Miracle-dz/UniFAR-FTUs huggingface dataset:
L-Type Calcium Channel C Terminus Autoregulates Transcription

Calcium homeostasis is critical for cardiac myocyte function and must be tightly regulated. The guiding hypothesis of this study is that a carboxyl-terminal cleavage product of the cardiac L-type calcium channel (CaV1.2) autoregulates expression. First, we confirmed that the CaV1.2 C terminus (CCt) is cleaved in murine cardiac myocytes from mature and developing ventricle. Overexpression of full-length CCt caused a 34±8% decrease of CaV1.2 promoter activity, and truncated CCt caused an 80±3% decrease of CaV1.2 promoter (n=12). The full-length CCt distributes into cytosol and nucleus. A deletion mutant of CCt has a greater relative affinity for the nucleus than full-length CCt, and this is consistent with increased repression of CaV1.2 promoter activity by truncated CCt. Chromatin immunoprecipitation analysis revealed that CCt interacts with the CaV1.2 promoter in adult ventricular cardiac myocytes at promoter modules containing Nkx2.5/Mef2, C/EBp, and a cis regulatory module. The next hypothesis tested was that CCt contributes to transcriptional signaling associated with cellular hypertrophy. We explored whether fetal cardiac myocyte CaV1.2 was regulated by serum in vitro. We tested atrial natriuretic factor promoter activity as a positive control and measured the serum response of CaV1.2 promoter, protein, and L-type current (ICa,L) from fetal mouse ventricular myocytes. Serum increased atrial natriuretic factor promoter activity and cell size as expected. Serum withdrawal increased CaV1.2 promoter activity, mRNA, and ICa,L. Moreover, serum withdrawal decreased the relative nuclear localization of CCt. A combination of promoter deletion mutant analyses, and the response of promoter mutants to serum withdrawal support the conclusion that CCt, a proteolytic fragment of CaV1.2, autoregulates CaV1.2 expression in cardiac myocytes. These data support the novel mechanism that a mobile segment of CaV1.2 links Ca handling to nuclear signaling.
FREE AND OPEN-SOURCE SIMULATION SOFTWARE "URURAU"

Ururau is a free and open-source software written in the Java programming language. The Ururau is able to develop models of simulation at any of the component layers of the software structure. This means that models can be constructed on the layer of the library (lower level), in the core of the software (new palettes, for example) or top layer of the graphical interface. Then, if you want to build simulation models with non-commercial software, with the option to either write its code both in Java as in a graphical user interface of simple operation, you have the option of using Ururau.
A Lightweight Authentication Scheme for E-Health Applications in the Context of Internet of Things

The strong development of the Internet of Things (IoT) is changing traditional perceptions of the current Internet towards a vision of smart objects interacting with each other. In this vision e-health applications are one of the most promising applications in IoT. However, security issues are the major obstacle for their deployment. Among these issues, authentication of the different interconnected entities and exchanged data confidentiality constitutes the main concerns for users that need to be addressed. In this paper, we propose a new lightweight authentication scheme for an e-health application. This scheme allows both of sensors and the Base Station (BS) to authenticate each other in order to secure the collection of health-related data. Our scheme uses nonces and Keyed-Hash message authentication (HMAC) to check the integrity of authentication exchanges. In addition, it provides authentication with less energy consumption, and it terminates with a session key agreement between each sensor and the Base Station. To assess our scheme, we carry out a performance and security analysis. The obtained results show that our scheme saves energy. In addition, it is resistant against different types of attacks.
EGFR Interacts with the Fusion Protein of Respiratory Syncytial Virus Strain 2-20 and Mediates Infection and Mucin Expression

Respiratory syncytial virus (RSV) is the major cause of viral lower respiratory tract illness in children. In contrast to the RSV prototypic strain A2, clinical isolate RSV 2–20 induces airway mucin expression in mice, a clinically relevant phenotype dependent on the fusion (F) protein of the RSV strain. Epidermal growth factor receptor (EGFR) plays a role in airway mucin expression in other systems; therefore, we hypothesized that the RSV 2–20 F protein stimulates EGFR signaling. Infection of cells with chimeric strains RSV A2-2-20F and A2-2-20GF or over-expression of 2–20 F protein resulted in greater phosphorylation of EGFR than infection with RSV A2 or over-expression of A2 F, respectively. Chemical inhibition of EGFR signaling or knockdown of EGFR resulted in diminished infectivity of RSV A2-2-20F but not RSV A2. Over-expression of EGFR enhanced the fusion activity of 2–20 F protein in trans. EGFR co-immunoprecipitated most efficiently with RSV F proteins derived from “mucogenic” strains. RSV 2–20 F and EGFR co-localized in H292 cells, and A2-2-20GF-induced MUC5AC expression was ablated by EGFR inhibitors in these cells. Treatment of BALB/c mice with the EGFR inhibitor erlotinib significantly reduced the amount of RSV A2-2-20F-induced airway mucin expression. Our results demonstrate that RSV F interacts with EGFR in a strain-specific manner, EGFR is a co-factor for infection, and EGFR plays a role in RSV-induced mucin expression, suggesting EGFR is a potential target for RSV disease.
A resonant gate-drive circuit capable of high-frequency and high-efficiency operation

This paper deals with a new resonant gate-drive circuit for power MOSFETs. The proposed gate-drive circuit is characterized by a resonant inductor connected in series to the gate terminal of the MOSFET. It is possible to charge or discharge the input capacitance of the MOSFET by using the series resonance between the inductor and the input capacitance. Experimental results are shown to verify the viability of the resonant gate-drive circuit. As a result, the proposed resonant gate-drive circuit reduces its power consumption by a factor of ten, compared with a conventional one. A high-frequency MOSFET inverter driven by the proposed gate-drive circuits exhibits a high efficiency more than 99% at a 360-kHz and 1-kW operation.
On the physics of harmonic injection in a traveling wave tube

The physics of signal injection to shape the output spectrum in a traveling wave tube (TWT) is studied using an analytic solution to the approximate nonlinear S-MUSE model and with the large signal code LATTE. The results verify the long-standing conjecture that a frequency canceled by signal injection is composed of a component due to the injected signal and a component due to the nonlinearity of the TWT. Furthermore, the structures of the solutions are exploited to explain and predict behavior for various signal injection schemes. The scenarios studied include second harmonic injection to reduce the second harmonic and enhance the fundamental, multiple harmonic injection to eliminate the sensitive output power dependence on injected phase, second harmonic injection to reduce intermodulation distortion, and multiple signal injection to reduce the intermodulation spectrum. Insights are given regarding the effectiveness of an injection depending on whether the injected signal is within or outside the linear gain bandwidth of the TWT.
What does the design of effective CSCL require and how do we study its effects?

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THE ANALYSIS OF STRESS RELAXATION DATA OF SOME VISCOELASTIC FOODS USING A TEXTURE ANALYZER

Uniaxial compression test for dough and several commercial products like jello, mozzarella cheese, cheddar cheese, tofu and sausage (cooked and uncooked) was performed using a texture analyzer (TA). Percent stress relaxation (%SR ), k1 (initial rate of relaxation), k2 (extent of relaxation) and relaxation time (RT) were calculated and compared for different products. The TA software was used to convert the raw SR data into a linear form. Constants k1 and k2 were determined from the intercept and slope of the linear data. Higher values of %SR and k2 (90 and 9, respectively) indicated higher elasticity for jello, whereas wheat flour dough samples showed the lowest values (20–30) for %SR and 1 to 2 for k2. The RT and k1 values were not good indicators for differentiating different products based on their viscoelastic behavior. Measurement of RT was limited by the maximum time for which the data were collected, whereas k1, because of its mathematical form, needed careful interpretation. In this study, %SR was found to be a good measure to interpret viscoelasticity of different food samples.
Immunohistochemical Identification of Kidney Nephron Segments in the Dog, Rat, Mouse, and Cynomolgus Monkey

Kidney is a major target organ in preclinical studies. In recent years, intense research has been undertaken to characterize novel renal toxicity biomarkers. In this context, we studied nephron segment specific antibodies against aquaporin-1 (AQP-1), α-glutathione-S-transferase (alpha-GST), Tamm-Horsfall protein (TH), calbindin-D28K (CalD), and aquaporin-2 (AQP-2), using an immunoperoxidase method on formalin-fixed paraffin-embedded kidney tissues of dogs, rats, mice, and Cynomolgus monkeys. AQP-1 was specific for proximal tubules and thin descending limbs of Henle’s loops and AQP-2 for connecting and collecting ducts in dogs, rats, mice, and Cynomolgus monkeys. Alpha-GST stained the straight part of proximal tubules in dogs and proximal convoluted tubule and straight part of proximal tubules in rats. TH was specific for thick ascending limbs of Henle’s loops in mice, rats, dogs, and Cynomolgus monkeys and stained additionally scattered cells in cortical connecting/collecting ducts of dogs. CalD was found in distal convoluted tubules and cortical connecting and collecting ducts of dogs, rats, and mice and in distal convoluted tubules, connecting ducts, and cortical and medullary collecting ducts of Cynomolgus monkey. This panel of antibodies may be a helpful tool to identify renal tubules by light microscopy in preclinical studies and to validate new biomarkers of renal toxicity.
Detection of somatic BRCA1/2 mutations in ovarian cancer – next‐generation sequencing analysis of 100 cases

The overall prevalence of germline BRCA1/2 mutations is estimated between 11% and 15% of all ovarian cancers. Individuals with germline BRCA1/2 alterations treated with the PARP1 inhibitors (iPARP1) tend to respond better than patients with wild‐type BRCA1/2. Additionally, also somatic BRCA1/2 alterations induce the sensitivity to iPARP1. Therefore, the detection of both germline and somatic BRCA1/2 mutations is required for effective iPARP1 treatment. The aim of this study was to identify the frequency and spectrum of germline and somatic BRCA1/2 alterations in a group of Polish patients with ovarian serous carcinoma. In total, 100 formalin‐fixed paraffin‐embedded (FFPE) ovarian serous carcinoma tissues were enrolled to the study. Mutational analysis of BRCA1/2 genes was performed by using next‐generation sequencing. The presence of pathogenic variants was confirmed by Sanger sequencing. In addition, to confirm the germline or somatic status of the mutation, the nonneoplastic tissue was analyzed by bidirectional Sanger sequencing. In total, 27 (28% of patient samples) mutations (20 in BRCA1 and 7 in BRCA2) were identified. For 22 of 27 patients, nonneoplastic cells were available and sequencing revealed the somatic character of two BRCA1 (2/16; 12.5%) and two BRCA2 (2/6; 33%) mutations. Notably, we identified six novel frameshift or nonsense BRCA1/2 mutations. The heterogeneity of the detected mutations confirms the necessity of simultaneous analysis of BRCA1/2 genes in all patients diagnosed with serous ovarian carcinoma. Moreover, the use of tumor tissue for mutational analysis allowed the detection of both somatic and germline BRCA1/2 mutations.
Occurrence of campylobacter species in healthy well-nourished and malnourished children

The occurrence of Campylobacter species in healthy, well-nourished and healthy, malnourished children of low socioeconomic level in Southern Chile was determined. Campylobacter carriers were significantly most frequent among malnourished (31.4%) than among well-nourished (9.9%) children. Six species were isolated from malnourished children whereas four were found among well-nourished children. C. upsaliensis was the most frequent (13.3%) species isolated from malnourished children, followed by C. lari (7.6%) and C. fetus ssp. fetus (1.9%).
Degeneracy and redundancy in cognitive anatomy

A: Because she knows how to get Arizona's budget back on track. Again, participants judged either reasonableness or circularity, and did so by either ranking or rating arguments. Two-branch arguments were ranked as less circular than one-branch arguments, indicating structural sensitivity, and repetition created less perceived circularity when the opponent had already acknowledged the repeated claim, suggesting pragmatic sensitivity. However, when rated rather than ranked, circularity was unaffected by branching or opponent response. Without explicit comparison, participants were apparently less sensitive to structure and pragmatics in the circularity task. In the case of the reasonableness task, repetition in two-branch arguments was slightly less reasonable than in one-branch arguments, whether ranked or rated. This is the opposite of what was found in the circularity task. As with circularity, acknowledgements were the most acceptable condition for repetition. Thus, pragmatics played a role in reasonableness judgments, but differences remained between circularity and reasonableness judgments , suggesting that they draw on structural and pragmatic components differently. Implications and future research This study and others suggest that structural and pragmatic components are dissociable in informal argument (see also [10,12 – 14]). The results also provide further evidence for the usefulness of Rips's structural rules for informal argument. As Rips notes, the structural and pragmatic components are not equally attended to in all cases, perhaps because a particular task focuses us on one to the exclusion of the other, or because people are not always as sensitive to factors as they ought to be. This needs further investigation, and raises important questions about models of informal argument as normative or descriptive. When participants are less sensitive to a particular component, is this an error in reasoning, or do theories need to specify circumstances when these deviations are appropriate? Also needed is a consideration of socio-cultural and personal factors in argument strategies. Arguers might value preserving relationships or showing someone up more than coordinating claims and evidence [10]. A broader consideration of pragmatic factors will be needed to improve our understanding of informal argument. the bifurcation/bootstrapping method, and Convince Me: computer-based techniques for studying beliefs and their revision. Artificial life provides important theoretical and meth-odological tools for the investigation of Piaget's developmental theory. This new method uses artificial neural networks to simulate living phenomena in a computer. A recent study by Parisi and Schlesinger suggests that artificial life might reinvigorate the Piagetian framework. We contrast artificial life …
Direct Detection and Differentiation of Pathogenic Leptospira Species Using a Multi-Gene Targeted Real Time PCR Approach

Leptospirosis is a growing public and veterinary health concern caused by pathogenic species of Leptospira. Rapid and reliable laboratory tests for the direct detection of leptospiral infections in animals are in high demand not only to improve diagnosis but also for understanding the epidemiology of the disease. In this work we describe a novel and simple TaqMan-based multi-gene targeted real-time PCR approach able to detect and differentiate Leptospira interrogans, L. kirschneri, L. borgpeteresenii and L. noguchii, which constitute the veterinary most relevant pathogenic species of Leptospira. The method uses sets of species-specific probes, and respective flanking primers, designed from ompL1 and secY gene sequences. To monitor the presence of inhibitors, a duplex amplification assay targeting both the mammal β-actin and the leptospiral lipL32 genes was implemented. The analytical sensitivity of all primer and probe sets was estimated to be <10 genome equivalents (GE) in the reaction mixture. Application of the amplification reactions on genomic DNA from a variety of pathogenic and non-pathogenic Leptospira strains and other non-related bacteria revealed a 100% analytical specificity. Additionally, pathogenic leptospires were successfully detected in five out of 29 tissue samples from animals (Mus spp., Rattus spp., Dolichotis patagonum and Sus domesticus). Two samples were infected with L. borgpetersenii, two with L. interrogans and one with L. kirschneri. The possibility to detect and identify these pathogenic agents to the species level in domestic and wildlife animals reinforces the diagnostic information and will enhance our understanding of the epidemiology of leptopirosis.
Structural concrete condition monitoring using a long period grating-based humidity sensor

An optically based sensor has been designed, fabricated and characterized in research to determine moisture ingress in a range of structural concrete samples subjected to a variety of changing environmental conditions. The approach taken to the creation of these novel humidity sensors is using long period grating (LPG) technology in an optical fibre. The sensor is configured by coating LPGs with a thin layer of polymer, following which it was characterized and its performance cross-compared with that of other sensors. The thin layer of polyvinyl alcohol (PVA), whose refractive index varies as a function of humidity level, provides a means to change the optical propagation in the fibre and thus to induce the a wavelength shift in the attenuation bands of its transmission spectrum.
PKR and PKR-like Endoplasmic Reticulum Kinase Induce the Proteasome-dependent Degradation of Cyclin D1 via a Mechanism Requiring Eukaryotic Initiation Factor 2α Phosphorylation*

Cyclin D1 plays a critical role in controlling the G1/S transition via the regulation of cyclin-dependent kinase activity. Several studies have indicated that cyclin D1 translation is decreased upon activation of the eukaryotic initiation factor 2α (eIF2α) kinases. We examined the effect of activation of the eIF2α kinases PKR and PKR-like endoplasmic reticulum kinase (PERK) on cyclin D1 protein levels and translation and determined that cyclin D1 protein levels decrease upon the induction of PKR and PERK catalytic activity but that this decrease is not due to translation. Inhibition of the 26 S proteasome with MG132 rescued cyclin D1 protein levels, indicating that rather than inhibiting translation, PKR and PERK act to increase cyclin D1 degradation. Interestingly, this effect still requires eIF2α phosphorylation at serine 51, as cyclin D1 remains unaffected in cells containing a non-phosphorylatable form of the protein. This proteasome-dependent degradation of cyclin D1 requires an intact ubiquitination pathway, although the ubiquitination of cyclin D1 is not itself affected. Furthermore, this degradation is independent of phosphorylation of cyclin D1 at threonine 286, which is mediated by the glycogen synthase kinase 3β and mitogen-activated protein kinase pathways as described in previous studies. Our study reveals a novel functional cross-talk between eIF2α phosphorylation and the proteasomal degradation of cyclin D1 and that this degradation is dependent upon eIF2α phosphorylation during short, but not prolonged, periods of stress.