bluuebunny/crossref_metadata_2025_split huggingface dataset:
Onset of fault reactivation in the Eastern Cordillera of Colombia and proximal Llanos Basin; response to Caribbean–South American convergence in early Palaeogene time
Authors: Bayona German , Cardona Agustin , Jaramillo Carlos , Mora Andres , Montes Camilo , Caballero Victor , Mahecha Hernando , Lamus Felipe , Montenegro Omar , Jimenez Giovanny , Mesa Andres , Valencia Victor 
Published: March 2013

Abstract
The inversion of Mesozoic extensional structures in the Northern Andes has controlled the location of syn-orogenic successions and the dispersal of detritus since latest Maastrichtian time. Our results are supported by detailed geological mapping, integrated provenance (petrography, heavy minerals, geochronology) analysis and chronostratigraphical correlation (palynological and geochronology data) of 13 areas with Palaeogene strata across the central segment of the Eastern Cordillera. Spatial and temporal variation of sedimentation rates and provenance data indicate that mechanisms driving the location of marginal and intraplate uplifts and tectonic subsidence vary among syn-orogenic depocentres. In the late Maastrichtian–mid-Palaeocene time, crustal tilting of the Central Cordillera favoured reverse reactivation of the western border of the former extensional Cretaceous basin. The hanging wall of the reactivated fault separated two depocentres: a western depocentre (in the Magdalena Valley) and an eastern depocentre (presently along the axial zone of the Eastern Cordillera, Llanos foothills and Llanos Basin). In late Palaeocene–early Eocene time, as eastern subduction of the Caribbean Plate and intraplate magmatics advanced eastwards, reactivation of older structures migrated eastwards up to the Llanos Basin and disrupted the eastern depocentre. In early Eocene time, these three depocentres were separated by two low-amplitude uplifts that exposed dominantly Cretaceous sedimentary cover. Syn-orogenic detrital sediments supplied from the eastwards-tilted Central Cordillera reached areas of the axial domain of the Eastern Cordillera, whereas unstable metamorphic and sedimentary fragments recorded in the easternmost depocentre were supplied by basement-cored uplifts with Cretaceous and Palaeozoic sedimentary cover reported in the southern Llanos Basin. This tectonic configuration of low-amplitude uplifts separating intraplate syn-orogenic depocentres and intraplate magmatic activity in Palaeocene time was primary controlled by subduction of the Caribbean Plate.

Supplementary material:

Appendix 1 presents detailed descriptions of analytical methods used in this manuscript. Appendixes 2 to 4 include raw data of sandstone petrography, heavy minerals and U–Pb detrital zircon geochronology, respectively. All this material is available at
http://www.geolsoc.org.uk/18597
.
Inversion tectonics under increasing rates of shortening and sedimentation: Cenozoic example from the Eastern Cordillera of Colombia
Authors: Mora Andrés , Reyes-Harker Andrés , Rodriguez Guillermo , Tesón Eliseo , Ramirez-Arias Juan Carlos , Parra Mauricio , Caballero Víctor , Mora José Pedro , Quintero Isaid , Valencia Víctor , Ibañez Mauricio , Horton Brian K. , Stockli Daniel F. 
Published: March 2013

Abstract

The Northern Andes of Colombia is a key locality for understanding tectonic inversion of symmetric rifts. A review of available data on structural geometry and deformation timing, and new thermochronology and provenance data from selected localities, enable the construction of balanced cross-sections and shortening budgets. During early deformation in the Palaeocene, most shortening was focused in the western sector of the orogen, in the Central Cordillera and the Magdallena Valley, although widely spaced and mild inversion occur in areas as far to the east as the Llanos Basin. After a period of tectonic quiescence in the Middle Eocene, deformation resumed across a former early Mesozoic graben in the Eastern Cordillera. Peak shortening rates and out-of-sequence reactivation of the main inversion faults were in place in latest Miocene time, during a phase of topographical growth. Our results indicate that coeval activation of basement highs and adjacent slower-slip shortcuts appear to be characteristic of inverted symmetric grabens. However, before reactivation and brittle faulting occur, strain hardening is required. Deformation rates in the Eastern Cordillera correlate with the westwards velocity of the South American Plate. A threshold convergence rate of approximately 2 cm year
−1
seems to be necessary to activate shortening in the upper plate.
Cowden Syndrome-Related Mutations in PTEN Associate with Enhanced Proteasome Activity
Authors: He Xin , Arrotta Nicholas , Radhakrishnan Deepa , Wang Yu , Romigh Todd , Eng Charis 
Published: March 2013

Abstract
Germline mutations in PTEN have been described in a spectrum of syndromes that are collectively known as PTEN hamartoma tumor syndrome (PHTS). In addition to being mutated in the germline in PHTS, somatic loss-of-function PTEN mutations are seen in a wide range of sporadic human tumors. Here, we show evidence of upregulated proteasome activity in PHTS-derived lymphoblasts, Pten knock-in mice and cell lines expressing missense and nonsense PTEN mutations. Notably, elevated nuclear proteasome activity occurred in cells expressing the nuclear mislocalized PTEN-K62R mutant, whereas elevated cytosolic proteasome activity was observed in cells expressing the cytosolic-predominant mutant PTEN (M3M4 and C136R). Treatment with proteasome inhibitor MG-132 was able to restore both nonsense and missense mutant PTEN protein levels in vitro. PHTS patients with destabilizing PTEN mutations and proteasome hyperactivity are more susceptible to develop neurologic symptoms such as mental retardation and autism than mutation-positive patients with normal proteasome activity. A detailed molecular and functional analysis shows that PTEN mutants most likely cause proteasome hyperactivity via 2 different mechanisms, namely, induction of proteotoxic stress and loss of protein phosphatase activity. These results provide novel insights into the cellular functions of PTEN and reveal molecular mechanisms whereby PTEN mutations increase proteasome activity and lead to neurologic phenotypes. Cancer Res; 73(10); 3029–40. ©2013 AACR.
Bortezomib and SAHA Synergistically Induce ROS-Driven Caspase-Dependent Apoptosis of Nasopharyngeal Carcinoma and Block Replication of Epstein–Barr Virus
Authors: Hui Kwai Fung , Lam Benjamin H.W. , Ho Dona N. , Tsao Sai Wah , Chiang Alan K.S. 
Published: March 2013

AbstractA novel drug combination of a proteasome inhibitor, bortezomib, and a histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), was tested in nasopharyngeal carcinoma (NPC), both in vitro and in vivo. Dose-response of different concentrations of bortezomib and SAHA on inhibition of cell proliferation of NPC was determined. Mechanisms of apoptosis and effects on lytic cycle activation of Epstein–Barr virus (EBV) were investigated. Combination of bortezomib and SAHA (bortezomib/SAHA) synergistically induced killing of a panel of NPC cell lines. Pronounced increase in sub-G1, Annexin V–positive, and terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling (TUNEL)–positive cell populations were detected after treatment with bortezomib/SAHA when compared with either drug alone. Concomitantly, markedly augmented proteolytic cleavage of PARP, caspase-3, -7, -8, and -9, reactive oxygen species (ROS) generation, and caspase-8–dependent histone acetylation were observed. ROS scavenger, N-acetyl cysteine, diminished the apoptotic effects of bortezomib/SAHA, whereas caspase inhibitor Z-VAD-FMK significantly suppressed the apoptosis without decreasing the generation of ROS. Bortezomib inhibited SAHA's induction of EBV replication and abrogated production of infectious viral particles in NPC cells. Furthermore, bortezomib/SAHA potently induced apoptosis and suppressed the growth of NPC xenografts in nude mice. In conclusion, the novel drug combination of bortezomib and SAHA is highly synergistic in the killing of NPC cells in vitro and in vivo. The major mechanism of cell death is ROS-driven caspase-dependent apoptosis. Bortezomib antagonizes SAHA's activation of EBV lytic cycle in NPC cells. This study provides a strong basis for clinical testing of the combination drug regimen in patients with NPC. Mol Cancer Ther; 12(5); 747–58. ©2013 AACR.
Bcl-2/Bcl-xL Inhibition Increases the Efficacy of MEK Inhibition Alone and in Combination with PI3 Kinase Inhibition in Lung and Pancreatic Tumor Models
Authors: Tan Nguyen , Wong Maureen , Nannini Michelle A. , Hong Rebecca , Lee Leslie B. , Price Stephen , Williams Karen , Savy Pierre Pascal , Yue Peng , Sampath Deepak , Settleman Jeffrey , Fairbrother Wayne J. , Belmont Lisa D. 
Published: March 2013

Abstract
Although mitogen-activated protein (MAP)–extracellular signal-regulated kinase (ERK) kinase (MEK) inhibition is predicted to cause cell death by stabilization of the proapoptotic BH3-only protein BIM, the induction of apoptosis is often modest. To determine if addition of a Bcl-2 family inhibitor could increase the efficacy of a MEK inhibitor, we evaluated a panel of 53 non–small cell lung cancer and pancreatic cancer cell lines with the combination of navitoclax (ABT-263), a Bcl-2/Bcl-xL (BCL2/BCL2L1) antagonist, and a novel MAP kinase (MEK) inhibitor, G-963. The combination is synergistic in the majority of lines, with an enrichment of cell lines harboring KRAS mutations in the high synergy group. Cells exposed to G-963 arrest in G1 and a small fraction undergo apoptosis. The addition of navitoclax to G-963 does not alter the kinetics of cell-cycle arrest, but greatly increases the percentage of cells that undergo apoptosis. The G-963/navitoclax combination was more effective than either single agent in the KRAS mutant H2122 xenograft model; BIM stabilization and PARP cleavage were observed in tumors, consistent with the mechanism of action observed in cell culture. Addition of the phosphatidylinositol 3-kinase (PI3K, PIK3CA) inhibitor GDC-0941 to this treatment combination increases cell killing compared with double- or single-agent treatment. Taken together, these data suggest the efficacy of agents that target the MAPK and PI3K pathways can be improved by combination with a Bcl-2 family inhibitor. Mol Cancer Ther; 12(6); 853–64. ©2013 AACR.
Metabolic Alterations in Lung Cancer–Associated Fibroblasts Correlated with Increased Glycolytic Metabolism of the Tumor
Authors: Chaudhri Virendra K. , Salzler Gregory G. , Dick Salihah A. , Buckman Melanie S. , Sordella Raffaella , Karoly Edward D. , Mohney Robert , Stiles Brendon M. , Elemento Olivier , Altorki Nasser K. , McGraw Timothy E. 
Published: March 2013

Abstract
Cancer cells undergo a metabolic reprogramming but little is known about metabolic alterations of other cells within tumors. We use mass spectrometry–based profiling and a metabolic pathway–based systems analysis to compare 21 primary human lung cancer–associated fibroblast lines (CAF) to “normal” fibroblast lines (NF) generated from adjacent nonneoplastic lung tissue. CAFs are protumorigenic, although the mechanisms by which CAFs support tumors have not been elucidated. We have identified several pathways whose metabolite abundance globally distinguished CAFs from NFs, suggesting that metabolic alterations are not limited to cancer cells. In addition, we found metabolic differences between CAFs from high and low glycolytic tumors that might reflect distinct roles of CAFs related to the tumor's glycolytic capacity. One such change was an increase of dipeptides in CAFs. Dipeptides primarily arise from the breakdown of proteins. We found in CAFs an increase in basal macroautophagy which likely accounts for the increase in dipeptides. Furthermore, we show a difference between CAFs and NFs in the induction of autophagy promoted by reduced glucose. In sum, our data suggest that increased autophagy may account for metabolic differences between CAFs and NFs and may play additional as yet undetermined roles in lung cancer. Mol Cancer Res; 11(6); 579–92. ©2013 AACR.
Insights Into Atrioventricular Nodal Function From Patients Displaying Dual Conduction Properties
Authors: Mendenhall G. Stuart , Voigt Andrew , Saba Samir 
Published: March 2013

Background—
There is a significant variability observed in the conduction properties of the atrioventricular node. In a subset of hearts, impulse transmission tends to fall into two distinct conduction regions, termed the slow and fast pathway, and a further subset are capable of dual conduction of a single input stimulus, termed double firing.

Methods and Results—
In this article, we closely characterize two distinct responses in patients with double firing properties of the atrioventricular node, separating these into discrete types: those with slow and fast pathway interaction and interdependence (interactive), and those with independent pathway properties (orthogonal). We use novel mathematical techniques to evaluate the relative decrement and unique properties of conduction during the overlapping slow and fast pathway conduction zones.

Conclusions—
Our analysis demonstrates two distinct patterns of pathway conduction in double firing patients, termed interactive and orthogonal. We show parallel overlapping segments of slow and fast pathway decremental conduction curves in interactive pathways, with no such findings with orthogonal conduction. These findings suggest anatomic correlates of pathway conduction, with interactive pathways likely having a common distal segment and orthogonal pathways able to independently activate downstream structures.
Echocardiography-Guided Left Ventricular Lead Placement for Cardiac Resynchronization Therapy
Authors: Saba Samir , Marek Josef , Schwartzman David , Jain Sandeep , Adelstein Evan , White Pamela , Oyenuga Olusegun A. , Onishi Tetsuari , Soman Prem , Gorcsan John 
Published: March 2013

Background—
Cardiac resynchronization therapy improves mortality and morbidity in patients with heart failure (HF) with wide QRS complex and diminished left ventricular (LV) function, but response is variable.

Methods and Results—

The Speckle Tracking Assisted Resynchronization Therapy for Electrode Region (STARTER) was a prospective, double-blind, randomized controlled trial testing the hypothesis that an incremental benefit to cardiac resynchronization therapy would be gained by echo-guided (EG) transvenous LV lead placement versus a routine fluoroscopic approach. EG LV lead placement was attempted at the site of latest time to peak radial strain by speckle tracking echocardiography. The prespecified primary end point was first HF hospitalization or death. Of 187 New York Heart Association class II to IV patients with HF (62% ischemic; ejection fraction 26±6%; QRS 159±27 ms), 110 were randomized to EG and 77 to routine strategies. Primary events included 30 deaths and 37 HF hospitalizations over 1.8 years. Using intention-to-treat, patients randomized to an EG strategy had a significantly more favorable event-free survival (hazard ratio, 0.48; 95% confidence interval, 0.28–0.82;
P
=0.006). Exact or adjacent concordance of LV lead with latest site could be achieved in 85% of the EG group and occurred fortuitously in 66% of controls (
P
=0.010) and was associated with an improvement in event-free survival (hazard ratio, 0.40; 95% confidence interval, 0.22–0.71;
P
=0.002).

Conclusions—
A strategy of EG LV lead placement for cardiac resynchronization therapy improved patient outcomes by reducing the combined risk of death or HF hospitalizations and has implications for delivery of cardiac resynchronization therapy.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00156390.
Multicenter Prospective Observational Study on Acute and Chronic Heart Failure
Authors: Tavazzi Luigi , Senni Michele , Metra Marco , Gorini Marco , Cacciatore Giuseppe , Chinaglia Alessandra , Di Lenarda Andrea , Mortara Andrea , Oliva Fabrizio , Maggioni Aldo P. ,   on the behalf of IN-HF (Italian Network on Heart Failure) Outcome Investigators
Published: March 2013

Background—
Clinical observational studies on heart failure (HF) deal mostly with hospitalized patients, few with chronic outpatients, all with no or limited longitudinal observation.

Methods and Results—
This is a multicenter, nationwide, prospective observational trial on a population of 5610 patients, 1855 hospitalized for acute HF (AHF) and 3755 outpatients with chronic HF (CHF), followed up for 1 year. The cumulative total mortality rate at 1 year was 24% in AHF (19.2% in 797 patients with de novo HF and 27.7% in 1058 with worsening HF) and 5.9% in CHF. Cardiovascular deaths accounted for 73.1% and 65.3% and HF deaths for 42.4% and 40.5% of total deaths in AHF and CHF patients, respectively. One-year hospitalization rates were 30.7% in AHF and 22.7% in CHF patients. Among the independent predictors of 1-year all-cause death, age, low systolic blood pressure, anemia, and renal dysfunction were identified in both acute and chronic patients. A few additional variables were significant only in AHF (signs of cerebral hypoperfusion, low serum sodium, chronic obstructive pulmonary disease, and acute pulmonary edema), whereas others were observed only in CHF patients (lower body mass index, higher heart rate, New York Heart Association class, large QRS, and severe mitral regurgitation).

Conclusions—
In this contemporary data set, patients with CHF had a relatively low mortality rate compared with those with AHF. Rates of adverse outcomes in patients admitted for AHF remain very high either in-hospital or after discharge. Most deaths were cardiovascular in origin and ≈40% of deaths were directly related to HF.
Rethinking European Nature Conservation Legislation: Towards Sustainable Development
Authors: Kistenkas F.H. 
Published: March 2013

European nature conservation law with its habitats assessment as demanded by Article 6 of the 1992 Habitats Directive is recently being regarded as rigid, rather static and not fully updated with modern sustainability and climate change demands.
As a consequence nature conservation law is said to be not always capable to facilitate sustainable development. A balancing of both ecology and socio-economic interests rather than a singular ecological criteria assessment might give way to sustainable combinations of land use in or nearby nature reserves.
While previous authors call for updating and restructuring the Habitats Directive, this paper argues that the EU legislative framework, consisting of European treaty law with its environmental law principles as well as the wording of Article 6 itself, already offers adequate opportunities to re-interpret the EU nature conservation directives within the context of sustainable land use, thus giving way to a less dogmatic approach entirely in line with modern sustainable development demands.
Fatigue and Related Factors in People With Type 2 Diabetes
Authors: Singh Rupali , Kluding Patricia M. 
Published: March 2013

Purpose The purpose of this study was to examine the presence and severity of fatigue in people with type 2 diabetes. Methods The Fatigue Severity Scale (FSS), Fatigue Assessment Scale (FAS), and Visual Analog Fatigue Scale (VAFS) were administered by anonymous survey of 37 individuals with and 33 individuals without diabetes to assess the presence of fatigue. Data on age, gender, weight, height, year of diagnosis, and number/type of complications were also collected. Nonparametric tests tested for differences in fatigue measures between the groups, and distribution characteristics of the FAS, FSS, and VAFS scores were examined. Spearman rank correlation coefficients examined the relationships between the variables. Results People with diabetes scored higher on all 3 fatigue assessment scales as compared to controls (FAS: 25.11 vs 19.94, P = .001; FSS: 4.30 vs 2.59, P = .000; VAFS: 4.64 vs 1.75, P = .000). Data were normally distributed for FSS in the group with diabetes and the group without diabetes, and scores of FAS, FSS, and VAFS showed no ceiling effects. A positive correlation was noted between fatigue measures and number of complications ( r = .482; P = .003). Conclusions Higher levels of fatigue were noted in people with type 2 diabetes as compared to healthy age-matched control; however, the cause and impact of these changes remain unclear. FSS is a recommended tool for measuring fatigue in this population. Further studies are needed to explore the contributing factors to fatigue in those with diabetes.
Race as a Factor for Intensification of Diabetes Medications
Authors: Bullock Katura C. , Edwards Krystal L. , Greene Ronald Shane , Shah Sachin R. , Blaszczyk Amie Taggart 
Published: March 2013

Purpose The purpose of this study was to investigate if patients of nonwhite race are less likely to receive insulin therapy for treatment of poorly controlled diabetes than patients of white race. Methods A retrospective review was performed of patients with an A1C >10%. The primary objective was to determine any difference in the initiation of insulin between white and nonwhite patients. Secondary outcomes measured the impact of clinic type and provider specialty on the initiation of insulin therapy. Exclusion criteria included those patients with type 1 diabetes mellitus, those who were previously receiving insulin, and those without an outpatient clinic visit within 14 days of an A1C >10%. Results A total of 277 patients were included. Of these patients, 132 (47.7%) were white, followed by 95 (34.2%) black non-Hispanic patients and 30 (10.8%) Hispanic/Latino patients. No difference was found in receipt of insulin therapy for nonwhite patients as compared to white patients (12.5 vs 21.4, P = .117). Neither clinic type nor provider specialty impacted initiation of insulin therapy. No changes to medication regimen were made at 35% of clinic visits. Conclusions Failure to intensify diabetic medications was common in this outpatient setting. There were no disparities in the receipt of insulin therapy between white and nonwhite patients.