Universities Research Association

Abstract Neonate rats were injected systemically with thymidine‐H 3 and killed after different periods of survival. Cell proliferation, migration and transformation in the brain were studied autoradiographically. It was established that cells multiplying in the ependymal and subependymal walls of the olfactory ventricle migrate outward into the olfactory bulb, where they become differentiated into granule cells. These postnatally formed granule cells contribute to the formation of the granular and several other layers of the olfactory bulb. Cells multiplying at a high rate in the wall of the lateral ventricle migrate to the hippocampus and contribute to the formation of the granule cells in the granular layer of the dentate gyrus. Cells multiplying at a high rate in the external and internal granular layers of the cerebellum become differentiated into granule cells, and, to a lesser extent, other types of nerve cells of the cerebellar cortex. Evidence was also obtained of the postnatal origin of many of the granule cells of the cochlear nucleus. Postnatal neurogenesis is restricted to these short‐axoned granule cells or microneurons; the long‐axoned nerve cells or macroneurons of the brain are formed prenatally.

It is possible, by using alternating-gradient focusing, to design circular accelerators with magnetic guide fields which are constant in time, and which can accommodate stable orbits at all energies from injection to output energy. Such accelerators are in some respects simpler to construct and operate, and moreover, they show promise of greater output currents than conventional synchrotrons and synchrocyclotrons. Two important types of magnetic field patterns are described, the radial-sector and spiral-sector patterns, the former being easier to understand and simpler to construct, the latter resulting in a much smaller accelerator for a given energy. A theory of orbits in fixed-field alternating-gradient accelerators has been worked out in linear approximation, which yields approximate general relationships between machine parameters, as well as more accurate formulas which can be used for design purposes. There are promising applications of these principles to the design of fixed-field synchrotrons, betatrons, and high-energy cyclotrons.

BACKGROUND: Isoflurane induces cell apoptosis by an unknown mechanism. The authors hypothesized that isoflurane activates inositol 1,4,5-trisphosphate (IP3) receptors on the endoplasmic reticulum (ER) membrane, causing excessive calcium release, triggering apoptosis. METHODS: The authors determined isoflurane-induced cytotoxicity by measuring caspase-3 activity, lactate dehydrogenase release, MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) reduction, and imaging analysis of cell damage markers (annexin V and propidium iodide staining) in different cell types. The authors used the chicken B lymphocyte with a total knock-out of IP3 receptors, PC12 cells with elevated IP3 receptor activity (transfected with L286V presenilin 1), striatal cells with a knock-in of Q111 Huntingtin, and each cell line's corresponding wild-type controls. The authors also measured the isoflurane-evoked changes of calcium concentration in cytosol and/or mitochondria in these cells. RESULTS: Isoflurane induced apoptosis concentration- and time-dependently, and sequentially elevated cytosolic and then mitochondrial calcium in the chicken B-lymphocyte wild-type but not the IP3 receptor total knock-out cells. Thapsigargin, a calcium adenosine triphosphatase inhibitor on ER membranes, induced apoptosis and elevations of calcium in cytosol and mitochondria in both chicken B-lymphocyte wild-type and IP3 receptor total knock-out cells. Isoflurane induced significantly more neurotoxicity and greater calcium release from the ER in L286V PC12 and Q111 Huntingtin striatal cells than in their corresponding wild-type controls, both of which were significantly inhibited by the IP3 receptor antagonist xestospongin C. CONCLUSION: These findings suggest that isoflurane activates the ER membrane IP3 receptor, producing excessive calcium release and triggering apoptosis. Neurons with enhanced IP3 receptor activity, as in certain cases of familial Alzheimer or Huntington disease, may be especially vulnerable to isoflurane cytotoxicity.

The metalloprotease ADAM10/Kuzbanian catalyzes the ligand-dependent ectodomain shedding of Notch receptors and activates Notch. Here, we show that the human tetraspanins of the evolutionary conserved TspanC8 subfamily (Tspan5, Tspan10, Tspan14, Tspan15, Tspan17, and Tspan33) directly interact with ADAM10, regulate its exit from the endoplasmic reticulum, and that four of them regulate ADAM10 surface expression levels. In an independent RNAi screen in Drosophila, two TspanC8 genes were identified as Notch regulators. Functional analysis of the three Drosophila TspanC8 genes (Tsp3A, Tsp86D, and Tsp26D) indicated that these genes act redundantly to promote Notch signaling. During oogenesis, TspanC8 genes were up-regulated in border cells and regulated Kuzbanian distribution, Notch activity, and cell migration. Furthermore, the human TspanC8 tetraspanins Tspan5 and Tspan14 positively regulated ligand-induced ADAM10-dependent Notch1 signaling. We conclude that TspanC8 tetraspanins have a conserved function in the regulation of ADAM10 trafficking and activity, thereby positively regulating Notch receptor activation.

We screened plasma samples (minipools of 96 samples, corresponding to 53,234 blood donations) from France that had been processed with solvent-detergent for hepatitis E virus RNA. The detection rate was 1 HEV-positive sample/2,218 blood donations. Most samples (22/24) from viremic donors were negative for IgG and IgM against HEV.

Research has found that season of birth is associated with later health and professional outcomes; what drives this association remains unclear. In this paper we consider a new explanation: that children born at different times in the year are conceived by women with different socioeconomic characteristics. We document large seasonal changes in the characteristics of women giving birth throughout the year in the United States. Children born in the winter are disproportionally born to women who are more likely to be teenagers and less likely to be married or have a high school degree. We show that controls for family background characteristics can explain up to half of the relationship between season of birth and adult outcomes. We then discuss the implications of this result for using season of birth as an instrumental variable; our findings suggest that, though popular, season-of-birth instruments may produce inconsistent estimates. Finally, we find that some of the seasonality in maternal characteristics is due to summer weather differentially affecting fertility patterns across socioeconomic groups.

The spatial organization of genes and chromosomes plays an important role in the regulation of several DNA processes. However, the principles and forces underlying this nonrandom organization are mostly unknown. Despite its small dimension, and thanks to new imaging and biochemical techniques, studies of the budding yeast nucleus have led to significant insights into chromosome arrangement and dynamics. The dynamic organization of the yeast genome during interphase argues for both the physical properties of the chromatin fiber and specific molecular interactions as drivers of nuclear order.

BACKGROUND: The optimal management of patients with splenic marginal zone lymphoma/marginal zone lymphoma (SMZL) is controversial. The objective of this retrospective study was to compare the outcomes of patients with SMZL who received treatment with rituximab, rituximab plus chemotherapy, or chemotherapy alone. METHODS: The Leukemia Service database was searched for patients with splenic lymphoma who were registered between May 1995 and October 2004. The indications for treatment were the same as those used for patients with chronic lymphocytic leukemia. RESULTS: SMZL was confirmed in 70 patients. The median age was 64 years. The median number of CD20 molecules per cell was 69 x 10(3). Forty-three patients required systemic therapy; rituximab in 26 patients, chemotherapy plus rituximab in 6 patients, and chemotherapy alone in 11 patients. Ten additional patients underwent splenectomy, and 17 patients were in the observation group. The overall response rates were 88% with rituximab, 83% with rituximab plus chemotherapy, and 55% with chemotherapy alone; the 3-year survival rates were 95%, 100%, and 55%, respectively. The 3-year failure-free survival (FFS) rates were 86%, 100%, and 45% in the rituximab, rituximab plus chemotherapy, and chemotherapy alone groups, respectively. Rituximab treatments resulted in longer survival and FFS compared with chemotherapy. Rituximab alone resulted in disappearance of splenomegaly in 92% of patients and normalization of absolute lymphocyte counts. In univariate analysis, younger age and rituximab-based therapy were predictive of longer FFS. CONCLUSIONS: Rituximab with or without chemotherapy was found to have major activity in patients with SMZL. These results may be associated with high levels of cellular CD20 antigen sites. Rituximab should be the treatment of choice, at least in older patients with SMZL who have comorbid diseases.

It is widely documented that places with higher levels of income inequality have lower rates of social mobility. But it is an open question as to whether this reflects a causal relationship. We propose that one channel by which higher rates of income inequality might lead to lower rates of upward mobility is through lower rates of human capital investment among low-income individuals. Specifically, we posit that greater levels of income inequality could lead low-income youth to perceive a lower return to investment in their own human capital. Such an effect would offset any potential "aspirational" effect coming from higher educational wage premiums. The data are consistent with this prediction: low-income youth are more likely to drop out of school if they live in a place with a greater gap between the bottom and middle of the income distribution. This finding is robust to a number of specification checks and tests for confounding factors. This analysis offers an explanation for how income inequality might lead to a perpetuation of economic disadvantage and has implications for the types of interventions and programs that would effectively promote upward mobility among low-SES youth.

We present optical and near-infrared observations of the dim afterglow of GRB 020124, obtained between 2 and 68 hours after the gamma-ray burst. The burst occurred in a very faint (R > 29.5) Damped Ly-alpha Absorber (DLA) at a redshift of z = 3.198 +- 0.004. The derived column density of neutral hydrogen is log(N_H) = 21.7 +- 0.2 and the rest-frame reddening is constrained to be E(B-V) < 0.065, i.e., A_V < 0.20 for standard extinction laws with R_V ~ 3. The resulting dust-to-gas ratio is less than 11 % of that found in the Milky Way, but consistent with the SMC and high-redshift QSO DLAs, indicating a low metallicity and/or a low dust-to-metals ratio in the burst environment. A grey extinction law (large R_V), produced through preferential destruction of small dust grains by the GRB, could increase the derived A_V and dust-to-gas ratio. The dimness of the afterglow is however fully accounted for by the high redshift: If GRB 020124 had been at z = 1 it would have been approximately 1.8 mag brighter--in the range of typical bright afterglows.

A fruitful emerging literature reveals that shocks to uncertainty can explain asset returns, business cycles and financial crises. The literature equates uncertainty shocks with changes in the variance of an innovation whose distribution is common knowledge. But how do such shocks arise? This paper argues that people do not know the true distribution of macroeconomic outcomes. Like Bayesian econometricians, they estimate a distribution. Using real-time GDP data, we measure uncertainty as the conditional standard deviation of GDP growth, which captures uncertainty about the distributions estimated parameters. When the forecasting model admits only normally-distributed outcomes, we find small, acyclical changes in uncertainty. But when agents can also estimate parameters that regulate skewness, uncertainty fluctuations become large and counter-cyclical. The reason is that small changes in estimated skewness whip around probabilities of unobserved tail events (black swans). The resulting forecasts resemble those of professional forecasters. Our uncertainty estimates reveal that revisions in parameter estimates, especially those that affect the risk of a black swan, explain most of the shocks to uncertainty.

Examining Arrokoth The New Horizons spacecraft flew past the Kuiper Belt object (486958) Arrokoth (also known as 2014 MU 69 ) in January 2019. Because of the great distance to the outer Solar System and limited bandwidth, it will take until late 2020 to downlink all the spacecraft's observations back to Earth. Three papers in this issue analyze recently downlinked data, including the highest-resolution images taken during the encounter (see the Perspective by Jewitt). Spencer et al. examined Arrokoth's geology and geophysics using stereo imaging, dated the surface using impact craters, and produced a geomorphological map. Grundy et al. investigated the composition of the surface using color imaging and spectroscopic data and assessed Arrokoth's thermal emission using microwave radiometry. McKinnon et al. used simulations to determine how Arrokoth formed: Two gravitationally bound objects gently spiraled together during the formation of the Solar System. Together, these papers determine the age, composition, and formation process of the most pristine object yet visited by a spacecraft. Science , this issue p. eaay3999 , p. eaay3705 , p. eaay6620 ; see also p. 980

Broad-band optical observations of the extraordinarily bright optical afterglow of the intense gamma-ray burst GRB 991208 started ~2.1 days after the event and continued until 4 Apr. 2000. The flux decay constant of the optical afterglow in the R-band is -2.30 ± 0.07 up to ~5 days, which is very likely due to the jet e ffect, and it is followed by a much steeper decay with constant -3.2 ± 0.2, the fastest one ever seen in a GRB optical afterglow. A negative detection in several all-sky films taken simultaneously with the event, that otherwise would have reached naked eye brightness, implies either a previous additional break prior to ~2 days after the occurrence of the GRB (as expected from the jet effect) or a maximum, as observed in GRB 970508. The existence of a se cond break might indicate a steepening in the electron spectrum or the superposition of two events, resembling GRB 000301C. Once the afterglow emission vanished, contribution of a bright underlying supernova was found on the basis of the late-time R-band measurements, but the light curve is not sufficiently well sampled to rule out a dust echo explanation. Our redshift determination of indicates that GRB 991208 is at 3.7 Gpc (for km s-1 Mpc-1, and ), implying an isotropic energy release of 1.15 1053 erg which may be relaxed by beaming by a factor >102. Precise astrometry indicates that the GRB coincides within 0.2″ with the host galaxy, thus supporting a massive star origin. The absolute magnitude of the galaxy is MB = -18.2, well below the knee of the galaxy luminosity function and we derive a star-forming rate of () yr-1, which is much larger than the present-day rate in our Galaxy. The quasi-simultaneous broad-band photometric spectral energy distribution of the afterglow was determined ~3.5 day after the burst (Dec. 12.0) implying a cooling frequency below the optical band, i.e. supporting a jet model with 2.30 as the index of the power-law electron distribution.

We present optical and near-infrared follow-up observations of the X-Ray Flash (XRF) of July 23 2003. Our observations in the R-band cover the temporal range from 4.2 h to 64 days after the high energy event. We also present the results of multicolor imaging extending to the K-band on three epochs. The lightcurve of the R-band afterglow the first week after the burst is similar to the lightcurve for long duration Gamma-Ray Bursts (GRBs), i.e., a broken power-law with a late time slope of alpha=2.0 (F_nu propto t^-alpha). Furthermore, the spectral energy distribution (SED) has a power-law (F_nu propto nu^beta) shape with slope beta=-1.0. However, the decay slope at t&lt;1 day is shallow, consistent with zero. This is in qualitative agreement with the prediction that XRFs are off-axis classical GRBs. After the first week there is a strong bump in the lightcurve, which peaks at around 16 days. The SED after the peak becomes significantly redder. We discuss the possible interpretations of this bump, and conclude that an underlying supernova is the most likely explanation since no other model appears consistent with the evolution of the SED. Finally, we present deep spectroscopy of the burst both in the afterglow and in the bump phase. A firm upper limit of z=2.3 is placed on the redshift of XRF030723 from the lack of Ly-alpha forest lines in the spectrum of the afterglow. The lack of significant absorption and emission lines in either of the two spectra excludes a spectroscopic redshift determination.

Abstract— The irradiation of native DNA's by ultraviolet radiation of different wave lengths changes their absorption spectra. The changes are similar to those found for the formation of dimers between adjacent thymines in polynucleotide chains. The decreases in absorbance at 270 mµ produced by 280 mµ irradiation are reversed to a large extent by subsequent 239 mµ irradiation. The magnitude of the absorbance changes produced by large doses of 280 mµ correspond to the formation of dimers between approximately 50 per cent of all the TT sequences in the DNA. An incident dose of 100 erg/mm 2 of 280 mµ radiation forms about one dimer per molecule of calf thymus DNA of molecular weight 6 times 10 6 . The irradiation of heat‐denatured DNA produces larger absorbance changes than are observed in native DNA. The absorbance changes in denatured DNA arise in part from a heat‐reversible reaction, presumably involving cytidine, part from the formation of thymine dimers, and part from some unknown photoproducts. The reversal of thymine dimers by short wave length irradiation does not pioduce an equivalent change in the melting temperature of the DNA.

Jupiter’s moon Europa has a subsurface ocean beneath an icy crust. Conditions within the ocean are unknown, and it is unclear whether it is connected to the surface. We observed Europa with the James Webb Space Telescope (JWST) to search for active release of material by probing its surface and atmosphere. A search for plumes yielded no detection of water, carbon monoxide, methanol, ethane, or methane fluorescence emissions. Four spectral features of carbon dioxide (CO 2 ) ice were detected; their spectral shapes and distribution across Europa’s surface indicate that the CO 2 is mixed with other compounds and concentrated in Tara Regio. The 13 CO 2 absorption is consistent with an isotopic ratio of 12 C/ 13 C = 83 ± 19. We interpret these observations as indicating that carbon is sourced from within Europa.

Child care denotes any arrangement used by a working parent for care of a child, including self-care. This paper is concerned with the factors that influence the demand for market modes of child care by two parent families with working mothers. An econometric model is specified that relates the demand for child care to price, income, and other economic variables. Because of the discrete nature of the child care decision, the multinomial logit probability model is used to analyze the data. The empirical results suggest that the demand for child care is sensitive to both prices and income.

In April 2023, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. The phylum was expanded by one new family, 14 new genera, and 140 new species. Two genera and 538 species were renamed. One species was moved, and four were abolished. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV.

The authors study the quorumcasting problem which is a generalization of multicasting. While multicasting consists of sending a message to a select group of m nodes in a system of n nodes, quorumcasting sends a message to any q out of these m nodes. The need to communicate with an arbitrary q-subset of a predefined set arises in many distributed applications, such as distributed synchronization and updating a replicated resource. Two straightforward solutions are to send the message to individual members one at a time until q members have responded and to use multicasting to deliver the message to all members. The former solution will have excessive delay and the latter can cause congestion in nodes and/or in the network. The solutions proposed here use a minimum cost tree spanning a q-subset. By choosing an appropriate set of q nodes, the communications cost can be minimized. They present several heuristics to find low cost solutions for the quorumcast routing problem and evaluate the heuristics by comparing their solutions with exact solutions obtained from enumerating the solution space. The heuristic solutions are also compared with "random" solutions, where the q quorum sites are selected at random, and then the problem is treated like a multicast. The results of their tests show that the heuristics compare favorably with the optimal solutions, and that the random solutions perform rather poorly in comparison with the heuristics.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>

Student use of pop-up text windows that support or extend information found in a high school social studies text provides a detailed look into the instructional effectiveness of a set of hypermedia study guides. Twenty-five students, 19 male and 6 female, with a mean age of 14.6 years participated in this study. Thirteen were students with learning disabilities and 12 were remedial students. Findings from the study indicate that hypertext (text-only) support provides adequate reinforcement to move remedial students and students with learning disabilities toward continued, unprompted use of a hypermedia study guide, and that short-term and long-term retention of information can be expected from text-only information support. Students who had access to the hypermedia study guides exhibited better information retention than students who did not use the hypermedia study guides.