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In this paper, a novel 30 V fully isolated n-channel lateral DMOS (nLDMOS) with low specific on-resistance (RON,sp) is proposed and experimentally realized using 0.35 µm Bipolar-CMOS-DMOS (BCD) process. We optimized the process parameters, such as doping concentration of the high-voltage drift n-well (HVNW) layer, P-buried layer (PBL) and pre deep n-well (Pre-DNW) layer, for achieving a superior tradeoff between high breakdown voltage (BV) and the low RON,sp. The proposed nLDMOS is fully isolated from the substrate to support negative bias to drain and has a very lower RON,sp than other competitors in the similar technology, which is critical for devices used in high-voltage, high-current switching applications such as HVIC's. The fabricated device exhibits a BV of 42 V with RON,sp as low as 15 mohm-mm2 . Besides, the new structure is fully compatible with standard 0.35 µm BCD technology, with a margin of up to 15% in process variation, which is large enough to meet the industrial requirement for mass production. Hence, it is not only high performance but also a low-cost solution. Keywords: nLDMOS, Substrate current, 0.35 µm BCD technology, Specific on-resistance (RON,sp), Breakdown voltage (BV)

Axolotls (Ambystoma mexicanum) may heal their skin wounds scar-free in both paedomorphs and metamorphs. In previous studies on small punch skin wounds, rapid re-epithelialisation was noted in these two axolotl morphs. However, large wound size in mammals may affect wound healing. In this study, large circumferential full thickness excision wounds on the hind limbs were created on juvenile paedomorphic and metamorphic axolotls. The results showed re-epithelialisation was more quickly initiated in paedomorphs than in metamorphs after wounding. The migrating rate of epidermis on the wound bed was faster in paedomorphs than in metamorphs and thus completion of re-epithelialisation was faster in paedomorphs than in metamorphs. Within these re-epithelialisation periods, neither basement membrane nor dermis was reformed. Epidermal cell proliferation was detected by EdU-labelling technique. In the normal unwounded skin, epidermal proliferation rate was higher in paedomorphs than in metamorphs. After wounding, the epidermal proliferation rate was significantly lower in the migrating front on the wound bed than in the normal skin in paedomorphs. The EdU-labelling rate between normal skin and migration front was not different in metamorphs. Lacking of more proliferating epidermal cells on the wound bed indicated that the new epidermis here derived rather from migrating epidermal cells than from cell proliferation in situ. In conclusion, re-epithelialisation in the large wound might be fully completed in both morphs despite it was initiated earlier and with faster rate in paedomorphs than in metamorphs. The new epidermis on the wound bed derived mainly from cell migration than by cell proliferation in the re-epithelialisation period. J. Morphol. 278:228-235, 2017. © 2016 Wiley Periodicals,Inc.

Differential bevel gear strength calculation, The main purpose is to evaluate whether the gear can meet the strength and life requirements under load; There is a mature theoretical gear strength calculation formula, However, due to the theoretical gear strength calculation, the tooth shape is different from the actual tooth shape, In turn, the theoretical calculation strength is different from the actual manufacturing strength. This research is based on existing products in the industry, Calculate the theoretical strength using the parameters of this product, And use the same bevel gear forging mathematical model as the product, Calculate gear strength through dynamic software LS-Dyna, Comparing the gear strength with the actual tooth profile and the gear strength of the actual tooth profile, The gear strength obtained by LS-Dyna can be approximated by the theoretical calculation gear strength, In this way, you can quickly know at the beginning of the design whether the designed gear strength can withstand the load.

Growing evidence has indicated that opioids enhance replication of human immunodeficiency virus and hepatitis C virus in target cells. However, it is unknown whether opioids can enhance replication of other clinically important viral pathogens. In this study, the interaction of opioid agonists and human influenza A/WSN/33 (H1N1) virus was examined in human lung epithelial A549 cells. Cells were exposed to morphine, methadone or buprenorphine followed by human H1N1 viral infection. Exposure to methadone differentially enhanced viral propagation, consistent with an increase in virus adsorption, susceptibility to virus infection and viral protein synthesis. In contrast, morphine or buprenorphine did not alter H1N1 replication. Because A549 cells do not express opioid receptors, methadone-enhanced H1N1 replication in human lung cells may not be mediated through these receptors. The interaction of methadone and H1N1 virus was also examined in adult mice. Treatment with methadone significantly increased H1N1 viral replication in lungs. Our data suggest that use of methadone facilitates influenza A viral infection in lungs and might raise concerns regarding the possible consequence of an increased risk of serious influenza A virus infection in people who receive treatment in methadone maintenance programs.

Methamphetamine (Meth) is one of the most frequently abused drugs worldwide. Recent studies have indicated that antibodies with high affinity for Meth reduce its pharmacological effects. The purpose of this study was to develop a technique for virus-based passive immunization against Meth effects. We generated a recombinant adeno-associated virus serotype-8 vector (AAV-MethAb) carrying the gene for a Meth-specific monoclonal antibody (MethAb). Infection of 293 cells with AAV-MethAb resulted in the expression and secretion of antibodies which bind to Meth. The viral vector was then examined in adult ICR mice. Systemic administration of AAV-MethAb resulted in long-term expression of MethAb in the serum for up to 29 weeks. Serum collected from the animals receiving AAV-MethAb retained a high specificity for (+)-Meth. Animals were challenged with Meth five weeks after viral injection. Meth levels in the brain and serum were reduced while Meth-induced locomotor activity was significantly attenuated. In conclusion, AAV-MethAb administration effectively depletes Meth from brain and serum while reducing the behavioral response to Meth, and thus is a potential therapeutic approach for Meth abuse.

Parvovirus 4 (PARV4) is one of the emerging human parvoviruses discovered recently. PARV4 has long-lasting persistence in tissues after primary infection, but persistent PARV4 viremia has yet to be effectively detected in humans. In the present work, longitudinal serum samples from eleven patients with antiphospholipid syndrome were tested by nested polymerase chain reaction for the presence of PARV4 DNA. In one patient, PARV4 4 DNA was detected in all longitudinal serum samples collected over a period of 119 months. In addition, PARV4 DNA was present in two or more longitudinal serum samples from seven other patients. Two possible explanations are a persistent infection with intermittent low viral load below detection limit and a recurrent reactivation of latent infection. In conclusion, to our knowledge, this is the first direct evidence of detection of persistent PARV4 infection. Placental transmission may be one of the major routes of PARV4 infection in endemic areas if women of child-bearing age have continuous or intermittent circulating PARV4 DNA seen in our patients.

Among the cytochrome P 450 (CYP) enzymes, CYP3A4 is most abundantly existed and metabolizes most of the drugs. We have shown human dermal fibroblasts (HDFs) express low levels of CYPs, but could be engineered to express much higher levels to be used as drug metabolism prediction. To seek better cell source for engineering, the basal mRNA expression and enzyme activities of CYP3A4 in HDFs ( n = 5), bone marrow-derived mesenchymal stem cells (BMMSCs, n = 7), and adipose-derived stem cells (ADSCs, n = 3) were compared. The basal CYP3A4 expression and activity in BMMSCs and ADSCs were significantly higher than in HDFs. However, the coefficient of variation of CYP3A4 expression was very high in each cell type. Comparing the expression levels of 4 regulators glucocorticoid receptor, pregnane X receptor ( PXR ), hepatocyte nuclear factor 4α, and hydrocarbon receptor nuclear translocator in the total 15 cell samples, we found the only basal PXR expression was significantly correlated with CYP3A4 expression. The gender and age of patients were not significant determinants in the expressions of PXR and CYP3A4 . In conclusion, BMMSCs and ADSCs expressed higher levels of CYP3A4 than HDFs and the expression of CYP3A4 might be mainly determined by basal PXR expression.

Methamphetamine is a highly addictive psychostimulant with tens of millions of abusers around the world. There is no effective or approved medication for treating an addiction to it. Monoclonal antibodies with a high affinity for methamphetamine have the potential to sequester the drug in the vascular compartment and reduce entry into the brain, thereby acting as peripheral pharmacokinetic antagonists without inducing adverse effects on neurons. However, to maintain the antibodies at an effective level, repeated administration is required, which would be expensive and problematic for patient compliance. In this study, we intended to investigate whether using a recombinant adeno-associated virus-mediated gene transfer technique can be an effective approach to achieve long-term expression of anti-methamphetamine monoclonal antibodies in mouse models. We generated a recombinant adeno-associated virus vector encoding the heavy and light chains of an anti-methamphetamine monoclonal antibody, which was constructed in a single open reading frame and linked with a 2A self-processing sequence. In the context of virus-mediated gene transfer, the expression of full-length and functional monoclonal antibodies was successfully demonstrated in vitro and in vivo. Further investigations are ongoing concerning dose optimization, longterm expression, and protection from methamphetamine challenge in mouse models.

Aims Patients with Sjogren's syndrome (SS) are reported to have an increased severity of irritating bladder symptoms, including urinary frequency and urgency. The mechanism remains unclear. The aim of this study is to elucidate the possible etiologies underlying this problem. Methods Data from 23 female patients with SS (15 primary and 8 secondary) who were treated in the urology clinic for chronic, irritating bladder symptoms were studied. Evaluation of each subject is composed of lower urinary tract symptoms (LUTS), bladder diary entries, and urodynamic studies, which also included an ice water test (IWT) to detect the presence of a C-fiber mediated micturition pathway. Interstitial cystitis (IC) was diagnosed with post-hydrodilatation cystoscopic findings of glomerulations and a KCl test. Results These patients complained predominantly of overactive bladder symptoms (OAB), including frequency (n = 20, 87%), nocturia (n = 16, 66%), and urgency (n = 12, 52%). Based on the aforementioned evaluations, four patients (17%) had polyuria with normal bladder function, nine patients (39%) had detrusor overactivity (DO), seven patients (32%) had bladder hypersensitivity (including two patients (9%) diagnosed with IC), and three patients (13%) had negative findings. Ice water instillation neither elicited novel involuntary contractions, both in those with or without DO. Five of the six patients (83%) with DO versus one of the four patients (25%) without DO responded to antimuscarinic therapy. Conclusions Various factors contribute to the irritating bladder symptoms in patients with SS, with DO being predominant. The LUTS developed in patients with SS are not due to any specific single etiology and that each patient must be individually carefully evaluated. Neurourol. Urodynam. 30:97–101, 2011. © 2010 Wiley-Liss, Inc.

OGtree is a web-based tool for constructing genome trees of prokaryotic species based on a measure of combining overlapping-gene content and overlapping-gene order in their whole genomes. The overlapping genes (OGs) are defined as adjacent genes whose coding sequences overlap partially or entirely. In fact, OGs are ubiquitous in microbial genomes and more conserved between species than non-OGs. Based on these properties, it has been suggested that OGs can serve as better phylogenetic characters than non-OGs for reconstructing the evolutionary relationships among microbial genomes. OGtree takes the accession numbers of prokaryotic genomes as its input. It then downloads their complete genomes from the National Centre for Biotechnology Information and identifies OGs in each genome and their orthologous OGs in other genomes. Next, OGtree computes an overlapping-gene distance between each pair of input genomes based on a combination of their OG content and orthologous OG order. Finally, it utilizes distance-based methods of building tree to reconstruct the genome trees of input prokaryotic genomes according to their pairwise OG distance. OGtree is available online at http://bioalgorithm.life.nctu.edu.tw/OGtree/.

The Penicillium genus of fungi is a frequently reported cause of allergic reactions. However, only a limited number of allergens have been reported. In Penicillium spp., many allergens show higher IgE-binding activity in culture filtrate extracts than in cellular extracts. In order to investigate the IgE-reactive profile of mold-sensitized patients, secreted IgE-reactive proteins from Penicillium citrinum were identified by 2-DE, serum immunoblotting, and nanoLC-MS/MS. Among the IgE-reactive spots, one known allergen, Pen c 13, and four novel allergens were identified. The cDNAs coding for Pen c 32 and Pen c 30 were cloned using designed primers based on nanoLC-MS/MS analysis. The amino acid sequences of Pen c 32 and Pen c 30 were, respectively, found to have extensive similarity with those of pectate lyases and catalases from various fungi. Native Pen c 30 was shown to have catalase activity and to bind to serum IgE from 48% of mold-allergic patients and induced immediate type skin reactions in a sensitized patient. Here, we present a proteome approach which resulted in the identification of four novel secreted allergens. These novel allergens might be useful in allergy diagnosis and in the treatment of mold-allergic disorders.

Following the constant improvements in technology and rapid developments in the computers, communications, and consumer electronics (3C) industry, mobile devices have become assistive tools for everyday life. They are lightweight, thin, and convenient for carry and their functionality is akin to a portable computer. However, these devices are normally equipped with small displays. At times when a larger screen is needed, such as when sharing information, watching videos, or discussing in groups of people, the physical device must be passed between all members in the group. Therefore, this study proposes a convenient way to integrate the resources, including display, computation, communication, etc., of multiple mobile devices to create a portable cloud for various applications. This study focused on display integration, combining multiple device screens into one large screen for data display, interaction, and sharing in meetings, for entertainment, or at school. The screens of mobile devices in different locations can also be integrated to create a dynamic billboard. This study also incorporated near field communication (NFC) to share data from one device with all other integrated devices. Wi-Fi Direct was used for group device communication to eliminate the need of Internet connection.

Anti-CD45 antibody exhibits multiple biological effects on human mononuclear cells (MNC) and polymorphonuclear neutrophils (PMN). We intended to determine whether anti-CD45 antibody could affect arachidonic acid metabolism and thereby, the interactions between human naïve MNC and PMN.Human naïve MNC and PMN were incubated with monoclonal anti-human CD45 IgG F(ab')(2) antibody or non-specific IgG F(ab')(2) for 30 min. The mRNA expression of cyclooxygenase type 1 (COX-1), type 2 (COX-2), 5-lipoxygenase (5-LOX) and leukotriene A(4) hydrolase (LTA(4) hydrolase) in both cells was detected by RT-PCR and quantified by densitometric determination. The presence of COX-1 and COX-2 molecules in the cells was detected by Western blot. The concentration of PGE(2) and LTB(4) in cultured supernatants was measured by EIA kits.Anti-CD45 IgG F(ab')(2) up-regulated LTA(4) hydrolase mRNA expression and LTB(4) production, but down-regulated COX-1 and COX-2 mRNA expression and PGE2 production, of naïve MNC compared to non-specific IgG F(ab')(2). In contrast, a reverse modulation by the specific antibody on PMN was observed including up-regulation of cyclooxygenase pathway and down-regulation of lipoxygenase pathway.A novel activity of anti-CD45 with reverse modulation on cyclooxygenase/lipoxygenase pathways was found such that the expression of COX-1 and COX-2 in PMN, and 5-LOX and LTA(4) hydrolase in MNC were enhanced.

It is generally thought that parvovirus B19 is stable genetically. Consistently, genetic drift has not been found in patients with persistent B19 infection. In this report, longitudinal genetic changes in NS1 and VP1 gene of B19 isolates from three AIDS patients with persistent B19 infection were studied. One of the three patients was not treated with highly active anti-retroviral therapy (HAART). B19 viral DNA from these patients was amplified by polymerase chain reaction (PCR) and then sequenced directly. A single genetic change was found in the B19 isolate obtained from the patient not treated with HAART on Day 10 after intravenous immunoglobulin (IVIG) treatment. The nucleotide sequences of B19 isolated from this patient, then remained unchanged over a period of 11 months. Analysis of NS1 clones derived from his longitudinal viral isolates showed the existence of quasi-species but genetic drift was not found. One of the other two patients treated with HAART experienced treatment failure; he was later treated with mega-HAART. In contrast to the genetic stability of B19 isolates from the patient not treated with HAART, multiple genetic changes were discovered in the viral isolates from the two other patients after HAART and mega-HAART, respectively. Through analysis of B19 clones, the frequency of clones containing these mutations confirmed the genetic drift. Nucleotide substitutions seen in VP2 gene of isolates with genetic drift from both patients were all non-conserved, suggesting that they are positively selected.

Background/purpose Sjogren's syndrome (SS) is characterized by diminished exocrine secretions with the resultant symptoms of dry mouth and dry eye. As genetic predisposition and ethnicity may alter the effectiveness of drug treatment, evaluation of the efficacy and safety of the secretagogue pilocarpine hy-drochloride in the treatment of xerostomia in patients with SS in different populations is needed. Methods Forty-four patients with SS were enrolled in this double-blind, placebo-controlled trial. Patients were randomized to receive 5 mg pilocarpine (Salagen) or placebo tablet four times daily for 12 weeks. Global evaluation and subjective responses of patients were assessed by questionnaires with visual analog scales and categorical checkboxes. Saliva production was also measured by modified Saxon's test. Results Pilocarpine treatment significantly improved global assessment of dry mouth, symptoms associated with dry mouth (mouth comfort, ability to sleep and ability to speak), and saliva production compared to placebo. The drug was well tolerated and the most common adverse effect was sweating (5/23, 21.7%) resulting from the muscarinic agonist action of the drug. No serious drug-related adverse effect was found in this study. Conclusion The results of this study suggest that therapy with 5 mg pilocarpine four times daily is effective, safe and well tolerated for the relief of oral symptoms in patients with SS in Taiwan.

Lupus cystitis was rare but frequently resulted in obstructive uropathy and had a strong association with gastrointestinal(GI) symptoms. We treated six patients with systemic lupus erythematosus(SLE) and obstructive uropathy from January 1996 to December 2001 in a university hospital. Evidence of cystitis was obtained from cystoscopic biopsy or the presence of thickened bladder wall in image study. Similar to other reports, five patients had GI manifestations such as abdominal pain, nausea/vomiting, diarrhoea or ileus. In addition, mesenteric lymphadenopathy or pancreatitis was noted in three patients. Two patients had been treated for idiopathic thrombocytopenicpurpura (ITP), four and 20 years ago, respectively. All six patients had antibodies to double-stranded DNA (dsDNA). Five patients each had antibodies to cardiolipin (IgG aCL) or SSA. The high prevalence of anti-SSA had also been reported in Chinese lupus patients with intestinal pseudo-obstruction, a clinical manifestation frequently associated with bilateral ureterohydronephrosis. Two patients died of intractable infection after the surgical procedures for persistent ureterohydronephrosis and both patients had antibodies to ribosomal P proteins. Lupus cystitis might not be so rare in Chinese patients with SLE. The diagnosis should be kept in mind when lupus patients have urinary and/or GI symptoms.

Methamphetamine (meth) is a highly addictive psychostimulant that is among the most widely abused illicit drugs, with an estimated over 35 million users in the world. Several lines of evidence suggest that chronic meth abuse is a major factor for increased risk of infections with human immunodeficiency virus and possibly other pathogens, due to its immunosuppressive property. Influenza A virus infections frequently cause epidemics and pandemics of respiratory diseases among human populations. However, little is known about whether meth has the ability to enhance influenza A virus replication, thus increasing severity of influenza illness in meth abusers. Herein, we investigated the effects of meth on influenza A virus replication in human lung epithelial A549 cells. The cells were exposed to meth and infected with human influenza A/WSN/33 (H1N1) virus. The viral progenies were titrated by plaque assays, and the expression of viral proteins and cellular proteins involved in interferon responses was examined by Western blotting and immunofluorescence staining. We report the first evidence that meth significantly reduces, rather than increases, virus propagation and the susceptibility to influenza infection in the human lung epithelial cell line, consistent with a decrease in viral protein synthesis. These effects were apparently not caused by meth’s effects on enhancing virus-induced interferon responses in the host cells, reducing viral biological activities, or reducing cell viability. Our results suggest that meth might not be a great risk factor for influenza A virus infection among meth abusers. Although the underlying mechanism responsible for the action of meth on attenuating virus replication requires further investigation, these findings prompt the study to examine whether other structurally similar compounds could be used as anti-influenza agents.

Background Chromosome translocation associated with neurodevelopmental disorders provides an opportunity to identify new disease-associated genes and gain new insight into their function. During chromosome analysis, we identified a reciprocal translocation between chromosomes 1p and 12q, t(1; 12)(p32.1; q21.3), co-segregating with microcephaly, language delay, and severe psychomotor retardation in a mother and her two affected boys. Methods Fluorescence in situ hybridization (FISH), long-range PCR, and direct sequencing were used to map the breakpoints on chromosomes 1p and 12q. A reporter gene assay was conducted in human neuroblastoma (SKNSH) and Chinese hamster ovary (CHO) cell lines to assess the functional implication of the fusion sequences between chromosomes 12 and 1. Results We determined both breakpoints at the nucleotide level. Neither breakpoint disrupted any known gene directly. The breakpoint on chromosome 1p was located amid a gene-poor region of ~ 1.1 Mb, while the breakpoint on chromosome 12q was located ~ 3.4 kb downstream of the ALX1 gene, a homeobox gene. In the reporter gene assay, we discovered that the fusion sequences construct between chromosomes 12 and 1 had a ~ 1.5 to 2-fold increased reporter gene activity compared with the corresponding normal chromosome 12 sequences construct. Conclusion Our findings imply that the translocation may enhance the expression of the ALX1 gene via the position effect and result in the clinical symptoms of this family. Our findings may also expand the clinical phenotype spectrum of ALX1-related human diseases as loss of the ALX1 function was recently reported to result in abnormal craniofacial development.

Background The transmission routes of PARV4 are not completely understood. The first PARV4 serological study suggested that PARV4 is transmitted predominantly through parenteral route. Objectives To set up an immunoblot system for studying the epidemiology of PARV4 infection in HIV-1 infected patients in Taiwan. Study design Recombinant fusion proteins SUMOVP2 (a.a. 272–630 of PARV4 open reading frame 2) and SUMOVP3 (a.a. 604–914) were made and used as antigens in immunoblot. Plasma samples were from HIV-1 infected intravenous drug users IDU (69), homosexuals (66) and heterosexuals (68). Results PARV4 IgG seropositive rate was 73.9%, 71.2% and 58.8%; IgM seropositive rate was 40.5%, 16.7% and 17.6% in IDUs, homosexuals and heterosexuals, respectively. Longitudinal samples were available from two homosexuals positive for IgM anti-PARV4, persistent IgM response was found over a period of 9 and 21 months, respectively. Conclusions PARV4 is a common viral infection in HIV-1 infected homosexuals and heterosexuals in Taiwan. The detection of IgM anti-PARV4 does not always suggest recent PARV4 infection.