What Do We Know About Geographical Knowledge Spillovers and Regional Growth? A Survey of the Literature

Modern (endogenous) growth theory tells us that knowledge spillovers are crucial for the growth of high-income economies. Against this background the paper provides a survey of theoretical and empirical findings highlighting the question of how geographically limited knowledge diffusion can help to explain clusters of regions with persistently different levels of growth. The paper discusses this topic in two steps: First, the theoretical concept of knowledge spillovers is outlined by discussing the different types of knowledge, the spatial dimension of knowledge spillovers, and the geographical mechanisms and structural conditions of knowledge diffusion. This discussion shows that the literature on knowledge spillovers focuses on the hypotheses that such spillovers lead to dynamic externalities and – in the geographical dimension – to agglomeration effects, both of which constitute path dependence in the economic growth of regions. Second, the paper analyses the empirical evidence for these theoretical findings. Existing empirical work mainly supports the theoretically derived hypotheses. This applies especially with focus on the spatial limited character of knowledge spillovers as well as the importance of knowledge transfer for regional productivity and innovative behaviour. --knowledge spillovers,regional growth,research and development,innovation,diffusion of innovations

What Do We Know About Geographical Knowledge Spillovers and Regional Growth? A Survey of the Literature

Modern (endogenous) growth theory tells us that knowledge spillovers are crucial for the growth of high-income economies. Against this background the paper provides a survey of theoretical and empirical findings highlighting the question of how geographically limited knowledge diffusion can help to explain clusters of regions with persistently different levels of growth. The paper discusses this topic in two steps: First, the theoretical concept of knowledge spillovers is outlined by discussing the different types of knowledge, the spatial dimension of knowledge spillovers, and the geographical mechanisms and structural conditions of knowledge diffusion. This discussion shows that the literature on knowledge spillovers focuses on the hypotheses that such spillovers lead to dynamic externalities and - in the geographical dimension - to agglomeration effects, both of which constitute path dependence in the economic growth of regions. Second, the paper analyses the empirical evidence for these theoretical findings. Existing empirical work mainly supports the theoretically derived hypotheses. This applies especially with focus on the spatial limited character of knowledge spillovers as well as the importance of knowledge transfer for regional productivity and innovative behaviour

Development of intraindividual value structures in middle childhood: A multicultural and longitudinal investigation

Objective We examined changes in value interrelations during middle childhood. In line with the Personal Values Theory, we expected a value system, with individuals similarly valuing related motivations, and setting priorities between conflicting motivations. We hypothesized this system to develop dynamically during middle childhood as children deepen their understanding of their own values. Method Using unfolding analysis, we estimated intraindividual value structure coherence, that is, the extent to which the interrelations among a child's values are similar to the hypothesized interrelations. Cross-Cultural Study 1 (N = 4615, 6–12-year-old children) included children from 12 countries. Cross-Sequential Study 2 (N = 629, 6–10-year-old children at Time 1) included three annual measurements. Results In Study 1, we found a curvilinear association between age and intraindividual value structure coherence: Children's values were more coherent at ages 9–10 than before or after. Study 2 confirmed this pattern of within-individual development. Conclusions We propose that development in coherence with the theoretical value structure offers insight into children's understanding of values as well as changes in value priorities

Neue katalytische Bleichaktivatoren auf Basis von Mangan-Chelatkomplexen

Die vorliegende Arbeit befasst sich primär mit der Synthese verschiedener drei- oder vierzähniger N,O-Chelatliganden, welche es ermöglichen sollen, ein Manganatom zu komplexieren und in unterschiedlichen Oxidationsstufen zu stabilisieren. Die Liganden sollen in wässriger Umgebung und weitestgehend unabhängig vom pH-Wert stabil sein und eine hohe Resistenz gegen einen oxidativen Abbau aufweisen. Diese Grundvoraussetzungen ergeben sich aus der Zielsetzung, die auf Basis dieser Liganden synthetisierten Komplexverbindungen als Bleichkatalysatoren zur Aktivierung des günstigen Oxidationsmittels H2O2 in Waschmitteln einsetzen zu können. Die so erhaltenen Bleichkatalysatoren sollen mit allen typischen Inhaltsstoffen einer Waschmittelrezeptur kompatibel sein und durch andere im Waschmittel anwesende Stoffe nicht zerstört werden. Der Schwerpunkt auf die Verwendung von Mangan als redoxaktives Zentrum ergibt sich daraus, dass Mangan in einer Vielzahl möglicher Oxidationsstufen stabile Verbindungen bildet und als Redoxkatalysator in Bleichlaugen hohe Aktivitäten aufweist. Weitere Vorteile sind dessen biologische Unbedenklichkeit und die Tatsache, dass bereits eine Aktivierung von Wasserstoffperoxid durch Mangankomplexe nachgewiesen werden konnte (vgl. Kap. 3.3). Die Eignung der erhaltenen Komplexverbindungen wird dabei in normierten Waschtests im Rahmen einer Zusammenarbeit mit der Fa. HENKEL überprüft

Exercise in multiple sclerosis -- an integral component of disease management

Multiple sclerosis (MS) is the most common chronic inflammatory disorder of the central nervous system (CNS) in young adults. The disease causes a wide range of symptoms depending on the localization and characteristics of the CNS pathology. In addition to drug-based immunomodulatory treatment, both drug-based and non-drug approaches are established as complementary strategies to alleviate existing symptoms and to prevent secondary diseases. In particular, physical therapy like exercise and physiotherapy can be customized to the individual patient's needs and has the potential to improve the individual outcome. However, high quality systematic data on physical therapy in MS are rare. This article summarizes the current knowledge on the influence of physical activity and exercise on disease-related symptoms and physical restrictions in MS patients. Other treatment strategies such as drug treatments or cognitive training were deliberately excluded for the purposes of this article

Whole exome sequencing of microdissected splenic marginal zone lymphoma: a study to discover novel tumor-specific mutations

BACKGROUND: Splenic marginal zone lymphoma (SMZL) is an indolent B-cell non-Hodgkin lymphoma and represents the most common primary malignancy of the spleen. Its precise molecular pathogenesis is still unknown and specific molecular markers for diagnosis or possible targets for causal therapies are lacking. METHODS: We performed whole exome sequencing (WES) and copy number analysis from laser-microdissected tumor cells of two primary SMZL discovery cases. Selected somatic single nucleotide variants (SNVs) were analyzed using pyrosequencing and Sanger sequencing in an independent validation cohort. RESULTS: Overall, 25 nonsynonymous somatic SNVs were identified, including known mutations in the NOTCH2 and MYD88 genes. Twenty-three of the mutations have not been associated with SMZL before. Many of these seem to be subclonal. Screening of 24 additional SMZL for mutations at the same positions found mutated in the WES approach revealed no recurrence of mutations for ZNF608 and PDE10A, whereas the MYD88 L265P missense mutation was identified in 15 % of cases. An analysis of the NOTCH2 PEST domain and the whole coding region of the transcription factor SMYD1 in eight cases identified no additional case with a NOTCH2 mutation, but two additional cases with SMYD1 alterations. CONCLUSIONS: In this first WES approach from microdissected SMZL tissue we confirmed known mutations and discovered new somatic variants. Recurrence of MYD88 mutations in SMZL was validated, but NOTCH2 PEST domain mutations were relatively rare (10 % of cases). Recurrent mutations in the transcription factor SMYD1 have not been described in SMZL before and warrant further investigatio

a study to discover novel tumor-specific mutations

Background Splenic marginal zone lymphoma (SMZL) is an indolent B-cell non- Hodgkin lymphoma and represents the most common primary malignancy of the spleen. Its precise molecular pathogenesis is still unknown and specific molecular markers for diagnosis or possible targets for causal therapies are lacking. Methods We performed whole exome sequencing (WES) and copy number analysis from laser-microdissected tumor cells of two primary SMZL discovery cases. Selected somatic single nucleotide variants (SNVs) were analyzed using pyrosequencing and Sanger sequencing in an independent validation cohort. Results Overall, 25 nonsynonymous somatic SNVs were identified, including known mutations in the NOTCH2 and MYD88 genes. Twenty-three of the mutations have not been associated with SMZL before. Many of these seem to be subclonal. Screening of 24 additional SMZL for mutations at the same positions found mutated in the WES approach revealed no recurrence of mutations for ZNF608 and PDE10A, whereas the MYD88 L265P missense mutation was identified in 15 % of cases. An analysis of the NOTCH2 PEST domain and the whole coding region of the transcription factor SMYD1 in eight cases identified no additional case with a NOTCH2 mutation, but two additional cases with SMYD1 alterations. Conclusions In this first WES approach from microdissected SMZL tissue we confirmed known mutations and discovered new somatic variants. Recurrence of MYD88 mutations in SMZL was validated, but NOTCH2 PEST domain mutations were relatively rare (10 % of cases). Recurrent mutations in the transcription factor SMYD1 have not been described in SMZL before and warrant further investigation

Advanced resistivity model for arbitrary magnetization orientation applied to a series of compressive- to tensile-strained (Ga,Mn)As layers

The longitudinal and transverse resistivities of differently strained (Ga,Mn)As layers are theoretically and experimentally studied as a function of the magnetization orientation. The strain in the series of (Ga,Mn)As layers is gradually varied from compressive to tensile using (In,Ga)As templates with different In concentrations. Analytical expressions for the resistivities are derived from a series expansion of the resistivity tensor with respect to the direction cosines of the magnetization. In order to quantitatively model the experimental data, terms up to the fourth order have to be included. The expressions derived are generally valid for any single-crystalline cubic and tetragonal ferromagnet and apply to arbitrary surface orientations and current directions. The model phenomenologically incorporates the longitudinal and transverse anisotropic magnetoresistance as well as the anomalous Hall effect. The resistivity parameters obtained from a comparison between experiment and theory are found to systematically vary with the strain in the layer.Comment: 14 pages, 11 figures, submitted to Phys. Rev.

Gastrointestinal Stromal Tumors: Clinical Symptoms, Location, Metastasis Formation, and Associated Malignancies in a Single Center Retrospective Study

Background and Aims: Gastrointestinal stromal tumors (GISTs) are rare malignancies but the most common mesenchymal tumors of the digestive tract. Recent advances in diagnostic imaging and an increasing incidence will confront us more frequently with stromal tumors. This single center study aimed to characterize GIST patients in terms of tumor location, clinical presentation, metastasis formation, as well as associated secondary malignancies. Methods: In a retrospective study, 104 patients with a histologically confirmed diagnosis of GIST, collected between 1993 and 2011, were characterized for several clinical features. Results: The most common GIST location was the stomach (67.6%) followed by the small intestine (16.2%). Gastrointestinal bleeding (55.8%) and abdominal pain (38.5%) were the most frequently reported symptoms whereas about one-third of patients remained clinically asymptomatic (31.6%); 14.4% of patients had either synchronous or metachronous metastases and there was a significant prevalence also in the low risk group. The proportion of secondary malignant associated neoplasms was 31% in our GIST cohort, among which gastrointestinal, genitourinary tumors, and breast cancer were the most prevalent. Conclusion: There was a considerable risk for metastasis formation and the development of secondary neoplasias that should encourage discussion about the appropriate surveillance strategy after surgery for GIST

Deep-Phenotyping the Less Severe Spectrum of PIGT Deficiency and Linking the Gene to Myoclonic Atonic Seizures

The two aims of this study were (i) to describe and expand the phenotypic spectrum of PIGT deficiency in affected individuals harboring the c.1582G>A; p.Val528Met or the c.1580A > G; p.Asn527Ser variant in either homozygous or compound heterozygous state, and (ii) to identify potential genotype-phenotype correlations and any differences in disease severity among individuals with and without the PIGT variants. The existing literature was searched to identify individuals with and without the two variants. A detailed phenotypic assessment was performed of 25 individuals (both novel and previously published) with the two PIGT variants. We compared severity of disease between individuals with and without these PIGT variants. Twenty-four individuals carried the PIGT variant Val528Met in either homozygous or compound heterozygous state, and one individual displayed the Asn527Ser variant in a compound heterozygous state. Disease severity in the individual with the Asn527Ser variant was compatible with that in the individuals harboring the Val528Met variant. While individuals without the Asn527Ser or Val528Met variant had focal epilepsy, profound developmental delay (DD), and risk of premature death, those with either of the two variants had moderate to severe DD and later onset of epilepsy with both focal and generalized seizures. Individuals homozygous for the Val528Met variant generally became seizure-free on monotherapy with antiepileptic drugs, compared to other PIGT individuals who were pharmaco-resistant. Two patients were diagnosed with myoclonic-atonic seizures, and a single patient was diagnosed with eyelid myoclonia. Our comprehensive analysis of this large cohort of previously published and novel individuals with PIGT variants broadens the phenotypical spectrum and shows that both Asn527Ser and Val528Met are associated with a milder phenotype and less severe outcome. Our data show that PIGT is a new candidate gene for myoclonic atonic epilepsy. Our genotype-phenotype correlation will be useful for future genetic counseling. Natural history studies of this mild spectrum of PIGT-related disorder may shed light on hitherto unknown aspects of this rare disorder