Miracle-dz/UniFAR-FTUs huggingface dataset:
Simulation as Science Discovery: Ways of Interactive Meaning-Making

This article addresses how computer-based simulations may support conceptual learning in science education. The study investigates how these interactions unfold, and explores how it may inform design. The article reports on project-based learning in schools where four pairs of students from upper secondary school use a future climate simulator integrated in a web-based learning environment. Our analytical focus is on how the students make use of the simulator to make meaning through the process. The analysis shows a considerable variety in how the students interact with the simulator, and in how they engage in a conceptual level of understanding. The findings indicate that the design was engaging, and three main modes of surprisingly stable uses were identified: utilizing the simulator as a way to get facts, enjoying the aesthetics of interaction as playability, and finally, making use of the simulator as a tool for discovery through cumulative micro-experiments.
A systematic review assessing soft tissue augmentation techniques.

AIM The aim of the present review was to systematically assess the dental literature in terms of soft tissue grafting techniques. The focused question was: is one method superior over others for augmentation and stability of the augmented soft tissue in terms of increasing the width of keratinized tissue (part 1) and gain in soft tissue volume (part 2). METHODS A Medline search was performed for human studies focusing on augmentation of keratinized tissue and/or soft tissue volume, and complemented by additional hand searching. Relevant studies were identified and statistical results were reported for meta-analyses including the test minus control weighted mean differences with 95% confidence intervals, the I-squared statistic for tests of heterogeneity, and the number of significant studies. RESULTS Twenty-five (part 1) and three (part 2) studies met the inclusion criteria; 14 studies (part 1) were eligible for comparison using meta-analyses. An apically positioned flap/vestibuloplasty (APF/V) procedure resulted in a statistically significantly greater gain in keratinized tissue than untreated controls. APF/V plus autogenous tissue revealed statistically significantly more attached gingiva compared with untreated controls and a borderline statistical significance compared with APF/V plus allogenic tissue. Statistically significantly more shrinkage was observed for the APF/V plus allogenic graft compared with the APF/V plus autogenous tissue. Patient-centered outcomes did not reveal any of the treatment methods to be superior regarding postoperative complications. The three studies reporting on soft tissue volume augmentation could not be compared due to lack of homogeneity. The use of subepithelial connective tissue grafts (SCTGs) resulted in statistically significantly more soft tissue volume gain compared with free gingival grafts (FGGs). CONCLUSIONS APF/V is a successful treatment concept to increase the width of keratinized tissue or attached gingiva around teeth. The addition of autogenous tissue statistically significantly increases the width of attached gingiva. For soft tissue volume augmentation, only limited data are available favoring SCTGs over FGG.
Neural interactions in unilateral colliculus and between bilateral colliculi modulate auditory signal processing

In the auditory pathway, the inferior colliculus (IC) is a major center for temporal and spectral integration of auditory information. There are widespread neural interactions in unilateral (one) IC and between bilateral (two) ICs that could modulate auditory signal processing such as the amplitude and frequency selectivity of IC neurons. These neural interactions are either inhibitory or excitatory, and are mostly mediated by γ-aminobutyric acid (GABA) and glutamate, respectively. However, the majority of interactions are inhibitory while excitatory interactions are in the minority. Such unbalanced properties between excitatory and inhibitory projections have an important role in the formation of unilateral auditory dominance and sound location, and the neural interaction in one IC and between two ICs provide an adjustable and plastic modulation pattern for auditory signal processing.
On reliability modelling of fault-tolerant distributed systems

The problem of predicting the reliability of a distributed system based on the principles of Byzantine agreement is addressed. The system is considered inoperable or failed if Byzantine agreement cannot be guaranteed. The reliability models depend on a unified model of interactive consistency, which is based on a unique fault taxonomy appropriate for distributed systems. The unified model takes advantage of the fact that some faults may not be of an arbitrary nature, while still allowing for the fact that some faults may be arbitrary. A closed-form expression for the reliability and the mean time to failure of systems base on the unified model is derived. Each processor is allowed to have multiple failure modes, and the contribution of the interactive consistency algorithm is explicitly taken into account. The practical value of this unified model in designing ultrareliable systems is demonstrated by several examples. <<ETX>>
Open‐label study of oral CEP‐701 (lestaurtinib) in patients with polycythaemia vera or essential thrombocythaemia with JAK2‐V617F mutation

JAK2‐V617F is central to the pathogenesis of myeloproliferative neoplasms. We examined whether lestaurtinib decreased JAK2‐V617F allele burden and evaluated its clinical benefits and tolerability in patients with polycythaemia vera (PV) and essential thrombocythaemia (ET). This phase 2, open‐label, multicentre study was designed to detect ≥15% reduction in JAK2‐V617F allele burden in 15% of patients. Eligible patients received lestaurtinib 80 mg twice daily for 18 weeks and could participate in a 1‐year extension phase of treatment. Of 39 enrolled patients, 27 (69%) had PV; 12 (31%) had ET. While the pre‐specified responder rate of 15% was not met, lestaurtinib modestly reduced JAK2‐V617F allele burden and reduced spleen size in a subset of patients. Of 37 patients in the full efficacy analysis, 5 (14%) responded clinically. Every patient had ≥1 adverse event, most commonly gastrointestinal (95%). Fifteen patients (38%) experienced serious adverse events; 23 (59%) withdrew due to adverse events. This is the first reported study of JAK2‐inhibitor treatment in patients with PV/ET and highlights both the need for further studies to assess the role of JAK2 inhibition in treatment of PV/ET and the use of JAK2‐V617F as a biomarker for response. This trial was registered at www.clinicaltrials. gov as NCT00586651.
Mitochondrial Involvement and Impact in Aging Skeletal Muscle

Atrophy is a defining feature of aging skeletal muscle that contributes to progressive weakness and an increased risk of mobility impairment, falls, and physical frailty in very advanced age. Amongst the most frequently implicated mechanisms of aging muscle atrophy is mitochondrial dysfunction. Recent studies employing methods that are well-suited to interrogating intrinsic mitochondrial function find that mitochondrial respiration and reactive oxygen species emission changes are inconsistent between aging rat muscles undergoing atrophy and appear normal in human skeletal muscle from septuagenarian physically active subjects. On the other hand, a sensitization to permeability transition seems to be a general property of atrophying muscle with aging and this effect is even seen in atrophying muscle from physically active septuagenarian subjects. In addition to this intrinsic alteration in mitochondrial function, factors extrinsic to the mitochondria may also modulate mitochondrial function in aging muscle. In particular, recent evidence implicates oxidative stress in the aging milieu as a factor that depresses respiratory function in vivo (an effect that is not present ex vivo). Furthermore, in very advanced age, not only does muscle atrophy become more severe and clinically relevant in terms of its impact, but also there is evidence that this is driven by an accumulation of severely atrophied denervated myofibers. As denervation can itself modulate mitochondrial function and recruit mitochondrial-mediated atrophy pathways, future investigations need to address the degree to which skeletal muscle mitochondrial alterations in very advanced age are a consequence of denervation, rather than a primary organelle defect, to refine our understanding of the relevance of mitochondria as a therapeutic target at this more advanced age.
TARGETING ACTIVATED LYMPHOCYTES WITH PHOTODYNAMIC THERAPY: SUSCEPTIBILITY OF MITOGEN‐STIMULATED SPLENIC LYMPHOCYTES TO BENZOPORPHYRIN DERIVATIVE (BPD) PHOTOSENSITIZATION

Abstract— Benzoporphyrin derivative monoacid ring A (BPD), a hydrophobic chlorin‐like porphyrin derivative, which fluoresces strongly at 690 nm, may have potential for both oncologic and nononcologic applications in photodynamic therapy (PDT). To study the influence of cellular characteristics on the uptake of BPD, the murine tumor cell line (P815), and in vitro and in vivo concanavalin A (Con A)‐stimulated and unstimulated murine splenic lymphocytes were incubated with 2 µg/mL BPD at 37°C for 0–60 min. At various times, cells were lysed and the amount of BPD taken up by the cells was quantified by fluorescence measurements. The subsets of cells taking up BPD were analyzed using a panel of monoclonal antibodies and the Coulter XL* fluorescence‐activated cell sorter. Furthermore, Con A‐stimulated and unstimulated spleen cells were incubated with 0–50 ng/mL of BPD for 1 h prior to exposure to red light (7.2 J/cm2). Cell survival 24 h post‐PDT was measured by the MTT assay. We found that the rapidly dividing tumor cell line and mitogen‐stimulated murine T cells (mainly CD4V IL‐2R+) took up significantly more BPD (5–10‐fold) than do unstimulated splenic lymphocytes. Increased BPD uptake correlated with greater photoinactivation when these cells were exposed to light at a wavelength of 690 nm. These findings suggest that activated cells of the immune system may be a target for photoinactivation by BPD.
SHIELD: An Automated Framework for Static Analysis of SDN Applications

Software-Defined Network (SDN) is getting popular and increasingly deployed in both of academia and industry. As a result of which, its security issue is being magnified as a critical controversy, and some pioneering researchers have investigated the vulnerabilities of SDN to discover the feasibility of compromising SDN networks. Especially, they prove that a simple malicious/buggy SDN application running on an SDN controller can kill an SDN control plane because it usually has a right to access the resources of SDN controller. To address this issue, we focus on the malicious SDN application themselves (i.e., how to understand if an SDN application is malicious). In this context, we consider analyzing SDN applications before running in a static manner. We present SHIELD, a new automated framework for static analysis of SDN applications carefully considering SDN abilities. SHIELD provides the Control-Flow Graph (CFG) and critical flows of SDN applications. We evaluate the effectiveness of SHIELD with 33 real world applications (both benign and malicious applications), and from the results, we define 10 malicious behaviors of SDN applications.
Colloidal quasicrystals with 12-fold and 18-fold diffraction symmetry

Micelles are the simplest example of self-assembly found in nature. As many other colloids, they can self-assemble in aqueous solution to form ordered periodic structures. These structures so far all exhibited classical crystallographic symmetries. Here we report that micelles in solution can self-assemble into quasicrystalline phases. We observe phases with 12-fold and 18-fold diffraction symmetry. Colloidal water-based quasicrystals are physically and chemically very simple systems. Macroscopic monodomain samples of centimeter dimension can be easily prepared. Phase transitions between the fcc phase and the two quasicrystalline phases can be easily followed in situ by time-resolved diffraction experiments. The discovery of quasicrystalline colloidal solutions advances the theoretical understanding of quasicrystals considerably, as for these systems the stability of quasicrystalline states has been theoretically predicted for the concentration and temperature range, where they are experimentally observed. Also for the use of quasicrystals in advanced materials this discovery is of particular importance, as it opens the route to quasicrystalline photonic band gap materials via established water-based colloidal self-assembly techniques.
Identification and characterization of improved nitrogen efficiency in interspecific hybridized new-type Brassica napus.

BACKGROUND AND AIMS Oilseed rape (Brassica napus) is an important oil crop worldwide. The aim of this study was to identify the variation in nitrogen (N) efficiency of new-type B. napus (genome A(r)A(r)C(c)C(c)) genotypes, and to characterize some critical physiological and molecular mechanisms in response to N limitation. METHODS Two genotypes with contrasting N efficiency (D4-15 and D1-1) were identified from 150 new-type B. napus lines, and hydroponic and pot experiments were conducted. Root morphology, plant biomass, N uptake parameters and seed yield of D4-15 and D1-1 were investigated. Two traditional B. napus (genome A(n)A(n)C(n)C(n)) genotypes, QY10 and NY7, were also cultivated. Introgression of exotic genomic components in D4-15 and D1-1 was evaluated with molecular markers. KEY RESULTS Large genetic variation existed among traits contributing to the N efficiency of new-type B. napus. Under low N levels at the seedling stage, the N-efficient new-type D4-15 showed higher values than the N-inefficient D1-1 line and the traditional B. napus QY10 and NY7 genotypes with respect to several traits, including root and shoot biomass, root morphology, N accumulation, N utilization efficiency (NutE), N uptake efficiency (NupE), activities of nitrate reductase (NR) and glutamine synthetase (GS), and expression levels of N transporter genes and genes that are involved in N assimilation. Higher yield was produced by the N-efficient D4-15 line compared with the N-inefficient D1-1 at maturity. More exotic genome components were introgressed into the genome of D4-15 (64·97 %) compared with D1-1 (32·23 %). CONCLUSIONS The N-efficient new-type B. napus identified in this research had higher N efficiency (and tolerance to low-N stress) than traditional B. napus cultivars, and thus could have important potential for use in breeding N-efficient B. napus cultivars in the field.
Cerebral blood flow response to flavanol-rich cocoa in healthy elderly humans

Background and Purpose Cerebral ischemia is a common, morbid condition accompanied by cognitive decline. Recent reports on the vascular health benefits of flavanol-containing foods signify a promising approach to the treatment of cerebral ischemia. Our study was designed to investigate the effects of flavanol-rich cocoa (FRC) consumption on cerebral blood flow in older healthy volunteers. Methods We used transcranial Doppler (TCD) ultrasound to measure mean blood flow velocity (MFV) in the middle cerebral artery (MCA) in thirty-four healthy elderly volunteers (72 ± 6 years) in response to the regular intake of FRC or flavanol-poor cocoa (FPC). Results In response to two weeks of FRC intake, MFV increased by 8% ± 4% at one week (p = 0.01) and 10% ± 4% (p = 0.04) at two weeks. In response to one week of cocoa, significantly more subjects in the FRC as compared with the FPC group had an increase in their MFV (p < 0.05). Conclusions In summary, we show that dietary intake of FRC is associated with a significant increase in cerebral blood flow velocity in the MCA as measured by TCD. Our data suggest a promising role for regular cocoa flavanol’s consumption in the treatment of cerebrovascular ischemic syndromes, including dementias and stroke.
Diagnosis of Celiac Disease in Clinical Practice: Physician's Alertness to the Condition Essential

Goals We have for several years been training health personnel to recognize celiac disease, and have advocated serologic screening in risk groups. The aim was to establish whether this approach would offer an alternative to population screening, which has yielded a prevalence of 1% in Finland. Background The number of detected celiac disease cases is much lower than that obtained in serologic screening studies. Study Nationwide recommendations for the detection of celiac disease were published in 1998, and training of health personnel took place in 2001 to 2002. The prevalence of celiac disease was calculated from the national registry of patients receiving reimbursement for dietary costs, attested by physician's statement. In 1 of the 10 statements the diagnostic criteria and clinical manifestations were scrutinized. Results The nationwide prevalence of celiac disease was 0.45%; 0.7% in the highest to 0.3% in the lowest area. The annual number of new patients increased from 5/100,000 in the early 1980s to 20/100,000 today. The percentage of patients found in risk groups (relatives of celiac disease patients, patients with extraintestinal symptoms or concomitant autoimmune disorders) was currently 16.3% in the high and 6.6% in the low prevalence area. Seventeen percent of patients had dermatitis herpetiformis, and its incidence was declining. Conclusions A maximal prevalence of 0.7% of celiac disease was ascertained; educating primary health care staff regarding the protean manifestations of the disease seemed to be the key issue. The increase in incidence implies that a prevalence of 1.0% is possible, rendering population screening unnecessary.
Altered Venous Function in Hypertensive Rats

The vascular beds of the upper or lower body of rats were perfused through the aorta with oxygenated Krebs-Ringer solution containing dextran (7 g/100 ml), at 37°C. Perfusion was stopped every 10 minutes, and the pressure rise in the jugular or the femoral vein was recorded during rapid infusion (15.3–90.0 ml/min) of Krebs-Ringer solution into the inferior vena cava. The following groups of rats were studied: (1) six male genetically hypertensive rats (GHR), 9–11 months old, New Zealand strain; (2) seven female GHR, 5-6 months old, New Zealand strain; (3) eight male spontaneously hypertensive rats (SHR), 4 months old, Okamoto strain; (4) five male rats with two-kidney Goldblatt hypertension (2-KGH), 30 days postclipping; (5) seven male 2-KGH rats, 65 days postclipping; (6) eight male rats with one-kidney Goldblatt hypertension (1-KGH), 40 days postclipping; (7) weight- and sex-matched normotensive control rats of the appropriate strain; and (8) weight- and sex-matched two-kidney and one-kidney, sham-clipped normotensive rats. Preliminary studies showed that rapid infusion into the venous circulation fills the veins, but there is no entry of fluid into the arterial side of the circulation. Compared to controls, the venous pressure-volume curves of GHR (male and female), SHR, 1-KGH rats and 2-KGH rats, 65 (but not 30) days postclipping, were shifted toward the pressure axis (P < 0.05). The shift of the venous pressure-volume curves persisted following the reduction of vasoconstrictor tone by killing the rats or by the administration of sodium nitroprusside (0.1 mg/ml perfusate), or by both. The findings suggest decreased venous capacity in hypertensive rats.
Sequential biphasic changes in claudin1 and claudin4 expression are correlated to colorectal cancer progression and liver metastasis

Terminal progression of colorectal cancer (CRC) culminates in liver metastasis. To identify genes that are involved in the metastatic phenotype, cDNA microarrays were used to analyse mRNA expression profiles of colorectal carcinoma (CC)531 rat colon adenocarcinoma cells for changes related to their homing into the liver. Briefly, CC531 cells were intraportally implanted into the liver of Wag‐Rij rats and re‐isolated after 3, 6, 9, 14 and 21 days. Compared to control CC531 cells, claudin1 and claudin4 were among the ≥8‐fold initially down‐regulated genes. The co‐culture of tumour cells with isolated rat hepatocytes and Kupffer cells did not induce down‐regulation of either claudin1 or 4. When the environment effective on circulating tumour cells was simulated by cell culture conditions favouring their adhesion, only claudin4 showed augmented expression. Knockdown of claudin1 and claudin4 mediated by small interfering RNA caused significantly increased migration and decreased clonogenic growth of tumour cells (P < 0.05), but had no effect on their proliferation. These experimental results were paralleled by increased claudin1 and claudin4 expression in human CRC samples in Union for International Cancer Control (UICC) stages I–III, as evaluated by real‐time PCR. Increased claudin4 levels were correlated with significantly reduced overall survival (log‐rank test, P= 0.018). Further, significantly (P < 0.05) reduced expression of claudin1 and claudin4 was observed in stage IV and liver metastasis by immunohistochemistry. In conclusion, sequential biphasic changes in claudin1 and claudin4 expression occur during the homing of rat CC531 CRC cells to the liver. This modulation is reflected by significant changes in claudin expression in human primary and metastatic CRC.
Assembly Requirements and Role of CotH during Spore Coat Formation in Bacillus subtilis

ABSTRACT We report Western blot data showing that the 42.8-kDa product of the previously characterized cotH locus (8) is a structural component of the Bacillus subtilis spore coat. We show that the assembly of CotH requires both CotE and GerE. In agreement with these observations, the ultrastructural analysis of purified spores suggests that CotH is needed for proper formation of both inner and outer layers of the coat.