The Dwarf Spheroidal Companions to M31: WFPC2 Observations of Andromeda I

Images have been obtained with the Hubble Space Telescope WFPC2 camera of Andromeda I, a dwarf spheroidal (dSph) galaxy that lies in the outer halo of M31. The resulting color-magnitude diagrams reveal for the first time the morphology of the horizontal branch in this system. We find that, in a similar fashion to many of the galactic dSph companions, the horizontal branch (HB) of And~I is predominantly red. Combined with the metal abundance of this dSph, this red HB morphology indicates that And I can be classified as a ``second parameter'' system in the outer halo of M31. This result then supports the hypothesis that the outer halo of M31 formed in the same extended chaotic manner as is postulated for the outer halo of the Galaxy.Comment: 26 pages using aas2pp4.sty, including 2 tables and 7 figures, to be published in AJ. Figure 1 is in gif form. To include in main ps file, use xv to create a ps file called Da_Costa.fig1.ps and uncomment appropriate lines in .tex fil

Dihydropyrimidine-thiones and clioquinol synergize to target beta-amyloid cellular pathologies through a metal-dependent mechanism

The lack of therapies for neurodegenerative diseases arises from our incomplete understanding of their underlying cellular toxicities and the limited number of predictive model systems. It is critical that we develop approaches to identify novel targets and lead compounds. Here, a phenotypic screen of yeast proteinopathy models identified dihydropyrimidine-thiones (DHPM-thiones) that selectively rescued the toxicity caused by β-amyloid (Aβ), the peptide implicated in Alzheimer’s disease. Rescue of Aβ toxicity by DHPM-thiones occurred through a metal-dependent mechanism of action. The bioactivity was distinct, however, from that of the 8-hydroxyquinoline clioquinol (CQ). These structurally dissimilar compounds strongly synergized at concentrations otherwise not competent to reduce toxicity. Cotreatment ameliorated Aβ toxicity by reducing Aβ levels and restoring functional vesicle trafficking. Notably, these low doses significantly reduced deleterious off-target effects caused by CQ on mitochondria at higher concentrations. Both single and combinatorial treatments also reduced death of neurons expressing Aβ in a nematode, indicating that DHPM-thiones target a conserved protective mechanism. Furthermore, this conserved activity suggests that expression of the Aβ peptide causes similar cellular pathologies from yeast to neurons. Our identification of a new cytoprotective scaffold that requires metal-binding underscores the critical role of metal phenomenology in mediating Aβ toxicity. Additionally, our findings demonstrate the valuable potential of synergistic compounds to enhance on-target activities, while mitigating deleterious off-target effects. The identification and prosecution of synergistic compounds could prove useful for developing AD therapeutics where combination therapies may be required to antagonize diverse pathologies.D.F.T was funded by NRSA Fellowship NIH 5F32NS061419. D.F.T. and S.L. were supported by WIBR funds in support of research on Regenerative Disease, the Picower/JPB Foundation, and the Edward N. and Della L. Thome Foundation. G.A.C. and S.L. were funded by a Howard Hughes Medical Institute (HHMI) Collaborative Innovation Award. L.E.B., R.T., and S.E.S. were funded by NIH GM086180, NIH GM067041, and NIH GM111625. (5F32NS061419 - NRSA Fellowship NIH; WIBR funds in support of research on Regenerative Disease; Picower/JPB Foundation; Edward N. and Della L. Thome Foundation; Howard Hughes Medical Institute (HHMI) Collaborative Innovation Award; GM086180 - NIH; NIH GM067041 - NIH; NIH GM111625 - NIH)https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5705239/Accepted manuscrip

Stringent constraint on the scalar-neutrino coupling constant from quintessential cosmology

An extremely light ($m_{\phi} \ll 10^{-33} {\rm eV}$), slowly-varying scalar field $\phi$ (quintessence) with a potential energy density as large as 60% of the critical density has been proposed as the origin of the accelerated expansion of the Universe at present. The interaction of this smoothly distributed component with another predominately smooth component, the cosmic neutrino background, is studied. The slow-roll approximation for generic $\phi$ potentials may then be used to obtain a limit on the scalar-neutrino coupling constant, found to be many orders of magnitude more stringent than the limits set by observations of neutrinos from SN 1987A. In addition, if quintessential theory allows for a violation of the equivalence principle in the sector of neutrinos, the current solar neutrino data can probe such a violation at the 10^{-10} level.Comment: 7 pages, MPLA in press, some parts disregarded and a footnote adde

A Black Hole of > 6 Solar Masses in the X-ray Nova XTE J1118+480

Observations of the quiescent X-ray nova XTE J1118+480 with the new 6.5-m MMT have revealed that the velocity amplitude of the dwarf secondary is 698 +/- 14 km/s and the orbital period of the system is 0.17013 +/- 0.00010 d. The implied value of the mass function, f(M) = 6.00 +/- 0.36 solar masses, provides a hard lower limit on the mass of the compact primary that greatly exceeds the maximum allowed mass of a neutron star. Thus we conclude that the compact primary is a black hole. Among the eleven dynamically established black-hole X-ray novae, the large mass function of XTE J1118+480 is rivaled only by that of V404 Cyg. We estimate that the secondary supplies 34% +/- 8% of the total light at 5900A and that its spectral type is in the range K5V to M1V. A double-humped I-band light curve is probably due to ellipsoidal modulation, although this interpretation is not entirely secure because of an unusual 12-minute offset between the spectroscopic and photometric ephemerides. Assuming that the light curve is ellipsoidal, we present a provisional analysis which indicates that the inclination of the system is high and the mass of the black hole is correspondingly modest. The broad Balmer emission lines (FWHM = 2300-2900 km/s) also suggest a high inclination. For the range of spectral types given above, we estimate a distance of 1.8 +/- 0.6 kpc.Comment: 4 pages, 2 figures, to appear in ApJ Letters; Minor changes to Fig 1

Calcium and magnesium absorption and retention by growing goats offered diets with different calcium sources

Calcium addition is necessary in order to balance the high phosphorus concentrations that are characteristic of high-concentrate ruminant diets. However, calcium sources differ in their bioavailability. Our objective was to determine apparent calcium and magnesium absorption and retention in goats offered diets containing different sources of calcium. Spanish-Boer goats (n = 18; 19.6 ± 1.88 kg) were stratified by body weight (BW) and sex and randomized to dietary treatments consisting of Purina Antlermax 16 containing either calcium carbonate (CC), Calmin (CM) or Milk Cal (MC). Goats were adapted to a control, corn-based high-concentrate diet on pasture and then moved to individual 1.0 × 1.5-m pens with plastic coated expanded metal floors, and adjusted to their respective diets along with removal of hay from the diet over a 7-d period. Goats were then offered their respective diets at a total of 2% of BW in equal feedings at 8:30 AM and 5:00 PM for an additional 14-d adaption period to diet and facilities followed by a 7-d collection of total urine and feces. Data were analyzed using PROC MIXED of SAS. Calcium and magnesium intake were not different (P ≥ 0.12) among diets. Calcium and magnesium apparent absorption and retention (g/d and % of intake) were greatest (P \u3c 0.05) in goats offered CC and did not differ (P ≥ 0.20) between goats offered the CM and MC diets. Therefore, calcium and magnesium were more available for goats from the diet containing calcium carbonate compared with diets containing Calmin and Milk Cal

Decay of the Z Boson into Scalar Particles

In extensions of the standard model, light scalar particles are often possible because of symmetry considerations. We study the decay of the Z boson into such particles. In particular, we consider for illustration the scalar sector of a recently proposed model of the 17-keV neutrino which satisfies all laboratory, astrophysical, and cosmological constraints.Comment: 11 pages (2 figures, not included) (Revised, Oct 1992). Some equations have been corrected and 1 figure has been eliminate

How Well Does the Latest Anthropomorphic Test Device Mimic Human Impact Responses?

One of the goals of the NASA Occupant Protection Group is to understand the human tolerance to dynamic loading. This knowledge has to come through indirect approaches such as existing human response databases, anthropometric test devices (ATD), animal testing, postmortem human subjects, and models. This study investigated the biofidelity of the National Highway Traffic Safety Administration's ATD named the THOR (test device for human occupant restraint). If THOR responds comparably to humans, then it could potentially be used as a human surrogate to help validate space vehicle requirements for occupant protection. The THOR responses to frontal and spinal impacts (ranging from 8 to 12 G with rise times of 40, 70, and 100 ms) were measured and compared to human volunteer responses (95 trials in frontal and 58 in spinal) previously collected by the U. S. Air Force on the same horizontal impact accelerator. The impact acceleration profiles tested are within the expected range of multipurpose crew vehicle (MPCV) landing dynamics. A correlation score was calculated for each THOR to human comparison using CORA (CORrelation and Analysis) software. A twoparameter beta distribution model fit was obtained for each dependent variable using maximum likelihood estimation. For frontal impacts, the THOR head xacceleration peak response correlated with the human response at 8 and 10G 100 ms but not 10G 70 ms. The phase lagged the human response. Head zacceleration was not correlated. Chest xacceleration was in phase, had a higher peak response, and was well correlated with lighter subjects (Cora = 0.8 for 46 kg vs. Cora = 0.4 for 126 kg). Head xdisplacement had a leading phase. Several subjects responded with the same peak displacement but the mean of the group was lower. The shoulder xdisplacement was in phase but had higher peaks than the human response. For spinal impacts, the THOR head xacceleration was not well correlated. Head and chest zacceleration was in phase but had a higher peak response. Chest zacceleration was highly correlated with heavier subjects at lower G pulses (Cora = 0.86 for 125 kg at 8 G). The human response was variable in shoulder zdisplacement but the THOR was in phase and was comparable to the mean peak response. Head xand zdisplacement was in phase but had higher peaks. Seat pan forces were well correlated, were in phase, but had a larger peak response than most subjects. The THOR does not respond to frontal and spinal impacts exactly the same way that a human does. Some responses are well matched and others are not. Understanding the strengths and weaknesses of this ATD is an important first step in determining its usefulness in occupant protection at NAS