Labor Mobility and Productivity Growth

[cat] Els models de creixement amb aprenentatge suposen que el coneixement après en producció es transmet de forma lliure i instantània a tota l'economia. En con- seqüència, l'economia presenta economies d'escala creixents i el creixement de la productivitat (TFP) és endògena. No obstant, el supòsit de difusió instantània del coneixement és poc realista. La difusió del coneixement necessita temps i algun canal de transmissió. En aquest article suposem que el coneixement es transmet amb la contractació de treballadors nous (learning-by-hiring). En el nostre model la difusió instantània i lliure de coneixement pot ocórrer només dins d'un sector. La difusió de coneixement entre sectors pot ocórrer només a través de la mobilitat de treballadors, i per tant, el mercat de treball determina el nivell i la taxa de creixement de productivitat (TFP). Estudiem com els costos de mobilitat laboral modifiquen l'equilibri sota dos escenaris: creixement endogen i exogen. A més, demostrem que d'altres ineficiències del mercat laboral, com són les taxes o els costos de cerca, poden reduir la mobilitat laboral, i per tant, modificar la TFP.

Labor Mobility and Productivity Growth

[cat] Els models de creixement amb aprenentatge suposen que el coneixement après en producció es transmet de forma lliure i instantània a tota l'economia. En con- seqüència, l'economia presenta economies d'escala creixents i el creixement de la productivitat (TFP) és endògena. No obstant, el supòsit de difusió instantània del coneixement és poc realista. La difusió del coneixement necessita temps i algun canal de transmissió. En aquest article suposem que el coneixement es transmet amb la contractació de treballadors nous (learning-by-hiring). En el nostre model la difusió instantània i lliure de coneixement pot ocórrer només dins d'un sector. La difusió de coneixement entre sectors pot ocórrer només a través de la mobilitat de treballadors, i per tant, el mercat de treball determina el nivell i la taxa de creixement de productivitat (TFP). Estudiem com els costos de mobilitat laboral modifiquen l'equilibri sota dos escenaris: creixement endogen i exogen. A més, demostrem que d'altres ineficiències del mercat laboral, com són les taxes o els costos de cerca, poden reduir la mobilitat laboral, i per tant, modificar la TFP.

Growth Models with Exogenous Saving Rates, Unemployment and Wage Inertia

[cat] El propòsit d'aquest article és introduir una mercat de treball no competitiu i atur en el model de creixement amb taxes d'estalvi exògenes que es pot trobar en els llibres de text de creixement (Sala‐i‐Martín, 2000; Barro and Sala‐i‐Martín, 2003; Romer, 2006). Primer, derivem un marc general amb una funció de producció neoclàssica per analitzar la relació entre creixement i ocupació. Utilitzem aquest marc per estudiar les dinàmiques conjuntes del creixement i l'ocupació sota diferents regles de fixació salarial.

Effects of Sucroferric Oxyhydroxide Compared to Lanthanum Carbonate and Sevelamer Carbonate on Phosphate Homeostasis and Vascular Calcifications in a Rat Model of Chronic Kidney Failure.

Elevated serum phosphorus, calcium, and fibroblast growth factor 23 (FGF23) levels are associated with cardiovascular disease in chronic renal disease. This study evaluated the effects of sucroferric oxyhydroxide (PA21), a new iron-based phosphate binder, versus lanthanum carbonate (La) and sevelamer carbonate (Se), on serum FGF23, phosphorus, calcium, and intact parathyroid hormone (iPTH) concentrations, and the development of vascular calcification in adenine-induced chronic renal failure (CRF) rats. After induction of CRF, renal function was significantly impaired in all groups: uremic rats developed severe hyperphosphatemia, and serum iPTH increased significantly. All uremic rats (except controls) then received phosphate binders for 4 weeks. Hyperphosphatemia and increased serum iPTH were controlled to a similar extent in all phosphate binder-treatment groups. Only sucroferric oxyhydroxide was associated with significantly decreased FGF23. Vascular calcifications of the thoracic aorta were decreased by all three phosphate binders. Calcifications were better prevented at the superior part of the thoracic and abdominal aorta in the PA21 treated rats. In adenine-induced CRF rats, sucroferric oxyhydroxide was as effective as La and Se in controlling hyperphosphatemia, secondary hyperparathyroidism, and vascular calcifications. The role of FGF23 in calcification remains to be confirmed.

Disentangling the formation of contrasting tree line physiognomies combining model selection and Bayesian parameterization for simulation models.

Alpine tree-line ecotones are characterized by marked changes at small spatial scales that may result in a variety of physiognomies. A set of alternative individual-based models was tested with data from four contrasting Pinus uncinata ecotones in the central Spanish Pyrenees to reveal the minimal subset of processes required for tree-line formation. A Bayesian approach combined with Markov chain Monte Carlo methods was employed to obtain the posterior distribution of model parameters, allowing the use of model selection procedures. The main features of real tree lines emerged only in models considering nonlinear responses in individual rates of growth or mortality with respect to the altitudinal gradient. Variation in tree-line physiognomy reflected mainly changes in the relative importance of these nonlinear responses, while other processes, such as dispersal limitation and facilitation, played a secondary role. Different nonlinear responses also determined the presence or absence of krummholz, in agreement with recent findings highlighting a different response of diffuse and abrupt or krummholz tree lines to climate change. The method presented here can be widely applied in individual-based simulation models and will turn model selection and evaluation in this type of models into a more transparent, effective, and efficient exercise.

Selecting, testing and modifying a model for identifying potential key customers

Tämä työ tehtiin globaaliin elektroniikka-alan yritykseen. Diplomityö liittyy haasteeseen, jonka lisääntynyt globalisaatio ja kiristyvä kilpailu ovat luoneet: case yrityksen on selvitettävä kuinka se voi saavuttaa kasvutavoitteet myös tulevaisuudessa hankkimalla uusia asiakkaita ja olemalla yhä enenevissä määrin maailmanlaajuisesti läsnä. Tutkimuksen tavoite oli löytää sopiva malli potentiaalisten avainasiakkaiden identifiointiin ja valintaan, sekä testata ja modifioida valittua mallia case yrityksen tarpeiden mukaisesti. Erityisesti raakadatan kerääminen, asiakkaiden houkuttelevuuskriteerit ja kohdemarkkinarako olivat asioita, jotka tarvitsivat tutkimuksessa huomiota. Kirjallisuuskatsauksessa keskityttiin yritysmarkkinoihin, eri asiakassuhteenhallinnan lähestymistapoihin ja avainasiakkaiden määrittämiseen. CRM:n, KAM:n ja Customer Insight-ajattelun perusteet esiteltiin yhdessä eri avainasiakkaiden identifiointimallien kanssa. Valittua Chevertonin mallia testattiin ja muokattiin työn empiirisessä osassa. Tutkimuksen empiirinen kontribuutio on modifioitu malli potentiaalisten avainasiakkaiden identifiointiin. Se auttaa päätöksentekijöitä etenemään systemaattisesti ja organisoidusti askel askeleelta kohti potentiaalisten asiakkaiden listaa tietyltä markkina-alueelta. Työ tarjoaa työkalun tähän prosessiin sekä luo pohjaa tulevaisuuden tutkimukselle ja toimenpiteille.

Fusion weld metal solidification:Continuum from weld interface to centerline

We present a brief résumé of the history of solidification research and key factors affecting the solidification of fusion welds. There is a general agreement of the basic solidification theory, albeit differing - even confusing - nomenclatures do exist, and Cases 2 and 3 (the Chalmers' basic boundary conditions for solidification, categorized by Savage as Cases) are variably emphasized. Model Frame, a tool helping to model the continuum of fusion weld solidification from start to end, is proposed. It incorporates the general solidification models, of which the pertinent ones are selected for the actual modeling. The basic models are the main solidification Cases 1…4. These discrete Cases are joined with Sub-Cases: models of Pfann, Flemings and others, bringing needed Sub-Case variables into the model. Model Frame depicts a grain growing from the weld interface to its centerline. Besides modeling, the Model Frame supports education and academic debate. The new mathematical modeling techniques will extend its use into multi-dimensional modeling, introducing new variables and increasing the modeling accuracy. We propose a model: melting/solidification-model (M/S-model) - predicting the solute profile at the start of the solidification of a fusion weld. This Case 3-based Sub-Case takes into account the melting stage, the solute back-diffusion in the solid, and the growth rate acceleration typical to fusion welds. We propose - based on works of Rutter & Chalmers, David & Vitek and our experimental results on copper - that NEGS-EGS-transition is not associated only with cellular-dendritic-transition. Solidification is studied experimentally on pure and doped copper with welding speed range from 0 to 200 cm/min, with one test at 3000 cm/min. Found were only planar and cellular structures, no dendrites - columnar or equiaxed. Cell sub structures: rows of cubic elements we call "cubelettes", "cell-bands" and "micro-cells", as well as an anomalous crack morphology "crack-eye", were detected, as well as microscopic hot crack nucleus we call "grain-lag cracks", caused by a grain slightly lagging behind its neighbors in arrival to the weld centerline. Varestraint test and R-test revealed a change of crack morphologies from centerline cracks to grainand cell boundary cracks with an increasing welding speed. High speed made the cracks invisible to bare eye and hardly detectable with light microscope, while electron microscope often revealed networks of fine micro-cracks.

Planarians as a model to assess in vivo the role of matrix metalloproteinase genes during homeostasis and regeneration

Matrix metalloproteinases (MMPs) are major executors of extracellular matrix remodeling and, consequently, play key roles in the response of cells to their microenvironment. The experimentally accessible stem cell population and the robust regenerative capabilities of planarians offer an ideal model to study how modulation of the proteolytic system in the extracellular environment affects cell behavior in vivo. Genome-wide identification of Schmidtea mediterranea MMPs reveals that planarians possess four mmp-like genes. Two of them (mmp1 and mmp2) are strongly expressed in a subset of secretory cells and encode putative matrilysins. The other genes (mt-mmpA and mt-mmpB) are widely expressed in postmitotic cells and appear structurally related to membrane-type MMPs. These genes are conserved in the planarian Dugesia japonica. Here we explore the role of the planarian mmp genes by RNA interference (RNAi) during tissue homeostasis and regeneration. Our analyses identify essential functions for two of them. Following inhibition of mmp1 planarians display dramatic disruption of tissues architecture and significant decrease in cell death. These results suggest that mmp1 controls tissue turnover, modulating survival of postmitotic cells. Unexpectedly, the ability to regenerate is unaffected by mmp1(RNAi). Silencing of mt-mmpA alters tissue integrity and delays blastema growth, without affecting proliferation of stem cells. Our data support the possibility that the activity of this protease modulates cell migration and regulates anoikis, with a consequent pivotal role in tissue homeostasis and regeneration. Our data provide evidence of the involvement of specific MMPs in tissue homeostasis and regeneration and demonstrate that the behavior of planarian stem cells is critically dependent on the microenvironment surrounding these cells. Studying MMPs function in the planarian model provides evidence on how individual proteases work in vivo in adult tissues. These results have high potential to generate significant information for development of regenerative and anti cancer therapies.

N-acetylcysteine treatment ameliorates the skeletal phenotype of a mouse model of diastrophic dysplasia.

Diastrophic dysplasia (DTD) is a recessive chondrodysplasia caused by mutations in SLC26A2, a cell membrane sulfate-chloride antiporter. Sulfate uptake impairment results in low cytosolic sulfate, leading to cartilage proteoglycan (PG) undersulfation. In this work, we used the dtd mouse model to study the role of N-acetyl-l-cysteine (NAC), a well-known drug with antioxidant properties, as an intracellular sulfate source for macromolecular sulfation. Because of the important pre-natal phase of skeletal development and growth, we administered 30 g/l NAC in the drinking water to pregnant mice to explore a possible transplacental effect on the fetuses. When cartilage PG sulfation was evaluated by high-performance liquid chromatography disaccharide analysis in dtd newborn mice, a marked increase in PG sulfation was observed in newborns from NAC-treated pregnancies when compared with the placebo group. Morphometric studies of the femur, tibia and ilium after skeletal staining with alcian blue and alizarin red indicated a partial rescue of abnormal bone morphology in dtd newborns from treated females, compared with pups from untreated females. The beneficial effect of increased macromolecular sulfation was confirmed by chondrocyte proliferation studies in cryosections of the tibial epiphysis by proliferating cell nuclear antigen immunohistochemistry: the percentage of proliferating cells, significantly reduced in the placebo group, reached normal values in dtd newborns from NAC-treated females. In conclusion, NAC is a useful source of sulfate for macromolecular sulfation in vivo when extracellular sulfate supply is reduced, confirming the potential of therapeutic approaches with thiol compounds to improve skeletal deformity and short stature in human DTD and related disorders.

Direct tumor recognition by a human CD4(+) T-cell subset potently mediates tumor growth inhibition and orchestrates anti-tumor immune responses.

Tumor antigen-specific CD4(+) T cells generally orchestrate and regulate immune cells to provide immune surveillance against malignancy. However, activation of antigen-specific CD4(+) T cells is restricted at local tumor sites where antigen-presenting cells (APCs) are frequently dysfunctional, which can cause rapid exhaustion of anti-tumor immune responses. Herein, we characterize anti-tumor effects of a unique human CD4(+) helper T-cell subset that directly recognizes the cytoplasmic tumor antigen, NY-ESO-1, presented by MHC class II on cancer cells. Upon direct recognition of cancer cells, tumor-recognizing CD4(+) T cells (TR-CD4) potently induced IFN-γ-dependent growth arrest in cancer cells. In addition, direct recognition of cancer cells triggers TR-CD4 to provide help to NY-ESO-1-specific CD8(+) T cells by enhancing cytotoxic activity, and improving viability and proliferation in the absence of APCs. Notably, the TR-CD4 either alone or in collaboration with CD8(+) T cells significantly inhibited tumor growth in vivo in a xenograft model. Finally, retroviral gene-engineering with T cell receptor (TCR) derived from TR-CD4 produced large numbers of functional TR-CD4. These observations provide mechanistic insights into the role of TR-CD4 in tumor immunity, and suggest that approaches to utilize TR-CD4 will augment anti-tumor immune responses for durable therapeutic efficacy in cancer patients.

Waddlia: An emerging pathogen and a model organism to study the biology of chlamydiae.

Waddlia chondrophila is an emerging pathogen associated with abortion in cattle. In humans, a growing body of evidence supports its pathogenic role in miscarriage and in respiratory tract infection. The human pathogenicity of W. chondrophila is further supported by the presence of several virulence factors including a catalase, a functional T3SS and several adhesins. Despite this medical importance, no commercial tests are available and diagnostic of this strict intracellular bacterium mainly relies on serology, PCR and immunohistochemistry. So far, the epidemiology of W. chondrophila remains largely unexplored and zoonotic, waterborne or interhuman transmission has been considered. Apart from its pathogenic role, chlamydiologists are also interested in W. chondrophila in order to better understand biological mechanisms conserved and shared with Chlamydia spp. Indeed, W. chondrophila proved to be a useful model organism to study the pathobiology of chlamydiae thanks to its rapid replication, its large size allowing precise subcellular protein localization, as well as its growth in Dictyostelium amoebae.

Dpp spreading is required for medial but not for lateral wing disc growth.

Drosophila Decapentaplegic (Dpp) has served as a paradigm to study morphogen-dependent growth control. However, the role of a Dpp gradient in tissue growth remains highly controversial. Two fundamentally different models have been proposed: the 'temporal rule' model suggests that all cells of the wing imaginal disc divide upon a 50% increase in Dpp signalling, whereas the 'growth equalization model' suggests that Dpp is only essential for proliferation control of the central cells. Here, to discriminate between these two models, we generated and used morphotrap, a membrane-tethered anti-green fluorescent protein (GFP) nanobody, which enables immobilization of enhanced (e)GFP::Dpp on the cell surface, thereby abolishing Dpp gradient formation. We find that in the absence of Dpp spreading, wing disc patterning is lost; however, lateral cells still divide at normal rates. These data are consistent with the growth equalization model, but do not fit a global temporal rule model in the wing imaginal disc.

Mouse Model of Respiratory Tract Infection Induced by Waddlia chondrophila.

Waddlia chondrophila, an obligate intracellular bacterium belonging to the Chlamydiales order, is considered as an emerging pathogen. Some clinical studies highlighted a possible role of W. chondrophila in bronchiolitis, pneumonia and miscarriage. This pathogenic potential is further supported by the ability of W. chondrophila to infect and replicate within human pneumocytes, macrophages and endometrial cells. Considering that W. chondrophila might be a causative agent of respiratory tract infection, we developed a mouse model of respiratory tract infection to get insight into the pathogenesis of W. chondrophila. Following intranasal inoculation of 2 x 108 W. chondrophila, mice lost up to 40% of their body weight, and succumbed rapidly from infection with a death rate reaching 50% at day 4 post-inoculation. Bacterial loads, estimated by qPCR, increased from day 0 to day 3 post-infection and decreased thereafter in surviving mice. Bacterial growth was confirmed by detecting dividing bacteria using electron microscopy, and living bacteria were isolated from lungs 14 days post-infection. Immunohistochemistry and histopathology of infected lungs revealed the presence of bacteria associated with pneumonia characterized by an important multifocal inflammation. The high inflammatory score in the lungs was associated with the presence of pro-inflammatory cytokines in both serum and lungs at day 3 post-infection. This animal model supports the role of W. chondrophila as an agent of respiratory tract infection, and will help understanding the pathogenesis of this strict intracellular bacterium.

Secondary growth of the Arabidopsis hypocotyl-vascular development in dimensions.

The secondary thickening of plant organs in extant dicotyledons is a massive growth process that constitutes the major carbon sink in perennial, woody plants. Yet, our understanding of its molecular genetic control has been mostly obtained by its analysis in an herbaceous annual model, Arabidopsis. Recent years have seen increased interest in this somewhat under-researched topic, and various (non-)cell autonomous factors that guide the extent and vascular patterning of secondary growth have been identified. Concomitantly, a more detailed understanding of vascular differentiation processes has been obtained through analyses of primary growth, mostly in the root meristem. A future challenge will be the integration of these patterning and differentiation modules together with cambial activity into the 4-dimensional frame of secondary thickening.

MALT1 activity controls Kaposi's sarcoma-associated herpesvirus latency and growth of primary effusion lymphoma

The identification of cancer-specific enzymatic activities that can be therapeutically targeted is key to the development of suitable anti-cancer drugs. Primary effusion lymphoma (PEL) is a rare and incurable malignancy that can occur in immunodeficient patients as a consequence of latent infection of B-cells with Kaposi's sarcoma-associated herpesvirus, KSHV (also known as human herpesvirus-8, HHV8). Malignant growth of KSHV-infected B cells requires the constitutive activity of the transcription factor NF-KB, which controls expression of viral genes required for maintenance of viral latency and suppression of the viral lytic program. Here we identify the protease mucosa-associated lymphoid tissue transformation protein 1 (MALTI), a key driver of NF-KB activation in lymphocytes, as an essential component in KSHV-dependent NF-KB activation and growth of latently infected PEL cell lines. Inhibition of the MALTI protease activity induced a switch from the latent to the lytic stage of viral infection, and led to reduced growth and survival of PEL cell lines in vitro and in a xenograft model. These results demonstrate a key role for the proteolytic activity of MALTI in PEL, and provide a rationale for the pharmacological targeting of MALTI in PEL therapy. -- L'identification d'activités enzymatiques propre au cancer est clé dans le développement des nouvaux médicaments anti-cancer. Le lymphome primitif des séreuses est un lymphome rare et incurable qui peut se developer chez les patients immunodéficients. Il est la conséquence d'une infection latente des cellules B, dûe à l'herpes virus 8, plus connu comme herpes virus associé au sarcome de Kaposi (KSHV). La croissance maligne des cellules B infecteés par KSHV requière l'activité constitutive du facteur de transcription NF-KB qui contrôle l'expression des genes viraux requis pour la maintenance latente et la suppression du programme de lyse du virus. Avec cette étude, nous avons identifié la protease MALTI comme un composant essentiel dans l'activation de NF-KB dans les cellules B du lymphome primitif des séreuses. L'inhibition de l'activité de la protéase MALTI induit un virement de la phase latente à la phase lytique du KSHV et conduit à une reduction de la viabilité des cellules tumorales in vitro et dans un modèle de xénogreffe. Ces résultats démontrent un rôle clé pour l'activité protéolytique de MALTI dans le développement du lymphome primitif des séreuses et soutiennent l'idée que MALTI pourrait être une cible pharmacologique dans la thérapie de cette forme rare du lymphome.