Miracle-dz/UniFAR-FTUs huggingface dataset:
Farnesyl diphosphate synthase is involved in the resistance to zoledronic acid of osteosarcoma cells

We recently demonstrated original anti‐tumor effects of zoledronic acid (Zol) on osteosarcoma cell lines independently of their p53 and Rb status. The present study investigated the potential Zol‐resistance acquired by osteosarcoma cells after prolonged treatment. After 12 weeks of culture in the presence of 1 μm Zol, the effects of high doses of Zol (10–100 μm) were compared between the untreated rat (OSRGA, ROS) and human (MG63, SAOS2) osteosarcoma cells and Zol‐pretreated cells in terms of cell proliferation, cell cycle analysis, migration assay and cytoskeleton organization. Long‐term treatment with 1 μm Zol reduced the sensitivity of osteosarcoma cells to high concentrations of Zol. Furthermore, the Zol‐resistant cells were sensitive to conventional anti‐cancer agents demonstrating that this resistance process is independent of the multidrug resistance phenotype. However, as similar experiments performed in the presence of clodronate and pamidronate evidenced that this drug resistance was restricted to the nitrogen‐containing bisphosphonates, we then hypothesized that this resistance could be associated with a differential expression of farnesyl diphos‐phate synthase (FPPS) also observed in human osteosarcoma samples. The transfection of Zol‐resistant cells with FPPS siRNA strongly increased their sensitivity to Zol. This study demonstrates for the first time the induction of metabolic resistance after prolonged Zol treatment of osteosarcoma cells confirming the therapeutic potential of Zol for the treatment of bone malignant pathologies, but points out the importance of the treatment regimen may be important in terms of duration and dose to avoid the development of drug metabolic resistance.
Dynamic and Distributed Load Balancing Scheme in Multi-gateway Based 6LoWPAN

In 6LoWPAN, all the nodes access the Internet through the gateways, which are on the border to legacy IP networks and handle ingress and egress data traffic. A gateway as the traffic center may easily become the congestion-concentrated point so that causes reliability problems and performance degradation. Gateway bottleneck is the dominant reason for network capacity and throughput constriction, since all traffic should pass through the GW. Even though we apply multiple gateways, the network capacity and network throughput cannot increase linearly with the number of gateways because of the imbalance of traffic load among gateways. The load balancing between gateways is a key technology to reduce the traffic congestion thereby enlarging the network capacity, satisfying the capacity fairness among nodes, and removing network reliability issue. In this paper, we propose a dynamic and distributed load balancing scheme to achieve a global load fairness, motivated by water flow behavior, named MLEq (Multi-gateway Load Balancing Scheme for Equilibrium). We implement our load balancing scheme in ns-2 simulator and it is verified by extensive simulations. As a result, we show that throughput can be improved by the proposed scheme and the load can be fairly distributed over LoWPAN. More importantly, the results show that network capacity and throughput can increase linearly with the number of gateways.
Cold-restraint stress increases rat fecal pellet output and colonic transit.

Increased fecal pellet output that occurs during cold-restraint stress (CRS) was evaluated systematically. Free-feeding rats, which exhibit a reduced occurrence of gastric ulcers under these conditions, were studied. CRS significantly increased fecal pellet production and fluid content. However, the fecal output produced during CRS was not associated with increased gut secretory activity or somatic motor activity associated with cold restraint and did not occur in anesthetized animals. Cold and restraint stress were additive in producing increased fecal output. Significant dose-related decreases in fecal output were produced by drugs that decrease gut transit (i.e., B-HT 920, clonidine, Lomotil, loperamide, and lidamidine). Anticholinergic-antisecretory drugs, antidepressants, and tranquilizers had little effect on fecal output or fluid content. Changes in gastrointestinal transit did not contribute to the increased fecal output during CRS. Transit in the lower small intestine was not altered, but the cecum tended to empty more contents into the large intestine during CRS. Colonic transit was dramatically affected by CRS, which eliminated retrograde transit and produced the evacuation of the majority of colonic contents. The increased colonic transit produced by CRS was decreased in a dose-related fashion by hexamethonium, nifedipine, loperamide, and B-HT 920. In several time-response and drug-inhibition studies during CRS, both fecal pellet output and colonic transit were affected similarly. These data indicate that CRS appears to change central nervous system output to the colon and that it alters colonic smooth muscle motility in a manner that facilitates colonic transit and evacuation. Small intestinal transit is not involved in this phenomenon and is regulated differently during CRS.
Randomized controlled pilot study of an occupational time-use intervention for people with serious mental illness.

OBJECTIVE We assessed the efficacy and clinical utility of a new occupational time-use intervention, Action Over Inertia, designed to improve occupational balance and engagement among community-dwelling people with serious mental illness. METHOD Using a randomized controlled design, we assigned 24 participants to an intervention group or standard care group. Participants were community-dwelling people with serious mental illness receiving assertive community treatment services. Data on time use, occupational balance, and engagement were collected and compared at baseline and 12-wk posttest. RESULTS Eighteen participants completed the pilot study. Treatment group participants increased their occupational balance by spending an average of 47 min more per day in activity than the control group (p = .05). Differences in occupational engagement were not shown, but evidence of clinical utility was found. CONCLUSION This pilot study of Action Over Inertia has shown evidence of efficacy and clinical utility.
Regularity and convergence results in the calculus of variations on metric spaces

This dissertation studies regularity, convergence and stability properties for minimizers of variational integrals on metric measure spaces. The treatise consists of four articles in which the Moser iteration, Harnack’s inequality and Harnack’s convergence principle are considered in connection with quasiminimizers of the p-Dirichlet integral. In addition, we study a nonlinear eigenvalue problem in this setting. This is done in metric spaces equipped with a doubling measure and supporting a weak (1, p)-Poincaré inequality. AMS subject classifications (2000): 35J20, 35J60, 35P30, 49J27, 49J52, 49N60
Optimal Estimation and Detection in Homogeneous Spaces

This paper presents estimation and detection techniques in homogeneous spaces that are optimal under the squared error loss function. The data is collected on a manifold which forms a homogeneous space under the transitive action of a compact Lie group. Signal estimation problems are addressed by formulating Wiener-Hopf equations for homogeneous spaces. The coefficient functions of these equations are the signal correlations which are assumed to be known. The resulting coupled integral equations on the manifold are converted to Wiener-Hopf convolutional integral equations on the group. These are solved using the Peter-Weyl theory of Fourier transform on compact Lie groups. The computational complexity of this algorithm is reduced using the bi-invariance of the correlations with respect to a stabilizer subgroup. The theory of matched filtering for isotropic signal fields is developed for signal classification where given a set of template signals on the manifold and a noisy test signal, the objective is to optimally detect the template buried in the test signal. This is accomplished by designing a filter on the manifold that maximizes the signal-to-noise-ratio (SNR) of the filtered output. An expression for the SNR is obtained as a ratio of quadratic forms expressed as Haar integrals over the transformation group. These integrals are expressed in the Fourier domain as infinite sums over the irreducible representations. Simplification of these sums is achieved by invariance properties of the signal function and the noise correlation function. The Wiener filter and matched filter are developed for an abstract homogeneous space and then specialized to the case of spherical signals under the action of the rotation group. Applications of these algorithms to denoising of 3D surface data, visual navigation with omnidirectional camera and detection of compact embedded objects in the stochastic background are discussed with experimental results.
The relationship between individual differences in working memory and filtering task-irrelevant information, in children and adults

Kharitonova, Maria. (Ph.D., Psychology, Neuroscience, Department of Psychology & Neuroscience, University of Colorado at Boulder) The relationship between individual differences in working memory and filtering task-irrelevant information, in children and adults Dissertation directed by Professor Yuko Munakata We are constantly bombarded with myriad pieces of information, of which only a portion is directly relevant to our immediate experiences. What determines how much irrelevant information we filter, and how quickly we can adjust the amount of filtering? This dissertation explores the possibility that working memory (WM), an ability to actively maintain task-relevant information, plays a critical role in dynamically adjusting filtering strategy, based on task demands. High filtering could result from upregulating top-down control, leading to processing only the task-relevant information. Low filtering could result from loosening this control, to allow for a larger amount of information to be processed. This account was tested in three different experiments, with both adults and six-year-old children. Experiment 1 showed that high WM could support both high and low filtering, within the same adult participants. High WM was associated with high filtering in a paradigm where filtering task-irrelevant information was advantageous, because filtering the distractors reduced WM demand. In contrast, high WM was associated with low filtering in a task-switching paradigm, where low filtering was advantageous, because currently irrelevant features became relevant on subsequent switch trials. Experiment 2 modified the high-filtering-demand task of Experiment 1 to have both highand
Arabidopsis SEIPIN Proteins Modulate Triacylglycerol Accumulation and Influence Lipid Droplet Proliferation[OPEN]

SEIPIN isoforms participate in the storage of neutral lipids in plant cells by differentially modulating the number and size of cytosolic lipid droplets produced from the endoplasmic reticulum. The lipodystrophy protein SEIPIN is important for lipid droplet (LD) biogenesis in human and yeast cells. In contrast with the single SEIPIN genes in humans and yeast, there are three SEIPIN homologs in Arabidopsis thaliana, designated SEIPIN1, SEIPIN2, and SEIPIN3. Essentially nothing is known about the functions of SEIPIN homologs in plants. Here, a yeast (Saccharomyces cerevisiae) SEIPIN deletion mutant strain and a plant (Nicotiana benthamiana) transient expression system were used to test the ability of Arabidopsis SEIPINs to influence LD morphology. In both species, expression of SEIPIN1 promoted accumulation of large-sized lipid droplets, while expression of SEIPIN2 and especially SEIPIN3 promoted small LDs. Arabidopsis SEIPINs increased triacylglycerol levels and altered composition. In tobacco, endoplasmic reticulum (ER)-localized SEIPINs reorganized the normal, reticulated ER structure into discrete ER domains that colocalized with LDs. N-terminal deletions and swapping experiments of SEIPIN1 and 3 revealed that this region of SEIPIN determines LD size. Ectopic overexpression of SEIPIN1 in Arabidopsis resulted in increased numbers of large LDs in leaves, as well as in seeds, and increased seed oil content by up to 10% over wild-type seeds. By contrast, RNAi suppression of SEIPIN1 resulted in smaller seeds and, as a consequence, a reduction in the amount of oil per seed compared with the wild type. Overall, our results indicate that Arabidopsis SEIPINs are part of a conserved LD biogenesis machinery in eukaryotes and that in plants these proteins may have evolved specialized roles in the storage of neutral lipids by differentially modulating the number and sizes of lipid droplets.
Pulmonary Embolism and Intracardiac Type A Thrombus with an Unexpected Outcome

Detection of right heart thrombi (RHT) in the context of pulmonary thromboembolism (PE) is uncommon (4–18%) and increases the risk of mortality beyond the presence of PE alone. Type A thrombi are serpiginous and highly mobile and are thought to be originated from large veins and captured in-transit within the right heart. Optimal management of RHT is still uncertain. A 79-year-old woman, with a history of recent total hysterectomy with adnexectomy and a Wells procedure, presented to the emergency department following an episode of syncope. Computed tomography revealed bilateral PE and the presence of a right atrial thrombus. Transthoracic echocardiography demonstrated a free-floating type A thrombus in the right atrium, protruding into the right ventricle, and signs of pulmonary hypertension and right ventricle dysfunction. Considering the recent surgery and clinical stability, treatment with heparin alone was decided. Subsequent clinical improvement was observed and echocardiographic follow-up revealed complete thrombus dissolution and complete recovery of right ventricle function. Most authors recommend treatment of PE with RHT with thrombolysis or embolectomy followed by anticoagulation, although evidence is scarce. Individual risk of hemorrhage and operatory-related mortality should be taken into account when defining the treatment strategy especially when benefit is not firmly established.
Fluorescent Lead(IV) Sulfide Nanoparticles Synthesized by Idiomarina sp. Strain PR58-8 for Bioimaging Applications

ABSTRACT The fabrication of nanoparticles by microorganisms presents a “green” method for generating biocompatible nanomaterials. We discovered the intracellular biosynthesis of fluorescent lead(IV) sulfide nanoparticles by the moderate halophile, Idiomarina sp. strain PR58-8. The bacterium tolerated up to 8 mM Pb(NO3)2 during growth. Non-protein thiols dose-dependently increased in response to metal exposure, which suggests they are involved in the growth of PbS2 crystals and lead detoxification. Using X-ray diffraction, transmission electron microscopy (TEM), high-resolution TEM, and energy dispersive analysis of X-rays, the nanoparticles were characterized as spherical β-PbS2 nanoparticles (PbS2NPs) with a tetragonal crystal lattice, a crystallite domain size of 2.38 nm, and an interplanar distance of 0.318 nm. A narrow symmetric emission spectrum with a Gaussian distribution and an emission maximum at 386 nm was obtained when the particles were excited at 570 nm. The PbS2NPs exhibited a large Stokes' shift (8,362 cm−1) and a relatively high quantum yield (67%). These properties, along with fluorescence that was maintained in various microenvironments and their biocompatibility, make these nanoparticles excellent candidates for bioimaging. The particles were internalized by HeLa cells and evenly distributed within the cytoplasm, exhibiting their potential for in situ bioimaging applications. The “as-synthesized” lead(IV) sulfide nanoparticles may provide expanded opportunities for targeted bioimaging via modifying the surface of the particles. IMPORTANCE This article reports the intracellular synthesis of fluorescent lead(IV) sulfide nanoparticles (PbS2NPs) by a microorganism. All previous reports on the microbial synthesis of lead-based nanoparticles are on lead(II) sulfide that exhibits near-infrared fluorescence, requiring expensive instrumentation for bioimaging. Bioimaging using PbS2NPs can be achieved using routine epifluorescence microscopes, as it fluoresces in the visible range. The research on PbS2 nanoparticles to date is on their chemical synthesis employing toxic precursors, extreme pH, pressure, and temperature, resulting in cytotoxic products. In this context, the synthesis of PbS2 nanoparticles by Idiomarina sp. strain PR58-8, described in this work, occurs at ambient temperature and pressure and results in the generation of biocompatible nanoparticles with no hazardous by-products. The excellent fluorescence properties that these particles exhibit, as well as their abilities to easily penetrate the cells and evenly distribute within the cytoplasm, make them exceptional candidates for bioimaging applications. This study demonstrated the synthesis and fluorescence bioimaging application of microbially synthesized PbS2 nanoparticles.
A Systematic Examination of Gain- and Loss-Framed Content in Educational Resources Targeting the Prevention of Performance Enhancing Substance Use Among Athletes

The purpose of this study was to systematically identify educational health messages aimed at preventing doping among adolescent athletes to determine and evaluate the degree to which they include gain- and loss-framed content. We systematically searched for educational resources that targeted the prevention of performance-enhancing substance use and reviewed their content for framed messages. Our search yielded 60 resources with 88.40% non-framed and 11.37% loss-framed. The resources included almost no gain-framed content (0.23%) despite theoretical suggestions that gain-framed messages may be effective in this context. Our findings suggest a need to test gain-framed doping prevention messages as a means to enhance the efficacy of doping prevention initiatives.
Yeast and Human Frataxin Are Processed to Mature Form in Two Sequential Steps by the Mitochondrial Processing Peptidase*

Frataxin is a nuclear-encoded mitochondrial protein which is deficient in Friedreich’s ataxia, a hereditary neurodegenerative disease. Yeast mutants lacking the yeast frataxin homologue (Yfh1p) show iron accumulation in mitochondria and increased sensitivity to oxidative stress, suggesting that frataxin plays a critical role in mitochondrial iron homeostasis and free radical toxicity. Both Yfh1p and frataxin are synthesized as larger precursor molecules that, upon import into mitochondria, are subject to two proteolytic cleavages, yielding an intermediate and a mature size form. A recent study found that recombinant rat mitochondrial processing peptidase (MPP) cleaves the mouse frataxin precursor to the intermediate but not the mature form (Koutnikova, H., Campuzano, V., and Koenig, M. (1998) Hum. Mol. Gen. 7, 1485–1489), suggesting that a different peptidase might be required for production of mature size frataxin. However, in the present study we show that MPP is solely responsible for maturation of yeast and human frataxin. MPP first cleaves the precursor to intermediate form and subsequently converts the intermediate to mature size protein. In this way, MPP could influence frataxin function and indirectly affect mitochondrial iron homeostasis.
Sweat chloride is not a useful marker of clinical response to Ivacaftor

Clinical trials have revealed that Ivacaftor significantly reduces sweat chloride in patients with cystic fibrosis who carry the G551D mutation. This finding has been incorporated into the commissioning guidelines in the UK with a sweat chloride reduction of 30% or below 60 mmol/L, specified as the main criteria for continued funding of Ivacaftor for individual patients. In a cohort of 24 adults who were prescribed Ivacaftor, there was no correlation between absolute or relative reductions in sweat chloride and improvements in lung function. This questions the validity of sweat chloride as a surrogate marker of clinical efficacy.
The Pathogenesis of Auditory Verbal Hallucinations in Schizophrenia: A Clinical–Phenomenological Account

Abstract: Although hallucinations are among the most studied psychiatric symptoms, their pathogenesis remains largely unknown and their experiential complexities are rarely accounted for. In schizophrenia, auditory verbal hallucinations are by far the most frequently reported type of hallucination. In this study, we explore verbal hallucinations in schizophrenia and we argue that these are best understood not as abnormal perceptions, but as cognitive phenomena arising from a partial dissolution of certain structures of self-consciousness. Consistent with recent empirical and conceptual studies in phenomenological psychiatry, we claim that specific alterations of self-awareness tend to precede the emergence of verbal hallucinations in schizophrenia. We illustrate these altered states of self-awareness in three detailed case vignettes of hallucinating schizophrenia spectrum patients. We propose a clinical–phenomenological account of the pathogenesis of verbal hallucinations in schizophrenia, suggesting that pathological changes in the experience of space and morbid objectification of inner speech may lead to crystalized verbal hallucinations.
Endocrine Mucin-Producing Sweat Gland Carcinoma: Twelve New Cases Suggest That It Is a Precursor of Some Invasive Mucinous Carcinomas

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is an underrecognized low-grade carcinoma with predilection to the eyelid. Only 4 cases of this entity have been described in the literature. Here, we describe 12 cases of EMPSGC. The lesions were twice as frequent in females than males with an average age of 70 years (range, 48-84 years). Clinically, they presented as a slowly growing cyst or swelling. The most common site of occurrence was the lower eyelid (8 cases). Two lesions occurred on the upper eyelid and 2 on the cheek. Histologically, they were well-circumscribed, typically multinodular tumors with solid or partially cystic nodules, frequently showing areas of papillary architecture. Focal cribriform arrangements were also present. The nodules were formed by uniform small- to medium-sized oval to polygonal epithelial cells with lightly eosinophilic to bluish cytoplasm. The nuclei were bland with diffusely stippled chromatin and inconspicuous nucleoli. Intracytoplasmic and extracellular mucin was usually present. Mitotic activity was present but never brisk. All tumors examined immunohistochemically expressed at least one neuroendocrine marker, synaptophysin or chromogranin. CD57 and neuron specific enolase, secondary markers of neuroendocrine differentiation, were expressed in most cases. All tumors tested expressed estrogen and progesterone receptors, cytokeratin 7, low molecular cytokeratin Cam5.2, and epithelial membrane antigen and were negative for cytokeratin 20 and S-100 protein. Calponin, smooth muscle actin, and p63 immunohistochemical stains did not disclose myoepithelial cells around larger tumor nests in most cases, supporting the notion that EMPSGC is an invasive carcinoma. In 10 cases, cystic areas lined by benign epithelium indistinguishable from eccrine ducts were present. In some foci, the benign ductal epithelium was undermined or replaced by carcinoma in situ with similar cytologic features to the solid or papillary areas of EMPSGC. Myoepithelial cells were preserved in the areas of in situ carcinoma. In 6 cases, EMPSGC was associated with invasive mucinous carcinoma. In situ carcinoma and mucinous carcinoma also expressed neuroendocrine markers. Clinical follow-up showed no recurrences or metastases, consistent with low-grade carcinoma. The series provides histologic evidence for a multistage progression of noninvasive sweat gland neuroendocrine carcinoma to EMPSGC and then to mucinous carcinoma of the eyelid. Although the data from this series support the notion that the prognosis of EMPSGC and mucinous carcinoma is good, longer follow-up is needed for better understanding of their pathogenesis and clinical behavior.