bluuebunny/crossref_metadata_2025 huggingface dataset:
Integration of Photo-Patternable Low-κ Material into Advanced Cu Back-End-Of-The-Line
Authors: Lin Qinghuang , Nelson Alshakim , Chen Shyng-Tsong , Brock Philip , Cohen Stephan A. , Davis Blake , Kaplan Richard , Kwong Ranee , Liniger Eric , Neumayer Debra , Patel Jyotica , Shobha Hosadurga , Sooriyakumaran Ratnam , Purushothaman Sampath , Miller Robert , Spooner Terry , Wisnieff Robert
Published: May 2010

We report herein the demonstration of a simple, low-cost Cu back-end-of-the-line (BEOL) dual-damascene integration using a novel photo-patternable low-κ dielectric material concept that dramatically reduces Cu BEOL integration complexity. This κ=2.7 photo-patternable low-κ material is based on the SiCOH-based material platform and has sub-200 nm resolution capability with 248 nm optical lithography. Cu/photo-patternable low-κ dual-damascene integration at 45 nm node BEOL fatwire levels has been demonstrated with very high electrical yields using the current manufacturing infrastructure. The photo-patternable low-κ concept is, therefore, a promising technology for highly efficient semiconductor Cu BEOL manufacturing.
Cu Dual-Damascene Interconnects with Direct Chemical Mechanical Polishing Process on Porous Low-k Film
Authors: Izumitani Junko , Kodama Daisuke , Kido Shigenori , Chibahara Hiroyuki , Oka Yoshihiro , Goto Kinya , Suzumura Naohito , Fujisawa Masahiko , Miyatake Hiroshi
Published: May 2010

To reduce the effective dielectric constant (k
eff) value for 32 nm node technology and beyond, the effects of a direct chemical mechanical polishing (CMP) process on porous low-k film without a protective cap layer were investigated. It was confirmed that a capless structure on porous low-k film is effective in reducing the resistance–capacitance (RC) products, but it causes degradation of wire-to-wire breakdown voltage characteristics. The most important point of a direct CMP process is to control the amount of damage to the polished surface. In this study, two types of low-k film were compared in combination with a variety of CMP process conditions. As results, we found that a direct CMP process has a positive effect on wire-to-wire current leakage and time-dependent dielectric breakdown (TDDB) reliability where a porous low-k film deposited by modified conditions is used. By optimizing the deposition and curing conditions, it is possible to control the distribution of different pore sizes in porous low-k film, which allows us to realize a highly reliable capless structure.
Integration of Porogen-Based Low-k Films: Influence of Capping Layer Thickness and Long Thermal Anneals on Low-k Damage and Reliability
Authors: Roest David De , Vereecke Bart , Huffman Craig , Heylen Nancy , Croes Kristof , Arai Hirofumi , Takamure Noboru , Beynet Julien , Sprey Hessel , Matsushita Kiyohiro , Kobayashi Nobuyoshi , Verdonck Patrick , Demuynck Steven , Beyer Gerald , Tokei Zsolt , Struyf Herbert
Published: May 2010

This paper discusses integration aspects of a porous low-k film (k ∼2.45) cured with a broadband UV lamp. Different process splits are discussed which could contribute to avoid integration induced damage and improve reliability. The main factor contributing to a successful integration is the presence of a thick (protecting) cap layer partially remaining after chemical mechanical polishing (CMP), which leads to yielding structures with a k
eff of ∼2.6, a breakdown voltage of ∼6.9 MV/cm and time dependent dielectric breakdown (TDDB) lifetimes in the excess of 100 years. Long thermal anneals restore the k-value but degrade lifetime.
High-Etching-Selectivity Barrier SiC (k<3.5) Film for 32-nm-Node Copper/Low-k Interconnects
Authors: Nakahira Junya , Nagano Shuji , Gawase Akifumi , Ohashi Yoshi , Shimizu Hideharu , Chikaki Shinichi , Oda Noriaki , Kondo Seiichi , Hasaka Satoshi , Saito Shuichi
Published: May 2010

Copper (Cu)/low-k interconnects were fabricated using novel Cu diffusion-barrier SiC films deposited with a novel precursor, 1,1-divinyl-silacyclopentane (DVScP). At 46% overetching time, the yield of the via-contact with the dielectric barrier of conventional SiC films was seriously reduced, while that of the novel SiC films was hardly reduced. By using the novel SiC films, the thickness of diffusion barriers was successfully reduced to 15 nm, matching the 32 nm node and beyond. By using the novel SiC films, the dielectric constant of the barrier films was decreased and their thickness was reduced with no yield reduction of the via-contact. As a result, the product of wiring resistance and capacitance (RC product) was reduced by 11.4%. The time-dependent dielectric breakdown (TDDB) lifetime of Cu interconnects with the SiC films was similar to that with the SiCO films.
Statistical Analysis of Lifetime Distribution of Time-Dependent Dielectric Breakdown in Cu/Low-k Interconnects by Incorporation of Overlay Error Model
Authors: Yokogawa Shinji , Tsuchiya Hideaki
Published: May 2010

We propose a method for the statistical analysis of a via-to-line time-dependent dielectric breakdown (TDDB) test under misalignment impacts. The √E and overlay error models are incorporated into the lifetime distribution analysis in the framework of the Weibull regression model. The doubly truncated normal distribution effectively describes the space-decrease distribution that is estimated using the overlay error model. Incorporating these physical and statistical characteristics into the lifetime distribution analysis yields more reliable distribution parameters and helps to distinguish outliers as early failures with rejection of misalignment impacts.
Photoinduced Leakage Currents in Silicon Carbon Nitride Dielectrics for Copper Diffusion Barriers
Authors: Kobayashi Kiyoteru , Ide Taketoshi
Published: May 2010

The current conduction in silicon carbon nitride (SiCN) dielectric films subjected to ultraviolet (UV) illumination at room temperature has been investigated. After exposure of SiCN single-layer and SiCN–SiO2 double-layer films to 4.9-eV UV illumination, leakage currents through both films substantially increased under positive and negative gate biases. The current increased as a function of the change in paramagnetic defect density, which was obtained from electron spin resonance signals of the SiCN and SiCN–SiO2 films subjected to 4.9-eV UV illumination. We suggest that the paramagnetic defects, which have been identified as neutrally charged silicon dangling bonds, act as generation centers and that their formation is responsible for the current increase. The conduction mechanisms of the photoinduced leakage current are discussed in detail.
Step Coverage Quality of Cu Films by Supercritical Fluid Deposition Compared with Chemical Vapor Deposition
Authors: Momose Takeshi , Sugiyama Masakazu , Kondoh Eiichi , Shimogaki Yukihiro
Published: May 2010

Feasibility of step coverage (SC) by supercritical fluid deposition (SCFD) of Cu was evaluated using a finite element method (FEM) simulation with experimentally estimated kinetics and transport properties of the precursor. This SC by Cu-SCFD was compared with that by chemical vapor deposition (CVD). SCFD showed superior SC, especially for ultra narrow features less than 1 µm wide, although CVD has a higher diffusion coefficient. This superior SC was due to the non-linear reaction kinetics of SCFD (CVD has linear reaction kinetics), where precursor concentration had negligible effect on growth rate when the precursor concentration was higher than about 1 mol/L.
Novel Precursor for Development of Si–C2H4–Si Networks in SiCH for Application as a Low-k Cap Layer beyond 22 nm Nodes
Authors: Shimizu Hideharu , Tajima Nobuo , Kada Takeshi , Nagano Shuji , Ohashi Yoshi , Hasaka Satoshi
Published: May 2010

SiCH films are a potentially very useful low-k cap layer for covering Cu trenches in ultralarge-scale integration (ULSI) devices. To induce Si–C2H4–Si networks in SiCH film structures, 1,1-divinyl silacyclopentane (DVScP) and 5-silaspiro-[4,4]-nonane (SSN) were designed and prepared. Isobutyl trimethyl silane (iBTMS) and diisobutyl dimethyl silane (DiBDMS) were also designed to form Si–CH2–Si networks in the SiCH molecular structure. SiCH films were formed by plasma-enhanced chemical vapor deposition (PECVD), for use as a low-k cap layer and a Cu diffusion barrier on top of the Cu trenches. We demonstrated additional Si–C2H4–Si networks that can effectively suppress Cu diffusion in SiCH low-k barrier films with a reduced k-value of 3.1.
Proposal of New Precursors for Plasma-Enhanced Chemical Vapor Deposition of SiOCH Low-k Films with Plasma Damage Resistance
Authors: Ohashi Yoshi , Tajima Nobuo , Xu Yonghua , Kada Takeshi , Nagano Shuji , Shimizu Hideharu , Hasaka Satoshi
Published: May 2010

We propose new precursors for bulk low-k films with plasma damage resistance. Our newly designed precursors contain long-chain hydrocarbon groups such as i-butyl and n-propyl groups. Using these precursors, we successfully produced films containing Si–CH2–Si groups by plasma-enhanced chemical vapor deposition (PECVD). The plasma damage resistance of these films under NH3 plasma treatment was studied. It was found that the increase in the k-value (Δk) is smaller in films with more Si–CH2–Si groups.
Analysis on Copper Photocorrosion Induced by Illuminance in Chemical Mechanical Planarization Equipment Using Photodiode and Quartz Crystal Microbalance
Authors: Shima Shohei , Wada Yutaka , Tokushige Katsuhiko , Fukunaga Akira , Tsujimura Manabu
Published: May 2010

Photoassisted corrosion of copper (Cu) was evaluated using a photodiode and a quartz crystal microbalance (QCM). A chip-type silicon (Si) photodiode with a large junction area was used in place of actual Si devices. When the illuminated photodiode was connected to the anode and cathode electrodes in an electrolyte, it worked as a voltage source between the two electrodes, and the corrosion rate was governed by the current between the electrodes. The corrosion rate is nearly proportional to the illuminance at less than 100 lx, and corrosion initiates at an illuminance as low as 1 lx. In the geometrical aspect of the photoassisted corrosion system, the corrosion rate is proportional to the square root of the area ratio of a P-connected Cu line to an N line, and is proportional to the illuminated area of the junction in a photodiode. The wavelength of the illuminating light markedly affects the photoassisted corrosion.
Stress Analysis for Chip–Package Interaction of Cu/Low-k Multilayer Interconnects
Authors: Kumagai Yukihiro , Ohta Hiroyuki , Fujisawa Masahiko , Iwamoto Takeshi , Ohsaki Akihiko
Published: May 2010

Delamination failure of a low-k interlayer dielectric (ILD) layer of Cu/low-k multilayer interconnects during a thermal cycle test was investigated by mechanical stress simulation. A three-dimensional (3D) multilevel modeling method was used to analyze the stress that occurred in a fine-scale film stack in a large-scale package. The maximum stress occurred at the low-k/cap film interface that was located at the bottom surface of the low-k ILD layer. This maximum-stress interface coincides with the interface where the delamination occurred. Using this method, the effects of the number of ILD layers, the Young's modulus of the ILD, and the package type on the failure were investigated. This method is useful for reducing delamination failure.
Metabolic amplifying pathway increases both phases of insulin secretion independently of β-cell actin microfilaments
Authors: Mourad Nizar I. , Nenquin Myriam , Henquin Jean-Claude
Published: May 2010

Two pathways control glucose-induced insulin secretion (IS) by β-cells. The triggering pathway involves ATP-sensitive potassium (KATP) channel-dependent depolarization, Ca2+ influx, and a rise in the cytosolic Ca2+ concentration ([Ca2+]c), which triggers exocytosis of insulin granules. The metabolic amplifying pathway augments IS without further increasing [Ca2+]c. The underlying mechanisms are unknown. Here, we tested the hypothesis that amplification implicates actin microfilaments. Mouse islets were treated with latrunculin B and cytochalasin B to depolymerize actin or jasplakinolide to polymerize actin. They were then perifused to measure [Ca2+]c and IS. Metabolic amplification was studied during imposed steady elevation of [Ca2+]c by tolbutamide or KCl or by comparing the magnitude of [Ca2+]c and IS changes produced by glucose and tolbutamide. Both actin polymerization and depolymerization augmented IS triggered by all stimuli without increasing (sometimes decreasing) [Ca2+]c, which indicates a predominantly inhibitory function of microfilaments in exocytosis at a step distal to [Ca2+]c increase. When [Ca2+]c was elevated and controlled by KCl or tolbutamide, the amplifying action of glucose was facilitated by actin depolymerization and unaffected by polymerization. Both phases of IS were larger in response to high-glucose than to tolbutamide in low-glucose, although triggering [Ca2+]c was lower. This difference in IS, due to amplification, persisted when the IS rate was doubled by actin depolymerization or polymerization. In conclusion, metabolic amplification is rapid and influences the first as well as the second phase of IS. It is a late step of stimulus-secretion coupling, which does not require functional actin microfilaments and could correspond to acceleration of the priming process conferring release competence to insulin granules.
IFNγ-dependent SOCS3 expression inhibits IL-6-induced STAT3 phosphorylation and differentially affects IL-6 mediated transcriptional responses in endothelial cells
Authors: Bluyssen Hans A. R. , Rastmanesh M. Mehdi , Tilburgs Chantal , Jie Kim , Wesseling Sebastiaan , Goumans Marie-Jose , Boer Peter , Joles Jaap A. , Braam Branko
Published: May 2010

IL-6 has pro- and anti-inflammatory effects and is involved in endothelial cell (EC) dysfunction. The anti-inflammatory effects of IL-6 are mediated by signal transducer and activator of transcription-3 (STAT3), which is importantly controlled by suppressor of cytokine signaling 3 (SOCS3). Therefore, cytokines that modulate SOCS3 expression might inhibit the anti-inflammatory effects of IL-6. We hypothesized that in EC, interferon-γ (IFNγ)-induced SOCS3 expression leads to inhibition of IL-6-induced STAT3 activation and IL-6-dependent expression of anti-, but not pro-inflammatory, target genes. IFNγ activated STAT1 and STAT3 and increased SOCS3 expression in EC. IL-6 only activated STAT3 and induced SOCS3 expression. IFNγ pretreatment of EC inhibited IL-6-induced STAT3 activation accompanied by increased SOCS3 protein. Inhibition of SOCS3 expression, using costimulation, Act-D, and small interfering RNA (siRNA), subsequently implicated the importance of IFNγ-induced SOCS3 in this phenomenon. Pretreatment of EC with IFNγ also affected the transcriptional program induced by IL-6. We identified 1) IL-6 anti-inflammatory target genes that were inhibited by IFNγ, 2) IFNγ-target genes of pro-inflammatory nature that were increased in response to IL-6 in the presence of IFNγ, and 3) a set of target genes that were increased upon IL-6 or IFNγ alone, or combined IFNγ and IL-6. In summary, by increasing SOCS3 expression in EC, IFNγ can selectively inhibit STAT3-dependent IL-6 signaling. This in turn leads to decreased expression of some EC protective genes. In contrast, other genes of pro-inflammatory nature are not inhibited or even increased. This IFNγ-induced shift in IL-6 signaling to a pro-inflammatory phenotype could represent a novel mechanism involved in EC dysfunction.
Insulin sensitivity and body composition in cirrhosis: changes after TIPS
Authors: Holland-Fischer Peter , Nielsen Michael Festersen , Vilstrup Hendrik , Tønner-Nielsen Dennis , Mengel Anette , Schmitz Ole , Grønbæk Henning
Published: May 2010

Insertion of a transjugular intrahepatic porto-systemic shunt (TIPS) increases body cell mass (BCM) in patients with liver cirrhosis. The responsible mechanism is unidentified, but may involve changes in insulin sensitivity and glucose metabolism. Eleven patients with liver cirrhosis were examined before and 6 mo after a TIPS procedure with bioimpedance analyses, 2-h oral glucose tolerance tests, and two-step hyperinsulinemic euglycemic clamp with tracer-determined endogenous glucose production. After TIPS, BCM increased by 4.8 kg [confidence interval (CI): 2.7–7.3]. Fasting (f)-insulin increased from 123 ± 81 to 193 ± 124 pmol/l ( P = 0.03), whereas f-glucose was unchanged (6.0 ± 0.8 vs. 6.2 ± 1.0 mmol/l). Glucose and insulin oral glucose tolerance test area under the curve increased by 14% (CI: 7–22%) and 53% (CI: 14–90%), respectively, P < 0.05. The C-peptide-to-insulin ratio decreased by 21% (CI: 8-35%, P = 0.01). Insulin sensitivity based on glucose infusion rate (4.69 ± 1.82 vs. 4.85 ± 2.37 mg·kg−1·min−1) and glucose tracer-based rate of disappearance were unchanged (5.01 ± 1.61 vs. 4.97 ± 2.13 mg·kg−1·min−1). Despite a further increase in peripheral hyperinsulinemia, f-endogenous glucose production did not change between study days (2.01 ± 0.42 vs. 2.42 ± 0.58 mg·kg−1·min−1) and was suppressed equally by insulin (1.1 ± 0.1 vs. 1.0 ± 0.1 mg·kg−1·min−1). Insulin clearance, growth hormone, cortisol, and glucagon levels were unchanged. BCM improvement did not correlate with the measured variables. After TIPS, BCM rose, despite enhanced hyperinsulinemia and aggravated glucose intolerance, but unchanged peripheral and hepatic insulin sensitivity. This apparent discrepancy may be ascribed to shunt-related decreased insulin exposure to the liver cells. However, the anabolic effect of TIPS seems not to be related to improvements in insulin sensitivity and remains mechanistically unexplained.
Neural control of the female urethral and anal rhabdosphincters and pelvic floor muscles
Authors: Thor Karl B. , de Groat William C.
Published: May 2010

The urethral rhabdosphincter and pelvic floor muscles are important in maintenance of urinary continence and in preventing descent of pelvic organs [i.e., pelvic organ prolapse (POP)]. Despite its clinical importance and complexity, a comprehensive review of neural control of the rhabdosphincter and pelvic floor muscles is lacking. The present review places historical and recent basic science findings on neural control into the context of functional anatomy of the pelvic muscles and their coordination with visceral function and correlates basic science findings with clinical findings when possible. This review briefly describes the striated muscles of the pelvis and then provides details on the peripheral innervation and, in particular, the contributions of the pudendal and levator ani nerves to the function of the various pelvic muscles. The locations and unique phenotypic characteristics of rhabdosphincter motor neurons located in Onuf's nucleus, and levator ani motor neurons located diffusely in the sacral ventral horn, are provided along with the locations and phenotypes of primary afferent neurons that convey sensory information from these muscles. Spinal and supraspinal pathways mediating excitatory and inhibitory inputs to the motor neurons are described; the relative contributions of the nerves to urethral function and their involvement in POP and incontinence are discussed. Finally, a detailed summary of the neurochemical anatomy of Onuf's nucleus and the pharmacological control of the rhabdosphincter are provided.
Piscine PTHrP regulation of calcium and phosphate transport in winter flounder renal proximal tubule primary cultures
Authors: Guerreiro Pedro M. , Canario Adelino V. M. , Power Deborah M. , Renfro J. Larry
Published: May 2010

Multiple factors control calcium (Ca2+) and inorganic phosphate (Pi) transport in the fish nephron, and the recently discovered members of the piscine parathyroid hormone-like protein family are likely participants in such regulatory mechanisms. The effects of an NH2-terminal peptide (amino acids 1–34) of Takifugu rubripes parathyroid hormone-related protein, (1–34)PTHrP, on Ca2+and Pitransport were investigated in winter flounder ( Pseudopleuronectes americanus ) proximal tubule cells in primary culture (fPTCs). RT-PCR performed on RNA extracted from fPTCs and from intact kidney tissue indicated that expression of PTHrP and types 1 and 3 PTH/PTHrP receptors occurred both in vivo and in vitro and that circulating levels of PTHrP measured by specific radioimmunoassay averaged 2.5 ± 0.13 ng/ml. fPTC monolayers were mounted in Ussing chambers, and under neutral electrochemical conditions, addition of 10 nM (1–34)PTHrP to the basolateral side induced a slight increase in Ca2+transport rate from luminal to peritubular side, significantly stimulating net Ca2+reabsorption. (1–34)PTHrP also significantly increased the Pisecretory flux, and slightly reduced Pireabsorption, evoking a significant increase in Pinet secretion. This stimulatory effect was partially inhibited by bisindolylmaleimide, an inhibitor of protein kinase C. Incubation of ex vivo flounder renal tubules with (1–34)PTHrP resulted in apparent reduction of Na+-Picotransporter type II (NaPi-II) protein in tubule membranes. PTHrP seems therefore to participate in the modulation of Ca2+and Pihomeostasis by fish kidney.
Reduced systolic pressure load decreases cell-cycle activity in the fetal sheep heart
Authors: O'Tierney P. F. , Anderson D. F. , Faber J. J. , Louey S. , Thornburg K. L. , Giraud G. D.
Published: May 2010

The fetal heart is highly sensitive to changes in mechanical load. We have previously demonstrated that increased cardiac load can stimulate cell cycle activity and maturation of immature cardiomyocytes, but the effects of reduced load are not known. Sixteen fetal sheep were given either continuous intravenous infusion of lactated Ringer solution (LR) or enalaprilat, an angiotensin-converting enzyme inhibitor beginning at 127 days gestational age. After 8 days, fetal arterial pressure in the enalaprilat-infused fetuses (23.8 ± 2.8 mmHg) was lower than that of control fetuses (47.5 ± 4.7 mmHg) ( P < 0.0001). Although the body weights of the two groups of fetuses were similar, the heart weight-to-body weight ratios of the enalaprilat-infused fetuses were less than those of the LR-infused fetuses (5.6 ± 0.5 g/kg vs. 7.0 ± 0.6 g/kg, P < 0.0001). Dimensions of ventricular myocytes were not different between control and enalaprilat-infused fetuses. However, there was a significant decrease in cell cycle activity in both the right ventricle ( P < 0.005) and the left ventricle ( P < 0.002) of the enalaprilat-infused fetuses. Thus, we conclude a sustained reduction in systolic pressure load decreases hyperplastic growth in the fetal heart.
Effect of glycogen availability on human skeletal muscle protein turnover during exercise and recovery
Authors: Howarth Krista R. , Phillips Stuart M. , MacDonald Maureen J. , Richards Douglas , Moreau Natalie A. , Gibala Martin J.
Published: May 2010

We examined the effect of carbohydrate (CHO) availability on whole body and skeletal muscle protein utilization at rest, during exercise, and during recovery in humans. Six men cycled at ∼75% peak O2 uptake (V̇o2peak) to exhaustion to reduce body CHO stores and then consumed either a high-CHO (H-CHO; 71 ± 3% CHO) or low-CHO (L-CHO; 11 ± 1% CHO) diet for 2 days before the trial in random order. After each dietary intervention, subjects received a primed constant infusion of [1-13C]leucine and l-[ring-2H5]phenylalanine for measurements of the whole body net protein balance and skeletal muscle protein turnover. Muscle, breath, and arterial and venous blood samples were obtained at rest, during 2 h of two-legged kicking exercise at ∼45% of kicking V̇o2peak, and during 1 h of recovery. Biopsy samples confirmed that the muscle glycogen concentration was lower in the L-CHO group versus the H-CHO group at rest, after exercise, and after recovery. The net leg protein balance was decreased in the L-CHO group compared with at rest and compared with the H-CHO condition, which was primarily due to an increase in protein degradation (area under the curve of the phenylalanine rate of appearance: 1,331 ± 162 μmol in the L-CHO group vs. 786 ± 51 μmol in the H-CHO group, P < 0.05) but also due to a decrease in protein synthesis late in exercise. There were no changes during exercise in the rate of appearance compared with rest in the H-CHO group. Whole body leucine oxidation increased above rest in the L-CHO group only and was higher than in the H-CHO group. The whole body net protein balance was reduced in the L-CHO group, largely due to a decrease in whole body protein synthesis. These data extend previous findings by others and demonstrate, using contemporary stable isotope methodology, that CHO availability influences the rates of skeletal muscle and whole body protein synthesis, degradation, and net balance during prolonged exercise in humans.
Temporal Patterns of Inputs to Cerebellum Necessary and Sufficient for Trace Eyelid Conditioning
Authors: Kalmbach Brian E. , Ohyama Tatsuya , Mauk Michael D.
Published: May 2010

Trace eyelid conditioning is a form of associative learning that requires several forebrain structures and cerebellum. Previous work suggests that at least two conditioned stimulus (CS)-driven signals are available to the cerebellum via mossy fiber inputs during trace conditioning: one driven by and terminating with the tone and a second driven by medial prefrontal cortex (mPFC) that persists through the stimulus-free trace interval to overlap in time with the unconditioned stimulus (US). We used electric stimulation of mossy fibers to determine whether this pattern of dual inputs is necessary and sufficient for cerebellar learning to express normal trace eyelid responses. We find that presenting the cerebellum with one input that mimics persistent activity observed in mPFC and the lateral pontine nuclei during trace eyelid conditioning and another that mimics tone-elicited mossy fiber activity is sufficient to produce responses whose properties quantitatively match trace eyelid responses using a tone. Probe trials with each input delivered separately provide evidence that the cerebellum learns to respond to the mPFC-like input (that overlaps with the US) and learns to suppress responding to the tone-like input (that does not). This contributes to precisely timed responses and the well-documented influence of tone offset on the timing of trace responses. Computer simulations suggest that the underlying cerebellar mechanisms involve activation of different subsets of granule cells during the tone and during the stimulus-free trace interval. These results indicate that tone-driven and mPFC-like inputs are necessary and sufficient for the cerebellum to learn well-timed trace conditioned responses.
The Lateral Paragigantocellular Nucleus Modulates Parasympathetic Cardiac Neurons: A Mechanism for Rapid Eye Movement Sleep-Dependent Changes in Heart Rate
Authors: Dergacheva Olga , Wang Xin , Lovett-Barr Mary R. , Jameson Heather , Mendelowitz David
Published: May 2010

Rapid eye movement (REM) sleep is generally associated with a withdrawal of parasympathetic activity and heart rate increases; however, episodic vagally mediated heart rate decelerations also occur during REM sleep. This alternating pattern of autonomic activation provides a physiological basis for REM sleep-induced cardiac arrhythmias. Medullary neurons within the lateral paragigantocellular nucleus (LPGi) are thought to be active after REM sleep recovery and play a role in REM sleep control. In proximity to the LPGi are parasympathetic cardiac vagal neurons (CVNs) within the nucleus ambiguus (NA), which are critical for controlling heart rate. This study examined brain stem pathways that may mediate REM sleep-related reductions in parasympathetic cardiac activity. Electrical stimulation of the LPGi evoked inhibitory GABAergic postsynaptic currents in CVNs in an in vitro brain stem slice preparation in rats. Because brain stem cholinergic mechanisms are involved in REM sleep regulation, we also studied the role of nicotinic neurotransmission in modulation of GABAergic pathway from the LGPi to CVNs. Application of nicotine diminished the GABAergic responses evoked by electrical stimulation. This inhibitory effect of nicotine was prevented by the α7 nicotinic receptor antagonist α-bungarotoxin. Moreover, hypoxia/hypercapnia (H/H) diminished LPGi-evoked GABAergic current in CVNs, and this inhibitory effect was also prevented by α-bungarotoxin. In conclusion, stimulation of the LPGi evokes an inhibitory pathway to CVNs, which may constitute a mechanism for the reduced parasympathetic cardiac activity and increase in heart rate during REM sleep. Inhibition of this pathway by nicotinic receptor activation and H/H may play a role in REM sleep-related and apnea-associated bradyarrhythmias.
GABA Shapes a Systematic Map of Binaural Sensitivity in the Auditory Cortex
Authors: Razak Khaleel A. , Fuzessery Zoltan M.
Published: May 2010

A consistent organizational feature of auditory cortex is a clustered representation of binaural properties. Here we address two questions. What is the intrinsic organization of binaural clusters and to what extent does intracortical processing contribute to binaural representation. We address these issues in the auditory cortex of the pallid bat. The pallid bat listens to prey-generated noise transients to localize and hunt terrestrial prey. As in other species studied, binaural clusters are present in the auditory cortex of the pallid bat. One cluster contains neurons that require binaural stimulation to be maximally excited, and are commonly termed predominantly binaural (PB) neurons. These neurons do not respond to monaural stimulation of either ear but show a peaked sensitivity to interaural intensity differences (IID) centered near 0 dB IID. We show that the peak IID varies systematically within this cluster. The peak IID is also correlated with the best frequency (BF) of neurons within this cluster. In addition, the IID selectivity of PB neurons is shaped by intracortical GABAergic input. Iontophoresis of GABAA receptor antagonists on PB neurons converts a majority of them to binaurally inhibited (EI) neurons that respond best to sounds favoring the contralateral ear. These data indicate that the cortex does not simply inherit binaural properties from lower levels but instead sharpens them locally through intracortical inhibition. The IID selectivity of the PB cluster indicates that the pallid bat cortex contains an increased representation of the frontal space that may underlie increased localization accuracy in this region.
Motor Memory and Local Minimization of Error and Effort, Not Global Optimization, Determine Motor Behavior
Authors: Ganesh G. , Haruno M. , Kawato M. , Burdet E.
Published: May 2010

Many real life tasks that require impedance control to minimize motion error are characterized by multiple solutions where the task can be performed either by co-contracting muscle groups, which requires a large effort, or, conversely, by relaxing muscles. However, human motor optimization studies have focused on tasks that are always satisfied by increasing impedance and that are characterized by a single error-effort optimum. To investigate motor optimization in the presence of multiple solutions and hence optima, we introduce a novel paradigm that enables us to let subjects repetitively (but inconspicuously) use different solutions and observe how exploration of multiple solutions affect their motor behavior. The results show that the behavior is largely influenced by motor memory with subjects tending to involuntarily repeat a recent suboptimal task-satisfying solution even after sufficient experience of the optimal solution. This suggests that the CNS does not optimize co-activation tasks globally but determines the motor behavior in a tradeoff of motor memory, error, and effort minimization.
Genotoxic and Cytotoxic Safety Evaluation of Papain (Carica papayaL.) Using In Vitro Assays
Authors: Silva Claudia R. da , Oliveira Marcia B. N. , Motta Ellen S. , Almeida Gabriella S. de , Varanda Leandro L. , Pádula Marcelo de , Leitão Alvaro C. , Caldeira-de-Araújo Adriano
Published: May 2010

Papain, a phytotherapeutic agent, has been used in the treatment of eschars and as a debriding chemical agent to remove damaged or necrotic tissue of pressure ulcers and gangrene. Its benefits in these treatments are deemed effective, since more than 5000 patients, at the public university hospital at Rio de Janeiro, Brazil, have undergone papain treatment and presented satisfactory results. Despite its extensive use, there is little information about toxic and mutagenic properties of papain. This work evaluated the toxic and mutagenic potential of papain and its potential antioxidant activity against induced-H2O2oxidative stress inEscherichia colistrains. Cytotoxicity assay, Growth inhibition test, WP2-Mutoxitest and Plasmid-DNA treatment, and agarose gel electrophoresis were used to investigate if papain would present any toxic or mutagenic potential as well as if papain would display antioxidant properties. Papain exhibited negative results for all tests. This agent presented an activity protecting cells againstH2O2-induced mutagenesis.
Inflammatory Mediators and Insulin Resistance in Obesity: Role of Nuclear Receptor Signaling in Macrophages
Authors: Fuentes Lucía , Rőszer Tamás , Ricote Mercedes
Published: May 2010

Visceral obesity is coupled to a general low-grade chronic inflammatory state characterized by macrophage activation and inflammatory cytokine production, leading to insulin resistance (IR). The balance between proinflammatory M1 and antiinflammatory M2 macrophage phenotypes within visceral adipose tissue appears to be crucially involved in the development of obesity-associated IR and consequent metabolic abnormalities. The ligand-dependent transcription factors peroxisome proliferator activated receptors (PPARs) have recently been implicated in the determination of the M1/M2 phenotype. Liver X receptors (LXRs), which form another subgroup of the nuclear receptor superfamily, are also important regulators of proinflammatory cytokine production in macrophages. Disregulation of macrophage-mediated inflammation by PPARs and LXRs therefore underlies the development of IR. This review summarizes the role of PPAR and LXR signaling in macrophages and current knowledge about the impact of these actions in the manifestation of IR and obesity comorbidities such as liver steatosis and diabetic osteopenia.
Blockade of NR2A-Containing NMDA Receptors Induces Tau Phosphorylation in Rat Hippocampal Slices
Authors: Allyson Julie , Dontigny Eve , Auberson Yves , Cyr Michel , Massicotte Guy
Published: May 2010

Physiological activation of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors has been proposed to play a key role in both neuronal cell function and dysfunction. In the present study, we used selective NMDA receptor antagonists to investigate the involvement of NR2A and NR2B subunits in the modulatory effect of basal NMDA receptor activity on the phosphorylation of Tau proteins. We observed, in acute hippocampal slice preparations, that blockade of NR2A-containing NMDA receptors by the NR2A antagonist NVP-AAM077 provoked the hyperphosphorylation of a residue located in the proline-rich domain of Tau (i.e., Ser199). This effect seemed to be Ser199 specific as there was no increase in phosphorylation at Ser262 and Ser409 residues located in the microtubule-binding and C-terminal domains of Tau proteins, respectively. From a mechanistic perspective, our study revealed that blockade of NR2A-containing receptors influences Tau phosphorylation probably by increasing calcium influx into neurons, which seems to rely on accumulation of new NR1/NR2B receptors in neuronal membranes and could involve the cyclin-dependent kinase 5 pathway.
Multimodal Indexing of Multilingual News Video
Authors: Ghosh Hiranmay , Kopparapu Sunil Kumar , Chattopadhyay Tanushyam , Khare Ashish , Wattamwar Sujal Subhash , Gorai Amarendra , Pandharipande Meghna
Published: May 2010

The problems associated with automatic analysis of news telecasts are more severe in a country like India, where there are many national and regional language channels, besides English. In this paper, we present a framework for multimodal analysis of multilingual news telecasts, which can be augmented with tools and techniques for specific news analytics tasks. Further, we focus on a set of techniques for automatic indexing of the news stories based on keywords spotted in speech as well as on the visuals of contemporary and domain interest. English keywords are derived from RSS feed and converted to Indian language equivalents for detection in speech and on ticker texts. Restricting the keyword list to a manageable number results in drastic improvement in indexing performance. We present illustrative examples and detailed experimental results to substantiate our claim.
Sympathetic Neurotransmitters and Tumor Angiogenesis—Link between Stress and Cancer Progression
Authors: Tilan Jason , Kitlinska Joanna
Published: May 2010

Recent evidence supports a longstanding hypothesis that chronic stress can influence tumor growth and progression. It has been shown that sympathetic neurotransmitters, such as catecholamines and neuropeptides, can affect both cancer cell growth and tumor vascularization. Depending on neurotransmitter and type of tumor, these effects can be both stimulatory and inhibitory. Norepinephrine (NE) and epinephrine (E) are potent stimulators of vascularization, acting both by inducing the release of angiogenic factors from tumor cells and directly on endothelial cell (EC) functions. As a result, activation of the adrenergic system increases growth of various types of tumors and has been shown to mediate stress-induced augmentation of tumor progression. Dopamine (DA), on the other hand, interferes with VEGF signaling in endothelial cells, blocks its angiogenic functions and inhibits tumor growth. Another sympathetic neurotransmitter coreleased with NE, neuropeptide Y (NPY), directly stimulates angiogenesis. However, proangiogenic actions of NPY can be altered by its direct effect on tumor cell proliferation and survival. In consequence, NPY can either stimulate or inhibit tumor growth, depending on tumor type. Hence, sympathetic neurotransmitters are powerful modulators of tumor growth and can become new targets in cancer therapy.
Level Sets of Random Fields and Applications: Specular Points and Wave Crests
Authors: Flores Esteban , León R José R.
Published: May 2010

We apply Rice′s multidimensional formulas, in a mathematically rigorous
way, to several problems which appear in random sea modeling. As a first example, the probability
density function of the velocity of the specular points is obtained in one or two dimensions as well
as the expectation of the number of specular points in two dimensions. We also consider, based on a
multidimensional Rice formula, a curvilinear integral with respect to the level curve. It follows that its
expected value allows defining the Palm distribution of the angle of the normal of the curve that defines
the waves crest. Finally, we give a new proof of a general multidimensional Rice formula, valid for all
levels, for a stationary and smooth enough random fields X : ℝd → ℝj(d > j).
Energy and Environmental Performance of Bioethanol from Different Lignocelluloses
Authors: Luo Lin , van der Voet Ester , Huppes Gjalt
Published: May 2010

Climate change and the wish to reduce the dependence on oil are the incentives for the development of alternative energy sources. The use of lignocellulosic biomass together with cellulosic processing technology provides opportunities to produce fuel ethanol with less competition with food and nature. Many studies on energy analysis and life cycle assessment of second-generation bioethanol have been conducted. However, due to the different methodology used and different system boundary definition, it is difficult to compare their results. To permit a direct comparison of fuel ethanol from different lignocelluloses in terms of energy use and environmental impact, seven studies conducted in our group were summarized in this paper, where the same technologies were used to convert biomass to ethanol, the same system boundaries were defined, and the same allocation procedures were followed. A complete set of environmental impacts ranging from global warming potential to toxicity aspects is used. The results provide an overview on the energy efficiency and environmental performance of using fuel ethanol derived from different feedstocks in comparison with gasoline.
Discrepancy between mRNA and Protein Expression of Neutrophil Gelatinase-Associated Lipocalin in Bronchial Epithelium Induced by Sulfur Mustard
Authors: Ebrahimi Majid , Roudkenar Mehryar Habibi , Imani Fooladi Abbas Ali , Halabian Raheleh , Ghanei Mostafa , Kondo Hisatake , Nourani Mohammad Reza
Published: May 2010

Sulfur mustard (SM) is a potent vesicant that has been employed as a chemical weapon in various conflicts during the 20th century. More recently, mustard was used in the Iraq conflict against Iranian troops and civilians. At the present time there are more than 40.000 people suffering from pulmonary lesions special bronchiolitis obliterans (BOs) due to mustard gas. SM increases the endogenous production of reactive oxygen species (ROS). Neutrophil Gelatinase-associated Lipocalin 2 (Lcn2, NGAL) is a member of the lipocalin superfamily for which a variety of functions such as cellular protection against oxidative stress have been reported. Ten normal and Twenty SM-induced COPD patient individuals were studied. Assessment of NGAL expressions in healthy and the patients endobrinchial biopsies were performed by semiquantitative RT-PCR, real-time RT-PCR, and Immunohistochemistry analysis. While Normal control samples expressed same level of mRNA NGAL, expression level of mRNA-NGAL was upregulated about 1.4- to 9.8-folds compared to normal samples. No significant immunoreactivity was revealed in both samples. As we are aware this is the first report of induction of NGAL in patients exposed to SM. NGAL may play an important role in cellular protection against oxidative stress toxicity induced by mustard gas in airway wall of patients.
Synopsis of Preterm Birth Genetic Association Studies: The Preterm Birth Genetics Knowledge Base (PTBGene)
Authors: Dolan S.M. , Hollegaard M.V. , Merialdi M. , Betran A.P. , Allen T. , Abelow C. , Nace J. , Lin B.K. , Khoury M.J. , Ioannidis J.P.A. , Bagade S. , Zheng X. , Dubin R.A. , Bertram L. , Velez Edwards D.R. , Menon R.
Published: May 2010

Aim: Our goal wasto produce a field synopsis of genetic associations with preterm birth and to set up a publicly available online database summarizing the data. Methods: We performed a systematic review and meta-analyses to identify genetic associations with preterm birth. We have set up a publicly available online database of genetic association data on preterm birth called PTBGene (http://ric.einstein.yu.edu/ptbgene/index.html) and report on a structured synopsis thereof as of December 1, 2008. Results: Data on 189 polymorphisms in 84 genes have been included and 36 meta-analyses have been performed. Five gene variants (4 in maternal DNA, one in newborn DNA) have shown nominally significant associations, but all have weak epidemiological credibility. Conclusion: After publishing this field synopsis, the PTBGene database will be regularly updated to keep track of the evolving evidence base of genetic factors in preterm birth with the goal of promoting knowledge sharing and multicenter collaboration among preterm birth research groups.
Gestationsdiabetes
Authors: Lang U. , Fink D. , Kimming R.
Published: May 2010

Der Gestationsdiabetes ist ein klinisches Bild, das als erstmalig in einer Schwangerschaft aufgetretene oder identifizierte Kohlenhydratstoffwechselstörung der Mutter definiert ist. Die erfasste Häufigkeit dieser Stoffwechselstörung variiert je nach Population und Intensität der diagnostischen Suche. Unstrittig ist, dass Erkennung und Behandlung eines Gestationsdiabetes Kurz- und Langzeitprognose von Mutter und Fetus sowie des Neugeborenen verbessern. Kontrovers diskutiert werden Diagnosekriterien, Screeningmassnahmen und Therapiemodalitäten. Grundlage der die Mutter, die Plazenta und den Feten einbeziehenden Pathophysiologie ist die starke Korrelation zwischen maternalen Blutglukosewerten und Komplikationsraten. Vereinheitlichte Diagnose- und Therapiekriterien auf der Basis definierter Morbiditätskriterien sind in Anbetracht des Langzeit- und Lebenszeitrisikos insbesondere für das ungeborene Kind notwendig.
Insulinbestimmung aus dem Fruchtwasser versus mittlere Blutglukose zur Therapieentscheidung beim Gestationsdiabetes: Eine Analyse des kindlichen Outcome
Authors: Holzapfel-Bauer Margit , Magnet Eva , Eder Martina , Haas Josef , Desoye Gernot , Lang Uwe
Published: May 2010

Fragestellung: Eine Analyse des geburtshilflichen und neonatalen Outcomes bei Gestationsdiabetikerinnen, die sich zur Therapieentscheidung einer Amniozentese zur Fruchtwasserinsulinbestimmung unterzogen oder Blutzuckertagesprofile mit Ermittlung der mittleren Blutglukose oder beide Methoden wählten. Material und Methodik: 408 Schwangerschaften mit Gestationsdiabetes wurden retrospektiv untersucht. 307 Schwangere wurden mit Diät behandelt (Klasse A) und 101 mit Diät und Insulin (Klasse AB). Geburtshilfliche und anthropometrische Daten wurden in Abhängigkeit der verwendeten Untersuchungsmethode innerhalb der Klassen mit Pearsons χ2 oder dem exakten Fisher-Test verglichen. Ergebnisse:Klasse A – Ältere Schwangere entschieden sich signifikant häufiger für die nichtinvasive Methode (p = 0,007). Das Gestationsalter bei der Geburt (p = 0,396) sowie der Geburtsmodus (p = 0,79) zeigten keine signifikanten Unterschiede. Dasselbe galt für das mittlere Geburtsgewicht (p = 0,348) und ein Geburtsgewicht >75. Perzentile (p = 0,473). Ein Geburtsgewicht >90. Perzentile trat signifikant häufiger bei Schwangerschaften auf, die mit beiden Methoden getestet wurden (p = 0,005). Der mittlere Ponderal-Index (PI; p = 0,434), die Nabelarterien- (p = 0,065) und Nabelvenen-pH-Werte (p = 0,052) sowie die Apgar-Werte nach 1 (p = 0,56) und 5 min (p = 0,072) erbrachten keinen Unterschied. Allerdings war ein Apgar <7 nach 1 min signifikant häufiger bei Kindern von Schwangeren, mit beiden Testmethoden. Keine Unterschiede fanden sich für die Nabelschnurglukose (p = 0,325) und Nabelschnurinsulin (p = 0,535). Klasse AB – In dieser Klasse fanden sich keine signifikanten Unterschiede für die untersuchten Parameter: Alter der Mutter (p = 0,062), Gestationsalter bei der Geburt (p = 0,219), Geburtsmodus (p = 0,386), mittleres Geburtsgewicht (p = 0,59), Geburtsgewicht >75. und >90. Perzentile (p = 0,701 und p = 0,487), mittlerer PI (p = 0,156), Nabelarterien- und -venen-pH (p = 0,197 und p = 0,056), Apgar-Werte nach 1 und 5 min (p = 0,58 und p = 0,52), Nabelschnurinsulin und -glukose (p = 0,67 und p = 0,11). Schlussfolgerungen: Diese retrospektive Analyse zeigte keinen Vorteil für das geburtshilfliche und neonatale Outcome bei Gestationsdiabetikerinnen, deren Therapie aufgrund der Höhe des Fruchtwasserinsulins festgelegt wurde, weshalb diese Methode als eine von mehreren Optionen angesehen werden muss.