Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels.

Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health.

Lifecourse socioeconomic status and type 2 diabetes : the role of chronic inflammation in the English Longitudinal Study of Ageing.

We examined the association between lifecourse socioeconomic status (SES) and the risk of type 2 diabetes at older ages, ascertaining the extent to which adult lifestyle factors and systemic inflammation explain this relationship. Data were drawn from the English Longitudinal Study of Ageing (ELSA) which, established in 2002, is a representative cohort study of ≥50-year olds individuals living in England. SES indicators were paternal social class, participants' education, participants' wealth, and a lifecourse socioeconomic index. Inflammatory markers (C-reactive protein and fibrinogen) and lifestyle factors were measured repeatedly; diabetes incidence (new cases) was monitored over 7.5 years of follow-up. Of the 6218 individuals free from diabetes at baseline (44% women, mean aged 66 years), 423 developed diabetes during follow-up. Relative to the most advantaged people, those in the lowest lifecourse SES group experienced more than double the risk of diabetes (hazard ratio 2.59; 95% Confidence Interval (CI) = 1.81-3.71). Lifestyle factors explained 52% (95%CI:30-85) and inflammatory markers 22% (95%CI:13-37) of this gradient. Similar results were apparent with the separate SES indicators. In a general population sample, socioeconomic inequalities in the risk of type 2 diabetes extend to older ages and appear to partially originate from socioeconomic variations in modifiable factors which include lifestyle and inflammation.

Two-photon excitation fluorometry in detection of infectious diseases

Because of the heavily overlapping symptoms, pathogen-specific diagnosis and treatment of infectious diseases is difficult based on clinical symptoms alone. Therefore, patients are often treated empirically. More efficient treatment and management of infectious diseases would require rapid point-of-care compatible in vitro diagnostic methods. However, current point-of-care methods are unsatisfactory in performance and in cost structure. The lack of pointof- care methods results in unnecessary use of antibiotics, suboptimal use of virus-specific drugs, and compromised patient care. In this thesis, the applicability of a two-photon excitation fluorometry is evaluated as a tool for rapid detection of infectious diseases. New separation-free immunoassay methodologies were developed and validated for the following application areas: general inflammation markers, pathogen-specific antibodies, pathogen-specific antigens, and antimicrobial susceptibility testing. In addition, dry-reagent methodology and nanoparticulate tracers are introduced in context to the technique. The results show that the new assay technique is a versatile tool for rapid detection of infectious diseases in many different application areas. One particularly attractive area is rapid multianalyte testing of respiratory infections, where the technique was shown to allow simple assay protocols and comparable performance to the state-of-the-art laboratory methods. If implemented in clinical diagnostic use, the new methods could improve diagnostic testing routines, especially in rapid testing of respiratory tract infections.

Företagshistoriker

Samlingen med signum ESF Bibl. Hist. finns vid Ekonomiska biblioteket och innehåller företags- och organisationshistoriker. Företags- och organisationshistoriker finns också vid huvudbiblioteket i en samling med signum HB Xf1. Speciellt en donation av företagshistoriker kan nämnas, donator var Elsa Bruun. Historikerna vid Ekonomiska biblioteket kan sökas i databasen Alma med sökfunktionen Signum och söktermen ESF Bibl. Hist.

Sociala frågor och socialpolitik

Samlingen med signum HB VIc2 finns vid huvudbiblioteket och innehåller litteratur om sociala frågor och socialpolitik till och med år 1999. Liknande litteratur finns i Åbo i anslutning till ämnet Samhällsekonomi ävensom i Vasa vid biblioteket Tritonia i anslutning till ämnet Socialpolitik. Litteratur om sociala frågor och socialpolitik har ingått i bokdonationer såväl från hemlandet som från Sverige. Några donatorer kan nämnas som exempel, K.A. Fagerholm, Carl von Bonsdorff, Elsa Bruun och Allan Wallenius. Friexemplaren som erhållits från och med 1919 samt inköp har kompletterat samlingen. Litteraturen vid huvudbiblioteket söks i Alma med sökfunktionen Signum och söktermen HB VIc2. En del litteratur tryckt före 1980 söks manuell i den systematiska kortkatalogen. Retroaktiv inmatning i Alma gör att också litteratur tryckt mellan 1830 och 1979 med tiden blir sökbar i Alma. Från och med år 2000 ingår litteraturen vid huvudbiblioteket om sociala frågor och socialpolitik i en numerus currens-samling. Publikationer från vissa inhemska organisationer fogas fortlöpande till en separat småtryckssamling, som har signum HB VIc2 småtr.

Statistik

Samlingen med signum HB VIa finns vid huvudbiblioteket och innehåller litteratur om statistik. Samlingen är mycket omfattande. Särskilt bör nämnas att Finlands officiella statistik, Sveriges officiella statistik och statistiska årsböcker ingår i samlingen, men de enskilda volymerna har inte registrerats var för sig. I anslutning till ämnet Statistik finns dessutom betydande samlingar statistisk litteratur. Statistik litteratur har ingått i många bokdonationer som exempel av Thyra Renqvist och Elsa Bruun. Friexemplar som erhållits från 1919 samt inköp har kompletterat samlingen. Registrerad statistisk litteratur söks i Alma med sökfunktionen Signum och söktermen HB VIa. En del litteratur tryckt före 1980 skall sökas manuellt i huvudbibliotekets systematiska kortkatalog, men retroaktiv inmatning i Alma av litteratur tryckt mellan 1830 och 1979 pågår. Från och med år 2000 ingår registrerad statistisk litteratur i en numerus currens-samling.

Knapsack sets for cryptography

The basic goal of this study is to extend old and propose new ways to generate knapsack sets suitable for use in public key cryptography. The knapsack problem and its cryptographic use are reviewed in the introductory chapter. Terminology is based on common cryptographic vocabulary. For example, solving the knapsack problem (which is here a subset sum problem) is termed decipherment. Chapter 1 also reviews the most famous knapsack cryptosystem, the Merkle Hellman system. It is based on a superincreasing knapsack and uses modular multiplication as a trapdoor transformation. The insecurity caused by these two properties exemplifies the two general categories of attacks against knapsack systems. These categories provide the motivation for Chapters 2 and 4. Chapter 2 discusses the density of a knapsack and the dangers of having a low density. Chapter 3 interrupts for a while the more abstract treatment by showing examples of small injective knapsacks and extrapolating conjectures on some characteristics of knapsacks of larger size, especially their density and number. The most common trapdoor technique, modular multiplication, is likely to cause insecurity, but as argued in Chapter 4, it is difficult to find any other simple trapdoor techniques. This discussion also provides a basis for the introduction of various categories of non injectivity in Chapter 5. Besides general ideas of non injectivity of knapsack systems, Chapter 5 introduces and evaluates several ways to construct such systems, most notably the "exceptional blocks" in superincreasing knapsacks and the usage of "too small" a modulus in the modular multiplication as a trapdoor technique. The author believes that non injectivity is the most promising direction for development of knapsack cryptosystema. Chapter 6 modifies two well known knapsack schemes, the Merkle Hellman multiplicative trapdoor knapsack and the Graham Shamir knapsack. The main interest is in aspects other than non injectivity, although that is also exploited. In the end of the chapter, constructions proposed by Desmedt et. al. are presented to serve as a comparison for the developments of the subsequent three chapters. Chapter 7 provides a general framework for the iterative construction of injective knapsacks from smaller knapsacks, together with a simple example, the "three elements" system. In Chapters 8 and 9 the general framework is put into practice in two different ways. Modularly injective small knapsacks are used in Chapter 9 to construct a large knapsack, which is called the congruential knapsack. The addends of a subset sum can be found by decrementing the sum iteratively by using each of the small knapsacks and their moduli in turn. The construction is also generalized to the non injective case, which can lead to especially good results in the density, without complicating the deciphering process too much. Chapter 9 presents three related ways to realize the general framework of Chapter 7. The main idea is to join iteratively small knapsacks, each element of which would satisfy the superincreasing condition. As a whole, none of these systems need become superincreasing, though the development of density is not better than that. The new knapsack systems are injective but they can be deciphered with the same searching method as the non injective knapsacks with the "exceptional blocks" in Chapter 5. The final Chapter 10 first reviews the Chor Rivest knapsack system, which has withstood all cryptanalytic attacks. A couple of modifications to the use of this system are presented in order to further increase the security or make the construction easier. The latter goal is attempted by reducing the size of the Chor Rivest knapsack embedded in the modified system. '