bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antithrombotic activity of protein S infused without activated protein C in a baboon thrombosis model
Authors: Marzec Ulla , Gruber Andras , Hanson Stephen R. , Heeb Mary J. 
Published: February 2012

SummaryProtein S (ProS) is an essential plasma protein that enhances the anticoagulant activity of activated protein C (APC). In vitro, purified native human Zn2+-containing ProS also exerts direct anticoagulant activity by inhibiting prothrombinase and extrinsic FXase activities independently of APC. We investigated antithrombotic effects of ProS infused without APC in a baboon shunt model of thrombogenesis that employs a device consisting of arterial and venous shear flow segments. In in vitro experiments, the Zn2+-containing human ProS used for the studies displayed >10-fold higher prothrombinase inhibitory activity and anticoagulant activity in tissue factor-stimulated plasma, and four-fold higher inhibition of the intrinsic pathway than the Zn2+-deficient ProS used. In the thrombosis model, ProS (33 μg/minute for 1 hour) or saline was infused locally; platelet and fibrin deposition in the shunt were measured over 2 hours. During experiments performed at 50 ml/minute blood flow, Zn2+-containing ProS inhibited platelet deposition 73–96% in arterialtype flow segments and 90–99% in venous-type flow segments; Zn2+-deficient ProS inhibited platelet deposition 52% in arterial-type flow segments and 65–73% in venous-type flow segments. At 100 ml/min blood flow rate, Zn2+-containing ProS inhibited platelet deposition by 39% and 73% in the respective segments; Zn2+-deficient ProS inhibited platelet deposition by 5% and 0% in the respective segments. Zn2+-containing ProS suppressed fibrin deposition by 67–90%. Systemic APC-independent ProS activity was significantly increased and thrombin-antithrombin complex levels were significantly decreased after infusion of ProS. Thus, infused human Zn2+-containing ProS is antithrombotic in primates, and may have therapeutic potential even in protein C-deficient human patients.These studies were presented in part in abstract form at an oral presentation at the XXIth Congress of the International Society on Thrombosis and Haemo -stasis, Geneva, Switzerland, August 2007.
GPIIb/IIIa inhibitors: From bench to bedside and back to bench again
Authors: Armstrong Paul C. , Peter Karlheinz 
Published: February 2012

SummaryFrom the discovery of the platelet glycoprotein (GP) IIb/IIIa and identification of its central role in haemostasis, the integrin GPIIb/IIIa (αIIbβ3, CD41/CD61) was destined to be an anti-thrombotic target. The subsequent successful development of intravenous ligand-mimetic inhibitors occurred during a time of limited understanding of integrin physiology. Although efficient inhibitors of ligand binding, they also mimic ligand function. In the case of GPIIb/IIIa inhibitors, despite strongly inhibiting platelet aggregation, paradoxical fibrinogen binding and platelet activation can occur. The quick progression to development of small-molecule orally available inhibitors meant that this approach inherited many potential flaws, which together with a short half-life resulted in an increase in mortality and a halt to the numerous pharmaceutical development programs. Limited clinical benefits, together with the success of other anti-thrombotic drugs, in particular P2Y12 ADP receptor blockers, have also led to a restrictive use of intravenous GPIIb/ IIIa inhibitors. However, with a greater understanding of this key platelet-specific integrin, GPIIb/IIIa remains a potentially attractive target and future drug developments will be better informed by the lessons learnt from taking the current inhibitors back to the bench. This overview will review the physiology behind the inherent problems of a ligand-based integrin inhibitor design and discuss novel promising approaches for GPIIb/IIIa inhibition.
Seasonal Relationships between Large-Scale Climate Variability and Antarctic Sea Ice Concentration
Authors: Simpkins Graham R. , Ciasto Laura M. , Thompson David. W. J. , England Matthew H. 
Published: March 2012

Abstract
The observed relationships between anomalous Antarctic sea ice concentration (SIC) and the leading patterns of Southern Hemisphere (SH) large-scale climate variability are examined as a function of season over 1980–2008. Particular emphasis is placed on 1) the interactions between SIC, the southern annular mode (SAM), and El Niño–Southern Oscillation (ENSO); and 2) the contribution of these two leading modes to the 29-yr trends in sea ice. Regression, composite, and principal component analyses highlight a seasonality in SH sea ice–atmosphere interactions, whereby Antarctic sea ice variability exhibits the strongest linkages to the SAM and ENSO during the austral cold season months. As noted in previous work, a dipole in SIC anomalies emerges in relation to the SAM, characterized by centers of action located near the Bellingshausen/Weddell and Amundsen/eastern Ross Seas. The structure and magnitude of this SIC dipole is found to vary considerably as a function of season, consistent with the seasonality of the overlying atmospheric circulation anomalies. Relative to the SAM, the pattern of sea ice anomalies linked to ENSO exhibits a similar seasonality but tends to be weaker in amplitude and more diffuse in structure. The relationships between ENSO and sea ice also exhibit a substantial nonlinear component, highlighting the need to consider both season and phase of the ENSO cycle when diagnosing ENSO–SIC linkages. Trends in SIC over 1980–2008 are not significantly related to trends in either the SAM or ENSO during any season, including austral summer when the trend in the SAM is most pronounced.
Tympanostomy Tube In Vitro Biofilm Potential of Common Otopathogens
Authors: Ojano‐Dirain Carolyn , Antonelli Patrick J. 
Published: February 2012

ObjectivePost‐tympanostomy tube otorrhea has been linked to microbial biofilms. The purpose of this study was to compare the tympanostomy tube‐biofilm–forming propensity of common otopathogens Pseudomonas aeruginosa, Staphylococcus aureus, Haemophilus influenzae, and Streptococcus pneumoniae.Study DesignControlled, in vitro.SettingAcademic research laboratory.Subjects and MethodsFluoroplastic coupons (1656 total, 46 per treatment per incubation period) were exposed to plasma and cultured with 3 strains each of the bacterial species for 2, 4, or 7 days. Half of the coupons were treated with antibiotics to kill planktonic bacteria. Total and biofilm colony counts and electron microscopy were performed.ResultsS aureus formed biofilm after 2 days, not different from 4‐ or 7‐day biofilms (P >. 05), and was most tolerant to antibiotic treatment. P aeruginosa also formed biofilms at 2 days, reached a plateau at 4 days (P >. 05), and decreased at 7 days (P <. 01). H influenzae formed biofilm only after 4 days (P ≤. 04). S pneumoniae did not form biofilm without catalase supplementation. With catalase, 1 S pneumoniae strain showed a delay in biofilm formation similar to H influenzae (P <. 0001), while the other 2 strains formed biofilms after 2 days.ConclusionsTympanostomy tube biofilm formation occurs with common middle ear pathogens but most readily with S aureus and P aeruginosa. Further investigation is needed to determine if these findings may, in part, explain the occasionally refractory nature of post‐tympanostomy tube otorrhea associated with S aureus and P aeruginosa.
Burn Out Stress, Pass on to Success
Authors: Kumar G. Rajesh , Rajamohan S. 
Published: February 2012

Stress is one of the reasons behind the psychological imbalance of an individual and to manage stress is an invitation to consider a different understanding of the nature of illness, unhappiness and stress to transform stress into vitality, energy into power and knowledge into wisdom. This article is therefore to make an individual aware of various effects of stress, let it be positive or negative. This article also suggests various remedies to burn out stress and make an individual happy and perform effectively in day to day life or in an organization. Patience and calmness must be practiced by everyone to solve all the problems which come one after the other and play spoil sport. This article includes workplace stress and organizational stress along with their causes and remedies to overcome them. Also, stresses due to family responsibilities and steps taken by government for the employees. It also gives an idea about stress faced by women in the workplace and in the family. Various dietary control methods are also mentioned to keep one stress free and active. Stress is necessary in life as it makes an individual more determine and gives enough clout to face any challenge with great sheer and endurance and to bounce back to normal life with a positive attitude to hit the bull's eye.
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.
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

Abstract
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

AbstractMutations 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

Abstract
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

Abstract

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

Abstract

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

Abstract
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

AbstractBackgroundCD4+CD25+forkhead box P3 (FoxP3)+regulatory T cells (T reg cells) are known to suppress adaptive immune responses, key control tolerance and autoimmunity.MethodsWe 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).ResultsCD4+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.ConclusionsOur 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.