bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing quality of medical death certification: Concordance between gold standard diagnosis and underlying cause of death in selected Mexican hospitals
Authors: Hernández Bernardo , Ramírez-Villalobos Dolores , Romero Minerva , Gómez Sara , Atkinson Charles , Lozano Rafael
Published: August 2011

Background

In Mexico, the vital registration system relies on information collected from death certificates to generate official mortality figures. Although the death certificate has high coverage across the country, there is little information regarding its validity. The objective of this study was to assess the concordance between the underlying cause of death in official statistics obtained from death certificates and a gold standard diagnosis of the same deaths derived from medical records of hospitals.

Methods

The study sample consisted of 1,589 deaths that occurred in 34 public hospitals in the Federal District and the state of Morelos, Mexico in 2009. Neonatal, child, and adult cases were selected for causes of death that included infectious diseases, noncommunicable diseases, and injuries. We compared the underlying cause of death, obtained from medical death certificates, against a gold standard diagnosis derived from a review of medical records developed by the Population Health Metrics Research Consortium. We used chance-corrected concordance and accuracy as metrics to evaluate the quality of performance of the death certificate.

Results

Analysis considering only the underlying cause of death resulted in a median chance-corrected concordance between the cause of death in medical death certificates versus the gold standard of 54.3% (95% uncertainty interval [UI]: 52.2, 55.6) for neonates, 38.5% (37.0, 40.0) for children, and 66.5% (65.9, 66.9) for adults. The accuracy resulting from the same analysis was 0.756 (0.747, 0.769) for neonates, 0.683 (0.663, 0.701) for children, and 0.780 (0.774, 0.785) for adults. Median chance-corrected concordance and accuracy increased when considering the mention of any cause of death in the death certificate, not just the underlying cause. Concordance varied substantially depending on cause of death, and accuracy varied depending on the true cause-specific mortality fraction composition.

Conclusions

Although we cannot generalize our conclusions to Mexico as a whole, the results demonstrate important problems with the quality of the main source of information for causes of death used by decision-makers in settings with highly technological vital registration systems. It is necessary to improve death certification procedures, especially in the case of child and neonatal deaths. This requires an important commitment from the health system and health institutions.
Pulmonary medium vessel vasculitis in an 11 year old boy: Hughes Stovin syndrome as a variant of polyarteritis nodosa?
Authors: de Vries Willemien , Koppelman Gerard H , Roofthooft Marc TR , Bootsma Hendrika , Leijsma Martha K , Armbrust Wineke
Published: August 2011

We present the case of an 11-year-old boy presenting with haemoptysis, dyspnoea and weight loss as a manifestation of isolated pulmonary vasculitis, leading to pulmonary hypertension. He also appeared to have a longstanding dural venous sinus thrombosis. This rare presentation, especially in childhood, might represent a case of the seldomly reported Hughes-Stovin syndrome. The patient achieved remission after therapy with cyclophosphamide pulses and high-dose steroids. Based on the presented case and review of the literature, we propose that this syndrome might be a variant of polyarteritis nodosa. This report highlights diagnostic issues and describes a successful treatment regimen.
The PPAR-γ agonist pioglitazone modulates inflammation and induces neuroprotection in parkinsonian monkeys
Authors: Swanson Christine R , Joers Valerie , Bondarenko Viktoriya , Brunner Kevin , Simmons Heather A , Ziegler Toni E , Kemnitz Joseph W , Johnson Jeffrey A , Emborg Marina E
Published: August 2011

Background

Activation of the peroxisome proliferator-activated receptor gamma (PPAR-γ) has been proposed as a possible neuroprotective strategy to slow down the progression of early Parkinson's disease (PD). Here we report preclinical data on the use of the PPAR-γ agonist pioglitazone (Actos®; Takeda Pharmaceuticals Ltd.) in a paradigm resembling early PD in nonhuman primates.

Methods

Rhesus monkeys that were trained to perform a battery of behavioral tests received a single intracarotid arterial injection of 20 ml of saline containing 3 mg of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Twenty-four hours later the monkeys were assessed using a clinical rating scale, matched accordingly to disability, randomly assigned to one of three groups [placebo (n = 5), 2.5 (n = 6) or 5 (n = 5) mg/kg of pioglitazone] and their treatments started. Three months after daily oral dosing, the animals were necropsied.

Results

We observed significant improvements in clinical rating score (P = 0.02) in the animals treated with 5 mg/kg compared to placebo. Behavioral recovery was associated with preservation of nigrostriatal dopaminergic markers, observed as higher tyrosine hydroxylase (TH) putaminal optical density (P = 0.011), higher stereological cell counts of TH-ir (P = 0.02) and vesicular monoamine transporter-2 (VMAT-2)-ir nigral neurons (P = 0.006). Stereological cell counts of Nissl stained nigral neurons confirmed neuroprotection (P = 0.017). Pioglitazone-treated monkeys also showed a dose-dependent modulation of CD68-ir inflammatory cells, that was significantly decreased for 5 mg/kg treated animals compared to placebo (P = 0.018). A separate experiment to assess CSF penetration of pioglitazone revealed that 5 mg/kg p.o. induced consistently higher levels than 2.5 mg/kg and 7.5 mg/kg. p.o.

Conclusions

Our results indicate that oral administration of pioglitazone is neuroprotective when administered early after inducing a parkinsonian syndrome in rhesus monkeys and supports the concept that PPAR-γ is a viable target against neurodegeneration.
Nef-mediated enhancement of cellular activation and human immunodeficiency virus type 1 replication in primary T cells is dependent on association with p21-activated kinase 2
Authors: Olivieri Kevin C , Mukerji Joya , Gabuzda Dana
Published: August 2011

Background

The HIV-1 accessory protein Nef is an important determinant of lentiviral pathogenicity that contributes to disease progression by enhancing viral replication and other poorly understood mechanisms. Nef mediates diverse functions including downmodulation of cell surface CD4 and MHC Class I, enhancement of viral infectivity, and enhancement of T cell activation. Nef interacts with a multiprotein signaling complex that includes Src family kinases, Vav1, CDC42, and activated PAK2 (p21-activated kinase 2). Although previous studies have attempted to identify a biological role for the Nef-PAK2 signaling complex, the importance of this complex and its constituent proteins in Nef function remains unclear.

Results

Here, we show that Nef mutants defective for PAK2-association, but functional for CD4 and MHC Class I downmodulation and infectivity enhancement, are also defective for the ability to enhance viral replication in primary T cells that are infected and subsequently activated by sub-maximal stimuli (1 μg/ml PHA-P). In contrast, these Nef mutants had little or no effect on HIV-1 replication in T cells activated by stronger stimuli (2 μg/ml PHA-P or anti-CD3/CD28-coated beads). Viruses bearing wild-type Nefs, but not Nef mutants defective for PAK2 association, enhanced NFAT and IL2 receptor promoter activity in Jurkat cells. Moreover, expression of wild-type Nefs, but not mutant Nefs defective for PAK2 association, was sufficient to enhance responsiveness of primary CD4 and CD8 T cells to activating stimuli in Nef-expressing and bystander cells. siRNA knockdown of PAK2 in Jurkat cells reduced NFAT activation induced by anti-CD3/CD28 stimulation both in the presence and absence of Nef, and expression of a PAK2 dominant mutant inhibited Nef-mediated enhancement of CD25 expression.

Conclusion

Nef-mediated enhancement of cellular activation and viral replication in primary T cells is dependent on PAK2 and on the strength of the activating stimuli, and correlates with the ability of Nef to associate with PAK2. PAK2 is likely to play a role in Nef-mediated enhancement of viral replication and immune activation in vivo.
Behavioral Evidence for the Differential Regulation of p-p38 MAPK and p-NF-κB in Rats with Trigeminal Neuropathic Pain
Authors: Lee Min K , Han Seung R , Park Min K , Kim Min J , Bae Yong C , Kim Sung K , Park Jae S , Ahn Dong K
Published: August 2011

Background:

We investigated the differential regulation of p-p38 MAPK or p-NF- κB in male Sprague-Dawley rats with inferior alveolar nerve injury resulting from mal-positioned dental implants. For this purpose, we characterized the temporal expression of p-p38 MAPK or p-NF- κB in the medullary dorsal horn and examined changes in nociceptive behavior after a blockade of p-p38 MAPK or p-NF- κB pathways in rats with trigeminal neuropathic pain.

Results:

Under anesthesia, the left lower second molar was extracted and replaced with a mini dental implant to intentionally injure the inferior alveolar nerve. Western and immunofluorescence analysis revealed that p-p38 MAPK is upregulated in microglia following nerve injury and that this expression peaked on postoperative day (POD) 3 through 7. However, the activation of p-NF- κB in astrocyte peaked on POD 7 through 21. The intracisternal administration of SB203580 (1 or 10 μg), a p38 MAPK inhibitor, on POD 3 but not on POD 21 markedly inhibits mechanical allodynia and the p-p38 MAPK expression. However, the intracisternal administration of SN50 (0.2 or 2 ng), an NF- κB inhibitor, on POD 21 but not on POD 3 attenuates mechanical allodynia and p-NF- κB expression. Dexamethasone (25 mg/kg) decreases not only the activation of p38 MAPK but also that of NF- κB on POD 7.

Conclusions:

These results suggest that early expression of p-p38 MAPK in the microglia and late induction of p-NF- κB in astrocyte play an important role in trigeminal neuropathic pain and that a blockade of p-p38 MAPK at an early stage and p-NF- κB at a late stage might be a potential therapeutic strategy for treatment of trigeminal neuropathic pain.
Medicinal plants used for traditional veterinary in the Sierras de Córdoba (Argentina): An ethnobotanical comparison with human medicinal uses
Authors: Martínez Gustavo J , Luján María C
Published: August 2011

Background

This is a first description of the main ethnoveterinary features of the peasants in the Sierras de Córdoba. The aim of this study was to analyze the use of medicinal plants and other traditional therapeutic practices for healing domestic animals and cattle. Our particular goals were to: characterize veterinary ethnobotanical knowledge considering age, gender and role of the specialists; interpret the cultural features of the traditional local veterinary medicine and plant uses associated to it; compare the plants used in traditional veterinary medicine, with those used in human medicine in the same region.

Methods

Fieldwork was carried out as part of an ethnobotanic regional study where 64 informants were interviewed regarding medicinal plants used in veterinary medicine throughout 2001-2010. Based participant observation and open and semi-structured interviews we obtained information on the traditional practices of diagnosis and healing, focusing on the veterinary uses given to plants (part of the plant used, method of preparation and administration). Plants speciemens were collected with the informants and their vernacular and scientific names were registered in a database. Non-parametric statistic was used to evaluate differences in medicinal plant knowledge, use, and valorization by local people. A comparison between traditional veterinary medicine and previous human medicine studies developed in the region was performed by analyzing the percentages of common species and uses, and by considering Sorensen's Similarity Index.

Results

A total of 127 medicinal uses were registered, corresponding to 70 species of plants belonging to 39 botanic families. Veterinary ethnobotanical knowledge was specialized, restricted, in general, to cattle breeders (mainly men) and to a less degree to healers, and was independent of the age of the interviewees. Native plants were mostly used as skin cicatrizants, disinfectants or for treating digestive disorders. Together with a vast repertoire of plant pharmacopoeia, the therapies also involve religious or ritualistic practices and other popular remedies that evidence the influence of traditional Hispanic-European knowledge. Although the traditional veterinary knowledge seems to be similar or else is inlcuded in the local human ethnomedicine, sharing a common group of plants, it has distinct traits originated by a constant assessment of new applications specifically destined to the treatment of animals.

Conclusions

Veterinary medicine is a fountain of relevant vernacular knowledge, a permanent source for testing new applications with valuable ethnobotanical interest. Knowledge on medicinal applications of native plants will allow future validations and tests for new homeopathic or phytotherapeutic preparations.
A retrosynthetic biology approach to metabolic pathway design for therapeutic production
Authors: Carbonell Pablo , Planson Anne-Gaëlle , Fichera Davide , Faulon Jean-Loup
Published: August 2011

Background

Synthetic biology is used to develop cell factories for production of chemicals by constructively importing heterologous pathways into industrial microorganisms. In this work we present a retrosynthetic approach to the production of therapeutics with the goal of developing an in situ drug delivery device in host cells. Retrosynthesis, a concept originally proposed for synthetic chemistry, iteratively applies reversed chemical transformations (reversed enzyme-catalyzed reactions in the metabolic space) starting from a target product to reach precursors that are endogenous to the chassis. So far, a wider adoption of retrosynthesis into the manufacturing pipeline has been hindered by the complexity of enumerating all feasible biosynthetic pathways for a given compound.

Results

In our method, we efficiently address the complexity problem by coding substrates, products and reactions into molecular signatures. Metabolic maps are represented using hypergraphs and the complexity is controlled by varying the specificity of the molecular signature. Furthermore, our method enables candidate pathways to be ranked to determine which ones are best to engineer. The proposed ranking function can integrate data from different sources such as host compatibility for inserted genes, the estimation of steady-state fluxes from the genome-wide reconstruction of the organism's metabolism, or the estimation of metabolite toxicity from experimental assays. We use several machine-learning tools in order to estimate enzyme activity and reaction efficiency at each step of the identified pathways. Examples of production in bacteria and yeast for two antibiotics and for one antitumor agent, as well as for several essential metabolites are outlined.

Conclusions

We present here a unified framework that integrates diverse techniques involved in the design of heterologous biosynthetic pathways through a retrosynthetic approach in the reaction signature space. Our engineering methodology enables the flexible design of industrial microorganisms for the efficient on-demand production of chemical compounds with therapeutic applications.
An improved kinetic model for the acetone-butanol-ethanol pathway of Clostridium acetobutylicum and model-based perturbation analysis
Authors: Li Ru-Dong , Li Yuan-Yuan , Lu Ling-Yi , Ren Cong , Li Yi-Xue , Liu Lei
Published: August 2011

Background

Comprehensive kinetic models of microbial metabolism can enhance the understanding of system dynamics and regulatory mechanisms, which is helpful in optimizing microbial production of industrial chemicals. Clostridium acetobutylicum produces solvents (acetone-butanol–ethanol, ABE) through the ABE pathway. To systematically assess the potential of increased production of solvents, kinetic modeling has been applied to analyze the dynamics of this pathway and make predictive simulations. Up to date, only one kinetic model for C. acetobutylicum supported by experiment has been reported as far as we know. But this model did not integrate the metabolic regulatory effects of transcriptional control and other complex factors. It also left out the information of some key intermediates (e.g. butyryl-phosphate).

Results

We have developed an improved kinetic model featured with the incorporation of butyryl-phosphate, inclusion of net effects of complex metabolic regulations, and quantification of endogenous enzyme activity variations caused by these regulations. The simulation results of our model are more consistent with published experimental data than the previous model, especially in terms of reflecting the kinetics of butyryl-phosphate and butyrate. Through parameter perturbation analysis, it was found that butyrate kinase has large and positive influence on butanol production while CoA transferase has negative effect on butanol production, suggesting that butyrate kinase has more efficiency in converting butyrate to butanol than CoA transferase.

Conclusions

Our improved kinetic model of the ABE process has more capacity in approaching real circumstances, providing much more insight in the regulatory mechanisms and potential key points for optimization of solvent productions. Moreover, the modeling strategy can be extended to other biological processes.
Perceptions and viewpoints on proceedings of the Fifteenth Assembly of Heads of State and Government of the African Union Debate on Maternal, Newborn and Child Health and Development, 25–27 July 2010, Kampala, Uganda
Authors: Sambo Luis Gomes , Kirigia Joses Muthuri , Ki-Zerbo Georges
Published: August 2011

Background

Out of 358000 maternal deaths that occurred globally in 2008, 57.8% occurred in continental Africa. Africa had a maternal mortality ratio of 590 compared to 14 in developed regions, 68 in Latin America and Caribbean, and 190 in Asia. This article reflects on the discussions held during the Fifteenth Assembly of the Heads of State and Government of the African Union on the reasons why the maternal mortality ratio is so high in Africa and what can be done to reduce it.

Methods

Methods employed included panel and open public discussions among the Heads of State and Government of the African Union. The article uses the WHO health systems strengthening framework, which consists of six pillars (information systems, leadership and governance, health workforce, financing, and medical products, vaccines and technologies, and health services) to describe the proceedings of the discussions.

Discussion

The high maternal mortality ratios in countries were attributed to weak national health information systems; leadership and governance challenges related to poverty, health illiteracy, poor transport networks and communications infrastructure, risky cultural practices, armed conflicts and domestic violence, dearth of women empowerment; inadequate levels of skilled birth attendants; inadequate domestic and external funding; stock-outs of consumable inputs; and limited coverage of maternal and child health interventions.

In order to accelerate progress towards MDGs 4 and 5, the Heads of State and Government recommended that countries should make maternal deaths notifiable and institutionalize maternal death audits; develop, fund and implement policies and strategies geared at improving maternal, newborn and child health; accelerate inter-sectoral action to address the broad health determinants; increase the number of skilled birth attendants; fulfil commitment to allocate at least 15% of the national budget to the health sector and allocate adequate resources to prevent stock-outs of essential medicines and reproductive health commodities; leverage health promotion approaches to raise national awareness; and ensure that there is a health centre within a radius of four kilometres equipped to provide good quality integrated maternal, newborn and child health services.

Conclusions

There was consensus among the discussants that there was urgent need to speed up actions for strengthening health systems to improve coverage of maternal, newborn and child health services; and to address broad determinants of women, newborn and children’s health for sustained improvements in health and other development goals.
Stink Bug Feeding Induces Fluorescence in Developing Cotton Bolls
Authors: Xia Jinjun , Mustafic Adnan , Toews Michael D , Haidekker Mark A
Published: August 2011

Background

Stink bugs (Hemiptera: Pentatomidae) comprise a critically important insect pest complex affecting 12 major crops worldwide including cotton. In the US, stink bug damage to developing cotton bolls causes boll abscission, lint staining, reduced fiber quality, and reduced yields with estimated losses ranging from 10 to 60 million dollars annually. Unfortunately, scouting for stink bug damage in the field is laborious and excessively time consuming. To improve scouting accuracy and efficiency, we investigated fluorescence changes in cotton boll tissues as a result of stink bug feeding.

Results

Fluorescent imaging under long-wave ultraviolet light showed that stink bug-damaged lint, the inner carpal wall, and the outside of the boll emitted strong blue-green fluorescence in a circular region near the puncture wound, whereas undamaged tissue emissions occurred at different wavelengths; the much weaker emission of undamaged tissue was dominated by chlorophyll fluorescence. We further characterized the optimum emission and excitation spectra to distinguish between stink bug damaged bolls from undamaged bolls.

Conclusions

The observed characteristic fluorescence peaks associated with stink bug damage give rise to a fluorescence-based method to rapidly distinguish between undamaged and stink bug damaged cotton bolls. Based on the fluorescent fingerprint, we envision a fluorescence reflectance imaging or a fluorescence ratiometric device to assist pest management professionals with rapidly determining the extent of stink bug damage in a cotton field.
Differential gene expression in Schistosoma japonicum schistosomula from Wistar rats and BALB/c mice
Authors: Peng Jinbiao , Han Hongxiao , Gobert Geoffrey N , Hong Yang , Jiang Weibin , Wang Xinzhi , Fu Zhiqiang , Liu Jinming , Shi Yaojun , Lin Jiaojiao
Published: August 2011

Background

More than 46 species of mammals can be naturally infected with Schistosoma japonicum in the mainland of China. Mice are permissive and may act as the definitive host of the life cycle. In contrast, rats are less susceptible to S. japonicum infection, and are considered to provide an unsuitable micro-environment for parasite growth and development. Since little is known of what effects this micro-environment has on the parasite itself, we have in the present study utilised a S. japonicum oligonucleotide microarray to compare the gene expression differences of 10-day-old schistosomula maintained in Wistar rats with those maintained in BALB/c mice.

Results

In total 3,468 schistosome genes were found to be differentially expressed, of which the majority (3,335) were down-regulated (≤ 2 fold) and 133 were up-regulated (≥ 2 fold) in schistosomula from Wistar rats compared with those from BALB/c mice. Gene ontology (GO) analysis revealed that of the differentially expressed genes with already established functions or close homology to well characterized genes in another organisms, many are related to important biological functions or molecular processes. Among the genes that were down-regulated in schistosomula from Wistar rats, some were associated with metabolism, signal transduction and development. Of these genes related to metabolic processes, areas including translation, protein and amino acid phosphorylation, proteolysis, oxidoreductase activities, catalytic activities and hydrolase activities, were represented. KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis of differential expressed genes indicated that of the 328 genes that had a specific KEGG pathway annotation, 324 were down-regulated and were mainly associated with metabolism, growth, redox pathway, oxidative phosphorylation, the cell cycle, ubiquitin-mediated proteolysis, protein export and the MAPK (mitogen-activated protein kinases) signaling pathway.

Conclusions

This work presents the first large scale gene expression study identifying the differences between schistosomula maintained in mice and those maintained in rats, and specifically highlights differential expression that may impact on the survival and development of the parasite within the definitive host. The research presented here provides valuable information for the better understanding of schistosome development and host-parasite interactions.
Adult mortality in the cities of Bulawayo and Harare, Zimbabwe: 1979‐2008
Authors: Dlodlo Riitta A , Fujiwara Paula I , Hwalima Zanele E , Mungofa Stanley , Harries Anthony D
Published: August 2011

Background

Zimbabwe has been severely affected by the HIV/AIDS and tuberculosis epidemics, with an estimated 80% of tuberculosis patients being HIV infected. We set out to use annual population‐mortality records from the cities of Harare and Bulawayo to describe trends and possible causes of mortality from 1979 to 2008. The specific objectives were to document overall, sex and age‐specific mortality, proportion of deaths attributed to AIDS and tuberculosis, and changes in death rates since the start of antiretroviral therapy in 2004.

Methods

This retrospective descriptive study used existing mortality records of the Health Services departments in Harare and Bulawayo. Data points included: estimated yearly total population; groupings by sex and age; deaths (total and by sex and age groups for each year of the study period); and most frequently reported causes of death (for age groups <15 years, 15‐44 years and ≥45 years). Data on deaths were aggregated by year, and crude, sex‐ and age‐specific death rates were calculated per 1000 population. Tuberculosis and HIV‐related disease‐specific death rates and proportion of deaths attributed to these conditions were computed.

Results

In both cities, crude death rates were lowest in the late 1980s, increased three‐ to five‐fold by the early 2000s, and began a slow and, in the case of Bulawayo, intermittent decline from 2004. Sex‐specific death rates followed a similar trend, being higher in males than in females. The death rates in the age groups <5 years, 15‐44 years and ≥45 years showed significant increases, with a gradual levelling off and decline from 2002 onwards; death rates in those aged 5‐14 years were relatively unaffected. Tuberculosis and HIV caused 70% of deaths in the age group of 15‐44 years from the early 1990s.

Conclusions

This study used routinely collected population‐mortality data that are rare in resource‐limited settings, and it described, for the first time in Zimbabwe, the effects of the HIV/AIDS epidemic and the introduction of antiretroviral therapy on death rates in two large cities. After a substantial rise in crude mortality rates, there has been a decline associated with the introduction of ART. Such routine population data must continue to be collected, collated and analyzed.
A cell-intrinsic role for CaMKK2 in granulocyte lineage commitment and differentiation
Authors: Teng Ellen C , Racioppi Luigi , Means Anthony R
Published: August 2011

Granulocytes serve a critical function in host organisms by recognizing and destroying invading microbes, as well as propagating and maintaining inflammation at sites of infection. However, the molecular pathways underpinning the development of granulocytes are poorly understood. Here, we identify a role for CaMKK2 in the restriction of granulocytic fate commitment and differentiation of myeloid progenitor cells. Following BMT, engraftment by Camkk2−/− donor cells resulted in the increased production of mature granulocytes in the BM and peripheral blood. Similarly, Camkk2−/− mice possessed elevated numbers of CMP cells and exhibited an accelerated granulopoietic phenotype in the BM. Camkk2−/− myeloid progenitors expressed increased levels of C/EBPα and PU.1 and preferentially differentiated into Gr1+Mac1+ granulocytes and CFU-G in vitro. During normal granulopoiesis in vivo or G-CSF-induced differentiation of 32D myeloblast cells in vitro, CaMKK2 mRNA and protein were decreased as a function of time and were undetectable in mature granulocytes. Expression of ectopic CaMKK2 in Camkk2−/− CMPs was sufficient to rescue aberrant granulocyte differentiation and when overexpressed in 32D cells, was also sufficient to impede granulocyte differentiation in a kinase activity-dependent manner. Collectively, our results reveal a novel role for CaMKK2 as an inhibitor of granulocytic fate commitment and differentiation in early myeloid progenitors.
HMGN2 Inducibly Binds a Novel Transactivation Domain in Nuclear PRLr to Coordinate Stat5a-Mediated Transcription
Authors: Fiorillo Alyson A. , Medler Terry R. , Feeney Yvonne B. , Liu Yi , Tommerdahl Kalie L. , Clevenger Charles V.
Published: August 2011

The direct actions of transmembrane receptors within the nucleus remain enigmatic. In this report, we demonstrate that the prolactin receptor (PRLr) localizes to the nucleus where it functions as a coactivator through its interactions with the latent transcription factor signal transducer and activator of transcription 5a (Stat5a) and the high-mobility group N2 protein (HMGN2). We identify a novel transactivation domain within the PRLr that is activated by ligand-induced phosphorylation, an event coupled to HMGN2 binding. The association of the PRLr with HMGN2 enables Stat5a-responsive promoter binding, thus facilitating transcriptional activation and promoting anchorage-independent growth. We propose that HMGN2 serves as a critical regulatory factor in Stat5a-driven gene expression by facilitating the assembly of PRLr/Stat5a onto chromatin and that these events may serve to promote biological events that contribute to a tumorigenic phenotype. Our data imply that phosphorylation may be the molecular switch that activates a cell surface receptor transactivation domain, enabling it to tether chromatin-modifying factors, such as HMGN2, to target promoter regions in a sequence-specific manner.
Estrogen Sulfotransferase Inhibits Adipocyte Differentiation
Authors: Wada Taira , Ihunnah Chibueze A. , Gao Jie , Chai Xiaojuan , Zeng Su , Philips Brian J. , Rubin J. Peter , Marra Kacey G. , Xie Wen
Published: August 2011

The estrogen sulfotransferase (EST) is a phase II drug-metabolizing enzyme known to catalyze the sulfoconjugation of estrogens. EST is highly expressed in the white adipose tissue of male mice, but the role of EST in the development and function of adipocytes remains largely unknown. In this report, we showed that EST played an important role in adipocyte differentiation. EST was highly expressed in 3T3-L1 preadipocytes and primary mouse preadipocytes. The expression of EST was dramatically reduced in differentiated 3T3-L1 cells and mature primary adipocytes. Overexpression of EST in 3T3-L1 cells prevented adipocyte differentiation. In contrast, preadipocytes isolated from EST knockout (EST−/−) mice exhibited enhanced differentiation. The inhibitory effect of EST on adipogenesis likely resulted from the sustained activation of ERK1/2 MAPK and inhibition of insulin signaling, leading to a failure of switch from clonal expansion to differentiation. The enzymatic activity of EST was required for the inhibitory effect of EST on adipogenesis, because an enzyme-dead EST mutant failed to inhibit adipocyte differentiation. In vivo, overexpression of EST in the adipose tissue of female transgenic mice resulted in smaller adipocyte size. Taken together, our results suggest that EST functions as a negative regulator of adipogenesis.
Abca12-mediated lipid transport and Snap29-dependent trafficking of lamellar granules are crucial for epidermal morphogenesis in a zebrafish model of ichthyosis
Authors: Li Qiaoli , Frank Michael , Akiyama Masashi , Shimizu Hiroshi , Ho Shiu-Ying , Thisse Christine , Thisse Bernard , Sprecher Eli , Uitto Jouni
Published: August 2011

Zebrafish (Danio rerio) can serve as a model system to study heritable skin diseases. The skin is rapidly developed during the first 5–6 days of embryonic growth, accompanied by expression of skin-specific genes. Transmission electron microscopy (TEM) of wild-type zebrafish at day 5 reveals a two-cell-layer epidermis separated from the underlying collagenous stroma by a basement membrane with fully developed hemidesmosomes. Scanning electron microscopy (SEM) reveals an ordered surface contour of keratinocytes with discrete microridges. To gain insight into epidermal morphogenesis, we have employed morpholino-mediated knockdown of the abca12 and snap29 genes, which are crucial for secretion of lipids and intracellular trafficking of lamellar granules, respectively. Morpholinos, when placed on exon-intron junctions, were >90% effective in preventing the corresponding gene expression when injected into one- to four-cell-stage embryos. By day 3, TEM of abca12 morphants showed accumulation of lipid-containing electron-dense lamellar granules, whereas snap29 morphants showed the presence of apparently empty vesicles in the epidermis. Evaluation of epidermal morphogenesis by SEM revealed similar perturbations in both cases in the microridge architecture and the development of spicule-like protrusions on the surface of keratinocytes. These morphological findings are akin to epidermal changes in harlequin ichthyosis and CEDNIK syndrome, autosomal recessive keratinization disorders due to mutations in the ABCA12 and SNAP29 genes, respectively. The results indicate that interference of independent pathways involving lipid transport in the epidermis can result in phenotypically similar perturbations in epidermal morphogenesis, and that these fish mutants can serve as a model to study the pathomechanisms of these keratinization disorders.
Wandering spleen with torsion and complete infarction
Authors: Chu Jianping , Li Ziping , Luo Boning , Yang Jianyong
Published: August 2011

Wandering spleen is rare and is associated with a high incidence of splenic torsion and infarction. Presenting symptoms range from an asymptomatic, incidentally palpated abdominal mass to an acutely ill patient. Because wandering spleen is uncommon in the pediatric population, a heightened awareness of the condition is required for accurate diagnosis and appropriate management. We present a case of a 4-year-old girl who presented with acute abdomen and was surgically confirmed to have a wandering spleen with torsion and complete infarction.
Epistaxis in patients with hereditary hemorrhagic telangiectasia treated with selective arterial embolization
Authors: Trojanowski Piotr , Jargiełło Tomasz , Trojanowska Agnieszka , Klatka Janusz
Published: August 2011

Background

Hereditary hemorrhagic telangiectasia (HHT) is a rare systemic fibrovascular dysplasia also known as Rendu-Osler-Weber disease. Epistaxis is often the first and foremost symptom of the disease and recurrent epistaxis is the main complaint.

Purpose

Evaluation of effectiveness and safety of endovascular treatment of epistaxis in HHT patients.

Material and Methods

Between June 2004 and January 2008, 14 patients with HHT underwent embolization of external carotid artery (ECA) branches due to severe epistaxis. There were eight men and six women aged 27–42 years. Patients were referred for endovascular treatment when primary management with electrocautery and nasal packing was ineffective. Arteries suspected of bleeding were catheterized super-selectively with micro-catheters to perform embolization. Polyvinyl alcohol particles (PVA) or embospheres in diameter of 500–700-µm were used as an embolic material.

Results

Embolization was technically successful in 11 (78.5%) patients. Immediate, complete control of bleeding was achieved in 12 (85%) patients. During long-term follow-up recurrent nasal bleeding occurred in six (43%) patients 6–24 months after treatment. There were no severe complications after embolization. Nine patients experienced mild facial pain which resolved within three days after the treatment. Three patients in whom arterial spasm was observed, suffered from facial paraesthesia lasting for 3–5 days after embolization. Out of 14 patients, 12 were available for 24-month follow-up evaluation. All except one claimed reduction in frequency and severity of epistaxis which had a positive impact on their quality of life.

Conclusion

Endovascular embolization of epistaxis in patients with HHT is an effective and safe procedure although it cannot provide a long-term cure in most cases. Embolization reduces the frequency, severity and duration of nasal bleeding in patients with HHT, improving patients' quality of life.
Cash-Out or Flameout! Opportunity Cost and Entrepreneurial Strategy: Theory, and Evidence from the Information Security Industry
Authors: Arora Ashish , Nandkumar Anand
Published: August 2011

We analyze how entrepreneurial opportunity cost conditions performance. Departing from the common practice of using survival as a measure of entrepreneurial performance, we model both failure and cash-out (liquidity event) as conditioned by the same underlying process. High-opportunity-cost entrepreneurs prefer a shorter time to success, even if this also implies failing more quickly, whereas entrepreneurs with fewer outside alternatives will choose less aggressive strategies and, consequently, linger on longer. We formalize this intuition with a simple model. Using a novel data set of information security start-ups, we find that entrepreneurs with high opportunity costs are not only more likely to cash out more quickly but are also more likely to fail faster. Not only is survival a poor indicator of performance, but its use as one obscures the relationship between entrepreneurial characteristics, entrepreneurial strategies, and outcomes.

This paper was accepted by David Hsu, entrepreneurship and innovation.
Tournaments Without Prizes: Evidence from Personnel Records
Authors: Blanes i Vidal Jordi , Nossol Mareike
Published: August 2011

We use a quasi-experimental research design to study the effect of giving workers feedback on their relative performance. The setting is a firm in which workers are paid piece rates and where, for exogenous reasons, management begins to reveal to workers their relative position in the distribution of pay and productivity. We find that merely providing this information leads to a large and long-lasting increase in productivity that is costless to the firm. Our findings are consistent with the interpretation that workers' incipient concerns about their relative standing are activated by information about how they are performing relative to others.

This paper was accepted by Olav Sorenson, organizations.
Corporate Social Responsibility and Competitive Advantage: Overcoming the Trust Barrier
Authors: Du Shuili , Bhattacharya C. B. , Sen Sankar
Published: August 2011

This research builds on the complementary corporate social responsibility (CSR) literatures in strategy and marketing to provide insight into the efficacy of CSR as a challenger's competitive weapon against a market leader. Through an investigation of a real-world CSR initiative, we show that the challenger can reap superior business returns (i.e., more positive attitudinal and behavioral outcomes) among consumers who had participated in its CSR initiative, relative to those who were merely aware of the initiative. Specifically, participant consumers demonstrate the desired attitudinal and behavioral changes in favor of the challenger, regardless of their affective trust in the leader, whereas aware consumers' reactions become less favorable as their affective trust in the leader increases. Furthermore, participant consumers, but not aware ones, form a communal, trust-based bond with the challenger.

This paper was accepted by Pradeep Chintagunta and Preyas Desai, special issue editors.

This paper was accepted by Pradeep Chintagunta and Preyas Desai, special issue editors.
On Some Equations Related to Ma's Conjecture
Authors: Luo Jiagui , Togbé Alain , Yuan Pingzhi
Published: August 2011

In 1992, Ma made a conjecture related to Pell equations. In this paper, we use Störmer's theorem and related results on Pell equations to prove some particular cases of Ma's conjecture.
Number of Weighted Subsequence Sums with Weights in {1, –1}
Authors: Adhikari Sukumar Das , Chintamani Mohan N.
Published: August 2011

Let
Logarithmic convergence rate of Levenberg–Marquardt method with application to an inverse potential problem
Authors: Böckmann Christine , Kammanee Athassawat , Braunß Andreas
Published: August 2011

We prove logarithmic convergence rate of the Levenberg–Marquardt method in a Hilbert space if a logarithmic source condition is satisfied. This method is applied to an inverse potential problem. Numerical implementations demonstrate the convergence rate.
Exponential instability in the Gel'fand inverse problem on the energy intervals
Authors: Isaev Mikhail Ismailovitch
Published: August 2011

We consider the Gel'fand inverse problem and continue studies of Mandache (Inverse Problems 17: 1435–1444, 2001). We show that the Mandache-type instability remains valid even in the case of Dirichlet-to-Neumann map given on the energy intervals. These instability results show, in particular, that the logarithmic stability estimates of Alessandrini (Appl. Anal. 27: 153–172, 1988), Novikov and Santacesaria (J. Inverse Ill-Posed Probl., 2010) and especially of Novikov (2010) are optimal (up to the value of the exponent).
Fluctuation-induced forces in critical crosslinked polymer blends
Authors: El Fassi Saâd , Benhamou Mabrouk , Agouzouk Abdellatif , Boughou Mohamed , Kaïdi Hamid , Yaznasni Mohamed El , Ridouane Hamid
Published: August 2011

In this paper, we report on the computation of the induced forces in crosslinked polymer blends, with immersed small colloidal particles (nanoparticles) or confined to two parallel plates (film). We assume that the particles or the walls prefer to be attracted by one polymer, close to the spinodal temperature where a microphase separation takes place. This is the so-called “critical adsorption”. As an assumption, the particle diameter or the film thickness is considered to be small enough in comparison with the size of microdomains (“mesh size”). The critical fluctuations of the crosslinked mixture induce a pair potential between particles located in the non-preferred phase or between the confining walls. The purpose is to recall how this Casimir pair potential can be determined, as a function of the interparticle distance or the walls separation. To achieve calculations, use is made of an extended de Gennes model that takes into account the colloid-polymer and polymer-wall interactions. Finally, the obtained results are compared to those relatively to uncrosslinked polymer blends in the same geometries, and the main conclusion is that the induced force is reduced by the presence of permanent crosslinks.
An effective tool to characterize adhesion at the interface of binary polymer blends: a free volume study
Authors: Raj Jaya Madhu , Altaweel Abdullah Mohammed Ali Mohammed , Chandrashekara Malavalli Nagarajaiah , Ramya Puttegowda , Ravikumar Harijan Basavaraju , Ranganathaiah Chikkakuntappa
Published: August 2011

In this work, an effective method of characterizing the adhesion at the interface of partially miscible and immiscible binary polymer is used. Three polymer blends namely PS/PMMA, PP/NBR and PVC/SAN were irradiated with e-beam and microwaves, in order to bring about interfacial modification, and were characterized in terms of free volume measured by Positron Lifetime technique. The changes in free volume parameters upon e-beam and microwave irradiation on the two systems clearly shows improved interaction between the blend constituents as a result of cross-linking through hydrogen bond formation. However, the extent of interfacial modification brought in at different weight compositions is not forthcoming. Therefore, the hydrodynamic interaction parameter α, which accounts for friction at the interface between the dissimilar chains of the blend constituents, is evaluated from the very same free volume data. Since α represents the strength of hydrodynamic interaction, it could be taken as an indicator of the adhesion strength at the interface. Present results showed that both e-beam and microwave irradiations can be used to stabilize the interfaces in binary polymer blends as evidenced by hydrodynamic interaction.
Electrostrictive polymer composite for energy harvesters and actuators
Authors: Cottinet Pierre-Jean , Guyomar Daniel , Guiffard Benoit , Lebrun Laurent , Putson Chatchai
Published: August 2011

Polymers have attractive properties when compared with inorganic materials: they are lightweight, inexpensive, pliable, and easily processed and manufactured. They can be configured into complex shapes and their properties can be tailored according to demand. With the rapid advances in materials used in science and technology, various substances embedded with intelligence at the molecular level are being developed. A type of electroactive polymer known as electrostrictive has shown considerable promise for a variety of applications, such as actuation with a strain thickness of 15% for an electric field of 10 V/μm. Polyurethane-based nanocomposite films were prepared by incorporating a carbon black nanopowder (C) into the polymer matrix. Electric field-induced strain measurements revealed that a loading of 1 vt% C (volume percentage of carbon black nanopowder) increased the strain level by a factor of 2.5 at a moderate field strength (10 V/μm). Moreover, another application for this material concerned the harvesting of mechanical energy, which constitutes an attractive alternative to the strict reliance on traditional batteries with limited lifetimes. For instance, an effective conversion from the mechanical-to-electric domains of 2.3 μW/cm3, under a transverse vibration level of 0.25% at 100 Hz, has been demonstrated for nylon. The final results indicated that the dielectric constant was a crucial parameter for energy harvesting.
Thermodynamic analysis of phase separation of a thermoplastic in a variant epoxy/monoamine-diamine system: influence of epoxy molecular structure
Authors: Lopez Joaquin , Rico Maite , Montero Belen , Ramirez Carmen
Published: August 2011

A thermodynamic study of phase separation induced by the polymerization process was carried out in a variant epoxy/amine system modified with polystyrene (PS) by means of a model based on the Flory-Huggins theory in which the polydispersity of components was taken into account. Modification of the epoxy/amine system was to continually change its molecular structure from a linear polymer to a highly crosslinked polymer using a monoamine and a diamine mixed in different proportions. The cloud-point curves during polymerization for five epoxy/monoamine-diamine systems with PS blends were experimentally measured. Application of the thermodynamic model led to obtaining the corresponding phase diagrams. All studied blends showed an upper critical solution temperature behavior and an increase in miscibility was observed by increasing the monoamine/diamine ratio. The polydispersity of components caused a molecular fractionation leading to a difference in the conversion of separate phases.