Allyl chloride is used in the

Allyl chloride is used in the synthesis of allyl compounds [2]; as an intermediate for the manufacture of polymers, resins, plastics [3]; for varnishes and adhesives; and in the synthesis of pharmaceuticals and insecticides [4]. In the United States, this chemical is listed as a high production volume (HPV) chemical (65FR81686), which means that >1 million pounds was produced or imported into the United States in 1990 and/or in 1994 [5]. In workplaces where allyl chloride is produced or used, occupational exposure to allyl chloride may occur through inhalation and dermal contact [6].
Allyl chloride has already been tested for mutagenicity by the following short-term tests: Salmonella reversion test with strains TA1535 and TA100 (with and without activation), a forward and back mutation system in Streptomyces coelicolor, and two forward mutation systems in Aspergillus nidulans. Spot and plate incorporation assay techniques are also employed. Allyl chloride was active in Salmonella typhimurium and Salmonella coelicolor and negative in A. nidulans[7]. In our previous study [8], allyl chloride did not induce chromosomal aberrations in Chinese hamster lung (CHL/IU) cells; we therefore proceeded to perform an in vivo MN assay. This was necessary to improve the evaluation of the carcinogenic potential of this compound.
The purpose of the MN test is to screen for cytogenetic damage that results in the formation of micronuclei containing lagging chromosome fragments or whole chromosomes. Micronuclei were first used to quantify chromosomal damage and are now recognized as one of the most successful and reliable assays for genotoxic carcinogens [9].
In the in vivo MN test, mammalian bone marrow carboxypeptidase are treated with allyl chloride. Many toxicological studies other than the MN test have been conducted, although the available genotoxic data on allyl chloride remain controversial with and without mammalian metabolic activation (S9). Therefore, to secure quality assurance, further study was necessary that was based on good laboratory practice (GLP) guidelines.
Table 1 shows physicochemical and toxicological information regarding allyl chloride. Using the Globally Harmonized System of Classification and Labeling of Chemicals (GHS) classification, a “mutagen” is an agent that increases the occurrence of mutations in populations of cells and/or organisms. Substances and mixtures in this hazard class are assigned to one of two hazard categories. Category 1 has two subcategories (Table 2). Many studies have focused on the mutagenicity of allyl chloride (Table 3; however, with the exception of our previous study [8], no study has used GLP tests. Allyl chloride is nevertheless has category 2 germ cell mutagen notified classification and labeling, according to Classification, Labelling, and Packaging (CLP) criteria [10] on the evidence of these non-GLP dataset. The CLP regulation ensures that the hazards presented by chemicals are clearly communicated to workers and consumers in the European Union (EU) through the classification and labeling of chemicals. A public notice of the Ministry of Employment and Labor (MoEL) of Korea (Sejong, Korea) [11] has also classified it as a Category 2 germ cell mutagen following European Union Classification, Labelling, and Packaging classification (EU-CLP).
Therefore, the MN assay accorded by GLP guidelines [12] was necessary to determine its mutagenicity exactly and propose it to a regulatory body such as the MoEL of Korea.

Materials and methods

Results and discussion
There were no specific symptoms among the animals that were orally exposed to allyl chloride. The body weight of the animals exposed to this chemical ranged 35.74–40.20 g (Table 4). There were no environmental factors that may have affected the quality or integrity of the study results, which includes any significant behavioral changes (i.e., neurophysiological activity).
Preliminary tests were performed to determine the maximum dosage. The proliferation of bone marrow cells was not inhibited in this test. The presence of micronucleated PCEs was visually scored by optical microscopy using a fluorescence microscope (Fig. 2).

The mortality rate due to MDRAB infection in the NICU

The mortality rate due to MDRAB infection in the NICU during the study carboxypeptidase was 20.34%. A mortality rate as high as 37.5% was reported in a previous NICU study. In Taiwan, a previous study on adult patients with MDRAB infection reported a 30-day mortality rate of 49%, and another study at the same hospital on pediatric patients reported a 30-day mortality rate of 42.3%.
Some of the statistically significant risk factors for mortality in this study were unexpected, such as an NICU stay < 7 days, no prolonged hospitalization, no surgical history, no BPD, no recurrent sepsis, no prolonged intubation, shorter ventilator use, shorter NCPAP use, shorter central line use, shorter PCVC use, and shorter TPN and/or Intrafat use. Most of the patients who died in the current study (9/12 patients; Table 1) had a shorter NICU stay and had been in the NICU for < 7 days when they became infected with MDRAB. The definition of mortality due to MDRAB infection in this study was death occurring within 7 days of a positive culture result. Thus, these nine neonates died after < 2 weeks hospitalization. As a large proportion of the cases of mortality died early, this may have led to errors in the statistical analysis. All parameters including “duration” may therefore not be reliable, even if it showed statistical significance. For example, complications such as BPD and recurrent sepsis needed > 2 weeks to reach their definition. Invasive procedures including the use of a ventilator, central lines, and TPN and/or Intrafat seemed to be negative risk facts, although this may also be because the patients died early and further studies are needed to clarify this issue. With regards to surgical history, only one of the 12 neonates underwent surgery (Table 1). The unequal distribution carboxypeptidase of these two groups may mean that this factor is not suitable for statistical analysis. With regards to umbilical vein use, six neonates died and six did not (Table 2). It is possible that the statistical significance in the umbilical vein use group increased the risk of mortality.
In a previous study, the authors found that anemia and leukopenia were risk factors for mortality, but not thrombocytopenia. In the current study, it was also found that leukopenia and thrombocytopenia were indicators of a poor prognosis. Thirteen out of 59 neonates had both leukopenia and thrombocytopenia, of whom six died of MDRAB infection. In addition, the timely use of colistin in the current study resulted in a lower mortality rate. There were no records of impaired renal function among the studied neonates, even in the colistin group. Due to the clusters of MDRAB infection noted in the NICU during the study period and the high mortality rate associated with MDRAB infection, using colistin as the empirical antibiotic if neonates show signs of sepsis, and especially when neonates in close proximity have MDRAB infection, is recommended.

Conflicts of interest


The incidence of health care-associated infection (HCAI) caused by Gram-negative bacteria, particularly multidrug-resistant bacteria, has gradually increased and exerted a global impact on public health. Moreover, infections caused by resistant microorganisms would lead to many adverse outcomes, including extended length of stay, higher health care costs, and greater hospital morbidity and mortality.Acinetobacter baumannii has recently emerged as a major pathogen causing HCAI and is notorious for its capacity to rapidly accumulate mechanisms of antibiotics resistance. Multidrug-resistant A. baumannii can cause various types of HCAI, including bacteremia, pneumonia, meningitis, urinary tract infection, and wound infections. Prior use of broad-spectrum antibiotics was demonstrated to be a major risk factor for acquiring multidrug-resistant A. baumannii infections.
Although several studies have investigated the relationship between antibiotic consumption and antibiotic resistance, the inconsistent results among these studies may be attributable to differences in resistance profiles and antibiotic prescribing practices in different countries. These findings support the necessity of monitoring aggregate antibacterial drug use at local and national levels in order to evaluate the associations between the use of antibiotics and emerging antibiotic resistances. This study investigated the correlations between antibiotic consumption and incidence of HCAI caused by IRAB from 2005 to 2010 at a hospital in southern Taiwan.

Among five patients receiving antimicrobial drugs months before the

Among five patients receiving antimicrobial drugs 6 months before the survey, one had antibiotic and antifungal drug, two had antibiotic, and two had antifungal drug. The duration for carboxypeptidase ranged from 90 to 180 days and for antifungal drugs ranged from 7 to 130 days. Four of the five patients were colonized by yeasts. Candida isolates were susceptible to fluconazole despite the fact that they were recovered from patients receiving fluconazole therapy before the survey.

As the disease progresses, HIV-infected patients become more vulnerable to a variety of opportunistic infections, including candidiasis. The prevalence of oropharyngeal yeast colonization in HIV-positive patients varies from 44% to 62% in the antiretroviral therapy era. In the current study, 51.4% of HIV-infected patients had yeast colonization in the oropharyngeal cavity. We also found a higher rate of oropharyngeal yeast colonization in HIV-positive patients if their CD4 lymphocyte counts were ≤200 cells/μL. This finding is similar to that of previous studies. In addition to the low CD4 lymphocyte count, several other factors could influence the occurrence and distribution of oropharyngeal yeast colonization.
Phelan et al and Lamster et al reported a much higher prevalence rate of oral Candida infection in intravenous drug users than in homosexual men. Even in seronegative patients, a higher percentage of oral candidiasis was observed among intravenous drug users. Opioids, particularly morphine and its derivatives, have been shown to depress the immune system by influencing the function of T lymphocytes. Therefore, in HIV-infected patients who also receive injections of opioids, their immunity could be further depressed by the dual effect of opioids and HIV. In the current study, we found the prevalence of oropharyngeal yeast colonization was significantly higher in HIV seropositive intravenous drug users than in homosexual men. This observation lends further support to the immunosuppressive effect of opioids in HIV-infected patients. Nevertheless, whether abuse of opoids is detrimental to immunity needs further investigation.
PI, an important component of highly active antiretroviral therapy, blocks the action of the HIV protease, which is required for protein processing in the viral replication cycle.In vitro studies demonstrated that PIs could inhibit secreted aspartic proteases of C. albicans and consequently attenuate their adherence to epithelial cells, interrupt the integrity of yeast cell membrane, and decrease the viability of Candida. These results suggested that the reduction of oral Candida colonization in HIV-infected patients who received antiretroviral therapy might not only be due to reconstitution of the immune system, it could also result from the effect of direct inhibition to secreted aspartic proteases by PIs.
Despite these in vitro studies, there is limited literature comparing the clinical differences of antiretroviral regimens on the prevalence of oropharyngeal yeast colonization in HIV-infected patients. Cassone et al found that PI-containing antiretroviral therapy exerted an early, immune reconstitution-independent effect on attenuation of oral candidiasis compared with NNRTI-containing regimens. Pomarico et al investigated the effect of antiretroviral therapy on oral candidiasis and found that PI-containing regimens reduced the prevalence rate of oral candidiasis in HIV-positive children. However, Delgado et al reported that PI-containing regimens exerted no different effect on the oral carriage of Candida when compared with NNRTI-containing regimens. Interestingly, the current study demonstrated that the prevalence of yeast colonization in oropharyngeal cavity was significantly higher in patients receiving PI-containing antiretroviral therapy than in those with NNRTI-containing regimens. Moreover, this difference was independent of the patients’ CD4 cell count and plasma HIV viral load. However, all of these clinical studies, including the current report, were not randomized, double-blind, parallel-group investigations. To better understand the influence of different antiretroviral regimens on the distribution of oropharyngeal Candida colonization in HIV-infected patients, further well-designed head-to-head comparison studies are warranted.

The analysis of a subpopulation

The analysis of a subpopulation of the REDUCE study brings interesting clues to understand the role of inflammation in mainly painful symptoms or like chronic prostatitis and the chronic pelvic pain syndromes-type pain in patients labeled as BPH patients. Meanwhile, it was found that “On the basis of data from epidemiological studies suggesting a reasonable percentage of men enrolled in REDUCE would have prostatitis or prostatitis-like symptoms,” along with the fact that the use of dutasteride can improve such symptoms. Then it appears increasingly evident that in the population of patients with a prevalence of storage symptoms, we need to assess the presence of prostate inflammation. And the latter, a coexisting MetS, can affect the outcome of the unblocking operation, as well as affect the clinical symptoms. Careful assessment of the state of an inflamed prostate is likely to be a decisive step to set the proper medical or surgical therapy, obviously placed in a holistic view of the patient who is no longer “a prostate surgery patient” but a patient with obstructive symptoms or storage symptoms into a total clinical context.
This work confirms the correctness of the intuition of Galen that in presence of purulent lesions advised: “” (“Where there is pus, (there) evacuate it”); an inflamed prostate, often with micro abscesses, conceptually responds to Galen\’s policy and must be removed.

Emerging evidence suggests that prostatic inflammation may play a role in benign prostatic hyperplasia (BPH) development and progression. Furthermore, the presence of prostatic inflammatory infiltrates may influence the carboxypeptidase and the severity of lower urinary tract symptoms (LUTS) and/or BPH at different stage. In particular, in naïve and/or untreated patients with BPH, metabolic syndrome (MetS), a well-established cause carboxypeptidase of systemic inflammation, is associated with an increased risk of storage symptoms; in pharmacologically treated patients, those with low-grade inflammation presented a 3.5 higher LUTS improvement than high-grade group; in patients undergoing transurethral resection of the prostate (TURP), we confirmed the association between MetS and prostate inflammation and demonstrated that patients with inflammatory infiltrates mostly benefit from TURP, particularly regarding storage symptoms.

According to world-wide estimates, human papillomavirus (HPV) infection is responsible for 4.8% of all cancers. The association between HPV and cervical cancer has been well known for many decades, but the link between HPV and cancers of the penis has only recently been confirmed. HPV deoxyribonucleic acid (DNA) is detectable in 30%-60% of all invasive penile squamous cell carcinomas (PSCCs), and prevalence varies across different series. HPV16 and to a lesser extent HPV18 are the most frequent viral types associated with PSCC; HPV31 and HPV33 are rarely detected. In circumcised men, HPV prevalence is lower than in uncircumcised men, and penile cancer is rare in populations that routinely practice circumcision. Some published studies state that HPV16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, and 68 have been associated with intraepithelial neoplasia and carcinoma of the cervix. The studies indicate that these types of HPV were considered primary high-risk (carcinogenic) genotypes. Moreover, 3 current reviews stated that many of these aforementioned types of HPV were considered with PSCC.
Urinary tract infection (UTI) represents the most common bacterial infection in children. In the first 3 months of life, UTIs were present in 2.4% of circumcised boys, and 20.1% of uncircumcised boys, who presented with fever. UTI is an important cause of morbidity and mortality in children. If poorly treated or undiagnosed, it may lead to poor renal growth, recurrent pyelonephritis, impaired glomerular function, early hypertension, end-stage renal disease, and pre-eclampsia. Periurethral colonization may be an important initial step toward an ascending UTI.

Acquired events were shown in a dot

Acquired events were shown in a dot plot scatter gram based on forward- (FSC) and side-scatter (SSC). Two gates were set to include only fluorospheres and lymphocytes, respectively, and analyses were restricted to these two populations. A histogram with log values for FI on the x-axis and cell number on the y-axis was used for the analyses (Fig. 1). MFI of fluorospheres, MFI and fluorescence histogram Coefficient of Variation (fhCV) of CD-positive carboxypeptidase were measured. In order to avoid any possible bias due to sample processing or cytometer conditions, the Relative Fluorescence Intensity (RFI) was calculated making a ratio between lymphocytes and fluorospheres MFIs and used for further analyses (Henderson et al., 1998). Finally, since a heterogeneous fluorescence distribution was detected for CD21, analyses were performed including all CD21-positive lymphocytes (CD21tot) and only lymphocytes with higher CD21 expression (CD21high), respectively (Fig. 1).
According to the distribution of data, paired-samples Wilcoxon or t-test was performed to compare RFI and fhCV of each antigen between T0 and T24. Influence of experiment (group 1 and 2), time (T0 and T24), sex (male and female), breed (purebred and crossbred) and age (<2 yrs, 2–10 yrs and >10 yrs) on RFI of CD4 was assessed through GLM univariate analysis. The statistical software IBM SPSS Statistics v23.0 for Windows was used for statistical analyses. Significance was set at p≤0.05 for all tests.

Different FI-based studies have been published in the veterinary literature. Still, FI normalization remains a challenging issue, and different approaches have been attempted to date. In one study on platelet activation (Moritz et al., 2005), in one assessing CD11b expression on neutrophils (Maeda et al., 2010) and in one assessing the prognostic value of MHC class II expression in canine B-cell lymphomas (Rao et al., 2011) MFI values from the population of interest were compared to the MFI of negative controls (either healthy subjects, untreated cells or non neoplastic tissue), but fluorescence normalization was not attempted. In another paper assessing the quality of canine PB samples stored in a preservative medium, the mere MFI values were considered (Cian et al., 2014). Finally, a ratio between the MFI of the population of interest and the MFI of control cells from the same individual (non neoplastic neutrophils and unstained cells, respectively) was used in two papers (Comazzi et al., 2006b; Gelain et al., 2014). None of these methods of FI evaluation has ever been validated.
One study in human medicine compared different FI normalization methods (Dendrou et al., 2009). Significant time effects on MFI values were found, despite the numerous expedients adopted to avoid technical variability. In addition, isotype MFIs showed a large variation even among samples analysed one the same day. Authors conclude that use of mere MFI values should be avoided and isotype controls are not usable for FI normalization, whereas the use fluorospheres to normalize results improves repeatability of FI analysis.
Based on the study by Dendrou and colleagues, fluorospheres should be considered the method of choice for FI normalization. Unfortunately, they are quite expensive, whereas internal biological controls (cell subsets with stable MFI within the population) may be more accessible for veterinary laboratories. An optimal internal control should be characterized by a FI as much stable as possible, both among different subjects and upon storage. Therefore, we analysed the variability of expression of the main lymphoid antigens, using standard fluorospheres to normalize FI. Based on these analyses, CD4, cyCD79b and CD21high showed the lowest cell-to-cell and dogs-to-dog variability. However, cyCD79b and CD21high have weaknesses that decrease their potential use as internal FI controls. On one hand, staining for cyCD79b requires permeabilization procedures that are cost- and time-consuming. On the other hand, CD21high population is difficult to define in a clear and repeatable way because of the low CD21+ cell number. In fact, B-lymphocytes are less represented than T-lymphocytes in peripheral blood from healthy dogs (Faldyna et al., 2001) and T-antigens might be more suitable to be used as a standard, since the collection of a statistically adequate number of T-cells is simpler to achieve. Finally, fhCV of both cyCD79b and CD21high varied with storage.

Among the micro organisms discovered by Escherich he

Among the micro-organisms discovered by Escherich, he carboxypeptidase intensively investigated the “Bacterium coli commune”, which 8 years after his death in 1911, was named for the first time “”. This posthumous honour made Escherich worldwide known in the medical profession. The importance of among commensal in the gut and as pathogenic bacteria in the gut and at other mucosae is immense. Additionally, since the birth of molecular cloning,  has been used as a host for introduced DNA sequences and today, it still is used in labs worldwide as a host for foreign DNA sequences and their protein products.

A 2013 survey of the experimental and scientific use of animals in the European Union indicated that rodents account for 75% of all animals used in biomedical research while pigs represent less than 1% (Commission, 2013). Although rodent models have often yielded valuable information related to human diseases (Fairbairn et al., 2011; Takao and Miyakawa, 2015), other studies have been skeptical toward the use of rodents to model human responses to infectious diseases (Martinez et al., 2006; Seok et al., 2013). For example, in vitro models of lipoplysaccaride (LPS)-stimulated Mφs suggest that the transcriptome of human and mouse Mφs only Exhibit 30–50% similarity (Martinez et al., 2006). A number of recent reports suggest that pigs may more faithfully reproduce the human immune response in models of infectious disease (Dawson, 2011; Dawson et al., 2013; Groenen et al., 2012; Meurens et al., 2012) and greater human-pig similarities in LPS-stimulated Mφs have been observed (Kapetanovic et al., 2012). Although pigs are considered phylogenetically further away from humans than mice, pigs and humans have a more similar level of selection pressure (Groenen et al., 2012), and pigs are closer to humans than mice in protein structural similarity (Dawson, 2011). Our studies indicate that the frequency of protein domain structural preservation between human and pig is nearly twice that of mouse to human and pig to mouse (Dawson, 2011). Furthermore, a large scale analysis of immune response genes revealed that pigs have 11-, 6- and 2- fold less unique genes than do the mouse, cow or human (Dawson et al., 2013). Overall familial gene expansion of immune response genes in pigs relative to humans is less than half the rate of mice (Dawson et al., 2013). This expansion is most prominently in a class of proteins known as pattern recognition receptors (PRRs) that are involved in the recognition of damage-associated molecular patterns (DAMPs), microbe-associated molecular patterns (MAMPs) and pathogen-associated molecular patterns (PAMPs). Although these data reinforce the concept that pigs are useful models for humans, an in depth comparative analysis of human, mouse, and pig PRRs has not been previously conducted.

Pattern recognition receptors (PRRs)
At least 11 broad families of germline-encoded PRRs have been identified as important components of innate immunity across host species. Table 1 shows a comparison of PRR gene families among humans, pigs, and mice. PRRs evolved under a high level of selection pressure as host species expressed mechanisms to deal with an ever-changing number of pathogens that also evolved strategies to evade and disable the host immune response. Our reanalysis of all PRR superfamily groups is shown in Table 1. These data showed a >25% family gene expansion in eight out of 11 PPR families (73%) in the mouse relative to humans or pigs. The most dramatic expansions were detected in the Absent in melanoma 2 (AIM2)-like receptor superfamily, nucleotide-binding domain, leucine-rich repeat–containing (NLR) superfamily, and the NK cell receptor subfamily of the C-type lectin (CLEC) superfamily. No expansion of >25% was observed in pigs relative to humans and mice, and two superfamily contraction in pigs (NLR, AIM2-like receptors) and one in mice (CD1 superfamily) were observed relative to humans.

The HPV DNA genome can

The HPV16 DNA genome can be divided into an early and a late region (Fig. 1A) (Howley and Lowy, 2006). The early region is coding for E1, E2, E4, E5, E6 and E7 and is followed by the early polyA signal pAE, while the late region encodes L1 and L2 and is followed by the late polyA signal pAL. The early promoter p97 is situated upstream of the E6 gene and could potentially produce mRNAs encoding all HPV proteins, while the late promoter p670 is situated upstream of the E1 gene and therefore cannot be used to express the E6 and E7 genes (Schwartz, 2013; Baker and Calef, 1997). HPV16 gene expression is controlled at the level of transcription (Bernard, 2013), which is regulated by both HPV16 E2 and by cellular factors (McBride, 2013; Thierry, 2009). HPV16 gene expression is also regulated at the level of polyadenylation which includes a switch from the early polyA signal (pAE) to the late polyA signal (pAL), and at the level of splicing as evidenced by the high number of alternatively spliced mRNAs that produced during the viral life carboxypeptidase (Johansson and Schwartz, 2013; Schwartz, 2013; Graham, 2008; Jia and Zheng, 2009).
The efficiency by which a splice site is used is determined by cis-acting regulatory RNA elements termed splicing enhancers and silencers (Cartegni et al., 2002). Many of the HPV16 splice sites are controlled by cis acting RNA elements (Johansson and Schwartz, 2013). For example, the efficiently used 3′-splice site SA3358 used by both early and late HPV16 mRNAs is dependent on a strong splicing enhancer located downstream of SA3358 (Rush et al., 2005; Somberg and Schwartz, 2010; Li et al., 2013). This enhancer interacts with ASF/SF2 (SRSF1), SRp30c (SRSF9) and SRp20 (SRSF3) (Somberg and Schwartz, 2010; Li et al., 2013; Somberg et al., 2011; Jia et al., 2009, 2010). Lack of splicing to SA3358 reduces polyadenylation at pAE, demonstrating that the splicing enhancer downstream of SA3358 is a key regulatory element in the HPV16 life cycle (Rush et al., 2005; Li et al., 2013). Furthermore, HPV16 late splice sites SD3632 and SA5639 that are used exclusively to produce the late L1 mRNAs, are under control of splicing silencers that interact with hnRNP A1 for SA5639 (Zhao et al., 2004, 2007; Zhao and Schwartz, 2008), and with hnRNP D-proteins and hnRNP A2/B1 for SD3632 (Li et al., 2013). On the other hand, hnRNP A1 enhances splicing of the HPV16 early mRNAs (Rosenberger et al., 2010). The HPV16 early polyA signal is also subject to regulation, and a reduction in polyadenylation efficiency is required for activation of HPV16 late gene expression (Zhao et al., 2005; Jeon and Lambert, 1995). The HPV16 E2 protein interferes with the polyadenylation complex at pAE thereby inducing HPV16 late gene expression (Johansson et al., 2012). The HPV16 early polyA signal is under positive control of the upstream, untranslated region (Zhao et al., 2005; Jeon and Lambert, 1995) and by downstream elements spanning the L2 coding region (Oberg et al., 2005). In contrast, the late polyA signal is strongly suppressed by sequences in the late UTR that are active at least in mitotic cells (Graham, 2008). Thus, RNA processing plays a major role in HPV16 gene regulation (Johansson and Schwartz, 2013).
Although it is well established that the state of the chromatin control transcription of cellular genes, recently published results indicate that chromatin and epigenetic properties of chromosomal DNA within genes such as nucleosome positioning, histone methylation, acetylation and phosphorylation may contribute to the control carboxypeptidase of RNA splicing and polyadenylation by recruiting RNA processing factors to DNA sequences encoding splicing regulatory RNA elements (Braunschweig et al., 2013; Brown et al., 2012; Acuna et al., 2013; Schwartz and Ast, 2010; Luco and Misteli, 2011; Iannone and Valcárcel, 2013). For example, H3K36me3 and H3K9me3 are enriched over exons and may recruit splicing factors (Barski et al., 2007; Wang et al., 2008; Luco et al., 2010; Pradeepa et al., 2012; Saint-Andre et al., 2011), while high levels of H3K9Ac are associated with exon skipping (Zhou et al., 2011; Schor et al., 2009). Posttranslational modifications of histones on the HPV16 genome could therefore potentially control HPV16 gene expression. It has also recently been shown that the HPV16 genome is subject to epigenetic modifications over the viral replication cycle, in particular DNA methylation although the significance of these modifications is unclear (Szalmás and Kónya, 2009; Steenbergen et al., 2014). Furthermore, chromatin immunoprecipitations performed on HeLa cell chromatin have indicated that histone marks on the HPV18 sequences in HeLa cells are unevenly distributed over the HPV18 genome, suggesting a role for histone modifications in the control of HPV18 gene expression (Johannsen and Lambert, 2013). The papillomavirus E2 proteins interact with chromatin and could potentially control gene expression by interfering with histone function (McBride et al., 2012). We therefore wished to investigate if epigenetic properties of the HPV16 genome could potentially control HPV16 gene expression.

br Fig nbsp xA Pressure distribution in claw vacuum

Fig. 10. Pressure distribution in claw vacuum pumps. (a) The proposed profile. (b) The reference profile.Figure optionsDownload full-size imageDownload high-quality image (195 K)Download as PowerPoint slide

4.3. Temperature distributions

Temperature distributions of claw vacuum pumps of the proposed profile and the reference profile are shown as Fig. 11. The two figures are in the same position of the end of carboxypeptidase process; and the temperature distributions are uniform throughout the working chamber. The temperature in compression chambers of the proposed profile is higher than that of the reference profile, because pressure in compression chambers of the proposed profile is higher than that of the reference profile.

Fig. 11. Temperature distribution in claw vacuum pumps. (a) The proposed profile. (b) The reference profile.Figure optionsDownload full-size imageDownload high-quality image (177 K)Download as PowerPoint slide

5. Stress analysis

Claw type vacuum pump is a kind of long-term operation of machinery, and it has the certain requirement for the strength of the rotor. So it is necessary to study the strength of these two kinds of rotors.

The pressure distributions of Fig. 10 are loaded as boundary conditions, and the inner surfaces of claw rotors are fixed. The boundary conditions are: 1 × 105Pa on the recess side of the claw rotors, and 0.5 × 105Pa on the other side of the claw rotors. The stress calculations of the proposed profile and the reference profile are carried out. The stress distributions of left claw rotors are shown in Fig. 12.

Fig. 12. Stress distributions of right rotors. (a) The proposed profile. (b) The reference profile.Figure optionsDownload full-size imageDownload high-quality image (239 K)Download as PowerPoint slide

Fig. 12 reveals that the stress distribution of the proposed profile is smaller than the reference profile. The maximum stress of the reference profile is 9 × 105 Pa, which is twice as large as the maximum stress of the proposed profile. At the cusp position of the reference rotor, the stress is 3.9 × 105 Pa; and at the corresponding position of the proposed rotor, the stress of circular arc is 1.3 × 105 Pa, which is 66.7% lower than that of the cusp.

The stress distributions of right claw rotors are shown in Fig. 13. The boundary conditions are: 0.5 × 105 Pa on the recess side of the claw rotors, and 1 × 105 Pa on the other side of the claw rotors.

Fig. 13. Stress distributions of left rotors. (a) The proposed profile. (b) The reference profile.Figure optionsDownload full-size imageDownload high-quality image (238 K)Download as PowerPoint slide

It can be seen from Fig. 13 that the stress distributions in reference profile and the proposed profile are almost similar. But the maximum stress of the reference profile is 3 × 105 Pa which is still a bit higher than that of the proposed profile which maximum stress is 2.8 × 105 Pa.

Therefore, the maximum stress of the proposed profile is lower than that of the reference profile with the same pressure boundary conditions; and the stress performances of the proposed profile are better than that of the reference profile.

6. Conclusion

(1)A novel circular arc claw rotor profile consisting of equidistant curves of epitrochoidal arc and circular arcs for claw vacuum pumps has been proposed, its equations as well as changing rules have also been obtained. The proposed profile for left and right rotors can mesh with each other correctly.(2)Compared with the reference profile under the same conditions, the proposed profile has better performances of small recess volume, big compression ratio and low stress distributions.(3)The proposed profile is more suitable for high load operation conditions, such as high pressure, high temperature and high rotation velocity; and the applications of the claw machinery using the proposed profile can be extended to claw compressors and claw expanders.(4)The proposed profile effectively increases the running life of claw rotors, enriches the type of claw rotor profile, and promotes the development of claw vacuum pumps.

br Image Analysis br The diaphragmatic

Image Analysis

The diaphragmatic motions on sequential chest radiographs (dynamic image data) during tidal breathing were analyzed using prototype software (Konica Minolta, Inc.) installed in an independent workstation (Operating system: Windows 7 Pro SP1; Microsoft, Redmond WA; CPU: Intel Core i5-5200U, 2.20 GHz; memory 16 GB). The edges of the diaphragms on each dynamic chest radiograph were automatically determined by means of edge detection using a Prewitt Filter 18 ;  19. A board-certified radiologist with 14 years of experience in interpreting chest radiography selected the highest point of each carboxypeptidase as the point of interest on the radiograph of the resting end-expiratory position (Fig 2a). These points were automatically traced by the template-matching technique throughout the respiratory phase (Fig 2b, Supplementary Video S1), and the vertical excursions of the bilateral diaphragm were calculated (Fig 2c): the null point was set at the end of the expiratory phase, that is, the lowest point (0 mm) of the excursion on the graph is the highest point of each diaphragm at the resting end-expiratory position. Then the peak motion speed of each diaphragm was calculated during inspiration and expiration by the differential method (Fig 2c). If several respiratory cycles were involved in the 10 to 15-second examination time, the averages of the measurements were calculated.

Figure 2. Representative sequential chest radiographs and the graphs of excursion and peak motion of the diaphragms obtained by chest dynamic radiography (“dynamic X-ray phrenicography”). (a) Radiograph of the resting end-expiratory position. (b) Radiograph of the resting end-inspiratory position. (c) Graph showing the vertical excursions and the peak motion speeds of the bilateral diaphragm. A board-certified radiologist placed a point of interest (red point) on the highest point of each diaphragm on the radiograph at the resting end-expiratory position (a). These points were automatically traced by the template-matching technique throughout the respiratory phase (double arrows in b) (Supplementary Video S1); red double arrow indicates the vertical excursion of the right diaphragm and blue double arrow indicates that of the left diaphragm. Based on locations of the points on sequential radiographs, the vertical excursions and the peak motion speeds of the bilateral diaphragm were calculated (c). The lowest point (0 mm) of the excursion on the graph indicated that the highest point of each diaphragm was at the resting end-expiratory position (ie, null point was set at the end-expiratory phase) (c). (Color version of figure is available online.)Figure optionsDownload full-size imageDownload high-quality image (305 K)Download as PowerPoint slide

Pulmonary Function Tests

The pulmonary function tests were performed carboxypeptidase in all participants on the same day of the imaging study. Parameters of pulmonary function tests were measured according to the American Thoracic Society guidelines 20 ;  21 using a pulmonary function instrument with computer processing (DISCOM-21 FX, Chest MI Co, Tokyo, Japan).