Miracle-dz/UniFAR-FTUs huggingface dataset:
Polyphenol-rich extract of Salvia chinensis exhibits anticancer activity in different cancer cell lines, and induces cell cycle arrest at the G0/G1-phase, apoptosis and loss of mitochondrial membrane potential in pancreatic cancer cells

Pancreatic cancer (PC) is one of the most aggressive types of human malignancy, which has an overall 5-year survival rate of <2%. PC is the fourth most common cause of cancer-associated mortality in the western world. At present, there is almost no effective treatment available for the treatment of PC. The aim of the present study was to evaluate the anticancer potential of a polyphenol enriched extract obtained from Salvia chinensis, a Chinese medicinal plant. An MTT assay was used to evaluate the cell viability of five cancer cell lines and one normal cell line. In addition, the effects of the extract on apoptotic induction, cell cycle phase distribution, DNA damage and loss of mitochondrial membrane potential (ΛΨm) were evaluated in MiapaCa-2 human PC cells. The effects of the extract on cell cycle phase distribution and ΛΨm were assessed by flow cytometry, using propidium iodide and rhodamine-123 DNA-binding fluorescent dyes, respectively. Fluorescence microscopy, using 4′,6-diamidino-2-phenylindole as a staining agent, was performed in order to detect the morphological changes of the MiapaCa-2 cancer cells and the presence of apoptotic bodies following treatment with the extract. The results of the present study demonstrated that the polyphenol-rich extract from S. chinensis induced potent cytotoxicity in the MCF-7 human breast cancer cells, A549 human lung cancer cells, HCT-116 and COLO 205 human colon cancer cells, and MiapaCa-2 human PC cells. The COLO 205 and MCF-7 cancer cell lines were the most susceptible to treatment with the extract, which exhibited increased rate of growth inhibition. Fluorescence microscopy revealed characteristic morphological features of apoptosis and detected the appearance of apoptotic bodies following treatment with the extract in the PC cells. Flow cytometric analysis demonstrated that the extract induced G0/G1 cell cycle arrest in a dose-dependent manner. In addition, treatment with the extract induced a significant and concentration-dependent reduction in the ΛΨm of the PC cells.
Some issues related to evidence-based implantology

This article reviews relevant dental literature to answer some frequent questions related to evidence-based implantology. There are hundreds of implant systems on the market, but the majority lack clinical documentation. Recommended number of implants for full-arch fixed prostheses is four or five in the mandible but at least six in the maxilla. Less expensive implant-retained overdentures make implant treatment available to a greater portion of edentulous subjects. Mandibular overdentures on two implants, and even one implant, have shown excellent long-term outcomes. In the maxilla, less than four implants are not recommended for good results. Single implant restorations have good prognosis, but placement of the implant should be postponed until adulthood. Osseointegrated implants have revolutionized clinical dentistry. However, in a global perspective, implants make up only a small part of all prosthodontic treatment. Knowledge and skill in conventional prosthodontics must be maintained as it will remain the most common part of the specialty.
The long-term outcomes of the second generation of familial nonmedullary thyroid carcinoma are more aggressive than sporadic cases.

BACKGROUND Familial nonmedullary thyroid carcinoma (FNMTC) is frequently detected, but the prevalence or the aggressiveness of FNMTC is still unclear. We aimed to investigate the prevalence, clinical characteristics, and prognosis of FNMTC. METHODS This study included 3056 nonmedullary thyroid carcinoma (NMTC) patients who were pathologically confirmed to exhibit differentiated thyroid carcinoma from January 1962 through March 2010. The duration of follow-up was 6.2±6.2 years. RESULTS The prevalence of FNMTC was 9.6%; 37.9% of the FNMTC patients exhibited a parent-offspring relationship, and 62.1% exhibited a sibling relationship. FNMTC was smaller in tumor size (1.2±0.9 vs. 1.4±1.1 cm) and more multifocal (33.6% vs. 27.0%) than sporadic cases. FNMTC presented higher recurrence rates (29.5% vs. 19.8%) and shorter recurrence-free survival than sporadic NMTC (p=0.046). When we compared sporadic NMTC with parent-offspring or sibling FNMTC separately, parent-offspring FNMTC was more multifocal (39.3% vs. 27.0%), while sibling FNMTC was more prevalent in female patients (89.6% vs. 82.5%) and presented smaller tumors (1.2±0.8 vs. 1.4±1.1 cm) than sporadic NMTC. The recurrence rate was higher than that of sporadic NMTC in parent-offspring FNMTC (35.6% vs. 19.8%) but not in sibling FNMTC. Among the 123 parent-offspring FNMTC cases, the second generation exhibited an earlier age at the diagnosis (38±11 vs. 57±11 years), more extrathyroidal invasion (57.8% vs. 29.4%), a higher recurrence rate (50.0% vs. 19.0%), and shorter recurrence-free survival (p=0.015) than the first generation. CONCLUSION FNMTC was found to have a very high prevalence in our population. Parent-offspring FNMTC demonstrated higher recurrence than sporadic NMTC; specifically, the second generation of parent-offspring FNMTC cases exhibited more aggressive clinical characteristics than the first generation.
Fractures during childhood and adolescence in healthy boys: relation with bone mass, microstructure, and strength.

CONTEXT In healthy boys, fractures result from trauma of various severity, suggesting contribution of an intrinsic biomechanical fragility. OBJECTIVES Our objective was to characterize bone mineral mass, microstructure, and strength in boys with and without fractures. PARTICIPANTS AND DESIGN We followed 176 healthy boys from 7.4 ± 0.5 to 15.2 ± 0.5 (mean ± sd) yr of age. OUTCOMES Areal (a) bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry at radius metaphysis and diaphysis, total hip, femoral neck and diaphysis, and L2-L4 vertebrae. Volumetric (v) BMD and microstructure were assessed by high-resolution peripheral computerized tomography at both distal tibia and radius. Bone strength was evaluated by micro-finite element analysis. RESULTS A total of 156 fractures were recorded in 87 of 176 boys with peak incidence between 10 and 13 yr. At 7.4 yr, subjects with fractures had lower aBMD in all sites and at 15.2 yr in femoral and spinal, but not in radius, sites. At that age, boys with fractures displayed lower trabecular (Tb) vBMD (P = 0.029) and number (P = 0.040), stiffness (P = 0.024), and failure load (P = 0.016) at distal tibia, but not distal radius. Odds ratios of fracture risk per 1 sd decrease were 1.80 (P = 0.006) for femoral neck aBMD and 1.46 (P = 0.038) for distal tibia Tb vBMD, 1.59 (P = 0.031) for Tb number, 1.53 (P = 0.072) for stiffness, and 1.60 (P = 0.056) for failure load. CONCLUSION In a homogeneous cohort of healthy boys, fractures recorded until 15.2 ± 05 yr of age were associated with lower femoral neck aBMD and with lower distal tibia trabecular vBMD and number, stiffness and failure load. These deficits in bone mineral mass, microstructure and strength could contribute to the occurrence of fractures during growth.
Centaurin-α1-Ras-Elk-1 Signaling at Mitochondria Mediates β-Amyloid-Induced Synaptic Dysfunction

Alzheimer's disease is thought to be caused by β-amyloid peptide (Aβ)-dependent synaptic dysfunction. However, the signaling pathways connecting Aβ and synaptic dysfunction remain elusive. Here we report that Aβ transiently increases the expression level of centaurin-α1 (CentA1) in neurons, which induces a Ras-dependent association of Elk-1 with mitochondria, leading to mitochondrial and synaptic dysfunction in organotypic hippocampal slices of rats. Downregulation of the CentA1–Ras-Elk-1 pathway restored normal mitochondrial activity, spine structural plasticity, spine density, and the amplitude and frequency of miniature EPSCs in Aβ-treated neurons, whereas upregulation of the pathway was sufficient to decrease spine density. Elevations of CentA1 and association of Elk-1 with mitochondria were also observed in transgenic mice overexpressing a human mutant form of amyloid precursor protein. Therefore, the CentA1–Ras-Elk-1 signaling pathway acts on mitochondria to regulate dendritic spine density and synaptic plasticity in response to Aβ in hippocampal neurons, providing new pharmacological targets for Alzheimer's disease.
Localization of lactoferrin and nonspecific cross‐reacting antigen in human breast carcinomas. An immunohistochemical study using the Avidin—biotin—peroxidase complex method

A retrospective immunocytochemical study was performed on 67 human breast carcinomas to determine whether the epithelial cell‐associated antigens, lactoferrin and nonspecific cross‐reacting antigen (NCA), could be used as markers in the prognostic assessment of breast cancers. Fixed paraffin sections were tested with anti‐lactoferrin and anti‐NCA. Lactoferrin and NCA were found in 7.5% and 19% of the cases, respectively. Furthermore, the association between these two antigens in tumor cells was significant (P < 0.05). Kappa‐casein was observed in all antigen‐positive cases. These antigens were observed more often in low‐grade ductal carcinomas that had positive estrogen and progestin receptors, but no relationship could be established between lactoferrin or NCA and other prognostic indicators, such as histologic type and grade of the tumor, stromal elastosis, or steroid receptors. Although more antigen might have been detected in unfixed, frozen specimens, the results indicate that lactoferrin and NCA possess minimal value as epithelial cell markers and no prognostic value when detected on routinely fixed, paraffin‐embedded samples.
Protein Kinase B Activity Is Sufficient to Mimic the Effect of Insulin on Glucagon Gene Transcription*

Insulin inhibits glucagon gene transcription, and insulin deficiency is associated with hyperglucagonemia that contributes to hyperglycemia in diabetes mellitus. However, the insulin signaling pathway to the glucagon gene is unknown. Protein kinase B (PKB) is a key regulator of insulin signaling and glucose homeostasis. Impaired PKB function leads to insulin resistance and diabetes mellitus. Therefore, the role of PKB in the regulation of glucagon gene transcription was investigated. After transient transfections of glucagon promoter-reporter genes into a glucagon-producing islet cell line, the use of kinase inhibitors indicated that the inhibition of glucagon gene transcription by insulin depends on phosphatidylinositol (PI) 3-kinase. Furthermore, insulin caused a PI 3-kinase-dependent phosphorylation and activation of PKB in this cell line as revealed by phospho-immunoblotting and kinase assays. Overexpression of constitutively active PKB mimicked the effect of insulin on glucagon gene transcription. Both insulin and PKB responsiveness of the glucagon promoter were abolished when the binding sites for the transcription factor Pax6 within the G1 and G3 promoter elements were mutated. Recruitment of Pax6 or its potential coactivator, the CREB-binding protein (CBP), to G1 and G3 by using the GAL4 system restored both insulin and PKB responsiveness. These data suggest that insulin inhibits glucagon gene transcription by signaling via PI 3-kinase and PKB, with the transcription factor Pax6 and its potential coactivator CBP being critical components of the targeted promoter-specific nucleoprotein complex. The present data emphasize the importance of PKB in insulin signaling and glucose homeostasis by defining the glucagon gene as a novel target gene for PKB.
Activated IL-1RI Signaling Pathway Induces Th17 Cell Differentiation via Interferon Regulatory Factor 4 Signaling in Patients with Relapsing-Remitting Multiple Sclerosis

IL-1β plays a crucial role in the differentiation of human Th17 cells. We report here that IL-1RI expression is significantly increased in both naive and memory CD4+ T cells derived from relapsing-remitting multiple sclerosis (RR MS) patients in comparison to healthy controls. Interleukin 1 receptor (IL-1R)I expression is upregulated in the in vitro-differentiated Th17 cells from RR MS patients in comparison to the Th1 and Th2 cell subsets, indicating the role of IL-1R signaling in the Th17 cell differentiation in RR MS. When IL-1RI gene expression was silenced using siRNA, human naive CD4+ T cells cultured in the presence of Th17-polarizing cytokines had a significantly decreased expression of interleukin regulatory factor 4 (IRF4), RORc, IL-17A, IL-17F, IL-21, IL-22, and IL-23R genes, confirming that IL-1RI signaling induces Th17 cell differentiation. Since IL-1R gene expression silencing inhibited IRF4 expression and Th17 differentiation, and IRF4 gene expression silencing inhibited Th17 cell differentiation, our results indicate that IL-1RI induces human Th17 cell differentiation in an IRF4-dependant manner. Our study has identified that IL-1RI-mediated signaling pathway is constitutively activated, leading to an increased Th17 cell differentiation in IRF4-dependent manner in patients with RR MS.
The Intergeniculate Leaflet, but Not the Visual Midbrain, Mediates Hamster Circadian Rhythm Response to Constant Light

Several studies have demonstrated a variety of effects of intergeniculate leaflet (IGL) lesions on circadian rhythm regulation. Recent studies have suggested the possibility that certain rhythm functions attributed to the IGLare actually controlled by retinorecipient midbrain nuclei or other brain areas connected to the IGL. The present investigations evaluated whether midbrain lesions previously shown to block the phasic actions of benzodiazepine would also reduce or eliminate the period-lengthening effect of constant light (LL), a function that has been attributed to the IGL. Experiment 1 established that the circadian period of controls lengthened by about 0.57 h when the animals were transferred from constant dark (DD) to LL, but the magnitude of change was attenuated by about 50% in animals with IGL lesions caused by the neurotoxin N-methyl-D-aspartate (NMDA). In experiment 2, controls were compared to groups receiving either NMDAlesions of the pretectum or tectum or knife cuts designed to sever connections between the IGL and more medial retinorecipient nuclei. As in experiment 1, there were no differences between groups with respect to circadian period in DD. However, unlike experiment 1, all groups lengthened period equally in LL (overall mean increase = 0.57 h). Thus, the effect of LL on circadian period appears to be a joint result of photic information arriving at the circadian clock directly from the retinohypothalamic tract and indirectly through the IGLvia the geniculohypothalamic tract, without involvement of visual midbrain. The results may have implications for the anatomical basis of Aschoff's rule.
Becoming a Brilliant Star

This paper provides an overview of the Brilliant Star model of human growth and development. The background for the need to develop a comprehensive model is offered as well as a description of the model’s ten domains and two core elements. The Brilliant Star model is a systems-based, ecological model that proposes a need to identify the knowledge, attitudes, and skills required for successful adulthood as well as the important contextual factors that influence an individual’s development.
Dynamics of Water Droplet Distortion and Break-Up in a Uniform Electric Field

Distortion of a free droplet in a uniform electric field is studied numerically using the Boundary Element Method. It is assumed that the droplet is made of an ideally conducting liquid. There exists a critical magnitude of the electric field intensity. The droplet oscillates for weaker electric fields and elongates until a thin jet emanating from the droplet tip is formed for stronger electric fields. Numerical predictions agree reasonably well with the available experimental data.
Shock Solutions for Particle-Laden Thin Films

We derive a lubrication model describing gravity-driven thin film flow of a suspension of heavy particles in viscous fluid. The main features of this continuum model are an effective mixture viscosity and a particle settling velocity, both depending on particle concentration. The resulting equations form a 2 × 2 system of conservation laws in the film thickness h(x, t) and in φh, where φ(x, t) is the particle volume fraction. We study flows in one dimension under the constant flux boundary condition, which corresponds to the classical Riemann problem, and we find the system can have either double-shock or singular shock solutions. We present the details of both solutions and examine the effects of the particle settling model and of the microscopic length scale b at the contact line.
A Sec63p-BiP complex from yeast is required for protein translocation in a reconstituted proteoliposome

Reconstituted proteoliposomes derived from solubilized yeast microsomes are able to translocate a secreted yeast mating pheromone precursor (Brodsky, J. L., S. Hamamoto, D. Feldheim, and R. Schekman. 1993. J. Cell Biol. 120:95-107). Reconstituted proteoliposomes prepared from strains with mutations in the SEC63 or KAR2 genes are defective for translocation; the kar2 defect can be overcome by the addition of purified BiP (encoded by the KAR2 gene). We now show that addition of BiP to wild-type reconstituted vesicles increases their translocation efficiency three-fold. To identify other ER components that are required for translocation, we purified a microsomal membrane protein complex that contains Sec63p. We found that the complex also includes BiP, Sec66p (gp31.5), and Sec67p (p23). The Sec63p complex restores translocation activity to reconstituted vesicles that are prepared from a sec63-1 strain, or from cells in which the SEC66 or SEC67 genes are disrupted. BiP dissociates from the complex when the purification is performed in the presence of ATP gamma S or when the starting membranes are from yeast containing the sec63-1 mutation. We conclude that the purified Sec63p complex is active and required for protein translocation, and that the association of BiP with the complex may be regulated in vivo.
Reproductive constraint is a developmental mechanism that maintains social harmony in advanced ant societies

A hallmark of eusociality in ants is the reproductive division of labor between queens and workers. Yet, nothing is known about the molecular mechanisms underlying reproduction in this group. We therefore compared the developmental genetic capacity of queens and workers to reproduce in several eusocially advanced species from the two largest subfamilies of ants, the Myrmicinae and Formicinae. In flies, the asymmetric localization of maternally encoded determinants (mRNAs and proteins) during oogenesis establishes oocyte polarity and subsequently ensures proper embryonic development. Vasa and nanos, two key maternal determinants, are properly localized in the posterior of queen oocytes, but their localization is impaired in those of the workers. This mislocalization leads to severe embryonic defects in worker progeny, and therefore, represents a constraint on worker reproduction that we call ‘reproductive constraint. ’ We show that reproductive constraint is phylogenetically widespread, and is at high levels in most species tested. Reproductive constraint can simultaneously reduce or eliminate the workers' ability to produce viable eggs for reproduction, while preserving their ability to produce trophic eggs for nutrition, and thus, may have been the basis for the evolutionary retention of worker ovaries in the majority of ants. We propose that high levels of reproductive constraint has most likely evolved as a consequence of selection at the colony level to reduce or eliminate any potential conflict over worker reproduction, therefore maintaining harmony and colony efficiency in advanced ant societies.
A test case generation technique and process

It has been proven that the software testing phase is one of the most critical and important phases in the software development life cycle. In general, the software testing phase takes around 40-70% of the effort, time, and cost. This area is well researched over a long period of time. Unfortunately, while many researchers have found methods of reducing time and cost during the testing process, there are still a number of important related issues that need to be researched. This paper introduces a new high level test case generation process with a requirement prioritization method to resolve the following research problems: unable to identify suitable test cases with limited resources, lack of an ability to identify critical domain requirements in the test case generation process and ignore a number of generated test cases. Also, this paper proposes a practical test case generation technique derived from use case
PCR-based detection of genes encoding virulence determinants in Staphylococcus aureus from bovine subclinical mastitis cases

The present study was carried out to genotypically characterize Staphylococcus aureus (S. aureus) isolated from bovine mastitis cases. A total of 37 strains of S. aureus were isolated during processing of 552 milk samples from 140 cows. The S. aureus strains were characterized phenotypically, and were further characterized genotypically by polymerase chain reaction using oligonucleotide primers that amplified genes encoding coagulase (coa), clumping factor (clfA), thermonuclease (nuc), enterotoxin A (entA), and the gene segments encoding the immunoglobulin G binding region and the X region of protein A gene spa. All of the isolates yielded an amplicon with a size of approximately 1,042 bp of the clfA gene. The amplification of the polymorphic spa gene segment encoding the immunoglobulin G binding region was observed in 34 isolates and X-region binding was detected in 26 isolates. Amplification of the coa gene yielded three different products in 20, 10, and 7 isolates. The amplification of the thermonuclease gene, nuc, was observed in 36 out of 37 isolates. All of the samples were negative for the entA gene. The phenotypic and genotypic findings of the present strategies might provide an understanding of the distribution of the prevalent S. aureus clones among bovine mastitis isolates, and might aid in the development of steps to control S. aureus infections in dairy herds.
Performance of Vitek 2 in Antimicrobial Susceptibility Testing of Pseudomonas aeruginosa Isolates with Different Mechanisms of β-Lactam Resistance

ABSTRACT A total of 78 isolates of Pseudomonas aeruginosa grouped according to the phenotype for ceftazidime and imipenem susceptibility/resistance were used to assess the accuracy of the Vitek 2 system in antimicrobial susceptibility testing. Comparisons were made with a MIC gradient test for piperacillin-tazobactam, ceftazidime, aztreonam, imipenem, meropenem, gentamicin, and ciprofloxacin. For the total of 546 isolate-antimicrobial combinations tested, the category agreement was 83.6%, with 2.0, 1.6, and 12.8% very major, major, and minor errors, respectively. Vitek 2 accuracy was influenced differently by the mechanism responsible for resistance, and interpretation of the results in relation to phenotype could improve the performance of the system.