bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation of Diamond Films Polished by Thermal Chemical Mechanical Polishing
Authors: Jun Ren , Kailiang Zhang , Fang Wang , Yujie Liu , Yujie Yuan
Published: March 2013

In this paper, CVD diamond films were planarized by thermal chemical mechanical polishing, in which two steps polishing methods (first polishing and final polishing) to diamond films were optimized. In the first polishing process, Al2O3 abrasives with particle size of 14μm were chosen to remove the rough surface of the diamond films. In the final polishing process, three kinds of polishing experiments containing different abrasives were compared. The experiment results demonstrated that the slurry with mixture abrasives and KMnO4 oxidant at the high temperature can improve the diamond films surface morphology effectively. As a result, the surface roughness was reduced from 280nm to 27.2nm, and the removal rate was up to 1.21μm /h.
On the Optimization of Prime Silicon Wafer Geometry in Final Chemical Mechanical Polishing
Authors: Dang Yuxing , Wang Yongtao , Ye Songfang , Xiao Qinghua , Zhang Guohu , Liu Bin
Published: March 2013

For the advanced Ultra-large Scale Integrated Circuits (ULSI) manufacturing, two key geometry parameters of the 300 mm prime silicon wafers: SFQR and GBIR are of major interest to the manufacturers. During the acceptance tests of the first China-made final-touch chemical-mechanical machine (CMP). We find that to enhance the geometry parameters, we have to know the geometry of incoming wafers and to modify the polishing head pressure accordingly. After investigation of the geometry of the incoming wafers, we find wafers with concave thickness profile would be deteriorated seriously after final-touch CMP. According to the shape of every wafer, we vary the backing pressure distribution of our special designed polishing head. Eventually, the wafer thickness geometry after modification could fulfill our demand, which demonstrates that our own-made machine could be used in mass production.
Development of Next Generation Post Copper CMP Cleaners
Authors: Kuroda Akira , Otake Atsushi , Bernatis Paul
Published: March 2013

Development of post copper CMP cleaning formulations that effectively remove the residues left from the CMP step and corrosion at the conductor and barrier to almost undetectable levels is described. Organic residue removal efficiency and corrosion of interconnects and barrier materials are discussed. Post CMP particle and residue defectivity data will also be presented to demonstrate the cleaning efficiency of the new formulations.
Ultra Low-k Damage Control and k Recovery for 28nm RC Improvement
Authors: Zhao Jing , Song Xinghua , Zhou Lei , Bai Fanfei , Peng BingQing , Zou Li , Zhao BaoJun , Chen Larry
Published: March 2013

To improve resistance-capacitance delay, porous ultra low-k dielectric materials are used in advanced copper damascene integration. However, the BEOL processes often lead to low-k film damage by removing the hydrophobic groups Si-CH3, and convert partially low-k materials surface from hydrophobic to hydrophilic one. During the wet related processes, the hydrophilic porous low-k film surface is easy to absorb moisture and potentially increase k-value. In this work, we developed the processes that can maintain ultra low-k film k-value either by repairing low-k damage or by removing moistrue. Dry etch plasma process is one of the main steps to result in low-k film damage. Post etch treatment (PET) was optimized to repair porous low-k film surface due to the etch damage. This improved process with less low-k damage can significantly reduced the moisture absorption in the following wet process and improve the capacitance by about 10%. Various thermal treatments post wet and post CMP processes were studied, including temperature, gases and pressures. From our results, post wet clean heat treatment can improve capacitance by about 5% and post CMP heat treatment can improve capacitance by about 10%. To decrease moisture absorption from atmosphere after the wafers were processed thru CMP, queue time from CMP to NDC deposition also was studied and the safe specification was also defined.
Optimization of M1 to Contact Connection in Sub-40nm Node
Authors: Zhang Liang , Fang Jingxun , Mao Zhibiao , Huang Hai , Li Fang , Yan Junhua , Yu Shirui , Huang Jun , Zhao Long , Zhang Huijun , Chen Fei , Leng Jianghua , Zhu Y. F. , Jing Xubin , Yu Liujiang , Zhang Yu , Cao Yongfeng , Pang Albert
Published: March 2013

This paper presents integration challenges associated with M1 to CT connection in Ultra low-k (ULK) Back-End-Of-Line (BEOL) interconnects for 40nm node and beyond. In advance IC fabrication, porous dielectric materials, such as BDII (related dielectric constant k about 2.5), are commonly used as insulator in copper interconnects for RC delay reduction. But the material of inter-dielectric layer is still high density SiO2-based. Hence, the difference in materials of PMD and IMD would potentially induce mismatch of physical properties of the two types of dielectric and cause deterioration of M1 to Contact connection, which would further impact product yield by contact open or other issues. Cross section pictures of failing M1 to CT connection were exhibited with a special spacer profile and investigated to illustrate the phenomenon. Solutions were proposed, through optimization of Etch, Wet clean and CMP to improve process window. Layout optimization is also suggested as OPC and DFM solution for related layers. Some of the solutions were examined by experiments with 40nm BEOL test masks. Results of physical and electric characterization were presented and discussed.
Electrical Characteristics of the Fluorinated MOHOS Flash Memory Using Fluorine Ion Implantation
Authors: Chen Yung-Yu , Lei Gen , Shen Yu-Jie
Published: March 2013

Fluorine ion implantation has been used to simultaneously fabricate fluorinated dielectrics of the metal/SiO2/HfO2/SiO2/Si (MOHOS) flash memory. Fluorine incorporation into the OHO stacked dielectrics not only reduces bulk defects and interface states, but also creates deep level traps, both of which are helpful to improve the electrical characteristics. Compared to the flash memory without fluorine incorporation, the fluorinated MOHOS flash memory therefore exhibits faster than 10x improvements on the program/erase speed, smaller than 8% charge loss after 10-year, and less than 14% window closure after 105 endurance cycles.
Pre-Amorphous Implant and Millisecond Annealing for NiPt Sheet Resistance and Junction Leakage Reduction
Authors: Ding Shi Cheng , Chen Larry , Yang Cheng Jui
Published: March 2013

With the aggressive scale down of MOSFET junction depth, nickel silicide (incorporated with platinum) is finally coming into picture with its low resistivity and silicon consumption. The sheet resistance and junction leakage are always a tradeoff during nickel silicide process development. This article introduces a novel nickel silicide process scheme to achieve low sheet resistance and low junction leakage at the same time. PAI(Pre-Amorphous Implant) is applying for sheet resistance reduction; the well controlled low process temperature during PAI and MSA (Milli-second Annealing) maintain the low junction leakage level.
(Invited) Development of Advanced Fan-Out Wafer Level Package
Authors: Jin Yonggang , Teysseyre Jerome , Ramasamy Anandan , Liu Yun , Huang Bing Hong
Published: March 2013

Fan-out WLP is one of embedded package processed on wafer level, also a key advanced packages with higher number of I/Os, integration flexibilities. Furthermore, it enables to integrate multiple dies vertically and horizontally in one package without using substrates. Thus, recently Fan-out WLP technology is moving forward to next generation packages, such as multi-die, low profile package and 3D SiP. Not only the electronic packages, Fan-out WLP but also is used for sensor, power IC and LED packages This paper reports developments of next generation Fan-out WLP for advanced packaging solutions.
New Flip-Chip Interconnect Technology for High Performance and High Reliability Applications
Authors: Yamaguchi Eiji , Tsuji Mutsuo , Shimoishizaka Nozomi , Nakano Takahiro , Hirata Katsunori
Published: March 2013

As the current and next generation devices are embracing geometries below 28nm and assuming finer 10nm order. And they are requiring softer low-k dielectric isolation on very thin large silicon dies. To perform a reliable die-to-package interconnect is becoming a challenge. Further, the existing interconnection method and expanding technology such as Cu wire/pillar given high pressure and stress that cause of assembly process and material sets character. They often results in damage of device structure. The interconnection for high performance is commonly used C4. And majority of products are applied it. This C4 interconnection method was developed and started to apply almost half century ago. It quite aged. But LSI technologies are innovating year by year. And therefore interconnection method should be innovated and changed to aim next generation devices. Furthermore Cu pillar is developed for only fine pitch area and not for high pin count LSI. This Cu pillar is not used for wide range of products. A new flip-chip bonding technology has been developed for such very sensitively fine wafer process rule’s LSI. And it is claimed to be “damage free and stress free”. It used soft bump formed by conductive paste on the substrate. These soft bumps require ultra-low bonding pressure on the pad of the die during complete interconnection. Thus the flip-chip bonding is not given any damage on ULK isolation layer. This damage free flip-chip bonding is also designed for ultra-low stress structure. The existing flip-chip products commonly used solder or Cu and organic substrate, it always have higher residual stress. The newly developed flip-chip bonding technology can realize ultra-low stress structure. It is caused by the set of material character. Especially this technology is assumed to use ceramic substrate. Ceramics substrate itself has very low warpage and high performance ability. Totally, this developed flip-chip is very advanced technology for next generation devices. Details of the process and material sets used for such fragile device structure are going to be present. Reliability results are shared, which further ensures the robustness of this process. Finally, the cost advantage through adaption of this process has also been elaborated. Also, other new package development activity is going to be introduced.
Palladium-Coated and Bare Copper Wire Study for Ultra-Fine Pitch Wire Bonding
Authors: Lim Adeline B.Y. , Chang Andrew C.K. , Lee Chee Xian , Yauw Oranna , Chylak Bob , Chen Zhong
Published: March 2013

There is growing interest in copper (Cu) wire bonding due to its significant cost savings over gold wire. However, concerns on corrosion susceptibility and package reliability have driven the industry to develop alternative materials. Recently, palladium-coated copper (PdCu) wire has become widely used as it is believed to improve reliability. In this paper, we experimented with 0.6 mil PdCu and bare Cu wires. Palladium distribution and grain structure of the PdCu Free Air Ball (FAB) were investigated. It was observed that Electronic Flame Off (EFO) current and the cover gas type have a significant effect on palladium distribution. The Free Air Ball (FAB) hardness was measured and correlated to palladium distribution and grain structure. First bond process responses were characterized. The impact of palladium on wire bondability and wire bond intermetallic using a high temperature storage test was studied. These results for PdCu wire were compared with bare Cu wire.
13.56 MHz RFID Tag IC Automatic Testing
Authors: Zhang Jian , Cai Shenqi
Published: March 2013

Radio Frequency Identification (RFID) technology is applied more widely in industry and daily life. One type of RFID product, passive tag, has many advantages over another type, battery-based active tag, such as longer product life, smaller size, lower cost, etc. Due to very low price of passive tag, how to test it fast and efficiently in production is a big challenge to ATE (Automatic Test Equipment) engineers. The non-deterministic latency from stimulus to response also brings much difficulty to testing. This paper introduces a complete ATE-based solution for testing of 13.56 MHz RFID passive tag, including a dedicated module to generate, filter and amplify modulation signal, and a real-time verification method, which overcomes the difficulty caused by non-deterministic latency. The paper demonstrates advantages of the real-time method by comparing test time with result of traditional method of data capturing then post processing.
Efficient Failure Data Collection for Memory BIST Diagnosis in Production Test
Authors: Yang Wu , Guo Ruifeng
Published: March 2013

Embedded memory test is usually done through memory BIST. During production, people not only want to know a memory is pass or fail, but also want to know which memory failed, the failure bit and its row/column. A popular diagnosis method called stop-on-error (SOE) can help achieve this goal. Characterization and debug package (CDP) based memory BIST SOE diagnosis has provided a standard interface between EDA software and ATE platform. The diagnosis algorithm and diagnosis related design information can be interacted with ATE hosting software and delivered to ATE hardware accordingly. This method has alleviated the dependency of running diagnosis on a specific ATE platform. The case studies show this flow helped both user interface development and performance improvement over the existing diagnosis method.
Using Logic BIST to Test the PIC Block in FPGA
Authors: Bian Aiqin
Published: March 2013

This paper presents using the Logic BIST (Build-in Self-test) implementation on the PIC (Program IO Cell) block test for FPGA. Self-test is achieved by utilizing the test resource available in the FPGA. Test vectors are generated and compared internally, which makes the PIC test package independent and compatible to sort test because this implementation requires only minimum number of IO pins. Therefore it makes the PIC block test more effectively by eliminating the need to consider the different packaging of the device, which dramatically lowers the manufacture test development cost and time. The experiment shows very promising results. The amount of the test patterns is reduced by 77%. The test development cycle time is reduced by 48% compared to the traditional test method. Though the number of pattern is reduced, the test coverage is not compromised which is guaranteed by taking all PIC test configurations into account. This implementation was illustrated on PIC block in this paper. But it is applicable to testing other FPGA typical blocks, such as EBR, DSP and PLC using the proposed logic BIST method.
Package Limited Current Rating Test Methodology
Authors: Zeng Yuanzhou , Lv Yafei , Hu Zhiping
Published: March 2013

The current trend in electronics is toward the use of power devices with higher current, smaller size and lower power dissipation. The requirement for power devices with compact size and high current conduction capability has increased tremendously in the past several years. In order to meet the market demanding, more and more new advanced package technologies such as PQFN with clip bond have been developed to reduce the package size while maintaining high current carrying capability. In the past, the maximum continuous current of a product with big package size such as TO220, TO252, TO263 and TO247 etc is limited by the silicon die itself. Along with more products are being developed into smaller packages such as PQFN/MLP, the maximum continuous current is becoming limited not by the silicon die but by the package instead, which we call it package limited current (PLC).
Golden Wafer Study and Application for Critical Dimension Scanning Electron Microscope Stability Control
Authors: Huang Yi , Cai Bo-Xiu , Meng Xiao-Ying , Li Wen-Hui , Lin Yi-Shih , Yang Si-Yuan Frank
Published: March 2013

In this work, we prepared one kind of metallic golden wafer coated with tantalum/tantalum nitride (Ta/TaN) films or single Ta film by either PVD (Physical Vapor Deposition ) process or ALD (Atomic layer deposition) process to alleviate the charge accumulation and mitigate the electrostatic enhanced impurity adsorption. Through this approach, the charging effect on line CD measurement is effectively eliminated. We compared the charging effect among normal wafer, metallic golden wafer, and the evaluated golden wafer’s life time in terms of charging effect prevention by means of a long-term test. Moreover, to extend the lifetime of golden wafer, a rework process was investigated to deoxidize the surface oxidation layer and prevent it from the charging induced long-term performance degradation. For CD-SEM stability control, we designed a daily monitor flow utilizing the golden wafer to ensure and maintain a healthy CDSEM condition for in-line product measurement. Finally, we extended the concept of this metallic golden wafer into other potential metrology related applications such as CD-SEM tool matching and calibration.
Electrical and TDDB Characteristics of High-k/Metal Gate MOS Capacitors with Different RTO Temperatures
Authors: Xu Hao , Yang Hong , Ren Shangqing , Luo Weichun , Wang Yanrong , Han Kai , Xiang Jinjuan , Wang Xiaolei , Ma Xueli , Wang Wenwu , Zhao Chao , Chen Dapeng , Ye Tianchun
Published: March 2013

The Electric and TDDB characteristics of Si/SiO2/HfO2/TiN gate MOS capacitor (EOT ~ 9.3 A ) with different RTO temperatures are systematically studied. The TDDB characteristics are sensitive to the RTO temperatures (700oC, 800oC and 900oC), and the higher RTO temperature is, the larger Weibull Slope is shown because of thicker EOT. Compared to 700oC and 900oC RTO, the 800oC RTO has the best TDDB lifetime for 63% failure.
The Failure Mechanism Worst Stress Condition for Hot Carrier Injection of NMOS
Authors: Song Zhuo , Chen Zhaoxing , Yong Atman Zhao , Song Yongliang , Wu Jeff , Chien Karry
Published: March 2013

Various voltage bias and temperature stress conditions are adopted for hot carrier injection (HCI) test by not only the different device type (N or PMOS) but also the different technology with various device feature sizes (such as W/L=10/0.28µm and 10/0.1µm). Due to different dominant mechanism for hot carrier generation and performance degradation corresponding to various devices, the appropriate stress condition selection is crucial to address the HCI lifetime for device. Based on the conditions that may occur in real application and according to the experimental data, this work discussed the worst stress condition including the voltage and temperature for NMOS device with specific device feature size. Theoretical explanation is presented for each case. An HCI stress condition guideline is summarized in the end.
Negative Bias Temperature Instability Characteristics and Degradation Mechanisms of pMOSFET with High-k/Metal Gate Stacks
Authors: Ren Shangqing , Yang Hong , Wang Wenwu , Xu Hao , Luo Weichun , Tang Bo , Tang Zhaoyun , Xu Jing , Yan Jiang , Zhao Chao , Ye Tianchun
Published: March 2013

In this work, NBTI characteristics of pMOSFET with high-k/metal gate stacks are systematic investigated and the degradation mechanisms are analyzed. The threshold voltage shift with stress time obeys power-law, but the power exponent is dependent on stress voltage, and it ranges from 0.26 to 0.16. The activation energy (Ea) under -1.4V stress is extracted as 0.24eV. Trap charging in the high-k layer dominates the NBTI degradation rather than interface state generation. The lifetime prediction prefers to power law model.
Process Optimization of HfAlO Trapping Layer for High Performance Charge Trap Flash Memory Application
Authors: Zhang Dong , Huo Zongliang , Yang Xiaonan , Liu Ziyu , Chen Guoxing , Han Yulong , Sun Zhong , Chu Yuqiong , Wang Chenjie , Yang Baohe , Liu Ming
Published: March 2013

In order to explore the correlation between process control of HfAlO film deposition and memory performance, 10nm HfAlO trapping layer was deposited by atom layer deposition (ALD) system, using three different deposition sequence of HfO2 and Al2O3 thin films (1nmHfO2/1nmAl2O3, 1nmHfO2/ 2nmAl2O3 and 3nmHfO2/1nmAl2O3). Comparing with HfO2 single trapping layer, the HfAlO samples stacked in the sequence of 1nmHfO2/1nmAl2O3 and 1nmHfO2/ 2nmAl2O3 have faster program/erase speed, lager memory window, and significantly improved data retention characteristics. This is due to the high dielectric constant of HfO2 and appropriate band offset of HfO2 to Al2O3, also with the extra interface inserted between HfO2 and Al2O3.
(Invited) Instability Assessment and Modeling Of Amorphous InGaZnO Thin Film Transistors Under Alternating Pulse Bias Stresses
Authors: Park Suehye , Cho Edward N , Yun Ilgu
Published: March 2013

Amorphous InGaZnO (a-IGZO) TFTs have attracted more demands due to the transparency and high mobility. Since TFTs are always exposed to both positive and negative gate bias, the alternating DC bias stress tests are required to ensure stable TFT characteristics. Moreover, the analysis about scaling-down behavior under bias stress condition is required. In this paper, the effects of alternating pulse bias stress on the threshold voltage shift (ΔVth) of a-IGZO TFTs with respect to the stress time duration (t
d) are analyzed by the variation of interface trap charges (Qit) and the channel electric field (E-field). In addition, the channel length-dependent tendency is verified using the concepts of the subgap density of states (DOS) and density of total trap states (NT).
(Invited) Equivalent Circuit Representation of Resonant Accelerometer
Authors: Jia Yubin , Hao Yilong , Huang Qinwen
Published: March 2013

The equivalent RLC circuit for the resonant accelerometer isdescribed in detail, which shows that equivalent circuit containstwo variable capacitances and two variable resistances due to theacceleration and amplitude. Using the electromechanical couplingfactor presented here and the mode function of the transversedeflection vibration of the double clamped beam, the equivalent circuit parameters related to the size of the accelerometer and thedrive voltage are derived. In short, the mechanical and electrical parameters of the resonant accelerometer can be calculated andanalyzed accurately by the formulae derived in this paper.
(Invited) Robust Subthreshold Circuit Design to Manufacturing and Environmental Variability
Authors: Hashimoto Masanori
Published: March 2013

Subthreshold circuits are drawing attention for ultra-low power application. However, subthreshold circuits have inherent problems that their performance is extremely sensitive to manufacturing and environmental variability and they are susceptible to soft errors. This paper reviews characteristics and problems of subthreshold circuits, and discusses some works for improving the robustness of subthreshold circuits from device, circuit and CAD perspective.
The role of plasminogen activator inhibitor-1 in gastric mucosal protection
Authors: Kenny Susan , Steele Islay , Lyons Suzanne , Moore Andrew R. , Murugesan Senthil V. , Tiszlavicz Laszlo , Dimaline Rod , Pritchard D. Mark , Varro Andrea , Dockray Graham J.
Published: March 2013

Gastric mucosal health is maintained in response to potentially damaging luminal factors. Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) disrupt protective mechanisms leading to bleeding and ulceration. The plasminogen activator system has been implicated in fibrinolysis following gastric ulceration, and an inhibitor of this system, plasminogen activator inhibitor (PAI)-1, is expressed in gastric epithelial cells. In Helicobacter pylori-negative patients with normal gastric histology taking aspirin or NSAIDs, we found elevated gastric PAI-1 mRNA abundance compared with controls; the increase in patients on aspirin was independent of whether they were also taking proton pump inhibitors. In the same patients, aspirin tended to lower urokinase plasminogen activator mRNA. Immunohistochemistry indicated PAI-1 localization to epithelial cells. In a model system using MKN45 or AGS-GR cells transfected with a PAI-1 promoter-luciferase reporter construct, we found no evidence for upregulation of PAI-1 expression by indomethacin, and, in fact, cyclooxygenase products such as PGE2 and PGI2 weakly stimulated expression. Increased gastric PAI-1 mRNA was also found in mice following gavage with ethanol or indomethacin, but plasma PAI-1 was unaffected. In PAI-1−/− mice, gastric hemorrhagic lesions in response to ethanol or indomethacin were increased compared with C57BL/6 mice. In contrast, in PAI-1-H/Kβ mice in which PAI-1 is overexpressed in parietal cells, there were decreased lesions in response to ethanol and indomethacin. Thus, PAI-1 expression is increased in gastric epithelial cells in response to mucosal irritants such as aspirin and NSAIDs probably via an indirect mechanism, and PAI-1 acts as a local autoregulator to minimize mucosal damage.
Bone marrow-derived alternatively activated macrophages reduce colitis without promoting fibrosis: participation of IL-10
Authors: Leung Gabriella , Wang Arthur , Fernando Maria , Phan Van C. , McKay Derek M.
Published: March 2013

Alternatively activated macrophages (AAMs) (or M2a) can inhibit colitis but may also be associated with fibrosis. Thus, by using the dinitrobenzene sulfonic (DNBS) murine model of colitis, this study aimed to determine whether 1) bone marrow (BM)-derived AAMs could reduce colitis, 2) any anticolitic effect of BM-AAMs was IL-10 dependent, and 3) repeated AAM treatments remained effective and were associated with fibrosis in the gut or other tissues. Balb/c mice received AAMs (106 intraperitoneally) from wild-type (WT) or IL-10−/− mice 48 h prior to DNBS (3 mg intrarectally) with disease assessed 72 h later, or they received three doses of DNBS at 2-wk intervals ± AAMs 6 h post-DNBS to mimic a treatment regimen. DNBS-treated mice developed colitis; this was significantly less severe in mice receiving WT AAMs and less so in animals given IL-10−/− AAMs, indicating a role for IL-10 in the inhibition of DNBS-driven colitis. Similarly, after the third AAM treatment lesser colonic histopathology was observed compared with time-matched DNBS-only-treated animals, and notably there was no evidence of increased fibroses in the colon, terminal ileum, lung, or liver of AAM-treated mice as assessed by quantitative PCR for prolyl-4-hydrolase, α-smooth muscle actin, and collagen (type IIIα) and histochemical and biochemical assessment of collagen deposition. This study provides mechanistic insight to the anticolitic capacity of AAMs and indicates that repeated adoptive transfer of ex vivo programmed BM-AAMs is safe and efficacious in the treatment of DNBS-induced murine colitis, providing additional support for their consideration as an immunotherapy.
Nrf2 is not required for epithelial prohibitin-dependent attenuation of experimental colitis
Authors: Kathiria Arwa S. , Butcher Mackenzie A. , Hansen Jason M. , Theiss Arianne L.
Published: March 2013

Inflammatory bowel disease is associated with increased reactive oxygen species (ROS) and decreased antioxidant response in the intestinal mucosa. Expression of the mitochondrial protein prohibitin (PHB) is also decreased during intestinal inflammation. Our previous study showed that genetic restoration of colonic epithelial PHB expression [villin-PHB transgenic (PHB Tg) mice] attenuated dextran sodium sulfate (DSS)-induced colitis/oxidative stress and sustained expression of colonic nuclear factor erythroid 2-related factor 2 (Nrf2), a cytoprotective transcription factor. This study investigated the role of Nrf2 in mediating PHB-induced protection against colitis and expression of the antioxidant response element (ARE)-regulated antioxidant genes heme oxygenase-1 (HO-1) and NAD(P)H quinone oxidoreductase-1 (NQO-1). PHB-transfected Caco-2-BBE human intestinal epithelial cells maintained increased ARE activation and decreased intracellular ROS levels compared with control vector-transfected cells during Nrf2 knockdown by small interfering RNA. Treatment with the ERK inhibitor PD-98059 decreased PHB-induced ARE activation, suggesting that ERK constitutes a significant portion of PHB-mediated ARE activation in Caco-2-BBE cells. PHB Tg, Nrf2−/−, and PHB Tg/Nrf2−/−mice were treated with DSS or 2,4,6-trinitrobenzene sulfonic acid (TNBS), and inflammation and expression of HO-1 and NQO-1 were assessed. PHB Tg/Nrf2−/−mice mimicked PHB Tg mice, with attenuated DSS- or TNBS-induced colitis and induction of colonic HO-1 and NQO-1 expression, despite deletion of Nrf2. PHB Tg/Nrf2−/−mice exhibited increased activation of ERK during colitis. Our results suggest that maintaining expression of intestinal epithelial cell PHB, which is decreased during colitis, reduces the severity of inflammation and increases colonic levels of the antioxidants HO-1 and NQO-1 via a mechanism independent of Nrf2.
Marcello Malpighi and the discovery of the pulmonary capillaries and alveoli
Authors: West John B.
Published: March 2013

Marcello Malpighi (1628–1694) was an Italian scientist who made outstanding contributions in many areas, including the anatomical basis of respiration in amphibia, mammals, and insects and also in the very different fields of embryology and botany. He was one of the first biologists to make use of the newly invented microscope and is best known as the discoverer of the pulmonary capillaries and alveoli. However, he also discovered the spiracles and tracheae that enable respiration in insects. His studies of the embryology of the chicken were far ahead of his time; he then turned to the anatomy of plants, where he made important contributions. Indeed, in some articles Malpighi is referred to as the father of embryology and in other publications as one of the fathers of plant anatomy. His work on the lung was chiefly carried out on the frog; he referred to this animal as the “microscope of nature” because it allowed him to see structures that were not visible in larger animals such as mammals. He also argued that nature undertakes its great works in larger animals after a series of attempts in lower animals. For breadth of interest, innovation, and productivity, it is not easy to think of his equal in the field of life sciences.
Inactivity-induced phrenic and hypoglossal motor facilitation are differentially expressed following intermittent vs. sustained neural apnea
Authors: Baertsch N. A. , Baker-Herman T. L.
Published: March 2013

Reduced respiratory neural activity elicits a rebound increase in phrenic and hypoglossal motor output known as inactivity-induced phrenic and hypoglossal motor facilitation (iPMF and iHMF, respectively). We hypothesized that, similar to other forms of respiratory plasticity, iPMF and iHMF are pattern sensitive. Central respiratory neural activity was reversibly reduced in ventilated rats by hyperventilating below the CO2apneic threshold to create brief intermittent neural apneas (5, ∼1.5 min each, separated by 5 min), a single brief massed neural apnea (7.5 min), or a single prolonged neural apnea (30 min). Upon restoration of respiratory neural activity, long-lasting (>60 min) iPMF was apparent following brief intermittent and prolonged, but not brief massed, neural apnea. Further, brief intermittent and prolonged neural apnea elicited an increase in the maximum phrenic response to high CO2, suggesting that iPMF is associated with an increase in phrenic dynamic range. By contrast, only prolonged neural apnea elicited iHMF, which was transient in duration (<15 min). Intermittent, massed, and prolonged neural apnea all elicited a modest transient facilitation of respiratory frequency. These results indicate that iPMF, but not iHMF, is pattern sensitive, and that the response to respiratory neural inactivity is motor pool specific.
Bubbles, microparticles, and neutrophil activation: changes with exercise level and breathing gas during open-water SCUBA diving
Authors: Thom Stephen R. , Milovanova Tatyana N. , Bogush Marina , Yang Ming , Bhopale Veena M. , Pollock Neal W. , Ljubkovic Marko , Denoble Petar , Madden Dennis , Lozo Mislav , Dujic Zeljko
Published: March 2013

The study goal was to evaluate responses in humans following decompression from open-water SCUBA diving with the hypothesis that exertion underwater and use of a breathing mixture containing more oxygen and less nitrogen (enriched air nitrox) would alter annexin V-positive microparticle (MP) production and size changes and neutrophil activation, as well as their relationships to intravascular bubble formation. Twenty-four divers followed a uniform dive profile to 18 m of sea water breathing air or 22.5 m breathing 32% oxygen/68% nitrogen for 47 min, either swimming with moderately heavy exertion underwater or remaining stationary at depth. Blood was obtained pre- and at 15 and 120 min postdive. Intravascular bubbles were quantified by transthoracic echocardiography postdive at 20-min intervals for 2 h. There were no significant differences in maximum bubble scores among the dives. MP number increased 2.7-fold, on average, within 15 min after each dive; only the air-exertion dive resulted in a significant further increase to 5-fold over baseline at 2 h postdive. Neutrophil activation occurred after all dives. For the enriched air nitrox stationary at depth dive, but not for other conditions, the numbers of postdive annexin V-positive particles above 1 μm in diameter were correlated with intravascular bubble scores (correlation coefficients ∼0.9, P < 0.05). We conclude that postdecompression relationships among bubbles, MPs, platelet-neutrophil interactions, and neutrophil activation appear to exist, but more study is required to improve confidence in the associations.
A ∼60-min brisk walk increases insulin-stimulated glucose disposal but has no effect on hepatic and adipose tissue insulin sensitivity in older women
Authors: Wang Xuewen , Patterson Bruce W. , Smith Gordon I. , Kampelman Janine , Reeds Dominic N. , Sullivan Shelby A. , Mittendorfer Bettina
Published: March 2013

The purpose of this study was to determine whether brisk walking improves multiorgan (liver, muscle, adipose tissue) insulin sensitivity in older women. Ten nonobese older women (age: 66.7 ± 1.5 yr, mean ± SE) completed two 2-stage hyperinsulinemic-euglycemic clamp procedures [insulin infusion rate stage 1: 10 mU/m2body surface area (BSA) per min; stage 2: 50 mU/m2BSA per min] in conjunction with stable isotope-labeled glucose and palmitate tracer infusions: one in the morning after a single, ∼1-h bout of brisk treadmill walking, the other after an equivalent period of rest in the late afternoon of the preceding day. We found that basal glucose rate of appearance (Ra) into plasma was not different after rest and after exercise (17.3 ± 0.8 and 17.1 ± 0.4 μmol/kg fat-free mass per min, respectively). The insulin-mediated decrease in glucose Ra during stage 1 of the clamp was also not different after rest and exercise (82.2% ± 3.4% and 77.7% ± 2.1%, respectively), but glucose rate of disappearance (Rd) during stage 2 of the clamp was significantly greater ( P < 0.05) after exercise than rest (88.0 ± 5.9 and 78.4 ± 6.5 μmol/kg fat-free mass per min, respectively). There were no differences in palmitate Ra during basal conditions or insulin infusion after exercise and after rest. Therefore, we conclude that a single bout of brisk walking for ∼1 h improves muscle insulin sensitivity but has no effect on liver and adipose tissue insulin sensitivity in older women.
A single bout of aerobic exercise promotes motor cortical neuroplasticity
Authors: McDonnell Michelle N. , Buckley Jonathan D. , Opie George M. , Ridding Michael C. , Semmler John G.
Published: March 2013

Regular physical activity is associated with enhanced plasticity in the motor cortex, but the effect of a single session of aerobic exercise on neuroplasticity is unknown. The aim of this study was to compare corticospinal excitability and plasticity in the upper limb cortical representation following a single session of lower limb cycling at either low or moderate intensity, or a control condition. We recruited 25 healthy adults to take part in three experimental sessions. Cortical excitability was examined using transcranial magnetic stimulation to elicit motor-evoked potentials in the right first dorsal interosseus muscle. Levels of serum brain-derived neurotrophic factor and cortisol were assessed throughout the experiments. Following baseline testing, participants cycled on a stationary bike at a workload equivalent to 57% (low intensity, 30 min) or 77% age-predicted maximal heart rate (moderate intensity, 15 min), or a seated control condition. Neuroplasticity within the primary motor cortex was then examined using a continuous theta burst stimulation (cTBS) paradigm. We found that exercise did not alter cortical excitability. Following cTBS, there was a transient inhibition of first dorsal interosseus motor-evoked potentials during control and low-intensity conditions, but this was only significantly different following the low-intensity state. Moderate-intensity exercise alone increased serum cortisol levels, but brain-derived neurotrophic factor levels did not increase across any condition. In summary, low-intensity cycling promoted the neuroplastic response to cTBS within the motor cortex of healthy adults. These findings suggest that light exercise has the potential to enhance the effectiveness of motor learning or recovery following brain damage.
Increased mechanical strain imposed on murine lungs during ventilation in vivo depresses airway responsiveness and activation of protein kinase Akt
Authors: Xue Z. , Zhang W. , Desai L. P. , Gao H. , Gunst S. J. , Tepper R. S.
Published: March 2013

Continuous positive airway pressure (CPAP) administered to tracheostomized rabbits and ferrets for 4 days or 2 wk suppresses bronchial reactivity in vivo and suppresses airway reactivity in lobes and tracheal segments isolated from these animals. In vitro studies of canine tracheal smooth muscle tissues indicate that mechanical loading suppresses the activation of the growth regulatory kinase, Akt, and that Akt is a negative regulator of smooth muscle differentiation. The transduction of mechanical signals in the tracheal tissues in vitro is mediated by integrin-associated adhesion complexes. To determine whether airway responsiveness and Akt activation are modulated by mechanical loads applied for short time periods to the airways of living animals in vivo, mice were mechanically ventilated for 2 h with high (5 cmH2O) or low (0–1 cmH2O) positive end-expiratory pressure (PEEP) and then ventilated at low PEEP for 30 min. Ventilation of mice with PEEP in vivo for 2 h depressed airway responsiveness to methacholine measured in vivo subsequent to the PEEP treatment. Airway narrowing in vitro in intraparenchymal airways in isolated lung slices and contractile responses of isolated tracheal segments in vitro were suppressed for at least 6 h subsequent to the in vivo exposure to PEEP. Tracheal segments isolated from high PEEP-treated mice exhibited significantly lower levels of Akt activation than tracheae from low PEEP-treated mice. The results indicate that mechanical loads imposed in vivo result in physiological and biochemical changes in the airway tissues after a relatively short 2-h period of in vivo loading.
Local metabolic rate during whole body vibration
Authors: Friesenbichler Bernd , Nigg Benno M. , Dunn Jeff F.
Published: March 2013

Whole body vibration (WBV) platforms are currently used for muscle training and rehabilitation. However, the effectiveness of WBV training remains elusive, since scientific studies vary largely in the vibration parameters used. The origin of this issue may be related to a lack in understanding of the training intensity that is imposed on individual muscles by WBV. Therefore, this study evaluates the training intensity in terms of metabolic rate of two lower-extremity muscles during WBV under different vibration parameters. Fourteen healthy male subjects were randomly exposed to 0 (control)-, 10-, 17-, and 28-Hz vibrations while standing upright on a vibration platform. A near-infrared spectrometer was used to determine the gastrocnemius medialis (GM) and vastus lateralis (VL) muscles' metabolic rates during arterial occlusion. The metabolic rates during each vibration condition were significantly higher compared with control for both muscles ( P < 0.05). Each increase in vibration frequency translated into a significantly higher metabolic rate than the previous lower frequency ( P < 0.05) for both muscles. The current study showed that the local metabolic rate during WBV at 28 Hz was on average 5.4 times (GM) and 3.7 times (VL) of the control metabolic rate. The substantial changes in local metabolic rate indicate that WBV may represent a significant local training stimulus for particular leg muscles.
Surviving Emphysematous Gastritis after Hepatectomy
Authors: Yu Harry Hok Yee , Tsang Simon , Cheung Tan To , Lo Chung Mau
Published: March 2013

Emphysematous gastritis is a rare variant of phlegmonous gastritis due to invasion of stomach wall by gas-forming bacteria. It is characterised by abnormal presence of gas in the stomach by imaging, in association with clinical sepsis. Patients suffering from this condition usually present with an underlying pathology. We are reporting a middle-aged Chinese male with hepatitis B virus related hepatocellular carcinoma. He underwent partial hepatectomy and was diagnosed with emphysematous gastritis 4 days after index operation. Emergency laparotomy, including upper endoscopy, was performed. He was managed with antibiotics and discharged 18 days after second operation. This paper shows a review of the literature about the disease, with particular attention to pathology, clinical features, and management.
Extinctions of Late Ice Age Cave Bears as a Result of Climate/Habitat Change and Large Carnivore Lion/Hyena/Wolf Predation Stress in Europe
Authors: Diedrich Cajus G.
Published: March 2013

Predation onto cave bears (especially cubs) took place mainly by lionPanthera leo spelaea(Goldfuss), as nocturnal hunters deep in the dark caves in hibernation areas. Several cave bear vertebral columns in Sophie’s Cave have large carnivore bite damages. Different cave bear bones are chewed or punctured. Those lets reconstruct carcass decomposition and feeding technique caused only/mainly by Ice Age spotted hyenasCrocuta crocuta spelaea, which are the only of all three predators that crushed finally the long bones. Both large top predators left large tooth puncture marks on the inner side of cave bear vertebral columns, presumably a result of feeding first on their intestines/inner organs. Cave bear hibernation areas, also demonstrated in the Sophie’s Cave, were far from the cave entrances, carefully chosen for protection against the large predators. The predation stress must have increased on the last and larger cave bear populations ofU. ingressus(extinct around 25.500 BP) in the mountains as result of disappearing other seasonally in valleys migrating mammoth steppe fauna due to climate change and maximum glacier extensions around 22.000 BP.
Electrical and Thermal Characterization of Electrospun PVP Nanocomposite Fibers
Authors: Khan Waseem S. , Asmatulu Ramazan , Eltabey Mohamed M.
Published: March 2013

Polyvinylpyrrolidone (PVP) solutions incorporated with multiwall carbon nanotubes (MWCNTs) were electrospun at various weight percentages, and then the electrical resistance and some thermal properties of these nanocomposite fibers were determined using a high‐accuracy electrical resistance measurement device. During the electrospinning process, system and process parameters, such as concentrations, applied voltage, tip‐to‐collector distance, and pump speeds, were optimized to receive the consistent nanocomposite fibers. When polymers are used in many industrial applications, they require high electrical and thermal conductivities. Most polymers exhibit low electrical conductivity values; however, in the presence of conductive inclusions, the electrical resistance of the MWCNT fibers was reduced from 50 MΩ to below 5 MΩ, which may be attributed to the higher electrical conductivities of these nanoscale inclusions and fewer voids under the applied loads. This study may open up new possibilities in the field for developing electrically conductive novel nanomaterials and devices for various scientific and technological applications.
Is Oxidative Stress in Mice Brain Regions Diminished by 2-[(2,6-Dichlorobenzylidene)amino]-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carbonitrile?
Authors: Fortes A. C. , Almeida A. A. C. , Oliveira G. A. L. , Santos P. S. , De Lucca Junior W. , Mendonça Junior F. J. B. , Freitas R. M. , Soares-Sobrinho J. L. , Soares M. F. R.
Published: March 2013

2-[(2,6-Dichlorobenzylidene)amino]-5,6-dihydro-4H-cyclopenta[b]thiophene-3-carbonitrile, 5TIO1, is a new 2-aminothiophene derivative with promising pharmacological activities. The aim of this study was to evaluate its antioxidant activity in different areas of mice central nervous system. Male Swiss adult mice were intraperitoneally treated with Tween 80 dissolved in 0.9% saline (control group) and 5TIO1 (0.1, 1, and 10 mg kg−1). Brain homogenates—hippocampus, striatum, frontal cortex, and cerebellum—were obtained after 24 h of observation. Superoxide dismutase and catalase activities, lipid peroxidation and nitrite content were measured using spectrophotometrical methods. To clarify the 5TIO1’s mechanism on oxidative stress, western blot analysis of superoxide dismutase and catalase was also performed. 5TIO1 decreased lipid peroxidation and nitrite content in all brain areas and increased the antioxidant enzymatic activities, specially, in cerebellum. The data of Western blot analysis did not demonstrate evidence of the upregulation of these enzymes after the administration of this compound. Our findings strongly support that 5TIO1 can protect the brain against neuronal damages regularly observed during neuropathologies.
Patient Perspective on Use of an Interactive Website for Sleep Apnea
Authors: Stepnowsky Carl , Edwards Christine , Zamora Tania , Barker Robert , Agha Zia
Published: March 2013

Incomplete patient adherence with nasal continuous positive airway pressure (CPAP) limits the effectiveness of treatment and results in suboptimal obstructive sleep apnea (OSA) outcomes. An interactive website specifically designed for patients with OSA was designed and utilized in a randomized clinical trial to test its effect on increasing CPAP adherence. The goal of this paper is to report on CPAP adherence, internet use, privacy concerns and user satisfaction in using the website. The original project was designed as a randomized, controlled clinical trial of Usual Care (UC, control) versus MyCPAP group (intervention). Questionnaires were administered to evaluate the patient perspective of using the MyCPAP website. Participation in the MyCPAP intervention resulted in higher CPAP adherence at the two-month time point relative to participation in the UC group (3.4  ±  2.4 and 4.1  ±  2.3 hrs/nt;P=0.02; mean  ±  SD). Participants randomized to the MyCPAP website increased their use of the internet to obtain OSA related information, but did not increase their use of the internet to get information on general health or medical conditions. Users had very little concern about their CPAP data being viewed daily or being sent over the internet. Future studies should consider the use of newer evaluation criteria for collaborative adaptive interactive technologies.