Genome-Wide Analysis of Severe Congenital Neutropenia and Leukemia Implications for leukemogenesis

The process of blood cell formation is known as hematopoiesis. During this process mature blood cells are formed in the bone marrow, followed by their release in the peripheral blood. Once in the periphery, mature blood cells exert their functions; erythrocytes play a crucial role in gas transport from the lungs to the peripheral organs and vice versa, platelets are essential for blood clotting and leukocytes, comprising granulocytes, monocytes/macrophages, lymphocytes and natural killer cells, are indispensable for the defense against micro-organisms. The mammalian blood system is self renewing and the number of blood cells is controlled by a tight balance of production and degradation. Throughout the entire life, mature blood cells derive from a small population of pluripotent hematopoietic stem cells (HSCs) within the bone marrow. HSCs have the exceptional ability to and self-renew and differentiate into progenitors of all hematopoietic lineages1. In this way, HSCs provide an unlimited source of blood cells. Hematopoietic progenitors on their turn develop through a number of differentiation stages into mature blood cells (Figure 1). The lifespan of mature blood cells is limited, consequently a constant production is necessary to maintain adequate blood cell numbers2. Hematopoiesis is largely controlled by external signals, e.g., hematopoietic growth factors and cell-cell interactions, within the bone marrow niche2, 3. These are essential for the production of sufficient numbers of blood cells under physiological conditions and provide opportunities to increase production if necessary, e.g., during blood loss or infections, a process known as “stress” or “emergency” hematopoiesis4, 5. Furthermore, extracellular signals can direct differentiation of hematopoietic progenitors into specific lineages. Growth factors that play a major role in this process are thrombopoeitin (TPO), essential for platelet production, erythropoietin (EPO), regulating the production of erythrocytes, and colony stimulating factors (CSFs), involved in myeloid cell development2, 6-8. The majority of leukocytes in the peripheral blood are neutrophilic granulocytes or neutrophils, which are essential for the early, aspecific immune response against microorganisms. The process of neutrophilic development is known as myelopoiesis. During this process, HSCs develop through a number of differentiation stages, i.e., myeloblasts, promyelocytes, neutrophilic myelocytes, neutrophilic metamyelocytes and neutrophilic band cells into mature neutrophils

Analyzing Four-Year Public University and Two-Year College Graduation Rates

This paper examines the graduation rates between 2000 and 2015 of United States colleges and universities at the national, state, and institutional levels. This research focuses on two-year and four-year programs. Rates are investigated longitudinally along with variables that distinguish between public/private institutions, percentages of full-time and part-time enrollments, a variety of completion times, and levels of academic achievement at entry that include SAT scores and high school GPAs. The paper uses a logistic growth function that has been used by other researchers to model four-, five-, and six-year graduation rates of individuals and selected cohort groups; graduation rate trajectories for students of differing academic achievement backgrounds are projected into the future to demonstrate maximum graduation rates expected for entering cohorts. Included is the analysis of national, state, and institutional graduation-rate results in four-year institutions of the 50 states; examples from 14 public colleges and universities in Indiana and several surrounding states are also considered. In addition to fitting their graduation rates to the logistic function and extracting associated growth variables, we use percentages of part-time students to predict two- and four-year graduation rates at the national, state, and institutional levels in the 50 states. The analysis examined the graduation rates between 2000 and 2015 of United States colleges and universities and showed no correlation between a state’s two-year and four-year cohort graduation rates; verified an inverse mathematical relationship between graduation rates and percentage of part-time students; confirmed that for median SAT scores of 800 or lower one expects very low on-time graduation rates

On the surface drift of the Southern Ocean

Drift rates of the sea surface have been calculated for the South Atlantic and South Indian Ocean sectors of the Southern Ocean using drift cards and FGGE buoys. Drift patterns and drift rates, based on results from 40,000 plastic drift cards placed from 1978 to 1981, indicate significant equatorward surface exchange between the Southern Ocean and subtropical ocean gyres. Card drift rates increase with latitude up to the 40-45S zone. Average zonal drift rates lie between 10.3 cm/s and 16.4 cm/s. Zonally averaged drift rates of FGGE buoys are also at a maximum between 40 and 45S but are 15% higher; lowest rates are 12.2 cm/s. Significant differences in the drift rates between sectors of the same zone reflect the influence of bottom topography

Protecting quantum entanglement from leakage and qubit errors via repetitive parity measurements

Protecting quantum information from errors is essential for large-scale quantum computation. Quantum error correction (QEC) encodes information in entangled states of many qubits, and performs parity measurements to identify errors without destroying the encoded information. However, traditional QEC cannot handle leakage from the qubit computational space. Leakage affects leading experimental platforms, based on trapped ions and superconducting circuits, which use effective qubits within many-level physical systems. We investigate how two-transmon entangled states evolve under repeated parity measurements, and demonstrate the use of hidden Markov models to detect leakage using only the record of parity measurement outcomes required for QEC. We show the stabilization of Bell states over up to 26 parity measurements by mitigating leakage using postselection, and correcting qubit errors using Pauli-frame transformations. Our leakage identification method is computationally efficient and thus compatible with real-time leakage tracking and correction in larger quantum processors.Comment: 22 pages, 15 figure

Influence of Echocardiographic Guidance on Positioning of the Buttoned Occluder for Transcatheter Closure of Atrial Septal Defects

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73381/1/j.1540-8175.1996.tb00878.x.pd

Light-activated azobenzene peptide inhibitor of the PD-1/PD-L1 interaction

Inhibiting the PD-1/PD-L1 protein–protein interaction is a key immunotherapy for cancer. Antibodies dominate the clinical space but are costly, with limited applicability and immune side effects. We developed a photo-controlled azobenzene peptide that selectively inhibits the PD-1/PD-L1 interaction when in the cis isomer only. Activity is demonstrated in in vitro and cellular assays

Do Positive Psychological Characteristics Modify the Associations of Physical Performance With Functional Decline and Institutionalization? Findings From the Longitudinal Aging Study Amsterdam

Objectives. To investigate whether 3 positive psychological characteristics, related to sense of control, modify the associations of physical performance levels with subsequent functional decline and institutionalization.Method. One thousand five hundred and thirty-two men and women participating in the Longitudinal Aging Study Amsterdam and not living in an institution in 2005-2006 were included. Mastery, self-efficacy, investment in independence, and objective physical performance scores were ascertained in 2005-2006. Functional decline and institutionalization were assessed after 3 years of follow-up.Results. The association between lower physical performance levels and increased odds of functional decline was modified by investment in independence, with a weaker association found among people with higher investment in independence scores than in people with lower scores even after adjustment for covariates. The association between lower physical performance levels and higher odds of institutionalization was marginally weaker among those people with above median levels of mastery (test of interaction p = .08). In men, an association between general self-efficacy and functional decline was found and maintained after adjustments.Conclusions. Positive psychological characteristics, related to sense of control, play a role in the transition between stages in the disablement process. Specific psychological characteristics may be associated with different stages of the disablement process and may in turn be affected by disablement

Theoretical Black Hole Mass Distributions

We derive the theoretical distribution function of black hole masses by studying the formation processes of black holes. We use the results of recent 2D simulations of core-collapse to obtain the relation between remnant and progenitor masses and fold it with an initial mass function for the progenitors. We examine how the calculated black-hole mass distributions are modified by (i) strong wind mass loss at different evolutionary stages of the progenitors, and (ii) the presence of close binary companions to the black-hole progenitors. Thus, we are able to derive the binary black hole mass distribution. The compact remnant distribution is dominated by neutron stars in the mass range 1.2-1.6Msun and falls off exponentially at higher remnant masses. Our results are most sensitive to mass loss from winds which is even more important in close binaries. Wind mass-loss causes the black hole distribution to become flatter and limits the maximum possible black-hole mass (<10-15Msun). We also study the effects of the uncertainties in the explosion and unbinding energies for different progenitors. The distributions are continuous and extend over a broad range. We find no evidence for a gap at low values (3-5Msun) or for a peak at higher values (~7Msun) of black hole masses, but we argue that our black hole mass distribution for binaries is consistent with the current sample of measured black-hole masses in X-ray transients. We discuss possible biases against the detection or formation of X-ray transients with low-mass black holes. We also comment on the possibility of black-hole kicks and their effect on binaries.Comment: 22 pages, submitted to Ap