Miracle-dz/UniFAR-FTUs huggingface dataset:
Extracellular matrix molecules implicated in hypertrophic and keloid scarring

Tissue regeneration repairs the fabric of the skin to maintain homeostasis after injury. The expression and proliferation of extracellular matrix (ECM) molecules in the dermis, mediated by a range of growth factors and cytokines, is a fundamental element of wound repair. Previous work focused on how these complex molecular mechanisms relate to the formation of raised dermal scars, including keloid and hypertrophic scars, characterized by excessive deposition of ECM molecules. However, the mechanisms in the wound repair pathway which lead to the differential expression and organization of ECM molecules observed in different types of scar tissue are not fully understood. To summarize what is known about the expression and composition of ECM molecules in abnormal scarring, an extensive search of the literature was conducted, focusing on keywords connected to skin scarring, hypertrophic scars and keloid disease. The transcription and translation of collagen I and III, fibronectin, laminin, periostin and tenascin are all increased in raised dermal scar tissue. However, hyaluronic acid, dermatopontin and decorin are decreased, and the expression and localisation of fibrillin and elastin fibres in the dermis are altered compared with normal skin and scars. Recent whole genome profiling and proteomic studies have led to the identification of regulatory elements with different expression profiles in hypertrophic and keloid tissue. If the mechanisms of raised dermal scar formation are to be elucidated and effective therapeutic treatments developed, an integrated approach to research is required, focussing on the interactions between ECM molecules, regulatory elements and pathways.
DIAGNOSTIC AND THERAPEUTIC CHALLENGES

A 71-year-old woman was referred to our clinic because of blurred vision in her left eye the day after uneventful cataract surgery. Best-corrected visual acuity in the right eye was 20/40 and in the left eye was light perception. Anterior segment examination of the left eye revealed a relative afferent pupillary defect and mild inflammatory signs of the conjunctiva and cornea. There was no flare in the anterior chamber. The intraocular lens was well centered in the capsular bag. Fundus examination of the left eye showed a diffuse whitening of the retina at the posterior pole and nasally to the optic nerve with a cherry-red spot of the macula (Figure 1). There was also a peripapillary subretinal hemorrhage involving the papillomacular bundle (PMB) (Figure 1). On the edge of the subretinal hemorrhage, fluorescein angiography (FA) showed a hyperfluorescent area (Figure 2); indocyanine green angiography revealed that it was originating from dilated polypoidal choroidal lesion (Figure 2). Nasally to the optic nerve, there were 2 triangular hyperfluorescent areas corresponding to the whitening areas of the retina (Figure 2). The right eye was unremarkable with mild nuclear sclerosis. Ocular history was unremarkable, and the medical history revealed recently diagnosed medically controlled hypertension. Echocardiography and carotid ecodoppler were negative. On medical record, preoperative best-corrected visual acuity of the left eye was 20/50 with a dense nuclear sclerosis of the lens. Fundus examination did not report any vascular or degenerative disorder of the chorioretinal; neither FA nor optical coherence tomography was performed. The patient underwent uneventful phacoemulsification of the cataract and in-the-bag intraocular lens implantation. No intraoperative or postoperative complications were reported. Because she refused topical anesthesia, a single medial percutaneous peribulbar anesthesia was performed. A 25-gauge 16-mm beveled disposable needle was used. The 5-mL injection contained a 50/50 mixture of 2% xylocaine and 0.5% marcaine, in combination with 150 IU of hyaluronidase. The patient was followed for the next few months, but visual acuity did not recover. This patient is presented for discussion of diagnosis.
Coating the surface: a model for expression of capsular polysialic acid in Escherichia coli K1

Capsules are well‐studied components of the bacterial surface that modulate interactions between the cell and its environment. Generally composed of polysaccharide, they are key virulence determinants in invasive infections in humans and other animals. Genetic determinants involved in capsule expression have been isolated from a number of organisms, but perhaps the best characterized is the kps cluster of Escherichia coli K1. In this review, the current understanding of the functions of the kps gene products is summarized. Further, a proposed mechanistic model for capsule expression is presented and discussed. The model is based on the premise that the numerous components of the kps cluster form a hetero‐oligomeric complex responsible for synthesis and concurrent translocation of the capsular polysialic acid through sites of inner and outer membrane fusion. We view the ATP‐binding cassette (ABC) transporter, KpsMT, to be central to the functioning of the complex, interacting with the biosynthetic apparatus as well as the extracytoplasmic components of the cluster to co‐ordinate synthesis and translocation. The model provides the basis for additional experimentation and reflects emerging similarities among systems responsible for macromolecular export in Gram‐ negative bacteria.
Excitatory amino acid induced oligodendrocyte cell death in vitro: receptor‐dependent and ‐independent mechanisms

Oligodendroglia play an important role in axonal conduction in the CNS and are sensitive to oxidative toxicity induced by glutamate in the absence of ionotropic glutamate receptors. In this study, oligodendrocyte signalling cascades were examined, in response to glutamate‐induced oxidative injury and to excitotoxicity. Rat cortical oligodendrocytes, differentiated in culture, were highly vulnerable to glutamate‐induced cell death. Competitive inhibition of cystine uptake and increased oxidative stress appeared responsible for this death, and caused an accumulation of intracellular peroxides as well as chromatin fragmentation and condensation. Glutamate receptor subtype agonists (quisqualate, ibotenate) known to inhibit cystine uptake were cytotoxic, but not NMDA itself; moreover, glutamate receptor antagonists were not protective. Oligodendrocytes were also vulnerable to overactivation of glutamate receptors, as kainic acid and AMPA proved to be toxic. AMPA toxicity required the presence of cyclothiazide, suggesting rapid desensitization of AMPA receptors. Glutamate‐induced oxidative stress and kainate/AMPA receptor stimulation activated the mitogen‐activated protein kinase (MAP kinase) pathway, as well as the transcription factor ELK. However, MAP kinase kinase inhibitors only protected against injury from glutamate‐induced oxidative stress. Oligodendrocytes were sensitive to oxygen–glucose deprivation injury as well, in a MAP kinase dependent fashion. Glutamate toxicity may conceivably be operative in neuropathological conditions that disrupt neuronal/oligodendrocyte interactions in axons, e.g. multiple sclerosis and ischaemia‐reperfusion injury.
ESAIM: Control, Optimisation and Calculus of Variations

It is established convergence to a particular equilibrium for weak solutions of abstract linear equations of the second order in time associated with monotone operators with nontrivial kernel. Concerning nonlinear hyperbolic equations with monotone and conservative potentials, it is proved a general asymptotic convergence result in terms of weak and strong topologies of appropriate Hilbert spaces. It is also considered the stabilization of a particular equilibrium via the introduction of an asymptotically vanishing restoring force into the evolution equation. Mathematics Subject Classification. 34E10, 34G05, 35B40, 35L70, 58D25. Received June 1, 2000. Revised April 3, 2001.
On the Ungerboeck and Forney Observation Models for Offset QPSK

Abstract : The Ungerboeck and Forney observation models for offset QPSK are derived for three different representations for OQPSK. The representations and their corresponding Ungerboeck observation models are different, but the trellises used by the maximum likelihood sequence estimators possess the same complexity. The Forney observation models are obtained in straight-forward way for the bit-based representations for OQPSK, but there is no Forney observation model in the traditional sense for the symbol-based OQPSK representation. In the case of the symbol-based OQPSK representation, a method for whitening the resulting non-linear system is described.
Genomic Epidemiology of Clostridium botulinum Isolates from Temporally Related Cases of Infant Botulism in New South Wales, Australia

ABSTRACT Infant botulism is a potentially life-threatening paralytic disease that can be associated with prolonged morbidity if not rapidly diagnosed and treated. Four infants were diagnosed and treated for infant botulism in NSW, Australia, between May 2011 and August 2013. Despite the temporal relationship between the cases, there was no close geographical clustering or other epidemiological links. Clostridium botulinum isolates, three of which produced botulism neurotoxin serotype A (BoNT/A) and one BoNT serotype B (BoNT/B), were characterized using whole-genome sequencing (WGS). In silico multilocus sequence typing (MLST) found that two of the BoNT/A-producing isolates shared an identical novel sequence type, ST84. The other two isolates were single-locus variants of this sequence type (ST85 and ST86). All BoNT/A-producing isolates contained the same chromosomally integrated BoNT/A2 neurotoxin gene cluster. The BoNT/B-producing isolate carried a single plasmid-borne bont/B gene cluster, encoding BoNT subtype B6. Single nucleotide polymorphism (SNP)-based typing results corresponded well with MLST; however, the extra resolution provided by the whole-genome SNP comparisons showed that the isolates differed from each other by >3,500 SNPs. WGS analyses indicated that the four infant botulism cases were caused by genomically distinct strains of C. botulinum that were unlikely to have originated from a common environmental source. The isolates did, however, cluster together, compared with international isolates, suggesting that C. botulinum from environmental reservoirs throughout NSW have descended from a common ancestor. Analyses showed that the high resolution of WGS provided important phylogenetic information that would not be captured by standard seven-loci MLST.
Decision-Making Support for the Correctness of Input Data at Runtime in Business Processes

In a business process, the information that flows between the activities can be introduced by those users who interact with the process. This introduced information could be incorrect due to a lack of knowledge or a mistake. For this reason and to make the business process execution consistent, we propose a Decision Support System (DSS) to inform the user about the possible and correct values that the input data can take. The DSS takes into account the business process model and the policy of the company. The policy concerning the input data and dataflow that the company manages can be represented by constraints (called Business Data Constraints (BDCs)). In order to ascertain all the possible values of the input data that permit the execution of the process following the defined goals, the DSS analyzes the business process model and the BDC, using the constraint programming paradigm.
Broad bean cultivars increase extrafloral nectary numbers, but not extrafloral nectar, in response to leaf damage

Phenotypic plasticity allows organisms to maximize fitness, by optimizing the expression of costly defensive traits. Broad bean, Vicia faba L. “Broad Windsor”, produces increased numbers of extrafloral nectaries (EFNs) in response to leaf damage to attract mutualistic partners and reduce herbivory. It is currently unknown, however, whether EFN induction is cultivar-specific or is a more general phenomenon. It has also not been determined whether broad beans increase nectar secretion rates in conjunction with EFN induction. We hypothesized that: a) as all broad beans have conspicuous EFNs, all cultivars should produce additional EFNs in response to leaf damage, and b) overall nectar secretion rates should increase with EFN numbers, to attract additional mutualists. We tested our hypothesis by subjecting three broad bean cultivars, Vicia faba L. “Broad Windsor”, “Stereo”, and “Witkiem” to mechanical leaf damage. The degree of change in plant traits associated with growth, in addition to EFN induction, was assessed 1 week after leaf damage. Extrafloral nectar volumes were also assessed, every 24 hours, pre- and post-leaf damage. We confirmed our first, but rejected our second, hypothesis. All cultivars produced additional EFNs, but none increased extrafloral nectar volumes, when experiencing leaf damage. Further experimentation is required to determine if energetic tradeoffs limit multiple forms of defense (i.e., EFN vs. nectar induction), or if this alternative strategy is adaptive for attracting and retaining mutualists. Understanding the costs and benefits of EFN vs. nectar induction will provide insight into the evolution of defensive mutualisms between plants and predatory arthropods.
Volitional regulation of the supplementary motor area with fMRI-BCI neurofeedback in Parkinson's disease: A pilot study

It is hypothesized that a dysfunction of the supplementary motor area (SMA), secondary to a deficit of the nigrostriatal dopamine system, partially contributes to the symptomatology of Parkinson's disease (PD), i.e., akinesia. In this pilot study we investigated the effect of real-time fMRI neurofeedback based volitional up-regulation of the SMA on hand motor performance of one PD patient and 3 healthy volunteers. The effect of learned self-regulation was evaluated with speeded, bimanual, sequenced button-pressing trials, assessed immediately after each baseline and up-regulation block. Our pilot results indicate that volitional up-regulation of SMA is accompanied by slowing of sequenced button presses.
A patento‐scientometric approach to venture capital investment prioritization

This paper proposes an approach to analyzing and prioritizing venture capital investments with the use of scientometric and patentometric indicators. The article highlights the importance of such investments in the development of technology‐based companies and their positive impacts on the economic development of regions and countries. It also notes that the managers of venture capital funds struggle to objectify the evaluation of investment proposals. This paper analyzes the selection process of 10 companies, five of which received investments by the largest venture capital fund in Brazil and the other five of which were rejected by this same fund. We formulated scientometric and patentometric indicators related to each company and conducted a comparative analysis of each by considering the indicators grouped by the nonfinancial criteria (technology, market, and divestiture team) from analysis of the investment proposals. The proposed approach clarifies aspects of the criteria evaluated and contributes to the construction of a method for prioritizing venture capital investments.
Growth inMedicare Expenditures for Patients With AcuteMyocardial Infarction

RESULTS Compared with the subjects from 1998 through 1999, those in 2008 were older and had more comorbidities but slightly less ischemic heart disease and cerebrovascular disease. Although there was a 19.2% decline in the rate of hospitalizations for AMI, overall expenditures per patient increased by 16.5% (absolute difference, $6094). Of the total risk-adjusted increase in expenditures, 25.6% occurred within 30 days (22.0% attributed to the index admission), and 74.4% happened 31 to 365 days after the index admission. Spending per beneficiary within 30 days increased by $1560 (7.5%), and spending between 31 and 365 days increased by $4535 (28.0%). Expenditures for skilled nursing facilities, hospice, home health agency, durable medical equipment, and outpatient care nearly doubled 31 to 365 days after admission. Mortality within 1 year declined from 36.0% in 1998 through 1999 to 31.7% in 2008; of the decline, 3.3% was in the 30 days following admission, and 1.0% was in days 31 to 365.
Ethanol exposure impairs LPS-induced pulmonary LIX expression: alveolar epithelial cell dysfunction as a consequence of acute intoxication.

BACKGROUND Alcohol intoxication impairs innate immune responses to bacterial pneumonia, including neutrophil influx. Lipopolysaccharide (LPS)-induced chemokine (LIX or CXCL5) is a recently described chemokine produced by type-II alveolar epithelial (AE2) cells which facilitates neutrophil recruitment. The effect of acute alcohol intoxication on AE2 cell expression of LIX is unknown. METHODS C57BL/6 mice were given an intraperitoneal (i.p.) injection of ethanol (4 g/kg) or saline 30 minutes prior to intratracheal (i.t.) injection with 10 mug Escherichia coli LPS. In vitro stimulation of primary AE2 cells or murine AE2 cell line MLE-12 was performed with LPS and tumor necrosis factor-alpha (TNF-alpha). RESULTS LIX protein is readily detectable in the lung but not in plasma following LPS administration, demonstrating "compartmentalization" of this chemokine during pulmonary challenge. In contrast to the CXC chemokines keratinocyte-derived chemokine and macrophage inflammatory protein-2, which are abundantly expressed in both lung tissue and alveolar macrophages, LIX expression is largely confined to the lung parenchyma. Compared to controls, intoxicated animals show a decrease in LIX and neutrophil number in bronchoalveolar lavage fluid following LPS challenge. Ethanol inhibits LIX at the transcriptional level. In vitro studies show that LPS and TNF-alpha are synergistic in inducing LIX by either primary AE2 or MLE-12 cells. Acute ethanol exposure potently and dose-dependently inhibits LIX expression by AE2 cells. Activation of nuclear factor-kappaB is critical to LIX expression in MLE-12 cells, and acute ethanol treatment interferes with early activation of this pathway as evidenced by impairing phosphorylation of p65 (RelA). Inhibition of p38 mitogen-activated protein kinase signaling, but not ERK1/2 activity, in MLE-12 cells by acute alcohol is likely an important cause of decreased LIX expression during challenge. CONCLUSIONS These data demonstrate direct suppression of AE2 cell innate immune function by ethanol and add to our understanding of the mechanisms by which acute intoxication impairs the lung's response to microbial challenge.
Evaluation and comparison of robust optimal experiment design criteria

This paper further develops a new approach to optimal experiment design for dynamical systems by introducing and comparing different robust optimal experiment design criteria. Until recently, solutions to the optimal experiment design problem were paradoxical in so far that the optimal experiment depended on the system parameters, i.e. the optimal experiment depended on the very thing that the experiment was aimed at finding. In a recent paper, we proposed an alternative approach, robust in nature, to the experiment design problem which, inter-alia, allowed for the possibility that the true parameters lay in a convex set. Here we further explore this robust solution. In particular, we examine the role played by different design criteria
Broadband class-E power amplifier with high cold output impedance suitable for load modulated dual branch amplifiers

The paper presents a design of a broadband high-efficiency class-E power amplifier (PA) for the advanced efficiency enhancement architectures applications. The design approach is based on presenting very high output reflection coefficient for a class E amplifier over broadband frequencies. An infinite reflection coefficient at load over the broadband frequency range enhances the application of class-E PAs as peaking amplifier in advanced efficiency enhancement architectures like Doherty, delta sigma etc. The proposed approach is validated using a Cree 6 W GaN prototype for a frequency band between 1.8–2.7 GHz. The prototype outputs more than 38 dBm output power with the drain efficiency higher than 55% over 40% of the fraction bandwidth. The drain voltage sweep of the fabricated PA shows that it can be also be employed in load modulated dual branch amplifiers and envelop tracking transmitter structures.
PB2 Residue 158 Is a Pathogenic Determinant of Pandemic H1N1 and H5 Influenza A Viruses in Mice

ABSTRACT Influenza A viruses are human and animal pathogens that cause morbidity and mortality, which range from mild to severe. The 2009 H1N1 pandemic was caused by the emergence of a reassortant H1N1 subtype (H1N1pdm) influenza A virus containing gene segments that originally circulated in human, avian, and swine virus reservoirs. The molecular determinants of replication and pathogenesis of H1N1pdm viruses in humans and other mammals are poorly understood. Therefore, we set out to elucidate viral determinants critical to the pathogenesis of this novel reassortant using a mouse model. We found that a glutamate-to-glycine substitution at residue 158 of the PB2 gene (PB2-E158G) increased the morbidity and mortality of the parental H1N1pdm virus. Results from mini-genome replication assays in human cells and virus titration in mouse tissues demonstrated that PB2-E158G is a pathogenic determinant, because it significantly increases viral replication rates. The virus load in PB2-E158G-infected mouse lungs was 1,300-fold higher than that of the wild-type virus. Our data also show that PB2-E158G had a much stronger influence on the RNA replication and pathogenesis of H1N1pdm viruses than PB2-E627K, which is a known pathogenic determinant. Remarkably, PB2-E158G substitutions also altered the pathotypes of two avian H5 viruses in mice, indicating that this residue impacts genetically divergent influenza A viruses and suggesting that this region of PB2 could be a new antiviral target. Collectively, the data presented in this study demonstrate that PB2-E158G is a novel pathogenic determinant of influenza A viruses in the mouse model. We speculate that PB2-E158G may be important in the adaptation of avian PB2 genes to other mammals, and BLAST sequence analysis identified a naturally occurring human H1N1pdm isolate that has this substitution. Therefore, future surveillance efforts should include scrutiny of this region of PB2 because of its potential impact on pathogenesis.