Antioxidant Treatment Regulates the Humoral Immune Response during Acute Viral Infection

Generation of reactive oxygen intermediates (ROI) following antigen receptor ligation is critical to promote cellular responses. However, the effect of antioxidant treatment on humoral immunity during a viral infection was unknown. Mice were infected with lymphocytic choriomeningitis virus (LCMV) and treated with Mn(III)tetrakis(4-benzoic acid)porphyrin chloride (MnTBAP), a superoxide dismutase mimetic, from days 0 to 8 postinfection. On day 8, at the peak of the splenic response in vehicle-treated mice, virus-specific IgM and IgG antibody-secreting cells (ASC) were decreased 22- and 457-fold in MnTBAP-treated animals. By day 38, LCMV-specific IgG ASC were decreased 5-fold in the bone marrow of drug-treated mice, and virus-specific antibodies were of lower affinity. Interestingly, antioxidant treatment had no effect on the number of LCMV-specific IgG memory B cells. In addition to decreases in ASC, MnTBAP treatment decreased the number of functional virus-specific CD4+ T cells. The decreased numbers of ASC observed on day 8 in drug-treated mice were due to a combination of Bim-mediated cell death and decreased proliferation. Together, these data demonstrate that ROI regulate antiviral ASC expansion and have important implications for understanding the effects of antioxidants on humoral immunity during infection and immunization

Genome-Wide Analysis of Copy Number Variation in Type 1 Diabetes

Type 1 diabetes (T1D) tends to cluster in families, suggesting there may be a genetic component predisposing to disease. However, a recent large-scale genome-wide association study concluded that identified genetic factors, single nucleotide polymorphisms, do not account for overall familiality. Another class of genetic variation is the amplification or deletion of >1 kilobase segments of the genome, also termed copy number variations (CNVs). We performed genome-wide CNV analysis on a cohort of 20 unrelated adults with T1D and a control (Ctrl) cohort of 20 subjects using the Affymetrix SNP Array 6.0 in combination with the Birdsuite copy number calling software. We identified 39 CNVs as enriched or depleted in T1D versus Ctrl. Additionally, we performed CNV analysis in a group of 10 monozygotic twin pairs discordant for T1D. Eleven of these 39 CNVs were also respectively enriched or depleted in the Twin cohort, suggesting that these variants may be involved in the development of islet autoimmunity, as the presently unaffected twin is at high risk for developing islet autoimmunity and T1D in his or her lifetime. These CNVs include a deletion on chromosome 6p21, near an HLA-DQ allele. CNVs were found that were both enriched or depleted in patients with or at high risk for developing T1D. These regions may represent genetic variants contributing to development of islet autoimmunity in T1D

Receiver development for BICEP Array, a next-generation CMB polarimeter at the South Pole

A detection of curl-type (B-mode) polarization of the primary CMB would be direct evidence for the inflationary paradigm of the origin of the Universe. The Bicep/Keck Array (BK) program targets the degree angular scales, where the power from primordial B-mode polarization is expected to peak, with ever-increasing sensitivity and has published the most stringent constraints on inflation to date. Bicep Array (BA) is the Stage-3 instrument of the BK program and will comprise four Bicep3-class receivers observing at 30/40, 95, 150 and 220/270 GHz with a combined 32,000+ detectors; such wide frequency coverage is necessary for control of the Galactic foregrounds, which also produce degree-scale B-mode signal. The 30/40 GHz receiver is designed to constrain the synchrotron foreground and has begun observing at the South Pole in early 2020. By the end of a 3-year observing campaign, the full Bicep Array instrument is projected to reach σr between 0.002 and 0.004, depending on foreground complexity and degree of removal of B-modes due to gravitational lensing (delensing). This paper presents an overview of the design, measured on-sky performance and calibration of the first BA receiver. We also give a preview of the added complexity in the time-domain multiplexed readout of the 7,776-detector 150 GHz receiver

Observing low elevation sky and the CMB Cold Spot with BICEP3 at the South Pole

BICEP3 is a 520 mm aperture on-axis refracting telescope at the South Pole, which observes the polarization of the cosmic microwave background (CMB) at 95 GHz to search for the B-mode signal from inflationary gravitational waves. In addition to this main target, we have developed a low-elevation observation strategy to extend coverage of the Southern sky at the South Pole, where BICEP3 can quickly achieve degree-scale E-mode measurements over a large area. An interesting E-mode measurement is probing a potential polarization anomaly around the CMB Cold Spot. During the austral summer seasons of 2018-19 and 2019-20, BICEP3 observed the sky with a flat mirror to redirect the beams to various low elevation ranges. The preliminary data analysis shows degree-scale E-modes measured with high signal-to-noise ratio

Analysis of Temperature-to-Polarization Leakage in BICEP3 and Keck CMB Data from 2016 to 2018

The Bicep/Keck Array experiment is a series of small-aperture refracting telescopes observing degree-scale Cosmic Microwave Background polarization from the South Pole in search of a primordial B-mode signature. As a pair differencing experiment, an important systematic that must be controlled is the differential beam response between the co-located, orthogonally polarized detectors. We use high-fidelity, in-situ measurements of the beam response to estimate the temperature-to-polarization (T → P) leakage in our latest data including observations from 2016 through 2018. This includes three years of Bicep3 observing at 95 GHz, and multifrequency data from Keck Array. Here we present band-averaged far-field beam maps, differential beam mismatch, and residual beam power (after filtering out the leading difference modes via deprojection) for these receivers. We show preliminary results of "beam map simulations," which use these beam maps to observe a simulated temperature (no Q/U) sky to estimate T → P leakage in our real data

Analysis of Temperature-to-Polarization Leakage in BICEP3 and Keck CMB Data from 2016 to 2018

The Bicep/Keck Array experiment is a series of small-aperture refracting telescopes observing degree-scale Cosmic Microwave Background polarization from the South Pole in search of a primordial B-mode signature. As a pair differencing experiment, an important systematic that must be controlled is the differential beam response between the co-located, orthogonally polarized detectors. We use high-fidelity, in-situ measurements of the beam response to estimate the temperature-to-polarization (T → P) leakage in our latest data including observations from 2016 through 2018. This includes three years of Bicep3 observing at 95 GHz, and multifrequency data from Keck Array. Here we present band-averaged far-field beam maps, differential beam mismatch, and residual beam power (after filtering out the leading difference modes via deprojection) for these receivers. We show preliminary results of "beam map simulations," which use these beam maps to observe a simulated temperature (no Q/U) sky to estimate T → P leakage in our real data

Polarization calibration of the BICEP3 CMB polarimeter at the South Pole

The BICEP3 CMB Polarimeter is a small-aperture refracting telescope located at the South Pole and is specifically designed to search for the possible signature of inflationary gravitational waves in the Cosmic Microwave Background (CMB). The experiment measures polarization on the sky by differencing the signal of co-located, orthogonally polarized antennas coupled to Transition Edge Sensor (TES) detectors. We present precise measurements of the absolute polarization response angles and polarization efficiencies for nearly all of BICEP3's ~800 functioning polarization-sensitive detector pairs from calibration data taken in January 2018. Using a Rotating Polarized Source (RPS), we mapped polarization response for each detector over a full 360 degrees of source rotation and at multiple telescope boresight rotations from which per-pair polarization properties were estimated. In future work, these results will be used to constrain signals predicted by exotic physical models such as Cosmic Birefringence

Observing low elevation sky and the CMB Cold Spot with BICEP3 at the South Pole

BICEP3 is a 520 mm aperture on-axis refracting telescope at the South Pole, which observes the polarization of the cosmic microwave background (CMB) at 95 GHz to search for the B-mode signal from inflationary gravitational waves. In addition to this main target, we have developed a low-elevation observation strategy to extend coverage of the Southern sky at the South Pole, where BICEP3 can quickly achieve degree-scale E-mode measurements over a large area. An interesting E-mode measurement is probing a potential polarization anomaly around the CMB Cold Spot. During the austral summer seasons of 2018-19 and 2019-20, BICEP3 observed the sky with a flat mirror to redirect the beams to various low elevation ranges. The preliminary data analysis shows degree-scale E-modes measured with high signal-to-noise ratio

Severe early onset preeclampsia: short and long term clinical, psychosocial and biochemical aspects

Preeclampsia is a pregnancy specific disorder commonly defined as de novo hypertension and proteinuria after 20 weeks gestational age. It occurs in approximately 3-5% of pregnancies and it is still a major cause of both foetal and maternal morbidity and mortality worldwide1. As extensive research has not yet elucidated the aetiology of preeclampsia, there are no rational preventive or therapeutic interventions available. The only rational treatment is delivery, which benefits the mother but is not in the interest of the foetus, if remote from term. Early onset preeclampsia (<32 weeks’ gestational age) occurs in less than 1% of pregnancies. It is, however often associated with maternal morbidity as the risk of progression to severe maternal disease is inversely related with gestational age at onset2. Resulting prematurity is therefore the main cause of neonatal mortality and morbidity in patients with severe preeclampsia3. Although the discussion is ongoing, perinatal survival is suggested to be increased in patients with preterm preeclampsia by expectant, non-interventional management. This temporising treatment option to lengthen pregnancy includes the use of antihypertensive medication to control hypertension, magnesium sulphate to prevent eclampsia and corticosteroids to enhance foetal lung maturity4. With optimal maternal haemodynamic status and reassuring foetal condition this results on average in an extension of 2 weeks. Prolongation of these pregnancies is a great challenge for clinicians to balance between potential maternal risks on one the eve hand and possible foetal benefits on the other. Clinical controversies regarding prolongation of preterm preeclamptic pregnancies still exist – also taking into account that preeclampsia is the leading cause of maternal mortality in the Netherlands5 - a debate which is even more pronounced in very preterm pregnancies with questionable foetal viability6-9. Do maternal risks of prolongation of these very early pregnancies outweigh the chances of neonatal survival? Counselling of women with very early onset preeclampsia not only comprises of knowledge of the outcome of those particular pregnancies, but also knowledge of outcomes of future pregnancies of these women is of major clinical importance. This thesis opens with a review of the literature on identifiable risk factors of preeclampsia