Miracle-dz/UniFAR-FTUs huggingface dataset:
PEGylated nanomedicines: recent progress and remaining concerns

Introduction: Recent biopharma deals related to nanocarrier drug delivery technologies highlight the emergence of nanomedicine. This is perhaps an expected culmination of many years of research demonstrating the potential of nanomedicine as the next generation of therapeutics with improved performance. PEGylated nanocarriers play a key role within this field. Areas covered: The drug delivery advantages of nanomedicines in general are discussed, focusing on nanocarriers and PEGylated nanomedicines, including products under current development/clinical evaluation. Well-established drug delivery benefits of PEGylation (e.g., prolonged circulation) are only briefly covered. Instead, attention is deliberately made to less commonly reported advantages of PEGylation, including mucosal delivery of nanomedicines. Finally, some of the issues related to the safety of PEGylated nanomedicines in clinical application are discussed. Expert opinion: The advent of nanomedicine providing therapeutic options of refined performance continues. Although PEGylation as a tool to improve the pharmacokinetics of nanomedicines is well established and is used clinically, other benefits of ‘PEGnology', including enhancement of physicochemical properties and/or biocompatibility of actives and/or drug carriers, as well as mucosal delivery, have attracted less attention. While concerns regarding the clinical use of PEGylated nanomedicines remain, evidence suggests that at least some safety issues may be controlled by adequate designs of nanosystems.
Temporal-frequency selectivity in monkey visual cortex

Abstract We investigated the dynamics of neurons in the striate cortex (V1) and the lateral geniculate nucleus (LGN) to study the transformation in temporal-frequency tuning between the LGN and V1. Furthermore, we compared the temporal-frequency tuning of simple with that of complex cells and direction-selective cells with nondirection-selective cells, in order to determine whether there are significant differences in temporal-frequency tuning among distinct functional classes of cells within V1. In addition, we compared the cells in the primary input layers of V1 (4a, 4cα, and 4cβ) with cells in the layers that are predominantly second and higher order (2, 3, 4b, 5, and 6). We measured temporal-frequency responses to drifting sinusoidal gratings. For LGN neurons and simple cells, we used the amplitude and phase of the fundamental response. For complex cells, the elevation of impulse rate (F0) to a drifting grating was the response measure. There is significant low-pass filtering between the LGN and the input layers of V1 accompanied by a small, 3-ms increase in visual delay. There is further low-pass filtering between V1 input layers and the second- and higher-order neurons in V1. This results in an average decrease in high cutoff temporal-frequency between the LGN and V1 output layers of about 20 Hz and an increase in average visual latency of about 12–14 ms. One of the most salient results is the increased diversity of the dynamic properties seen in V1 when compared to the cells of the lateral geniculate, possibly reflecting specialization of function among cells in V1. Simple and complex cells had distributions of temporal-frequency tuning properties that were similar to each other. Direction-selective and nondirection-selective cells had similar preferred and high cutoff temporal frequencies, but direction-selective cells were almost exclusively band-pass while nondirection-selective cells distributed equally between band-pass and low-pass categories. Integration time, a measure of visual delay, was about 10 ms longer for V1 than LGN. In V1 there was a relatively broad distribution of integration times from 40–80 ms for simple cells and 60–100 ms for complex cells while in the LGN the distribution was narrower.
Hormone-sensitive lipase in skeletal muscle: regulatory mechanisms.

AIM The enzymatic regulation of intramuscular triacylglycerol (TG) breakdown has until recently not been well understood. Our aim was to elucidate the role of hormone-sensitive lipase (HSL), which controls TG breakdown in adipose tissue. METHODS Isolated rat muscle as well as exercising humans were studied. RESULTS The presence of HSL was demonstrated in all muscle fibre types by Western blotting of muscle fibres isolated by collagenase treatment or after freeze-drying. The content of HSL varies between fibre types, being higher in oxidative than in glycolytic fibres. Analysed under conditions optimal for HSL, neutral lipase activity in muscle can be stimulated by adrenaline as well as by contractions. These increases are abolished by presence of anti-HSL antibody during analysis. Moreover, immunoprecipitation with affinity-purified anti-HSL antibody causes similar reductions in muscle HSL protein concentration and in measured neutral lipase responses to contractions. The immunoreactive HSL in muscle is stimulated by adrenaline via beta-adrenergic activation of protein kinase A (PKA). From findings in adipocytes it is likely that PKA phosphorylates HSL at residues Ser563, Ser659 and Ser660. Contraction probably also enhances muscle-HSL activity by phosphorylation, because the contraction-induced increase in HSL activity is increased by the protein phosphatase inhibitor okadaic acid and reversed by alkaline phosphatase. A novel signalling pathway in muscle by which HSL activity may be stimulated by protein kinase C (PKC) via extracellular signal regulated kinase (ERK) has been demonstrated. In contrast to previous findings in adipocytes, in muscle activation of ERK is not necessary for stimulation of HSL by adrenaline. However, contraction-induced HSL activation is mediated by PKC, at least partly via the ERK pathway. In fat cells ERK is known to phosphorylate HSL at Ser600. So, phosphorylation of different sites may explain that in muscle the effects of contractions and adrenaline on HSL activity are partially additive. In line with the view that the two stimuli act by different mechanisms, training increases the contraction-mediated, but diminishes the adrenaline mediated HSL activation in muscle. CONCLUSION The existence and regulation of HSL in skeletal muscle indicate a role of HSL in muscle TG metabolism.
CCAAT/Enhancer Binding Protein α Is a Regulatory Switch Sufficient for Induction of Granulocytic Development from Bipotential Myeloid Progenitors

ABSTRACT The transcription factor CCAAT/enhancer binding protein α (C/EBPα) regulates a number of myeloid cell-specific genes. To delineate the role of C/EBPα in human granulopoiesis, we studied its expression and function in human primary cells and bipotential (granulocytic/monocytic) myeloid cell lines. We show that the expression of C/EBPα initiates with the commitment of multipotential precursors to the myeloid lineage, is specifically upregulated during granulocytic differentiation, and is rapidly downregulated during the alternative monocytic pathway. Conditional expression of C/EBPα alone in stably transfected bipotential cells triggers neutrophilic differentiation, concomitant with upregulation of the granulocyte-specific granulocyte colony-stimulating factor receptor and secondary granule protein genes. Moreover, induced expression of C/EBPα in bipotential precursors blocks their monocytic differentiation program. These results indicate that C/EBPα serves as a myeloid differentiation switch acting on bipotential precursors and directing them to mature to granulocytes.
Children's sleep and autonomic function: low sleep quality has an impact on heart rate variability.

OBJECTIVES Short sleep duration and poor sleep quality in children have been associated with concentration, problem behavior, and emotional instability, but recently also with disrupted autonomic nervous function, which predicts cardiovascular health. Heart rate variability (HRV) was used as noninvasive indicator of autonomic function to examine the influence of sleep. DESIGN Cross-sectional and longitudinal observational study on the effect of sleep on HRV. PARTICIPANTS Belgian children (5-11 years) of the ChiBS study in 2010 (N = 334) and 2011 (N = 293). INTERVENTIONS N/A. METHODS Sleep duration was reported and in a subgroup sleep quality (efficiency, latency, awakenings) was measured with accelerometry. High-frequency (HF) power and autonomic balance (LF/HF) were calculated on supine 5-minute HRV measurements. Stress was measured by emotion and problem behavior questionnaires. Sleep duration and quality were used as HRV predictors in corrected cross-sectional and longitudinal regressions. Stress was tested as mediator (intermediate pathway) or moderator (interaction) in sleep-HRV associations. RESULTS In both cross-sectional and longitudinal analyses, long sleep latency could predict lower HF (parasympathetic activity), while nocturnal awakenings, sleep latency, low sleep efficiency, and low corrected sleep duration were related to higher LF/HF (sympathetic/parasympathetic balance). Parental reported sleep duration was not associated with HRV. The significances remained after correction for stress. Stress was not a mediator, but a moderator (enhancer) in the relationship between sleep quality and HRV. CONCLUSIONS Low sleep quality but not parent-reported low sleep duration leads to an unhealthier heart rate variability pattern (sympathetic over parasympathetic dominance). This stresses the importance of good sleep quality for cardiovascular health in children.
The origin of bone that forms in association with cancellous chips transplanted into muscle.

Summary New bone forms in association with autogenous cancellous bone chips transplanted into muscle. It could be argued that this new bone develops from local connective tissue cells as a result of metaplasia induced by chemical substances inherent in the chips and hence that the formation of new bone around chips does not prove that the covering osteogenic cells and osteoblasts of the chips survive the transplantation. In an attempt to ascertain whether the new bone that commonly forms around cancellous chips transplanted into muscle arises from local connective tissue cells as a result of metaplasia or from the covering cells of the chips, both untreated autogenous cancellous chips and thrice-frozen-and-thawed cancellous chips were transplanted into the muscles of five dogs. It was believed that although the thrice-freezing-and-thawing procedure would kill all the cells in and associated with the chips, it would not materially alter the chemical composition of possible bone-inducing substances contained in the chips. In none of five dogs did new bone form in association with the thrice-frozen-and-thawed chips. In all of five dogs new bone formed in association with the untreated chips. It is concluded that such bone as commonly forms around untreated autogenous cancellous chips that are transplanted into muscle arises from such covering cells of the chips, or undifferentiated marrow cells associated with them, as survive transplantation. The implications of the foregoing conclusions with regard to the use of bone chips of various kinds in attempts to set up new centres of osteogenesis in bone defects are discussed.
Ultrasonic image formation: implications for the image processing practitioner

This paper provides an overview of how ultrasound images are acquired and processed in typical commercial equipment, with emphasis on implications for image processing. We begin with a brief discussion of relevant acoustic theory, concentrating on bulk interaction of acoustic waves with tissue. We then discuss different transducer designs and their implications for image quality. Transmit and receive beam formation is discussed, including-the effects of transmit focus, receive focus, and time-multiplex techniques. Typical signal processing techniques used on the beamformed signal are discussed, along with the effect of operator controls. With this system description in hand, we conclude by examining overall clinical image duality. Typical image artifacts, including sidelobes, grating lobes, reverberation, range ambiguity, speckle, shadowing, and dropout are discussed. <<ETX>>
Sex-related differences in outcome after high-risk vascular surgery after the administration of beta-adrenergic-blocking drugs.

BACKGROUND Beta-adrenergic-blocking medications may have a cardioprotective effect after high-risk vascular surgery. This effect has been shown primarily in men and has not been independently shown in women. METHODS Retrospective data were collected from vascular surgery (primarily infrainguinal) patients. Adverse outcome was defined as myocardial infarction, new-onset congestive heart failure (CHF), significant arrhythmia, renal failure, or death. The incidence of adverse outcomes was compared independently for both men and women based on the administration of perioperative beta-blockade. Analysis was performed for the whole population and for the subset of patients who were not on preoperative beta-blockers (beta-blocker naïve). Risk-stratified analysis was used to determine which group received any effect from beta-blockade. Logistic regression was performed to determine the independent effect of perioperative beta-blockade in both sexes. RESULTS There were 594 men and 366 women. The incidence of adverse outcomes was lower when beta-blockers were administered in men (12.6% v 18.9%, p = 0.04) but not in women (17.8% v 13.7%, p = 0.37). Among beta-blocker-naïve subjects, men had significant reductions in myocardial infarction and renal failure, whereas women did not have a reduction in the incidence of any outcome. After risk-stratification, the high-risk women who received beta-blockade had a statistically worse outcome (36.8% v 5.9%, p = 0.02) because of an increased incidence of CHF. By logistic regression, beta-blockade improved outcomes in men but not women. CONCLUSION In this retrospective analysis, women did not benefit from perioperative beta-blockade. Women at high risk appeared to have a worse outcome because of a higher incidence of CHF.
Image Restoration with Multiple Directional Transforms

This thesis deals with the application of multiple directional transforms to image restoration, and discusses two cases of image restoration, image denoising and image fusion. In Chapter 1, the background of image restoration is described. First, image denoising problems are addressed. Image denoising is a principal problem of image processing and the purpose is to obtain an original picture as an ideal one. For photon acquisition systems, low-light image denoising is becoming in use in optical imaging applications such as astronomical imaging, fluorescence microscopy appliances, magnetic resonance imaging. In this case, the noises are strongly dependent on the signals and approximately obeys Poisson distribution, which leads difficulties in denoising process. The denoising problem for Poisson noise can be modeled by a modular fashion through variance stabilization. Using the variance stabilization, denoising techniques for additive Gaussian noises become available for Poisson denoising. This chapter summarizes some of such existing methods. Next, image fusion problems are dealt with. Image fusion is a technique to synthesize a full focused picture, in which all the contents are focused, from a set of partially focused images with different focal lengths. At present, there are several types of image fusion techniques. Those include spatial domain, feature space and transform domain techniques. In the spatial domain and feature space approaches, the synthesis performance heavily depends on the adopted segmentation algorithm, and they prone to fail fusion at object edges, while the transform domain approach is influenced by the adopted transform. In order to improve the quality of fused image, some disadvantages of existing methods are discussed in this chapter. This chapter mentions the possibility of improving the performance of Poisson denoising and image fusion from viewpoints different form existing researches. In Chapter 2, from comparison with Discrete Cosine Transform (DCT) and Discrete Wavelet Transform (DWT), the features of directional lapped orthogonal transforms (DirLOTs) are discussed and emphasized For preparation of Chapter 3 and later, explanations on DirLOTs are given through some figures and expressions. Based on the relationship between directivity of DirLOT and slant edge and texture of image, the possibility of the performance improvement of image restoration is described. In Chapter 3, a Poisson denoising method is proposed. Various discrete wavelet transforms have been used for Poisson image denoising. However, the transforms have disadvantages such as shift variance, aliasing, and lack of directional selectivity. PURE-LET is known as an efficient Poisson denoising
How constant is the Fermi coupling constant?

We discuss various astrophysical limits on the spatial and time variation of the Fermi coupling constant [ital G][sub [ital F]]. We consider two cases: (a) [ital G][sub [ital F]] and the fermion masses vary through a change in the vacuum expectation value of the Higgs field; (b) [ital G][sub [ital F]] varies while the fermion masses are held constant. In the former case, redshift measurements probe both the spatial and time variation of [ital G][sub [ital F]] through changes in the electron mass: the agreement between measurements of hyperfine and optical lines in distant galaxies and quasars indicates that [ital G][sub [ital F]] varies by less than 0.04% on cosmological length scales. Such measurements also show that [ital G][sub [ital F]] varies by less than 0.2% back to a redshift of [ital z]=3.4. If [ital G][sub [ital F]] varies without any change in the fermion masses, the best constraints on spatial variations in [ital G][sub [ital F]] come from supernova light curves, whose slopes depend upon the lifetime of [sup 56]Co. The similarities between light curves argue that the Fermi coupling constant [ital G][sub [ital F]] varies by less than 5% on cosmological scales. Big bang nucleosynthesis indicates that themore » Fermi coupling constant at [ital t][similar to]1 sec differed by less than [similar to]10--20 % from the contemporary terrestrial value, with the exact limits depending on which model we choose for the variation in [ital G][sub [ital F]]. Variation in [ital G][sub [ital F]] would allow big bang nucleosynthesis to produce a lower [sup 4]He abundance without changing significantly any of the other element abundances. « less
Effect of cytokine treatment (granulocyte colony-stimulating factor and stem cell factor) on hematopoiesis and the circulating pool of hematopoietic stem cells in mice.

The mobilization of hematopoietic stem cells (HSCs) into the peripheral blood of mice was induced by recombinant human granulocyte colony-stimulating factor (rhG-CSF) (250 microgram/kg/d) alone or combined with recombinant rat stem cell factor (rrSCF) (34 microgram/kg/d), injected subcutaneously (s.c.) once a day for 10 and 17 days. After administering G-CSF plus SCF or G-CSF alone for 10 days, the level of day-11 spleen colony-forming units (CFU-S-11) in the peripheral blood increased 169- and 93-fold, respectively. The effect was lower--30- and 17-fold--after 17 days of treatment. A 1.5- to three-fold decrease in CFU-S-11 content in the bone marrow of treated mice was observed. In normal mice, the content of long-term culture initiating cells (LTC-IC) in blood was below the threshold level. Cytokine treatment mobilized LTC-IC in the circulation. Following a 10- and 17-day course of G-CSF plus SCF, the proliferation of CFU-S-11 in the peripheral blood but not in the bone marrow increased from <10% in the controls to 44 and 72%, respectively, as measured by hydroxyurea (HU) suicide. Spleen-repopulating ability (SRA) of CFU-S (daughter CFU-S-8 content in an 11-day-old spleen colony) increased two-fold in the peripheral blood after a 10-day course and seven-fold after a 17-day course of combined cytokines. One month after the final cytokine injection, all hematopoietic indexes (including the number of different precursors, their proliferative rate, and their SRA) were near normal. The results suggest that the age structure of the mobilized progenitor population depends on both the cytokines used and the duration of the treatment: more immature CFU-S with higher proliferative activity and an increased SRA were mobilized preferentially after a 17-day course of combined cytokines.
Mmf1p, a Novel Yeast Mitochondrial Protein Conserved throughout Evolution and Involved in Maintenance of the Mitochondrial Genome

ABSTRACT A novel protein family (p14.5, or YERO57c/YJGFc) highly conserved throughout evolution has recently been identified. The biological role of these proteins is not yet well characterized. Two members of the p14.5 family are present in the yeast Saccharomyces cerevisiae. In this study, we have characterized some of the biological functions of the two yeast proteins. Mmf1p is a mitochondrial matrix factor, and homologous Mmf1p factor (Hmf1p) copurifies with the soluble cytoplasmic fraction. Δmmf1cells lose mitochondrial DNA (mtDNA) and have a decreased growth rate, while Δhmf1 cells do not display any visible phenotype. Furthermore, we demonstrate by genetic analysis that Mmf1p does not play a direct role in replication and segregation of the mtDNA. rho+ Δmmf1 haploid cells can be obtained when tetrads are directly dissected on medium containing a nonfermentable carbon source. Our data also indicate that Mmf1p and Hmf1p have similar biological functions in different subcellular compartments. Hmf1p, when fused with the Mmf1p leader peptide, is transported into mitochondria and is able to functionally replace Mmf1p. Moreover, we show that homologous mammalian proteins are functionally related to Mmf1p. Human p14.5 localizes in yeast mitochondria and rescues the Δmmf1-associated phenotypes. In addition, fractionation of rat liver mitochondria showed that rat p14.5, like Mmf1p, is a soluble protein of the matrix. Our study identifies a biological function for Mmf1p and furthermore indicates that this function is conserved between members of the p14.5 family.
Dynamic Overload Capability of VSC HVDC Interconnections for Frequency Support

In future power systems, reduced overall inertia caused by an increased dominance of asynchronous generation and interconnections would make frequency control particularly challenging. As the number and power rating of voltage source converter (VSC) HVDC systems increases, network service provision would be expected from such systems and to do so would require overload capacity to be included in the converter specifications. This paper studies the provision of frequency services from modular multilevel converter (MMC)-based VSC HVDC interconnections using temperature-constrained overload capability. Overload of the MMC-based HVDC system is achieved through controlled circulating currents, at the expense of higher losses, and subject to a control scheme that dynamically limits the overload available in order to keep the semiconductor junction temperatures within operational limits. Two frequency control schemes that use the obtained overload capacity to provide frequency response during emergency conditions are investigated. The controllers’ performance is demonstrated in the context of the future Great Britain transmission grid through a reduced equivalent test system. Simulation results show that even modest temperature margins which allow overload of MMC-based HVDC systems for a few seconds are effective as a primary frequency reserve and also reduce the loss of infeed requirements of such interconnections.