Cryptococcal meningitis presenting with recurrent syncope in a patient with chronic lymphoid leukemia: a case report

The clinical presentations of cryptococcal meningitis in HIV-negative patients may be different from that infected with HIV. We report a case of 75-year old male with chronic lymphoid leukemia presenting with recurrent syncope, bi-frontal headache and diplopia. This case discusses the atypical presentations of cryptococcal meningitis in HIV-negative patients and its importance of early diagnosis

IL-17C-mediated innate inflammation decreases the response to PD-1 blockade in a model of Kras-driven lung cancer

Chronic obstructive pulmonary disease (COPD) is associated with neutrophilic lung infammation and CD8 T cell exhaustion and is an important risk factor for the development of non-small cell lung cancer (NSCLC). The clinical response to programmed cell death-1 (PD-1) blockade in NSCLC patients is variable and likely afected by a coexisting COPD. The pro-infammatory cytokine interleukin-17C (IL-17C) promotes lung infammation and is present in human lung tumors. Here, we used a Krasdriven lung cancer model to examine the function of IL-17C in infammation-promoted tumor growth. Genetic ablation of Il-17c resulted in a decreased recruitment of infammatory cells into the tumor microenvironment, a decreased expression of tumor-promoting cytokines (e.g. interleukin-6 (IL-6)), and a reduced tumor proliferation in the presence of Haemophilus infuenzae- (NTHi) induced COPD-like lung infammation. Chronic COPD-like infammation was associated with the expression of PD-1 in CD8 lymphocytes and the membrane expression of the programmed death ligand (PD-L1) independent of IL-17C. Tumor growth was decreased in Il-17c defcient mice but not in wildtype mice after anti-PD-1 treatment. Our results suggest that strategies targeting innate immune mechanisms, such as blocking of IL-17C, may improve the response to anti-PD-1 treatment in lung cancer patients

High-Performance Silicon Photonic Single-Sideband Modulators for Cold Atom Interferometry

The most complicated and challenging system within a light-pulse atom interferometer (LPAI) is the laser system, which controls the frequencies and intensities of multiple laser beams over time to configure quantum gravity and inertial sensors. The main function of an LPAI laser system is to perform cold-atom generation and state-selective detection and to generate coherent two-photon process for the light-pulse sequence. Substantial miniaturization and ruggedization of the laser system can be achieved by bringing together most key functions of the laser and optical system onto a photonic integrated circuit (PIC). Here we demonstrate a high-performance silicon photonic carrier-suppressed single-sideband (CS-SSB) modulator PIC with dual-parallel Mach-Zehnder modulators (DP-MZMs) operating near 1560 nm, which can dynamically shift the frequency of the light for the desired function within the LPAI. Independent RF control of channels in SSB modulator enables the extensive study of imbalances in both the optical and RF phases and amplitudes to simultaneously reach 30 dB carrier suppression and unprecedented 47.8 dB sideband suppression with peak conversion efficiency of -6.846 dB (20.7 %). Using a silicon photonic SSB modulator with time-multiplexed frequency shifting in an LPAI laser system, we demonstrate cold-atom generation, state-selective detection, and the realization of atom interferometer fringes to estimate gravitational acceleration, $g \approx 9.77 \pm 0.01 \,\rm{m/s^2}$, in a Rubidium ($^{87}$Rb) atom system.Comment: 18 pages, 9 figure

Towards a compact atomic clock based on coherent population trapping and the grating magneto-optical trap

The combination of coherent population trapping (CPT) and laser cooled atoms is a promising platform for realizing the next generation of compact atomic frequency references. Towards this goal, we have developed an apparatus based on the grating magneto-optical trap (GMOT) and the high-contrast lin ⊥ lin CPT scheme in order to explore the performance that can be achieved. One important trade-off for cold-atom systems arises from the need to simultaneously maximize the number of cold atoms available for interrogation and the repetition rate of the system. This compromise can be mitigated by recapturing cold atoms from cycle to cycle. Here, we report a quantitative characterization of the cold atom number in the recapture regime for our system, which will enable us to optimize this trade-off. We also report recent measurements of the short-term frequency stability with a short-term Allan deviation of 3 × 10-11/τ up to an averaging time of τ = 10 s

Raman-Ramsey CPT with a grating magneto-optical trap

We describe an experiment which combines cold 87Rb atoms from a grating magneto-optical trap (GMOT) with Lin-perp-Lin coherent population trapping (CPT) and pulsed Ramsey interrogation. The bichromatic fields required for Lin-perp-Lin are generated by combining light from a single external cavity diode laser (ECDL) with an electro-optic modulator (EOM) and an acousto-optic modulator (AOM). With this laser system and the GMOT, we are able to produce Raman-Ramsey fringes using either the F' = 1 or the F' = 2 excited states of the 87 Rb D1 line. As a step towards realising a frequency standard based on the GMOT, we measure the Ramsey fringe amplitude as a function of the magnetic bias field and the excited state. We observe dark state interference with F' = 1 and show that this interference is suppressed with F' = 2, as expected from prior work on CPT with 87Rb in thermal vapour cells

Impact of laser frequency noise in coherent population trapping with cold atoms

Laser-cooled atoms and coherent population trapping (CPT) are promising tools for realizing a compact microwave frequency reference with excellent stability. To realize a high performance device, it is necessary to understand and minimize all sources of technical noise. Here, we investigate the role of laser frequency noise in cold-atom CPT with an apparatus based on the grating magneto-optical trap (GMOT). We compare the performance of our setup with an external cavity diode laser (ECDL) and a distributed feedback diode laser (DFB). With the DFB, laser frequency noise is one of the dominant noise sources in our system. With the ECDL, it is significantly reduced. We also report frequency stability measurements of our apparatus with a short-term Allan deviation Sigma_y (tau) ≈ 3(times)10-11/rt τ up to τ= 10 s

B‐cell receptors of EBV‐negative Burkitt lymphoma bind modified isoforms of autoantigens

Burkitt lymphoma (BL) represents the most aggressive B‐cell‐lymphoma. Beside the hallmark of IG‐MYC‐translocation, surface B‐cell receptor (BCR) is expressed, and mutations in the BCR pathway are frequent. Coincidental infections in endemic BL, and specific extra‐nodal sites suggest antigenic triggers. To explore this hypothesis, BCRs of BL cell lines and cases were screened for reactivities against a panel of bacterial lysates, lysates of Plasmodium falciparum, a custom‐made virome array and against self‐antigens, including post‐translationally modified antigens. An atypically modified, SUMOylated isoform of Bystin, that is, SUMO1‐BYSL was identified as the antigen of the BCR of cell line CA46. SUMO1‐BYSL was exclusively expressed in CA46 cells with K139 as site of the SUMOylation. Secondly, an atypically acetylated isoform of HSP40 was identified as the antigen of the BCR of cell line BL41. K104 and K179 were the sites of immunogenic acetylation, and the acetylated HSP40 isoform was solely present in BL41 cells. Functionally, addition of SUMO1‐BYSL and acetylated HSP40 induced BCR pathway activation in CA46 and BL41 cells, respectively. Accordingly, SUMO1‐BYSL‐ETA’ immunotoxin, produced by a two‐step intein‐based conjugation, led to the specific killing of CA46 cells. Autoantibodies directed against SUMO1‐BYSL were found in 3 of 14 (21.4%), and autoantibodies against acetylated HSP40 in 1/14(7.1%) patients with sporadic Burkitt‐lymphoma. No reactivities against antigens of the infectious agent spectrum could be observed. These results indicate a pathogenic role of autoreactivity evoked by immunogenic post‐translational modifications in a subgroup of sporadic BL including two EBV‐negative BL cell lines

COPDGene® 2019: Redefining the Diagnosis of Chronic Obstructive Pulmonary Disease

Background:Chronic obstructive pulmonary disease (COPD) remains a major cause of morbidity and mortality. Present-day diagnostic criteria are largely based solely on spirometric criteria. Accumulating evidence has identified a substantial number of individuals without spirometric evidence of COPD who suffer from respiratory symptoms and/or increased morbidity and mortality. There is a clear need for an expanded definition of COPD that is linked to physiologic, structural (computed tomography [CT]) and clinical evidence of disease. Using data from the COPD Genetic Epidemiology study (COPDGene®), we hypothesized that an integrated approach that includes environmental exposure, clinical symptoms, chest CT imaging and spirometry better defines disease and captures the likelihood of progression of respiratory obstruction and mortality. Methods:Four key disease characteristics - environmental exposure (cigarette smoking), clinical symptoms (dyspnea and/or chronic bronchitis), chest CT imaging abnormalities (emphysema, gas trapping and/or airway wall thickening), and abnormal spirometry - were evaluated in a group of 8784 current and former smokers who were participants in COPDGene® Phase 1. Using these 4 disease characteristics, 8 categories of participants were identified and evaluated for odds of spirometric disease progression (FEV1 > 350 ml loss over 5 years), and the hazard ratio for all-cause mortality was examined. Results:Using smokers without symptoms, CT imaging abnormalities or airflow obstruction as the reference population, individuals were classified as Possible COPD, Probable COPD and Definite COPD. Current Global initiative for obstructive Lung Disease (GOLD) criteria would diagnose 4062 (46%) of the 8784 study participants with COPD. The proposed COPDGene® 2019 diagnostic criteria would add an additional 3144 participants. Under the new criteria, 82% of the 8784 study participants would be diagnosed with Possible, Probable or Definite COPD. These COPD groups showed increased risk of disease progression and mortality. Mortality increased in patients as the number of their COPD characteristics increased, with a maximum hazard ratio for all cause-mortality of 5.18 (95% confidence interval [CI]: 4.15-6.48) in those with all 4 disease characteristics. Conclusions:A substantial portion of smokers with respiratory symptoms and imaging abnormalities do not manifest spirometric obstruction as defined by population normals. These individuals are at significant risk of death and spirometric disease progression. We propose to redefine the diagnosis of COPD through an integrated approach using environmental exposure, clinical symptoms, CT imaging and spirometric criteria. These expanded criteria offer the potential to stimulate both current and future interventions that could slow or halt disease progression in patients before disability or irreversible lung structural changes develop