Reconsidering Res Judicata: A Comparative Perspective

We aimed to prospectively investigate the paternal antigen-induced cytokine secretion by peripheral blood mononuclear cells (PBMCs) in response to hormone treatment in women undergoing in vitro fertilisation (IVF) and to examine the predictive value of the cytokine secretion profile in the outcome of IVF treatment, in a pilot study. Twenty-five women were included and IVF treatment was successful for six and unsuccessful for 19 women. Blood samples were collected before IVF treatment, on four occasions during IVF and four weeks after embryo transfer. The numbers of Th1-, Th2- and Th17-associated cytokine-secreting cells and cytokine levels in cell supernatants were analysed by enzyme-linked immunospot-forming (ELISpot), enzyme-linked immune-sorbent (ELISA) or Luminex assay. None of the cytokines (IFN-γ, IL-4, IL-5, IL-10, IL-12, IL-13, IL-17, TNF and GM-CSF) had any predictive value regarding IVF outcome. The majority of the cytokines reached their peak levels at ovum pick-up, suggesting an enhancing influence of the hormonal stimulation. Pregnancy was associated with a high number of IL-4-, IL-5- and IL-13-secreting cells four weeks after ET. In conclusion, the results do not support our hypothesis of a more pronounced peripheral Th1 and Th17 deviation towards paternal antigens in infertile women with an unsuccessful IVF outcome, although this is based on a small number of observations. A larger study is required to confirm this conclusion. Higher numbers of Th2-associated cytokine-secreting cells in pregnant women four weeks after ET do corroborate the hypothesis of a Th2 deviation during pregnancy

Utvärdering av stöd till utbyggnad av bredband: delrapport 1

Detta är en delrapport från utvärderingen av bredbandsstöd för svensk landsbygd. Stöden består av accessnät finansierat av landsbygdsprogrammet och ortssammanbindande nät finansierat av Europeiska regionala utvecklingsfonden (Eruf). Utvärderingen genomförs av SLU, institutionen för stad och land på uppdrag av Jordbruksverket och Tillväxtverket. Rapporten koncentrerar sig på två områden: effekter för företagare (kapitel 2) samt modeller för styrning av utbyggnaden (kapitel 3). För att utvärdera detta gjordes först en kunskapsöversikt. Därefter valdes regionerna Västerbotten, Värmland, Västra Götaland och Skåne för närmare studier under hela utvärderingen. I dessa regioner valdes i Lycksele, Sunne, Vara och Ystad kommuner ut för fältarbeten med intervjuer av olika aktörer och telefonenkät till företagarna. Sammanfattning av resultatet i form av svar på utvärderingsfrågorna: Hur mycket ökar omsättning i befintliga företag genom bredbandsutbyggnaden? (kapitel 2) Av de undersökta företagen har de med tillgång till snabbt bredband i genomsnitt en högre omsättningsökning än de som saknar snabb uppkoppling. Vårt material kan dock inte visa om skillnaden beror specifikt på tillgång till snabbt bredband. Företagarna uppger att bredbandet har stor betydelse för företaget i allmänhet, men att det inte har betydelse för omsättningssiffrorna. Blir det fler företag som får tillgång till bredband på minst 100 Mbit/s och går det att säga om antalet sysselsatta ökar i de gles- och landsbygdsregioner som får del av bredbandsutbyggnaden? (kapitel 2) Bredbandsstöden inom Eruf och landsbygdsprogrammet har lett eller kommer att leda till att fler företag får tillgång eller ökad möjlighet att ansluta sig till ett fibernät. Vad gäller sysselsättning hittar studien inga belägg för att bredbandstillgången leder till fler anställda i befintliga landsbygdsföretag. Däremot uppger en mindre andel företag att de inte hade kunnat fortsätta att bedriva verksamhet utan bredbandstillgång. Hur påverkar stöden landsbygdens tillgång till IT-infrastruktur? (Kapitel 3) Informanter i denna studie uppger att stöden har haft betydelse för utbyggnaden av fiber, och att fiberutbyggnad inte hade skett i samma utsträckning och/eller inom samma tidsintervall utan dessa. Det finns dock viss kritik mot att stöden inte hamnar i de områden som mest behöver dem, och mot att Jordbruksverket inte lyckats förhindra att stöd går till områden som hade kunnat byggas ut kommersiellt. Vilka är effekterna av styrmodellen– relativt alternativa modeller för styrning? (Kapitel 3) I denna studie identifierar vi två möjliga huvudkategorier för nationella styrmodeller för bredbandsutbyggnad: Ansökningsstyrd modell (nuvarande) och upphandlingsstyrd modell (tidigare, och på förslag för framtiden). Den förstnämnda kan beskrivas som en ”inifrån-och-ut”-modell och den sistnämnda som en ”utifrån-och-in”-modell, men vi visar i vår studie på att denna indelning är en grov generalisering. Även i dagens ansökningsstyrda modell finns exempel där kommun, region och län tagit stort ansvar i att samordna och styra stödmedlen för utbyggnad av bredband, och där initiativet alltså inte kommer ”inifrån” eller ”underifrån”. Vi finner tecken på att i många fall där 6 kommun och region arbetar aktivt med bredbandsfrågan har effekten av den nuvarande styrmodellen varit mer lyckad. Vi identifierar viktiga aspekter som bör tas hänsyn till vid val av framtida styrmodell, oavsett om det blir en ansökningsstyrd eller upphandlingsstyrd modell. Dessa handlar om betydelsen av det lokala engagemanget, vikten av styrning och koordinering, behovet av att hantera efteranslutningar, förenklade regelverk, hänsyn till geografiska förutsättningar, och vikten av ett samordnat bredbandstöd även om finansiering kommer ur olika EU-fonder

Reinstating Vacated Findings in Employment Discrimination Class Actions: Reconciling General Telephone Co. v. Falcon With Hill v. Western Electric Co.

Type 2 T-helper cell (Th2)-skewed immunity is associated with successful pregnancy and the ability to easily direct immune responses to a Th2-polarised profile may be an evolutionary benefit. The Th2-like immunity associated with allergic disease might generate favourable effects for the maintenance of pregnancy, but could also promote development of Th2-like immune responses and allergic disease in the offspring. The aim of this study was to explore, by using IgE as a stable proxy for Th2, the Th1/Th2 balance in allergic and non-allergic women by measuring allergen-specific and total IgE antibody levels in plasma during pregnancy and after delivery. Specific and total IgE antibody levels were determined by ImmunoCAP technology at five occasions during pregnancy (gestational weeks 10-12, 15-16, 25, 35 and 39), as well as at 2 and 12 months after delivery. Thirty-six women without and 20 women with allergic symptoms were included, of whom 13 were sensitised with allergic symptoms and 30 were non-sensitised without allergic symptoms. The levels of total IgE, but not allergen-specific IgE, were increased during early pregnancy when compared to 12 months after delivery in the sensitised women with allergic symptoms, but not in the non-sensitised women without allergic symptoms (pandlt;0.01). This increase in total IgE levels during early pregnancy only in the sensitised women with allergic symptoms indicates that allergy is associated with an enhanced Th2 deviation during pregnancy.Original Publication: Martina Sandberg, Anne Frykman, Yvonne Jonsson, Marie Persson, Jan Ernerudh, Göran Berg, Leif Matthiesen, Christina Ekerfelt and Maria Jenmalm, Total and allergen-specific IgE levels during and after pregnancy in relation to maternal allergy, 2009, JOURNAL OF REPRODUCTIVE IMMUNOLOGY, (81), 1, 82-88. http://dx.doi.org/10.1016/j.jri.2009.04.003 Copyright: Elsevier Science B.V., Amsterdam. http://www.elsevier.com/</p

The APO-K2 Catalog. I. 7,673 Red Giants with Fundamental Stellar Parameters from APOGEE DR17 Spectroscopy and K2-GAP Asteroseismology

We present a catalog of fundamental stellar properties for 7,673 evolved stars, including stellar radii and masses, determined from the combination of spectroscopic observations from the Apache Point Observatory Galactic Evolution Experiment (APOGEE), part of the Sloan Digital Sky Survey IV (SDSS), and asteroseismology from K2. The resulting APO-K2 catalog provides spectroscopically derived temperatures and metallicities, asteroseismic global parameters, evolutionary states, and asteroseismically-derived masses and radii. Additionally, we include kinematic information from \textit{Gaia}. We investigate the multi-dimensional space of abundance, stellar mass, and velocity with an eye toward applications in Galactic archaeology. The APO-K2 sample has a large population of low metallicity stars ($\sim$288 at [M/H] $\leq$ $-$1), and their asteroseismic masses are larger than astrophysical estimates. We argue that this may reflect offsets in the adopted fundamental temperature scale for metal-poor stars rather than metallicity-dependent issues with interpreting asteroseismic data. We characterize the kinematic properties of the population as a function of $\alpha$-enhancement and position in the disk and identify those stars in the sample that are candidate components of the \textit{Gaia-Enceladus} merger. Importantly, we characterize the selection function for the APO-K2 sample as a function of metallicity, radius, mass, $\nu_{\mathrm{max}}$, color, and magnitude referencing Galactic simulations and target selection criteria to enable robust statistical inferences with the catalog.Comment: 28 Pages, 14 Figures, 1 Table. Full table and selection function data available at https://github.com/Jesstella/APO-K2. Submitted April 18th 2023 with AJ, awaiting revie

Increased copy number at 3p14 in breast cancer

INTRODUCTION: The present study was conducted to investigate if chromosome band 3p14 is of any pathogenic significance in the malignant process of breast cancer. Genetic studies have implicated a tumour suppressor gene on chromosome arm 3p and we have proposed LRIG1 at 3p14 as a candidate tumour suppressor. The LRIG1 gene encodes an integral membrane protein that counteracts signalling by receptor tyrosine kinases belonging to the ERBB family. LRIG1 mRNA and protein are expressed in many tissues, including breast tissue. METHODS: In the present report we analysed the LRIG1 gene by fluorescence in situ hybridisation (FISH), LRIG1 mRNA by quantitative RT-PCR, and LRIG1 protein by western blot analysis. Two tumour series were analysed; one series consisted of 19 tumour samples collected between 1987 and 1995 and the other series consisted of 9 tumour samples with corresponding non-neoplastic breast tissues collected consecutively. RESULTS: The LRIG1 gene showed increased copy number in 11 out of 28 tumours (39%) and only one tumour showed a deletion at this locus. Increased LRIG1 copy number was associated with increased levels of LRIG1 mRNA (two of three tumours) and protein (four of four tumours) in the tumours compared to matched non-neoplastic breast tissue, as assessed by RT-PCR and western blot analysis. CONCLUSION: The molecular function of LRIG1 as a negative regulator of ERBB receptors questions the biological significance of increased LRIG1 copy number in breast cancer. We propose that a common, but hitherto unrecognised, breast cancer linked gene is located within an amplicon containing the LRIG1 locus at 3p14.3

Genetic and Evolutionary Analyses of the Human Bone Morphogenetic Protein Receptor 2 (BMPR2) in the Pathophysiology of Obesity

Human bone morphogenetic protein receptor 2 (BMPR2) is essential for BMP signalling and may be involved in the regulation of adipogenesis. The BMPR2 locus has been suggested as target of recent selection in human populations. We hypothesized that BMPR2 might have a role in the pathophysiology of obesity.Evolutionary analyses (dN/dS, Fst, iHS) were conducted in vertebrates and human populations. BMPR2 mRNA expression was measured in 190 paired samples of visceral and subcutaneous adipose tissue. The gene was sequenced in 48 DNA samples. Nine representative single nucleotide polymorphisms (SNPs) were genotyped for subsequent association studies on quantitative traits related to obesity in 1830 German Caucasians. An independent cohort of 925 Sorbs was used for replication. Finally, relation of genotypes to mRNA in fat was examined.The evolutionary analyses indicated signatures of selection on the BMPR2 locus. BMPR2 mRNA expression was significantly increased both in visceral and subcutaneous adipose tissue of 37 overweight (BMI>25 and <30 kg/m²) and 80 obese (BMI>30 kg/m²) compared with 44 lean subjects (BMI< 25 kg/m²) (P<0.001). In a case-control study including lean and obese subjects, two intronic SNPs (rs6717924, rs13426118) were associated with obesity (adjusted P<0.05). Combined analyses including the initial cohort and the Sorbs confirmed a consistent effect for rs6717924 (combined P = 0.01) on obesity. Moreover, rs6717924 was associated with higher BMPR2 mRNA expression in visceral adipose tissue.Combined BMPR2 genotype-phenotype-mRNA expression data as well as evolutionary aspects suggest a role of BMPR2 in the pathophysiology of obesity

Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.

We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease