bluuebunny/crossref_metadata_2025_split huggingface dataset:
Parametric sensitivity analysis for biochemical reaction networks based on pathwise information theory
Authors: Pantazis Yannis , Katsoulakis Markos A , Vlachos Dionisios G 
Published: October 2013

Abstract

Background
Stochastic modeling and simulation provide powerful predictive methods for the intrinsic understanding of fundamental mechanisms in complex biochemical networks. Typically, such mathematical models involve networks of coupled jump stochastic processes with a large number of parameters that need to be suitably calibrated against experimental data. In this direction, the parameter sensitivity analysis of reaction networks is an essential mathematical and computational tool, yielding information regarding the robustness and the identifiability of model parameters. However, existing sensitivity analysis approaches such as variants of the finite difference method can have an overwhelming computational cost in models with a high-dimensional parameter space.

Results
We develop a sensitivity analysis methodology suitable for complex stochastic reaction networks with a large number of parameters. The proposed approach is based on Information Theory methods and relies on the quantification of information loss due to parameter perturbations between time-series distributions. For this reason, we need to work on path-space, i.e., the set consisting of all stochastic trajectories, hence the proposed approach is referred to as “pathwise”. The pathwise sensitivity analysis method is realized by employing the rigorously-derived Relative Entropy Rate, which is directly computable from the propensity functions. A key aspect of the method is that an associated pathwise Fisher Information Matrix (FIM) is defined, which in turn constitutes a gradient-free approach to quantifying parameter sensitivities. The structure of the FIM turns out to be block-diagonal, revealing hidden parameter dependencies and sensitivities in reaction networks.

Conclusions
As a gradient-free method, the proposed sensitivity analysis provides a significant advantage when dealing with complex stochastic systems with a large number of parameters. In addition, the knowledge of the structure of the FIM can allow to efficiently address questions on parameter identifiability, estimation and robustness. The proposed method is tested and validated on three biochemical systems, namely: (a) a protein production/degradation model where explicit solutions are available, permitting a careful assessment of the method, (b) the p53 reaction network where quasi-steady stochastic oscillations of the concentrations are observed, and for which continuum approximations (e.g. mean field, stochastic Langevin, etc.) break down due to persistent oscillations between high and low populations, and (c) an Epidermal Growth Factor Receptor model which is an example of a high-dimensional stochastic reaction network with more than 200 reactions and a corresponding number of parameters.
Patterns of genetic differentiation at MHC class I genes and microsatellites identify conservation units in the giant panda
Authors: Zhu Ying , Wan Qiu-Hong , Yu Bin , Ge Yun-Fa , Fang Sheng-Guo 
Published: October 2013

AbstractBackgroundEvaluating patterns of genetic variation is important to identify conservation units (i.e., evolutionarily significant units [ESUs], management units [MUs], and adaptive units [AUs]) in endangered species. While neutral markers could be used to infer population history, their application in the estimation of adaptive variation is limited. The capacity to adapt to various environments is vital for the long-term survival of endangered species. Hence, analysis of adaptive loci, such as the major histocompatibility complex (MHC) genes, is critical for conservation genetics studies. Here, we investigated 4 classical MHC class I genes (Aime-C,Aime-F,Aime-I, andAime-L) and 8 microsatellites to infer patterns of genetic variation in the giant panda (Ailuropoda melanoleuca) and to further define conservation units.ResultsOverall, we identified 24 haplotypes (9 forAime-C, 1 forAime-F, 7 forAime-I, and 7 forAime-L) from 218 individuals obtained from 6 populations of giant panda. We found that the Xiaoxiangling population had the highest genetic variation at microsatellites among the 6 giant panda populations and higher genetic variation atAime-MHC class I genes than other larger populations (Qinling, Qionglai, and Minshan populations). Differentiation index (FST)-based phylogenetic and Bayesian clustering analyses forAime-MHC-I and microsatellite loci both supported that most populations were highly differentiated. The Qinling population was the most genetically differentiated.ConclusionsThe giant panda showed a relatively higher level of genetic diversity at MHC class I genes compared with endangered felids. Using all of the loci, we found that the 6 giant panda populations fell into 2 ESUs: Qinling and non-Qinling populations. We defined 3 MUs based on microsatellites: Qinling, Minshan-Qionglai, and Daxiangling-Xiaoxiangling-Liangshan. We also recommended 3 possible AUs based on MHC loci: Qinling, Minshan-Qionglai, and Daxiangling-Xiaoxiangling-Liangshan. Furthermore, we recommend that a captive breeding program be considered for the Qinling panda population.
Genetic control of renal tumorigenesis by the mouse Rtm1 locus
Authors: Jensen José Ricardo , Galvan Antonella , Borrego Andrea , Hanna Koury Cabrera Wafa , Ribeiro Orlando Garcia , Starobinas Nancy , De Franco Marcelo , Colecchia Maurizio , Bertolotti Alessia , Dragani Tommaso Antonio , Martinez Ibañez Olga Célia 
Published: October 2013

Abstract

Background
The genetic basis of susceptibility to renal tumorigenesis has not yet been established in mouse strains. Mouse lines derived by bidirectional phenotypic selection on the basis of their maximal (AIRmax) or minimal (AIRmin) acute inflammatory responsiveness differ widely in susceptibility to spontaneous and urethane-induced renal tumorigenesis. To map the functional loci modulating renal tumor susceptibility in these mice, we carried out a genome-wide genetic linkage study, using SNP arrays, in an (AIRmax x AIRmin)F2 intercross population treated with a single urethane dose at 1 week of age and phenotyped for renal tumors at 35 weeks of age.

Results
AIRmax mice did not develop renal tumors spontaneously nor in response to urethane, whereas in AIRmin mice renal tumors formed spontaneously (in 52% of animals) and after urethane induction (89%). The tumors had a papillary morphology and were positive for alpha-methylacyl-CoA racemase and negative for CD10. By analysis of 879 informative SNPs in 662 mice, we mapped a single quantitative trait locus modulating the incidence of renal tumors in the (AIRmax x AIRmin)F2 intercross population. This locus, which we named Renal tumor modifier QTL 1 (Rtm1), mapped to chromosome 17 at 23.4 Mb (LOD score = 15.8), with SNPs rs3696835 and rs3719497 flanking the LOD score peak. The A allele of rs3719497 from AIRmin mice was associated with a 2.5-fold increased odds ratio for renal tumor development. The LOD score peak included the Tuberous sclerosis 2 (Tsc2) gene which has already been implicated in kidney disease: loss of function by germline retroviral insertion is associated with spontaneous renal tumorigenesis in the Eker rat, and heterozygous-null Tsc2

(+/-)
mice develop renal cystadenomas.

Conclusions
We mapped Rtm1 as a single major locus modulating renal tumorigenesis in a murine intercross population. Thus, the AIR mouse lines can be considered a new genetic model for studying the role of germline and somatic molecular alterations in kidney neoplastic disease.
Comparison of baseline quality of life measures between renal cell carcinoma patients undergoing partial versus radical nephrectomy
Authors: Arnold Michelle L , Thiel David D , Diehl Nancy , Wu Kevin J , Ames Steve , Parker Alexander S 
Published: October 2013

Abstract

Background
To compare demographics, pathologic features, performance scores, comorbidities, symptoms and responses to quality of life (QoL) surveys between nephron-sparing surgery (NSS) and radical nephrectomy (RN) patients prior to surgical intervention. Previous investigators have compared QoL outcomes for patients undergoing RN and NSS; however, there are limited data comparing QoL-related characteristics at baseline between these groups.

Methods
We identified 144 patients with localized RCC who underwent either NSS (n = 71) or RN (n = 73) between May ‘07-November ‘12. We abstracted baseline data on demographic and clinic-pathologic variables as well as responses to the SF-36 and FACT-G surveys from our prospective registry. We amended the FACT-G with 8 additional questions designed to address RCC-specific QoL. For comparisons between the two groups, we employed Wilcoxon rank-sum and Fisher's Exact tests where appropriate.

Results
We observed RN patients to have more aggressive pathology. We noted no difference in performance scores between the two groups; however, RN patients were more likely to have higher Charlson scores (p = 0.022) and various symptoms at presentation (all p <0.001). For the QoL surveys, we did not observe differences on the FACT-G; however, we noted evidence of differential scores between the two groups on specific domains of the SF-36 (e.g. Mental Health; p 0.022) and the RCC-specific QoL questions added to the FACT-G.

Conclusions
We report baseline differences between RN and NSS patients on clinico-pathologic as well as QoL-related metrics. As issues of survivorship become increasingly important, our results underscore the need to consider baseline status in evaluations of QoL-related outcomes for patients undergoing surgery for RCC.
Vacuum Seed Sowing Manifold: a novel device for high-throughput sowing of Arabidopsis seeds
Authors: Barker Richard , Cox Benjamin , Mackie Thomas Rockwell , Masson Patrick 
Published: October 2013

Abstract
The small size of Arabidopsis provides both opportunities and difficulties for laboratory research. Large numbers of plants can be grown in a relatively small area making it easy to observe and investigate interesting phenotypes. Conversely, their small size can also make it difficult to obtain large quantities of tissue for investigation using modern molecular techniques. Sowing large numbers of their seed can overcome this; however, their small seed size makes this difficult. Here we present the Vacuum Seed Sowing Manifold (VSSM), a simple device that can be printed using a 3D printer and provides a new high throughput method to sow large numbers of seeds at a range of densities.
Clinicopathologic features and responses to radiotherapy of myeloid sarcoma
Authors: Chen Wan-Yu , Wang Chun-Wei , Chang Chin-Hao , Liu Heng-Hsiu , Lan Keng-Hsueh , Tang Jih-Luh , Tien Hwei-Fang , Kuo Sung-Hsin , Cheng Ann-Lii 
Published: October 2013

AbstractBackgroundTo evaluate clinicopathological features, radiotherapeutic parameters, and their associations with responses to radiotherapy (RT) in patients with myeloid sarcoma (MS).MethodsWe reviewed 20 patients receiving RT for MS lesions (in 43 RT courses) and analyzed the patients’ clinicopathologic features and radiotherapeutic parameters, and their associations with complete responses (CR) to RT using Fisher’s exact test and univariate logistic regression analysis. Generalized Estimating Equation was used to analyze all 43 irradiated lesions and account for the correlations in RT responses among lesions from the same patient.ResultsWe found that the underlying hematological diseases of the evaluated patients were acute myeloid leukemia (AML) in 14 patients (70%), chronic myeloid leukemia in 4 patients (20%), myelodysplastic syndrome with AML transformation in one patient (5%), and de novo MS in one patient (5%). Most patients (55%) received RT for MS at the time of relapse following bone marrow transplantation (BMT). The most common cytogenetic abnormality was t(8;21)(q22;q22). The median RT dose of 20 Gy (range 6–35 Gy), administered in 1.5-3.5 Gy fractions, provided a 63% CR rate. RT dose, sex, cytogenetics, and bone marrow status at the time of RT had no significant effect on CR. Younger age (<50 y,P = 0.06), BMT prior to RT (P = 0.05), and underlying AML (P = 0.05) were marginally associated with higher CR to RT.ConclusionsOur results indicate that a modest RT dose (20-30 Gy) achieves good local control of MS. Age, previous BMT, and underlying hematologic disease can affect RT response.
Movilidad social y desigualdad en el Buenos Aires del siglo XIX: el acceso a la propiedad de la tierra entre el rosismo y el orden liberal
Authors: Gelman Jorge , Santilli Daniel 
Published: October 2013

Abstract
Buena parte del discurso historiográfico sobre América Latina señala su fuerte resistencia al cambio económico y la poca movilidad social entre sus habitantes. Sin embargo los estudios sistemáticos para períodos previos al siglo XX son muy escasos. En este trabajo nos proponemos evaluar los procesos de movilidad social intrageneracional en Buenos Aires en las décadas centrales del siglo XIX, a través del acceso a la propiedad de la tierra y las posibilidades de acumulación o pérdida de la misma. Para ello utilizaremos tres bases de datos completas sobre los propietarios de bienes inmuebles de la provincia de Buenos Aires en 1839, 1855 y 1867, momentos en que la región atravesaba por importantes cambios económicos, políticos e institucionales. De esta manera buscamos valorar el impacto de estos cambios en las posibilidades de movilidad social de la población, y propiciar la discusión con las imágenes recibidas sobre el tema.
An investigation of the effect of AlloMatrix bone graft in distal radial fracture
Authors: D’Agostino P. , Barbier O. 
Published: October 2013

The osteoinductive properties of demineralised bone matrix have been demonstrated in animal studies. However, its therapeutic efficacy has yet to be proven in humans. The clinical properties of AlloMatrix, an injectable calcium-based demineralised bone matrix allograft, were studied in a prospective randomised study of 50 patients with an isolated unstable distal radial fracture treated by reduction and Kirschner (K-) wire fixation. A total of 24 patients were randomised to the graft group (13 men and 11 women, mean age 42.3 years (20 to 62)) and 26 to the no graft group (8 men and 18 women, mean age 45.0 years (17 to 69)).At one, three, six and nine weeks, and six and 12 months post-operatively, patients underwent radiological evaluation, assessments for range of movement, grip and pinch strength, and also completed the Disabilities of Arm, Shoulder and Hand questionnaire. At one and six weeks and one year post-operatively, bone mineral density evaluations of both wrists were performed.No significant difference in wrist function and speed of recovery, rate of union, complications or bone mineral density was found between the two groups. The operating time was significantly higher in the graft group (p = 0.004). Radiologically, the reduction parameters remained similar in the two groups and all AlloMatrix extraosseous leakages disappeared after nine weeks.This prospective randomised controlled trial did not demonstrate a beneficial effect of AlloMatrix demineralised bone matrix in the treatment of this category of distal radial fractures treated by K-wire fixation.Cite this article: Bone Joint J 2013;95-B:1514–20.
Corail uncemented hemiarthroplasty with a Cathcart head for intracapsular hip fractures
Authors: Kendrick B. J. L. , Wilson H. A. , Lippett J. E. , McAndrew A. R. , Andrade A. J. M. D. 
Published: October 2013

The National Institute for Health and Clinical Excellence (NICE) guidelines from 2011 recommend the use of cemented hemi-arthroplasty for appropriate patients with an intracapsular hip fracture. In our institution all patients who were admitted with an intracapsular hip fracture and were suitable for a hemi-arthroplasty between April 2010 and July 2012 received an uncemented prosthesis according to our established departmental routine practice. A retrospective analysis of outcome was performed to establish whether the continued use of an uncemented stem was justified. Patient, surgical and outcome data were collected on the National Hip Fracture database. A total of 306 patients received a Cathcart modular head on a Corail uncemented stem as a hemi-arthroplasty. The mean age of the patients was 83.3 years (sd 7.56; 46.6 to 94) and 216 (70.6%) were women. The mortality rate at 30 days was 5.8%. A total of 46.5% of patients returned to their own home by 30 days, which increased to 73.2% by 120 days. The implant used as a hemi-arthroplasty for intracapsular hip fracture provided satisfactory results, with a good rate of return to pre-injury place of residence and an acceptable mortality rate. Surgery should be performed by those who are familiar with the design of the stem and understand what is required for successful implantation. Cite this article: Bone Joint J 2013;95-B:1538–43.
Thyroid status and functional and cognitive status at baseline and survival after 3 years of follow-up: the OCTABAIX study
Authors: Formiga Francesc , Ferrer Assumpta , Padros Gloria , Contra Anna , Corbella Xavier , Pujol Ramon , _ _ 
Published: October 2013

ObjectiveSubclinical thyroid disorders are common in older individuals. Health risks associated with subclinical hypothyroidism in older adults are unclear. The aim of the study is to evaluate whether thyroid status in elderly subjects correlates with physical and cognitive function at baseline and with 3-year mortality.DesignA population-based, prospective cohort of the OCTABAIX study (307 inhabitants aged 85 years at baseline).MethodsChronic drug prescription, functional status (Barthel and Lawton indices) and cognitive status according to the Spanish version of the Mini-Mental State Examination were recorded. Quality of life was assessed using the visual analogue scale of the quality of life test. Concentrations of TSH and thyroxine were measured. Participants were classified in accordance with clinical categories of thyroid function.ResultsTwenty (6.5%) individuals had subclinical hypothyroidism and five (1.6%) had subclinical hyperthyroidism. Compared with euthyroid subjects (n=280; 91.8%), subclinical hypo- and hyperthyroidism subjects were not significantly associated with poor physical or cognitive function at baseline. Fifty-one (15.1%) subjects died during the 36 months of follow-up. TSH values and subclinical hypo- and hyperthyroidism were not associated with an increased overall mortality risk (hazard ratio (HR) 1.086, 95% CI 0.987–1.196 and HR 0.905, 95% CI 0.902–1.053 respectively).ConclusionsThis study does not support the association of TSH or thyroid disorders with physical or cognitive function at baseline or with 3-year mortality in the oldest old subjects.
Új lehetőségek a sebészet gyakorlati oktatásában
Authors: Kormos Katalin , Sándor József , Haidegger Tamás , Ferencz Andrea , Csukás Domokos , Bráth Endre , Szabó Györgyi , Wéber György 
Published: October 2013

Absztrakt
A laparoscopos sebészet gyors elterjedése a világon egyúttal az új eljárás oktatásához szükséges módszerek bevezetését is szükségessé tette. Az alkalmazott „gyakorlódobozok” hasznos segítséget jelentettek, majd a „látszólagos valóság” technikája a szimulációs gyakorlás újabb lehetőségét teremtette meg. A sebészet történetében először nyílt rá mód, hogy az orvostanhallgató vagy rezidens kézügyességét mérőszámokkal lehessen jellemezni, a szimulált sebészi beavatkozások mint „komoly játékok” ismerhetők meg. A modern képalkotó eljárások alapján már a műtét előtt megtervezhetők az, egy adott beavatkozás során végzendő mozdulatsorok, melyek ismételhetők, gyakorolhatók, és így a műtét biztonságos kivitelezését is elősegítik. A nyílt műtéteket eljárásspecifikus műanyag táblákon lehet a gyakorlatban elvégezni, illetve interaktív érintőképernyős eszköz használatával és e-learning útján is meg lehet ismerni.
Conditions governing the generalisation of threshold bound states by N attractive delta potentials in one and three dimensions
Authors: Dharani Marappan , Sahu Basudeb , Shastry Chakrakodi 
Published: October 2013

Abstract
This paper proves that for N attractive delta function potentials the number of bound states (Nb) satisfies 1 ≤ N
b ≤ N in one dimension (1D), and is 0 ≤ N
b ≤ N in three dimensions (3D). Algebraic equations are obtained to evaluate the bound states generated by N attractive delta potentials. In particular, in the case of N attractive delta function potentials having same separation a between adjacent wells and having the same strength λV, the parameter g=λVa governs the number of bound states. For a given N in the range 1–7, both in 1D and 3D cases the numerical values of gn, where n=1,2,..N are obtained. When g=gn, Nb ≤ n where Nb includes one threshold energy bound state. Furthermore, gn are the roots of the Nth order polynomial equations with integer coefficients. Based on our numerical calculations up to N=40, even when N becomes large, 0 ≤ g
n ≤ 4 and $\frac{{\Sigma g_n }}
{N} \simeq 2
$ and this result is expected to be generally valid. Thus, for g > 4 there will be no threshold or zero energy bound state, and if g≈ 2 for a given large N, the number of bound states will be approximately N/2. The empirical formula gn = 4/[1+exp((N
0 − n)/β)] gives a good description of the variation of gn as a function of n. This formula is useful in estimating the number of bound states for any N and g both in 1D and 3D cases.
Accuracy evaluation of a two-wire technique for osteotomy positioning in the tibial plateau levelling procedure
Authors: Knuchel-Takano A. , Brissot H. , Nelissen P. , Bush M. , Owen M. , Woodbridge N. 
Published: October 2013

SummaryObjectives: To evaluate a tibial plateau levelling osteotomy (TPLO) saw blade positioning technique and to retrospectively evaluate the accuracy of the osteotomy position.Methods: Preoperative and postoperative radiographs of 72 cases that had a TPLO surgery using a two-wire technique were reviewed. Three measurements (A1, B1, C1) were obtained in preoperative planning using a computer template system (Orthoview Vet) which mapped the intended osteotomy position. The postoperative radiographs were analysed to determine the variability of these three measurements (A2, B2, C2) and therefore the accuracy of the osteotomy.Results: On average the least variable measurement was B2 (5%) followed by C2 (7%) and then A2 (13%). The maximum mean difference between the intended position and achieved position was 1.5 mm.Clinical significance: Despite there being a significant difference between the intended and the actual position of the osteotomy, the variation between the intended and actual tibial tuberosity width was small (5%). None of the cases suffered a tibial tuberosity fracture, which also supports the clinical value of this technique. Care must be taken to avoid inadvertent cutting of the Kirschner guide wires.
Computational Large‐Scale Mapping of Protein‐Protein Interactions Using Structural Complexes
Authors: Shoemaker Benjamin , Wuchty Stefan , Panchenko Anna R. 
Published: October 2013

AbstractAlthough the identification of protein interactions by high‐throughput methods progresses at a fast pace, “interactome” datasets still suffer from high rates of false positives and low coverage. To map the interactome of any organism, this unit presents a computational framework to predict protein‐protein or gene‐gene interactions utilizing experimentally determined evidence of structural complexes, atomic details of binding interfaces and evolutionary conservation. Curr. Protoc. Protein Sci. 73:3.9.1‐3.9.9. © 2013 by John Wiley & Sons, Inc.