bluuebunny/crossref_metadata_2025 huggingface dataset:
Social Security Schemes for the Unorganized Sector in India: A Critical Analysis
Authors: Mahmood S. Athar
Published: February 2012

The concept of Social Security is related to the high ideals of human dignity and social justice. It is the security provided by the society to its members, particularly the weaker ones, so that they can lead a normal and decent life even under adverse circumstances.

This paper aims to study and critically analyze the various social security schemes for the unorganized sector in India. The unorganized sector is massive and comprises the bulk of the countryís workforce. They are the people who need social security the most and so the government has designed certain schemes exclusively for this sector.

The paper has been divided into four parts. While the first part is introductory in nature and attempts to explain the concept of Social Security, the second part describes the unorganized sector in India providing its characteristics and features. Some data is also provided to present a clear picture of this sector.

In the third part, various Social Security schemes for the unorganized sector are described. To present an overview, information is tabulated for most of the schemes that are grouped under four headings namely Centrally Funded Schemes, Social Insurance Schemes, Social Assistance Schemes and Public Initiatives.

Finally, the schemes described are critically analyzed. It has been pointed out that schemes have not been able to achieve their purpose despite genuine efforts by the government and non profit organizations. Some suggestions to overcome these problems are provided towards the end. These include phasing out of the implementation of the schemes, proper legislation and decentralization of administration of the schemes.
Status of Financial Inclusion in Haryana: An Evidence of Commercial Banks
Authors: Kodan Anand S. , Chhikara Kuldip S.
Published: February 2012

In this paper, we have analyzed the status of financial inclusion in Haryana from 2001 to 2009, on the basis of deposit and credit accounts per 1000 people, population per bank office, and uses ratio. The parametric and non-parametric statistical tools have been applied to analyze the various dimensions of the financial inclusion. The study clearly shows that there is no significant difference between the Haryana and India in financial inclusion, but, the status of Haryana is somewhat better as compared to aggregate status of India.
Group Factors and its Relationship with Job and Life Satisfaction in Diverse Organizations
Authors: Riasudeen S. , Srinivasan P. T.
Published: February 2012

This research focuses upon understanding whether the group factors will serve as predictors and explain the variance in individual's job and life satisfaction. A purposive sampling was adopted for the selection of 475 employees from the four different firms having global operations. A structured questionnaire was distributed amongst respondents and data were analyzed with hierarchical stepwise multiple regression analysis in order to assess the extent of variance in job satisfaction and life satisfaction. The results of the analysis indicate that the dimensions of group factors emerged as significant predictors of job satisfaction and life satisfaction in the diverse organizations.
Ratios to Manage HR Functions
Authors: Mohan A. Chandra , Valliammal M. , Poonguzhali R.
Published: February 2012

The HR function was run like a welfare agency rather than being a part of the business. The emergence of knowledge economy makes Human Resource as an important investment and people as assets. HR Management has to involve in strategy formulation and implementation and has to transform itself. It has to speak the languages of business, in quantitative and objective terms. This article attempts to provide a quantitative base for the HR function by coming up with various ratios, which can help the organization in making the HR function more effective and evaluate its contribution in terms of benefits provided and return on investment.
Employee Reactions to Personnel Practices as a Result of their Perceived Causes
Authors: Orpen Christopher
Published: February 2012

The study tests the hypothesis, derived from attribution theory, that employee reactions to personnel practices are strongly influenced by what employees feel managers really are trying to achieve through the practices, that is what are their perceived causes. External reasons (enhancing productivity, following laws and precedents, extending managerial control) were attributed by significantly more employees to the functions than internal reasons (communicating openly, treating employees equitably, respecting individuals). Employees making internal attributions were more involved, motivated and satisfied at work than those making external attributions, as hypothesized.
Developments in UK executive agencies: Re-examining the ‘disaggregation–reaggregation’ thesis
Authors: Elston Thomas
Published: March 2012

Executive agencies remain key players in UK government. However, reflecting their declining political profile, little research has emerged on the longer term evolution of this key new public management (NPM) infrastructure. Although widely cited, the ‘disaggregation–reaggregation’ thesis – which posits that a significant reversal has taken place, following the extensive agencification of the 1990s – has received little systematic evaluation. As political interest in the agency model reawakens under the Coalition Government, it is necessary to understand how the agency landscape has evolved while outside of the limelight. Accordingly, this article examines developments across 1988–2010 along two dimensions: ‘structural’, relating to organisational boundaries; and ‘functional’, relating to the department–agency task division. Viewed within this structural–functional framework, considerable merit is found in the disaggregation–reaggregation thesis, although not entirely in the terms in which it has come to be accepted. The limited extent of formal ‘de-agencification’, particularly, challenges existing reports of the expansion and decline of agencies, and raises important issues for the future research agenda.
Truncation errors of assumed shape modeling for flexible-link manipulators
Authors: Heidari Fatemeh , Vakil Mohammad , Fotouhi Reza , Nikiforuk Peter N
Published: March 2012

The assumed mode shape method has been widely used to derive finite degree-of-freedom dynamic models for flexible-link manipulators, which theoretically have infinite degree-of-freedom dynamics. For a single flexible manipulator, this approximation changes locations of the zeros of transfer functions between base torque and end-effector displacement. The change in locations of zeros considerably affects accuracy of the model and therefore the performance of model-based controllers. This article presents a comprehensive study on the change in locations of zeros due to the truncation associated with assumed mode shape method. It is shown that the locations of approximate zeros depend on four non-dimensional parameters, whereas the locations of analytical zeros depend on only two non-dimensional parameters. Approximate zeros are obtained from assumed mode shape method models, whereas analytical zeros are derived from infinite order models. A thorough study of the differences between approximate zeros and analytical zeros versus the number of mode shapes as well as all the physical parameters is performed. Moreover, guidelines are provided to select the numbers of mode shapes such that the approximate zeros become close to the analytical zeros. These guidelines can easily be used by control and modeling engineers, making them valuable for modeling and control of flexible robot manipulators.
Investigation and prediction of springback in rotary-draw tube bending process using finite element method
Authors: Sözen Levent , Guler Mehmet A , Bekar Deniz , Acar Erdem
Published: March 2012

Rotary-draw tube bending operation is one of the most universal methods used for the tube forming processes. Similar to the other forming methods, some problems such as wall thinning, cross-section distortion, wrinkling, and springback can also be seen on the tubes formed by rotary-draw bending operations. Springback is a very common problem and its prediction plays a crucial role in increasing the efficiency of the tube bending operations and also to overcome the difficulties in the assembly processes. Tube diameter, wall thickness, bend radius, bend angle, and coefficient of friction can be considered as the most effective parameters that cause the variation of springback magnitude. In this study, not a simple one-at-a-time sensitivity analysis, but a thorough investigation of the springback phenomena involving interactions between the geometrical and mechanical parameters is done and surrogate models are developed via the data obtained from finite element analysis using a multi-purpose explicit and implicit finite element software LS-DYNA to analyze the non-linear response of structures. The constructed surrogate models can be utilized to perform fast prediction of springback for a given combination of parameters. Three different surrogate modeling techniques are exploited and it is found that the linear polynomial response surface approximations can provide acceptable accuracy. Finally, experiments are conducted to validate the accuracy of surrogate models. It is observed that the cross-validation error predictions are close to the errors observed in the experiments.
Long co-planar mode III fatigue crack growth under non-proportional mixed mode loading in rail steel
Authors: Akama Makoto , Kiuchi Akira
Published: March 2012

Fatigue tests have been performed to obtain the co-planar crack growth rate in rail steel under non-proportional mixed mode I and mode III cycles. In addition, a finite element analysis (FEA) has been performed to investigate the crack growth behaviour under this loading. The experiments showed that a long co-planar crack could be produced under this loading. Based on fracture surface observations obtained using a scanning electron microscope and FEA, the long co-planar crack growth was thought to be driven mainly by mode III loading and the role of mode I was as an assistant; keeping the crack face open. It was also observed that the crack tended to branch when the degree of overlap between the mode I and mode III cycles increased. Comparing the crack growth rate data under loading with that under non-proportional mixed mode I and II cycles, it was found that the co-planar growth rates were similar regardless of whether the main driving force was in-plane shear or out-of-plane shear.
The influence of glacier surface processes on the short-term evolution of supraglacial tree vegetation: The case study of the Miage Glacier, Italian Alps
Authors: Pelfini Manuela , Diolaiuti Guglielmina , Leonelli Giovanni , Bozzoni Mauro , Bressan Nicoletta , Brioschi Daniele , Riccardi Anna
Published: March 2012

Supraglacial debris cover allows vegetation to colonize glacier surface, and whenever it is enough stable and thick, also shrubs and trees can germinate and grow. Supraglacial tree growth and distribution patterns on the glacier are closely connected with the debris-covered glacier dynamics and evolution. The aim of the research reported here was to evaluate the tree age and tree distribution patterns on the glacier tongue and the influence of ice-cliff backwasting, close to glacier terminus, on tree loss. We analysed the fragile and fast-changing environment that is present on the lower ablation sector of the Miage Glacier (Mont Blanc Massif, Italian Alps) where some ice cliffs are present and backwasting and downwasting phenomena occur. Tree features and short-term evolution were analysed with respect to glacier variations (mainly surface displacements and ice ablation) and geometry changes of the two most representative ice cliffs. The supraglacial trees’ life time resulted to be mainly controlled by glacier surface displacements and by the occurrence of backwasting and downwasting processes, whereas tree germination was associated with fine debris presence. These factors, controlling plants’ life and growth on the glacier, are an actual limit when supraglacial trees are analysed to reconstruct past environmental changes occurred on the glacier tongue. Moreover, we found that a large number of trees die under conditions of dominating backwasting inducing the loss of debris substrate (condition met especially on the northern glacier lobe). Instead, in the case of prevalence of downwasting (condition mainly observed on the southern glacier lobe), trees more easily survive and flow downvalley transported by the glacier flux.
A bending-mode galfenol electric power harvester
Authors: Yoo Jin-Hyeong , Flatau Alison B
Published: February 2012

Iron–gallium alloys (galfenol) are promising transducer materials that combine high magnetostriction, desirable mechanical properties, high permeability, and a wide operational temperature range. In this study, we present results from a proof-of-concept prototype energy harvester that produces an output voltage proportional to the load-induced bending of the galfenol element caused by a base acceleration of the device. The device consists of a polycrystalline galfenol strip bonded to an aluminum cantilever beam, which has an effective length of 35.81 mm. Two brass pieces, each containing a permanent magnet, are used to mass load each end of the beam and to provide a magnetic bias field through the galfenol strip. The voltage induced in an induction coil closely wound around the cantilever beam captures the time rate of change of magnetic flux within the galfenol strip as the beam vibrates. The first bending-mode resonant frequency of the device was 223 Hz. The power generated from the prototype when subjected to a 1g acceleration at 222 Hz was 2.2 mW (root mean square), which corresponded to an efficiency of more than 60% for the electrical power output per unit mechanical power input to the harvester.
Mind Your Words
Authors: Van Dam Nicholas T. , Hobkirk Andréa L. , Danoff-Burg Sharon , Earleywine Mitch
Published: March 2012

Mindfulness, a construct that entails moment-to-moment effort to be aware of present experiences and positive attitudinal features, has become integrated into the sciences. The Five Facet Mindfulness Questionnaire (FFMQ), one popular measure of mindfulness, exhibits different responses to positively and negatively worded items in nonmeditating groups. The current study employed confirmatory factor analysis with a large undergraduate sample to examine the validity of a hierarchical mindfulness model and whether response patterns related to item wording arose from method effects. Results indicated that a correlated facets model better explained the data and that negative and positive wording constituted substantive method effects. This study suggests that the FFMQ measures components that may relate to, but do not seem to directly reflect, a latent variable of mindfulness. The authors recommend against the use of an FFMQ total score, favoring individual scale scores, and further examination of method effects in mindfulness scales.
Neuroanthropology and the dialectical imperative
Authors: Domínguez D Juan F
Published: February 2012

In this article, the ontology, epistemology and methodology of anthropology are questioned with the purpose of arguing for the possibility of a neuroanthropological approach capable of investigating the relationships between the neural, the experiential and the cultural. The author contends that the dichotomization of objects and subjects, objectivism and subjectivism, and explanation and understanding that characterizes anthropology is no longer viable and that a dialectical alternative is required that regards each member of these dyads as standing in a dependent relationship to one another. It is shown that this dialectical view ultimately calls for the investigation of the neural and mental dimensions of human activity as they are embedded in their cultural matrix. The discussion is substantiated by reference to debates around how to bridge the gap between the mental and the neural. The author draws on his experience in anthropology and imaging neuroscience to assess the process of knowledge generation in both fields with a view to showing that science and humanism are interdependent. Following from this, neuroanthropology, and anthropology more broadly, are characterized as having to oscillate between scientific humanism and humanistic scientism.
Insulin-like growth factor binding protein-1 in insulin resistance and cardiovascular disease
Authors: Mehta Shweta , Livingstone Callum , Borai Anwar , Ferns Gordon
Published: March 2012

Insulin-like growth factors (IGFs) are peptide hormones that have significant structural homology with insulin. IGF binding proteins (IGFBPs), in particular IGFBP-1, are important determinants of IGF activity such as enhancing peripheral glucose uptake, decreasing hepatic glucose output and modifying lipid metabolism. Herein factors which alter IGFBP-1 and the utility of measuring IGFBP-1 are considered as the role of IGFBP-1 is explored within the context of insulin resistance and the development of cardiovascular disease.
Sequential organization of text messages and mobile phone calls in interconnected communication sequences
Authors: Laursen Ditte
Published: March 2012

This article investigates how text messages and mobile phone calls interrelate as parts of continuous communication sequences. Based on the recorded mobile communication of 14-year-olds in Denmark and a conversation-analytic approach, the article will show that after a text message in a continuous communication sequence, four different types of conversation may follow: the answer (after a text message demanding a reply), the reminder (in case of a missing text message), the resumption of conversation (after a closed text message exchange) and the confirmation (after a text message with a request for/promise of a call). In itself, the change from text message to conversation requires no interactional efforts from the participants. However, changes of mode are related to the different communicative possibilities the text message and the phone call offer: text messages and calls have distinct formal qualities that govern their uses, and participants in a given sequence move between the two modes, exploiting the potential of each as they ascribe meaning to the written and spoken media.
Sex Differences in Pain
Authors: Keogh Edmund
Published: March 2012

• There is good evidence that men and women differ with respect to the perception and experience of pain. • Women on average report more pain when compared to men, and there seem to be more painful conditions where women exhibit a greater prevalence than where men do. • Sex differences in pain vary according to age, with many differences occurring during the reproductive years. • The sex of an individual is still not routinely investigated in many studies. • There are a range of mechanisms that may be involved in explaining these sex differences, from sex hormones to health seeking behaviours.
Chronic Urogenital Pain in Men
Authors: Curran Natasha
Published: March 2012

• Current terminology uses the 2008 European Association of Urology guidelines, but variably used historical terms suggest inflammation or infection that is rarely found. • Central sensitisation is important in causing visceral and muscle hyperalgesia throughout the pelvis. • There can be considerable overlap between urogenital pain conditions. • Men who have a chronic urological pain condition often have a disturbance of urinary, bowel and sexual function. • Working with urologists as well as a multidisciplinary team is essential.
Relaxation and Mindfulness in Pain: A Review
Authors: Dunford Emma , Thompson Miles
Published: March 2012

• This article reviews the existing, peer-reviewed evidence for the use of relaxation and mindfulness in both acute and chronic pain. • There is some evidence that relaxation can reduce pain outcomes in both acute and chronic pain, however there is evidence that these improvements are not maintained over time. • More limited research suggests that mindfulness can lead to improvements in psychological measures and physical functioning and these improvements appear to be maintained at follow-up. • Further research is needed. Both researchers and practitioners need to be clearer on the outcomes that their techniques best facilitate and the processes which are active within them.
Persistent Pain after Dental Surgery
Authors: Renton Tara
Published: March 2012

• This article aims to cover post surgical trigeminal neuropathy and other conditions related to chronic trigeminal pain not specifically covered elsewhere in this series. • Is estimated to occur in 4–5% of patients overall, considerably less compared with other site surgeries. • Due to the high volume surgery undertaken in this region chronic post surgical pain remains common. • Relatively few clinicians are aware of this condition and as a result it is frequently poorly managed.
Trigeminal Neuralgia—A Debilitating Facial Pain
Authors: McMillan Roddy
Published: March 2012

• Trigeminal neuralgia (TN) is characterised by sudden usually unilateral severe, brief, stabbing, recurrent episodes of pain in the distribution of one or more branches of the trigeminal nerve. • Diagnosis is largely based on clinical history due to the current lack of objective investigations. • MRI can identify those patients who have TN secondary to an underlying pathology such as multiple sclerosis. • The first line medical management remains carbamazepine, with oxcarbazepine being the second choice medication. • Both percutaneous techniques targeting the Gasserian ganglion and microvascular decompression can be considered effective in the management of TN. Microvascular decompression is considered to provide on average, the longest pain free period post surgery. • There are a number of TN associations and support groups which provide a valued service to patients and clinicians. • Due to a dearth of high quality studies in many aspects of the condition, TN requires further research to be conducted.
Recent Developments in Neuropathic Pain Mechanisms: Implications for Treatment
Authors: Rahman Wahida , Dickenson Anthony H
Published: March 2012

• Neuropathic pain is defined as “pain arising as a direct consequence of a lesion or disease affecting the somatosensory system”. • Characteristic symptoms include an increased evoked pain response to noxious (hyperalgesia) and innocuous (allodynia) stimuli, spontaneous pain, shooting electric shock like pain. Sensory deficits can also exist. • Available treatments are not adequate in many patients due to many factors including the complexity of the pain state, disease progression, intolerable side effects and low analgesic efficacy. • A number of peripheral, spinal and supraspinal mechanisms of hyperexcitability underlie neuropathic pain, these include changes in the activity and expression of voltage gated sodium, calcium and potassium channels, as well as TRPV1 channels and alterations in the activity of neuroimmue pathways. • NeP patients often experience depression, anxiety, sleep disturbances etc. alongside their pain. These comorbidites significantly reduce quality of life and as such are key treatment considerations. • Improved understanding of NeP mechanisms is encouraging targeting of treatment to the mechanisms that produce painful symptoms as opposed to the etiology of disease.
Opinion: Labour Analgesia in the Developing World; Why Not
Authors: Dobson Michael
Published: March 2012

• The provision of western-style safe, highly effective labour analgesia requires levels of training, staffing and technology that make its applicability in the developing world in current circumstances questionable. This review examines the reasons.
Chronic Post Surgical Pain
Authors: Bruce Julie , Quinlan Jane
Published: March 2012

• Chronic post-surgical pain (CPSP) is a recognised adverse consequence of surgery; surgery is common, therefore the population at risk is considerable. • Putative risk factors for CPSP include genetic predisposition, demographic, clinical (pain history, type of surgery, anaesthesia, acute pain severity), and psychological factors (vulnerability vs resilience). • Evidence of prevention is limited: long-term benefit from pre-emptive/perioperative analgesia has not been demonstrated consistently. • Large scale prospective studies with detailed pre, intra and postoperative multifactorial assessments are required to refine understanding of the aetiology and prognosis of CPSP.
Graft invariant natural killer T-cell dose predicts risk of acute graft-versus-host disease in allogeneic hematopoietic stem cell transplantation
Authors: Chaidos Aristeidis , Patterson Scott , Szydlo Richard , Chaudhry Mohammed Suhail , Dazzi Francesco , Kanfer Edward , McDonald Donald , Marin David , Milojkovic Dragana , Pavlu Jiri , Davis John , Rahemtulla Amin , Rezvani Katy , Goldman John , Roberts Irene , Apperley Jane , Karadimitris Anastasios
Published: February 2012

Invariant natural killer T (iNKT) cells are powerful immunomodulatory cells that in mice regulate a variety of immune responses, including acute GVHD (aGVHD). However, their clinical relevance and in particular their role in clinical aGVHD are not known. We studied whether peripheral blood stem cell (PBSC) graft iNKT-cell dose affects on the occurrence of clinically significant grade II-IV aGVHD in patients (n = 57) undergoing sibling, HLA-identical allogeneic HSCT. In multivariate analysis, CD4− iNKT-cell dose was the only graft parameter to predict clinically significant aGVHD. The cumulative incidence of grade II-IV aGVHD in patients receiving CD4− iNKT-cell doses above and below the median were 24.2% and 71.4%, respectively (P = .0008); low CD4− iNKT-cell dose was associated with a relative risk of grade II-IV aGVHD of 4.27 (P = .0023; 95% CI, 1.68-10.85). Consistent with a role of iNKT cells in regulating aGVHD, in mixed lymphocyte reaction assays, CD4− iNKT cells effectively suppressed T-cell proliferation and IFN-γ secretion in a contact-dependent manner. In conclusion, higher doses of CD4− iNKT cells in PBSC grafts are associated with protection from aGVHD. This effect could be harnessed for prevention of aGVHD.
Frequency and prognostic impact of mutations in SRSF2, U2AF1, and ZRSR2 in patients with myelodysplastic syndromes
Authors: Thol Felicitas , Kade Sofia , Schlarmann Carola , Löffeld Patrick , Morgan Michael , Krauter Jürgen , Wlodarski Marcin W. , Kölking Britta , Wichmann Martin , Görlich Kerstin , Göhring Gudrun , Bug Gesine , Ottmann Oliver , Niemeyer Charlotte M. , Hofmann Wolf-Karsten , Schlegelberger Brigitte , Ganser Arnold , Heuser Michael
Published: March 2012

Mutations in genes of the splicing machinery have been described recently in myelodysplastic syndromes (MDS). In the present study, we examined a cohort of 193 MDS patients for mutations in SRSF2, U2AF1 (synonym U2AF35), ZRSR2, and, as described previously, SF3B1, in the context of other molecular markers, including mutations in ASXL1, RUNX1, NRAS, TP53, IDH1, IDH2, NPM1, and DNMT3A. Mutations in SRSF2, U2AF1, ZRSR2, and SF3B1 were found in 24 (12.4%), 14 (7.3%), 6 (3.1%), and 28 (14.5%) patients, respectively, corresponding to a total of 67 of 193 MDS patients (34.7%). SRSF2 mutations were associated with RUNX1 (P < .001) and IDH1 (P = .013) mutations, whereas U2AF1 mutations were associated with ASXL1 (P = .005) and DNMT3A (P = .004) mutations. In univariate analysis, mutated SRSF2 predicted shorter overall survival and more frequent acute myeloid leukemia progression compared with wild-type SRSF2, whereas mutated U2AF1, ZRSR2, and SF3B1 had no impact on patient outcome. In multivariate analysis, SRSF2 remained an independent poor risk marker for overall survival (hazard ratio = 2.3; 95% confidence interval, 1.28-4.13; P = .017) and acute myeloid leukemia progression (hazard ratio = 2.83; 95% confidence interval, 1.31-6.12; P = .008). These results show a negative prognostic impact of SRSF2 mutations in MDS. SRSF2 mutations may become useful for clinical risk stratification and treatment decisions in the future.
Overcoming reprogramming resistance of Fanconi anemia cells
Authors: Müller Lars U. W. , Milsom Michael D. , Harris Chad E. , Vyas Rutesh , Brumme Kristina M. , Parmar Kalindi , Moreau Lisa A. , Schambach Axel , Park In-Hyun , London Wendy B. , Strait Kelly , Schlaeger Thorsten , DeVine Alexander L. , Grassman Elke , D'Andrea Alan , Daley George Q. , Williams David A.
Published: February 2012

Fanconi anemia (FA) is a recessive syndrome characterized by progressive fatal BM failure and chromosomal instability. FA cells have inactivating mutations in a signaling pathway that is critical for maintaining genomic integrity and protecting cells from the DNA damage caused by cross-linking agents. Transgenic expression of the implicated genes corrects the phenotype of hematopoietic cells, but previous attempts at gene therapy have failed largely because of inadequate numbers of hematopoietic stem cells available for gene correction. Induced pluripotent stem cells (iPSCs) constitute an alternate source of autologous cells that are amenable to ex vivo expansion, genetic correction, and molecular characterization. In the present study, we demonstrate that reprogramming leads to activation of the FA pathway, increased DNA double-strand breaks, and senescence. We also demonstrate that defects in the FA DNA-repair pathway decrease the reprogramming efficiency of murine and human primary cells. FA pathway complementation reduces senescence and restores the reprogramming efficiency of somatic FA cells to normal levels. Disease-specific iPSCs derived in this fashion maintain a normal karyotype and are capable of hematopoietic differentiation. These data define the role of the FA pathway in reprogramming and provide a strategy for future translational applications of patient-specific FA iPSCs.
Genetic and physical interaction of Meis2, Pax3 and Pax7 during dorsal midbrain development
Authors: Agoston Zsuzsa , Li Naixin , Haslinger Anja , Wizenmann Andrea , Schulte Dorothea
Published: March 2012

Background

During early stages of brain development, secreted molecules, components of intracellular signaling pathways and transcriptional regulators act in positive and negative feed-back or feed-forward loops at the mid-hindbrain boundary. These genetic interactions are of central importance for the specification and subsequent development of the adjacent mid- and hindbrain. Much less, however, is known about the regulatory relationship and functional interaction of molecules that are expressed in the tectal anlage after tectal fate specification has taken place and tectal development has commenced.

Results

Here, we provide experimental evidence for reciprocal regulation and subsequent cooperation of the paired-type transcription factors Pax3, Pax7 and the TALE-homeodomain protein Meis2 in the tectal anlage. Using in ovo electroporation of the mesencephalic vesicle of chick embryos we show that (i) Pax3 and Pax7 mutually regulate each other's expression in the mesencephalic vesicle, (ii) Meis2 acts downstream of Pax3/7 and requires balanced expression levels of both proteins, and (iii) Meis2 physically interacts with Pax3 and Pax7. These results extend our previous observation that Meis2 cooperates with Otx2 in tectal development to include Pax3 and Pax7 as Meis2 interacting proteins in the tectal anlage.

Conclusion

The results described here suggest a model in which interdependent regulatory loops involving Pax3 and Pax7 in the dorsal mesencephalic vesicle modulate Meis2 expression. Physical interaction with Meis2 may then confer tectal specificity to a wide range of otherwise broadly expressed transcriptional regulators, including Otx2, Pax3 and Pax7.
Protein expression of PKCZ (Protein Kinase C Zeta), Munc18c, and Syntaxin-4 in the insulin pathway in endometria of patients with polycystic ovary syndrome (PCOS)
Authors: Rivero Rodrigo , Garin Claire-Alix , Ormazabal Paulina , Silva Andrea , Carvajal Rodrigo , Gabler Fernando , Romero Carmen , Vega Margarita
Published: March 2012

Background

Polycystic Ovary Syndrome (PCOS) is an endocrine-metabolic disorder commonly associated with insulin resistance (IR). Previous studies indicate about the expression of molecules involved in the insulin pathway in endometria of women with PCOS-IR. Therefore, the aim of the present study was to evaluate the effect of insulin and testosterone in the expression of these proteins in the endometria and immortal endometrial stromal cell line (T-HESCs).

Methods

We examined the protein levels of Munc18c, PKC zeta, phospho-PKC Zeta, and Syntaxin-4. Protein levels were assessed by Western Blot and/or immunohistochemistry in proliferative endometria (NPE = 6) and in PCOS endometria with insulin resistance (PCOSE-IR = 6). We also evaluated whether high concentrations of insulin (100 nM) and/or testosterone (100 nM), during a 24 h stimulatory period, affected the expression of these proteins in an immortal endometrial stromal cell line (T-HESCs). Once stimulated, proteins were extracted from cells and were assessed by Western Blot analysis. Immunocytochemistry was performed to detect AR in T-HESC cells.

Results

Western Blot data showed decreased expression (p < 0,05) of Munc18c and phospho-PKC Zeta in PCOS-IR endometria (PCOSE-IR) with respect to the control (NPE). In the in vitro study, Western Blot analysis showed decreased levels of Munc18c, PKC Zeta and phospho-PKC Zeta with the different hormonal treatments when compared to the control condition (no hormonal stimulation) (p < 0,05). The AR was present in the endometrial stromal cell line (T-HESC).

Conclusion

The conditions of hyperinsulinism and hyperandrogenism present in PCOS-IR patients modulate the expression and/or phosphorylation of the proteins involved in the insulin pathway at the endometrial level. These data extend to the T-HESCs cells results, where insulin and testosterone exert an effect on both the expression and phosphorylation of proteins present in the pathway.
Increases in solar conversion efficiencies of the ZrO2 nanofiber-doped TiO2 photoelectrode for dye-sensitized solar cells
Authors: Wang Jiao , Jin En Mei , Park Ju-Young , Wang Wan Lin , Zhao Xing Guan , Gu Hal-Bon
Published: March 2012

In this paper, in order to improve the efficiency of dye-sensitized solar cells, we introduced zirconia [ZrO2] nanofibers into a mesoporous titania [TiO2] photoelectrode. The photoelectrode consists of a few weight percent of ZrO2 nanofibers and a mesoporous TiO2 powder. The mixed ZrO2 nanofibers and the mesoporous TiO2 powder possessed a larger surface area than the corresponding mesoporous TiO2 powder. The optimum ratio of the ZrO2 nanofiber was 5 wt.%. The 5 wt.% ZrO2-mixed device could get a short-circuit photocurrent density of 15.9 mA/cm2, an open-circuit photovoltage of 0.69 V, a fill factor of 0.60, and a light-to-electricity conversion efficiency of 6.5% under irradiation of AM 1.5 (100 mW/cm2).
CD4+ CD25+ FoxP3+ regulatory T cells suppress cytotoxicity of CD8+ effector T cells: implications for their capacity to limit inflammatory central nervous system damage at the parenchymal level
Authors: Göbel Kerstin , Bittner Stefan , Melzer Nico , Pankratz Susann , Dreykluft Angela , Schuhmann Michael K , Meuth Sven G , Wiendl Heinz
Published: February 2012

Background

CD4+CD25+forkhead box P3 (FoxP3)+regulatory T cells (T reg cells) are known to suppress adaptive immune responses, key control tolerance and autoimmunity.

Methods

We challenged the role of CD4+T reg cells in suppressing established CD8+T effector cell responses by using the OT-I/II systemin vitroand an OT-I-mediated, oligodendrocyte directedex vivomodel (ODC-OVA model).

Results

CD4+T reg cells dampened cytotoxicity of an ongoing CD8+T effector cell attackin vitroand within intact central nervous system tissueex vivo. However, their suppressive effect was limited by the strength of the antigen signal delivered to the CD8+T effector cells and the ratio of regulatory to effector T cells. CD8+T effector cell suppression required T cell receptor-mediated activation together with costimulation of CD4+T reg cells, but following activation, suppression did not require restimulation and was antigen non-specific.

Conclusions

Our results suggest that CD4+T reg cells are capable of suppressing CD8+T effector cell responses at the parenchymal site, that is, limiting parenchymal damage in autoimmune central nervous system inflammation.
Differential regulation of protein synthesis in skeletal muscle and liver of neonatal pigs by leucine through an mTORC1-dependent pathway
Authors: Suryawan Agus , Nguyen Hanh V , Almonaci Rosemarie D , Davis Teresa A
Published: February 2012

Neonatal growth is characterized by a high protein synthesis rate that is largely due to an enhanced sensitivity to the postprandial rise in insulin and amino acids, especially leucine. The mechanism of leucine's action in vivo is not well understood. In this study, we investigated the effect of leucine infusion on protein synthesis in skeletal muscle and liver of neonatal pigs. To evaluate the mode of action of leucine, we used rapamycin, an inhibitor of mammalian target of rapamycin (mTOR) complex-1 (mTORC1). Overnight-fasted 7-day-old piglets were treated with rapamycin for 1 hour and then infused with leucine (400 μmol·kg-1·h-1) for 1 hour. Leucine infusion increased the rate of protein synthesis, and ribosomal protein S6 kinase 1 (S6K1) and eukaryotic initiation factor (eIF) 4E-binding protein-1 (4E-BP1) phosphorylation in gastrocnemius and masseter muscles (P < 0.05), but not in the liver. The leucine-induced stimulation of protein synthesis and S6K1 and 4E-BP1 phosphorylation were completely blocked by rapamycin, suggesting that leucine action is by an mTORC1-dependent mechanism. Neither leucine nor rapamycin had any effect on the activation of the upstream mTORC1 regulators, AMP-activated protein kinase and protein kinase B, in skeletal muscle or liver. The activation of eIF2α and elongation factor 2 was not affected by leucine or rapamycin, indicating that these two pathways are not limiting steps of leucine-induced protein synthesis. These results suggest that leucine stimulates muscle protein synthesis in neonatal pigs by inducing the activation of mTORC1 and its downstream pathway leading to mRNA translation.
Differential regulation of MHC II and invariant chain expression during maturation of monocyte-derived dendritic cells
Authors: Landsverk Ole J B , Ottesen Anett H , Berg-Larsen Axel , Appel Silke , Bakke Oddmund
Published: February 2012

DCs are potent initiators of adaptive immune responses toward invading pathogens. Upon reception of pathogenic stimuli, DCs initiate a complex differentiation program, culminating in mature DCs with an extreme capacity to activate naïve T cells. During this maturation, DCs reduce the synthesis and turnover of MHC II molecules. This allows for a stable population of MHC II, presenting peptides captured at the time and place of activation, thus provoking specific immune responses toward the activating pathogen. The efficient loading of antigenic peptides onto MHC II is vitally dependent on the accessory molecule Ii, which aids in the assembly of the MHC II α- and β-chains in the ER and directs their trafficking to the endocytic compartments, where they encounter endocytosed antigen. However, Ii plays additional roles in DC function by influencing migration, antigen uptake, and processing. To examine the biosynthetic background for diverse Ii functions in DCs, we investigated mRNA and protein levels of Ii compared with MHC II in human moDCs during maturation using various stimuli. We find that the production of Ii did not correlate with that of MHC II and that mature DCs maintain abundant levels of Ii despite a reduced production of new MHC II.
Generalized nonelliptic moveout approximation in τ-p domain
Authors: Stovas Alexey , Fomel Sergey
Published: February 2012

We have derived a generalized nonelliptic moveout approximation in the [Formula: see text] domain that is a companion to the generalized nonhyperbolic moveout approximation in the [Formula: see text] domain. Approximation requires five parameters: three parameters that can be determined from the zero-slowness ray and two parameters that can be determined from one additional ray. We convert the generalized approximation from the [Formula: see text] domain to the [Formula: see text] domain and vice versa. The generalized nonelliptic moveout approximation in the [Formula: see text] domain admits other moveout approximations as special cases. Several analytical and numerical tests showed a superior accuracy of the generalized nonelliptic moveout approximation.
Neuropsychological Performance in Survivors of Breast Cancer More Than 20 Years After Adjuvant Chemotherapy
Authors: Koppelmans Vincent , Breteler Monique M.B. , Boogerd Willem , Seynaeve Caroline , Gundy Chad , Schagen Sanne B.
Published: February 2012

Purpose

Adjuvant chemotherapy for breast cancer can have adverse effects on cognition shortly after administration. Whether chemotherapy has any long-term effects on cognition is largely unknown, yet it becomes increasingly relevant because of the widespread use of chemotherapy for early-stage breast cancer and the improved survival. We investigated whether cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy for breast cancer is associated with worse cognitive performance more than 20 years after treatment.

Patients and Methods

This case-cohort study compared the cognitive performance of patients with breast cancer who had a history of adjuvant CMF chemotherapy treatment (six cycles; average time since treatment, 21 years; n = 196) to that of a population-based sample of women never diagnosed with cancer (n = 1,509). Participants were between 50 and 80 years of age. Exclusion criteria were ever use of adjuvant endocrine therapy, secondary malignancy, recurrence, and/or metastasis.

Results

The women exposed to chemotherapy performed significantly worse than the reference group on cognitive tests of immediate (P = .015) and delayed verbal memory (P = .002), processing speed (P < .001), executive functioning (P = .013), and psychomotor speed (P = .001). They experienced fewer symptoms of depression (P < .001), yet had significantly more memory complaints on two of three measures that could not be explained by cognitive test performance.

Conclusion

Survivors of breast cancer treated with adjuvant CMF chemotherapy more than 20 years ago perform worse, on average, than random population controls on neuropsychological tests. The pattern of cognitive problems is largely similar to that observed in patients shortly after cessation of chemotherapy. This study suggests that cognitive deficits following breast cancer diagnosis and subsequent CMF chemotherapy can be long lasting.
Down's-syndrome-related kinase Dyrk1A modulates the p120-catenin–Kaiso trajectory of the Wnt signaling pathway
Authors: Hong Ji Yeon , Park Jae-Il , Lee Moonsup , Muñoz William A. , Miller Rachel K. , Ji Hong , Gu Dongmin , Ezan Jerome , Sokol Sergei Y. , McCrea Pierre D.
Published: March 2012

The Wnt pathways contribute to many processes in cancer and development, with β-catenin being a key canonical component. p120-catenin, which is structurally similar to β-catenin, regulates the expression of certain Wnt target genes, relieving repression conferred by the POZ- and zinc-finger-domain-containing transcription factor Kaiso. We have identified the kinase Dyrk1A as a component of the p120-catenin–Kaiso trajectory of the Wnt pathway. Using rescue and other approaches in Xenopus laevis embryos and mammalian cells, we found that Dyrk1A positively and selectively modulates p120-catenin protein levels, thus having an impact on p120-catenin and Kaiso (and canonical Wnt) gene targets such as siamois and wnt11. The Dyrk1A gene resides within the Down's syndrome critical region, which is amplified in Down's syndrome. A consensus Dyrk phosphorylation site in p120-catenin was identified, with a mutant mimicking phosphorylation exhibiting the predicted enhanced capacity to promote endogenous Wnt-11 and Siamois expression, and gastrulation defects. In summary, we report the biochemical and functional relationship of Dyrk1A with the p120-catenin–Kaiso signaling trajectory, with a linkage to canonical Wnt target genes. Conceivably, this work might also prove relevant to understanding the contribution of Dyrk1A dosage imbalance in Down's syndrome.
Super-resolution imaging visualizes the eightfold symmetry of gp210 proteins around the nuclear pore complex and resolves the central channel with nanometer resolution
Authors: Löschberger Anna , van de Linde Sebastian , Dabauvalle Marie-Christine , Rieger Bernd , Heilemann Mike , Krohne Georg , Sauer Markus
Published: March 2012

One of the most complex molecular machines of cells is the nuclear pore complex (NPC), which controls all trafficking of molecules in and out of the nucleus. Because of their importance for cellular processes such as gene expression and cytoskeleton organization, the structure of NPCs has been studied extensively during the last few decades, mainly by electron microscopy. We have used super-resolution imaging by direct stochastic optical reconstruction microscopy (dSTORM) to investigate the structure of NPCs in isolated Xenopus laevis oocyte nuclear envelopes, with a lateral resolution of ~15 nm. By generating accumulated super-resolved images of hundreds of NPCs we determined the diameter of the central NPC channel to be 41±7 nm and demonstrate that the integral membrane protein gp210 is distributed in an eightfold radial symmetry. Two-color dSTORM experiments emphasize the highly symmetric NPCs as ideal model structures to control the quality of corrections to chromatic aberration and to test the capability and reliability of super-resolution imaging methods.