bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel reporter of notch signalling indicates regulated and random notch activation during vertebrate neurogenesis
Authors: Vilas-Boas Filipe , Fior Rita , Swedlow Jason R , Storey Kate G , Henrique Domingos 
Published: September 2011

Abstract

Background
Building the complex vertebrate nervous system involves the regulated production of neurons and glia while maintaining a progenitor cell population. Neurogenesis starts asynchronously in different regions of the embryo and occurs over a long period of time, allowing progenitor cells to be exposed to multiple extrinsic signals that regulate the production of different cell types. Notch-mediated cell-cell signalling is one of the mechanisms that maintain the progenitor pool, however, little is known about how the timing of Notch activation is related to the cell cycle and the distinct modes of cell division that generate neurons. An essential tool with which to investigate the role of Notch signalling on cell by cell basis is the development a faithful reporter of Notch activity.

Results
Here we present a novel reporter for Notch activity based on the promoter of the well characterised Notch target chick Hes5-1, coupled with multiple elements that confer instability, including a destabilized nuclear Venus fluorescent protein and the 3' untranslated region (UTR) of Hes5-1. We demonstrate that this reporter faithfully recapitulates the endogenous expression of Hes5-1 and that it robustly responds to Notch activation in the chick neural tube. Analysis of the patterns of Notch activity revealed by this reporter indicates that although Notch is most frequently activated prior to mitosis it can be activated at any time within the cell cycle. Notch active progenitors undergoing mitosis generate two daughters that both continue to experience Notch signalling. However, cells lacking Notch activity before and during mitosis generate daughters with dissimilar Notch activity profiles.

Conclusions
A novel Notch reporter with multiple destabilisation elements provides a faithful read-out of endogenous Notch activity on a cell-by-cell basis, as neural progenitors progress through the cell cycle in the chick neural tube. Notch activity patterns in this cell population provide evidence for distinct Notch signalling dynamics underlying different cell division modes and for the involvement of random initiation of Notch signalling within the neuroepithelium. These findings highlight the importance of single-cell analysis in the study of the complexity of Notch activity and provide new insights into the mechanisms underlying cell fate decisions in neural progenitors.
Pegylated interferon-alfa-2a monotherapy in patients infected with HCV genotype 2 and importance of rapid virological response
Authors: Etoh Reiko , Imazeki Fumio , Kurihara Tomoko , Fukai Kenichi , Fujiwara Keiichi , Arai Makoto , Kanda Tatsuo , Mikata Rintaro , Yonemitsu Yutaka , Yokosuka Osamu 
Published: September 2011

Abstract

Background
Pegylated (PEG)-interferon (IFN)-alfa-2a plus ribavirin (RBV) therapy for 24 weeks is now a standard treatment protocol for patients with hepatitis C virus (HCV) genotype 2. As RBV cannot be used in certain situations, we examined whether PEG-IFN-alfa-2a monotherapy for 24 weeks or less would be sufficient to obtain a sustained virological response (SVR) in patients infected with HCV genotype 2.

Methods
Forty-nine consecutive patients with HCV genotype 2 received PEG-IFN-alfa-2a (180 μg/week) subcutaneously without oral RBV for 8-64 weeks. HCV RNA level was determined by COBAS AMPLICOR HCV Test, v2.0.

Results
HCV RNA was equal to or less than 100 KIU/mL (defined as low viral load) in 15 of 49 patients, and the remaining 34 had HCV RNA above 100 KIU/mL (defined as high viral load). All 15 patients with low viral load achieved rapid virological response (RVR; HCV RNA negative at week 4), and also achieved SVR with an average treatment duration of 17.1 weeks. The 34 patients with high viral load were treated for 33.7 weeks on average, and 19 of them (55.9%) achieved RVR. The SVR rates of these patients were significantly higher in those with RVR than without RVR (16/19 vs. 6/15 p = 0.0074).

Conclusion
PEG-IFN-alfa-2a monotherapy for 24 weeks or less might be sufficient to treat selected patients with HCV genotype 2, especially those with low viral load and becoming negative for HCV RNA by week 4 of treatment.
NF-kappaB activation within macrophages leads to an anti-tumor phenotype in a mammary tumor lung metastasis model
Authors: Connelly Linda , Barham Whitney , Onishko Halina M , Chen Lianyi , Sherrill Taylor P , Zabuawala Tahera , Ostrowski Michael C , Blackwell Timothy S , Yull Fiona E 
Published: September 2011

Abstract
Introduction
Metastasis from primary tumor to the lungs is a major cause of the mortality associated with breast cancer. Both immune and inflammatory responses impact whether circulating mammary tumor cells successfully colonize the lungs leading to established metastases. Nuclear factor -kappaB (NF-κB) transcription factors regulate both immune and inflammatory responses mediated in part by the activities of macrophages. Therefore, NF-κB activity specifically within macrophages may be a critical determinant of whether circulating tumor cells successfully colonize the lungs.

Methods
To investigate NF-κB signaling within macrophages during metastasis, we developed novel inducible transgenic models which target expression of the reverse tetracycline transactivator (rtTA) to macrophages using the cfms promoter in combination with inducible transgenics that express either an activator (cIKK2) or an inhibitor (IκBα-DN). Doxycyline treatment led to activation or inhibition of NF-κB within macrophages. We used a tail vein metastasis model with mammary tumor cell lines established from MMTV-Polyoma Middle T-Antigen-derived tumors to investigate the effects of modulating NF-κB in macrophages during different temporal windows of the metastatic process.

Results
We found that activation of NF-κB in macrophages during seeding leads to a reduction in lung metastases. The mechanism involved expression of inflammatory cytokines and reactive oxygen species, leading to apoptosis of tumor cells and preventing seeding in the lung. Activation of NF-κB within macrophages after the seeding phase has no significant impact on establishment of metastases.

Conclusions
Our results have identified a brief, defined window in which activation of NF-κB has significant anti-metastatic effects and inhibition of NF-κB results in a worse outcome.
RANDOM NETWORKS AND MIXING LAWS
Authors: Madden Theodore R. 
Published: September 2011

Random networks are investigated as models of heterogeneous media. A general approximate structure is used where the networks are described as a system of embedded networks, and the critical behavior and averaging behavior of such networks are developed. These results are applied to a study of the electrical conductivity of porous media, with special attention to an Archie's law behavior. It appears that the wide range of crack and pore widths in rocks makes the resulting conductivity relatively insensitive to the topology of their interconnections and allows one to make reasonable predictions of rock conductivities, given the distribution of crack and pore widths. It also appears that with low porosity rocks the conductivity is controlled by the microcrack population which only accounts for a fraction of the total porosity. It would seem, therefore, that Archie's law is a feature of some general trend between porosity and crack and pore width distributions rather than a fundamental property of porous media. The law of the geometric mean is an accurate predictor of the physical properties of a mixture of different materials. This mixing law can result from an equal balance of series and parallel arrangements which can be produced by an appropriate distribution of shapes. A brief look is given to problems of anisotropic distributions for the conductivity problem and it is shown how the averaging process greatly dilutes the microscopic anisotropy in producing the macroscopic properties.
A FIELD TEST OF THE MAGNETOMETRIC RESISTIVITY (MMR) METHOD
Authors: Edwards R. N. , Howell E. C. 
Published: September 2011

The electrical prospecting method, known as the Magnetometric Resistivity (MMR) method, is based on the measurement of the low level (about 100 milligamma), low‐frequency (1–5 Hz) magnetic fields associated with noninductive current flow in the ground. The horizontal component of the magnetic field is measured along profiles which are at right angles to a baseline joining two widely separated current electrodes. The field test was conducted on a plateau in the western cordillera, where the topography is characterized by steep hills, bold ridges, gullies and narrow canyons. A steep faulted contact between basement rocks of differing resistivity is exposed on one flank of the plateau, beneath over 500 m of Tertiary volcanics and sediments. The object of the test was to determine if the basement contact could be mapped by the MMR method, working entirely on top of the plateau. The plan position of the contact could be inferred approximately from measurements at the outcrop. The object was achieved with a minimum of data processing. Using a theoretical model which resembles a thick, outcropping vertical dike of infinite vertical extent, the contrast in resistivity across the contact is estimated. A further model, that of an exponential “alpha” center, is also fitted to the data in an effort to pin‐point an anomalous region which may have unusually high conductivity.
Disorders of gender identity
Authors: Barrett James 
Published: September 2011

SummaryGender identity disorders are not common. The most frequent is dual-role transvestism, but it rarely needs medical attention. The least frequent is transsexualism. Transsexualism is not usually indicative of serious psychopathology. Diagnoses should be made by a gender identity clinic and never by the patient, and a clear change of gender role should precede any hormone treatment. Patients must have lived and thrived entirely in their new gender role for at least 2 years before any genital surgery is undertaken. However, bilateral mastectomy might be considered for females after a year of life in a male role. With these selection criteria, the outcomes of surgery are generally good. In the UK, individuals may legally change their recorded sex, usually after gender reassignment treatment.
Mania in late life
Authors: Richards Felicity , Curtice Martin 
Published: September 2011

SummaryMania in late life is a serious disorder that demands specialist assessment and management. However, it is greatly under-researched, with only a paucity of studies specifically analysing older populations. The mainstay of the old age psychiatry workload will inevitably be concerned with assessing and managing dementia and depression, but the steady rise in the aging population with longer survival means that there will be an increase in absolute numbers of older people presenting with mania. There are no specific treatment algorithms available for mania in late life. This article reviews mania and hypomania in late life and concentrates on diagnosis, assessment and treatment, as well as on the management considerations associated with this important age group.
Abortion and mental health: quantitative synthesis and analysis
of research published 1995–2009
Authors: Coleman Priscilla K. 
Published: September 2011

BackgroundGiven the methodological limitations of recently published qualitative
reviews of abortion and mental health, a quantitative synthesis was
deemed necessary to represent more accurately the published literature
and to provide clarity to clinicians.AimsTo measure the association between abortion and indicators of adverse
mental health, with subgroup effects calculated based on comparison
groups (no abortion, unintended pregnancy delivered, pregnancy delivered)
and particular outcomes. A secondary objective was to calculate
population-attributable risk (PAR) statistics for each outcome.MethodAfter the application of methodologically based selection criteria and
extraction rules to minimise bias, the sample comprised 22 studies, 36
measures of effect and 877 181 participants (163 831 experienced an
abortion). Random effects pooled odds ratios were computed using adjusted
odds ratios from the original studies and PAR statistics were derived
from the pooled odds ratios.ResultsWomen who had undergone an abortion experienced an 81% increased risk of
mental health problems, and nearly 10% of the incidence of mental health
problems was shown to be attributable to abortion. The strongest subgroup
estimates of increased risk occurred when abortion was compared with term
pregnancy and when the outcomes pertained to substance use and suicidal
behaviour.ConclusionsThis review offers the largest quantitative estimate of mental health
risks associated with abortion available in the world literature. Calling
into question the conclusions from traditional reviews, the results
revealed a moderate to highly increased risk of mental health problems
after abortion. Consistent with the tenets of evidence-based medicine,
this information should inform the delivery of abortion services.
Differential outcome of schizophrenia: where we are and where we would like to be
Authors: Gureje Oye , Cohen Alex 
Published: September 2011

SummaryStudies examining comparative outcomes of schizophrenia in high-income countries with those in low- and middle-income countries remain of interest to researchers and may be of value in understanding some environmental factors that influence the course and outcome of the disorder. The view that the disorder has a better outcome in low- and middle-income countries compared with high-income countries, even though widespread and supported by a set of World Health Organization (WHO) studies, requires further testing and exploration. Unfortunately, although not insurmountable, the obstacles for such studies both in terms of implementation and interpretation are considerable.
Schizophrenia with the 22q11.2 deletion and additional genetic
defects: case history
Authors: Toyosima M. , Maekawa M. , Toyota T. , Iwayama Y. , Arai M. , Ichikawa T. , Miyashita M. , Arinami T. , Itokawa M. , Yoshikawa T. 
Published: September 2011

SummaryThe 22q11.2 deletion is the most prominent known genetic risk factor for
schizophrenia, but its penetrance is at most approximately 50% suggesting
that additional risk factors are required for disease progression. We
examined a woman with schizophrenia with this deletion for such risk
factors. She had high plasma pentosidine levels (‘carbonyl stress’) and a
frameshift mutation in the responsible gene, GLO1. She also
had a constant exotropia, so we examined the PHOX2B gene
associated with both schizophrenia and strabismus, and detected a 5-alanine
deletion. We propose that the combination of these genetic defects may have
exceeded the threshold for the manifestation of schizophrenia.
Increasing the employment rate for people with longer-term mental health problems
Authors: Rinaldi Miles , Montibeller Tatiana , Perkins Rachel 
Published: September 2011

Aims and methodTo examine the effects of implementing the individual placement and support (IPS) approach within four community mental health teams (CMHTs). Demographic, clinical and vocational data were collected through a repeated cross-sectional survey. Additionally, a service user experience survey was conducted.ResultsThe IPS approach appears to have a significant effect on the employment rates of service users; a higher proportion felt able to return to employment and a smaller proportion believed they were unable to work because of their mental health problems. Employment rates for service users appear to be independent of general employment rates.Clinical implicationsImplementing IPS appears to increase the employment rates in CMHTs resulting in increased service user expectations of being able to return to work.
Effect of Lifestyle Intervention on Features of Polycystic Ovarian Syndrome, Metabolic Syndrome, and Intima-Media Thickness in Obese Adolescent Girls
Authors: Lass Nina , Kleber Michaela , Winkel Katrin , Wunsch Rainer , Reinehr Thomas 
Published: September 2011

Abstract

Context:
Polycystic ovarian syndrome (PCOS) is associated with cardiovascular risk factors (CRF). Lifestyle intervention is regarded as therapy of choice even if studies in adolescent girls with PCOS are scarce.

Objective:
Our objective was to analyze the impact of lifestyle intervention on menses irregularities, hyperandrogenemia, CRF, and intima-media thickness (IMT) in adolescent girls with PCOS.

Patients:
Patients included 59 obese girls with PCOS aged 12–18 yr.

Intervention:
Intervention was a 1-yr lifestyle intervention based on nutrition education, exercise training, and behavior therapy.

Main Outcome Measures:
Menses cycles, IMT, waist circumference, blood pressure, fasting lipids, insulin, glucose, testosterone, dehydroepiandrosterone sulfate, androstenedione, and SHBG were evaluated.

Results:
In contrast to the 33 girls without weight loss, the 26 girls reducing their body mass index during the lifestyle intervention (by a mean of −3.9 kg/m2) improved most CRF and decreased their IMT (by a mean of −0.01 cm). Testosterone concentrations decreased (by a mean of −0.3 nmol/liter) and SHBG concentrations increased (by a mean of +8 ng/ml) significantly in girls with weight loss in contrast to girls with increasing weight. The prevalence of amenorrhea (−42%) and oligoamenorrhea (−19%) decreased in the girls with weight loss. The changes in insulin in the 1-yr follow-up were significantly correlated to changes in testosterone (r = 0.38; P = 0.002) and SHBG (r = −0.35; P = 0.048). A linear regression model with changes in IMT as dependent variable demonstrated a significant association with changes in blood pressure and weight status but not with changes in testosterone.

Conclusions:
Weight loss due to lifestyle intervention is effective to treat menses irregularities, normalize androgens, and improve CRF and IMT in obese adolescent girls with PCOS.
Bivalirudin Dosing Adjustments for Reduced Renal Function with or Without Hemodialysis in the Management of Heparin-Induced Thrombocytopenia
Authors: Tsu Laura V , Dager William E 
Published: September 2011

Background: While not approved by the Food and Drug Administration for treatment of heparin-induced thrombocytopenia (HIT), except in patients undergoing percutaneous interventions, the direct thrombin inhibitor bivalirudin is a treatment option that is gaining use. An initial dose of bivalirudin 0.15–0.2 mg/kg/h, adjusted to an activated partial thromboplastin time (aPTT) of 1.5–2.5 times the baseline value, has been suggested. Initial dosing in patients with renal dysfunction, including those on hemodialysis, is unclear. Objective: To evaluate initial bivalirudin dosing requirements in patients with and without renal dysfunction, including patients on different forms of dialysis. Methods: A retrospective analysis of 135 patients treated with bivalirudin for HIT between June 2004 and October 2009 was conducted at a tertiary care medical center. The patients were divided into groups, based on renal function. Patients receiving dialysis were divided into 3 subgroups based on the mode of hemodialysis: intermittent hemodialysis (IHD, n = 24), sustained low-efficiency daily diafiltration (SLEDD, n = 12), or continuous renal replacement therapy (CRRT, n = 5). Patients not receiving dialysis were separated into 3 subgroups based on calculated creatinine clearance (CrCl): CrCl >60 mL/min (n = 52), CrCl 30–60 mL/min (n = 26), and CrCl <30 mL/min (n = 16). Results: Compared with patients with normal renal function (CrCl >60 mL/min), patients with differing degrees of renal dysfunction (CrCl 30–60 and <30 mL/min) required lower doses of bivalirudin to achieve aPTT goal (0.13 vs 0.08 vs 0.05 mg/kg/h, respectively; p < 0.001). Patients on dialysis (IHD, SLEDD, CRRT) also required dose reductions (0.07, 0.09, and 0.07 mg/kg/h) compared with patients with normal renal function, but higher dosing requirements than patients not receiving dialysis with CrCl <30 mL/min. Conclusions: Patients with renal dysfunction require a reduced dose of bivalirudin to reach a therapeutic aPTT goal. Slightly higher doses may be observed in patients receiving hemodialysis.
Spektrale Bandselektion für das Filterdesign optischer Inspektionssysteme
Authors: Michelsburg Matthias , Gruna Robin , Vieth Kai-Uwe , Puente León Fernando 
Published: September 2011

Zusammenfassung
Die automatische Inspektion mit Methoden der Bildverarbeitung wird in vielen Bereichen — beispielsweise in der Nahrungsmittelindustrie — eingesetzt, um die gewünschte Qualität eines Produkts zu gewährleisten. Für besonders anspruchsvolle Inspektionsaufgaben reicht das Signal einer einzelnen Graustufen- oder RGB-Farbkamera nicht aus, um ein zufriedenstellendes Ergebnis zu erreichen. Durch Hinzunahme von Spektralbereichen außerhalb des sichtbaren Wellenlängenbereichs kann eine Klassifikation verbessert werden. Eine wichtige Rolle spielt hierbei der Nahinfrarotbereich, welcher in der Spektroskopie seit vielen Jahren zur Qualitätskontrolle und Analytik genutzt wird. Hyperspektrale Bildaufnahmen liefern zu jedem Bildpunkt ein hoch aufgelöstes Spektrum, finden jedoch in industriellen Inspektionsanlagen aufgrund der hohen Kosten, der aufwändigen Signalverarbeitung und der begrenzten Geschwindigkeit weniger Anwendung. Durch Reduktion der Messung auf diejenigen spektralen Bereiche, mit welchen eine gute Klassifikation möglich ist, kann ein einfacheres und schnelleres Inspektionssystem entworfen werden. An einem Beispiel aus dem Bereich der Schüttgutsortierung wird ein Ansatz zur Auswahl von optischen Filtern mithilfe hyperspektraler Bildaufnahmen vorgestellt und bewertet.
Crystal structures of thiazine-indigo pigments, determined from single-crystal and powder diffraction data
Authors: Buchsbaum Christian , Paulus Erich F. , Schmidt Martin U. 
Published: September 2011

Abstract
The crystal structures of two polymorphs of thiazine-indigo, C16H10N2O2S2 were determined by single crystal X-ray diffraction. 7,7′-dimethyl-thiazine-indigo, 7,7′-dimethoxy-thiazine-indigo and 7-monochloro-thiazine-indigo are isostructural to β-thiazine-indigo and 7,7′-dichloro-thiazine-indigo; their structures are refined by Rietveld methods. 7-monochloro-thiazine-indigo shows a head-to-tail-disorder. 6,6′-bis(trifluoromethyl)-thiazine-indigo is not isotypic to any other thiazine-indigo compound. Polymorph screenings were performed; three of the six compounds are polymorphic. In all determined structures the molecules are essentially planar; all molecules are connected by double hydrogen bonds to form parallel chains, but there are three different arrangement of chains. The structures are compared with the chain-structures of other organic pigments like indigo, quinacridone and diketopyrrolopyrrole derivatives.