bluuebunny/crossref_metadata_2025_split huggingface dataset:
Agglomeration, Related Variety, and Vertical Integration
Authors: Cainelli Giulio , Iacobucci Donato 
Published: April 2012

abstractSeveral recent studies have investigated the relationship between the geographic concentration of production and vertical integration, based on the hypothesis that the spatial agglomeration of firms in the same industry facilitates input procurement, thereby reducing the degree of vertical integration. This article contributes to this debate in two ways: first, we focus on interindustry vertical integration, and second, we consider the effects on vertical integration of unrelated and vertically related variety at the local level. The latter was measured using information from input‐output tables and captured the opportunities for outsourcing within the local system. A data set of 24,663 Italian business groups in 2001 was used to estimate Tobit models to investigate the influence of vertically related variety and other agglomeration forces on the degree of vertical integration of groups. We found that vertical integration is influenced by industry specialization at the local level and that higher vertically related variety reduces the need for firms to integrate activities, since they have more opportunities to acquire intermediate goods and services within the local system. We analyze the manufacturing and different macroareas and show that this relationship is also influenced by technology and differences in the organization of economic activities at the local level.
An Equivalent Plate Model for Sandwiched Panels With Thermoviscous
Fluid Core
Authors: Inayat Hussain Husnain , Guyader Jean-Louis 
Published: April 2012

Abstract
A method has been developed to predict the damping behavior of an equivalent plate formed from sandwich panels with a thermoviscous fluid core, which is based on an asymptotic approach. The technique works on the break-up of the basic physical quantities such as pressure, temperature, and particle velocities as constants and linear functions of the z coordinate, which signifies the perpendicular direction from the plate mid-surface. The asymptotic modeling is performed in a very thin and highly thermoviscous fluid layer on the full set of linearized Navier Stokes equations. The use of highly viscous fluid layers such as Rhodorsil® 47 oils, yields high damping loss factors, which are of the order of 10−1. The effects of the panel thickness and the fluid core thickness are also studied. It is shown that the damping loss factor of the equivalent plate is independent of the frequency. Experimental validation provides a good agreement with the theoretical results.
Graphical Facial
Expression Analysis and Design Method: An Approach to Determine Humanoid Skin
Deformation
Authors: Tadesse Yonas , Priya Shashank 
Published: April 2012

Abstract
The architecture of human face is complex consisting of 268 voluntary muscles that perform coordinated action to create real-time facial expression. In order to replicate facial expression on humanoid face by utilizing discrete actuators, the first and foremost step is the identification of a pair of origin and sinking points (SPs). In this paper, we address this issue and present a graphical analysis technique that could be used to design expressive robotic faces. The underlying criterion in the design of faces being deformation of a soft elastomeric skin through tension in anchoring wires attached on one end to the skin through the sinking point and the other end to the actuator. The paper also addresses the singularity problem of facial control points and important phenomena such as slacking of actuators. Experimental characterization on a prototype humanoid face was performed to validate the model and demonstrate the applicability on a generic platform.
Nontypeable Pneumococci Can Be Divided into Multiple
cps
Types, Including One Type Expressing the Novel Gene
pspK
Authors: Park In Ho , Kim Kyung-Hyo , Andrade Ana Lucia , Briles David E. , McDaniel Larry S. , Nahm Moon H. 
Published: April 2012

ABSTRACT

Although virulence of
Streptococcus pneumoniae
is associated with its capsule, some pathogenic
S. pneumoniae
isolates lack capsules and are serologically nontypeable (NT). We obtained 64 isolates that were identified as NT “pneumococci” (i.e., bacteria satisfying the conventional definition but without the multilocus sequence typing [MLST]-based definition of
S. pneumoniae
) by the traditional criteria. All 64 were optochin sensitive and had
lytA
, and 63 had
ply
. Twelve isolates had
cpsA
, suggesting the presence of a conventional but defective capsular polysaccharide synthesis (
cps
) locus. The 52
cpsA-
negative isolates could be divided into three null capsule clades (NCC) based on
aliC
(
aliB-
like ORF1),
aliD
(
aliB-
like ORF2), and our newly discovered gene,
pspK
, in their
cps
loci.
pspK
encodes a protein with a long alpha-helical region containing an LPxTG motif and a YPT motif known to bind human pIgR. There were nine isolates in NCC1 (
pspK
+
but negative for
aliC
and
aliD
), 32 isolates in NCC2 (
aliC
+
aliD
+
but negative for
pspK
), and 11 in NCC3 (
aliD
+
but negative for
aliC
and
pspK
). Among 52
cpsA-
negative isolates, 41 were identified as
S. pneumoniae
by MLST analysis. All NCC1 and most NCC2 isolates were
S. pneumoniae
, whereas all nine NCC3 and two NCC2 isolates were not
S. pneumoniae
. Several NCC1 and NCC2 isolates from multiple individuals had identical MLST and
cps
regions, showing that unencapsulated
S. pneumoniae
can be infectious among humans. Furthermore, NCC1 and NCC2
S. pneumoniae
isolates could colonize mice as well as encapsulated
S. pneumoniae
, although
S. pneumoniae
with an artificially disrupted
cps
locus did not. Moreover, an NCC1 isolate with
pspK
deletion did not colonize mice, suggesting that
pspK
is critical for colonization. Thus, PspK may provide pneumococci a means of surviving in the nasopharynx without capsule.

IMPORTANCE
The presence of a capsule is critical for many pathogenic bacteria, including pneumococci. Reflecting the pathogenic importance of the pneumococcal capsule, pneumococcal vaccines are designed to elicit anticapsule antibodies. Additional evidence for the pathogenic importance of the pneumococcal capsule is the fact that in pneumococci all the genes necessary for capsule production are together in one genetic locus, which is called the
cps
locus. However, there are occasional pathogenic pneumococci without capsules, and how they survive in the host without the capsule is unknown. Here, we show that in these acapsular pneumococci, the
cps
loci have been replaced with various novel genes and they can colonize mouse nasopharynges as well as capsulated pneumococci. Since the genes that replace the
cps
loci are likely to be important in host survival, they may show new and/or alternative capsule-independent survival mechanisms used by pneumococci.
Modulation of Akt/mTOR Signaling Overcomes Sunitinib Resistance in Renal and Prostate Cancer Cells
Authors: Makhov Peter B. , Golovine Konstantin , Kutikov Alexander , Teper Ervin , Canter Daniel J. , Simhan Jay , Uzzo Robert G. , Kolenko Vladimir M. 
Published: April 2012

Abstract
Tyrosine kinase inhibitors exhibit impressive activity against advanced renal cell carcinoma. However, recent clinical studies have shown an equivocal response to sunitinib in patients with castration-resistant prostate cancer. The tumor suppressor PTEN acts as a gatekeeper of the phosphoinositide 3-kinase (PI3K)/Akt/mTOR cell–survival pathway. Our experiments showed that PTEN expression inversely correlates with sunitinib resistance in renal and prostate cancer cells. Restoration of PTEN expression markedly increases sensitivity of tumor cells to sunitinib both in vitro and in vivo. In addition, pharmacologic manipulation of PI3K/Akt/mTOR signaling with PI3K/mTOR inhibitor, GDC-0980, mTOR inhibitor, temsirolimus, or pan-Akt inhibitor, GSK690693, was able to overcome sunitinib resistance in cancer cells. Our findings underscore the importance of PTEN expression in relation to sunitinib resistance and imply a direct cytotoxic effect by sunitinib on tumor cells in addition to its antiangiogenic actions. Mol Cancer Ther; 11(7); 1510–7. ©2012 AACR.
Thermal Targeting of an Acid-Sensitive Doxorubicin Conjugate of Elastin-like Polypeptide Enhances the Therapeutic Efficacy Compared with the Parent Compound In Vivo
Authors: Moktan Shama , Perkins Eddie , Kratz Felix , Raucher Drazen 
Published: April 2012

Abstract
Elastin-like polypeptides (ELP) aggregate in response to mild hyperthermia, but remain soluble under normal physiologic conditions. ELP macromolecules can accumulate in solid tumors because of the enhanced permeability and retention effect. Tumor retention of ELPs can be further enhanced through hyperthermia-induced aggregation of ELPs by local heating of the tumor. We evaluated the therapeutic potential of ELPs in delivering doxorubicin in the E0771 syngeneic mouse breast cancer model. The ELP-Dox conjugate consisted of a cell-penetrating peptide at the N-terminus and the 6-maleimidocaproyl hydrazone derivative of doxorubicin at the C-terminus of ELP. The acid-sensitive hydrazone linker ensured release of doxorubicin in the lysosomes/endosomes after cellular uptake of the drug conjugate. ELP-Dox dosed at 5 mg doxorubicin equivalent/kg, extended the plasma half-life of doxorubicin to 5.5 hours. In addition, tumor uptake of ELP-Dox increased 2-fold when hyperthermia was applied, and was also enhanced compared to free doxorubicin. Although high levels of doxorubicin were found in the heart of animals treated with free doxorubicin, no detectable levels of doxorubicin were found in ELP-Dox–treated animals, indicating a correlation between tumor targeting and reduction of potential cardiac toxicity by ELP-Dox. At an optimal dose of 12 mg doxorubicin equivalent/kg, ELP-Dox in combination with hyperthermia induced a complete tumor growth inhibition, which was distinctly superior to free drug that only moderately inhibited tumor growth. In summary, our findings show that thermal targeting of ELP increases the potency of doxorubicin underlying the potential of exploiting ELPs to enhance the therapeutic efficacy of conventional anticancer drugs. Mol Cancer Ther; 11(7); 1547–56. ©2012 AACR.
Downscaled Climate Change Scenarios for Baja California and the North American Monsoon during the Twenty-First Century
Authors: Cavazos Tereza , Arriaga-Ramírez Sarahí 
Published: April 2012

Abstract
Regional climate change scenarios for Baja California/Southern California (BCC) and the North American monsoon (NAM) were produced as part of the Baja California State Climate Change Action Program (PEACC-BC). Bias-corrected and spatially downscaled scenarios (BCSD) from six general circulation models (GCMs) with a total of 12 realizations were analyzed for two scenarios of the Intergovernmental Panel on Climate Change (IPCC) Special Report on Emissions Scenarios (SRES): B1 (low emissions) and A2 (high emissions) during the twenty-first century. A validation of the original GCM realizations and the BCSD scenarios with observed data during 1961–90 show that the ensemble GCM produces too much precipitation during autumn and winter, which could be the cause of the observed delay of the summer monsoon rains; the ensemble BCSD considerably improves the mean annual cycles and spatial distributions of precipitation and temperature in the region. However, both ensembles greatly underestimate the observed interannual variability of precipitation. BCSD scenarios of temperature and precipitation during the twenty-first century were evaluated on the basis of the multimodel median change relative to 1961–90. The scenarios of precipitation change show large interannual variations and larger uncertainties than the scenarios of temperature change. The A2 scenarios show the largest reductions of precipitation in the last 20 yr of the twenty-first century; a decrease of 30% is projected for BCC mainly in winter and spring, while precipitation in the NAM region could be weakened by 20% during winter, spring, and summer. After 2050, a significant reduction of precipitation is expected in northwestern Mexico and the southwestern United States south of 35°N, and temperature changes larger than 2°C warming.
Quantitative Comparison of the Spatial Distribution of Radar and Gauge Rainfall Data
Authors: Yoon Seong-Sim , Phuong Anh Tran , Bae Deg-Hyo 
Published: April 2012

Abstract
The common statement that a rain gauge network usually provides better observation at specific points while weather radar provides more accurate observation of the spatial distribution of rain field over a large area has never been subjected to quantitative evaluation. The aim of this paper is to evaluate the statement by using some statistical criteria. The Monte Carlo simulation experiment, inverse distance weighting (IDW) interpolation method, and cross-validation technique are used to investigate the relation between the accuracy of the interpolated rainfall and the rain gauge density. The radar reflectivity–rainfall intensity (Z–R) relationship is constructed by the least squares fitting method from observation data of radar and rain gauges. The variation in this relationship and the accuracy of the radar rainfall with rain gauge density are evaluated by using the Monte Carlo simulation experiment. Three storm events are selected as the case studies. The obtained results show that the accuracy of interpolated and radar rainfall increases nonlinearly with increasing gauge density. The higher correlation coefficient (γ) value of radar-rainfall estimation, compared to gauge interpolation, especially in the convective storm, proves that radar observation provides a more accurate spatial structure of the rain field than gauge observation does.
Juxtaglomerular apparatus hyperplasia under dual angiotensin blockade. A footprint of adequate RAS inhibition or a concern for renal fibrosis?
Authors: Fernandez-Fernandez Beatriz , Ortiz Alberto , Gomez-Guerrero Carmen , Barat Antonio , Martín-Cleary Catalina , Egido Jesús 
Published: April 2012

Abstract

Background
Dual renin-angiotensin system blockade with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers has been advocated to minimize proteinuria. However, recent trials have questioned the renal safety of this approach. Our understanding on the molecular effects of dual blockade in humans is incomplete.

Case presentation
We present a patient with corticoid resistant nephrotic syndrome who developed marked juxtaglomerular apparatus hyperplasia and renin expression in the context of dual angiotensin system blockade.

Conclusions
Although renin may have profibrotic effects mediated by (pro)renin receptor activation, this report raises questions on the potential consequences of local renin activation on chronic kidney disease in patients with dual angiotensin blockade.
Lean oncology: a new model for oncologists
Authors: Montesarchio Vincenzo , Grimaldi Antonio Maria , Fox Bernard A , Rea Antonio , Marincola Francesco M , Ascierto Paolo A 
Published: April 2012

Abstract
The history of the term Lean is relatively recent and originates from the Toyota Production System (TPS). The term "Lean" means "thin", which refers to a mental process, operational, productive, no-frills, quick but not hasty, consequential to the previous event. The Lean process flows seamlessly into the result, eliminates unnecessary complications to the effect, prevents unnecessary equipment processes. The idea is to 'do more with less', like using the (few) available resources in the most productive way possible, through the elimination of all types of waste that inevitably accompanies every stage of a production process. Lean management is primarily a management philosophy, a system of values and behaviors that goes beyond the mere application of the instrument and that, once internalized, will form the nucleus of the corporate culture. "Lean Oncology" is a term coined to identify a methodology of care and treatment to cancer patients, consisting on process simplification, streamlining of the organizational and routes of drug treatment, detection and elimination of waste. Its main objective is the centrality of the patient.
The Economic impact of Non-communicable Diseases on households in India
Authors: Engelgau Michael M , Karan Anup , Mahal Ajay 
Published: April 2012

Abstract

Background
In India, Non Communicable Diseases (NCDs) and injuries account for an estimated 62% of the total age-standardized burden of forgone Disability Adjusted Life Years (DALYs). Public and private financing of clinical services to reduce the NCD burden is a major challenge.

Methods
We used National Sample Survey Organization (NSSO) survey data from 1995-96 and 2004 covering nearly 200 thousand households to assess healthcare utilization patterns and out of pocket health spending by disease category. For this purpose, self-reported diseases and conditions were categorized into NCDs and non-NCDs. Survey data were used to assess how households financed their overall health expenditures and related this pattern to specific health conditions. We measured catastrophic spending on NCD-related hospitalization, defined as occurring when health expenditures exceeded 40% of a household's ability to pay, that is, household consumption spending less combined survival consumption expenditure; and impoverishment when per capita expenditure within the household decreased to below the poverty line once health spending was netted out.

Results
The share of NCDs in out of pocket health expenses incurred by households increased over time, from 31.6 percent in 1995-96 to 47.3 percent in 2004. In both years, own savings and income were the most important source of financing for many health conditions, typically between 40-60 percent of all spending, whereas 30-35 percent was from borrowing. The odds of catastrophic hospitalization expenditures for cancer was nearly 170% greater and for CVD and injuries 22 percent greater than the odds due to communicable diseases. Impoverishment patterns were similar.

Conclusions
Out of pocket expenses for treating NCDs rose sharply over the period from 1995-96 to 2004. When NCDs are present, the financial risks to which Indians households are exposed are significant.
Evolutionary constraints and expression analysis of gene duplications in Rhodobacter sphaeroides 2.4.1
Authors: Peters Anne E , Bavishi Anish , Cho Hyuk , Choudhary Madhusudan 
Published: April 2012

Abstract

Background
Gene duplication is a major force that contributes to the evolution of new metabolic functions in all organisms. Rhodobacter sphaeroides 2.4.1 is a bacterium that displays a wide degree of metabolic versatility and genome complexity and therefore is a fitting model for the study of gene duplications in bacteria. A comprehensive analysis of 234 duplicate gene-pairs in R. sphaeroides was performed using structural constraint and expression analysis.

Results
The results revealed that most gene-pairs in in-paralogs are maintained under negative selection (ω ≤ 0.3), but the strength of selection differed among in-paralog gene-pairs. Although in-paralogs located on different replicons are maintained under purifying selection, the duplicated genes distributed between the primary chromosome (CI) and the second chromosome (CII) are relatively less selectively constrained than the gene-pairs located within each chromosome. The mRNA expression patterns of duplicate gene-pairs were examined through microarray analysis of this organism grown under seven different growth conditions. Results revealed that ~62% of paralogs have similar expression patterns (cosine ≥ 0.90) over all of these growth conditions, while only ~7% of paralogs are very different in their expression patterns (cosine < 0.50).

Conclusions
The overall findings of the study suggest that only a small proportion of paralogs contribute to the metabolic diversity and the evolution of novel metabolic functions in R. sphaeroides. In addition, the lack of relationships between structural constraints and gene-pair expression suggests that patterns of gene-pair expression are likely associated with conservation or divergence of gene-pair promoter regions and other coregulation mechanisms.
Rapid paracellular transmigration of Campylobacter jejuni across polarized epithelial cells without affecting TER: role of proteolytic-active HtrA cleaving E-cadherin but not fibronectin
Authors: Boehm Manja , Hoy Benjamin , Rohde Manfred , Tegtmeyer Nicole , Bæk Kristoffer T , Oyarzabal Omar A , Brøndsted Lone , Wessler Silja , Backert Steffen 
Published: April 2012

Abstract

Background

Campylobacter jejuni is one of the most important bacterial pathogens causing food-borne illness worldwide. Crossing the intestinal epithelial barrier and host cell entry by C. jejuni is considered the primary reason of damage to the intestinal tissue, but the molecular mechanisms as well as major bacterial and host cell factors involved in this process are still widely unclear.

Results
In the present study, we characterized the serine protease HtrA (high-temperature requirement A) of C. jejuni as a secreted virulence factor with important proteolytic functions. Infection studies and in vitro cleavage assays showed that C. jejuni’s HtrA triggers shedding of the extracellular E-cadherin NTF domain (90 kDa) of non-polarised INT-407 and polarized MKN-28 epithelial cells, but fibronectin was not cleaved as seen for H. pylori’s HtrA. Deletion of the htrA gene in C. jejuni or expression of a protease-deficient S197A point mutant did not lead to loss of flagella or reduced bacterial motility, but led to severe defects in E-cadherin cleavage and transmigration of the bacteria across polarized MKN-28 cell layers. Unlike other highly invasive pathogens, transmigration across polarized cells by wild-type C. jejuni is highly efficient and is achieved within a few minutes of infection. Interestingly, E-cadherin cleavage by C. jejuni occurs in a limited fashion and transmigration required the intact flagella as well as HtrA protease activity, but does not reduce transepithelial electrical resistance (TER) as seen with Salmonella, Shigella, Listeria or Neisseria.

Conclusion
These results suggest that HtrA-mediated E-cadherin cleavage is involved in rapid crossing of the epithelial barrier by C. jejuni via a very specific mechanism using the paracellular route to reach basolateral surfaces, but does not cleave the fibronectin receptor which is necessary for cell entry.
Dynamical systems analysis of spike-adding mechanisms in transient bursts
Authors: Nowacki Jakub , Osinga Hinke M , Tsaneva-Atanasova Krasimira 
Published: April 2012

Abstract
Transient bursting behaviour of excitable cells, such as neurons, is a common feature observed experimentally, but theoretically, it is not well understood. We analyse a five-dimensional simplified model of after-depolarisation that exhibits transient bursting behaviour when perturbed with a short current injection. Using one-parameter continuation of the perturbed orbit segment formulated as a well-posed boundary value problem, we show that the spike-adding mechanism is a canard-like transition that has a different character from known mechanisms for periodic burst solutions. The biophysical basis of the model gives a natural time-scale separation, which allows us to explain the spike-adding mechanism using geometric singular perturbation theory, but it does not involve actual bifurcations as for periodic bursts. We show that unstable sheets of the critical manifold, formed by saddle equilibria of the system that only exist in a singular limit, are responsible for the spike-adding transition; the transition is organised by the slow flow on the critical manifold near folds of this manifold. Our analysis shows that the orbit segment during the spike-adding transition includes a fast transition between two unstable sheets of the slow manifold that are of saddle type. We also discuss a different parameter regime where the presence of additional saddle equilibria of the full system alters the spike-adding mechanism.