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Objective: Lung cancer poses a tremendous threat to the modern world. According to Taiwan’s Ministry of Health and Welfare, lung cancer took first place in total cancer deaths in 2021. This study investigated the overall lung cancer survival based on histopathology between 2010 and 2016 in Taiwan. Method: Data from 2010 to 2016 was collected from the Taiwan Cancer Registry (TCR). The characteristics and overall survival of 71,334 lung cancer patients were analyzed according to the tumor, node, metastasis (TNM) 7th staging system. Univariate and multivariate analyses were performed to identify differences in 1-year, 3-year, and 5-year survival between different histopathologies of lung cancer. Results: The 1-year overall survival rate increased from 54.07% in 2010 to 66.14% in 2016. The 3-year overall survival rate increased from 26.57% in 2010 to 41.12% in 2016 in all patients. Among the histopathologies of lung cancer, 3-year overall survival of adenocarcinoma patients increased the most and largely contributed to the increased 3-year overall survival of all lung cancer patients. Conclusions: The introduction of target therapy has led to a tremendous increase in overall survival for lung adenocarcinoma patients. However, target therapy differs by histopathology. Choosing the right target therapy and determining the correct histopathology of lung cancer is a pivotal key in increasing the overall survival of patients. Together with immune therapy, the landscape of lung cancer treatments is changing.

Introduction: Multiple myeloma (MM) is a neoplastic malignancy characterized by the abnormal proliferation of plasma cells with excessive antibody production in the bone marrow. It accounts for approximately 1.8% of all new cancer cases and 2.1% of cancer deaths in the United States and occurs most frequently among older adults (age > 75). While there are a number of treatments with high response rates, MM relapses frequently within a few years and is considered incurable. Herein, experimental studies and results of a new therapeutic agent under development, TE-1146, are reported. TE-1146 is an antibody drug conjugate (ADC) composed of two therapeutic agents already in use in MM, namely, an anti-CD38 antibody, daratumumab (Dara), and lenalidomide (Lena). Method: TE-1146 is designed by employing “HIDAR” technology platform, which enables the preparation of homogeneous ADCs with high DAR (drug to antibody ratio). In the TE-1146 molecules, the Fab is replaced by scFv and a cysteine-containing Zn2+-binding motif is engineered at the C-termini of the H chains. Lena molecules are assembled into drug bundles containing 3 Lena molecules and a maleimide group. Two drug bundles are conjugated site-specifically to the Zn2+-activated SH groups of the reconfigured antibody molecule, creating an ADC with DAR of 6. TE-1146 was investigated for cytolytic effects against human MM cell lines H929 in cell cultures in vitro and transplanted H929 tumor in NOD-SCID mice in vivo, in comparison with Dara, Lena, and their combination. Results: In human plasma, TE-1146 has stability comparable with Dara, and the Lena molecules in the drug bundles remain conjugated. In cultures of H929 cells, TE-1146 caused the lysis of H929 cells at least 100 times more effectively than Dara, Lena, and Dara/Lena combination, based on IC50 comparison. It was shown that H929 cells internalized and degraded TE-1146 and freed Lena. In NOD-SCID mice, the subcutaneously transplanted H929 cells were allowed to grow into solid tumors in 14 days, and TE-1146 and other agents for comparison were administered intraperitoneally. It was found that one single dose of TE-1146 at 20 nmol/kg (conjugated with Lena at 120 nmol/kg) could retard the growth of the transplanted tumor and ultimately eliminate the tumor over 28-42 days, while the combination of one dose Dara at 20-80 nmol/kg and Lena of 46 μmol/kg given daily could not eliminate the tumor. The amount of Lena used in the combination treatment over a 28-day course is 10,700 times that of Lena in TE-1146. Conclusion: Lenalidomide is extremely powerful in killing multiple myeloma cells if brought into the MM cells. It is estimated that a very minute amount, probably less than 0.01%, of intraperitoneally injected lenalidomide gets into the transplanted MM tumor in the mouse model. TE-1146 may be a more effective and less toxic drug than Daratumumab/Lenalidomide combination in treating patients with hard-to-treat MM. Citation Format: Yueh-Hsiang Yu, Ming-Yu Hsieh, Pei-Wen Wu, Hui-Ju Lee, Pei-Hsuan Lin, Carmay Lim, Hsing-Mao Chu, Tse Wen Chang. An ADC composed of daratumumab and lenalidomide is extremely powerful in killing multiple myeloma cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB209.

Nasopharyngeal carcinoma (NPC) is one of the most aggressive malignant tumors of the head and neck. Xanthohumol (Xn) is a compound extracted in a high concentration from the hard resin of hops (Humulus lupulus L.), the basic raw material of beer. This study investigated the apoptotic effect and anticancer properties of Xn in human NPC cell lines. Our study demonstrated that at the concentration 40 μM, Xn significantly reduced cell viability and promoted cell cycle arrest in the G2/M phase in two cell lines. The results indicated that Xn induced apoptosis in NPC cell lines through annexin V/propidium iodide staining, chromatin condensation, and apoptosis-related pathways. Xn upregulated the expression of apoptosis-related proteins, namely DR5, cleaved RIP, caspase-3, caspase-8, caspase-9, PARP, Bim, and Bak, and it downregulated the expression of Bcl-2. Xn upregulated the c-Jun N-terminal kinase (JNK) in the mitogen-activated protein kinase (MAPK), and the inhibition of JNK clearly resulted in decreasing expression of Xn-activated cleaved caspase-3 and PARP. Our research provides sufficient evidence to confirm that Xn induces the MAPK JNK pathway to promote apoptosis of NPC and is expected to become a safe and acceptable treatment option for human NPC.

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To examine the effects of emotional distress, illness perception, and mental adjustment on return to work (RTW) among patients with head and neck cancer (HNC) and identify factors associated with RTW. A cross-sectional study with convenience sampling was conducted in Taiwan. Structured questionnaires were used to collect data on RTW status and to explore possible factors related to RTW. RTW status was assessed by a single question. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale, illness perception was assessed by the Brief Illness Perception Questionnaire, and mental adjustment was assessed using the Mini-mental Adjustment to Cancer Scale. Sociodemographic and disease background data were also collected and analyzed. Factors related to RTW were identified by multivariate logistic regression. A total of 150 patients with HNC were recruited into the study. Of them, 58 (38.7%) returned to work after treatment. Compared to those who did not RTW, patients who did RTW had lower levels of emotional distress (anxiety and depression), better illness perception (cognitive illness representations and illness comprehensibility), and better mental adjustment (hopelessness and helplessness, anxious preoccupation, avoidance, and fatalism). Multivariable analysis indicated that anxiety (OR = 0.863, p < 0.05), avoidance (OR = 1.280, p < 0.001), cognitive illness representations (OR = 0.891, p < 0.01), illness comprehensibility (OR = 1.271, p < 0.05), higher education level (OR = 3.048–3.609, p < 0.05), married status (OR = 5.220, p < 0.05), tumor site in oral cavity (OR = 5.057, p < 0.05), and no reconstruction (OR = 3.415, p < 0.05) were significantly associated with RTW. The issue of RTW among patients with HNC is related to multidimensional factors, including sociodemographic, psychological, and disease-related situations. We suggest that programs for emotional rehabilitation and occupational counseling need to be developed to assist patients with HNC to RTW at an early stage.

Objective In this study, patients with head and neck adenoid cystic carcinoma were investigated with respect to disease characteristics, treatments, and potentially prognostic variables. Materials and Methods Between January 1995 and December 2010, 29 patients with ACC of the head and neck treated at our institution were retrospectively reviewed. Results The 29 patients had a mean age of 54.7 years. Of the 29 patients, 4 (13.8%) underwent surgical resection only, 21 (72.4%) underwent surgery with radiotherapy, and 4 (13.8%) received postoperative chemoradiotherapy. Of 9 patients (31.0%) who experienced a recurrence within the follow-up period, 3 (10.3%) had local recurrence and 5 (17.2%) had distant metastasis; 1 (3.4%) patient had both local recurrence and distant metastatic spread. Conclusion ACC is a relatively rare tumor associated with long survival, even in metastatic settings. Despite aggressive therapy with surgery, radiotherapy, and chemo- therapy, a marked potential for local and distant recurrence still remains.

Background: To investigate the effectiveness of educating program among primary and secondary school students in Papua New Guinea, where has the highest incidence of oral cancer all over the world. Methods: A cross-sectional school based survey was arranged in primary and secondary school in Papua New Guinea in June, 2015. A self-administrated questionnaire was administered before and after education done by health experts from Taiwan. The subjects were chosen by random. The schools provided the students we educated and did the questionnaires on. Results: Ninety five primary school students and 55 secondary school students in Papua New Guinea participated in the study. Before education, both groups lacked the knowledge that betel quid is harmful to health and had no motivation to quit betel quid consumption with the average score 4.580 out of the total score of 8 for primary school students, and the average score of 4.600 out of the total score of 8 for secondary school students. After education, improvements were noted in knowledge of betel quid among both groups, and reached the statistical significance for secondary school students (mean difference 0.700 ± 0.277, 95% CI 0.164–1.248, p-value = 0.018). Conclusion: A great achievement was gained by a short time of education. To prevent the incidence and mortality of oral cancer in Papua New Guinea, education programs should be arranged aggressively and effectively. Keywords: Betel nut, Betel quid, Education, Papua New Guinea

A dual-band dual-polarization stacked antenna array for weather observation by calculating the direct and reflected GPS signals is introduced. A single antenna element was composed of two square ring patches manufactured in two different thickness of dielectric substrates. This antenna array was assembled by 2 × 3 antenna elements on a 200 mm × 300 mm ground plane. A feeding network was developed for receiving the right-handed circular polarization (RHCP) and left-handed circular polarization (LHCP) signals simultaneously. The measured reflection coefficient in the passband were lower than −10 dB and the isolation between two ports were 29.9 dB at 1227 MHz and 14.7 dB at 1575 MH as demonstrated. The measured results depicted that the peak gain was about 10.8 dB at 1227 MHz and 12.3 dB at 1575 MHz and the axial ratio were both blew 2.3 dB. It was seen that 3-dB beam width were approximately 40° × 54° at 1227 MHz and 30° × 44° at 1575 MHz.

This study evaluated the efficacy of tegafur-uracil for advanced oral cancer. From January 2008 to December 2013, clinical data from 356 patients with stage III or IV oral squamous cell carcinoma who received curative surgical resection and postoperative concurrent chemoradiotherapy, treated with or without tegafur-uracil, were analyzed from a prospectively designed database. Tegafur-uracil was orally administered to 114 of the 356 patients. Disease-specific survival (DSS), disease-free survival (DFS), and overall survival (OS) rates were studied. In our study, the 5-year OS (p = 0.0008), DFS (p = 0.0034), and DSS (p = 0.0029) rates were significantly better in the tegafur-uracil group than in the control group. Distant metastasis occurred in 16.28% of patients in the tegafur-uracil group and 45.28% in the control group (odds ratio 4.3). The distant metastasis rate in the tegafur-uracil group was significantly lower than the control group, indicating that administration of tegafur-uracil after curative surgical treatment and concurrent chemoradiotherapy prevented distant metastasis and improved the OS, DFS, and DSS rate. The result of tegafur-uracil treatment in patients with advanced oral cancer showed significant improvement in the 5-year OS, DFS, and DSS rate, while also showing a decreased distant metastasis rate. Tegafur-uracil treatment is a useful, effective, and well-tolerated anticancer treatment for advanced oral cancer.

Due to the rapid development in semiconductor technology, MEMS (microelectromechanical system)-based sensors have been widely used in commercial and military applications. These sensors are characterized by their small size, low cost, low power consumption. However, MEMS sensors are noted for their low accuracy, limiting the applicability in high precision navigation and control. In this paper, a MEMS gyroscope array is developed to account for the limitation of an individual sensor. The key is to develop a robust M-estimation filter to process the sensor array data in real time so as to provide a more accurate estimate of the angular rate, to render fault tolerance capability, and to facilitate signal quality index for system integration. The robust M-estimation Kalman filter is implemented in a DSP/FPGA platform to account for random bias and random walk. In addition, the M-estimation technique is used to accommodate outliers. Allan variance and FFT method are employed as an analyzing tool to quantify the performance. It is verified that the proposed robust M-estimation filter is capable of suppressing non-Gaussian impulse noise and providing a high-accuracy angular rate measurement.

We describe the integrated power, area and thermal modeling framework in the Structural Simulation Toolkit (SST) for large-scale high performance computer simulation. It integrates various power and thermal modeling tools and computes run-time energy dissipation for core, network on chip, memory controller and shared cache. It also has functionality to update the leakage power as temperature changes. We illustrate the utilization of the framework by applying it to explore interconnect options in manycore systems with consideration of temperature variation and leakage feedback. We compare power, energy-delay-area product (EDAP), and energy-delay product (EDP) of four manycore configurations-1 core, 2 cores, 4 cores and 8 cores per cluster. Results from simulation with or without consideration of temperature variation both show that the 4-core per cluster configuration has the best EDAP and EDP. Even so, considering temperature variation increases total power dissipation. We demonstrate the importance of considering temperature variation in the design ow. With this power, area and thermal modeling capability, SST can be used for hardware/software co-design of future Exascale systems.

Macrophage motility is vital in innate immunity. Lipopolysaccharide (LPS)-mediated macrophage migration requires the enhancement of Src expression and enzymatic activity, which can be regulated by inducible nitric oxide synthase (iNOS). As a major short-chain fatty acid with histone deacetylase (HDAC) inhibitor activity, butyrate exerts anti-inflammatory effect by regulating the expression of cytokines. However, the influence of butyrate on macrophage movement was vague. In this study, we observed that butyrate inhibited migration of both RAW264.7 and rat peritoneal macrophages elicited by LPS. Unlike its myeloid relatives (i.e. Lyn, Fgr and Hck) whose expression was almost unaltered in the presence or absence of butyrate in LPS-treated macrophages, LPS-mediated Src induction was greatly suppressed by butyrate and that could be attributable to reduced level of the src transcript. Similar phenomenon was also detected in LPS-treated macrophages exposed to another HDAC inhibitor, trichostatin A (TSA). Consistent with the indispensability of iNOS in promoting macrophage mobilization via Src up-regulation and the activation of both Src and FAK, we did observe concomitant decrement of iNOS, Src and the suppressed activity of Src and FAK in butyrate- or TSA-pretreated macrophages following LPS exposure. These results imply that by virtue of reduction of Src, butyrate could effectively hamper LPS-triggered macrophage locomotion.

A complementary metal oxide semiconductor (CMOS) phase/frequency detector (PFD) is presented. An improved CMOS D-type master-slave flip-flop is described and adopted in the PFD. Higher speed and lower power operation is attributed to the reduced node capacitance. Charge-sharing phenomena are circumvented in the proposed flip-flop and PFD. The maximum frequency of operation of the PFD is analytically studied. Device-sizing equations, based upon a first-order approximation, for the PFD are derived. The proposed PFD shows improvements in both phase and frequency sensitivities at high operating frequencies. HSPICE simulations of a phase-locked loop (PLL) employing the improved PFD demonstrate a faster frequency acquisition. The PLL simulations also verify that the maximum operating frequency of the PFD is in agreement with our analytical results.

Extraadrenal paragangliomas are rare pediatric tumors with variable symptoms that cause difficultly in diagnosis and delayed treatment. We report the case of a 10-year-old boy who presented to the pediatric emergency department with acute chest pain and dyspnea mimicking a non-ST-segment elevation acute myocardial infarction. He was subsequently found to have an extraadrenal paraganglioma after a series of imaging and laboratory examinations. The mass was subsequently removed, and the diagnosis of extraadrenal paraganglioma was confirmed histologically. Acute coronary syndrome as the presenting feature of extraadrenal paragangliomas in pediatric population is an even rarer clinical entity.

An ensemble is a group of related simulation runs, each consisting of the same set of variables, in a shared high-dimensional space describing a particular problem domain. Ensemble analysis looks at the combined behaviors and features of the simulations to discover higher-level patterns that describe aspects of the underlying problem space. Sensitivity analysis is a type of ensemble analysis that evaluates how changes in simulation input parameters correlate with simulation results. Commonly, simple regression and multiple regression techniques are used to correlate single inputs to single outputs, or groups of inputs to a single output, respectively. However, neither of these approaches evaluates the collective relationships among multiple inputs and outputs. Existing visualization tools are fundamentally designed to view no more than a few simulations in combination. Ensembles containing hundreds or thousands of simulations require a different type of analysis, different visual abstractions, and a different system architecture to effectively manage integrating so many results. We present Slycat, a scalable, collaborative, remote analysis and visualization system designed for ensemble analysis. Slycat uses Canonical Correlation Analysis (CCA) to model relationships between input and output variables, providing a generalized correlation capability that analyzes any variable subsets from the two variable groups. Using linked views, we provide multiple representations of the CCA results for an ensemble, each showing the results at a different level of abstraction. The tight integration of analysis and visualization allows analysts to iteratively explore their data, forming and testing hypotheses about how simulation input parameters are driving output results in their ensembles. We provide two real-life examples using electrical circuit simulation ensembles of differing scales to demonstrate Slycat’s utility in answering common analysis questions. Slycat is available under an open source license through github.

A novel meandered parallel coupled-line structure is proposed to suppress the first spurious passband of a microstrip bandpass filter. The meandered parallel coupled line can equalize the modal transmission phases at any interested frequency such as first spurious passband frequency due to its dispersive response. Several filters are designed and fabricated on a substrate with a dielectric constant of 10.2 and a thickness of 50 mil (1.27 mm) to demonstrate the validity of the proposed method. The example filters are chosen to be of large fractional bandwidth and with a relatively high dielectric-constant substrate where, in these cases, the first spurious passband near twice of the passband frequency (2fo) seriously degrades the conventional parallel coupled filter's upper stopband performance. The upper stopband performance of the proposed filters drastically improves that the measured first spurious passband are suppressed to better than -50 dB for all example filters. Besides, a meandered coupled line not only suppresses the filter's first passband, but also largely shrinks its length. The characteristics of the proposed structure and the design procedures of the filter are described in detail

Lithium chloride (LiCl) has long been used as a mood stabilizer for bipolar mood depression patients. However, its biological effects on immune cells are unclear yet. In this study, we observed that upon LiCl stimulation, the motility and the content of total protein tyrosine phosphorylation in RAW264.7 macrophages and murine peritoneal macrophages (PEMs) were significantly increased. The inhibition of LiCl-induced macrophage migration by PP2 (an inhibitor for Src family kinases (SFKs)) suggested the involvement of SFKs in this process. Interestingly, LiCl induced NF-kB activation, and while Src was greatly induced, the expression of its myeloid relatives (i.e. Lyn, Fgr, Hck) was almost unaltered in RAW264.7 cells. Knockdown of Src suppressed LiCl-elicited movement and the level of FAK Pi-Tyr861, which could be reversed by siRNA-resistant Src. Consistent with Src and migration increment was iNOS-dependent in macrophages, markedly reduced Src expression, activity and cell migration were observed in iNOS-null PEMs treated with LiCl. Moreover, FAK knockdown suppressed LiCl-stimulated macrophage motility, suggesting the involvement of FAK in this process. Remarkably, similar increment of iNOS, Src, FAK Pi-Tyr861 and migration ability could also be detected in RAW264.7 treated with other GSK3β inhibitors (i.e. SB216763 and Kenpaullone). These results corroborate that through inhibition of GSK3β, the iNOS/Src/FAK axis occupies a critical role in macrophage locomotion in response to LiCl.

Double-stranded RNA (dsRNA) induces phosphorylation of Toll-like receptor 3 (TLR3) at tyrosine 759 and subsequently triggers signaling pathways to promote interferon-β (IFN-β) production. In this study, we found that dsRNA stimulation induces biphasic TLR3 Tyr-759 phosphorylation in macrophages. In addition to the immediate TLR3 Tyr-759 phosphorylation, we identified a second wave of Tyr-759 phosphorylation accompanied by an increase of both Src and ifn-β transcription in the later phase of dsRNA stimulation. Interestingly, Src phosphorylated TLR3 Tyr-759 in vitro and in vivo. However, knockdown of Src abolished the late phase of TLR3 Tyr-759 phosphorylation and decreased the nuclear accumulation of interferon regulatory factors 3 and 7 (IRF3 and -7) and IFN-β production. Reintroduction of Src restored all of these molecular changes. Notably, via down-regulation of Src, dsRNA-elicited TLR3 Tyr-759 phosphorylation, the nuclear accumulation of IRF3/IRF7, and IFN-β generation were inhibited in inducible nitric-oxide synthase (iNOS)-null macrophages. TLR3 knockdown destabilized Src and reduced the nuclear level of IRF3/IRF7 and IFN-β production in macrophages exposed to LPS (a TLR4 ligand known to induce Src and IFN-β expression). Ectopic expression of wild type TLR3, but not its 759-phenylalanine mutant, restored Src activity and ifn-β transcription. Taken together, these results suggested an essential role of the iNOS/Src/TLR3 axis in IFN-β production in macrophages.

A novel one-section bandstop filter (BSF), which possesses the characteristics of compact size, wide bandwidth, and low insertion loss is proposed and fabricated. This bandstop filter was constructed by using single quarter-wavelength resonator with one section of anti-coupled lines with short circuits at one end. The attenuation-pole characteristics of this type of bandstop filters are investigated through TEM transmission-line model. Design procedures are clearly presented. The 3-dB bandwidth of the first stopband and insertion loss of the first passband of this BSF is from 2.3 GHz to 9.5 GHz and below 0.3 dB, respectively. There is good agreement between the simulated and experimental results.

Ectopic kidney is a rare condition. Giant hydronephrosis is also an uncommon lesion in children and is usually due to ureteropelvic junction obstruction. We report a case of 7-year-old girl presenting with abdominal fullness. The imaging characteristics of magnetic resonance urography of the lesions are reported. The findings from the radiologic investigations were suggestive of a dysplastic ectopic pelvic kidney with giant hydronephrosis. Subsequent surgery confirmed the diagnosis. An ectopic kidney with giant hydronehrosis is an extremely rare condition in children and can present as an asymptomatic abdominal mass. A careful survey for other structural anomalies is mandatory in such cases.

High on-chip temperatures adversely affect the reliability of processors, and reliability has become a serious concern as high performance computing moves towards exascale. While dynamic thermal management techniques can effectively constrain the chip temperature, most prior work has focused on temperature and reliability optimization of a single processor. In this work, we propose a topology-aware workload allocation policy to optimize the reliability of multi-chip multicore systems at runtime. Our results show that the proposed policy improves the system reliability by up to 123.3% compared to existing temperature balancing policies when systems have medium to high utilization. We also demonstrate that the policy is scalable to larger systems and its performance overhead is minimal.

Toll-like receptors (TLRs) are crucial in macrophage phagocytosis, which is pivotal in host innate immune response. However, the detailed mechanism is not fully defined. Here, we demonstrated that the induction of Src and Eps8 in LPS-treated macrophages was TLR4- and MyD88-dependent, and their attenuation reduced LPS-promoted phagocytosis. Confocal microscopy indicated the colocalization of Eps8 and TLR4 in the cytosol and at the phagosome. Consistently, both Eps8 and TLR4 were present in the same immunocomplex regardless of LPS stimulation. Inhibition of this complex formation by eps8 siRNA or overexpression of pleckstrin homology domain-truncated Eps8 (i.e. 261-p97(Eps8)) decreased LPS-induced TLR4-MyD88 interaction and the following activation of Src, focal adhesion kinase, and p38 MAPK. Importantly, attenuation of Eps8 impaired the bacterium-killing ability of macrophages. Thus, Eps8 is a key regulator of the LPS-stimulated TLR4-MyD88 interaction and contributes to macrophage phagocytosis.

Resiliency will be one of the toughest challenges in future exascale systems. Memory errors contribute more than 40% of the total hardware-related failures and are projected to increase in future exascale systems. The use of error correction codes (ECC) and checkpointing are two effective approaches to fault tolerance. While there are numerous studies on ECC or checkpointing in isolation, this is the first paper to investigate the combined effect of both on overall system performance and power. Specifically, we study the impact of various ECC schemes (SECDED, BCH, and chip-kill) in conjunction with checkpointing on future exascale systems. Our simulation results show that while chipkill is 13% better for computation-intensive applications, BCH has a 28% advantage in system energy-delay product (EDP) for memory-intensive applications. We also propose to use BCH in tagged memory systems with commodity DRAMs where chipkill is impractical. Our proposed architecture achieves 2.3× better system EDP than state-of-the-art tagged memory systems.

The presentations of cardiac myxoma are diverse, from asymptomatic to a variety of symptoms due to embolization. Occlusion of abdominal aortic bifurcation by straddled myxoma is not common; however, obstructive level above renal artery is very rare. We present a patient with cardiac myxoma who presented with acute onset of paraplegia. The aorta was occluded from the level of the liver dome to the renal arteries, and catastrophic outcome (ischemia/reperfusion) following its removal.

Background A stochastic simulator was implemented to study EGFR signal initiation in 3D with single molecule detail. The model considers previously unexplored contributions to receptor-adaptor coupling, such as receptor clustering and diffusive properties of both receptors and binding partners. The agent-based and rule-based approach permits consideration of combinatorial complexity, a problem associated with multiple phosphorylation sites and the potential for simultaneous binding of adaptors. Results The model was used to simulate recruitment of four different signaling molecules (Grb2, PLCγ1, Stat5, Shc) to the phosphorylated EGFR tail, with rules based on coarse-grained prediction of spatial constraints. Parameters were derived in part from quantitative immunoblotting, immunoprecipitation and electron microscopy data. Results demonstrate that receptor clustering increases the efficiency of individual adaptor retainment on activated EGFR, an effect that is overridden if crowding is imposed by receptor overexpression. Simultaneous docking of multiple proteins is highly dependent on receptor-adaptor stability and independent of clustering. Conclusions Overall, we propose that receptor density, reaction kinetics and membrane spatial organization all contribute to signaling efficiency and influence the carcinogenesis process.

The Toll-like receptors (TLRs) play a pivotal role in innate immunity for the detection of highly conserved, pathogen-expressed molecules. Previously, we demonstrated that lipopolysaccharide (LPS, TLR4 ligand)-increased macrophage motility required the participation of Src and FAK, which was inducible nitric oxide synthase (iNOS)-dependent. To investigate whether this iNOS/Src/FAK pathway is a general mechanism for macrophages to mobilize in response to engagement of TLRs other than TLR4, peptidoglycan (PGN, TLR2 ligand), polyinosinic–polycytidylic acid (polyI:C, TLR3 ligand) and CpG-oligodeoxynucleotides (CpG, TLR9 ligand) were used to treat macrophages in this study. Like LPS stimulation, simultaneous increase of cell motility and Src (but not Fgr, Hck, and Lyn) was detected in RAW264.7, peritoneal macrophages, and bone marrow-derived macrophages exposed to PGN, polyI:C and CpG. Attenuation of Src suppressed PGN-, polyI:C-, and CpG-elicited movement and the level of FAK Pi-Tyr861, which could be reversed by the reintroduction of siRNA-resistant Src. Besides, knockdown of FAK reduced the mobility of macrophages stimulated with anyone of these TLR ligands. Remarkably, PGN-, polyI:C-, and CpG-induced Src expression, FAK Pi-Tyr861, and cell mobility were inhibited in macrophages devoid of iNOS, indicating the importance of iNOS. These findings corroborate that iNOS/Src/FAK axis occupies a central role in macrophage locomotion in response to engagement of TLRs.