Miracle-dz/UniFAR-FTUs huggingface dataset:
An analysis of glass – ceramic research and commercialization

G has been an important material since the early stages of civilization. Glass–ceramics are polycrystalline materials obtained by controlled crystallization of certain glasses that contain one or more crystalline phases dispersed in a residual glass matrix. The distinct chemical nature of these phases and their nanostructures or microstructures have led to various unusual combinations of properties and applications in the domestic, space, defense, health, electronics, architecture, chemical, energy, and waste management fields. In 1739, French chemist René-Antoine Ferchault de Réaumur was the first person known to produce partially crystallized glass. Réaumur heat-treated soda–lime–silica glass bottles in a bed of gypsum and sand for several days, and the process turned the glass into a porcelain-like opaque material. Although Réaumur had succeeded in converting glass into a polycrystalline material, unfortunately the new product sagged, deformed, and had low strength because of uncontrolled surface crystallization.
Modeling pathogenesis of primary liver cancer in lineage-specific mouse cell types.

BACKGROUND & AIMS Human primary liver cancer is classified into biologically distinct subgroups based on cellular origin. Liver cancer stem cells (CSCs) have been recently described. We investigated the ability of distinct lineages of hepatic cells to become liver CSCs and the phenotypic and genetic heterogeneity of primary liver cancer. METHODS We transduced mouse primary hepatic progenitor cells, lineage-committed hepatoblasts, and differentiated adult hepatocytes with transgenes encoding oncogenic H-Ras and SV40LT. The CSC properties of transduced cells and their ability to form tumors were tested by standard in vitro and in vivo assays and transcriptome profiling. RESULTS Irrespective of origin, all transduced cells acquired markers of CSC/progenitor cells, side populations, and self-renewal capacity in vitro. They also formed a broad spectrum of liver tumors, ranging from cholangiocarcinoma to hepatocellular carcinoma, which resembled human liver tumors, based on genomic and histologic analyses. The tumor cells coexpressed hepatocyte (hepatocyte nuclear factor 4α), progenitor/biliary (keratin 19, epithelial cell adhesion molecule, A6), and mesenchymal (vimentin) markers and showed dysregulation of genes that control the epithelial-mesenchymal transition. Gene expression analyses could distinguish tumors of different cellular origin, indicating the contribution of lineage stage-dependent genetic changes to malignant transformation. Activation of c-Myc and its target genes was required to reprogram adult hepatocytes into CSCs and for tumors to develop. Stable knockdown of c-Myc in transformed adult hepatocytes reduced their CSC properties in vitro and suppressed growth of tumors in immunodeficient mice. CONCLUSIONS Any cell type in the mouse hepatic lineage can undergo oncogenic reprogramming into a CSC by activating different cell type-specific pathways. Identification of common and cell of origin-specific phenotypic and genetic changes could provide new therapeutic targets for liver cancer.
Spatial Ecology of the Oregon Gartersnake, Thamnophis atratus hydrophilus, in a Free-Flowing Stream Environment

Abstract Spatial patterns of animals have important implications for population dynamics and can reveal other key aspects of a species' ecology. Movements and the resulting spatial arrangements have fitness and genetic consequences for both individuals and populations. We studied the spatial and dispersal patterns of the Oregon Gartersnake, Thamnophis atratus hydrophilus, using capture–recapture techniques. Snakes showed aggregated dispersion. Frequency distributions of movement distances were leptokurtic; the degree of kurtosis was highest for juvenile males and lowest for adult females. Males were more frequently recaptured at locations different from their initial capture sites, regardless of age class. Dispersal of neonates was not biased, whereas juvenile and adult dispersal were male-biased, indicating that the mechanisms that motivate individual movements differed by both age class and sex. Males were recaptured within shorter time intervals than females, and juveniles were recaptured within shorter time intervals than adults. We attribute differences in capture intervals to higher detectability of males and juveniles, a likely consequence of their greater mobility. The aggregated dispersion appears to be the result of multi-scale habitat selection, and is consistent with the prey choices and related foraging strategies exhibited by the different age classes. Inbreeding avoidance in juveniles and mate-searching behavior in adults may explain the observed male-biased dispersal patterns.
Cytotoxic Potential of Lung CD8+ T Cells Increases with Chronic Obstructive Pulmonary Disease Severity and with In Vitro Stimulation by IL-18 or IL-15

Lung CD8+ T cells might contribute to progression of chronic obstructive pulmonary disease (COPD) indirectly via IFN-γ production or directly via cytolysis, but evidence for either mechanism is largely circumstantial. To gain insights into these potential mechanisms, we analyzed clinically indicated lung resections from three human cohorts, correlating findings with spirometrically defined disease severity. Expression by lung CD8+ T cells of IL-18R and CD69 correlated with severity, as did mRNA transcripts for perforin and granzyme B, but not Fas ligand. These correlations persisted after correction for age, smoking history, presence of lung cancer, recent respiratory infection, or inhaled corticosteroid use. Analysis of transcripts for killer cell lectin-like receptor G1, IL-7R, and CD57 implied that lung CD8+ T cells in COPD do not belong to the terminally differentiated effector populations associated with chronic infections or extreme age. In vitro stimulation of lung CD8+ T cells with IL-18 plus IL-12 markedly increased production of IFN-γ and TNF-α, whereas IL-15 stimulation induced increased intracellular perforin expression. Both IL-15 and IL-18 protein expression could be measured in whole lung tissue homogenates, but neither correlated in concentration with spirometric severity. Although lung CD8+ T cell expression of mRNA for both T-box transcription factor expressed in T cells and GATA-binding protein 3 (but not retinoic acid receptor-related orphan receptor γ or α) increased with spirometric severity, stimulation of lung CD8+ T cells via CD3ε-induced secretion of IFN-γ, TNF-α, and GM-CSF, but not IL-5, IL-13, and IL-17A. These findings suggest that the production of proinflammatory cytokines and cytotoxic molecules by lung-resident CD8+ T cells contributes to COPD pathogenesis.
Complement Evasion Mediated by Enhancement of Captured Factor H: Implications for Protection of Self-Surfaces from Complement

In an attempt to evade annihilation by the vertebrate complement system, many microbes capture factor H (FH), the key soluble complement-regulating protein in human plasma. However, FH is normally an active complement suppressor exclusively on self-surfaces and this selective action of FH is pivotal to self versus non-self discrimination by the complement system. We investigated whether the bacterially captured FH becomes functionally enhanced and, if so, how this is achieved at a structural level. We found, using site-directed and truncation mutagenesis, surface plasmon resonance, nuclear magnetic resonance spectroscopy, and cross-linking and mass spectrometry, that the N-terminal domain of Streptococcus pneumoniae protein PspC (PspCN) not only binds FH extraordinarily tightly but also holds it in a previously uncharacterized conformation. Functional enhancement arises from exposure of a C-terminal cryptic second binding site in FH for C3b, the activation-specific fragment of the pivotal complement component, C3. This conformational change of FH doubles its affinity for C3b and increases 5-fold its ability to accelerate decay of the binary enzyme (C3bBb) responsible for converting C3 to C3b in an amplification loop. Despite not sharing critical FH-binding residues, PspCNs from D39 and Tigr4 S. pneumoniae exhibit similar FH-anchoring and enhancing properties. We propose that these bacterial proteins mimic molecular markers of self-surfaces, providing a compelling hypothesis for how FH prevents complement-mediated injury to host tissue while lacking efficacy on virtually all other surfaces. In hemolysis assays with 2-aminoethylisothiouronium bromide–treated erythrocytes that recapitulate paroxysmal nocturnal hemoglobinuria, PspCN enhanced protection of cells by FH, suggesting a new paradigm for therapeutic complement suppression.
Nest box exploration may stimulate breeding physiology and alter mRNA expression in the medial preoptic area of female European starlings

ABSTRACT Environmental resources are proposed to fine-tune the timing of breeding, yet how they may do so remains unclear. In female European starlings (Sturnus vulgaris), nest cavities are limited resources that are necessary for breeding. Females that explore nest cavities, compared with those that do not, readily perform sexually motivated behaviors. We assigned female starlings to aviaries with: (1) no nest boxes, (2) nest boxes, or (3) nest boxes, plants, flowing water, insects and berries to test the hypothesis that environmental resources alter neural systems to stimulate mating behavior. Compared with other females, females that were housed with and explored nest boxes had higher estradiol, higher preproenkephalin (PENK) mRNA and lower levels of D1 and D2 dopamine receptor mRNA in the medial preoptic area (mPOA); a region in which opioids and dopamine modify female sexual behaviors and sexual motivation. Additionally, in the mPOA, PENK and tyrosine hydroxylase mRNA positively predicted, whereas estrogen receptor beta mRNA negatively predicted, nest box exploration. In the ventromedial hypothalamus (a region in which estradiol acts to stimulate sexual behavior), estrogen receptor alpha mRNA was highest in females that had access to but did not explore nest cavities. It is likely that seasonal increases in estradiol modify mRNA in the mPOA to facilitate nest cavity exploration. It is also possible that nest cavity exploration further alters gene expression in the mPOA, functioning to coordinate mating with resource availability. Thus, nest cavity exploration may be a form of self-stimulation that alters neural systems to fine-tune sexual behavior. Summary: Environmental resources crucial for breeding may alter breeding physiology and circuits controlling sexual and sexually motivated behaviors to coordinate breeding with resource availability.
Das Erkennen von Emotionen aus Ausdrucksbewegungen des Gesichts

The investigation presented in this paper concerns the relevance of motion information for the recognition of emotions. Facial expressions of the basic emotions (according to Ekman) were shown to 48 subjects. The scenes were either static or dynamic under nromal or light-point presentation conditions. The observers had to match facial expressions to emotional meanings. The results show that motion information alone is a relevant source for the recognition of emotions. Furthermore, the role of motion information in the recognition of specific emotions seems to vary for the different emotions.
Surface Roughness, Microhardness, and Microleakage of a Silorane-Based Composite Resin after Immediate or Delayed Finishing/Polishing

Objective. This study evaluated the effect of immediate or delayed finishing/polishing using different systems on the surface roughness, hardness, and microleakage of a silorane-based composite. Material and Methods. Specimens were made with silorane-based composite (Filtek P90, 3M ESPE) and assigned to the treatments: control (light-cured); aluminum oxide discs (Sof-Lex, 3M ESPE); diamond-impregnated silicone tips (Astropol, Ivoclar Vivadent); aluminum oxide-impregnated silicone tips (Enhance, Dentsply). Half of the specimens were finished/polished immediately and the rest after 7 days. Surface roughness (Ra, μm; n = 20) and Vickers microhardness (50 g; 45 s; n = 10) were measured. Cavities were prepared in bovine incisors and filled with Filtek P90. The fillings received immediate or delayed finishing/polishing (n = 10) and were subjected to dye penetration test (0.5% basic fuchsin, 24 h). Data were analyzed by ANOVA and Scheffe, Kruskal-Wallis, and Mann-Whitney tests (p < 0.05). Results. The finishing/polishing system significantly influenced roughness and microhardness (p < 0.0001). For enamel, microleakage was not affected by the finishing/polishing system (p = 0.309). For dentin, Sof-Lex discs and Astropol points promoted greater microleakage than Enhance points (p = 0.033). Conclusion. Considering roughness, microhardness, and microleakage together, immediate finishing/polishing of a silorane-based composite using aluminum oxide discs may be recommended.
A Common Ancestral Asn242Ser Mutation in TMEM67 Identified in Multiple Iranian Families with Joubert Syndrome

Background: Joubert syndrome (JS) is a clinically and genetically heterogeneous group of rare neurodevelopmental disorder characterised by peculiar midbrain-hindbrain malformation, known as the “molar tooth” sign. JS can manifest a broad range of signs and symptoms. The most common features of JS are hypotonia, ataxia, developmental delay/intellectual disability, abnormal eye movements, and neonatal breathing abnormalities. To date, 29 genes have been shown to cause JS. Methods: We employed whole-genome single nucleotide polymorphism genotyping in a group of Iranian families with JS and Sanger sequencing of a known mutation associated with JS located in a single homozygous regions shared by affected members of the families. Results: Homozygosity mapping uncovered a shared ∼2.2-Mb run of homozygosity on chromosome 8q21.3-q22.1 encompassing the known JS-causing TMEM67 gene. Sanger sequencing of a known mutation (NM_153704.5: c.725A>G; p.Asn242Ser) in TMEM67 identified from studying another Iranian family using whole-exome sequencing confirmed the presence of the homozygous mutation in 22 affected members of 12 nuclear families. “Molar tooth” sign of brain magnetic resonance imaging, moderate-to-severe neurodevelopmental delay, and abnormal eye movements were the most common features of affected individuals. In addition, liver disease, seizure, behavioural abnormalities, failure to thrive, and kidney disease were observed variably in some of the patients. Conclusion: We propose that Asn242Ser is a founder mutation in the Iranian population, which might explain a significant proportion of JS cases from eastern Iran. Therefore, screening for this variant should be considered for genetic testing in Iranian patients with JS. In addition, this finding is important for developing population-specific genetic testing in Iran.
JAK2V617F activating mutation is associated with the myeloproliferative type of chronic myelomonocytic leukaemia

Background: Chronic myelomonocytic leukaemia (CMML) is a haematopoietic malignancy with heterogeneous clinical and morphological features. It is classified in the World Health Organization myeloproliferative-myelodysplastic overlap category. JAK2V617F mutation can be found in a large percentage of patients with myeloproliferative neoplasms. Aims: To investigate the association between JAK2V617F mutation and clinical, haematological and bone marrow histological features in CMML and to verify whether the mutation is associated with the myeloproliferative type of the disease. Methods: 78 consecutive patients with newly diagnosed CMML from 2004 to 2008 were included in the study. JAK2V617F mutation was assessed using direct sequencing of exon 14 or by allele-specific PCR from total peripheral blood or bone marrow samples. Results: JAK2V617F mutation was identified in eight cases (10.2%). All patients with the mutation presented with splenomegaly and had a significantly higher haemoglobin level and neutrophil count than patients without the mutation. All bone marrow biopsies of JAK2V617F-mutated CMML showed increased erythropoiesis, a marked myeloid and megakaryocytic hyperplasia with occasionally clustered megakaryocytes, and a mild or moderate (grade 1 or 2) fibrosis; six cases showed an increased number of dilated sinusoids and reactive lymphoid nodules. Conclusions: The results indicate that JAK2V617F mutation is associated with clinical and morphological features of the myeloproliferative type of CMML. Therefore, JAK2 mutation analysis together with bone marrow morphology could help in a more appropriate classification of the disease.
Condensin function at centromere chromatin facilitates proper kinetochore tension and ensures correct mitotic segregation of sister chromatids

The condensin complex is essential for sister chromatid segregation in eukaryotic mitosis. Nevertheless, in budding yeast, condensin mutations result in massive mis‐segregation of chromosomes containing the nucleolar organizer, while other chromosomes, which also contain condensin binding sites, remain genetically stable. To investigate this phenomenon we analyzed the mechanism of the cell‐cycle arrest elicited by condensin mutations. Under restrictive conditions, the majority of condensin‐deficient cells arrest in metaphase. This metaphase arrest is mediated by the spindle checkpoint, particularly by the spindle‐kinetochore tension‐controlling pathway. Inactivation of the spindle checkpoint in condensin mutants resulted in frequent chromosome non‐disjunction, eliminating the bias in chromosome mis‐segregation towards rDNA‐containing chromosomes. The spindle tension defect in condensin‐impaired cells is likely mediated by structural defects in centromere chromatin reflected by the partial loss of the centromere histone Cse4p. These findings show that, in addition to its essential role in rDNA segregation, condensin mediates segregation of the whole genome by maintaining the centromere structure in Saccharomyces cerevisiae.
Speeding up MCMC by Delayed Acceptance and Data Subsampling

ABSTRACT The complexity of the Metropolis–Hastings (MH) algorithm arises from the requirement of a likelihood evaluation for the full dataset in each iteration. One solution has been proposed to speed up the algorithm by a delayed acceptance approach where the acceptance decision proceeds in two stages. In the first stage, an estimate of the likelihood based on a random subsample determines if it is likely that the draw will be accepted and, if so, the second stage uses the full data likelihood to decide upon final acceptance. Evaluating the full data likelihood is thus avoided for draws that are unlikely to be accepted. We propose a more precise likelihood estimator that incorporates auxiliary information about the full data likelihood while only operating on a sparse set of the data. We prove that the resulting delayed acceptance MH is more efficient. The caveat of this approach is that the full dataset needs to be evaluated in the second stage. We therefore propose to substitute this evaluation by an estimate and construct a state-dependent approximation thereof to use in the first stage. This results in an algorithm that (i) can use a smaller subsample m by leveraging on recent advances in Pseudo-Marginal MH (PMMH) and (ii) is provably within O(m− 2) of the true posterior.
Functional Heterogeneity of Vaccine-Induced CD8+ T Cells1

The functional status of circulating vaccine-induced, tumor-specific T cells has been questioned to explain their paradoxical inability to inhibit tumor growth. We enumerated with HLA-A*0201/peptide tetramers (tHLA) vaccine-elicited CD8+ T cell precursor frequency among PBMC in 13 patients with melanoma undergoing vaccination with the HLA-A*0201-associated gp100:209–217(210 M) epitope. T cell precursor frequency increased from undetectable to 12,400 ± 3,600 × 106 CD8+ T cells after vaccination and appeared heterogeneous according to previously described functional subtypes: CD45RA+CD27+ (14 ± 2.6% of tHLA-staining T cells), naive; CD45RA−CD27+ (14 ± 3.2%), memory; CD45RA+CD27− (43 ± 6%), effector; and CD45RA−CD27− (30 ± 4.1%), memory/effector. The majority of tHLA+CD8+ T cells displayed an effector, CD27− phenotype (73%). However, few expressed perforin (17%). Epitope-specific in vitro stimulation (IVS) followed by 10-day expansion in IL-2 reversed this phenotype by increasing the number of perforin+ (84 ± 3.6%; by paired t test, p < 0.001) and CD27+ (from 28 to 67%; by paired t test, p = 0.01) tHLA+ T cells. This conversion probably represented a change in the functional status of tHLA+ T cells rather than a preferential expansion of a CD27+ (naive and/or memory) PBMC, because it was reproduced after IVS of a T cell clone bearing a classic effector phenotype (CD45RA+CD27−). These findings suggest that circulating vaccine-elicited T cells are not as functionally active as inferred by characterization of IVS-induced CTL. In addition, CD45RA/CD27 expression may be more informative about the status of activation of circulating T cells than their status of differentiation.
Glucocorticoid Signaling in the Cell

Glucocorticoids contribute to the maintenance of basal and stress‐related homeostasis in all higher organisms, and influence a large proportion of the expressed human genome, and their effects spare almost no organs or tissues. Glucocorticoids regulate many functions of the central nervous system, such as arousal, cognition, mood, sleep, the activity and direction of intermediary metabolism, the maintenance of a proper cardiovascular tone, the activity and quality of the immune and inflammatory reaction, including the manifestations of the sickness syndrome, and growth and reproduction. The numerous actions of glucocorticoids are mediated by a set of at least 16 glucocorticoid receptor (GR) isoforms forming homo‐ or hetero‐dimers. The GRs consist of multifunctional domain proteins operating as ligand‐dependent transcription factors that interact with many other cell signaling systems, including large and small G proteins. The presence of multiple GR monomers and homo‐ or hetero‐dimers expressed in a cell‐specific fashion at different quantities with quantitatively and qualitatively different transcriptional activities suggest that the glucocorticoid signaling system is highly stochastic. Glucocorticoids are heavily involved in human pathophysiology and influence life expectancy. Common behavioral and/or somatic complex disorders, such as anxiety, depression, insomnia, chronic pain and fatigue syndromes, obesity, the metabolic syndrome, essential hypertension, diabetes type 2, atherosclerosis with its cardiovascular sequelae, and osteoporosis, as well as autoimmune inflammatory and allergic disorders, all appear to have a glucocorticoid‐regulated component.