bluuebunny/crossref_metadata_2025 huggingface dataset:
Proteomic analysis reveals Hrs ubiquitin‐interacting motif‐mediated ubiquitin signaling in multiple cellular processes
Authors: Pridgeon Julia W. , Webber Elizabeth A. , Sha Di , Li Lian , Chin Lih‐Shen
Published: November 2008

Despite the critical importance of protein ubiquitination in the regulation of diverse cellular processes, the molecular mechanisms by which cells recognize and transmit ubiquitin signals remain poorly understood. The endosomal sorting machinery component hepatocyte growth factor‐regulated tyrosine kinase substrate (Hrs) contains a ubiquitin‐interacting motif (UIM), which is believed to bind ubiquitinated membrane cargo proteins and mediate their sorting to the lysosomal degradation pathway. To gain insight into the role of Hrs UIM‐mediated ubiquitin signaling in cells, we performed a proteomic screen for Hrs UIM‐interacting ubiquitinated proteins in human brain by using an in vitro expression cloning screening approach. We have identified 48 ubiquitinated proteins that are specifically recognized by the UIM domain of Hrs. Among them, 12 are membrane proteins that are likely to be Hrs cargo proteins, and four are membrane protein‐associated adaptor proteins whose ubiquitination may act as a signal to target their associated membrane cargo for Hrs‐mediated endosomal sorting. Other classes of the identified proteins include components of the vesicular trafficking machinery, cell signaling molecules, proteins associated with the cytoskeleton and cytoskeleton‐dependent transport, and enzymes involved in ubiquitination and metabolism, suggesting the involvement of Hrs UIM‐mediated ubiquitin signaling in the regulation of multiple cellular processes. We have characterized the ubiquitination of two identified proteins, Munc18‐1 and Hsc70, and their interaction with Hrs UIM, and provided functional evidence supporting a role for Hsc70 in the regulation of Hrs‐mediated endosome‐to‐lysosome trafficking.
A ϕC31 integrase‐mediated integration hotspot in favor of transgene expression exists in the bovine genome
Authors: Ou Hai‐Long , Huang Ying , Qu Li‐Juan , Xu Miao , Yan Jing‐Bin , Ren Zhao‐Rui , Huang Shu‐Zhen , Zeng Yi‐Tao
Published: November 2008

ϕC31 integrase, a site‐specific recombinase, can effectively mediate foreign genes bearing an attB sequence integrated into pseudo attP sites. We have previously identified two pseudo attP sites, BpsF1 and BpsM1 from the bovine genome. In this study, two new pseudo attP sites, BF4 and BF10, were discovered using half‐nested inverse PCR from cow fibroblasts. The genomic locations of these two pseudo attP sites were identified by direct sequencing and a BLAST search, and it was confirmed that they reside at positions 4q31 and 10q35 by fluorescence in situ hybridization analysis. Subsequently, the distinct integration frequencies of the four pseudo attP sites were examined. The BF4 site was identified as a hotspot where site‐specific integration occurred in most of the cell clones examined, accounting for 74% (42/57) of the integration; much more than the integration frequency for BF10 (7%; 4/57), BpsF1 (7%; 4/57) and BpsM1 (0/57). Interestingly, similar to other hotspots identified in the human and mouse genomes, in which transgenes integrated at hotspots result in high expression, the GFP gene integrated at hotspot BF4 was expressed at high levels in cow fibroblasts, as confirmed by fluorescence microscopy and FACS analysis. Furthermore, ELISA showed that the expression level of the GFP gene integrated at the BF4 site averaged ∼ 328 μg·mg−1, which is more than twofold higher than that integrated at the BF10 site. This study suggests that somatic cells carrying a desired gene integrated at the BF4 site can be used as nuclear donors to generate valuable transgenic animals by nuclear transfer.
Comparison of the Intramuscular, Intranasal or Sublingual Routes of Midazolam Administration for the Control of Soman‐Induced Seizures*
Authors: McDonough John H. , Van Shura Kerry E. , LaMont John C. , McMonagle Joseph D. , Shih Tsung‐Ming
Published: November 2008

Abstract:  This study evaluated the anticonvulsant effectiveness of midazolam to stop seizures elicited by the nerve agent soman when midazolam was administered by different routes (intramuscular, intranasal or sublingual) at one of two different times after the onset of seizure activity. Guinea pigs previously prepared with cortical electrodes to record brain electroencephalographic activity were pre‐treated with pyridostigmine (0.026 mg/kg, intramuscularly) 30 min. before challenge with a seizure‐inducing dose of the nerve agent soman (56 µg/kg, subcutaneously), and 1 min. later, they were administered 2.0 mg/kg atropine sulfate admixed with 25.0 mg/kg 2‐PAM Cl (intramuscularly). Groups of animals were administered differing doses of midazolam by the intramuscular, intranasal or sublingual route at either the onset of seizure activity or 40 min. after the onset of seizure activity that was detected in the electroencephalographic record. When given immediately after seizure onset, the anticonvulsant ED50 of intramuscular midazolam was significantly lower than that of intranasal midazolam, which in turn was significantly lower than sublingual midazolam at that time. At the 40‐min. treatment delay, the anticonvulsant ED50s of intramuscular or intranasal midazolam did not differ and both were significantly lower than the sublingual route. Higher doses of midazolam were required to stop seizures at the 40‐min. treatment delay time compared to immediate treatment. The speed of seizure control for intramuscular or intranasal midazolam was the same while sublingual midazolam acted significantly slower. Midazolam was effective in treating soman‐induced seizures when given by all three routes, but with differences in potency and speed of action.
A Subchronic Intravenous Toxicity Study of Magnesium Fructose‐1,6‐Diphosphate in Beagle Dogs
Authors: Wang Meng , Yao Jun , Chen Jia‐Ying , Bai Wen‐Xia , Mei Sheng‐Yao , Pan Wei‐Na , Pan Yu‐Ying , Yu Fei‐Long
Published: November 2008

Abstract:  Magnesium fructose‐1,6‐diphosphate is a novel agent of antimyocardial ischaemia. In the present study, the subchronic toxicity of magnesium fructose‐1,6‐diphosphate was investigated after 13‐week repeated intravenous administration in beagle dogs. The animals received doses of 0, 75, 150 and 300 mg/kg/day (three males and three females for each dose). During the study period, clinical signs, mortality, body weights, food consumption, electrocardiogram, urinalysis, haematology, clinical biochemistry, macroscopic findings, organ weights and histopathology were examined. The administration of magnesium fructose‐1,6‐diphosphate resulted in increased incidence of clinical signs, including salivation and emesis. These effects were transient and were noted in almost all dogs given 300 mg/kg/day and occasionally noted in the 150 mg/kg/day dose‐treated animals. Serum magnesium in the 150 mg/kg/day and 300 mg/kg/day dose‐treated animals was significantly increased after 6‐ and 13‐week administration, but recovered at the end of a 2‐week recovery period. At 6 weeks, a statistically significant decrease in serum electrolytes, including sodium and potassium, was observed in the treatment groups. There were no other treatment‐related findings. Under the conditions of the present study, magnesium fructose‐1,6‐diphosphate did not show any evidence of target organ toxicity. The no‐observed‐adverse‐effect level for 13‐week intravenous administration of magnesium fructose‐1,6‐diphosphate to beagle dogs was considered 75 mg/kg/day based on observations of clinical signs and serum electrolytes.
FSFI Scores of Women with Persistent Genital Arousal Disorder Compared with Published Scores of Women with Female Sexual Arousal Disorder and Healthy Controls
Authors: Leiblum Sandra R. , Seehuus Martin
Published: November 2008

Introduction

Although persistent genital arousal disorder (PGAD) has been mistaken for hypersexuality, there is no research documenting the sexual functioning of PGAD women to support or refute such an assumption.

Aim

To compare the Female Sexual Function Index (FSFI) scores of PGAD women to that of women diagnosed with female sexual arousal syndrome (FSAD) and healthy controls.

Methods

The FSFI scores of heterosexual women who met all five features qualifying for a diagnosis of PGAD (N = 172) on an online questionnaire were compared with previously published FSFI scores of women diagnosed with FSAD (N = 128) and healthy controls (N = 131).

Main Outcome Measure

Total and subscale scores on the FSFI.

Results

On every subscale of the FSFI with the exception of desire, the PGAD women obtained scores between that of the FSAD and the healthy control group. The FSAD women displayed the greatest problems in desire, arousal, lubrication, orgasm, and pain while women with PGAD reported somewhat more desire than the control group but did not meet the cutoff score for sexual dysfunction. PGAD women are more similar to the normal control group than women with FSAD.

Conclusions

There is no evidence to support the belief that women who meet criteria for a diagnosis of PGAD are “hypersexual.” In fact, their overall sexual functioning falls within the normal range and is significantly better than that of women diagnosed with FSAD.
Long-Term Assessment of the Physical, Mental, and Sexual Health Among Transsexual Women
Authors: Weyers Steven , Elaut Els , De Sutter Petra , Gerris Jan , T’Sjoen Guy , Heylens Gunter , De Cuypere Griet , Verstraelen Hans
Published: November 2008

Introduction

Transsexualism is the most extreme form of gender identity disorder and most transsexuals eventually pursue sex reassignment surgery (SRS). In transsexual women, this comprises removal of the male reproductive organs, creation of a neovagina and clitoris, and often implantation of breast prostheses. Studies have shown good sexual satisfaction after transition. However, long-term follow-up data on physical, mental and sexual functioning are lacking.

Aim

To gather information on physical, mental, and sexual well-being, health-promoting behavior and satisfaction with gender-related body features of transsexual women who had undergone SRS.

Methods

Fifty transsexual women who had undergone SRS ≥6 months earlier were recruited.

Main Outcome Measures

Self-reported physical and mental health using the Dutch version of the Short-Form-36 (SF-36) Health Survey; sexual functioning using the Dutch version of the Female Sexual Function Index (FSFI). Satisfaction with gender-related bodily features as well as with perceived female appearance; importance of sex, relationship quality, necessity and advisability of gynecological exams, as well as health concerns and feelings of regret concerning transition were scored.

Results

Compared with reference populations, transsexual women scored good on physical and mental level (SF-36). Gender-related bodily features were shown to be of high value. Appreciation of their appearance as perceived by others, as well as their own satisfaction with their self-image as women obtained a good score (8 and 9, respectively). However, sexual functioning as assessed through FSFI was suboptimal when compared with biological women, especially the sublevels concerning arousal, lubrication, and pain. Superior scores concerning sexual function were obtained in those transsexual women who were in a relationship and in heterosexuals.

Conclusions

Transsexual women function well on a physical, emotional, psychological and social level. With respect to sexuality, they suffer from specific difficulties, especially concerning arousal, lubrication, and pain.
Aluminum Phosphate–Mullite Composites for High‐Temperature Radome Applications
Authors: Wang Yiguang , Liu Jinling
Published: November 2008

An AlPO4–SiO2 powder with a composition of Al:P:Si=1.5:1:0.1 was synthesized by the sol–gel method using aluminum nitrate, phosphate acid, and tetraethoxysilane. The structural evolution of this material was characterized by thermal gravimetric analysis‐differential scanning calorimetry, Fourier transform infrared, and X‐ray diffraction. By adding silica in AlPO4, the sinterability of the AlPO4 was enhanced because of the reactions between excess alumina and silica to form mullite. The sintered composites have a high strength and good dielectric properties at 10 GHz. Because of the formation of mullite at high temperatures, the composites showed a hydrophobic property. These unique properties indicate that the sintered AlPO4–mullite composites are suitable for the radome application.
Dielectric Properties and Reliability of Zn0.95Mg0.05TiO3+0.25TiO2 MLCCs with Different Pd/Ag Ratios of Electrodes
Authors: Lee Ying‐Chieh
Published: November 2008

In order to study the micromechanism of silver migration that influences the dielectric properties and reliability of Zn0.95Mg0.05TiO3+0.25TiO2 (ZMT″) with 1 wt% 3ZnO–B2O3 multilayer ceramic capacitors (MLCCs), various silver (Ag)–palladium (Pd) ratios of conductors were used as inner electrodes. It was found that the electrical resistance of a MLCC sample with pure Ag as inner electrodes was degraded drastically to compared with the Ag/Pd inner electrodes at measuring temperatures ranging from 25°C to 175°C. It may be explained that the pure Ag migrates easily into the dielectric layer along the grain boundary during co‐firing. The ZMT″ MLCCs exhibited increasing dielectric constant and insulation resistance considerably with increasing sintering temperature. Moreover, the results also indicate that Ag diffusion changes the dielectric properties and decreases the breakdown voltage. A ZMT″ MLCC with a high Ag content in the inner electrode exhibits poor reliability, and the effect of Ag+ migration is markedly enhanced when the activation energy of the ZMT″ dielectric is considerably lowered due to the excessive formation of oxygen vacancies and the semiconducting Zn2TiO4 phase when Ag+ substitutes for Zn2+ during co‐firing.
Thermal Character of Geopolymers Synthesized from Class F Fly Ash Containing High Concentrations of Iron and α‐Quartz
Authors: Rickard William D. A. , Riessen Arie van , Walls Philip
Published: November 2008

This article reports the thermal characteristics of geopolymers prepared with a class F fly ash containing 15 wt% iron oxide and 20 wt%α‐quartz. The characterization techniques used included dilatometry, TGA, DTA, XRD, and SEM. Geopolymer specimens were prepared with nominal ratios of Si:Al=2.3 and Na:Al=0.85. Iron oxide in the fly ash precursor was found to play a critical role in the thermal expansion and morphology of geopolymers at temperatures >500°C. Volume changes of quartz on either side of the α–β phase transition cause only minor variations in thermal expansion.
QSAR Study of 2‐(1‐Propylpiperidin‐4‐yl)‐1H‐Benzimidazole‐4‐Carboxamide as PARP Inhibitors for Treatment of Cancer
Authors: Riahi Siavash , Pourbasheer Eslam , Dinarvand Rassoul , Ganjali Mohammad Reza , Norouzi Parviz
Published: November 2008

Quantitative structure–activity relationship of the 2‐(1‐propylpiperidin‐4‐yl)‐1H‐benzimidazole‐4‐carboxamide as a potent inhibitor of poly(ADP‐ribose) polymerase for cancer treatment was studied. A suitable set of molecular descriptors was calculated and the genetic algorithm was employed to select those descriptors that resulted in the best fitted models. Excellent results were obtained employing multiple linear regressions and critically discussed using a variety of statistical parameters. Furthermore, the model was validated using leave‐one‐out and leave‐ group‐out cross‐validation, external test set and chance correlation. A genetic algorithm‐multiple linear regression model with seven selected descriptors was obtained. This model, with high statistical significance (R 2 = 0.935,  = 0.894,  = 0.875, F = 53.481), could be used to predict poly(ADP‐ribose) polymerase inhibitor activity of the molecules.
Avulsion of the left renal artery following blunt abdominal trauma in a dog
Authors: Millward I. R.
Published: November 2008

A two‐year‐old, male, crossbreed dog was presented three days after being involved in a motor vehicle accident. Survey radiographs showed multiple pelvic fractures and poor intraperitoneal and retroperitoneal contrast. Ultrasound indicated the left kidney to be hypoperfused, and a thrombus was visible at the origin of the left renal artery. Ultrasound‐guided fine needle aspiration confirmed that free fluid visible in the retroperitoneal and peritoneal spaces was blood. No improvement was seen in the renal perfusion over a 43 hour period, and the intestinal hypomotility worsened over this time. The haemoperitoneum and the haemoretroperitoneum both resolved ultrasonographically within this 43 hour period. Surgery confirmed an avulsion of the left renal artery approximately 10 mm from its origin on the aorta and an avulsion of the left ureter at the ureteropelvic junction. An ureteronephrectomy was performed on the left kidney and the dog recovered uneventfully.
Current status and perspective of the insect industry in Korea
Authors: KIM Sun Am , KIM Kyung‐Moon , OH Boung‐Jun
Published: November 2008

Insects in Korea from ancient times were largely used in sericulture and apiculture and partly as medicines. Although silkworms are currently used as dietary supplements and medicine ingredients, the insect industry is not industrialized yet. Some insect species, such as beetles, stag beetles, and fireflies, are currently employed for sustainable agriculture as natural enemies and pollinators and also for education and as pets. Agricultural practice using natural enemies becomes the center of public interest. The market size of natural enemy use in 2008 is estimated at $14.2 to 16.2 million and that of pollinators is $10.9 to 11.7 million. Several local governments have successfully utilized insects as resources for festivals, expos or museums. A variety of insects are utilized for pet and educational purposes. The pet insect market in Korea was formed in the 2000s. The total market size of insect festivals and pet insects is around $44 million and $38.5~44.0 million, respectively. The total market size of the insect industry in Korea is estimated around $110 million, and is expected to increase up to $320 million by 2015. In the future, insects can be applied to foods, dietary supplements and medicines, and hygiene enabling disposal of food and animal wastes.
Pass‐through Effects of Global Commodity Prices on China's Inflation: An Empirical Investigation
Authors: Liu Ligang , Tsang Andrew
Published: November 2008

The present paper uses a two‐step approach to estimate the pass‐through effects of changes in international commodity prices and the RMB exchange rate on domestic consumer price inflation in China. We first estimate the pass‐through effects of international commodity prices on producer prices and then estimate the pass‐through effects of producer price inflation on consumer price inflation. We find that a 10‐percent increase in international commodity prices would lead to China's producer prices increasing by 1.2 percent 3 months later, which in turn would increase China's domestic inflation by 0.24 percent over the same period. However, a 10‐percent appreciation of the RMB exchange rate against the US dollar would help to reduce increases in producer prices by 4.4 percent over the following 3 months, which in turn would lead to a 0.89‐percent decline in consumer price inflation over the same period. Our findings suggest that appreciation of the RMB in an environment of rising global commodity prices and a weak US dollar could be an effective instrument to help contain inflation in China.
Policy Options for China's Bio‐ethanol Development and the Implications for Its Agricultural Economy
Authors: Qiu Huanguang , Huang Jikun , Keyzer Michiel , Van Veen Wim
Published: November 2008

The present paper analyzes the potential impacts of bio‐ethanol expansion on agricultural production, food prices and farmers' incomes in different regions of China. The results show that increase in demand for feedstock to produce bio‐ethanol will lead to large increase in the prices of agricultural products. The increase in prices will trigger a significant rise in the production of feedstock at the cost of lower rice and wheat production. The study also reveals that the impacts of bio‐ethanol on farmers' incomes vary largely among regions and farmer groups. Given the expected expansion of bio‐ethanol production in the future, and the limited land resources for feedstock production in China, the viability of different crops as feedstock for bio‐ethanol requires careful analysis before a large‐scale expansion of China's bio‐ethanol program. Bio‐ethanol production in China should be relying more on the second generation of bio‐ethanol technologies (i.e. using celluloses to produce bio‐ethanol), and China's government should increase research investment in this field.
Unusual Photoinduced Response of mTHPC Liposomal Formulation (Foslip)
Authors: Kachatkou Dzmitry , Sasnouski Siarhei , Zorin Vladimir , Zorina Tatyana , D’Hallewin Marie‐Ange , Guillemin Francois , Bezdetnaya Lina
Published: November 2008

Liposomal formulations of meso‐tetra(hydroxyphenyl)chlorin (mTHPC) have already been proposed with the aim to optimize photodynamic therapy. Spectral modifications of these compounds upon irradiation have not yet been investigated. The objective of this study was to evaluate photobleaching properties of mTHPC encapsulated into dipalmitoylphosphatidylcholine (DPPC) liposomes, Foslip. Fluorescence measurements in DPPC liposomes with different DPPC:mTHPC ratios demonstrated a dramatic decrease in fluorescence anisotropy with increasing local mTHPC concentration, thus suggesting strong interactions between mTHPC molecules in lipid bulk medium. Exposure of Foslip suspensions to small light doses (<50 mJ/cm2) resulted in a substantial drop in fluorescence, which, however, was restored after addition to the sample of a non‐ionic surfactant Triton X‐100. We attributed this behavior to photoinduced fluorescence quenching. This effect depended strongly on the molar DPPC:mTHPC ratio and was revealed only for high local mTHPC concentrations. The results were interpreted supposing energy migration between closely located mTHPC molecules with its subsequent dissipation by the molecules of photoproduct acting as excitation energy traps. We further assessed the effect of photoinduced quenching in plasma protein solution. Relatively slow kinetics of photoinduced Foslip response during incubation in the presence of proteins was attributed to mTHPC redistribution from liposomal formulations to proteins. Therefore, changes in mTHPC distribution pattern in biological systems would be consistent with changes in photoinduced quenching and would provide valuable information on mTHPC interactions with a biological environment.
Amelioration of Airway Stenosis in Rabbit Models by Photodynamic Therapy with Talaporfin Sodium (NPe6)
Authors: Nakagishi Yoshinori , Morimoto Noriko , Fujita Masanori , Ozeki Yuichi , Maehara Tadaaki , Kikuchi Makoto , Morimoto Yuji
Published: November 2008

It is difficult to treat patients with acquired airway stenosis, and the quality of life of such patients is therefore lowered. We have suggested the application of photodynamic therapy (PDT) as a new treatment for airway stenosis and have determined the efficacy of PDT in animal disease models using a second‐generation photosensitizer with reduced photosensitivity. An airway stenosis rabbit model induced by scraping of the tracheal mucosa was administered NPe6 (5 mg kg−1), and the stenotic lesion was irradiated with 670 nm light emitted from a cylindrical diffuser tip at 60 J cm−2 under bronchoscopic monitoring. PDT using NPe6 improved airway stenosis (P = 0.043) and respiratory stridor. A significant prolongation of survival time was seen in the PDT‐treated animals compared to that in the untreated animals (P = 0.025) and 44% of the treated animals achieved long‐term survival (>60 days). In conclusion, PDT using NPe6 is effective for improvement in airway stenosis.
Neuromelanins Isolated from Different Regions of the Human Brain Exhibit a Common Surface Photoionization Threshold
Authors: Bush William D. , Garguilo Jacob , Zucca Fabio A. , Bellei Chiara , Nemanich Robert J. , Edwards Glenn S. , Zecca Luigi , Simon John D.
Published: November 2008

Neuromelanin isolated from the premotor cortex, cerebellum, putamen, globus pallidus and corpus callosum of the human brain is studied by scanning probe and photoelectron emission microscopies and the results are compared with previously published work on neuromelanin from the substantia nigra. Scanning electron microscopy reveals common structure for all neuromelanins. All exhibit spherical entities of diameters between 200 and 400 nm, composed of smaller spherical substructures, ∼30 nm in diameter. These features are similar to that observed for many melanin systems including Sepia cuttlefish, bovine eye, and human eye and hair melanosomes. Photoelectron microscopy images were collected for all neuromelanins at specific wavelengths of ultraviolet light between 248 and 413 nm, using the spontaneous emission output from the Duke free electron laser. Analysis of the data establishes a common threshold photoionization potential for neuromelanins of 4.7 ± 0.2 eV, corresponding to an oxidation potential of −0.3 ± 0.2 V vs the normal hydrogen electrode (NHE). These results are consistent with previously reported potentials for neuromelanin from the substantia nigra of 4.5 ± 0.2 eV (−0.1 ± 0.2 V vs NHE). All neuromelanins exhibit a common low surface oxidation potential, reflecting their eumelanic component and their inability to trigger redox processes with neurotoxic effect.
The Emergence of Extensively Drug‐Resistant Tuberculosis: A Global Health Crisis Requiring New Interventions: Part I: The Origins and Nature of the Problem
Authors: Ellner Jerrold J.
Published: November 2008

Surveillance studies and outbreak investigations indicate that an extensively drug‐resistant (XDR) form of tuberculosis (TB) is increasing in prevalence worldwide. In outbreak settings among HIV‐infected, there is a high‐case fatality rate. Better outcomes occur in HIV‐uninfected, particularly if drug susceptibility test (DST) results are available rapidly to allow tailoring of drug therapy. This review will be presented in two segments. The first characterizes the problem posed by XDR‐TB, addressing the epidemiology and evolution of XDR‐TB and treatment outcomes. The second reviews technologic advances that may contribute to the solution, new diagnostics, and advances in understanding drug resistance and in the development of new drugs.
Therapeutic effect of subconjunctival injection of bevacizumab in the treatment of corneal neovascularization
Authors: You In‐Cheon , Kang In‐Seong , Lee Seung‐Hyun , Yoon Kyung‐Chul
Published: November 2008

Purpose:  To investigate the efficacy of subconjunctival injection of bevacizumab in the treatment of patients with corneal neovascularization.

Methods:  Twenty‐nine eyes of 29 patients with corneal neovascularization were treated with subconjunctival injection [1.25 mg/0.05 ml (seven eyes), 2.5 mg/0.1 ml (15 eyes) and 5.0 mg/0.2 ml (seven eyes)] of bevacizumab. Best‐corrected visual acuity, intraocular pressure and area of corneal neovascularization were measured before injection and at 1 week, 1 month and 3 months after treatment.

Results:  At 1 week, the mean neovascularized corneal area decreased significantly to 85.5 ± 18.0% (p = 0.01) in the eyes treated with 2.5 mg bevacizumab and to 73.1 ± 23.4% (p = 0.02) in the eyes treated with 5.0 mg bevacizumab. At 3 months, the mean neovascularized corneal area was 93.6 ± 10.6% (p = 0.10 compared to baseline; p < 0.01 compared to 1 week) in the eyes treated with 2.5 mg bevacizumab and 83.3 ± 25.8% (p = 0.03 compared to baseline; p = 0.02 compared to 1 week) in the eyes treated with 5.0 mg bevacizumab. However, there were no significant changes in the areas of the eyes injected with 1.25 mg bevacizumab.

Conclusion:  Subconjunctival injection of bevacizumab can partially reduce corneal neovascularization in the short term, and the efficacy of this treatment correlates with the injection dose.
Prospective Echocardiographic and Tissue Doppler Imaging Screening of a Population of Maine Coon Cats Tested for the A31P Mutation in the Myosin‐Binding Protein C Gene: A Specific Analysis of the Heterozygous Status
Authors: Carlos Sampedrano C. , Chetboul V. , Mary J. , Tissier R. , Abitbol M. , Serres F. , Gouni V. , Thomas A. , Pouchelon J.‐L.
Published: November 2008

Background:A mutation in the sarcomeric gene coding for the myosin‐binding protein C gene has been identified in a colony of Maine Coon cats with hypertrophic cardiomyopathy (MyBPC3‐A31P mutation). However, the close correlation between genotype and phenotype (left ventricular hypertrophy [LVH] and dysfunction) has never been assessed in a large population, particularly in heterozygous (Hetero) cats.

Objectives:To investigate LV morphology and function with echocardiography and tissue Doppler imaging (TDI) in a population of Maine Coon cats tested for the MyBPC3‐A31P mutation with focus on Hetero animals.

Animals:Ninety‐six Maine Coon cats.

Methods:Prospective observational study. Cats were screened for the MyBPC3‐A31P mutation and examined with both echocardiography and 2‐dimensional color TDI.

Results:Fifty‐two out of 96 cats did not have the mutation (wild‐type genotype, Homo WT), 38/96 and 6/96 were Hetero‐ and homozygous‐mutated (Homo M) cats, respectively. Only 11% of Hetero cats (4/38) had LVH and 29% (10/34) of Hetero cats without LVH were >4 years old (4.1–11.5 years). LVH was also detected in 2 Homo WT cats (4%). A significantly decreased (P< .05) longitudinal E/A (ratio between early and late diastolic myocardial velocities) in the basal segment of the interventricular septum was observed in Hetero cats without LVH (n = 34) compared with Homo WT cats without LVH (n = 50), thus confirming that the Hetero status is associated with regional diastolic dysfunction (P< .05).

Conclusions:The heterozygous status is not consistently associated with LVH and major myocardial dysfunction. Moreover, Homo WT cats can also develop LVH, suggesting that other genetic causes might be implicated.
Heat Conduction in Printed Circuit Boards: A Mesoscale Modeling Approach
Authors: Nakayama Wataru
Published: November 2008

An analytical model is developed to estimate the heat transfer performance of printed circuit board (PCBs). The PCB under study is the substrate for a ball-grid-array (BGA) package. Under the BGA, the PCB has a belt of densely populated through-vias that penetrate the laminate of horizontal copper and resin; outside the BGA-covered area the board is a copper/resin laminate and its surfaces are exposed to cooling air. Calculations are performed on a sample board having the dimensions 11×11 cm2 (footprint)×1.26 mm (thickness). The model of the board has two internal layers of continuous copper (0.03 mm thick) and through-vias under a 4.4×4.4 cm2 BGA package. The impacts of board design parameters on the temperature and the heat flow are presented; the parameters are the width of the insulation gap around the via, the area of copper coverage at the via bottom, and the population of vias.
Compact Thermal Models: A Global Approach
Authors: Sabry Mohamed-Nabil , Abdelmeguid Hossam Saleh
Published: November 2008

The construction and usage of compact thermal models (CTMs), for the thermal analysis as well as the design of cooling devices for electronic systems, are reviewed. These models have many advantages over the so called detailed models based on 3D simulations, mainly being a convenient and simple quantitative description of the modeled object, when constructional details are either unavailable or too detailed to be of use at the desired level of analysis. However, CTMs have manifested some deficiencies in many cases, in particular, multiple chip modules (MCM) and stacked dies. The opposite approach, detailed modeling, is more reliable, although extremely heavy. A new approach is proposed that solves this dilemma by bridging the gap between compact and detailed models. While retaining all advantages of CTMs, i.e., having a limited number of degrees of freedom and not requiring detailed constructional features, it can attain any required precision level depending on the degree of complexity adopted. It gives reliable results covering all operating conditions including MCM and stacked dies. Moreover, it gives access to data on surface temperature gradients that were never obtained before by compact models and are highly important for reliability issues.
Design for Reliability Applied to Packaging of a MOEMS Switch
Authors: Fasoro Abiodun A. , Mittal Manoj , Popa Dan O. , Agonafer Dereje A. , Stephanou Harry E.
Published: November 2008

Microelectromechanical systems (MEMSs) consist of moving mechanical microparts often integrated with electronics and optics that may be used for sensing or actuating purposes. MEMS and micro-opto-electromechanical system (MOEMS) packaging requirements vary widely with application, but they generally involve protecting the device from the damaging effects of the environment, such as moisture and dust. Reliability is often not considered as a design factor during product development. Rather, reliability is assessed using life tests, accelerated tests, and other techniques after a product has completed its development cycle. The goal of design for reliability (DfR) is to be proactive by introducing reliability early in product development so that concerns are identified and assessed at every stage, from the conception to obsolescence. In this paper, we present a framework for applying DfR principles to MOEMS packaging. Such an approach is desirable for several reasons. First, it reduces the cost and time for product development by departing from the “build-test-rebuild” approach. Second, it provides better understanding of the process input-output relationships, so the practitioner is better able to make informed design decisions. Lastly, this can lead to enhanced product performance, reliability, and reduced cost. To demonstrate the use of DfR in MOEMS packaging, we present a case study involving carrier level packaging of a MOEMS switch. The reliability requirements for this device are stringent, namely, a shelf life of 25years or more, requiring hermetic sealing through the use of metal seals and no organic compounds inside the package. Simulation and experiments are used systematically in order to guide the package design and process windows, ensuring that the device passes MIL-STD reliability tests. The packaging processes include fluxless die-to-carrier attachment, optical fiber-to-carrier attachment, and hermetic sealing. Results show that our packaging approach can determine adequate process windows using only a small number of reliability experiments.
Measurement of Transient Dynamic Response of Circuit Boards of a Handheld Device During Drop Using 3D Digital Image Correlation
Authors: Park S. B. , Shah Chirag , Kwak Jae B. , Jang Changsoo , Chung Soonwan , Pitarresi James M.
Published: November 2008

In this work, a new experimental methodology for analyzing the drop impact response is assessed using a pair of high-speed digital cameras and 3D digital image correlation software. Two different test boards are subjected to Joint Electron Device Engineering Council (JEDEC) standard free-fall impact conditions of half-sine pulse of 1500 G in magnitude and 0.5 ms in duration. The drop is monitored using a pair of synchronized high-speed cameras at a rate of up to 15,000 frames per second. The acquired images are subsequently analyzed to give full-field dynamic deformation, shape, and strain over the entire board during and after impact. To validate this new methodology for analyzing the impact response, the in-plane strain as well as the out-of-plane acceleration at selected locations were measured simultaneously during the drop using strain gauge and accelerometers and were compared with those obtained using high-speed cameras and 3D digital image correlation presented in this paper. Comparison reveals excellent correlation of the transient behavior of the board during impact and confirms the feasibility of using the full-field measurement technique used in this study.
Design and Implementation of Nonlinear Force Controllers for Friction Stir Welding Processes
Authors: Zhao Xin , Kalya Prabhanjana , Landers Robert G. , Krishnamurthy K.
Published: November 2008

In friction stir welding (FSW) processes, force control can be used to achieve good welding quality. This paper presents the systematic design and implementation of FSW force controllers. The axial and path forces are modeled as nonlinear functions of the FSW process parameters (i.e., plunge depth, tool traverse rate, and tool rotation speed). Equipment models, which include communication delays, are constructed to relate the commanded and measured actuator signals. Based on the dynamic process and equipment models, nonlinear feedback controllers for the axial and path forces are designed using the polynomial pole placement technique. The controllers are implemented in a Smith predictor-corrector structure to compensate for the inherent equipment communication delays, and the controller parameters are tuned to achieve the best closed loop response possible given equipment limitations. In the axial force controller implementation, a constant axial force is maintained, even when gaps are encountered during the welding process. In the path force controller implementation, a constant path force is maintained, even in the presence of gaps, and wormhole generation during the welding process is eliminated by regulating the path force.
A flexible homework method
Authors: Bao Lei , Stonebraker Stephen R. , Sadaghiani Homeyra
Published: November 2008

The traditional methods of assigning and grading homework in large enrollment physics courses have raised concerns among many instructors and students. In this paper we discuss a cost-effective approach to managing homework that involves making half of the problem solutions available to students before the homework is due. In addition, students are allowed some control in choosing which problems to solve. This paper-based approach to homework provides more detailed and timely support to students and increases the amount of self-direction in the homework process. We describe the method and present preliminary results on how students have responded.
Intracranial dural arterio-venous fistula
Authors: Wilson M , Enevoldson P , Menezes B
Published: November 2008

Intracranial dural arteriovenous fistulae are rare, acquired lesions that may present with intracranial haemorrhage or progressive neurological deficits. Their cause is uncertain, although they are often associated with intracranial venous thrombosis. Their importance lies in the fact that they are potentially curable by endovascular or neurosurgical procedures, but easily missed on routine brain imaging. In addition, clinical presentation is variable, with no easily recognisable “syndrome”. A high index of suspicion is therefore required, as well as familiarity with the characteristic radiological abnormalities seen on appropriate imaging.
The virtues of a deliberately mis-specified disease model in demonstrating a gene-environment interaction
Authors: Burstyn I , Kim H-M , Yasui Y , Cherry N M
Published: November 2008

Objectives:

This study seeks to assess the impact of measurement errors in cumulative exposure on estimates of a gene-environment interaction in a nested case-control study in occupational epidemiology. In the approach considered here, exposure intensity is assessed at the group level and the exposure duration individually (both with error). Genetic susceptibility is assumed to be known exactly. Differences in “gene” are assumed to affect disease risk only in exposed subjects.

Methods:

Three data analysis strategies were considered: one using a correctly specified disease model (exposure and exposure-gene interaction), and two using mis-specified disease models, one with “gene” as the only risk factor (“gene-only” model) and the other with main effects of both gene and exposure along with their interaction (“full” model).

Results:

In simulations, estimates of the gene-environment interaction based on the correctly specified disease model were greatly attenuated and power was diminished appreciably even when errors in exposure were modest. Significant associations were detected more frequently in the gene-only model when errors in exposure were large. When the “full” mis-specified model was fitted to the simulated data, it yielded erratic estimates. This is illustrated in an analysis of the interaction of cumulative exposure to organophosphate pesticides and paraoxonase gene on the risk of chronic neuropsychological effects among farmers who dip sheep.

Conclusion:

If “gene” contributes to disease risk only in the presence of exposure, the existence of the gene-environment interaction can be efficiently inferred from a deliberately mis-specified “gene-only” disease model in nested case-control studies.
Quantifying the Growth of Female Pacific Hake (Merluccius productus): An Example of Measuring Uncertainty and Bias in Non-linear Parameter Estimation
Authors: Welch David W. , McFarlane Gordon A.
Published: November 2008

Estimates of size-at-age are commonly reported in fisheries studies, but statistical uncertainty and intrinsic variability in the growth parameters are less frequently examined. We examine these questions using recently-developed statistical methods for quantifying uncertainty and bias in parameter estimates for nonlinear models with independent and additive Gaussian errors. We also describe diagnostic methods to determine when the usual method for examining parameter uncertainty, linearization, is unacceptable. Both our review and our approach to uncertainty are generally applicable to nonlinear estimation, and not solely restricted to growth models. We illustrate our approach with length-at-age data for female Pacific hake (Merluccius productus) from Georgia Strait, British Columbia. Between-year variation in somatic growth seems to be restricted to the two von Bertalanffy growth parameters K and L∞. Mean asymptotic length declined by about 10% since the late 1970's while the parameter K nearly tripled in value. Closer examination showed that the decline in somatic growth was restricted to the maximum size attained. We argue that the changes are most consistent with selective removal of the largest individuals from the population by the fishery, rather than a response of growth rates to either environmental or density-dependent factors.
Lake Morphometry and Light in the Surface Layer
Authors: Sterner Robert W.
Published: November 2008

Mean irradiance in the surface layer was calculated as a percent of incident irradiance using Secchi depths and thermocline depths for two sets of lakes: (1) 20 nearly circular lakes in northwest Minnesota, USA, sampled at a similar season, and (2) 1140 lakes of heterogeneous shapes in Ontario, Canada, sampled throughout the ice-free season. For both, as lake area increased, the thickness of the surface layer increased. Consequently, lakes larger in area had lower mean irradiance in their surface layer. Lake depth had less influence, but in the Ontario lakes, as depth increased, attenuation decreased, and mean irradiance increased. Lake area (log transformed) explained ca. one-half of the variation in mean irradiance in the homogeneous sampling of Minnesota lakes, while area and depth together explained less of the variation in the heterogeneous sampling of Ontario lakes. Shape, i.e. shoreline development, was unimportant compared with the gross measures of size, area and depth. Mean irradiance is complexly related to lake size; when depth increases slowly with area, larger lakes may have lower mean irradiance in their surface layers. But, when depth increases quickly with area, mean irradiance can be unrelated to area.
Diel Migration and Microhabitat Distribution of a Benthic Stream Assemblage
Authors: Rader Russell B. , Ward James V.
Published: November 2008

Macroinvertebrate microspatial distributions were determined on nonglazed brick substrates at three sites on the upper Colorado River. Site 1 was located above a reservoir, whereas Sites 2 and 3 were located 0.4 and 4.0 km, respectively, downstream from a deep-release dam. Replicate samples from each substrate surface (top, sides, front, back, and bottom) and from the interstices below brick substrates were collected during the day (ca 14:00–16:00) and at night (ca 21:00–23.00) in the summer and autumn of 1982. Although most macroinvertebrates occurred on "bottom" surfaces, "top," and "side" surfaces and the interstices were often utilized. Macroinvertebrates were least abundant on "back" and especially "front" surfaces. Total macroinvertebrate density on upper substrate surfaces was not significantly different at night compared with the day. However, there was a 47% increase in the density of Baetis spp. on upper surfaces during the night at Site 1, a diel shift in benthic substrate utilization that corresponded to drift periodicity. The density of Baetis spp. on upper surfaces during the night compared with the day was not significantly different at Sites 2 and 3. Large-sized Baetis spp. at Site 1, but not at Sites 2 and 3, used a greater proportion of upper substrate surfaces at night compared with the day.
Crossing Methodology and Genotypic Diversity in a Hatchery Strain of Rainbow Trout (Oncorhynchus mykiss)
Authors: Gile Stephen R. , Ferguson Moira M.
Published: November 2008

Genotype frequencies and heterozygosity at nine polymorphic enzyme loci were determined in 720 rainbow trout (Oncorhynchus mykiss) produced by three types of crosses: full-sib family, diallel, and pooled gamete. Five pairs of parental fish were crossed by each method within each of three experiments. Offspring produced by pooled crosses deviated significantly from equal parental genetic contributions while those from the diallels did not. Significant deviation in full-sib family offspring is attributable to only a single locus in one experiment. The deviations in the pooled cross may be the result of unequal male contributions. Cross types also differed significantly in genotype frequencies. Crossing methodology has potentially important effects on the genetic variation of cultured fishes.
Thermal Tolerances of the Predatory Cladocerans Bythotrephes cederstroemi and Leptodora kindti: Relationship to Seasonal Abundance in Western Lake Erie
Authors: Garton David W. , Berg David J. , Fletcher Robert J.
Published: November 2008

Abundances of two predatory cladocerans, recently introduced Bythotrephes cederstroemi (Schoedler) and native Leptodora kindti Focke, in western Lake Erie were negatively correlated in 1987, with the invader abundant in late autumn and the native more abundant in summer. Laboratory experiments were conducted in summer and autumn of 1988 to determine if differences in thermal tolerance could explain species replacement in these two ecologically similar species. Body mass, sex ratio, fecundity, and population abundance were also measured in summer and autumn populations. Mortality of Bythotrephes increased with temperature, while mortality of Leptodora increased both above and below ambient lake temperatures. Leptodora was less tolerant of low temperature (5–15 °C), and both species were equally tolerant of high temperature (20–30 °C). Seasonal acclimation to temperature was absent in Bythotrephes, while Leptodora showed seasonal shifts in thermal tolerance. Reduced fecundity, greater percentage of males, and presence of sexual eggs were evidence that Bythotrephes reached an environmental limit during summer. Decreased abundance of Leptodora in autumn can be explained by sensitivity to declining water temperature, but warm water temperature alone cannot explain numerical dominance of Leptodora in summer.