned movement at a precise time, which is correlated to the interval between the conditioned stimulus and unconditioned stimulus during the learning. This learning-dependent timing has been shown to depend on an intact cerebellar cortex, but which cellular process is responsible for this form of learning remains to be demonstrated. Here, we show that protein kinase C–dependent long-term depression in Purkinje cells is necessary for learning-dependent timing of Pavlovian-conditioned eyeblink responses.
Mechatronic design and control of a critical biped robot joint

This article presents the mechanical design, hardware architecture and control scheme for critic joints in biped robots. A dynamic simulator was developed in order to quantify torque and currents motor requirements for different gait trajectories. The particular characteristics of biped robots has led to an important design effort in transmission systems, which is deeply discussed before presenting our choice. A specific electronic architecture has been proposed in order to provide the maximum accuracy in trajectory tracking for critic joints. Thus, an absolute encoder located at the output shaft will provide, through the CAN bus, the necessary information to properly correct the joint reference from the global stabilizer. A model-free approach and a Smith predictor on the loop are combined to deal with the transmission uncertainty and the network delays, respectively.
InSAR measurement of crustal deformation transients during the earthquake preparation processes : a review

Crustal deformation is one of the most important parameters used for the observation and modelling of the seismic cycle of strain accumulation and release. The improvements of satellite Earth observation data and methods over the last two decades, have provided a way to measure crustal movements with good accuracy and spatial coverage. In particular, multi-temporal Synthetic Aperture Radar (SAR) satellite data sets and SAR interferometric techniques have demonstrated the capacity to obtain information on the dynamics of the deformation occurring during the various phases of the seismic cycle. In the last few years a number of papers have reported the occurrence of crustal deformation transients in the inter-seismic and post-seismic periods, and have speculated on their significance in the earthquake preparation processes. The foreseen steady flow of high quality SAR data provided by new satellites as Sentinel-1 and ALOS-2 is going to provide new pieces of evidence of these elusive phenomena, stimulating further observational and analytical research. In this paper we review data, methods and applications, to give the reader a view of the advantages and the limits of InSAR measurements for the investigation of transient surface deformation patterns.
An Audit of Cushioned Diabetic Footwear: Relation to Patient Compliance

The recurrence rate of neuropathic foot ulcers is reported in 51 diabetic patients regularly attending a diabetic foot clinic. All of the patients were provided with protective footwear reducing peak plantar pressure at the forefoot area by 50% (versus normal shoes), and were followed up for up to 4 years. Compliance with this footwear was recorded by assessing the daily time of wearing protective or normal shoes, and compliance with foot care was recorded from the entries in the patients charts. The results of this observational study demonstrate that wearing protective shoes for > 60% of the daytime significantly (p = 0.0002) reduced the ulcer relapse rate by > 50% in comparison with shorter wearing times for these shoes. In addition, patients without ulcer relapses had foot care significantly more frequently than patients with relapse (p < 0.05). It is concluded that cushioned protective footwear in association with frequent foot care is essential in the prevention of neuropathic diabetic foot ulcer recurrence.
From darkness to daylight: cathemeral activity in primates

Summary – Within the primate order, Haplorrhini and Strepsirrhini are adapted to diurnal or nocturnal lifestyle. However, Malagasy lemurs exhibit a wide range of activity patterns, from almost completely nocturnal to almost completely diurnal, while others are active over the 24-hours. Cathemerality, the term minted by Tattersall (1987) to define the latter activity style, has been recorded in Eulemur and Hapalemur, as well as in some populations of the New World monkey Aotus. As most animals specialize in a particular phase of the 24hour cycle, the cathemeral strategy is expected to be the consequence of powerful pressures. We will review hypotheses and findings on ultimate reasons of primate cathemeral activity, present proximate factors shaping the activity cycle and discuss the possible roles of feeding competition, food shortage and dietary quality, thermoregulation, and predation in making this activity advantageous. Overall, we will see how unstable environments and various community characteristics would tend to select for a flexible activity phase. Most attempts to explain cathemerality have relied on adaptive explanations, which assume that this activity is stable and deep-rooted. In contrast, some researchers have suggested that cathemerality represents a non-adaptive transitional state between nocturnality and diurnality. Chronobiology studies indicate that cathemeral species should be considered as dark active primates, thus favouring a recent origin. On the other hand, anatomical analyses demonstrate that the eye of cathemeral primates is a good compromise between the functional demands of vision under both nocturnal and diurnal conditions, thus suggesting an ancient origin. On the basis of recent phylogenetic trees we will discuss different scenarios for the evolution of cathemerality and diurnality in lemurs. Furthermore, we will evaluate the hypothesis that early primate ancestors may have needed to see well both in the daytime and at night, before becoming specialized in one direction. Finally, we will consider some interdisciplinary implications of the study of a day-night activity in primates.
Docetaxel in the treatment of breast cancer: current experience and future prospects

It has become clear over the past 10 years that docetaxel, a semisynthetic taxoid antineoplastic agent, is among the most promising compounds to have been developed in the 1990s for the treatment of breast cancer. Data indicate that this drug became standard therapy in the treatment of patients with metastatic disease who have failed anthracycline treatment, and secondarily showed very encouraging results in the first-line metastatic setting either in monochemotherapy or when docetaxel was combined with an anthracycline. More recently, docetaxel also became one of the standard therapies in the adjuvant and neoadjuvant settings, and a promising partner for novel biologic therapies. Current research is further exploring the effect of docetaxel on outcome of early breast cancer in order to fully determine the extent that this chemotherapeutic agent will change the natural history of breast cancer.
Coupling coefficient identification for maximum power transfer in WPT system via impedance matching

Maximum power transfer is a significant issue in wireless power transfer system, the common used method is impedance matching to track the optimal impedance point by using a power electronic converter. However, in a practical WPT system, the coupling coefficient will drift from the designed value due to the air gap, receiver structure and other environmental influence. As a result, the optimal impedance will drift from the designed value accordingly. This paper proposes a coupling coefficient identification and impedance matching method for maximum power transfer tracking. The method can identify the coupling coefficient and the load, and realize the impedance matching through changing the duty cycle of the Buck converter. The correctness of the proposed method has been proved by both the simulation and the experiment results.
Removal of Endotracheal Tube Obstruction With a Secretion Clearance Device

Accumulation of secretions may suddenly occlude an endotracheal tube (ETT), requiring immediate medical attention. The endOclear catheter (Endoclear LLC, Petoskey, Michigan) is a novel device designed to clear mucus and debris from an ETT and restore luminal patency. We present 3 subsequent cases of life-threatening partial ETT occlusions recorded over a period of 6 months at Massachusetts General Hospital. After conventional methods (standard tracheal suctioning and bronchoscopy) failed, the endOclear was used, with successful restoration of the airways in all 3 cases. The respiratory conditions rapidly improved, and all 3 patients tolerated the ETT-cleaning maneuver. These results show that such a device is safe and easy to use during an emergency airway situation for efficient and rapid removal of secretions from obstructed ETTs by respiratory therapists.
Performance Investigation of LCL Filters in Grid Connected Converters

The use of dispersed or distributed resources (DR) is rapidly increasing in modern distribution networks because of their potential advantages. As many types of these resources generate electrical energy in the form of DC voltage source, they need a DC/AC converter for energy transfer to the grid. Static converters are usually connected to the utility grid through a simple L filter to reduce the injected current harmonics. However, LCL filters can provide better harmonic attenuation and reduce the filter size at the same time. This paper is concerned with the subject of grid connected converters using LCL filter topology. Basic expressions related to LCL filters are derived and compared to that of L filter. Design criteria with respect to filter size, ripple current and resonance frequency are addressed. The control strategy is briefly described and it is shown that how the system can be stabilized by proper state plus output feedback