We previously reported preliminary findings that post induction imatinib mesylate (340 mg/m(2)/day), in combination with intensive chemotherapy, resulted in outcomes similar to blood and marrow ...transplant (BMT) for pediatric patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). We now report 5-year outcomes of imatinib plus intensive chemotherapy in 91 children (1-21 years) with and without allogeneic BMT (N=91). We explore the impacts of additional chromosomal abnormalities and minimal residual disease (MRD) by flow cytometry on outcomes. The 5-year disease-free survival was similar for Cohort 5 patients, treated with chemotherapy plus imatinib (70%±12%, n=28), sibling donor BMT patients (65%±11%, n=21) and unrelated donor BMT patients (59±15%; P=0.60, n=13). Patients with additional cytogenetic abnormalities had worse outcomes (P=0.05). End induction (pre-imatinib) MRD was not prognostic for Cohort 5 or allogeneic BMT patients, although limited by small numbers. The re-induction rate following relapse was similar to other higher-risk ALL groups. Longer-term follow-up confirms our initial observation of substantially good outcomes for children and adolescents with Ph+ ALL treated with imatinib plus intensive chemotherapy with no advantage for allogeneic BMT.
•The coating shows higher resistance to slurry impingement than 304 stainless steel.•The mass loss of the coating reaches the peak at an impact angle of 90°.•Two impingement mechanisms of the coating ...were found out at various impact angles.•Critical flow velocities were studied using potentiostatic tests under impingement.•Passive films formed at different impact velocities are of different thicknesses.
Erosion–corrosion (E–C) behaviour of a Fe-based amorphous metallic coating (AMC) compared with 304 stainless steel (304 s.s.) was studied under a slurry impingement condition in a sand-containing NaCl solution. AMC exhibited much higher resistance to E–C than 304 s.s. The weight loss reached the maximum at an impact angle of 90° and the critical flow velocity was about 15m/s for AMC, while 45° and 9m/s for 304 s.s. The increment in passive current density under impingement for AMC was about 10 times lower than 304 s.s. Passive films formed at different impact velocities were of different thicknesses.
The nodal-line semimetals have attracted immense interest due to the unique electronic structures such as the linear dispersion and the vanishing density of states as the Fermi energy approaching the ...nodes. Here, we report temperature-dependent transport and scanning tunneling microscopy (spectroscopy) STM(S) measurements on nodal-line semimetal ZrSiSe. Our experimental results and theoretical analyses consistently demonstrate that the temperature induces Lifshitz transitions at 80 and 106 K in ZrSiSe, which results in the transport anomalies at the same temperatures. More strikingly, we observe a V-shaped dip structure around Fermi energy from the STS spectrum at low temperature, which can be attributed to co-effect of the spin-orbit coupling and excitonic instability. Our observations indicate the correlation interaction may play an important role in ZrSiSe, which owns the quasi-two-dimensional electronic structures.
The manufacture of high-performance electronic devices with micrometre or even submicrometre dimensions by solution processing and direct printing, requires the ability to control accurately the flow ...and spread of functional liquid inks on surfaces. This can be achieved with the help of surface-energy patterns causing inks to be repelled and dewetted from pre-defined regions of the substrate. To exploit this principle for the fabrication of submicrometre device structures, a detailed understanding of the factors causing ink droplets to dewet on patterned surfaces is required. Here, we use hydrophobic surface-energy barriers of different geometries to study the influence of solution viscosity, ink volume, and contact angle on the process of dewetting of inkjet-printed droplets of a water-based conducting polymer. We demonstrate polymer field-effect transistor devices with channel length of 500 nm fabricated by surface-energy-assisted inkjet printing.
Abstract Painful peripheral neuropathies produced by nerve trauma are accompanied by substantial axonal degeneration and by a response in spinal cord microglia that is characterized by hypertrophy ...and increased expression of several intracellular and cell-surface markers, including ionizing calcium-binding adapter molecule 1 (Iba1) and Cd11b (a complement receptor 3 antigen recognized by the OX42 antibody). The microglia response has been hypothesized to be essential for the pathogenesis of the neuropathic pain state. In contrast, the painful peripheral neuropathies produced by low doses of cancer chemotherapeutics do not produce degeneration of axons in the peripheral nerve, although they do cause partial degeneration of the sensory axons' distal-most tips, that is the intraepidermal nerve fibers that form the axons' terminal receptor arbors. The question thus arises as to whether the relatively minor and distal axonal injury characterizing the chemotherapy-evoked neuropathies is sufficient to evoke the microglial response that is seen after traumatic nerve injury. We examined the lumbar spinal cord of rats with painful peripheral neuropathies due to the anti-neoplastic agents, paclitaxel, vincristine, and oxaliplatin, and the anti-retroviral agent, 2′,3′-dideoxycytidine (ddC), and compared them to rats with a complete sciatic nerve transection and the partial sciatic nerve injury produced in the chronic constriction injury model (CCI). As expected, microglia hypertrophy and increased expression of Iba1 were pronounced in the nerve transection and CCI animals. However, there was no microglia hypertrophy or increased Iba1 staining in the animals treated with paclitaxel, vincristine, oxaliplatin, or ddC. These results suggest that the mechanisms that produce neuropathic pain after exposure to chemotherapeutics may be fundamentally different than those operating after nerve trauma.
Abstract The dose-limiting side effect of the anti-neoplastic agent, paclitaxel, is a chronic distal symmetrical peripheral neuropathy that produces sensory dysfunction (hypoesthesia and neuropathic ...pain) but little or no distal motor dysfunction. Similar peripheral neuropathies are seen with chemotherapeutics in the vinca alkaloid, platinum-complex, and proteasome inhibitor classes. Studies in rats suggest that the cause is a mitotoxic effect on axonal mitochondria. If so, then the absence of motor dysfunction may be due to mitotoxicity that affects sensory axons but spares motor axons. To investigate this, paclitaxel exposure levels in the dorsal root, ventral root, dorsal root ganglion, peripheral nerve, and spinal cord were measured, and the ultrastructure and the respiratory function of mitochondria in dorsal roots and ventral roots were compared. Sensory and motor axons in the roots and nerve had comparably low exposure to paclitaxel and exposure in the spinal cord was negligible. However, sensory neurons in the dorsal root ganglion had a very high and remarkably persistent (up to 10 days or more after the last injection) exposure to paclitaxel. Paclitaxel evoked a significant increase in the incidence of swollen and vacuolated mitochondria in the myelinated and unmyelinated sensory axons of the dorsal root (as seen previously in the peripheral nerve) but not in the motor axons of the ventral root. Stimulated mitochondrial respiration in the dorsal root was significantly depressed in paclitaxel-treated animals examined 2–4 weeks after the last injection, whereas respiration in the ventral root was normal. We conclude that the absence of motor dysfunction in paclitaxel-evoked peripheral neuropathy may be due to the absence of a mitotoxic effect in motor neuron axons, whereas the sensory dysfunction may be due to a mitotoxic effect resulting from the primary afferent neuron's cell body being exposed to high and persistent levels of paclitaxel.
Treatment with effective antibiotics is one important strategy for syphilis control in China. This study aimed to evaluate the prevalence of azithromycin resistance to T. pallidum in China. A ...cross-sectional study was conducted among 391 patients with early syphilis recruited from STD clinics in eight cities during October 2008 and October 2011. The swabs were obtained from the moist lesions of the participating patients. A touchdown/nested PCR of the 23S ribosomal RNA (rRNA) gene was performed on DNA samples extracted from these specimens. The presence or absence of the A2058G point mutation, conferring resistance to azithromycin, was determined by restriction enzyme digestion analysis of the PCR amplicon by MboII. Two hundred and eleven patients with primary or secondary syphilis were found to have T. pallidum DNA in their moist lesions by PCR assays. The A2058G mutation was present in 91.9% (194/211, 95% CI, 87.2–95.1%) of these patients, with no significant differences noted between patients from the eastern part (93.8%), southern part (88.6%) and northern part (95.2%) of China (v2 = 2.303, p 0.316). Compared with patients who had not taken macrolides in previous years before study entry, the patients who had taken the antibiotics had a significantly higher prevalence of azithromycin resistance (97.0% vs. 62.5%), with an odds ratio of 19.65 (95% CI, 5.77–66.93). It can be concluded that prevalence of azithromycin resistance is substantial in China and consequently that the macrolides should not be used as a treatment option for early or incubating syphilis in China.
Adenosquamous carcinoma (ASC) of the lung is a heterogeneous disease that is composed of both adenocarcinoma components (ACC) and squamous cell carcinoma components (SCCC). Their genomic profile, ...genetic origin, and clinical management remain controversial.
Resected ASC and metastatic tumor in regional lymph nodes (LNs) were collected. The ACC and SCCC were separated by microdissection of primary tumor. The 1021 cancer-related genes were evaluated by next-generation sequencing independently in ACC and SCCC and LNs. Shared and private alterations in the two components were investigated. In addition, genomic profiles of independent cohorts of adenocarcinomas and squamous cell carcinomas were examined for comparison. We have also carried out a retrospective study of ASCs with known EGFR mutation status from 11 hospitals in China for their clinical outcomes.
The most frequent alterations in 28 surgically resected ASCs include EGFR (79%), TP53 (68%), MAP3K1 (14%) mutations, EGFR amplifications (32%), and MDM2 amplifications (18%). Twenty-seven patients (96%) had shared variations between ACC and SCCC, and pure SCCC metastases were not found in metastatic LNs among these patients. Only one patient with geographically separated ACC and SCCC had no shared mutations. Inter-component heterogeneity was a common genetic event of ACC and SCCC. The genomic profile of ASC was similar to that of 170 adenocarcinomas, but different from that of 62 squamous cell carcinomas. The incidence of EGFR mutations in the retrospective analysis of 517 ASCs was 51.8%. Among the 129 EGFR-positive patients who received EGFR-TKIs, the objective response rate was 56.6% and the median progression-free survival was 10.1 months (95% confidence interval: 9.0–11.2).
The ACC and SCCC share a monoclonal origin, a majority with genetically inter-component heterogeneity. ASC may represent a subtype of adenocarcinoma with EGFR mutation being the most common genomic anomaly and sharing similar efficacy to EGFR TKI.
•The adenocarcinoma component and squamous cell carcinoma component of adenosquamous carcinoma share a common clonal origin.•High incidence of trunk EGFR and TP53 mutation were noted in adenosqumous cell carcinoma, while the overall genomic profile of adenosqumous cell carcinoma is more similar to adenocarcinoma than squmous cell carcinoma.•EGFR-TKIs should be the standard first-line therapy for advanced stage adenosquamous carcinoma with EGFR mutation.
► We have successfully synthesized high-quality, large-area graphene using RF-PECVD technique at substrate temperature as relatively low as 650
°C on SiO
2/Si substrate covered with Ni thin film. ► ...During deposition, the trace amount of carbon (CH
4 gas flow rate of 2
sccm) is introduced into PECVD chamber and the deposition time is only 30
s, in which the carbon atoms diffuse into the Ni film and then segregate on its surface, forming single-layer or few-layer graphene. ► This investigation demonstrates that RF-PECVD technique is simple, low-cost, high-effective and reproducible for synthesizing graphene at relatively low temperature, compared to other CVD techniques.
We present a simple, low-cost and high-effective method for synthesizing high-quality, large-area graphene using radio frequency plasma enhanced chemical vapor deposition (RF-PECVD) on SiO
2/Si substrate covered with Ni thin film at relatively low temperatures (650
°C). During deposition, the trace amount of carbon (CH
4 gas flow rate of 2
sccm) is introduced into PECVD chamber and the deposition time is only 30
s, in which the carbon atoms diffuse into the Ni film and then segregate on its surface, forming single-layer or few-layer graphene. After deposition, Ni is removed by wet etching, and the obtained single continuous graphene film can easily be transferred to other substrates. This investigation provides a large-area, low temperature and low-cost synthesis method for graphene as a practical electronic material.
The fundamental challenge for designing transparent conductors used in photovoltaics, displays and solid-state lighting is the ideal combination of high optical transparency and high electrical ...conductivity. Satisfying these competing demands is commonly achieved by increasing carrier concentration in a wide-bandgap semiconductor with low effective carrier mass through heavy doping, as in the case of tin-doped indium oxide (ITO). Here, an alternative design strategy for identifying high-conductivity, high-transparency metals is proposed, which relies on strong electron-electron interactions resulting in an enhancement in the carrier effective mass. This approach is experimentally verified using the correlated metals SrVO3 and CaVO3, which, despite their high carrier concentration (>2.2 × 10(22) cm(-3)), have low screened plasma energies (<1.33 eV), and demonstrate excellent performance when benchmarked against ITO. A method is outlined to rapidly identify other candidates among correlated metals, and strategies are proposed to further enhance their performance, thereby opening up new avenues to develop transparent conductors.
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