Miracle-dz/UniFAR-FTUs huggingface dataset:
A New Perspective for Osteosarcoma Therapy: Proteasome Inhibition by MLN9708/2238 Successfully Induces Apoptosis and Cell Cycle Arrest and Attenuates the Invasion Ability of Osteosarcoma Cells in Vitro

Background: The proteasome exists in all eukaryotic cells and provides the main route of intracellular proteins degradation involved in cell growth and apoptosis. Proteasome inhibition could block protein degradation pathways and disturb regulatory networks, possibly leading to profound effects on cell growth, particularly in cancer cells. A proteasome inhibitor with an appropriate toxicity index for malignant cells rather than normal cells would be an attractive anticancer therapy. Methods: The human osteosarcoma (OS) cell lines MG-63 and Saos-2 and normal osteoblast cells were used to study the antitumour activity of the proteasome inhibitor MLN9708/2238. Results: MLN2238 inhibited cell growth, induced cell cycle arrest and apoptosis, and attenuated the invasion abilities of MG-63 and Saos-2 cells, with little cytotoxicity to normal cells. In addition, MLN2238 promoted antitumour mechanisms including the accumulation of E2F1, P53, P21 and other negative G2/M checkpoint proteins; up-regulated the relative expression ratio of BAX/BCL-2, APAF-1 and pro-apoptotic proteins of the BCL-2 family; triggered mitochondrial outer membrane permeabilization (MOMP); down-regulated BCL-2 and XIAP; activated caspase3/8/9; and suppressed MMP2/9 expression and secretion levels. Conclusions: The proteasome may be a novel biochemical target for OS treatment in vitro. Our study provides a promising mechanistic framework for MLN9708/2238 in OS treatment, supporting its clinical development.
Avascular necrosis of bone after allogeneic bone marrow transplantation: analysis of risk factors for 4388 patients by the Société Française de Greffe de Moëlle (SFGM)

Increasing numbers of patients are surviving after allogeneic bone marrow transplantation and are therefore at risk for developing late complications. Among these complications, avascular necrosis of bone has been reported, but only two single‐centre studies included sufficient patients to enable analysis of the risk factors for developing avascular necrosis. In this multicentre retrospective study the aim was to assess risk factors for this complication in a large number of patients.
Auditory streaming and the building of timbre.

In a natural environment, the auditory system must analyse an incoming wave train to determine two things: (a) which series of frequency components arose over time from the same source and should be integrated into a sequential stream, and (b) which set of simultaneous components arose from one source and should be fused into a timbre structure. A set of experiments was performed in which subject judged the stream organization and the timbre of a repeating cycle formed by a pair of more or less synchronous pure tones, B and C, and a preceding pure tone, A, whose frequency was varied in its proximity to that of the upper tone of the BC pair. These experiments demonstrated that fusion and sequential organization of streams are carried out using two sorts of information which compete to determine the best perceptual description of the input. Proximal frequencies between sequential components promotes a sequential organization and the simultaneity of onset of frequency components promotes perceptual fusion.
Differential gene expression profiles between two subtypes of ischemic stroke with blood stasis syndromes

Ischemic stroke is a cerebrovascular thrombotic disease with high morbidity and mortality. Qi deficiency blood stasis (QDBS) and Yin deficiency blood stasis (YDBS) are the two major subtypes of ischemic stroke according to the theories of traditional Chinese medicine. This study was conducted to distinguish these two syndromes at transcriptomics level and explore the underlying mechanisms. Male rats were randomly divided into three groups: sham group, QDBS/MCAO group and YDBS/MCAO group. Morphological changes were assessed after 24 h of reperfusion. Microarray analysis with circulating mRNA was then performed to identify differential gene expression profile, gene ontology and pathway enrichment analyses were carried out to predict the gene function, gene co-expression and pathway networks were constructed to identify the hub biomarkers, which were further validated by western blotting and Tunel staining analysis. Three subsets of dysregulated genes were acquired, including 445 QDBS-specific genes, 490 YDBS-specific genes and 1676 blood stasis common genes. Our work reveals for the first time that T cell receptor, MAPK and apoptosis pathway were identified as the hub pathways based on the pathway networks, while Nfκb1, Egfr and Casp3 were recognized as the hub genes by co-expression networks. This research helps contribute to a clearer understanding of the pathological characteristics of ischemic stroke with QDBS and YDBS syndrome, the proposed biomarkers might provide insight into the accurate diagnose and proper treatment for ischemic stroke with blood stasis syndrome.
A Novel Maximum Power Point Tracking Technique for Photovoltaic Module Based on Power Plane Analysis of $I$– $V$ Characteristics

A new method of tracking the maximum power point (MPP) of a photovoltaic (PV) module is presented in this paper, which exploits the effects of the inherent characteristic resistances of the PV cells. An analysis of the iv characteristics of the PV module in the iv plane revealed a possibility of predicting the MPP by finding the maximum possible power rectangle within the iv characteristic. The maximum possible power rectangle has been determined by a background online sweeping technique in the power region of the iv characteristic without disturbing the PV module. The power region in the iv characteristic can be determined by the effects of the characteristic resistances of the PV module. The results obtained through simulations and experiments have validated the proposed technique. The effectiveness of the proposed method has closely matched with the true MPP, and the successful experimental results obtained with a 100-Wp PV module indicate that the technique can be favorably implemented for stand-alone PV power systems.
Target tracking in state dependent wake clutter

Tracking methods attempt to follow the movement of a target of interest while suppressing irrelevant clutter. A particularly troublesome source of clutter is wakes that appear behind the target. This problem arises in sonar tracking of human divers, in the tracking of boats using surveillance radars, and also in radar tracking of ballistic missiles. Previous research has integrated a solution to this problem in the popular Probabilistic Data Association filter (PDAF).
Feasibility and Outcome of Descemet Membrane Endothelial Keratoplasty in Complex Anterior Segment and Vitreous Disease

Purpose: Descemet membrane endothelial keratoplasty (DMEK) is becoming the method of choice for treating Fuchs endothelial dystrophy and pseudophakic bullous keratopathy. We investigated whether DMEK can serve as a routine procedure in endothelial decompensation even in complex preoperative situations. Methods: Of a total of 1184 DMEK surgeries, 24 consecutive eyes with endothelial decompensation and complex preoperative situations were retrospectively analyzed and divided into 5 groups: group 1: irido-corneo-endothelial syndrome (n = 3), group 2: aphakia, subluxated posterior chamber intraocular lens or anterior chamber intraocular lens (n = 6), group 3: DMEK after trabeculectomy (n = 4), group 4: DMEK with simultaneous intravitreal injection (n = 6), and group 5: DMEK after vitrectomy (n = 5). Main outcome parameters were best-corrected visual acuity, central corneal thickness, endothelial cell density, rebubbling rate, and graft failure rate. Results: Best-corrected visual acuity (logMAR) increased from 0.98 to 0.53 (P = 0.002), 0.53 (P = 0.091), and 0.57 (P = 0.203) after 1, 3, and 6 months, respectively. Central corneal thickness decreased from 731 ± 170 to 546 ± 152 &mgr;m (P = 0.001), 514 ± 66 &mgr;m (P = 0.932), and 554 ± 98 &mgr;m (P = 0.004) after 1, 3, and 6 months, respectively. Donor endothelial cell density decreased from 2478 ± 185 to 1454 ± 193/mm2 (P < 0.001), 1301 ± 298/mm2 (P = 0.241), and 1374 ± 261/mm2 (P = 0.213), after 1, 3, and 6 months, respectively. The rebubbling rate was 46% (11/24). Four patients (17%) had secondary graft failure. Conclusions: Our data provide evidence that DMEK is feasible for the treatment of endothelial decompensation in complex preoperative situations.
In vitro batch fecal fermentation comparison of gas and short-chain fatty acid production using "slowly fermentable" dietary fibers.

UNLABELLED Sustained colonic fermentation supplies beneficial fermentative by-products to the distal colon, which is particularly prone to intestinal ailments. Blunted/delayed initial fermentation may also lead to less bloating. Previously, we reported that starch-entrapped alginate-based microspheres act as a slowly fermenting dietary fiber. This material was used in the present study to provide a benchmark to compare to other "slowly fermentable" fibers. Dietary fibers with previous reports of slow fermentation, namely, long-chain inulin, psyllium, alkali-soluble corn bran arabinoxylan, and long-chain β-glucan, as well as starch-entrapped microspheres were subjected to in vitro upper gastrointestinal digestion and human fecal fermentation and measured over 48 h for pH, gas, and short-chain fatty acids (SCFA). The resistant fraction of cooked and cooled potato starch was used as another form of fermentable starch and fructooligosaccharides (FOS) served as a fast fermenting control. Corn bran arabinoxylan and long-chain β-glucan initially appeared slower fermenting with comparatively low gas and SCFA production, but later fermented rapidly with little remaining in the final half of the fermentation period. Long-chain inulin and psyllium had slow and moderate, but incomplete, fermentation. The resistant fraction of cooked and cooled potato starch fermented rapidly and appeared similar to FOS. In conclusion, compared to the benchmark slowly fermentable starch-entrapped microspheres, a number of the purported slowly fermentable fibers fermented fairly rapidly overall and, of this group, only the starch-entrapped microspheres appreciably fermented in the second half of the fermentation period. PRACTICAL APPLICATION Consumption of dietary fibers, particularly commercial prebiotics, leads to uncomfortable feelings of bloating and flatulence due to their rapid degradation in our large intestine. This article employs claimed potential slowly fermenting fibers and compares their fermentation rates with a benchmark slow fermenting fiber that we fabricated in an in vitro simulation of the human digestive system. Results show a variety of fermentation profiles only some of which have slow and extended rate of fermentation.
High prevalence of neurovascular instability in neurodegenerative dementias

Orthostatic hypotension and carotid sinus hypersensitivity were assessed in patients meeting clinical criteria for dementia with Lewy bodies (DLB; n = 30) and AD (n = 35). Cardioinhibitory carotid sinus hypersensitivity (CI) was the most common sign (AD patients, 28%; DLB patients, 41%). Preliminary data from a secondary analysis excluding patients with hypertension or EKG evidence of ischemia suggested that CI may be significantly more common in DLB. Larger studies are needed to evaluate the implications for treatment and to explore the underlying mechanisms.
Reliability and Factor Structure of the Psychological Maltreatment and Neglect Scales of the Computer Assisted Maltreatment Inventory (CAMI)

The primary objective of this study was to evaluate the psychometric properties of the Psychological Maltreatment (PM) and Neglect subscales of the Computer Assisted Maltreatment Inventory (CAMI; DiLillo et al., 2010). The CAMI is a retrospective self-report measure that assesses multiple forms of child maltreatment (i.e., sexual, physical, psychological, neglect, exposure to interparental violence) retrospectively from adults. The CAMI's PM and Neglect subscales were administered to a geographically diverse sample of 400 college students and a sample of 412 newlyweds. Exploratory factor analyses were conducted for each group separately by subscale. Represented in the PM factor structures were items that depict emotional responsiveness, terrorizing/spurning, demanding/rigid, corrupting, and isolating parental behaviors. The Neglect scale included items depicting basic needs, cleanliness, abandonment, monitoring and medical neglect factors. Revised versions of the CAMI PM and Neglect subscales based on the factor analysis are presented.
Asymptotic Preserving Implicit-Explicit Runge-Kutta Methods for Nonlinear Kinetic Equations

We discuss Implicit-Explicit (IMEX) Runge Kutta methods which are particularly adapted to stiff kinetic equations of Boltzmann type. We consider both the case of easy invertible collision operators and the challenging case of Boltzmann collision operators. We give sufficient conditions in order that such methods are asymptotic preserving and asymptotically accurate. Their monotonicity properties are also studied. In the case of the Boltzmann operator, the methods are based on the introduction of a penalization technique for the collision integral. This reformulation of the collision operator permits to construct penalized IMEX schemes which work uniformly for a wide range of relaxation times avoiding the expensive implicit resolution of the collision operator. Finally we show some numerical results which confirm the theoretical analysis.
Cholinergic innervation of the rat hippocampus as revealed by choline acetyltransferase immunocytochemistry: A combined light and electron microscopic study

The cholinergic innervation of the rat hippocampus proper and fascia dentata was investigated by using a monoclonal antibody against choline acetyltransferase (ChAT). At the light microscopic level, thin varicose ChAT‐immunoreactive fibers were observed mainly in the vicinity of the pyramidal and granular layers where they formed a fine network around proximal dendrites of pyramidal and granule cells. In addition, many ChAT‐immunoreactive fibers were found in the hilar region and in stratum oriens, radiatum, and lacunosum‐moleculare of all hippocampal sectors.
Peroxiredoxin 6 is required for blood vessel integrity in wounded skin

Peroxiredoxin 6 (Prdx6) is a cytoprotective enzyme with largely unknown in vivo functions. Here, we use Prdx6 knockout mice to determine its role in UV protection and wound healing. UV-mediated keratinocyte apoptosis is enhanced in Prdx6-deficient mice. Upon skin injury, we observe a severe hemorrhage in the granulation tissue of knockout animals, which correlates with the extent of oxidative stress. At the ultrastructural level endothelial cells appear highly damaged, and their rate of apoptosis is enhanced. Knock-down of Prdx6 in cultured endothelial cells also increases their susceptibility to oxidative stress, thus confirming the sensitivity of this cell type to loss of Prdx6. Wound healing studies in bone marrow chimeric mice demonstrate that Prdx6-deficient inflammatory and endothelial cells contribute to the hemorrhage phenotype. These results provide insight into the cross-talk between hematopoietic and resident cells at the wound site and the role of reactive oxygen species in this interplay.
A difference between the effects of dietary calorie restriction on the estrous cycle and on the 24-hour adrenal cortical cycle in rodents.

INTRODUCTION THE presence of a physiological rhythm in the numbers of circulating eosinophils in intact animals including man and the absence of this rhythm in adrenalectomized humans have been reported (Halberg and Visscher, 1950, Halberg, 1951, Halberg et al. 1951). This report presents studies of the 24-hour changes in numbers of eosinophils in the mouse restricted in calories for several months. If, as seems likely, the 24-hour changes in eosinophils are due to changes in the output of adrenal cortical hormone, these results have a bearing on the question of whether such hormone output is influenced by caloric restriction. A comparable steroid rhythm, namely that responsible for the estrous cycle, is inhibited by undernourishment in animals and in humans (Loeb, 1921, Papanicolau and Stockard, 1920, Huseby et al. 1945). The finding of a marked 24-hour periodicity in eosinophil levels of underfed mice appears to be of interest in view of the limiting effect of dietary caloric restriction on the developm.
Predictive and Diagnostic Genetic Testing in Psychiatry

A version of this article originally appeared in the March 2010 issue of Psychiatric Clinics of North America. This work was supported by the Australian National Health and Medical Research Council (NHMRC) Program Grant (510135), Project Grant (510216), Public Health PhD scholarship (455414), and Career Development Award (350989). a School of Psychiatry, Prince of Wales Hospital, University of New South Wales, Randwick, Sydney, NSW 2031, Australia b Bipolar Disorders Clinic, Black Dog Institute, Hospital Road, Prince of Wales Hospital, Randwick, Sydney, NSW 2031, Australia c Brain Sciences UNSW, University of New South Wales, Sydney, NSW 2052, Australia d Psychosocial Research Group, Department of Medical Oncology, Prince of Wales Clinical School, Prince of Wales Hospital, University of New South Wales, Randwick, Sydney, NSW 2031, Australia e School of Psychiatry, University of New South Wales, Black Dog Institute Building, Hospital Road, Prince of Wales Hospital, Randwick, Sydney, NSW 2031, Australia f Prince of Wales Medical Research Centre, Prince of Wales Medical Research Institute, Barker Street, Randwick, Sydney, NSW 2031, Australia g Department of Biological Sciences, Macquarie University, Sydney, NSW 2109, Australia h School of Psychiatry, Consultation Liaison Psychiatry, St Vincent’s Hospital Victoria Street, University of New South Wales, Sydney, NSW 2010, Australia i Prince of Wales Medical Research Institute, Barker Street, Randwick, Sydney, NSW 2031, Australia j School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia * Corresponding author. School of Psychiatry, Prince of Wales Hospital, University of New South Wales, Randwick, Sydney, NSW 2031, Australia. E-mail address: phil.mitchell@unsw.edu. au
Correct Targeting of Plant ARF GTPases Relies on Distinct Protein Domains

Indispensable membrane trafficking events depend on the activity of conserved small guanosine triphosphatases (GTPases), anchored to individual organelle membranes. In plant cells, it is currently unknown how these proteins reach their correct target membranes and interact with their effectors. To address these important biological questions, we studied two members of the ADP ribosylation factor (ARF) GTPase family, ARF1 and ARFB, which are membrane anchored through the same N‐terminal myristoyl group but to different target membranes. Specifically, we investigated how ARF1 is targeted to the Golgi and post‐Golgi structures, whereas ARFB accumulates at the plasma membrane. While the subcellular localization of ARFB appears to depend on multiple domains including the C‐terminal half of the GTPase, the correct targeting of ARF1 is dependent on two domains: an N‐terminal ARF1 domain that is necessary for the targeting of the GTPase to membranes and a core domain carrying a conserved MxxE motif that influences the relative distribution of ARF1 between the Golgi and post‐Golgi compartments. We also established that the N‐terminal ARF1 domain alone was insufficient to maintain an interaction with membranes and that correct targeting is a protein‐specific property that depends on the status of the GTP switch. Finally, an ARF1–ARFB chimera containing only the first 18 amino acids from ARF1 was shown to compete with ARF1 membrane binding loci. Although this chimera exhibited GTPase activity in vitro, it was unable to recruit coatomer, a known ARF1 effector, onto Golgi membranes. Our results suggest that the targeting of ARF GTPases to the correct membranes may not only depend on interactions with effectors but also relies on distinct protein domains and further binding partners on the Golgi surface.
Long-Term Care Planning Study: Strengths and Learning Needs of Nursing Staff*

ABSTRACT This planning study was designed and conducted in a predominantly rural Canadian province to examine the strengths and learning needs of four categories of nursing staff practising in New Brunswick nursing homes. Participants included directors of care, registered nurses, licensed practical nurses, and resident attendants. The nursing homes ranged in size from 38 to 196 beds and were located throughout the province. In health and planning studies, ethnography conveys a coherent statement of peoples' local knowledge as culture-sharing groups (Muecke, 1994). The study derived information from the Nursing Home Act, reports, the literature, key informants, and direct observations of and interviews with participants. Leadership strengths defined the roles for categories of staff and supported the capacity of each category to identify their learning needs. In conclusion, nurses practising in nursing homes can and must take an active role in decision making for their learning. RÉSUMÉ La présente étude de planification a été conçue et effectuée dans une province canadienne essentiellement rurale, le Nouveau-Brunswick, afin d'y évaluer les forces et les besoins d'apprentissage de quatre catégories de personnel infirmier en poste dans des maisons de soins infirmiers. Des contrôleurs de soins, des infirmières, des infirmières auxiliaires et des aides gériatriques ont participé à cette étude. Les maisons de soins infirmiers, réparties dans l'ensemble de la province, comprenaient de 38 à 196 lits. Dans les études portant sur la santé et la planification, l'ethnographie comporte un énoncé cohérent des connaissances locales des gens en tant que groupes partageant leur culture (Muecke, 1994). L'étude a tiré ses renseignements de la Loi sur les maisons de soins infirmiers, de rapports, de la documentation, et de répondants clés, ainsi que des entrevues avec les participants et des observations qu'ils ont fournies. Les forces de leadership ont défini les rôles des catégories de personnel et soutenu la capacité de chacune afin de déterminer leurs besoins d'apprentissage. En conclusion, les infirmières exerçant leur profession dans les maisons de soins infirmiers peuvent et doivent jouer un rôle actif dans le processus décisionnel en rapport avec leur apprentissage.
Celtic origin of the C282Y mutation of hemochromatosis.

The C282Y mutation in the HFE gene is the main mutation causing hemochromatosis, and C282Y frequencies have been reported for various European populations. The aim of this review is to compile the Y allele frequencies of the C282Y mutation for twenty European populations. The most elevated value (6.88%) is observed in residual Celtic populations in UK and France, in accordance to the hypothesis of Simon et al. concerning a Celtic origin of the hereditary hemochromatosis mutation.