Miracle-dz/UniFAR-FTUs huggingface dataset:
Epidermal Growth Factor Receptor–Mediated Membrane Type 1 Matrix Metalloproteinase Endocytosis Regulates the Transition between Invasive versus Expansive Growth of Ovarian Carcinoma Cells in Three-Dimensional Collagen

The epidermal growth factor receptor (EGFR) is overexpressed in ovarian carcinomas and promotes cellular responses that contribute to ovarian cancer pathobiology. In addition to modulation of mitogenic and motogenic behavior, emerging data identify EGFR activation as a novel mechanism for rapid modification of the cell surface proteome. The transmembrane collagenase membrane type 1 matrix metalloproteinase (MT1-MMP, MMP-14) is a major contributor to pericelluar proteolysis in the ovarian carcinoma microenvironment and is subjected to extensive posttranslational regulation. In the present study, the contribution of EGFR activation to control of MT1-MMP cell surface dynamics was investigated. Unstimulated ovarian cancer cells display caveolar colocalization of EGFR and MT1-MMP, whereas EGFR activation prompts internalization via distinct endocytic pathways. EGF treatment results in phosphorylation of the MT1-MMP cytoplasmic tail, and cells expressing a tyrosine mutated form of MT1-MMP (MT1-MMP-Y573F) exhibit defective MT1-MMP internalization. As a result of sustained cell surface MT1-MMP activity, a phenotypic epithelial-mesenchymal transition is observed, characterized by enhanced migration and collagen invasion, whereas growth within three-dimensional collagen gels is inhibited. These data support an EGFR-dependent mechanism for regulation of the transition between invasive and expansive growth of ovarian carcinoma cells via modulation of MT1-MMP cell surface dynamics. (Mol Cancer Res 2009;7(6):809–20)
Laparoscopic radical prostatectomy: 10 years experience.

PURPOSE The authors assess the morbidity, functional results and oncologic follow-up of a series of laparoscopic radical prostatectomies performed in over a 10-year period. MATERIALS AND METHODS The data on 780 laparoscopic radical prostatectomies performed between September 1997 and December 2007 were stored in a personal database. The following parameters are described and critically analyzed: operative time, blood transfusions, conversions, length of hospital stay, complications, functional results of sexual potency and urinary continence, surgical margins and oncologic follow-up. RESULTS Operative time averaged 125 minutes, with a mean bleeding volume of 335 mL and mean hospital stay of 4.3 days. The rate of conversion to open surgery was 1.36% and the overall complication rate was 14.24%. The pathology analysis showed pT2 tumors in 82.60% and pT3 tumors in 17.39% of cases. The overall positive margin rate was 19.58%, with a biochemical recurrence of 10.27% at a mean follow-up of 62.5 months. Urinary continence and sexual potency yielded rates of 88% and 61%, respectively, 12 months after surgery. CONCLUSIONS Laparoscopic radical prostatectomy is a technically well-defined procedure that provides good oncologic and functional results after proper training.
LPA1 is a key mediator of intracellular signalling and neuroprotection triggered by tetracyclic antidepressants in hippocampal neurons

Both lysophosphatidic acid (LPA) and antidepressants have been shown to affect neuronal survival and differentiation, but whether LPA signalling participates in the action of antidepressants is still unknown. In this study, we examined the role of LPA receptors in the regulation of extracellular signal‐regulated protein kinases 1 and 2 (ERK1/2) activity and neuronal survival by the tetracyclic antidepressants, mianserin and mirtazapine in hippocampal neurons. In HT22 immortalized hippocampal cells, antidepressants and LPA induced a time‐ and concentration‐dependent stimulation of ERK1/2 phosphorylation. This response was inhibited by either LPA1 and LPA1/3 selective antagonists or siRNA‐induced LPA1 down‐regulation, and enhanced by LPA1 over‐expression. Conversely, the selective LPA2 antagonist H2L5186303 had no effect. Antidepressants induced cyclic AMP response element binding protein phosphorylation and this response was prevented by LPA1 blockade. ERK1/2 stimulation involved pertussis toxin‐sensitive G proteins, Src tyrosine kinases and fibroblast growth factor receptor (FGF‐R) activity. Tyrosine phosphorylation of FGF‐R was enhanced by antidepressants through LPA1. Serum withdrawal induced apoptotic death, as indicated by increased annexin V staining, caspase activation and cleavage of poly‐ADP‐ribose polymerase. Antidepressants inhibited the apoptotic cascade and this protective effect was curtailed by blockade of either LPA1, ERK1/2 or FGF‐R activity. Moreover, in primary mouse hippocampal neurons, mianserin acting through LPA1 increased phospho‐ERK1/2 and protected from apoptosis induced by removal of growth supplement. These data indicate that in neurons endogenously expressed LPA1 receptors mediate intracellular signalling and neuroprotection by tetracyclic antidepressants.
Expression profile of mucins (MUC1, MUC2, MUC5AC, and MUC6) in ovarian mucinous tumours: changes in expression from benign to malignant tumours

Mucins (MUCs) constitute a family of glycoproteins expressed by epithelial cells. They show specific tissue‐type expression, and are useful for differentiating between different cancers. Studies have shown changes in MUC expression with tumour progression in a variety of cancers. The aim of this study was to characterize the profile of MUC expression in benign, borderline and malignant intestinal‐type ovarian mucinous tumours (OMTs).
Flow-aware allocation for on-chip networks

Current Virtual-Channel routers disregard potentially useful information about on-chip communication flows. This often leads to inefficient resource utilisation in existing Networks-on-Chips for flow-based communication patterns. The flow-based traffic exhibited by forthcoming applications requiring large streaming datasets (sophisticated graphical interfaces, mobile connectivity, scientific applications, etc.) lead us to propose flow additions to a Virtual-Channel network. Our flow-based refinements infer the presence of, and allocate resources to flows rather than individual packets. As a consequence, we are able to demonstrate speedups of close to 40% for synthetic flow-based traffic patterns.
From Transitional to Mixed Society: Croatia between Two Modernizations

Lo scopo del saggio e di fornire qualche informazione in piu sull'attuale situazione della societa croata. Secondo i criteri stabiliti dalla Unione Europea per il processo d'integrazione e basati soltanto su fattori politici, economici e giuridici, solo adesso la Croazia starebbe entrando nella "fase matura della transizione". Dal punto di vista sociale, tuttavia, bisognerebbe precisare che il paese ha gia concluso la transizione: oggi, i rischi provengono in massima parte dalla globalizzazione. Una nuova fase, post-bellica, della transizione croata, ha portato alla stabilizzazione di nuovi valori, posizioni e identita sociali. Il presente saggio non e incentrato sulle direzioni e sui presumibili effeti delle nuove trasformazioni, ma sui gruppi sociali esistenti che precedono tali cambiamenti e che sono destinati a prendervi parte. Per necessita di sintesi, l'oggetto del saggio e preso in esame da due differenti punti di vista che derivano da due diversi impostazioni teoriche: l'uno relativo alle radici storiche e culturali della composita identita regionale della Croazia attuale ; l'altro inerente all'ampio contesto che ha fatto da sfondo alle trasformazioni sociali verificatesi nell'ultimo secolo e mezzo. Per fare intuire al lettore interessato la complessita delle varie identita culturali e dei molteplici legami regionali presenti in Croazia, si e ritenuto opportuno riportare brevemente la teoria dello "sviluppo sociale dei croati", elaborata prima della seconda guerra mondiale da Dinko Tomasic, un sociologo interdisciplinare, i cui testi in Croazia sono stati riscoperti solo agli inizi del periodo post-socialista. Allo stesso tempo, pero, e nostra intenzione spiegare il carattere misto dell'attuale societa croata e la natura delle trasformazioni che si stanno verificando, grazia alla teoria della "prima" e "seconda" (o "riflessiva") modernita, proposta da Ulrich Beck e successivamente adottata e parzialmente modificata da Anthony Giddens. Secondo chi scrive, la situazione croata puo essere compresa piu efficacemente, se il suo "sviluppo sociale" viene descritto come una evoluzione simultanea di due processi di modernizzazione, che differiscono tra loro per carattere e intensita. La relazione che ne deriva potrebbe essere descritta semplicemente come un insieme di elementi "tradizionali" e "moderni" piuttosto che come un'evoluzione simultanea di due processi di modernizzazione, ma e nostra opinione che tale definizione non renderebbe giustizia alla situazione croata.
Sharing knowledge across boundaries

Practical solutions concerning the strategic use of knowledge and its management depend upon the relevant organizational context. By applying the ‘learning ladder’ model (i.e. a compact way of describing the unfolding of multiple organizational knowledge creation, transformation and transfer processes), three different contexts are explored. First, the single firm is considered and the governance of its internal knowledge processes performed according to the tenets of the resource-based view of strategy. Second, the boundaries of the single firm are crossed and the characteristics of the processes of knowledge transfer and production between allied firms are considered. Finally, emerging features of how knowledge is managed among a large number of interdependent organizations and individuals are explored with reference to the case of open source software. The latter context highlights behaviours that seem, in a sense, at odds with the traditional principles of knowledge management. This is puzzling: conventional strategic and knowledge management frameworks break down precisely when dealing with the case of highly distributed, knowledge intensive businesses.
Understanding Adaptive Motor Control of the Paretic Upper Limb Early Poststroke

Background. During upper limb motor recovery after stroke, the greatest improvements occur typically in the first 5 weeks poststroke. It is unclear what patients learn during this early phase of recovery. Objective. To investigate the hypothesis that, early poststroke, patients learn to master the degrees of freedom in the paretic upper limb as reflected by dissociated shoulder and elbow movements during reach-to-grasp. Methods. Thirty-one patients with a first-ever ischemic stroke were included. Repeated 3-dimensional kinematic measurements were conducted at 14, 25, 38, 57, 92, and 189 days poststroke. Trunk, shoulder, elbow, and wrist rotations were measured during a reach-to-grasp task. Using principal component analysis the longitudinal changes in dissociated upper limb movements during reach-to-grasp were investigated. Twelve healthy subjects were included for comparison. Results. The main coordination pattern during reach-to-grasp in patients with stroke and healthy subjects consisted mostly of horizontal shoulder adduction and elbow extension. The standard deviation of this main pattern increased over time, with the largest increase in the first 5 weeks poststroke (F = 5.5, P < .001), but remained smaller than in healthy individuals. The standard deviation increased by 0.46° per day between 14 and 38 days and tapered off to 0.05° per day between 38 and 189 days poststroke. Conclusions. Our results suggest that restitution of motor control by dissociation of shoulder and elbow movements occurs mainly early poststroke. However, compared with healthy adults, most patients did not achieve fully dissociated upper limb movements at 26 weeks poststroke, suggesting that upper limb motor control after stroke remains adaptive.
Regulation of the neuronal KCNQ2 channel by Src – a dual rearrangement of the cytosolic termini underlies bidirectional regulation of gating

ABSTRACT Neuronal M-type K+ channels are heteromers of KCNQ2 and KCNQ3 subunits, and are found in cell bodies, dendrites and the axon initial segment, regulating the firing properties of neurons. By contrast, presynaptic KCNQ2 homomeric channels directly regulate neurotransmitter release. Previously, we have described a mechanism for gating downregulation of KCNQ2 homomeric channels by calmodulin and syntaxin1A. Here, we describe a new mechanism for regulation of KCNQ2 channel gating that is modulated by Src, a non-receptor tyrosine kinase. In this mechanism, two concurrent distinct structural rearrangements of the cytosolic termini induce two opposing effects: upregulation of the single-channel open probability, mediated by an N-terminal tyrosine, and reduction in functional channels, mediated by a C-terminal tyrosine. In contrast, Src-mediated regulation of KCNQ3 homomeric channels, shown previously to be achieved through the corresponding tyrosine residues, involves the N-terminal-tyrosine-mediated downregulation of the open probability, rather than an upregulation. We argue that the dual bidirectional regulation of KCNQ2 functionality by Src, mediated through two separate sites, means that KCNQ2 can be modified by cellular factors that might specifically interact with either one of the sites, with potential significance in the fine-tuning of neurotransmitters release at nerve terminals. Summary: Src regulates the KCNQ2 channel through a dual rearrangement of cytosolic termini that underlies upregulation of single-channel gating and a reduction in the number of functional channels.
Distributions of reproductive and somatic cell numbers in diverse Volvox (Chlorophyta) species.

BACKGROUND Volvox (Chlorophyta) asexual colonies consist of two kinds of cells: a large number of small somatic cells and a few large reproductive cells. The numbers of reproductive and somatic cells correspond directly to the major components of fitness - fecundity and viability, respectively. Volvox species display diverse patterns of development that give rise to the two cell types. QUESTIONS For Volvox species under fixed conditions, do species differ with respect to the distribution of somatic and reproductive cell numbers in a population of asexual clones? Specifically, do they differ with respect to the dispersion of the distribution, i.e. with respect to their intrinsic variability? If so, are these differences related to major among-species developmental differences? DATA DESCRIPTION For each of five Volvox species, we estimate the number of somatic and reproductive cells for 40 colonies and the number of reproductive cells for an additional 200 colonies. We sampled all colonies from growing, low-density, asexual populations under standard conditions. SEARCH METHOD We compare the distribution of reproductive cell numbers to a Poisson distribution. We also compare the overall dispersion of reproductive cell number among species by calculating the coefficient of variation (CV). We compare the bivariate (reproductive and somatic cell) dataset to simulated datasets produced from a simple model of cell-type specification with intrinsic variability and colony size variation. This allows us to roughly estimate the level of intrinsic variability that is most consistent with our observed bivariate data (given an unknown level of size variation). CONCLUSIONS The overall variability (CV) in reproductive cell number is high in Volvox compared with more complex organisms. Volvox species show differences in reproductive cell number CV that were not clearly related to development, as currently understood. If we used the bivariate data and tried to account for the effects of colony size variation, we found that the species that have fast embryonic divisions and asymmetric divisions have substantially higher intrinsic variability than the species that have slow divisions and no asymmetric divisions. Under our culture conditions, the Poisson distribution is a good description of intrinsic variability in reproductive cell number for some but not all Volvox species.
Sustained LFA‐1 cluster formation in the immune synapse requires the combined activities of L‐plastin and calmodulin

Formation of immune synapses (IS) between T cells and APC requires multiple rearrangements in the actin cytoskeleton and selective receptor accumulation in supramolecular activation clusters (SMAC). The inner cluster (central SMAC) contains the TCR/CD3 complex. The outer cluster (peripheral SMAC) contains the integrin LFA‐1 and Talin. Molecular mechanisms selectively stabilizing receptors in the IS remained largely unknown. Here, we demonstrate that sustained LFA‐1 clustering in the IS is a consequence of the combined activities of the actin‐bundling protein L‐plastin (LPL) and calmodulin. Thus, upon antigen‐recognition of T cells, LPL accumulated predominantly in the peripheral SMAC. siRNA‐mediated knock‐down of LPL led to a failure of LFA‐1 and Talin redistribution – however, not TCR/CD3 relocalization – into the IS. As a result of this LPL knock‐down, the T‐cell/APC interface became smaller over time and T‐cell proliferation was inhibited. Importantly, binding of calmodulin to LPL was required for the maintenance of LPL in the IS and consequently inhibition of calmodulin also prevented stable accumulation of LFA‐1 and Talin, but not CD3, in the IS.
Acquired immune and inflammatory myopathies: pathologic classification

Purpose of reviewWe discuss pathology-based characterization and classification of acquired immune and inflammatory myopathies (IIMs). Recent findingsSeveral types of IIMs do not fit well into the typical IIM subclassifications: dermatomyositis, polymyositis and inclusion body myositis (IBM). Myopathologic features that can provide additional diagnostic clarification in IIM are types of muscle fiber pathology; immune changes (cellular and humoral); and tissues with distinctive involvement (connective tissue, vessels and muscle fibers). Pathologic classification categories include immune myopathies with perimysial pathology (IMPP), a group that can be associated with antisynthetase antibodies; myovasculopathies, including childhood dermatomyositis; immune polymyopathies, active myopathies with little inflammation such as the myopathy with signal recognition particle antibodies; immune myopathies with endomysial pathology (IM-EP), illustrated by brachio-cervical inflammatory myopathy (BCIM); histiocytic inflammatory myopathies, like sarcoid myopathy; and inflammatory myopathies with vacuoles, aggregates and mitochondrial pathology (IM-VAMP), which have inclusion body myositis as a pathologic subtype and are poorly treatable. Some myopathologic features, like B-cell foci and alkaline phosphatase staining of capillaries or perimysium, are more likely to be present in treatable categories of IIM. SummaryMyopathology can be used to classify IIM. Identification of distinctive myopathologic changes in IIM can improve diagnostic and prognostic accuracy and focus treatment, therapeutic trials and studies of pathogenic factors.
Effect of parenteral selenium administration to sheep on prevalence and recovery from footrot.

BACKGROUND Insufficient intake of selenium (Se) is common in many regions, and can contribute to increased susceptibility to and prolonged recovery from infectious diseases. OBJECTIVE To determine the effect of Se administration in decreasing the severity and prevalence of footrot in sheep. ANIMALS Thirty-eight footrot-affected and 19 nonaffected sheep from a commercial flock of known high incidence of footrot. METHODS Placebo-controlled, prospective, 15-month clinical trial. Footrot-affected sheep were randomly assigned into 2 groups (n = 19) and injected with either 5 mg Se (footrot [FR]-Se) or saline (FR-Sal) at 1-month intervals for the duration of the study. Unaffected sheep (controls) received no treatment. Sheep feet were examined, trimmed, and scored for footrot with a scale of 0 (no footrot) to 4 (extensive) at 0, 3, 6, 9, and 15 months. Sheep were also bled at time 0 and then at 3, 6, and 15 months to assess whole blood Se concentrations. RESULTS At time 0, control sheep (255 +/- 11 ng/mL) had higher (P < .05) whole blood Se concentrations compared with FR-Se (205 +/- 12 ng/mL) and FR-Sal (211 +/- 14 ng/mL) sheep. By 6 months, FR-Se sheep (317 +/- 9 ng/mL) had whole blood Se concentrations greater (P < .05) than both control (281 +/- 14 ng/mL) and FR-Sal (277 +/- 16 ng/mL) sheep. FR-Se ewes showed a faster decline in highest lesion score at 3 (P= .012) and 6 (P= .0036) months, and a greater decrease in the number of feet with foot score >0 at 6 (P= .020) months compared with FR-Sal ewes. Sheep with blood Se concentrations <300 ng/mL were at 3.5 times greater risk (1.1-12.1 confidence interval, odds ratio) for FR, although this relationship was only significant (P= .04) at 6 months of the study. CONCLUSIONS AND CLINICAL IMPORTANCE In sheep with footrot, improved Se status in conjunction with routine control practices result in more rapid improvement of foot lesions.
A linear programming based channel coding strong converse for the BSC and BEC

This paper illustrates the application of the linear programming (LP) based framework proposed by the authors previously [1] in deriving improved converses for finite blocklength channel coding of a discrete memoryless binary symmetric channel (BSC) and binary erasure channel (BEC). Employing elementary concepts of optimization, finite blocklength channel coding converses for BSC and BEC are derived from first principles. The converses thus derived do not rely on information theoretic constructs like tilted information or information densities. Moreover, it is shown that the converses obtained imply the strong converse for BSC and BEC, thereby introducing a new approach for explaining the strong converse phenomenon.
Use of Animation Software in Simulation of On-Body Communications Channels at 2.45 GHz

As wearable electronic devices become increasingly popular, there is a growing interest in the design of body area networks (BAN). The propagation characteristics of such channels are of interest to assist in proper design of BAN systems. It has been shown that body movement is a primary factor in channel fading and hence channel modelling must include the effect of movement. In this letter, results are presented for a walking phantom created using animation software. Simulations of a walking avatar for three different channels at a frequency of 2.45 GHz are shown and compared to measurements made on a human body in an anechoic chamber. It is shown that such a phantom can give good prediction of mean and standard deviation of the propagation channel of a walking subject.