Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of mesenchymal‐epithelial interactions in normal and abnormal development of the mammary gland and prostate

Development of the mammary gland (MG) and prostate occurs via mesenchymal‐epithelia interactions. Epithelial MG buds are induced in ventral epidermis by mammary mesenchyme, which ultimately specifies the functional expression of the ability to produce milk. Mammary ductal branching is induced by embryonic mammary mesenchyme and is promoted by the mammary fat pad postnatally. These influences of connective tissue on the differentiation of mammary epithelium (ME) begin prenatally, but in adulthood, the connective tissue environment of adult ME profoundly influences epithelial growth, ductal branching, epithelial differentiation, and the ability of adult ME to produce milk.
Cytokine Levels as Potential Biomarkers for Predicting the Development of Posttraumatic Stress Symptoms in Casualties of Accidents

Background: Traumatic injuries are usually associated with increased secretion of pro-inflammatory cytokines, and are sometimes followed by the development of acute stress symptoms (ASS) and posttraumatic stress symptoms (PTSS). Aims: To measure serum pro- and anti-inflammatory cytokines in accident casualties and to associate it with ASS at hospitalization, and with PTSS 1 month later. Methods: Participants were 48 patients, aged 20–60, hospitalized following various orthopedic injuries including bone fractures, and 13 healthy volunteers matched for gender. At hospitalization (Time 1), 30 ml heparinized venous blood were drawn and cytokines levels in serum were assessed; participants filled out the Acute Stress Disorder Inventory (ASDI), COPE, and injury-related questionnaires. One month later (Time 2), 26 participants filled out the Posttraumatic Disorder Symptom Scale (PDS). Results: High serum levels of IL-6, IL-8, and TGF-β and low levels of serum IL-4 and IL-10 were found in injured patients as compared with controls. When controlling for age and severity of injury in the regression analysis, higher levels of IL-6 and IL-8 and lower TGF-β were predicted by higher ASS and higher use of and emotion-focused coping. Higher PTSS scores at Time 2 were predicted by higher levels of IL-8, lower levels of TGF-β, and higher ASS measured at Time 1. Conclusions: High levels of the pro-inflammatory cytokine IL-6 and IL-8 and lower levels of the regulatory cytokine TGF-β should be further assessed as a possible risk factor or a bio-marker of PTSS in accident casualties.
AraGEM, a Genome-Scale Reconstruction of the Primary Metabolic Network in Arabidopsis1[W]

Genome-scale metabolic network models have been successfully used to describe metabolism in a variety of microbial organisms as well as specific mammalian cell types and organelles. This systems-based framework enables the exploration of global phenotypic effects of gene knockouts, gene insertion, and up-regulation of gene expression. We have developed a genome-scale metabolic network model (AraGEM) covering primary metabolism for a compartmentalized plant cell based on the Arabidopsis (Arabidopsis thaliana) genome. AraGEM is a comprehensive literature-based, genome-scale metabolic reconstruction that accounts for the functions of 1,419 unique open reading frames, 1,748 metabolites, 5,253 gene-enzyme reaction-association entries, and 1,567 unique reactions compartmentalized into the cytoplasm, mitochondrion, plastid, peroxisome, and vacuole. The curation process identified 75 essential reactions with respective enzyme associations not assigned to any particular gene in the Kyoto Encyclopedia of Genes and Genomes or AraCyc. With the addition of these reactions, AraGEM describes a functional primary metabolism of Arabidopsis. The reconstructed network was transformed into an in silico metabolic flux model of plant metabolism and validated through the simulation of plant metabolic functions inferred from the literature. Using efficient resource utilization as the optimality criterion, AraGEM predicted the classical photorespiratory cycle as well as known key differences between redox metabolism in photosynthetic and nonphotosynthetic plant cells. AraGEM is a viable framework for in silico functional analysis and can be used to derive new, nontrivial hypotheses for exploring plant metabolism.
Multicenter Experience with Upper Gastrointestinal Polyps in Pediatric Patients with Familial Adenomatous Polyposis

BACKGROUND:Familial adenomatous polyposis (FAP) is a hereditary cancer syndrome that includes gastro-duodenal involvement, polyposis, and a propensity to adenocarcinoma necessitating endoscopic surveillance. There are few data describing pediatric upper gastrointestinal FAP resulting in conflicting screening recommendations.OBJECTIVES:To characterize pediatric gastroduodenal FAP and to investigate the association between symptoms at endoscopy and APC mutation analysis with endoscopic-histologic findings warranting surveillance.METHOD:A retrospective chart review was performed, including all children with FAP who underwent upper endoscopy (EGD) at two institutions; (UNMC: 1992–2002, JHH: 1983–2002), all biopsies were reviewed and the APC mutations present in the cohort of patients were correlated to the pattern of severity of endoscopic findings and the frequency of APC mutations identified through commercially available testing for FAP (Labcorp: 1998–2002). RESULTS:Twenty-four patients from 21 families underwent 49 EGDs. Eighty-three percent were asymptomatic at the time of endoscopy. The most common finding was fundic gland polyposis (FGP) (51%), of which 42% and 15% harbored dysplasia and changes indefinite for dysplasia, respectively. Periampullary duodenal adenomata were present in 41% of patients with one patient necessitating ampullectomy. Symptoms at endoscopy were not predictive of premalignant changes. In 15 patients where the APC mutation was known patients with dysplastic FGP, gastric, or duodenal adenoma were more likely to harbor a mutation between codons 1225–1694 than the reference population (p = 0.006). CONCLUSIONS:All pediatric patients with FAP warrant upper gastrointestinal screening and surveillance endoscopy from the time of initial colonoscopy irrespective of referable symptoms. Patients with APC mutation between codon 1225–1694 may be more susceptible to aggressive gastroduodenal involvement in FAP.
Enhancement in RED algorithm for isolation of DDOS attack in wired network

Security is one of the critical issue in any network, in order to have better performance and efficiency, better security parameters must be imposed on it. In this research security model of the network has been explained, further it is analyzed that various attacks are possible in the network that gives threat to security and one of such attack is DDoS attack, framework of DDoS attack is discussed in detail. Also AQM technique like RED has been analyzed. RED queue has been implemented to detect and isolate DDoS attack. To achieve malicious node detection, Min and Max threshold values are used. Results show that network performance has been improved to a great extent in terms of metrics such as packet loss, jitter and throughput.
Design of a 2.5μW 1GHz low phase noise pierce oscillator with nanowire NEMS resonator

Nanowire (NW) resonant nanoelectromechanical systems (NEMS) with integrated electronic signal transduction are attractive for realizing ultra-low-power nanomechanical radio-frequency (RF) signal processing. A major challenge lies in the high motional impedances of electrostatically-transduced high-frequency NW NEMS resonators. In this digest paper, we describe a technique for realizing oscillators that can achieve stable and low phase noise oscillations with such characteristic high motional impedances in NW NEMS. The technique is based on the basic theory of designing CMOS Pierce oscillators with low phase noise and low power consumption. We further design an oscillator with 1.5V power supply, which features a phase noise level of -104dBc/Hz at 10kHz offset from a 1GHz carrier, and consumes only 2. 5μW power. Cadence circuit simulations on oscillator performance demonstrate the theoretical insights from this study may be important for designing oscillators based on challenging nanoresonators with high motional impedances.
A Non-photosynthetic Diatom Reveals Early Steps of Reductive Evolution in Plastids

Nonphotosynthetic plastids retain important biological functions and are indispensable for cell viability. However, the detailed processes underlying the loss of plastidal functions other than photosynthesis remain to be fully understood. In this study, we used transcriptomics, subcellular localization, and phylogenetic analyses to characterize the biochemical complexity of the nonphotosynthetic plastids of the apochlorotic diatom Nitzschia sp. NIES-3581. We found that these plastids have lost isopentenyl pyrophosphate biosynthesis and ribulose-1,5-bisphosphate carboxylase/oxygenase-based carbon fixation but have retained various proteins for other metabolic pathways, including amino acid biosynthesis, and a portion of the Calvin-Benson cycle comprised only of glycolysis/gluconeogenesis and the reductive pentose phosphate pathway (rPPP). While most genes for plastid proteins involved in these reactions appear to be phylogenetically related to plastid-targeted proteins found in photosynthetic relatives, we also identified a gene that most likely originated from a cytosolic protein gene. Based on organellar metabolic reconstructions of Nitzschia sp. NIES-3581 and the presence/absence of plastid sugar phosphate transporters, we propose that plastid proteins for glycolysis, gluconeogenesis, and rPPP are retained even after the loss of photosynthesis because they feed indispensable substrates to the amino acid biosynthesis pathways of the plastid. Given the correlated retention of the enzymes for plastid glycolysis, gluconeogenesis, and rPPP and those for plastid amino acid biosynthesis pathways in distantly related nonphotosynthetic plastids and cyanobacteria, we suggest that this substrate-level link with plastid amino acid biosynthesis is a key constraint against loss of the plastid glycolysis/gluconeogenesis and rPPP proteins in multiple independent lineages of nonphotosynthetic algae/plants.
Update on approaches to the craniomaxillofacial skeleton

Purpose of reviewA myriad of surgical approaches to the craniomaxillofacial skeleton exist. Depending on the purpose of the procedure and the anatomic area to be addressed, classically used approaches include coronal approach, midfacial degloving, eyelid incisions, and other cutaneous incisions. Over the last decade, endoscopic approaches have become more popular. Whether external, transoral, or endoscopic, a detailed knowledge of the indications, anatomy, limitations, and potential complications is critical to the successful employment of these approaches. This article reviews the recent literature on classic as well as novel advancements to the craniofacial skeleton. Recent findingsMultiple studies in the last 5 years have investigated the approaches to the craniofacial skeleton. Most of these focus on trauma. Recent advances have concentrated on external versus endoscopic approaches to the mandibular condyle, an endoscopic approach to the midface and orbit, three-dimensional imaging of the facial skeleton, and improving upon the existing classic approaches and techniques. SummaryApproaches to the craniomaxillofacial skeleton continue to evolve with the refinement of classic approaches and advent of new technologies and approaches. This study reviews the recent literature and provides a comprehensive review of options for craniofacial exposure and the most up-to-date surgical options.
Randomised Comparison of Three Types of Continuous Anterior Abdominal Wall Block after Midline Laparotomy for Gynaecological Oncology Surgery

Effective analgesia after midline laparotomy surgery is essential for enhanced recovery programs. We compared three types of continuous abdominal wall block for analgesia after midline laparotomy for gynaecological oncology surgery. We conducted a single-centre, double-blind randomised controlled trial. Ninety-four patients were randomised into three groups to receive two days of programmed intermittent boluses of ropivacaine (18 ml 0.5% ropivacaine every four hours) via either a transversus abdominis plane (TAP) catheter, posterior rectus sheath (PRS) catheter, or a subcutaneous (SC) catheter. All groups received patient-controlled analgesia with morphine, and regular paracetamol and non-steroidal anti-inflammatory medication. Measured outcomes included analgesic and antiemetic usage and visual analog scores for pain, nausea, vomiting, and satisfaction. Eighty-eight patients were analysed (29 SC, 29 PRS and 30 TAP). No differences in the primary outcome were found (median milligrams morphine usage on day two SC 28, PRS 25, TAP 21, P=0.371). There were differences in secondary outcomes. Compared with the SC group, the TAP group required less morphine in recovery (0 mg versus 6 mg, P=0.01) and reported less severe pain on day one (visual analog scores 36.3 mm versus 55 mm, P=0.04). The TAP group used fewer doses of tropisetron on day one compared with the PRS group (8 versus 21, P=0.016). Programmed intermittent boluses of ropivacaine delivered via PRS, TAP and SC catheters can be provided safely to patients undergoing midline laparotomy surgery. Initially TAP catheters appear superior, reducing early opioid and antiemetic requirements and severe pain, but these advantages are lost by day two.
Simulation of cell proliferation in mouse oral epithelium, and the action of epidermal growth factor: evidence for a high degree of synchronization of the stem cells

Abstract. Computer simulation has been carried out to help to determine the cell‐proliferative mechanisms underlying data gathered from a double‐labelling experiment on the dorsal tongue of the mouse. Good fits to the data have been obtained by assuming that there is a high degree of synchrony in the stem cells, which have a 24‐h cell cycle time, and that daughters of these cells undergo two further divisions, with mean cell cycle times of 48 h, before differentiating. This results in one‐seventh of proliferative cells being stem cells, which ties in well with the concept of epidermal proliferative units. There is no need to assume that S‐phase duration changes diurnally. The administration of epidermal growth factor seems to increase the degree of synchrony. In such systems, the influx to S‐phase and the efflux from it have very sudden short peaks, which it is impossible to observe unless observations are taken very frequently. There are therefore implications for the designs of experiments that attempt to study diurnal rhythms or the effect of factors that disturb the normal proliferative pattern of cells.
Risk factors in the onset of neck/shoulder pain in a prospective study of workers in industrial and service companies

Aims: To quantify the relative contribution of work related physical factors, psychosocial workplace factors, and individual factors and aspects of somatisation to the onset of neck/shoulder pain. Methods: Four year prospective cohort study of workers from industrial and service companies in Denmark. Participants were 3123 workers, previously enrolled in a cross sectional study, where objective measurement of physical workplace factors was used. Eligible participants were followed on three subsequent occasions with approximately one year intervals. Outcomes of interest were: new onset of neck/shoulder pain (symptom cases); and neck/shoulder pain with pressure tenderness in the muscles of the neck/shoulder region (clinical cases). Results: During follow up, 636 (14.1%) participants reported neck/shoulder pain of new onset; among these, 82 (1.7%) also had clinical signs of substantial muscle tenderness. High shoulder repetition was related to being a future symptom case, and a future clinical case. Repetition was strongly intercorrelated with other physical measures. High job demands were associated with future status as a symptom case, and as a clinical case. A high level of distress predicted subsequent neck/shoulder pain, and neck/shoulder pain with pressure tenderness. Conclusions: High levels of distress, and physical and psychosocial workplace factors are predictors of onset of pain in the neck and/or shoulders, particularly pain with pressure tenderness in the muscles.
A Monte Carlo method for Bayesian inference in frailty models.

Many analyses in epidemiological and prognostic studies and in studies of event history data require methods that allow for unobserved covariates or "frailties. " Clayton and Cuzick (1985, Journal of the Royal Statistical Society, Series A 148, 82-117) proposed a generalization of the proportional hazards model that implemented such random effects, but the proof of the asymptotic properties of the method remains elusive, and practical experience suggests that the likelihoods may be markedly nonquadratic. This paper sets out a Bayesian representation of the model in the spirit of Kalbfleisch (1978, Journal of the Royal Statistical Society, Series B 40, 214-221) and discusses inference using Monte Carlo methods.
Regulation of Intracellular pH by Bovine Intervertebral Disc Cells

Extracellular acidity is an important determinant of intervertebral disc matrix turnover, possibly exerting effects through changes of intracellular pH<sub>i</sub> (pH). There is, however, little information concerning the ways in which these cells regulate their pH<sub>i</sub>. Fluorimetric techniques have been used in the present study to measure pH<sub>i</sub> in isolated intervertebral disc cells, and to characterise the membrane transport pathways by which it is regulated. Nucleus pulposus cells were obtained from bovine intervertebral discs by standard enzymatic digestion techniques, and loaded with the pH-sensitive fluoroprobe BCECF. Resting pH<sub>i</sub> was approximately 6.7 for cells suspended in either HEPES-buffered (HBS) or CO<sub>2</sub>/HCO<sub>3</sub><sup>–</sup>-buffered (BBS) media. Intrinsic buffering capacity was approximately 19 mM pH unit<sup>–1</sup> in HBS and was increased when cells were suspended in BBS. A combination of ion substitution and inhibitor studies for cells at steady-state pH<sub>i</sub> or acidified by exposure to NH<sub>4</sub>Cl revealed that in HBS Na<sup>+</sup> × H<sup>+</sup> exchange and an H<sup>+</sup>-ATPase extrude acid from these cells. Only one of these two systems, the Na<sup>+</sup> × H<sup>+</sup> exchanger, exhibited a sensitivity to pH<sub>i</sub>, identifying it as the regulator of pH<sub>i</sub> under these conditions. In BBS, an additional pathway which was dependent on extracellular Na<sup>+</sup>, extracellular HCO<sub>3</sub><sup>–</sup> and intracellular Cl<sup>–</sup> was detected. These properties are consistent with the four ion HCO<sub>3</sub><sup>–</sup>-dependent transporter, although the cation-rich, anion-poor extracellular matrix of the intervertebral disc means that such a pathway has only a marginal role in disc cell pH<sub>i</sub> regulation.
MiR-340 Inhibits Triple-Negative Breast Cancer Progression by Reversing EZH2 Mediated miRNAs Dysregulated Expressions

The anti-tumor efficacy of miR-340 has been recently characterized in cancers. However, the underlying mechanisms of miR-340 inhibited cell growth and invasion in triple-negative breast cancer (TNBC) have not been well elucidated. In this study, we found that miR-340 expression was negatively correlated with EZH2 (Enhancer of zeste homolog 2) expression in TNBC tissues and cell lines. Subsequent luciferase reporter assay confirmed that EZH2 was a novel molecule target of miR-340. Upregulated miR-340 levels by mimics transfection significantly inhibited the MDA-MB-231 and MDA-MB-468 breast cancer cells proliferation, invasion and migration, and induced more cell apoptosis. Meanwhile, miR-340 inhibited the tumor growth in an orthotopic MDA-MB-231 breast cancer mouse model. Furthermore, we found the reduced EZH2 expression by miR-340 mimics transfection decreased the DNMT1, H3K27me3, β-catenin and P-STAT3 expressions, which ultimately resulted in miR-21 activity blockage and miR-200a/b expression upregulation. The results of rescue experiments further confirmed that miR-340 inhibited triple-negative breast cancer progression through targeting EZH2. Taken together, our results identified miR-340 as a tumor suppressor in TNBC, moreover, an EZH2 medicated regulatory loop was established. Post-transcriptional suppression of EZH2 expression not only blocked STAT3 mediated miR-21 trans-activation, but also reversed the miR-200a/b silencing via reducing DNMT1 and H3K27me3 expressions. MiR-21 inhibition and miR-200a/b expression triggered by miR-340 ultimately cooperated in the TNBC progression.
Effect of rate‐dependent changes in the transient outward current on the action potential in sheep Purkinje fibres.

1. The rate of membrane potential change during the initial phase of rapid repolarization of the action potential in sheep Purkinje fibres has been measured by electronic differentiation. 2. Phase‐plane analysis has revealed that the potential dependence of rapid repolarization corresponds to the potential range over which the transient outward current , Ito, is recorded in voltage clamp experiments. 3. The initial rate of repolarization is strongly rate‐dependent and it is markedly reduced at high rates. 4. The effect of high rates of stimulation on the phase‐plane diagram is consistent with a reduction in I. 5. After an increase or decrease in rate there is an abrupt change in the initial rate of repolarization in the first response followed by slower changes over several hundred responses. 6. Recovery of the initial rate of repolarization occurs in two distinct phases after repetitive to activity: there is a rapid, approximately exponential phase of recovery in the first 10 s which is followed by a slower phase of recovery lasting several hundred seconds. 7. The rate‐dependent changes in the initial rate of repolarization are abolished by 4‐aminopyridine, 0.5‐1.0 mmol/l. 8. It is concluded that the rate‐dependent changes in the initial phase of repolarization are due to the similar changes in Ito described in a companion paper (Boyett, 1981). 9. Rate‐dependent changes in peak tension have been measured and they bear no relationship to the changes in the initial rate of repolarization. It is concluded that the major component of the transient outward current in sheep Purkinje fibers is unlikely to be a Ca‐activated current