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Background/aim Non-small cell lung cancer (NSCLC) is the most common type of lung cancer with poor prognosis. Lenvatinib is a multi-kinase inhibitor that has the potential to suppress tumor progression. Our previous study suggested that lenvatinib induces cytotoxicity and apoptosis in CL-1-5-F4 cells in vitro. However, whether lenvatinib suppresses NSCLC progression in vivo remains unclear. Materials and methods Tumor growth inhibition and normal tissue toxicity evaluation following lenvatinib treatment were performed on CL-1-5-F4-bearing mice. Results Tumor growth calculated by caliper and living cell intensity decreased by lenvatinib treatment as analysed by bioluminescence imaging. Phosphorylation of AKT, NF-κB, and NF-κB downstream proteins involved in tumor progression were reduced by lenvatinib in the tumor tissue. No pathological changes were found in the liver, kidney, and spleen after lenvatinib treatment. Conclusion Induction of apoptosis and suppression of AKT/NF-κB were associated with lenvatinib-induced inhibition of the progression of NSCLC in vivo.

Simple Summary In this manuscript, we reported that a newly developed recombinant human IL15 fused with albumin binding domain (hIL15-ABD) showed superior biological half-life, pharmacokinetic and anti-tumor immunity than wild-type (WT) hIL15. Our hIL-15-ABD can effectively enhance anti-tumor efficacy of anti-PD-L1 on colon cancer and melanoma animal models. The anti-tumor potential of hIL-15-ABD was associated with tumor microenvironment (TME) regulation, including the activation of NK cells and CD8+ T cells, the reduction of immunosuppressive cells (MDSCs and Tregs) and the suppression of immunosuppressive factors (IDO, FOXP3 and VEGF). In conclusion, our new hIL15-ABD combined with anti-PD-L1 antibody increased the activity of anti-tumor effector cells involved in both innate and adaptive immunities, decreased the TME’s immunosuppressive cells, and showed greater anti-tumor effect than that of either monotherapy. We suggested hIL15-ABD as the potential complementary agent may effectively augment the therapeutic efficacy of anti-PD-L1 antibody in colon cancer and melanoma model. Abstract Anti-PD-L1 antibody monotherapy shows limited efficacy in a significant proportion of the patients. A common explanation for the inefficacy is a lack of anti-tumor effector cells in the tumor microenvironment (TME). Recombinant human interleukin-15 (hIL15), a potent immune stimulant, has been investigated in clinical trial with encouraging results. However, hIL15 is constrained by the short half-life of hIL15 and a relatively unfavorable pharmacokinetics profile. We developed a recombinant fusion IL15 protein composed of human IL15 (hIL15) and albumin binding domain (hIL15-ABD) and explored the therapeutic efficacy and immune regulation of hIL-15, hIL15-ABD and/or combination with anti-PD-L1 on CT26 murine colon cancer (CC) and B16-F10 murine melanoma models. We demonstrated that hIL15-ABD has significant inhibitory effect on the CT26 and B16-F10 tumor growths as compared to hIL-15. hIL-15-ABD not only showed superior half-life and pharmacokinetics data than hIL-15, but also enhance anti-tumor efficacy of antibody against PD-L1 via suppressive effect on accumulation of Tregs and MDSCs and activation of NK and CD8+T cells. Immune suppressive factors including VEGF and IDO were also decreased by combination treatment. hIL15-ABD combined with anti-PD-L1 antibody increased the activity of anti-tumor effector cells involved in both innate and adaptive immunities, decreased the TME’s immunosuppressive cells, and showed greater anti-tumor effect than that of either monotherapy.

Background Although both chemotherapy and radiotherapy (RT) can sufficiently maintain tumor suppression of colorectal cancer (CRC), these treatments may trigger the expression of nuclear factor kappa B (NF-κB) and compromise patients' survival. Regorafenib suppresses NF-κB activity in various tumor types. However, whether regorafenib may act as a suitable radiosensitizer to enhance therapeutic efficacy of RT remains unknown. Materials and methods Here, we established a CRC-bearing animal model to investigate the therapeutic efficacy of regorafenib in combination with RT, through measurement of tumor growth, body weight, whole-body computed tomography (CT) scan and immunohisto-chemistry staining. Results Smallest tumor size and weight were found in the combination treatment group. In addition, RT-induced up-regulation of NF-κB and downstream proteins were diminished by regorafenib. Moreover, the body weight and liver pathology in the treated group were similar to those of the non-treated control group. Conclusion Regorafenib may enhance the anti-CRC efficacy of RT.

Glioblastoma is the most common primary malignant tumor of the central nervous system, with an annual incidence of 5.26 per 100000 people. The clinical outcome of standard therapy and the survival rate remain poor; therefore, there is an unmet need for a new strategy to treat this lethal disease. Although amentoflavone was known to have anticancer potential in various types of cancers, its antiglioblastoma ability and mechanism remain unrecognized. We demonstrated that amentoflavone may suppress glioblastoma invasion and migration by transwell assay. Moreover, we established NF-[Formula: see text]B reporter gene system and used that for verifying NF-[Formula: see text]B inhibition efficacy of amentoflavone on in vitro and in vivo studies. Here, we indicated that amentoflavone not only diminished NF-[Formula: see text]B activation, but also reduced NF-[Formula: see text]B-mediated downstream oncogenes expression, such as MMP-2, MMP-9, XIAP, cyclinD1 and VEGF, which was elucidated by Western blot and immunohistochemistry (IHC). Tumor growth inhibition and NF-[Formula: see text]B reduction was found in the amentoflavone treatment group, which was revealed by the glioblastoma-bearing animal model. In this study, we also used ERK inhibitor and NF-[Formula: see text]B inhibitor (QNZ) to confirm whether the beneficial result of amentoflavone on glioblastoma was mainly regulated by blockage of ERK/NF-[Formula: see text]B signaling. In summary, ERK/NF-[Formula: see text]B signaling pathway has a role in the inhibition of tumor growth by amentoflavone in glioblastoma.

Osteosarcoma is the most common type of bone cancer. Multimodality treatment involving chemotherapy, radiotherapy and surgery is not effective enough to control osteosarcoma. Regorafenib, the oral multi-kinase inhibitor, has been shown to have positive efficacy on disease progression delay in chemotherapy resistant osteosarcoma patients. However anti-cancer effect and mechanism of regorafenib in osteosarcoma is ambiguous. Thus, the aim of this study is to investigate the efficacy and molecular mechanism of regorafenib on osteosarcoma in vitro and in vivo. Human osteosarcomas U-2 OS or MG-63 were treated with regorafenib, miltefosine (protein kinase B (AKT) inhibitor), or PD98059 (mitogen-activated protein/extracellular signal-regulated kinase (MEK) pathway inhibitor) for 24 or 48 h. Cell viability, apoptotic signaling transduction, tumor invasion, expression of tumor progression-associated proteins and tumor growth after regorafenib treatment were assayed by MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, flow cytometry, transwell assay, Western blotting assay and in vivo animal experiment, respectively. In these studies, we also indicated that regorafenib suppressed cell growth by prompting apoptosis of osteosarcoma cells, which is mediated through inactivation of ERK and AKT signaling pathways. After regorafenib treatment, downregulation of related genes in invasion (vascular endothelial growth factor (VEGF) and matrix metallopeptidase 9 (MMP-9)), proliferation (CyclinD1) and anti-apoptosis (X-linked inhibitor of apoptosis protein (XIAP), myeloid cell leukemia-1 (MCL-1), and cellular FLICE (FADD-like IL-1β-converting enzyme)-inhibitory protein (C-FLIP)) were found. Moreover, upregulation of caspase-3 and caspase-8 cleavage were also observed. In sum, we suggest that regorafenib has potential to suppress osteosarcoma progression via inactivation of AKT and ERK mediated signaling pathway.

Active epidermal growth factor receptors (EGFR) signaling mediates the progression of colorectal cancer (CRC) through activation of downstream kinases and transcription factors. The increased expression of EGFR was associated with worse prognosis in patients with metastatic CRC (mCRC). Regorafenib, the oral kinase inhibitor approved for the treatment of mCRC, has been shown to reduce activation of downstream kinases of EGFR signal pathway in hepatocellular carcinoma and osteosarcoma. However, whether EGFR inactivation was participates in regorafenib-inhibited progression of CRC still remaining ambiguous. The major purpose of present study was to verify effect of regorafenib on EGFR signaling-mediated progression of CRC. Here, we investigated the effect of regorafenib or erlotinib (EGFR inhibitor) on tumor cell growth, invasion ability, apoptotic, and EGFR signal transduction in CRC in vitro and in vivo. Our results indicated regorafenib reduced EGF-induced EGFR and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activity. Both regorafenib and erlotinib significantly reduced cell invasion ability, activation of protein kinase C-δ (PKCδ), protein kinase B (AKT), extracellular signal-regulated kinases (ERK), and NF-κB. Regorafenib can trigger the inhibition of tumor cell growth and the induction of apoptosis through extrinsic/intrinsic apoptosis pathways. In addition, the expression of NF-κB-mediated proteins involved in tumor progression was also suppressed by regorafenib treatment. Taken together, regorafenib acts as a inhibitor of EGFR signaling that attenuated the activation of EGFR and EGFR related downstream signaling cascades in CRC. Our results suggested that the suppression of EGFR signaling was associated with regorafenib-inhibited progression of CRC.

To investigate the association between tumor response to thoracic radiotherapy and epidermal growth factor receptor (EGFR) mutation status in patients with lung adenocarcinoma, we collected 48 patients treated between January 2010 and December 2013. Of the 18 patients with EGFR mutation, 15 (83.3%) had a single mutation, and three (16.7%) had double mutation. Different EGFR mutation subtypes exhibited different responses to radiotherapy. The identified double EGFR mutations were associated with reduction of residual tumor burden (RTB) after radiotherapy. In univariate analysis, EGFR mutations in exon 18, 20, and 21 and double EGFR mutation were significant factors predicting RTB. In multivariate analysis, exon 20 mutation was the only significant factor. Patients with EGFR mutation seemed to have longer mean overall survival (OS) compared to the group with wild-type EGFR (31.1 vs. 26.6 months, p=0.49). The median and mean OS in patients with double EGFR mutation vs. wild-type EGFR were 20.1 vs. 16.9 months and 28.9 vs. 26.6 months, respectively. Further studies with larger sample size are warranted to clarify the association of EGFR mutation status with the lung tumor response after radiotherapy.

Non-small cell lung cancer (NSCLC) is a malignant lung cancer type with poor prognosis. NF-κB, the oncogenic transcription factor, has been recognized as an important mediator in progression of NSCLC. Regorafenib, a multikinase inhibitor, was demonstrated to inhibit tumor progression through suppression of ERK/NF-κB signaling in hepatocellular carcinoma cells in vitro and in vivo. However, whether regorafenib inhibit progression of NSCLC is ambiguous. Thus, the major purpose of present study was to evaluate anticancer efficacy and underlying mechanism of regorafenib on tumor progression in NSCLC in vitro and in vivo. CL-1-5-F4 cells were treated with regorafenib, NF-κB (QNZ) or AKT (LY294002) inhibitor for 24 or 48 h. Then, we performed cell viability assay, NF-κB reporter gene assay, transwell invasion assay and apoptosis related flow cytometry assay on cellular level to verify anti-cancer effect and mechanism of regorafenib. CL-1-5-F4 bearing animal model was treated with vehicle or regorafenib for 28 days. The therapeutic efficacy and mechanism of regorafenib in CL-1-5-F4 bearing animal model were investigated by tumor size evaluation, whole body computer tomography (CT) scan, Haemotoxylin and Eosin (H&E) stain and immunohistochemistry (IHC) stain. Our results demonstrated regorafenib significantly inhibited tumor growth and induced apoptosis through extrinsic/intrinsic pathways in NSCLC in vitro and in vivo. Furthermore, we also found the suppression of AKT/NF-κB signaling was required for regorafenib inhibited expression of progression-related and invasion-related proteins. Our finding indicated apoptosis induction and suppression of AKT/NF-κB signaling were associated with regorafenib-inhibited progression of NSCLC in vitro and in vivo.

Basaloid squamous cell carcinoma is a distinct variant of squamous cell carcinoma, and it is more aggressive and has a poorer prognosis than conventional squamous cell carcinoma. Basaloid squamous cell carcinoma has been reported to arise from many organs, mainly in the upper aerodigestive tract. Herein, the authors present a 77-year- old woman with a basaloid squamous cell carcinoma over her limbal conjunctiva in the OD.

The anticancer effect of curcumin has been widely reported. However, whether curcumin can enhance the radiosensitivity of human oral squamous cell carcinoma (OSCC) remains to be elucidated. The aim of the present study was to evaluate the efficacy of curcumin combined with radiation against OSCC. SAS cells were transfected with the luciferase gene (luc) and named SAS/luc. NF-κB/DNA binding activity, the surviving fraction and NF-κB-regulated effector protein expression were determined by electrophoretic mobility shift assay, clonogenic survival assay and western blotting, respectively. The therapeutic efficacy was evaluated in SAS/luc tumor-bearing mice by caliper measurement and bioluminescence imaging. Curcumin enhanced SAS/luc radiosensitivity through the inhibition of radiation-induced NF-κB activity and expression of effector proteins both in vitro and in vivo. With 4 Gy or greater radiation doses, synergistic effects of curcumin were observed. The combination group (curcumin plus radiation) had significantly better tumor control compared with that of curcumin or radiation alone. No significant body weight change of mice was found throughout the entire study. In conclusion, curcumin is a radiosensitizer against OSCC with negligible toxicity.

This study presents a design of the body contact in an 850 nm Si photodiode (PD) fabricated using standard 0.18-μm CMOS technology, and presents a systematic investigation of its effects on PD performance. This study confirms a good PD performance within 3 V bias and the establishment of the body current by directly measuring the body current, PD capacitance, and photocurrents. The body current from the biasing body contact was designed to eliminate the slow diffusion photocarriers in the substrate and increase bandwidth. The highest responsivity of 1.2 A/W was obtained from the PD without the body current, with biasing in the avalanche region. Adding the body bias increased the optimal bandwidth from 2.51 to 3.11 GHz, but reduced responsivity. However, the operating bias of the Si PD in the avalanche region was high, making it unsuitable for practical applications. While biasing PD at a low 3 V with a coordinated body bias, a bandwidth of 2.46 GHz was obtained with an acceptable responsivity of 0.1 A/W to allow low-voltage operation.

Background: The most common serious complication following acute ischemic stroke is pneumonia, which may increase mortality and worsen clinical outcomes. The purpose of this study was to investigate the predictors of 30-day mortality in patients with pneumonia following acute ischemic stroke. Methods: From June 2006 to May 2011, we retrospectively included 51 patients with pneumonia following acute ischemic stroke. We analyzed the clinical features, microbiologic data, and outcomes. Predictors of 30-day mortality were investigated by univariate and multivariate analysis. Results: The acute ischemic strokes were caused by large-artery atherosclerosis in 37 (72.5%) of the 51 patients. We found that the most common pathogen responsible for poststroke pneumonia was Klebsiella pneumoniae, followed by Pseudomonas aeruginosa and Escherichia coli. Ultimately, 12 patients died of progressive sepsis due to pneumonia after the acute ischemic stroke. The 30-day mortality rate was 23.5%. In the univariate analysis, patients who died within 30 days had higher National Institutes of Health Stroke Scale scores, higher CURB-65 scores, elevated instability of hemodynamic status, and lower Glasgow Coma Scale (GCS) scores. In Cox regression analysis, a GCS score of

Modular design is an effective design concept and method that adapts to fierce market competition and versatile customer requirement. Solving the key questions in applying modular design method is the important research topic of modern CAD technology. This paper studies the evaluation question of module combination program, and puts forward the evaluation model for CNC machine tool product. Analytic hierarchy process is used as the evaluation algorithm of combination program. The actual evaluation is carried out to verify the model and algorithm.

Background: Tuberculous pleural effusion is the second most common form of extrapulmonary tuberculosis. The relationship between the geriatric population and tuberculous pleural effusion has rarely been studied. Methods: This is a retrospective study. From January 2005 through February 2009, we retrospectively enrolled 51 patients older than 18 years of age that were diagnosed with tuberculous pleurisy. We analyzed the clinical presentations and laboratory data of pleural effusion in elderly and adult groups. Results: Of these patients, 32 were more than 65 years of age (elderly group) and 19 were less than 65 years of age (adult group). Chest pain occurred more frequently in the adult group than the elderly group (52.6 % vs. 15.6 %; p

According to regenerative chatter theory, this paper abstracts the machining process of XXX machine as a mathematical model firstly. The main process is end milling, so this paper abstracts the machine as an end-milling mathematical model, a delay motion equation with 2-DOF. All parameters of this equation can be acquired by modal analysis. Then SIMULINK model is created based on the mathematical model. According to the response characteristics of simulation analysis system, the method of determining threshold of steady area is acquired.

For the modular design in manufacturing paradigm of mass customization (MC), module combination is a complex process. To the study on this problem, this paper put forward a module combination method based on module family model. Based on the module family model and tree-type storage structure, this method used a “most similar module" search algorithm to carry out the module search, and applied analytic hierarchy process(AHP) to construct the hierarchy model for the evaluation of module combination configuration program. This module combination method has some theoretical and practical ignificance.

This paper took a kind of 3-TPT Parallel Machine Tool (PMT) as the object of research, and it mainly researched the measurement method to position coordinates of movable platform in PMT. First the paper introduced the structure of 3-TPT PMT. Then illustrated the device structure and the basic measurement principle for measuring the position coordinates of movable platform. Finally carried on the theoretical analysis to the specific measurement method and established the corresponding mathematics relationship. The measuring device that was presented in this paper had characteristics of direct-viewing measurement relationship, simple structure and low cost etc., and simultaneously the research results of this paper laid a theoretical foundation for improving the movement precision of this PMT and had important practical significance.

BACKGROUND: The A118G polymorphism of the mu-opioid receptor gene (OPRM1), resulting in the substitution of an amino acid, has been found to be associated with functional effects and response to opioid treatment. The purpose of this study was to assess whether this polymorphism contributes to the variability in response to tramadol/acetaminophen combination tablets (Ultracet) for treating oxaliplatin-induced painful neuropathy. METHODS: A total of 96 patients with adenocarcinoma of the colon or rectum (n = 84), or stomach (n = 12) who had developed oxaliplatin-induced painful neuropathy were enrolled. Ultracet was administered at 1 tablet every 6 hours, and pain was assessed and scored using a visual analog scale (VAS). The OPRM1 A118G polymorphism was examined with a polymerase chain reaction-direct sequencing method. RESULTS: The allelic frequency of variant (118G) allele was 39.6%, and the prevalence of OPRM1-118 AA, AG, and GG genotypes was 31.3% (n = 30), 58.3% (n = 56), and 10.4% (n = 10), respectively. For all patients, the mean pre-treatment and post-treatment VAS scores were 3.1 and 2.1, respectively (P < .001). Patients with AA genotype had a better analgesic effect than those with G allele variants (AG or GG genotypes). Pre-treatment and post-treatment VAS scores for patients with G allele variants were 3.1 and 2.6, respectively; however, for patients with AA genotype, pre-treatment and post-treatment VAS scores were 3.0 and 0.9, respectively (P < .001). The requirement for rescue analgesia was also higher for patients with G allele variants (P = .01). CONCLUSIONS: These data suggest that Ultracet is effective in the management of oxaliplatin-induced painful neuropathy. A118G polymorphism of OPRM1, by altered function of the mu-opioid receptor and consequential analgesic effect on opioid agents, could be a key determinant for decreased response to Ultracet. Cancer 2011;. © 2011 American Cancer Society.

Silicon photodiodes (PDs) of 850-nm-wavelength, in standard 0.18-μm CMOS technology, are systematically presented and discussed in this study. A basic p-n PD can obtain high responsivity of 0.3 A/W and response of 1.6 GHz while biasing in the avalanche process. However, Si PDs from different CMOS foundries would result in different performance due to the different n-/p-well doping profile. A basic p-n PD with body contact can effectively remove the slow diffusion carrier in the Si substrate and demonstrate improved response. Both body contact and deep n-well design in an octagonal PD can improve the performance of basic p-n PD significantly. The response is improved to 8.7 GHz with 0.8 A/W before breakdown. The improvement is due to the block and elimination of slow diffusion carriers in the Si substrate. Finally, Si PD with built-in n-p-n bipolar junction transistor and edge-coupled PD are proposed to further improve responsivity and response.

In Taiwan, where Mandarin is the official language, the survival of Taiwanese, the mother tongue of sixty percent of the island’s inhabitants, is threatened. In this article, the authors discuss data from previous and ongoing research on the role of language and the significance of language loss in the quest for a “Taiwanese identity.” Research shows that the dominance of Mandarin over Taiwanese plus the growing support for English in Taiwan are likely indications that current Mandarin/Taiwanese bilingualism is being replaced by Mandarin/English bilingualism. Canadian, Finnish, Basque and Catalonian models of language immersion programs will be proposed as an alternative to Taiwan’s current language policy. The authors argue that such models, when applied to a significant degree in Taiwan’s primary education system, will contribute to strengthening Taiwanese identity, to defending the right of youngsters to receive their education in their Taiwanese mother tongue, and to creating more effective English language training., Le mandarin, langue officielle de Taiwan, menace la survie du taiwanais, qui est la langue maternelle de soixante pour cent de la population de l’île. Dans le présent article, les auteurs discutent des résultats de leurs recherches précédentes et en cours et montrent la signifiance de la perte de la langue maternelle pour l’identité taiwanaise. Ils montrent également que la suprématie du mandarin sur le taiwanais et l’appui croissant en faveur de l’anglais à Taiwan laissent prévoir l’implantation d’un bilinguisme mandarin/anglais au détriment du bilinguisme mandarin/taiwanais. Les auteurs considèrent que les modèles d’enseignement bilingue immersif mis en place au Canada, en Finlande, dans le pays Basque et en Catalogne, s’ils étaient mis en oeuvre de façon généralisée à Taiwan, pourraient contribuer à renforcer l’identité taiwanaise, à défendre le droit des jeunes à une éducation dans leur langue maternelle et à favoriser l’enseignement plus efficace de l’anglais.

Oral squamous cell carcinoma often causes bone invasion resulting in poor prognosis and affects the quality of life for patients. Herein, we combined radiation with sorafenib, to evaluate the combination effect on tumor progression and bone erosion in an in situ human OSCC-bearing mouse model. Treatment procedure were arranged as following groups: (a) normal (no tumor); (b) control (with tumor); (c) sorafenib (10 mg/kg/day); (d) radiation (single dose of 6 Gy); (e) pretreatment (sorafenib treatment for 3 days prior to radiation) and (f) concurrent treatment (sorafenib and radiation on the same day). The inhibition of tumor growth and expression level of p65 of NF-κB in tumor tissues were the most significant in the pretreatment group. EMSA and Western blot showed that DNA/NF-κB activity and the expressions of NF-κB-associated proteins were down-regulated. Notably, little to no damage in mandibles and zygomas of mice treated with combination of sorafenib and radiation was found by micro-CT imaging. In conclusion, sorafenib combined with radiation suppresses radiation-induced NF-κB activity and its downstream proteins, which contribute to radioresistance and tumorigenesis. Additionally, bone destruction is also diminished, suggesting that combination treatment could be a potential strategy against human OSCC.

Treatment for non-small-cell lung cancer with gefitinib and erlotinib is efficacious. However, while many studies have reported on gefitinib-related interstitial lung disease (ILD), less published data are available regarding erlotinib-induced ILD. Here, we report a case of pulmonary adenocarcinoma who developed ILD due to gefitinib initially and erlotinib thereafter. The two episodes of ILD were treated successfully with the discontinuation of the tyrosine kinase inhibitors and high-dose intravenous corticosteroids.

This work investigates a new silicon (Si) photodiode (PD) by standard complementary metal-oxide-semiconductor (CMOS) process. The basic structure of the proposed Si PD is formed by multiple p-n diodes with shallow trench isolation oxide in between p- and n-region from Taiwan Semiconductor Manufacturing Company 0.18-mum CMOS technology. The proposed PD demonstrates a responsivity of 0.37 A/W at zero bias (lambda=823nm). At reverse bias (VR) of 14.3 V, the fabricated PD exhibits a high responsivity of 0.74 A/W, a -3-dB electrical bandwidth of 1.6 GHz, and an eye diagram at 3.5 Gb/s

Background Gefitinib (Iressa; AstreZeneca, Wilmington, DE) is effective in the treatment of NSCLC, especially in the Asian population. However, ILD is usually a serious pulmonary adverse effect and almost leads to cessation of gefitinib treatment. In this study, we investigated the incidence, clinical features, and prognosis of gefitinib-related ILD in Taiwanese patients with NSCLC. Patients and Methods This was a retrospective observational study conducted in 2 medical centers and a local teaching hospital. Results A total of 1080 patients with NSCLC, who received at least 1 dose (250 mg per day) of gefitinib treatment, were enrolled. Of these, 42 patients were diagnosed with ILD. Twenty-five of the 42 patients were diagnosed with gefitinib-related ILD (incidence, 2.3%). The main manifestations of ILD included dyspnea, cough, and hypoxemia. Six of the 25 patients (24%) with gefitinib-related ILD required invasive mechanical ventilation and all patients were treated with steroids. Twenty-two patients (88%) discontinued gefitinib treatment without further rechallenge. Ten (40%) patients died directly from ILD and in-hospital mortality was 52%. Eleven patients received subsequent cytotoxic chemotherapy with a mean of 33.5 days after ILD events. Kaplan-Meier analysis demonstrated that gefitinib nonresponder and gefitinib use rather than first-line treatment were associated with poor prognosis when ILD developed during gefitinib treatment. Conclusion Taiwanese patients with NSCLC had a relatively high incidence of ILD during gefitinib treatment. Gefitinib-related ILD is usually life-threatening, especially in gefitinib nonresponders and gefitinib use rather than first-line treatment.

With the optimization of sulfate-free cleaning the issue of haze under pellicle was almost eliminated. In consequence, current reasons for mask repelliclization needs are moving from pattern issues to more gross problems on back glass. Moreover, the longer life of photomasks allows a new problem to appear as growing defects on back glass, commonly ascribed to environmental conditions at user's site. The commonality of these problems is being independent on mask complexity and substrate. In order to avoid the criticalities of pellicle removal and cleaning treatment as well as the cost of necessary inspection after new pellicle application, the best solution is cleaning only the backside of the mask, provided that integrity of pellicle and pattern on front side are preserved In this article we present the results obtained by the use of the Mask cleaner DE050019TM on several cases. The efficiency of the treatment was assessed in terms if removal capability on different kinds of contaminations, either from use or mask aging. Pattern inspections were conducted in order to assess ESD robustness. Ionic residues were checked by IC aimed to compare with standard cleanings. This methodology demonstrated to be capable of maintaining a Particle Removal Efficiency>97% on all kinds of contaminations, without any damage to pellicle or harm to patterns, still maintaining residual ions at the same level as after cleaning by standard tools.

In fast long-distance networks (FLDN), TCP Reno was proved to have poor throughput performance and several variations were proposed to improve it by faster increasing of congestion window (cwnd). However, too fast increasing of cwnd will cause buffer overflow and the effect of TCP configurations on the queue buffer (qbuf) is a very important issue. In this paper, we study the relationships among the throughput, cwnd, and qbuf in FIDN. Some theorems are created from established mathematical models to characterize the behaviors of TCP in FIDN. We find that the qbuf not only relates to cwnd, but also to network configuration such as link bandwidth. Furthermore, we also simulate a bottlenecked topology to confirm the derived mathematic theorems. The proven theorems will bestead TCP configurations to improve TCP throughput in FIDN.

Fig. 1. Chronic tubulointerstitial nephritis with interstitial fibrosis and tubular atrophy. There are several tubular cysts (arrows) and focal lymphocytic infiltrations (arrowheads; hematoxylin and eosin stain, 40). A 49-year-oldman presented toTzu Chi General Hospital, Taipei, Taiwan, with cough, dyspnea, and general malaise. He had a history of bipolar disorder for > 20 years with regular follow-up at Taipei City Psychiatric Center (Taipei, Taiwan) and was under lithium therapy. He was admitted for antibiotic treatment under the impression of pneumonia and sepsis. Laboratory data revealed leukocytosis (white blood cells, 27.0 109/L), normocytic anemia (hemoglobin, 8.0 g/dL; mean cell volume, 88.5 fL), and azotemia (blood urea nitrogen, 111.6 mg/dL; creatinine, 3.69 mg/dL). In spite of aggressive management of respiratory failure and septic shock, the patient died 3 days later. At autopsy, the kidneys were grossly symmetrical. Several irregular, depressed scars were noted on the renal parenchyma. Microscopically, cortical and medullary interstitial fibrosis, interstitial lymphocytic infiltration, diffuse tubular atrophy, and tubular cysts with pericystic fibrosis (Fig. 1) indicated chronic tubulointerstitial nephritis accompanied by focal segmental (Fig. 2) and global glomerulosclerosis, diagnostic of chronic lithium nephropathy. The most common form of lithium nephropathy in patients on long-term lithium therapy is chronic tubulointerstitial nephritis, presenting most commonly as tubular atrophy, interstitial fibrosis, and lymphocytic infiltration. The presence of tubular cysts with pericystic fibrosis originating from the distal tubules and collecting ducts is highly characteristic of lithium nephropathy. Markowitz et al [1] reported global glomerulosclerosis in 24 of 24