Miracle-dz/UniFAR-FTUs huggingface dataset:
Epigenetic Effects of Endocrine Disrupting Chemicals

Recently, there is increasing evidences supported by animal studies emphasizing that exposure to environmental factors, nutritional conditions, xenobiotic chemicals, reproductive factors and low dose exposure to radiations can alter epigenetic programming and concomitantly enhance the risk of developing diseases. Endocrine disrupting chemicals (EDCs) can influence organization of developing brain, which may appear in expression of species typical social behaviors. Environmental exposures to EDCs are shown to increase the susceptibility against many kind of diseases. Currently, there are already several articles, books and journals about the epigenetic effects of EDCs available in media and internet. The aim of this thesis is to review these articles and to evaluate the possible consequences of being exposed to these agents in our daily life for the process of risk assessment of these chemicals. Epigenetic effects do not change the gene sequence. They affect the gene expression and therefore identification of expression profile in sensitive genes to epigenetic effects may be used as a biomarker for disease and environmental exposure. In the future, theses epigenetic biomarkers may help for early diagnosis of sensitivity of an individual for adult onset disease or maybe used to prevent the disease before the disease’s symptoms develop. When an organism grows and develops, precisely organized chemical reactions activate or deactivate parts of the genome at specific time and locations. The study of these chemical reactions and factors influencing them is called epigenetics. It has been observed that, transgenerationally modified progenies in their life are more prone to different kinds of diseases, such as mammary tumors, prostate disease, kidney disease, testis abnormalities and immune abnormalities. Our health depends on our normal development and reproductive ability. Healthy endocrine system is needed to have normal development and normal reproduction. Few years ago we thought that our life starts with the DNA we receive from our parents, but currents studies have shown that we receive more than just DNA from our parents. Famine, stress, fear and even drug use could all leave chemical marks on parent’s genetic material. Environmental exposure to EDCs during early development and pregnancy can modify epigenomes and induce trans-generationally asthma, autism, cancer, cardiovascular dysfunctions, diabetes, obesity, schizophrenia, infertility, reproductive diseases and dysfunction later in life. There is evidence showing that EDCs can induce epigenetic gene alterations by which these altered genes can be transferred into subsequent generations.
Effect of temperature on the passive electrical properties of the muscle fibre membrane

The electrical constants of different nerve and muscle fibres have been measured by several authors (Hodgkin & Rushton, 1946; Katz, 1948; Fatt & Katz, 1951; Weidmann, 1951) whose papers should be consulted for theory and general experimental procedure. The present paper gives the results of experiments made to study the effect of temperature changes on the membrane resistance and capacitance of striated frog muscle fibres.
Unravelling Nature's Networks: From Microarray and Proteomic Analysis to Systems Biology: University of Sheffield, 21–22 July 2003

Dramatic progress has been made recently in determining the genetic and molecular composition of cells. This has prompted the development of new approaches to the challenge of understanding how basic cellular mechanisms are coordinated to produce the dazzling complexity of living systems. To face this challenge fully, it is critical not only to know what genes and proteins are expressed in cells, but also to understand the spatiotemporal dynamics of their networks of interactions. The sheer scale and complexity of cellular interaction networks necessitates a multi-disciplinary effort in which sophisticated experimental techniques are employed in combination with computational analysis and mathematical modelling. Such approaches are beginning to provide insight into basic structures and mechanisms, and promise to become critical to the post-genomic mission of understanding the cell as a complex dynamical system. Determining network structure The basic topology of an interaction network is determined by the nodes (e.g. the genes or proteins) and by the edges between these nodes (interactions between genes and/or proteins). In addition to this, it is often appropriate to label the edges to show directionality of interactions (e.g. a transcription factor binding to a promoter) and the nature of an interaction (e.g. activating or inhibitory). The nodes and edges constitute the network (or graph). The network of all interacting species within a cell is enormous, and a full determination of its structure remains beyond the reach of current experimental techniques due to technical and practical constraints. However, in practice it is often more appropriate to focus on smaller sub-networks that play a direct role in a particular setting or process {such as the network of interactions involving the transcription factor nuclear factorκB (NF-κB) in inflammation [1]}. The structure of such sub-networks has traditionally been elucidated by intensive genetic and biochemical analysis. This results in reasonably detailed pictures of small fragments of the entire cellular
SURFACE ROUGHNESS OF TITANIUM ON BONE MORPHOGENETIC PROTEIN‐2 TREATED OSTEOBLAST CELLS IN VITRO

Surface topography plays a critical role in the interaction of dental implants with adjacent tissues. No statistical differences in oxide composition and surface contamination were observed between 600 grit and polished titanium surfaces. The expression of osteoblast phenotype was enhanced when osteoblast progenitor cells (2T9) were stimulated with bone morphogenetic protein-2 on polished and 600 grit titanium surfaces. Bone morphogenetic protein-2 stimulated phenotypic expression on 600 grit titanium surfaces was marked by prolonged alkaline phosphatase specific activity and more rapid osteocalcin production as compared with the polished titanium surfaces. Because the surface area of the 600 grit titanium surface was shown to be 8 percent greater than that of the polished titanium surface, it is possible that increased surface area played a role in the enhanced expression of the osteoblast phenotype. (Implant Dent 1997;6:19–24)
Induction of lytic cycle replication of Kaposi's sarcoma‐associated herpesvirus by herpes simplex virus type 1: involvement of IL‐10 and IL‐4

Previously, we identified that both human herpesvirus 6 and human immunodeficiency virus type 1 Tat were important cofactors that activated lytic cycle replication of Kaposi's sarcoma‐associated herpesvirus (KSHV). Here, we further investigated the potential of herpes simplex virus type 1 (HSV‐1) to influence KSHV replication. We demonstrated that HSV‐1 was a potentially important factor in the pathogenesis of Kaposi's sarcoma, as determined by production of lytic phase mRNA transcripts, viral proteins and infectious viral particles in BCBL‐1 cells. These results were further confirmed by an RNA interference experiment using small interfering RNA targeting KSHV ORF50 and a luciferase reporter assay testing ORF50 promoter‐driven luciferase activity. Finally, we discovered that production of human interleukin‐10 (IL‐10) and IL‐4 partially contributed to HSV‐1‐induced KSHV replication. Our data present the first direct evidence that HSV‐1 can activate KSHV lytic replication and suggest a role of HSV‐1 in KSHV pathogenesis.
Fosfomycin/tobramycin for inhalation in patients with cystic fibrosis with pseudomonas airway infection.

RATIONALE Fosfomycin/tobramycin for inhalation (FTI), a unique, broad-spectrum antibiotic combination, may have therapeutic potential for patients with cystic fibrosis (CF). OBJECTIVES To evaluate safety and efficacy of FTI (160/40 mg or 80/20 mg), administered twice daily for 28 days versus placebo, in patients greater than or equal to 18 years of age, with CF, chronic Pseudomonas aeruginosa (PA) airway infection, and FEV(1) greater than or equal to 25% and less than or equal to 75% predicted. METHODS This double-blind, placebo-controlled, multicenter study assessed whether FTI/placebo maintained FEV(1) % predicted improvements achieved following a 28-day, open-label, run-in course of aztreonam for inhalation solution (AZLI). MEASUREMENTS AND MAIN RESULTS A total of 119 patients were randomized to FTI (160/40 mg: n = 41; 80/20 mg: n = 38) or placebo (n = 40). Mean age was 32 years and mean FEV(1) was 49% predicted at screening. Relative improvements in FEV(1) % predicted achieved by the AZLI run-in were maintained in FTI groups compared with placebo (160/40 mg vs. placebo: 6.2% treatment difference favoring FTI, P = 0.002 [primary endpoint]; 80/20 mg vs. placebo: 7.5% treatment difference favoring FTI, P < 0.001). The treatment effect on mean PA sputum density was statistically significant for the FTI 80/20 mg group versus placebo (-1.04 log(10) PA colony-forming units/g sputum difference, favoring FTI; P = 0.01). Adverse events, primarily cough, were consistent with CF disease. Respiratory events, including dyspnea and wheezing, were less common with FTI 80/20 mg than FTI 160/40 mg. No clinically significant differences between groups were reported for laboratory values. CONCLUSIONS FTI maintained the substantial improvements in FEV(1) % predicted achieved during the AZLI run-in and was well tolerated. FTI is a promising antipseudomonal therapy for patients with CF.
Thinking outside the cell: how cell-free hemoglobin can potentiate acute lung injury.

intra-alveolar hemorrhage is a pathological feature of acute lung injury (ALI) that was recognized in the first description of the acute respiratory distress syndrome (ARDS) by Ashbaugh and colleagues in 1967 ([2][1]). Over the past four decades, the presence of red blood cells in the air space has
How to facilitate early diagnosis of CNS involvement in malignant lymphoma

ABSTRACT Introduction: Making the diagnosis of secondary CNS involvement in lymphoma can be difficult due to unspecific signs and symptoms, limited accessibility of brain/myelon parenchyma and low sensitivity and/or specifity of imaging and cerebrospinal fluid (CSF) examination currently available. Areas covered: MRI of the total neuroaxis followed by CSF cytomorphology and flow cytometry are methods of choice when CNS lymphoma (CNSL) is suspected. To reduce the numerous pitfalls of these examinations several aspects should be considered. New CSF biomarkers might be of potential diagnostic value. Attempts to standardize response criteria are presented. Expert commentary: Diagnosing CNSL remains challenging. Until diagnostic methods combining high sensitivity with high specifity are routinely introduced, high level of awareness and optimal utilization of examinations currently available are needed to early diagnose this potentially devastating disease.
Information Visualization on Organized Crime Trials

Today everyone on the Internet becomes an active writer. It is simpler than ever to produce and to share new knowledge on the net. Users risk to be overwhelmed by too much information. To handle unorganized data may involve a huge effort by people and this could lead to information overload. A promising way to face these problems is Information Visualization. This contribution is a report of using visuo-spatial reasoning to help sociology scholars to understand and to manage large amounts of textual data. We use a very interesting dataset, especially for sociologists and jurists, extracted from a collection of sentences of trials on organized crime activities in Sicily. We report the results obtained in so far clustering and visualizing data.
Electrocatalytic Drug Metabolism by CYP2C9 Bonded to A Self-Assembled Monolayer-Modified Electrode

Cytochrome P450 (P450) enzymes typically require the presence of at least cytochrome P450 reductase (CPR) and NADPH to carry out the metabolism of xenobiotics. To address whether the need for redox transfer proteins and the NADPH cofactor protein could be obviated, CYP2C9 was bonded to a gold electrode through an 11-mercaptoundecanoic acid and octanethiol self-assembled monolayer (SAM) through which a current could be applied. Cyclic voltammetry demonstrated direct electrochemistry of the CYP2C9 enzyme bonded to the electrode and fast electron transfer between the heme iron and the gold electrode. To determine whether this system could metabolize warfarin analogous to microsomal or expressed enzyme systems containing CYP2C9, warfarin was incubated with the CYP2C9-SAM-gold electrode and a controlled potential was applied. The expected 7-hydroxywarfarin metabolite was observed, analogous to expressed CYP2C9 systems, wherein this is the predominant metabolite. Current-concentration data generated with increasing concentrations of warfarin were used to determine the Michaelis-Menten constant (Km) for the hydroxylation of warfarin (3 μM), which is in good agreement with previous literature regarding Km values for this reaction. In summary, the CYP2C9-SAM-gold electrode system was able to carry out the metabolism of warfarin only after application of an electrical potential, but in the absence of either CPR or NADPH. Furthermore, this system may provide a unique platform for both studying P450 enzyme electrochemistry and as a bioreactor to produce metabolites without the need for expensive redox transfer proteins and cofactors.
Exploring Historical and Emerging Phishing Techniques and Mitigating the Associated Security Risks

Organizations invest heavily in technical controls for their Information Assurance (IA) infrastructure. These technical controls mitigate and reduce the risk of damage caused by outsider attacks. Most organizations rely on training to mitigate and reduce risk of non-technical attacks such as social engineering. Organizations lump IA training into small modules that personnel typically rush through because the training programs lack enough depth and creativity to keep a trainee engaged. The key to retaining knowledge is making the information memorable. This paper describes common and emerging attack vectors and how to lower and mitigate the associated risks.
Prediction of the conducted emission generated by the electrified railway traction system

This paper deals with simulation of an electrified railway AC traction system to predict the audio frequency conducted emissions in the return current. Those conducted emissions are obtained for evaluating the compliance of the traction system with the signaling system. In order to accurately simulate the system the methods to model each key subsystem is elaborated in this paper. Simulation results are verified by the experiments with the limits of one type of signaling system, called UM71 track circuit (1.7 kHz-2.6 kHz), which the traction system should comply with. Moreover factors impacting the level of emission are also discussed in this paper.
Autoimmune dorsal pancreatitis.

To the Editor: Autoimmune pancreatitis is a new clinical entity that has recently been described, and autoimmune mechanisms are involved in the pathogenesis. The disease is morphologically characterized by diffuse enlargement of the pancreas and diffuse irregularly narrowing of the main pancreatic duct. Several cases with segmental swelling of the pancreas or narrowing of the main pancreatic duct have shown features mimicking pancreatic carcinoma. We encountered 25 patients (20 men, 5 women; mean age, 68.4 years) in whom autoimmune pancreatitis was diagnosed using the following criteria: enlargement of the pancreas (n = 24); irregular narrowing of the main pancreatic duct (n = 25); hypergammag lobulinemia (n = 15); presence of autoantibodies (n = 14); histologic findings in the pancreas showing dense lymphoplasmacytic infiltration with fibrosis (n = 11); and effectiveness of steroid therapy (n = 13). Bile ducts exhibited stenosis in the lower portion (n = 20), upper and middle portion (n = 1), and intrahepatic bile duct (n = 1). Initial symptoms were obstructive jaundice (n = 16), abdominal pain (n = 5), general fatigue (n = 1), and uncertain (n = 3). Of these 25 patients, 14 exhibited diffuse narrowing of the main pancreatic duct, and the remaining 11 patients displayed segmental lesions of the pancreatic head. Both the ventral and dorsal pancreatic ducts were involved in 14 diffuse cases and 9 segmental cases. However, 2 patients (1 man and 1 woman) exhibited pathologic changes only in the dorsal pancreatic duct of the pancreatic head. Initial symptoms consisted of abdominal pain. Although the lower bile duct was moderately stenotic, none showed obstructive jaundice. Pancreatographic findings comprised an incomplete pancreas divisum (Fig. 1) and a normal pancreatic duct system with a longtype accessory pancreatic duct running straight from the upper dorsal pancreatic duct (Fig. 2), respectively. Both patients FIGURE 1. Retrograde pancreatogram of a patient with autoimmune pancreatitis shows segmental irregular narrowing of the dorsal pancreatic duct (long arrow), a normal ventral pancreatic duct (short arrow), and a short communicating branch.
Social meanings of adherence to antiretroviral therapy in Cambodia

Global expansion of antiretroviral therapy (ART) programmes for people living with HIV is the largest public health undertaking to date. Antiretroviral therapy adherence drives individual and programme outcomes, yet little is known regarding the determinants of these behaviours. We investigated beliefs and practices associated with ART use in Cambodia. In-depth interviews were conducted during 2005 with 27 people living with HIV who were recruited using a theoretical sampling strategy and analysed in Khmer and English using an inductive approach to code data and identify themes. Limited access to ART generated a sense of ART as rare and precious, with access granted by doctors once patients proved themselves dependable. The social construction of ART use was strict, precise and modern with ritualistic preparation and dosing procedures. Experiences of life-saving efficacy in self and others built a deep sense of trust. For many, ART was simply equated to life. Antiretroviral therapy dosing was prioritized and supported by an ever-present sense of remembering, reminder devices and social networks. Healthcare workers set norms and provided various forms of adherence support. Antiretroviral therapy use in Cambodia is shaped by the relationship between individuals and social and healthcare networks that set, encourage and enforce precise norms of ART use.
Distinct Patterns of Gene Expression Associated with Development of Fluconazole Resistance in Serial Candida albicansIsolates from Human Immunodeficiency Virus-Infected Patients with Oropharyngeal Candidiasis

ABSTRACT Resistance to fluconazole is becoming an increasing problem in the management of oropharyngeal candidiasis in human immunodeficiency virus-infected patients. Strains obtained from five patients developed decreased fluconazole susceptibility over time. DNA strain typing confirmed the high degree of relatedness among isolates from one patient and the variability among isolates from different patients. Expression of genes involved in development of fluconazole resistance was monitored in each isolate using probes specific for ERG11 (lanosterol 14α-demethylase), MDR1 (a major facilitator), andCDR (ATP-binding cassette or ABC transporter) genes. Increased expression of CDR genes was detected in the series of isolates from two patients. Isolates from one of the two patients also demonstrated increased ERG11 expression, whereas isolates from the other patient did not. Increased levels ofMDR1 mRNA correlated with increased resistance in sequential isolates from another patient. Initial overexpression ofMDR1 with subsequent overexpression of CDRgenes and a final isolate again overexpressing MDR1 were detected in serial isolates from another patient. In another patient, overexpression of these genes was not detected despite an eightfold increase in fluconazole MIC. In this patient, sequence data of theERG11 gene revealed no point mutations associated with decreased susceptibility. Five different patterns of gene expression were observed in isolates recovered from five patients who developed resistance. Therefore, these experiments demonstrate that a variety of mechanisms or combinations of mechanisms are associated with the development of fluconazole drug resistance. Additional studies are needed to estimate the frequency and clinical impact of these mechanisms of resistance.
Analysis of Cryptococcus neoformans Sexual Development Reveals Rewiring of the Pheromone-Response Network by a Change in Transcription Factor Identity

The fundamental mechanisms that control eukaryotic development include extensive regulation at the level of transcription. Gene regulatory networks, composed of transcription factors, their binding sites in DNA, and their target genes, are responsible for executing transcriptional programs. While divergence of these control networks drives species-specific gene expression that contributes to biological diversity, little is known about the mechanisms by which these networks evolve. To investigate how network evolution has occurred in fungi, we used a combination of microarray expression profiling, cis-element identification, and transcription-factor characterization during sexual development of the human fungal pathogen Cryptococcus neoformans. We first defined the major gene expression changes that occur over time throughout sexual development. Through subsequent bioinformatic and molecular genetic analyses, we identified and functionally characterized the C. neoformans pheromone-response element (PRE). We then discovered that transcriptional activation via the PRE requires direct binding of the high-mobility transcription factor Mat2, which we conclude functions as the elusive C. neoformans pheromone-response factor. This function of Mat2 distinguishes the mechanism of regulation through the PRE of C. neoformans from all other fungal systems studied to date and reveals species-specific adaptations of a fungal transcription factor that defies predictions on the basis of sequence alone. Overall, our findings reveal that pheromone-response network rewiring has occurred at the level of transcription factor identity, despite the strong conservation of upstream and downstream components, and serve as a model for how selection pressures act differently on signaling vs. gene regulatory components during eukaryotic evolution.
Effect of Transdermally Delivered Aspirin on Blood Coagulation Parameters

The efficacy of oral aspirin treatment in the secondary prevention of cardio and cerebro vascular disease is well known. However oral administration is often associated with abdominal discomfort. The feasibility of delivering aspirin transdermally from eudragit and polyvinyl acetate (PVA) matrix-type patches to enhance its antithrombotic efficiency of aspirin was investigated. Transdermal films containing mixture of eudragit RL: eudragit RS and polyvinyl acetate were fabricated. Eudragit RL: eudragit RS (5:1) films containing 30 mg/ transdermal patch aspirin showed maximum release (11.891.1g/cm 2 ) after 24 hrs as compared to PVA films. With regards to appearance eudragit films were also wrinkle free, uniform, flexible and transparent with good adhesion property to skin. The effect of turpentine oil and lemon oil at different concentrations on the in vitro percutaneous absorption of aspirin from eudragit copolymer patches through rat skin was investigated. Two formulation containing 50 mg/transdermal patch ASA with 0.042 ml turpentine oil and 0.042 ml lemon oil showed a significantly higher flux of ASA 4.22 g/cm 2 /hr and 38.52 g/cm 2 /hr respectively. The optimized formulations influenced the blood coagulation parameters (bleeding time, prothrombin time, Activated partial prothrombin time) significantly by means of affecting both the extrinsic coagulation system and the intrinsic coagulation system as compared to orally administered and control gel formulations.