bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a short form of Mini-Mental State Examination for the screening of dementia in older adults with a memory complaint: a case control study
Authors: Haubois Gladys , Annweiler Cédric , Launay Cyrille , Fantino Bruno , de Decker Laure , Allali Gilles , Beauchet Olivier
Published: October 2011

Background

Primary care physicians need a brief and accurate screening test of dementia. The objective of this study was to determine whether a short form of Mini-Mental State Examination (SMMSE) was as accurate as the Mini-Mental State Examination (MMSE) in screening dementia.

Methods

Based on case control design study, SMMSE and MMSE were assessed in 184 community-dwelling older adults (mean age 81.3 ± 6.5 years, 71.7% women) with memory complaint sent by their primary care physician to a memory clinic. Included participants were separated into two groups: cognitively healthy individuals and demented individuals.

Results

The trade-off between sensitivity and specificity of the SMMSE for clinically diagnosed dementia was 4. Based on the cut-off value ≤ 4 for SMMSE and a cut-off value ≤ 24 for MMSE, the sensitivity of both tests was similar (89.5% for SMMSE versus 90.0% for MMSE), whereas the specificity, the positive predictive values (PPV) and the negative predictive values (NPV) were higher for SMMSE compared to MMSE (85.4 versus 75.5% for specificity; 95.5% versus 92.8% for PPV; 70.0 versus 68.9 for NPV). The positive and negative Likehood Ratio (LR) of SMMSE were higher than those of MMSE (respectively, 6.1 versus 3.7; 8.1 versus 7.7). In addition, odds ratio (OR) for dementia was higher for the SMMSE compared to the MMSE (OR = 49.8 with 95% confident interval (CI) [18.0; 137.8] versus OR = 28.6 with 95% CI [11.6; 70.3]).

Conclusions

SMMSE seems to be an efficient short screening test for dementia among community-dwelling older adults with a memory complaint. Further research is needed to confirm its predictive values among unselected primary care older patients.
High sensitivity of an ELISA kit for detection of the gamma-isoform of 14-3-3 proteins: usefulness in laboratory diagnosis of human prion disease
Authors: Matsui Yuki , Satoh Katsuya , Miyazaki Toshiaki , Shirabe Susumu , Atarashi Ryuichiro , Mutsukura Kazuo , Satoh Akira , Kataoka Yasufumi , Nishida Noriyuki
Published: October 2011

Background

The gamma-isoform of the 14-3-3 protein (14-3-3 gamma) is expressed in neurons, and could be a specific marker for neuronal damage. This protein has been reported as a detectable biomarker, especially in the cerebrospinal fluid (CSF) of Creutzfeldt-Jakob disease (CJD) patients by Western blotting (WB) or enzyme-linked immunosorbent assays (ELISAs). Western blotting for 14-3-3 gamma is not sensitive, and the reported data are conflicting among publications. An ELISA specific for 14-3-3 gamma is not available.

Methods

CJD patients (n = 114 sporadic CJD patients, 7 genetic CJD, and 3 iatrogenic CJD) and 99 patients with other neurodegenerative diseases were examined in this study. The CSF samples obtained were analyzed by Western blotting for 14-3-3 gamma, and by ELISA for total tau protein. We evaluated the sensitivity and specificity of the newly developed sandwich ELISA for 14-3-3 gamma.

Results

The cut-off value of the 14-3-3 gamma ELISA was > 1, 683 AU/ml; and sensitivity was 95.2%, with 72.7% specificity. This specificity was the same for the total tau protein ELISA. Seven CJD cases were negative by WB but positive using the 14-3-3 gamma ELISA, indicating that the ELISA is more sensitive. All 21 cases of early stage CJD could be diagnosed using a combination of the 14-3-3γ ELISA and diffusion weighted MR imaging (DWI-MRI).

Conclusion

The 14-3-3 gamma ELISA was more sensitive than conventional WB, and was useful for laboratory diagnosis of CJD, similar to the ELISA for the tau protein. Using DWI-MRI and these ELISA tests on CSF, diagnosis of CJD will be possible even at early stages of the disease.
Striving to be prepared for the painful: Management strategies following a family member's diagnosis of advanced cancer
Authors: Sjolander Catarina , Hedberg Berith , Ahlstrom Gerd
Published: October 2011

Background

Cancer has consequences not only for the sick person but also for those who have a close relationship with that person. Greater knowledge about how family members manage the situation in the period immediately following the diagnosis means greater opportunity to provide the best possible support for the family. The purpose of this study was to explore management strategies that family members use when the patient is in the early stage of treatment for advanced cancer.

Methods

Twenty family members of cancer patients were included in the study shortly after the diagnosis. The patients had been diagnosed 8-14 weeks earlier with advanced lung cancer or gastrointestinal cancer. The data were collected in interviews with family members and subjected to qualitative latent content analysis. Through the identification of similarities and dissimilarities in the units of meaning, abstraction into codes and sub-themes became possible. The sub-themes were then brought together in one overarching theme.

Results

The overall function of management strategies is expressed in the theme Striving to be prepared for the painful. The family members prepare themselves mentally for the anticipated tragedy. Family relationships become increasingly important, and family members want to spend all their time together. They try to banish thoughts of the impending death and want to live as normal a life as possible. It becomes important to family members to live in the present and save their energy for the time when they will need it the most. How participants handle their worries, anxiety and sadness can be categorized into seven sub-themes or management strategies: Making things easier in everyday life, Banishing thoughts about the approaching loss, Living in the present, Adjusting to the sick person's situation, Distracting oneself by being with others, Shielding the family from grief, and Attempting to maintain hope.

Conclusions

The findings revealed that the family members have their own resources for handling the early stage of the cancer trajectory in an acceptable way. There is a need for longitudinal studies to generate knowledge for designing evidence-based intervention programmes that can prevent future ill-health in these vulnerable family members.
Malaria knowledge and long-lasting insecticidal net use in rural communities of central Côte d'Ivoire
Authors: Ouattara Allassane F , Raso Giovanna , Edi Constant VA , Utzinger Jürg , Tanner Marcel , Dagnogo Mamadou , Koudou Benjamin G
Published: October 2011

Background

To improve effectiveness of malaria control interventions, it is essential to deepen the knowledge of contextual factors that govern people's practice for preventive and curative measures. The aim of this study was to determine factors that influence the use of long-lasting insecticidal nets (LLINs) in three rural communities of Côte d'Ivoire, two of which benefited from recent interventions.

Methods

The study was carried out in 957 households in three villages (Bozi, N'Dakonankro and Yoho) located in central Côte d'Ivoire. Indicators of socioeconomic position (SEP), malaria knowledge and practice, placing special emphasis on LLINs, were investigated during a cross-sectional questionnaire survey. Principal component analysis was used to calculate the SEP of households by means of a list of household assets ownership. The concentration index was used to assess the direction of the association between SEP and a given variable. To compare groups or means, Fisher's exact test, χ2 and Kruskal-Wallis test were used, as appropriate.

Results

Significant differences were found between SEP and reported malaria symptoms, such as fever or hot body, convulsion, anaemia and jaundice (yellow eyes). Individuals from the least poor group cited more often the use of bed nets and insecticide-treated nets (ITNs) compared to poorer groups. The mean number of individuals reporting the use of bed nets and LLINs was different between groups with different educational level. Moreover, the mean number of LLINs in a household was influenced by the presence of children below five years of age.

Conclusion

The study not only confirmed that education and SEP play important roles in the prevention and control of malaria and promotion of health in general, but pointed at the basic essential knowledge and the key behavioural elements that should guide education and learning processes among the poorer segments of the population. In turn, such knowledge may change behaviour and lead to an increased utilization of LLINs.
Direct-writing of PbS nanoparticles inside transparent porous silica monoliths using pulsed femtosecond laser irradiation
Authors: Chahadih Abdallah , El Hamzaoui Hicham , Bernard Rémy , Boussekey Luc , Bois Laurence , Cristini Odile , Le Parquier Marc , Capoen Bruno , Bouazaoui Mohamed
Published: October 2011

Pulsed femtosecond laser irradiation at low repetition rate, without any annealing, has been used to localize the growth of PbS nanoparticles, for the first time, inside a transparent porous silica matrix prepared by a sol-gel route. Before the irradiation, the porous silica host has been soaked within a solution containing PbS precursors. The effect of the incident laser power on the particle size was studied. X-ray diffraction was used to identify the PbS crystallites inside the irradiated areas and to estimate the average particle size. The localized laser irradiation led to PbS crystallite size ranging between 4 and 8 nm, depending on the incident femtosecond laser power. The optical properties of the obtained PbS-silica nanocomposites have been investigated using absorption and photoluminescence spectroscopies. Finally, the stability of PbS nanoparticles embedded inside the host matrices has been followed as a function of time, and it has been shown that this stability depends on the nanoparticle mean size.
Selective formation of tungsten nanowires
Authors: Bien Daniel CS , Saman Rahimah Mohd , Badaruddin Siti Aishah Mohamad , Lee Hing Wah
Published: October 2011

We report on a process for fabricating self-aligned tungsten (W) nanowires with polycrystalline silicon core. Tungsten nanowires as thin as 10 nm were formed by utilizing polysilicon sidewall transfer technology followed by selective deposition of tungsten by chemical vapor deposition (CVD) using WF6 as the precursor. With selective CVD, the process is self-limiting whereby the tungsten formation is confined to the polysilicon regions; hence, the nanowires are formed without the need for lithography or for additional processing. The fabricated tungsten nanowires were observed to be perfectly aligned, showing 100% selectivity to polysilicon and can be made to be electrically isolated from one another. The electrical conductivity of the nanowires was characterized to determine the effect of its physical dimensions. The conductivity for the tungsten nanowires were found to be 40% higher when compared to doped polysilicon nanowires of similar dimensions.
Tuning the electronic band structure of PCBM by electron irradiation
Authors: Yoo Seung Hwa , Kum Jong Min , Cho Sung Oh
Published: October 2011

Tuning the electronic band structures such as band-edge position and bandgap of organic semiconductors is crucial to maximize the performance of organic photovoltaic devices. We present a simple yet effective electron irradiation approach to tune the band structure of [6, 6]-phenyl-C61-butyric acid methyl ester (PCBM) that is the most widely used organic acceptor material. We have found that the lowest unoccupied molecular orbital (LUMO) level of PCBM up-shifts toward the vacuum energy level, while the highest occupied molecular orbital (HOMO) level down-shifts when PCBM is electron-irradiated. The shift of the HOMO and the LUMO levels increases as the irradiated electron fluence increases. Accordingly, the band-edge position and the bandgap of PCBM can be controlled by adjusting the electron fluence. Characterization of electron-irradiated PCBM reveals that the variation of the band structure is attributed to the molecular structural change of PCBM by electron irradiation.
Mobile user-preference-based data dissemination on mobile P2P networks
Authors: Kim Dohoon , Kim Young-Gab , In Hoh Peter
Published: October 2011

A considerable number of studies have been performed recently on mobile peer-to-peer networks (MOPNETs), as the number of services based on mobile devices has increased. However, existing studies still reveal numerous shortcomings, such as bandwidth overhead, and redundant transmission in terms of multi-broadcast between peers. Especially, owing to the characteristics of MOPNETs, it is extremely important to determine broadcast size and to disseminate data within the limited environment of the network. The mechanism directly affects how well resource information in a mobile device is discovered and how data are transmitted. In this context, it is vital to efficiently disseminate data to be able to arrange hierarchal sequences of resource information of each mobile device for better search performance. Especially, it is also vital to determine the broadcast size, considering the consumption patterns of mobile users. In this article, we propose an adaptable algorithm that determines weighted values and disseminates data using the high-order Markov chain (HoMC). We apply weighted values in consideration of the MOPNET environment. In addition, the proposed HoMC-based Mobile User-preference-based Data Dissemination algorithm was simulated with a Qualnet simulator. Results show that the proposed algorithm performs 17.3% better, on average, in terms of data dissemination, than the existing dissemination methods.
A minimax inequality and its applications to fixed point theorems in CAT(0) spaces
Authors: Shabanian S , Vaezpour SM
Published: October 2011

In this paper, a CAT(0) version of famous Fan's minimax inequality is established and as its application, we obtain some fixed point theorems and best approximation theorems in CAT(0) spaces.

2000 Mathematics Subject Classification: 47H10.
Epstein - Barr virus latent membrane protein 1 suppresses reporter activity through modulation of promyelocytic leukemia protein-nuclear bodies
Authors: Sides Mark D , Block Gregory J , Chadwick Reid W , Shan Bin , Flemington Erik K , Lasky Joseph A
Published: October 2011

The Epstein-Barr virus (EBV) encoded Latent Membrane Protein 1 (LMP1) has been shown to increase the expression of promyelocytic leukemia protein (PML) and the immunofluorescent intensity of promyelocytic leukemia nuclear bodies (PML NBs). PML NBs have been implicated in the modulation of transcription and the association of reporter plasmids with PML NBs has been implicated in repression of reporter activity. Additionally, repression of various reporters in the presence of LMP1 has been noted. This study demonstrates that LMP1 suppresses expression of reporter activity in a dose responsive manner and corresponds with the LMP1 induced increase in PML NB intensity. Disruption of PML NBs with arsenic trioxide or a PML siRNA restores reporter activity. These data offer an explanation for previously conflicting data on LMP1 signaling and calls attention to the possibility of false-positives and false-negatives when using reporter assays as a research tool in cells expressing LMP1.
Soluble Epoxide Hydrolase Limits Mechanical Hyperalgesia during Inflammation
Authors: Brenneis Christian , Sisignano Marco , Coste Ovidiu , Altenrath Kai , Fischer Michael J , Angioni Carlo , Fleming Ingrid , Brandes Ralf P , Reeh Peter W , Woolf Clifford J , Geisslinger Gerd , Scholich Klaus
Published: October 2011

Background:

Cytochrome-P450 (CYP450) epoxygenases metabolise arachidonic acid (AA) into four different biologically active epoxyeicosatrienoic acid (EET) regioisomers. Three of the EETs (i.e., 8,9-, 11,12- and 14,15-EET) are rapidly hydrolysed by the enzyme soluble epoxide hydrolase (sEH). Here, we investigated the role of sEH in nociceptive processing during peripheral inflammation.

Results:

In dorsal root ganglia (DRG), we found that sEH is expressed in medium and large diameter neurofilament 200-positive neurons. Isolated DRG-neurons from sEH−/− mice showed higher EET and lower DHET levels. Upon AA stimulation, the largest changes in EET levels occurred in culture media, indicating both that cell associated EET concentrations quickly reach saturation and EET-hydrolyzing activity mostly effects extracellular EET signaling. In vivo, DRGs from sEH-deficient mice exhibited elevated 8,9-, 11,12- and 14,15-EET-levels. Interestingly, EET levels did not increase at the site of zymosan-induced inflammation. Cellular imaging experiments revealed direct calcium flux responses to 8,9-EET in a subpopulation of nociceptors. In addition, 8,9-EET sensitized AITC-induced calcium increases in DRG neurons and AITC-induced calcitonin gene related peptide (CGRP) release from sciatic nerve axons, indicating that 8,9-EET sensitizes TRPA1-expressing neurons, which are known to contribute to mechanical hyperalgesia. Supporting this, sEH−/− mice showed increased nociceptive responses to mechanical stimulation during zymosan-induced inflammation and 8,9-EET injection reduced mechanical thresholds in naive mice.

Conclusion:

Our results show that the sEH can regulate mechanical hyperalgesia during inflammation by inactivating 8,9-EET, which sensitizes TRPA1-expressing nociceptors. Therefore we suggest that influencing the CYP450 pathway, which is actually highly considered to treat cardiovascular diseases, may cause pain side effects.
Dietary use and conservation concern of edible wetland plants at indo-burma hotspot: a case study from northeast India
Authors: Jain A , Sundriyal M , Roshnibala S , Kotoky R , Kanjilal PB , Singh HB , Sundriyal RC
Published: October 2011

Background

The wetlands of the North East India fall among the global hotspots of biodiversity. However, they have received very little attention with relation to their intrinsic values to human kind; therefore their conservation is hardly addressed. These wetlands are critical for the sustenance of the tribal communities.

Methods

Field research was conducted during 2003 to 2006 in seven major wetlands of four districts of Manipur state, Northeast India (viz. Imphal-East, Imphal-West, Thoubal, and Bishnupur). A total of 224 wetland-plant-collectors were interviewed for the use and economics of species using semi-structured questionnaires and interview schedules. Imphal, Bishenpur and Thoubal markets were investigated in detail for influx and consumption pattern of these plants. The collectors were also inquired for medicinal use of wetland species. Nutritive values of 21 species were analyzed in laboratory. The vouchers were collected for all the species and deposited in the CSIR-NEIST (Formerly Regional Research Laboratory), Substation, Lamphelpat, Imphal, Manipur, India.

Results

We recorded 51 edible wetland species used by indigenous people for food and medicinal purposes. Thirty eight species had high medicinal values and used in the traditional system to treat over 22 diseases. At least 27 species were traded in three markets studied (i.e. Imphal, Thoubal and Bishenpur), involving an annual turnover of 113 tons of wetland edible plants and a gross revenue of Rs. 907, 770/- (US$1 = Rs. 45/-). The Imphal market alone supplies 60% of the total business. Eighty per cent of the above mentioned species are very often used by the community. The community has a general opinion that the availability of 45% species has depleted in recent times, 15 species need consideration for conservation while another 7 species deserved immediate protection measures. The nutrient analysis showed that these species contribute to the dietary balance of tribal communities.

Conclusions

Considering the importance of wild wetland plants in local sustenance, it is suggested to protect their habitats, develop domestication protocols of selected species, and build programs for the long-term management of wetland areas by involving local people. Some medicinal plants may also be used to develop into modern medicines.
Kinase inhibitors can produce off-target effects and activate linked pathways by retroactivity
Authors: Wynn Michelle L , Ventura Alejandra C , Sepulchre Jacques A , García Héctor J , Merajver Sofia D
Published: October 2011

Background

It has been shown in experimental and theoretical work that covalently modified signaling cascades naturally exhibit bidirectional signal propagation via a phenomenon known as retroactivity. An important consequence of retroactivity, which arises due to enzyme sequestration in covalently modified signaling cascades, is that a downstream perturbation can produce a response in a component upstream of the perturbation without the need for explicit feedback connections. Retroactivity may, therefore, play an important role in the cellular response to a targeted therapy. Kinase inhibitors are a class of targeted therapies designed to interfere with a specific kinase molecule in a dysregulated signaling pathway. While extremely promising as anti-cancer agents, kinase inhibitors may produce undesirable off-target effects by non-specific interactions or pathway cross-talk. We hypothesize that targeted therapies such as kinase inhibitors can produce off-target effects as a consequence of retroactivity alone.

Results

We used a computational model and a series of simple signaling motifs to test the hypothesis. Our results indicate that within physiologically and therapeutically relevant ranges for all parameters, a targeted inhibitor can naturally induce an off-target effect via retroactivity. The kinetics governing covalent modification cycles in a signaling network were more important for propagating an upstream off-target effect in our models than the kinetics governing the targeted therapy itself. Our results also reveal the surprising and crucial result that kinase inhibitors have the capacity to turn "on" an otherwise "off" parallel cascade when two cascades share an upstream activator.

Conclusions

A proper and detailed characterization of a pathway's structure is important for identifying the optimal protein to target as well as what concentration of the targeted therapy is required to modulate the pathway in a safe and effective manner. We believe our results support the position that such characterizations should consider retroactivity as a robust potential source of off-target effects induced by kinase inhibitors and other targeted therapies.
Effects of plasma concentrations of 5-fluorouracil on long-term survival after treatment with a definitive 5-fluorouracil/cisplatin-based chemoradiotherapy in Japanese patients with esophageal squamous cell carcinoma
Authors: Kuwahara Akiko , Yamamori Motohiro , Kadoyama Kaori , Nishiguchi Kohshi , Nakamura Tsutomu , Miki Ikuya , Tamura Takao , Okuno Tatsuya , Omatsu Hideaki , Sakaeda Toshiyuki
Published: October 2011

Background

A substantial body of literature has accumulated during the past 20 years showing the plasma concentrations of 5-fluorouracil (5-FU) to correlate with clinical response and/or toxicity in colorectal cancer, and head and neck cancer, but little information is available concerning effects on long-term survival. Here, Japanese patients with esophageal squamous cell carcinoma (ESCC) were followed up for 5 years after treatment with a definitive 5-FU/cisplatin (CDDP)-based chemoradiotherapy (CRT), and the association between prognosis and the plasma concentration of 5-FU was evaluated.

Methods

Forty-nine patients with ESCC, who were treated with a definitive 5-FU/CDDP-based CRT, were enrolled. A course consisted of the continuous infusion of 5-FU at 400 mg/m2/day for days 1-5 and 8-12, the infusion of CDDP at 40 mg/m2/day on days 1 and 8, and the radiation at 2 Gy/day on days 1 to 5, 8 to 12, and 15 to 19, with a second course repeated after a 2-week interval. Plasma concentrations of 5-FU were determined by high performance liquid chromatography at 5:00 PM on days 3, 10, 38 and 45, and at 5:00 AM on days 4, 11, 39 and 46.

Results

The overall 5-year survival rate was 42.9%. Age (P = 0.020), body weight (P = 0.019), and disease stage (P = 0.048) affected the survival, and the survival depended on the clinical response assessed at 1 month after the treatment (P = 0.001). Higher plasma concentrations of 5-FU resulted in a better clinical response (P = 0.043), and trended to prolong survival (P = 0.321).

Conclusions

The long-term survival after treatment with a definitive 5-FU/CDDP-based CRT possibly depends on the plasma concentrations of 5-FU, and further clinical studies with a larger number of cases are needed to clarify the relationship between them.
Enzymatic synthesis of DNA employing pyrophosphate-linked dinucleotide substrates
Authors: Song Xiao-Ping , Maiti Mohitosh , Herdewijn Piet
Published: October 2011

Background

One of the remaining questions in the understanding of the origin of Nature's information system is the way the first nucleic acids have been synthesized. This could have been realized using nucleoside triphosphates or imidazolides of nucleoside monophosphates as building blocks. Alternatively, dinucleoside pyrophosphates could have been used for this purpose. The advantage of using building blocks, composed of pyrophosphate-linked dinucleotides, could be that exponential growth of initial information (dinucleotides) without product inhibition might become possible.

Results

Herein, we demonstrate that dinucleoside pyrophosphates are able to act as substrate for HIV-1 RT and several thermostable DNA polymerases. In single incorporation assay, compound dAppdA was able to give a 100% conversion to the (P+1) strand by Therminator DNA polymerase and at a substrate concentration above 100 μM. Full-length elongation was obtained in a chain elongation experiment, with over 95% yield of (P+7) product by Taq and Vent (exo-) DNA polymerase. Interestingly, using heterodimer dAppdT addition of either nucleotide component of the dinucleotide substrate into the DNA chain can occur, which is defined by the template program.

Conclusions

This study shows that dinucleoside pyrophosphates can be considered as a new type of substrate for polymerases in the template-directed DNA synthesis. Using heterodimers as substrate, theoretically, it is possible to synthesize DNA enzymatically using two building blocks (dAppdT and dGppdC) instead of four. Given the poor Km value for the nucleotide incorporation, evolution of polymerases will become necessary to make this process of practical use.
Immune-related disorders in families of children with inflammatory bowel disease - A prospective cohort study
Authors: Sibtain Alyzée M , Spady Donald , El-Matary Wael
Published: October 2011

Background

The aim of this paper was to examine the prevalence of immune-related disorders in families of children with inflammatory bowel disease (IBD) compared to those without IBD.

Methods

Children ≤18 years of age presenting to the IBD clinic between September 2007 and August 2009 with an established diagnosis of IBD were recruited. Age and sex matched controls without IBD were recruited. The study was a single-centre prospective cohort study. Outcome measures were prevalence of immune-based/inflammatory diseases in families of both patients and controls.

Results

One hundred and eight children in each group were recruited. Asthma was the most frequently reported disease in families of the IBD patients (52.8%) and controls (46.3%). The prevalence of IBD in families of IBD patients was significantly higher than in those without IBD (OR 2.03, 95% CI 1.04-3.95).

Conclusions

The prevalence of immune-based disorders, as a group, in families of children with IBD was not significantly higher when compared to children without IBD.
p38 Mitogen-activated protein kinase signaling regulates streptococcal M1 protein-induced neutrophil activation and lung injury
Authors: Zhang Songen , Rahman Milladur , Zhang Su , Wang Yongzhi , Herwald Heiko , Jeppsson Bengt , Thorlacius Henrik
Published: October 2011

M1 serotype of Streptococcus pyogenes can cause STSS and acute lung damage. Herein, the purpose was to define the role of p38 MAPK signaling in M1 protein-induced pulmonary injury. Male C57BL/6 mice were treated with specific p38 MAPK inhibitors (SB 239063 and SKF 86002) prior to M1 protein challenge. Edema, neutrophil infiltration, and CXC chemokines were determined in the lung, 4 h after M1 protein administration. Flow cytometry was used to determine Mac-1 expression. Phosphorylation and activity of p38 MAPK were determined by immunoprecipitation and Western blot. IVM was used to analyze leukocyte-endothelium interactions in the pulmonary microcirculation. M1 protein challenge increased phosphorylation and activity of p38 MAPK in the lung, which was inhibited by SB 239063 and SKF 86002. Inhibition of p38 MAPK activity decreased M1 protein-induced infiltration of neutrophils, edema, and CXC chemokine formation in the lung, as well as Mac-1 up-regulation on neutrophils. IVM showed that p38 MAPK inhibition reduced leukocyte rolling and adhesion in the pulmonary microvasculature of M1 protein-treated mice. Our results indicate that p38 MAPK signaling regulates neutrophil infiltration in acute lung injury induced by streptococcal M1 protein. Moreover, p38 MAPK activity controls CXC chemokine formation in the lung, as well as neutrophil expression of Mac-1 and recruitment in the pulmonary microvasculature. In conclusion, these findings suggest that targeting the p38 MAPK signaling pathway may open new opportunities to protect against lung injury in streptococcal infections.
Serum IGF-I Is Not a Reliable Pharmacodynamic Marker of Exogenous Growth Hormone Activity in Mice
Authors: Bielohuby Maximilian , Schaab Michael , Kummann Moritz , Sawitzky Mandy , Gebhardt Rolf , Binder Gerhard , Frystyk Jan , Bjerre Mette , Hoeflich Andreas , Kratzsch Juergen , Bidlingmaier Martin
Published: October 2011

Serum IGF-I is a well-established pharmacodynamic marker of GH administration in humans and has been used for this purpose in animal studies. However, its general suitability in wild-type laboratory mice has not been demonstrated. Here we show that treatment with recombinant human GH (rhGH) in four different strains of laboratory mice increases body weight, lean body mass, and liver weight but does not increase hepatic expression and release of IGF-I. In contrast and as expected, hypophysectomized rats show a rapid increase in serum IGF-I after rhGH administration. The lack of IGF-I up-regulation in mice occurs despite hepatic activation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway and is not explained by GH dose, route of administration, origin of GH (i.e. recombinant human, bovine, and murine GH), treatment duration, genetic background, sex, or formation of neutralizing antibodies. Effects on other components of the GH/IGF pathway were highly influenced by genetic background and sex but not consistently affected by rhGH treatment. We conclude that IGF-I is not a reliable indicator of the biological effects of exogenous GH treatment in genetically and pharmacologically unmodified mice. We speculate that IGF-I release is already maximal in these animals and cannot be further increased by exogenous GH treatment. This is also suggested by the observation of restored IGF-I up-regulation in isolated murine hepatocytes after rhGH treatment. Total body weight, lean body mass, and liver weight may be more reliable phenotypic indicators in these models.
Mechanisms Underlying Metformin-Induced Secretion of Glucagon-Like Peptide-1 from the Intestinal L Cell
Authors: Mulherin Andrew J. , Oh Amy H. , Kim Helena , Grieco Anthony , Lauffer Lina M. , Brubaker Patricia L.
Published: October 2011

Glucagon-like peptide-17-36NH2 (GLP-1) is secreted by the intestinal L cell in response to both nutrient and neural stimulation, resulting in enhanced glucose-dependent insulin secretion. GLP-1 is therefore an attractive therapeutic for the treatment of type 2 diabetes. The antidiabetic drug, metformin, is known to increase circulating GLP-1 levels, although its mechanism of action is unknown. Direct effects of metformin (5–2000 μm) or another AMP kinase activator, aminoimidazole carboxamide ribonucleotide (100–1000 μm) on GLP-1 secretion were assessed in murine human NCI-H716, and rat FRIC L cells. Neither agent stimulated GLP-1 secretion in any model, despite increasing AMP kinase phosphorylation (P < 0.05–0.01). Treatment of rats with metformin (300 mg/kg, per os) or aminoimidazole carboxamide ribonucleotide (250 mg/kg, sc) increased plasma total GLP-1 over 2 h, reaching 37 ± 9 and 29 ± 9 pg/ml (P < 0.001), respectively, compared with basal (7 ± 1 pg/ml). Plasma activity of the GLP-1-degrading enzyme, dipeptidylpeptidase-IV, was not affected by metformin treatment. Pretreatment with the nonspecific muscarinic antagonist, atropine (1 mg/kg, iv), decreased metformin-induced GLP-1 secretion by 55 ± 11% (P < 0.05). Pretreatment with the muscarinic (M) 3 receptor antagonist, 1-1-dimethyl-4-diphenylacetoxypiperidinium iodide (500 μg/kg, iv), also decreased the GLP-1 area under curve, by 48 ± 8% (P < 0.05), whereas the antagonists pirenzepine (M1) and gallamine (M2) had no effect. Furthermore, chronic bilateral subdiaphragmatic vagotomy decreased basal secretion compared with sham-operated animals (7 ± 1 vs. 13 ± 1 pg/ml, P < 0.001) but did not alter the GLP-1 response to metformin. In contrast, pretreatment with the gastrin-releasing peptide antagonist, RC-3095 (100 μg/kg, sc), reduced the GLP-1 response to metformin, by 55 ± 6% (P < 0.01) at 30 min. These studies elucidate the mechanism underlying metformin-induced GLP-1 secretion and highlight the benefits of using metformin with dipeptidylpeptidase-IV inhibitors in patients with type 2 diabetes.
Facile and Continuous Synthesis of Ag@SiO2 Core–Shell Nanoparticles by a Flow Reactor System Assisted with Homogeneous Microwave Heating
Authors: Nishioka Masateru , Miyakawa Masato , Kataoka Haruki , Koda Hidekazu , Sato Koichi , Suzuki Toshishige M
Published: October 2011

Ag@SiO2 core–shell nanoparticles were synthesized by integration of a series of flow processes including microwave (MW)-assisted Ag nanoparticle formation followed by coating with SiO2 shell. TEM monitoring of the reaction intermediates revealed that two reaction pathways take place concurrently during the SiO2 shell coating. MW heating (70 °C, 1 s) remarkably reduced the SiO2 shell-formation reaction time.
Spatiotemporal Allocation of Advertising Budgets
Authors: Aravindakshan Ashwin , Peters Kay , Naik Prasad A.
Published: October 2011

This article develops a method for optimal allocation of resources based on an empirically validated model of how national and regional advertising generate sales over time. The authors derive the profit-maximizing total budget, its optimal split between national and regional spends, and its optimal allocation across multiple regions. They formulate a spatiotemporal model that accounts for spatial and serial dependence, spatial heterogeneity, neighborhood effects, and sales dynamics. Because of spatial and serial dependence, correlated multivariate Brownian motion drives the sales dynamics, resulting in a second-order differential equation for the Hamilton–Jacobi–Bellman (HJB) equation with multiple states (i.e., regional sales) and multiple controls (i.e., regional and national advertising expenditures). By solving the HJB equation analytically, the authors furnish closed-form expressions for the optimal total budget and its regional allocations. In addition, they develop a method to estimate the proposed model and apply it to market data from a leading German cosmetics company. Using the estimated parameters, they evaluate the optimal budget and allocations. Comparing them with actual company policy, the proposed approach enhances profit by 5.07%, and it not only identifies which regions under-or overspend but also reveals how much budget to shift from national to regional advertising (or vice versa).
Characteristics of PAG Based Bio-Hydraulic Fluid
Authors: Khemchandani Govind , Greaves Martin R.
Published: October 2011

Regulatory drivers both in the U.S. and in the European Union are attempting to promote the use of biodegradable lubricants in the marketplace. A base fluid that uses the first ever combination of biodegradable polyalkylene glycol (PAG) with a high oleic canola oil was developed to meet environmental accreditation standards. This combination utilizes the PAG to “upgrade” the vegetable oil in hydraulic fluid formulation and provide a base fluid that can solubilize the oxidation by-products and provide better deposit control compared to straight general purpose fluids that are based on vegetable oils. A general purpose bio-hydraulic fluid that use a blend of PAG and high oleic canola oil has shown enhanced performance characteristics in two critical tests namely an oxidation test (ASTM D 2893 B) and a hydraulic vane pump test (ASTM D 7043). These two tests clearly differentiate the superior attributes of the PAG-based bio-hydraulic fluid compared to a widely use general purpose biodegradable hydraulic fluid in the market place.
Quality Assurance in Spectroscopic Analysis of Petroleum Products and Lubricants
Authors: Nadkarni R. A. Kishore
Published: October 2011

Quality assurance (QA) has been a fact of life in virtually all chemical processes and industries for many decades. Quality is an ingrained attitude, the results of which have a positive impact on all operations. Production of quality data does not occur automatically and is not guaranteed by following any one procedure or even several established procedures. It needs dedicated effort, careful attention to details, and practice of recognized principles of quality assurance.
Applications of Mass Spectrometry in the Petroleum and Petrochemical Industries
Authors: Mendez Aaron , Colin Todd B.
Published: October 2011

Mass spectrometry is approaching its first 100 years of being one of the most universal, versatile, and sensitive methods of analysis. It is the fastest-growing analytical technique of this decade, based on the great variety of detectors and their combination. It is an essential tool in the life sciences, where new high-resolution instrumentation, interfaces, and mass ranges have been reached. J. J. Thomson, almost a century ago, stated that this would be a technique that would resolve analytical problems with far more sensitivity and ease of use; this seems to be now an unarguable statement.
Neutron Activation and Gamma Ray Spectrometry Applied to the Analysis of Petroleum Products
Authors: Nadkarni R. A. Kishore
Published: October 2011

After World War II, with its advent of nuclear energy, one of the peaceful uses of nuclear energy was the development of neutron activation analysis (NAA) as an accurate tool for characterizations of elements in a variety of matrices. NAA is a technique based on irradiation in a nuclear reactor or other irradiation source and measuring resultant radioactivity of specific isotopes; it is a very accurate and precise technique. A large body of data exists on the applications of this technique to crude oil and petroleum products. At one time, several universities in the United States, such as the University of Kentucky, University of California at San Diego, University of California at Irvine, Purdue University, University of Missouri, Georgia Tech, Texas A&M University, Cornell University, University of Oregon, University of Maryland, and Washington State University, had active programs in NAA of fossil fuels and other matrices. Because of the difficulty of access to a nuclear reactor and associated radiation hazards, however, it has found only limited use in petrochemical or oil company laboratories. But one does not need one's own nuclear reactor for NAA because several commercial companies provide such services at a reasonable price. The universities mentioned also provide irradiation services to interested parties.
Elemental Analysis of Crude Oils Using Spectroscopic Methods
Authors: Nadkarni R. A. Kishore
Published: October 2011

Crude oils are highly complex hydrocarbon samples with some organometallic compounds, inorganic sediment, and water. Nearly 300 individual hydrocarbons and more than 200 separate sulfur compounds have been identified in crude oils [1]. A number of trace elements have been found in crude oils, but other than vanadium and nickel, which are most abundant in crude oils, other metals present have not received much work. There is also interest in the sodium content of crude oil as an indicator of sea-water contamination during transport. Many of these trace elements are present in milligram per kilogram (parts per million, ppm) or sub-ppm levels and thus, only sophisticated analytical techniques will be able to quantify them accurately.
Affiliative Behavior Requires Juvenile, But Not Adult Neurogenesis
Authors: Wei Lan , Meaney Michael J. , Duman Ronald S. , Kaffman Arie
Published: October 2011

The capacity to interact with conspecifics is essential for stable social networks, reproduction, and survival in mammals. In rodents, social exploration and play behavior increase during the juvenile period, suggesting that this timeframe represents an important window for socialization. However, the cellular and molecular mechanisms necessary to support this developmental process have not been elucidated. Neurogenesis during the juvenile period, like that in adults, is mainly confined to the subgranular and subventricular zones. Nevertheless, the levels of neurogenesis are significantly higher during the juvenile period, suggesting unique functions not shared with adult neurogenesis. Here we use a transgenic mouse approach that allows for ablation of neurogenesis during different developmental phases. We find that ablating neurogenesis during either juvenile or adult phases altered anxiety and memory in adult female mice, demonstrating an age-independent function of new neurons for certain behaviors. Blocking neurogenesis during the juvenile period resulted in a profound impairment in the ability of these mice to interact with other adult females or to retrieve pups, without causing gross olfactory deficits. Interestingly, ablating neurogenesis in adult females had no effect on these social behaviors. This work defines a novel role for juvenile neurogenesis in establishing brain circuits necessary for socialization, and demonstrates that juvenile and adult neurogenesis make different contributions to social competency in adult female mice. Additional work is needed to determine whether ablation of juvenile neurogenesis in the subgranular zone and/or the subventricular zone is responsible for the social abnormalities seen after global elimination of juvenile neurogenesis.
Stress and Glucocorticoids Impair Memory Retrieval via β2-Adrenergic, Gi/o-Coupled Suppression of cAMP Signaling
Authors: Schutsky Keith , Ouyang Ming , Castelino Christina B. , Zhang Lei , Thomas Steven A.
Published: October 2011

Acute stress impairs the retrieval of hippocampus-dependent memory, and this effect is mimicked by exogenous administration of stress-responsive glucocorticoid hormones. It has been proposed that glucocorticoids affect memory by promoting the release and/or blocking the reuptake of norepinephrine (NE), a stress-responsive neurotransmitter. It has also been proposed that this enhanced NE signaling impairs memory retrieval by stimulating β1-adrenergic receptors and elevating levels of cAMP. In contrast, other evidence indicates that NE, β1, and cAMP signaling is transiently required for the retrieval of hippocampus-dependent memory. To resolve this discrepancy, wild-type rats and mice with and without gene-targeted mutations were stressed or treated with glucocorticoids and/or adrenergic receptor drugs before testing memory for inhibitory avoidance or fear conditioning. Here we report that glucocorticoids do not require NE to impair retrieval. However, stress- and glucocorticoid-induced impairments of retrieval depend on the activation of β2(but not β1)-adrenergic receptors. Offering an explanation for the opposing functions of these two receptors, the impairing effects of stress, glucocorticoids and β2agonists on retrieval are blocked by pertussis toxin, which inactivates signaling by Gi/o-coupled receptors. In hippocampal slices, β2signaling decreases cAMP levels and greatly reduces the increase in cAMP mediated by β1signaling. Finally, augmenting cAMP signaling in the hippocampus prevents the impairment of retrieval by systemic β2agonists or glucocorticoids. These results demonstrate that the β2receptor can be a critical effector of acute stress, and that β1and β2receptors can have quite distinct roles in CNS signaling and cognition.
Effective Connectivity during Processing of Facial Affect: Evidence for Multiple Parallel Pathways
Authors: Dima Danai , Stephan Klaas E. , Roiser Jonathan P. , Friston Karl J. , Frangou Sophia
Published: October 2011

The perception of facial affect engages a distributed cortical network. We used functional magnetic resonance imaging and dynamic causal modeling to characterize effective connectivity during explicit (conscious) categorization of affective stimuli in the human brain. Specifically, we examined the modulation of connectivity from posterior regions of the face-processing network to the lateral ventral prefrontal cortex (VPFC) during affective categorization and we tested for a potential role of the amygdala (AMG) in mediating this modulation. We found that explicit processing of facial affect led to prominent modulation (increase) in the effective connectivity from the inferior occipital gyrus (IOG) to the VPFC, while there was less evidence for modulation of the afferent connections from fusiform gyrus and AMG to VPFC. More specifically, the forward connection from IOG to the VPFC exhibited a selective increase under anger (as opposed to fear or sadness). Furthermore, Bayesian model comparison suggested that the modulation of afferent connections to the VPFC was mediated directly by facial affect, as opposed to an indirect modulation mediated by the AMG. Our results thus suggest that affective information is conveyed to the VPFC along multiple parallel pathways and that AMG activity is not sufficient to account for the gating of information transfer to the VPFC during explicit emotional processing.