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Ultrashort pulsed laser is a promising tool for processing transparent materials. We report on a new approach that simultaneously creates a pair of conjugate grooves on the bottom surface of a thin glass substrate at the duration of plowing a V-shaped microgroove on the top surface using the technique of direct laser ablation. We propose a hypothesis to explain the accompanying grooves’ formation mechanism and simulate Maxwell’s equations to verify its applicability. Measurements showed the surface roughness of the groove’s sidewalls was 0.14 $\mu \text{m}$ . This method requires no mask, can be directly performed in the atmosphere, and can simultaneously produce microgrooves on both sides of the substrate that render it an effective approach for producing high quality V-shaped microgrooves on both sides of the substrate.

The enactment of orphan drug-specific legislation pioneered by the USA was subsequently followed by many regions, including the European Union (EU), Australia, Japan, and Taiwan. Here, we discuss the associated regulations established and their impacts in the aforementioned regions, which are among the first with frameworks specific for orphan drugs. Varied scopes of rare diseases or orphan drugs, diverse incentives, and heterogeneous types of reimbursement systems imply the prioritization of the agencies concerned. The numbers of designated and approved drugs reflect the impact of the regulatory and reimbursement frameworks. A comparison of the frameworks and their impact in the respective regions could provide valuable information for developing and improving related frameworks for countries worldwide.

The main objective of this study was to investigate the epidemiology, drug resistance and β-lactamase genotype distribution of enteropathogenic Escherichia coli (EPEC) isolated from pediatric patients with diarrhea in southern China. The prevalence of EPEC in children with diarrhea was 3.53%. The commonest serotypes were O55:K59 and O126:K71, and the typical EPEC were more prevalent than atypical EPEC (51 vs 7). Isolates from this region were most commonly found to be resistant to ampicillin and cotrimoxazole, followed by chloramphenicol, ceftriaxone, and ceftazidime. More than 96% of the strains were susceptible to cefoperazone/sulbactam and imipenem. The most common β-lactamase genotypes identified in 58 strains were blaCTX-M-1 (60.3%), blaTEM (56.9%), blaCTX-M-9 (27.6%), and blaSHV (15.5%). Among 58 isolates, 22 strains were found to harbor one β-lactamase gene, and the proportions of resistance to ampicillin, cotrimoxazole, chloramphenicol, ceftriaxone, and ceftazidime, were 81.8%, 63.6%, 40.9%, 18.2%, and 9.1%, respectively. A further 30 strains carrying multiple β-lactamase genes had increased resistance to the above antimicrobial agents (100%, 83.3%, 70.0%, 60.0%, and 30.0%, respectively). In contrast, antibiotic resistance in the last 6 strains without a detectable β-lactamase gene was substantially reduced. Drug resistance may be associated with the β-lactamase gene number, with a greater the number of β-lactamase genes resulting in higher antibiotic resistance.

Purpose – The purpose of this paper is to evaluate the wear performance of carbon steel cladded with TiC powders by gas tungsten arc welding method. Because of poor wear resistance, carbon steels have limited industrial applications as tribological components. Design/methodology/approach – The cladding microstructures were characterized by optical microscope, scanning electron microscope (SEM) and X-ray energy dispersive spectrometer. The wear behavior of the clad layer was studied with a block-on-ring tribometer. Findings – The experimental results revealed that the metallurgical interface provided an excellent bond between the cladding and the carbon steel substrate. The cladding revealed no porosity or cracking, and particles were evenly distributed throughout the cladding layer. Hardness was increased from HRc 6.6 in the substrate to HRc 62 in the cladded layer due to the presence of the hard TiC phase. Originality/value – The experiments confirm that the cladding surfaces of TiC particles reduce wear rate and friction. Increasing TiC contents also improves hardness and wear resistance at room temperature and under dry sliding wear conditions.

Data exchange between heterogeneous CAD systems is the key problem in the field of CAD, and the popular solution to this problem is a feature-based method. Aiming at keeping the consistency of design intent in data exchange between heterogeneous CAD systems, this research focuses on the method of constraint conversion. First, two kinds of basic feature transformation ways are summarized, and this is the foundation of constraint conversion. Second, a novel identification of geometric elements based on the improved geometric certificate is proposed, and the identifier of geometric element is used to recognize the acting object of constraint. Third, the principles of constraint conversion are put forward, and the method of constraint conversion for a single feature is proposed according to the principles. Fourth, an algorithm of constraint conversion for the whole process of CAD data exchange is designed. Finally, the contrast experiment of CAD data exchange is completed, and the result of the experiment shows that the approach mentioned above is effective.

Group A Streptococcus is a common pathogen that causes pharyngitis, impetigo, myositis, and lethal streptococcal toxic shock syndrome. Streptococcal pyrogenic exotoxin B (SPE B) is strongly associated with the severity of disease. SPE B is a cysteine protease and matures itself by autocatalysis. We found that SPE B was directly associated with human S-adenosylhomocysteine hydrolase (AdoHcyase), an essential factor for a delayed-type immune response. AdoHcyase protein levels and enzymatic activities were significantly higher in human cells infected with the Streptococcus pyogenes SW510 speB mutant strain than in cells infected with the NZ131 wild-type strain. SPE B also inactivated AdoHcyase, shown by a decrease in homocysteine, the main product of AdoHcyase. We found that in vivo and in vitro, SPE B induced hypermethioninemia, which is caused by an AdoHcyase defect. We also found that AdoHcyase is a substrate of SPE B cysteine protease. SPE B, therefore, potentially causes immunosuppression by cleaving AdoHcyase.

PurposeThis paper aims to provide an improved multifractal method to extract the pavement cracks in the complicated background. Furthermore, the pavement surface images with or without crack can also be distinguished by this method.Design/methodology/approachThe framework of analyzing the image singularity is based on the sub‐pixel multifractal measure (SPMM). Performing the SPMM can give the sub‐pixel local distribution of the image gradient and a more precise singularity exponent distribution in the image. Meantime, using the singularity exponents and the most singular manifold (MSM), the image can be decomposed into a series of sets with different statistical and physical properties automatically and easily. One can extract the cracks according to the MSM.FindingsThe example shows that the physical and geometrical properties of the pavement images can be obtained by analyzing the distribution of singularity exponents and the greatest singularity exponent. The simulation results show that the SPMM has higher quality factor in the image edge detection. And the MSM detected this way reflects the most important information of the image.Originality/valuePerforming the SPMM can give a more precise singularity exponent distribution in the image.

The hepatitis B virus (HBV) large surface antigen (LHBS) mutant with deletion at the pre-S2 region accumulates in endoplasmic reticulum (ER) and is associated with HBV-induced hepatocellular carcinogenesis. In this study, we found that the pre-S2 LHBS mutant directly interacts with the Jun activation domain–binding protein 1 (JAB1). Association of pre-S2 LHBS with JAB1 dissociated JAB1 from the JAB1/IRE1 complex in ER. The free (active) JAB1 then translocated into cell nuclei and rendered the Cdk inhibitor p27Kip1 to cytosolic proteasome for degradation. The pre-S2 LHBS mutant induced hyperphosphorylation of tumor suppressor retinoblastoma (RB) via cyclin-dependent kinase 2 (Cdk2), a downstream molecule regulated by p27Kip1. This effect is independent of the ER stress signaling pathway. The transgenic mice carrying the pre-S2 mutant LHBS gene also exhibited Cdk2 activation, p27Kip1 degradation, as well as RB hyperphosphorylation. The mouse hepatocytes exhibited morphologic abnormalities such as chromatin condensation, multinucleation, and dysplasia of hepatocytes. In summary, the pre-S2 LHBS mutant causes p27Kip1 degradation through direct interaction with JAB1. The pre-S2 mutant LHBS is suggested to be a potential oncoprotein for HBV-related hepatocellular carcinoma. (Mol Cancer Res 2007;5(10):1063–72)

The multireference configuration interaction (MRCI) method is used to calculate a set of energies at different internuclear distances and six different computational levels. Six potential energy curves (PECs) are obtained. Four of them are fitted to analytical potential energy functions (APEFs) using the Murrel-Sorbie potential function, because the dissociation energies and bond lengths of the other ones are obviously not in agreement with the experimental values. Based on the PECs, the vibrational levels are determined by solving Schrodinger equation of nuclear motion, and corresponding spectroscopic parameters are accurately calculated respectively. The values of equilibrium positions and dissociation energies we obtained are compared with other theory and experimental data available at present.

The main objective of this study was to investigate the epidemiology, drug resistance and β-lactamase genotype distribution of enteropathogenic Escherichia coli (EPEC) isolated from pediatric patients with diarrhea in southern China. The prevalence of EPEC in children with diarrhea was 3.53%. The commonest serotypes were O55:K59 and O126:K71, and the typical EPEC were more prevalent than atypical EPEC (51 vs 7). Isolates from this region were most commonly found to be resistant to ampicillin and cotrimoxazole, followed by chloramphenicol, ceftriaxone, and ceftazidime. More than 96% of the strains were susceptible to cefoperazone/sulbactam and imipenem. The most common β-lactamase genotypes identified in 58 strains were blaCTX-M-1 (60.3%), blaTEM (56.9%), blaCTX-M-9 (27.6%), and blaSHV (15.5%). Among 58 isolates, 22 strains were found to harbor one β-lactamase gene, and the proportions of resistance to ampicillin, cotrimoxazole, chloramphenicol, ceftriaxone, and ceftazidime, were 81.8%, 63.6%, 40.9%, 18.2%, and 9.1%, respectively. A further 30 strains carrying multiple β-lactamase genes had increased resistance to the above antimicrobial agents (100%, 83.3%, 70.0%, 60.0%, and 30.0%, respectively). In contrast, antibiotic resistance in the last 6 strains without a detectable β-lactamase gene was substantially reduced. Drug resistance may be associated with the β-lactamase gene number, with a greater the number of β-lactamase genes resulting in higher antibiotic resistance.

Chronic hepatitis B virus (HBV) infection is the major cause of hepatocellular carcinoma (HCC). The pre-S(2) mutant large HBV surface antigen (LHBS) in type II ground glass hepatocytes (GGHs) has been recognized as an emerging viral oncoprotein; it directly interacts with the c-Jun activation domain-binding protein 1 (JAB1) and subsequently causes hyperphosphorylation of the tumor-suppressor retinoblastoma and, consequently, leads to disturbed cell cycle progression. The interaction of the pre-S(2) mutant LHBS with JAB1 could provide a potential target for chemoprevention. In this study, we found that the preneoplastic type II GGHs showed a significant decrease of the cyclin-dependent kinase inhibitor p27(Kip1), which serves as a marker for pre-S(2) mutant-JAB1 complex formation. The histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA) elevated expression of the tumor-suppressor thioredoxin-binding protein 2 (TBP2), which subsequently enhanced the JAB1-TBP2 interaction and abolished the pre-S(2) mutant LHBS-induced degradation of p27(Kip1), which, in turn, recovered the normal cell cycle checkpoint. The pre-S(2) mutant LHBS-induced pro-oncogenic effects: increased cell proliferation, nuclear/cytoplasmic ratio and proliferating cell nuclear antigen expression, were all greatly ameliorated after SAHA treatments, which suggested SAHA as a promising chemopreventive agent for the pre-S(2) mutant oncoprotein-induced HCC. In conclusion, this study provides the mechanism of histone deacetylase (HDAC) inhibitor in preventing the pre-S(2) mutant-induced oncogenic phenotype. The HDAC inhibitor SAHA is therefore a potential chemopreventive agent for high-risk chronic HBV patients who may develop HCC.

As an endo-β (1-4)-D: -glucuronidase, heparanase can specifically cleave carbohydrate chains of heparan sulfate (HS) and has been implicated in development of endothelial cells dsyfunction. The advanced glycation end products (AGEs) play a pivotal role in the pathology of diabetic complications. In the present study, we investigated the effect of AGE-bovine serum albumin (AGE-BSA) on heparanase expression in human microvascular endothelial cells (HMVECs) and the underlying molecular mechanisms. The results indicated that in vitro direct exposure of HMVECs to AGE-BSA (300, 1000, and 3000 μg/ml) could increase heparanase mRNA and protein expression in a dose and time-dependent manner. The effect of 1000 μg/ml AGE-BSA could be abolished by neutralization with antibody of the receptor for advanced glycation end products (RAGE). Moreover, pretreatment with inhibitors of nuclear factor-κB (NF-κB) or PI3-kinase did not affect heparanase expression induced by AGE-BSA. Nevertheless, small interference RNA (siRNA) for transcriptional factor FOXO4 could reduce the increase of heparanase expression in HMVECs induced by 1000 μg/ml AGE-BSA. These results suggest that AGEs could induce heparanase expression in HMVECs by RAGE and predominantly through activation of the FOXO4 transcription factor.

To study the value of iron metabolism indices, serum iron (SI), total iron blinding capacity (TIBC) and transferring (Tf), in thalassema.The serum samples from 9 children with silent alpha thalassema, 56 with standard alpha thalassema, 26 with HbH disease, 40 with beta+ thalassema, 56 with beta0 thalassema, 45 with iron deficiency anemia (IDA) and 70 healthy children were detected for SI, TIBC and Tf levels.The SI level increased (p0.01), while the TIBC level decreased significantly in the beta0 thalassema group compared with those in the other groups (p0.05 or 0.01), but the Tf level was not different. The Tf level of both the silent alpha thalassema and the standard alpha thalassema groups was statistically lower than that of the healthy group (p0.01), but the levels of SI and TIBC were similar to the healthy group. Though the SI level of the HbH disease group was similar to the healthy group, the TIBC and Tf levels were statistically lower (p0.01).Compared with Tf, SI and TIBC are better indices for monitoring iron loading in children with thalassema. The increased SI level and decreased TIBC level are two indices for the diagnosis of beta(0) thalassema in children with cellule anaemia.

The aim of study was to investigate the relationship between polymorphisms of FCGR2B232 1/T oligonucleotide and the susceptibility of children with idiopathic thrombocytopenic purpura (ITP). DNA from 76 patients with ITP and 37 controls was extracted. The SNPs of FCGR2B-232 was detected by polymerase chain reaction (PCR) combined with direct sequencing. The genotype distribution and allele frequency among different groups were compared. The results showed that the genotype (I/I, I/T, T/T) of FCGR2B-232 were 55.3%, 42.1%, and 2.6% in 76 patients with ITP, while 81.1%, 18.9%, 0% in 37 controls. The allele frequencies of FCGR2B-232 in patients with ITP were 76.3% (I232) and 23.7% (T232), but 90.5% and 9.5% in controls. There were significant differences in genotype distributions between the ITP patients and controls (chi(2) = 7.45, = 0.024). The enrichment in Thr232 allele carrier was also significant among the ITP patients as compared with the controls (chi(2) = 7.18, p = 0.007, odds ratio 3.47). There were also significant differences in allele frequencies between the ITP patients and controls [chi(2) = 6.54, p = 0.011, odds ratio 2.97, 95% CI (1.25 - 7.05)]. It is concluded that the polymorphisms of FCGR2B-232 significantly correlates with the susceptibility of children suffering from ITP. The minor Thr232 allele may be a risk genetic factor to ITP children.