Miracle-dz/UniFAR-FTUs huggingface dataset:
L-type Ca2+ current in guinea pig ventricular myocytes treated with modulators of tyrosine phosphorylation.

Guinea pig ventricular myocytes in whole cell configuration were treated with tyrosine kinase (TK) inhibitors [genistein (Gst), tyrphostin A23 (T23), and tyrphostin A25 (T25)] and with inactive analogs [daidzein, genistin, and tyrphostin A1 (T1)] to measure effects on L-type Ca2+ current ( I Ca,L). Gst inhibited I Ca,L(IC50 = 47 μM) without affecting its time course or shifting the I Ca,L-voltage relationship. At the highest concentration of isoflavone tested (200 μM), I Ca,L was inhibited by 66 ± 7% (Gst), 22 ± 2% (daidzein), and 1 ± 3% (genistin). Inhibition of I Ca,L by the active tyrphostins was significantly larger than inhibition by T1; at 200 μM the inhibitions were 72 ± 6% (T23), 71 ± 6% (T25), and 27 ± 6% (T1). The phosphotyrosine phosphatase inhibitor orthovanadate (1 mM) had a small stimulatory effect (6 ± 2%) on basal I Ca,L and blocked the inhibition of I Ca,L by TK inhibitors. The data suggest a role for the TK-phosphotyrosine phosphatase system in the regulation of cardiac Ca2+ channels.
Thromboxane A2 contributes to the enhanced tubuloglomerular feedback activity in young SHR.

We performed micropuncture studies to determine the role of thromboxane A2 in the exaggerated tubuloglomerular feedback (TGF) activity in young spontaneously hypertensive rats (SHR). Glomerular function was assessed by changes in proximal tubular stop-flow pressure (SFP) produced by different rates of orthograde perfusion through Henle's loop. Seven-week-old SHR exhibited an exaggerated TGF activity compared with Wistar-Kyoto rats (WKY) during euvolemia, confirming earlier studies. During control periods, the feedback-induced maximal SFP response (ΔSFP) was greater in SHR (18-19 vs. 12-13 mmHg in WKY), whereas basal SFP and proximal tubular free-flow pressure were similar in both strains. In one series, the thromboxane A2 agonist U-46619 was added to the tubular perfusate for a final concentration of 10-6 M. In WKY, ΔSFP was increased by 100% to 26 mmHg. In contrast, ΔSFP in young SHR was unaffected by the thromboxane A2agonist. In other animals, the thromboxane synthase inhibitor pirmagrel (50 mg/kg) was injected intravenously to inhibit thromboxane production. In SHR, pirmagrel decreased ΔSFP by 8.5 mmHg and reduced reactivity. Less attenuation was observed in WKY; ΔSFP was reduced by 3 mmHg, whereas reactivity was unchanged. In other studies, tubular perfusion with the thromboxane receptor inhibitor SQ-29548 (10-6 M) reduced ΔSFP more in SHR (7 vs. 3 mmHg in WKY) and also decreased reactivity more in SHR (2.3 vs. 0.5 mmHg ⋅ nl-1 ⋅ min-1). Coperfusion of SQ-29548 and U-46619 resulted in an 85% block of the effect of U-46619 on ΔSFP. Tubular perfusion with the agonist U-46619 during thromboxane synthase inhibition markedly enhanced ΔSFP in both strains, with a greater effect in WKY. These results suggest that elevated levels of thromboxane A2in young SHR contribute to the exaggerated TGF control of glomerular function in SHR during the developmental phase of hypertension.
Mutations in the voltage‐sensing domain affect the alternative ion permeation pathway in the TRPM3 channel

Mutagenesis at positively charged amino acids (arginines and lysines) (R1–R4) in the voltage‐sensor domain (transmembrane segment (S) 4) of voltage‐gated Na+, K+ and Ca2+ channels can lead to an alternative ion permeation pathway distinct from the central pore. Recently, a non‐canonical ion permeation pathway was described in TRPM3, a member of the transient receptor potential (TRP) superfamily. The non‐canonical pore exists in the native TRPM3 channel and can be activated by co‐stimulation of the endogenous agonist pregnenolone sulphate and the antifungal drug clotrimazole or by stimulation of the synthetic agonist CIM0216. Alignment of the voltage sensor of Shaker K+ channels with the entire TRPM3 sequence revealed the highest degree of similarity in the putative S4 region of TRPM3, and suggested that only one single gating charge arginine (R2) in the putative S4 region is conserved. Mutagenesis studies in the voltage‐sensing domain of TRPM3 revealed several residues in the voltage sensor (S4) as well as in S1 and S3 that are crucial for the occurrence of the non‐canonical inward currents. In conclusion, this study provides evidence for the involvement of the voltage‐sensing domain of TRPM3 in the formation of an alternative ion permeation pathway.
Fragments of Painted Plaster and Marble from the Roman Villas on Katoro Peninsula and Tiola Cape next to Umag Found During the Early Archaeological Researches in 1957 and 1970/71

Ovim člankom obrađeni su ulomci oslikane žbuke i mramora iz rimskih vila s lokaliteta Katoro i Katoro-Tiola, pokraj Umaga. Očuvani dekor pripadao je zidnoj i stropnoj površini. Datacija ulomaka predložena je na osnovu stilističke analize. Ulomci s oslikanim čipkastim bordurama karakterističnim za IV. stil na žutoj i bijeloj podlozi otkriveni su na lokalitetu Katoro, dok se na lokalitetu Katoro-Tiola očuvao jedan ulomak s prikazom čipkaste bordure iz kraja I. st. ili početka II. st. te malobrojni ulomci na bijeloj podlozi s raznim motivima za koje je predložena datacija u II. st. Mramornih nalaza na lokalitetu bilo je vrlo malo, ali svejedno prikazuju nekadašnje bogatstvo vile. Sačuvani ulomci dokazuju postojanje mramornih opus sectile podova kao i korištenje mramornih elemenata u horizontalnoj separaciji zidnih površina.
Safety and effectiveness of a single-piece hydrophobic acrylic intraocular lens (enVista®) – results of a European and Asian-Pacific study

Purpose To evaluate the safety and effectiveness of a single-piece hydrophobic acrylic intraocular lens (IOL) (enVista® MX60; Bausch and Lomb Incorporated, Rochester, NY, USA) following implantation to correct aphakia subsequent to extracapsular cataract extraction in adults. Subjects and methods This was an open-label, non-interventional, observational study conducted in 19 university and private-practice settings in Europe and the Asia-Pacific region to investigate clinical outcomes of the MX60 IOL in standard practice. Eligible subjects were at least 18 years of age and had undergone standard phacoemulsification and extracapsular cataract extraction with implantation of the MX60 IOL. The primary safety endpoint was the occurrence of adverse events, and the primary effectiveness endpoints included visual and refractive outcomes and stability, with data collected up to 2 years post-procedure. Results In this multicenter study, pooled data of 255 eyes were collected and analyzed. Excellent visual and refractive outcomes and stability were demonstrated. At postoperative visit 4 (61–180 days postoperative), 62.2% of subjects achieved a Snellen best-corrected distance visual acuity (CDVA) of 20/20 (decimal 1.00), and 97.8% of subjects achieved a CDVA of 20/40 (decimal 0.50) or better. One eye (1.0%) underwent neodymium:yttrium aluminum garnet capsulotomy at 12 months post-procedure. No glistenings of any grade were reported for any subject at any visit. Adverse events were infrequent and were consistent with incidences generally reported with cataract surgery. Conclusion This study, which enrolled all comers, provided evidence of the excellent safety and effectiveness of the MX60 IOL in standard practice. Favorable clinical outcomes included outstanding visual and refractive outcomes and stability. No glistenings were reported at any postoperative visit.
The Creative Process of Cultural Evolution

Even this saying itself is a variant of a similar statement attributed to Bernard of Chartres in the 12th Century, and inspired the title for a book by Steven Hawking and an album by Oasis. Creative ideas beget other creative ideas and, as a result, modifications accumulate, and we see an overall increase in the complexity of cultural novelty over time, a phenomenon sometimes referred to as the ratchet effect (Tomasello, Kruger, & Ratner, 1993). Although we may never meet the people or objects that creatively influence us, by assimilating what we encounter around us and bringing to bear our own insights and perspectives, we all contribute in our own way, however small, to a second evolutionary process -- the evolution of culture. This chapter explores how we can better understand culture by understanding the creative processes that fuel it, and better understand creativity by examining it from its cultural context. First, we look at some theoretical frameworks for how culture evolves and what these frameworks imply for the role of creativity. Then we will see how questions about the relationship between creativity and cultural evolution have been addressed using an agent-based model. We will also discuss studies of how creative outputs are influenced, in perhaps unexpected ways, by other ideas and individuals, and how individual creative styles "peek through" cultural outputs in different domains.
Effect of maternal foraging habitat on offspring quality in the loggerhead sea turtle (Caretta caretta)

Abstract Exploring a trade‐off between quantity and quality of offspring allows differences in the fitness between alternative life histories to be accurately evaluated. We addressed the mechanism that maintains alternative life histories (small oceanic planktivores vs. large neritic benthivores) observed in a loggerhead sea turtle (Caretta caretta) population, which has been suggested to be environmental, based on the lack of genetic structure and a large difference in reproductive output. We examined whether maternal foraging habitat affects offspring quality, by measuring the morphology, emergence success, and righting response of hatchlings following incubation in a common open sand area over the whole nesting season at Yakushima Island, Japan, and by recording early growth and survival of offspring that were reared in a common environment at a Japanese aquarium. Furthermore, we tested whether sea turtles adjust egg size in response to temporal shifts of the incubation environment. There were no significant differences in any hatchling traits between oceanic and neritic foragers (which were classified by stable isotope ratios), except for clutches laid during the warmest period of the nesting season. There were also no significant differences in the growth and survival of offspring originating from the two foragers. The size of eggs from both foragers significantly increased as the season progressed, even though the rookery had heavy rainfall, negating the need to counteract heat‐related reduction in hatchling morphology. In comparison, the sizes of adult body and clutches from both foragers did not vary significantly. The results further support our previous suggestions that the size‐related foraging dichotomy exhibited by adult sea turtles does not have a genetic basis, but derives from phenotypic plasticity. Adjustment in reproductive investment may be associated with: (1) predation avoidance, (2) founder effect, and/or (3) annual variation in egg size.
Mechanical Properties of Optimized Diamond Lattice Structure for Bone Scaffolds Fabricated via Selective Laser Melting

Developments in selective laser melting (SLM) have enabled the fabrication of periodic cellular lattice structures characterized by suitable properties matching the bone tissue well and by fluid permeability from interconnected structures. These multifunctional performances are significantly affected by cell topology and constitutive properties of applied materials. In this respect, a diamond unit cell was designed in particular volume fractions corresponding to the host bone tissue and optimized with a smooth surface at nodes leading to fewer stress concentrations. There were 33 porous titanium samples with different volume fractions, from 1.28 to 18.6%, manufactured using SLM. All of them were performed under compressive load to determine the deformation and failure mechanisms, accompanied by an in-situ approach using digital image correlation (DIC) to reveal stress–strain evolution. The results showed that lattice structures manufactured by SLM exhibited comparable properties to those of trabecular bone, avoiding the effects of stress-shielding and increasing longevity of implants. The curvature of optimized surface can play a role in regulating the relationship between density and mechanical properties. Owing to the release of stress concentration from optimized surface, the failure mechanism of porous titanium has been changed from the pattern of bottom-up collapse by layer (or cell row) to that of the diagonal (45°) shear band, resulting in the significant enhancement of the structural strength.
EWSR1 Fusions With CREB Family Transcription Factors Define a Novel Myxoid Mesenchymal Tumor With Predilection for Intracranial Location

Recurrent gene fusions involving EWSR1 with members of the cAMP response element binding protein (CREB) family (ATF1 and CREB1) have been reported in a diverse group of tumors including angiomatoid fibrous histiocytoma (AFH), soft tissue and gastrointestinal clear cell sarcoma, primary pulmonary myxoid sarcoma, and hyalinizing clear cell carcinoma of salivary gland. We have recently encountered a group of 5 myxoid mesenchymal tumors positive for EWSR1 fusions with one of the CREB family member (ATF1, CREB1, and CREM), with histologic features distinct from any of the previously described pathologic entities. Tumors occurred in children or young adults (12 to 23 y; mean, 18 y), with equal sex distribution. All except 1 were intracranial (intra-axial, 2; meningeal, 2), whereas 1 was perirectal. Histologically, the tumors were well circumscribed, often lobulated, composed of uniform ovoid to round cells, and arranged in cord-like or reticular structures in a myxoid background. All except 1 displayed unique sunburst amianthoid fibers. Immunohistochemically, tumors were positive for epithelial membrane antigen (5/5; 4 focal, 1 diffuse) and desmin (3/5). A novel EWSR1-CREM fusion was identified by RNA sequencing in the perirectal tumor, which was further confirmed by fluorescence in situ hybridization (FISH) and reverse transcription-polymerase chain reaction (RT-PCR). A second case with similar EWSR1-CREM fusion was identified by RT-PCR and FISH in a meningeal tumor. The remaining cases studied by FISH showed the presence of EWSR1-CREB1 fusion in 2 cases and EWSR1-ATF1 in 1. In conclusion, we report a distinct group of myxoid mesenchymal neoplasms occurring in children or young adults with a predilection for intracranial locations. Although the immunoprofile [epithelial membrane antigen (EMA), desmin] and the fusion type raise the possibility of a myxoid AFH, none of the typical histologic findings of AFH were present, suggesting a novel entity.
Exploiting the entire feature space with sparsity for automatic image annotation

The explosive growth of digital images requires effective methods to manage these images. Among various existing methods, automatic image annotation has proved to be an important technique for image management tasks, e.g., image retrieval over large-scale image databases. Automatic image annotation has been widely studied during recent years and a considerable number of approaches have been proposed. However, the performance of these methods is yet to be satisfactory, thus demanding more effort on research of image annotation. In this paper, we propose a novel semi supervised framework built upon feature selection for automatic image annotation. Our method aims to jointly select the most relevant features from all the data points by using a sparsity-based model and exploiting both labeled and unlabeled data to learn the manifold structure. Our framework is able to simultaneously learn a robust classifier for image annotation by selecting the discriminating features related to the semantic concepts. To solve the objective function of our framework, we propose an efficient iterative algorithm. Extensive experiments are performed on different real-world image datasets with the results demonstrating the promising performance of our framework for automatic image annotation.
Methylation polymorphism influences practice effects in children during attention tasks

ABSTRACT Epigenetic mechanisms mediate the influence of experience on gene expression. Methylation is a principal method for inducing epigenetic effects on DNA. In this paper, we examine alleles of the methylenetetrahydrofolate reductase (MTHFR) gene that vary enzyme activity, altering the availability of the methyl donor and thus changing the efficiency of methylation. We hypothesized that alleles of the MTHFR gene would influence behavior in an attention-related task in conjunction with genes known to influence attention. We found that seven-year-old children homozygous for the C allele of MTHFR in interaction with the catechol O-methyltransferase (COMT) gene showed greater improvement in overall reaction time (RT) and in conflict resolution with practice on the Attention Network Test (ANT). This finding indicates that methylation may operate on or through genes that influence executive network operation. However, MTHFR T allele carriers showed faster overall RT and conflict resolution. Some children showed an initial improvement in ANT RT followed by a decline in performance, and we found that alleles of the dopamine beta-hydroxylase (DBH) gene were related to this performance decline. These results suggest a genetic dissociation between improvement while learning a skill and reduction in performance with continued practice.
Clinical and Economic Consequences of Early Cancer After Kidney Transplantation in Contemporary Practice

Background Current clinical and economic consequences of cancer after kidney transplantation are incompletely defined. Methods We examined United States Renal Data System records of Medicare-insured kidney transplant recipients in 2000 to 2011 to determine clinical and economic impacts of cancer diagnosed within the first 3 years posttransplantation. Cancer diagnoses were identified using Medicare billing codes and categorized as nonmelanoma skin cancer (NMSC), viral-linked and “other” cancers. Associations of cancers with mortality and graft loss were estimated by time-varying Cox regression. Impacts of cancer diagnoses on inpatient and outpatient costs within each year were quantified by multivariate linear regression modeling. Results Among 67 157 recipients, by 3 years posttransplant, NMSC was diagnosed in 5.7%, viral-linked cancer in 1.9%, and “other” cancers in 6.3%. Viral-linked cancer was associated with more than 3-fold increased risk in subsequent mortality until the third transplant anniversary, and nearly twice the mortality risk after year 3. “Other” cancers had similar associations with death and graft loss, whereas NMSC was associated with 33% higher mortality beyond the third year posttransplant. Viral-linked cancer had the largest inpatient and outpatient cost impacts per case, followed by “other” cancer, whereas NMSC impacted only outpatient costs. Care of new cancer diagnoses was generally more costly than care of previously established diagnoses. Cancer accounted for 3% to 5.5% of total inpatient Medicare expenditures and 1.5% to 3.3% of outpatient expenditures in the first 3 years posttransplant. Conclusions Early posttransplant malignancy is an expensive and morbid condition that warrants attention in efforts to improve pretransplant screening and management protocols before and after transplant.
Histone deacetylase inhibitors correct the cholesterol storage defect in most Niemann-Pick C1 mutant cells[S]

Niemann-Pick C (NPC) disease is an autosomal recessive disorder that leads to excessive storage of cholesterol and other lipids in late endosomes and lysosomes. The large majority of NPC disease is caused by mutations in NPC1, a large polytopic membrane protein that functions in late endosomes. There are many disease-associated mutations in NPC1, and most patients are compound heterozygotes. The most common mutation, NPC1I1061T, has been shown to cause endoplasmic reticulum-associated degradation of the NPC1 protein. Treatment of patient-derived NPC1I1061T fibroblasts with histone deacetylase inhibitors (HDACis) vorinostat or panobinostat increases expression of the mutant NPC1 protein and leads to correction of the cholesterol storage. Here, we show that several other human NPC1 mutant fibroblast cell lines can also be corrected by vorinostat or panobinostat and that treatment with vorinostat extends the lifetime of the NPC1I1061T protein. To test effects of HDACi on a large number of NPC1 mutants, we engineered a U2OS cell line to suppress NPC1 expression by shRNA and then transiently transfected these cells with 60 different NPC1 mutant constructs. The mutant NPC1 did not significantly reduce cholesterol accumulation, but approximately 85% of the mutants showed reduced cholesterol accumulation when treated with vorinostat or panobinostat.
Dietary Intake of Antioxidant Vitamins and Carotenoids and Risk of Developing Active Tuberculosis in a Prospective Population-Based Cohort Study

Antioxidants may protect against oxidative stress, which is associated with tuberculosis (TB) disease. However, direct evidence for a protective association between dietary antioxidants and TB incidence in humans has been lacking. The relationship between intake of antioxidant vitamins (vitamins A, C, D, and E) and individual carotenoids (α-carotene, β-carotene, β-cryptoxanthin, lycopene, and lutein) and TB incidence was examined in the Singapore Chinese Health Study, a prospective cohort study of 63,257 adults aged 45-74 years enrolled during 1993-1998. Baseline intake of these antioxidants was estimated using a validated semiquantitative food frequency questionnaire including questions on use of dietary supplements. After an average of 16.9 years of follow-up, 1,186 incident active TB cases were identified among cohort participants. Compared with the lowest quartile, reduced risk of active TB was observed for the highest quartile of vitamin A intake (hazard ratio = 0.71, 95% confidence interval: 0.59, 0.85; P-trend < 0.01) and β-carotene intake (hazard ratio = 0.76, 95% confidence interval: 0.63, 0.91; P-trend < 0.01), regardless of smoking status. Lower TB risk was seen for vitamin C intake among current smokers only. Other vitamins and carotenoids were not associated with TB risk. These results suggest that vitamin C may reduce TB risk among current smokers by ameliorating oxidative stress, while vitamin A and β-carotene may have additional antimycobacterial properties.
Novel Candidate Genes Underlying Extreme Trophic Specialization in Caribbean Pupfishes

The genetic changes responsible for evolutionary transitions from generalist to specialist phenotypes are poorly understood. Here we examine the genetic basis of craniofacial traits enabling novel trophic specialization in a sympatric radiation of Cyprinodon pupfishes endemic to San Salvador Island, Bahamas. This recent radiation consists of a generalist species and two novel specialists: a small-jawed "snail-eater" and a large-jawed "scale-eater. " We genotyped 12 million single nucleotide polymorphisms (SNPs) by whole-genome resequencing of 37 individuals of all three species from nine populations and integrated genome-wide divergence scans with association mapping to identify divergent regions containing putatively causal SNPs affecting jaw size-the most rapidly diversifying trait in this radiation. A mere 22 fixed variants accompanied extreme ecological divergence between generalist and scale-eater species. We identified 31 regions (20 kb) containing variants fixed between specialists that were significantly associated with variation in jaw size which contained 11 genes annotated for skeletal system effects and 18 novel candidate genes never previously associated with craniofacial phenotypes. Six of these 31 regions showed robust signs of hard selective sweeps after accounting for demographic history. Our data are consistent with predictions based on quantitative genetic models of adaptation, suggesting that the effect sizes of regions influencing jaw phenotypes are positively correlated with distance between fitness peaks on a complex adaptive landscape.