First Exploration of Neutron Shell Structure below Lead and beyond N=126.

The nuclei below lead but with more than 126 neutrons are crucial to an understanding of the astrophysical r process in producing nuclei heavier than A∼190. Despite their importance, the structure and properties of these nuclei remain experimentally untested as they are difficult to produce in nuclear reactions with stable beams. In a first exploration of the shell structure of this region, neutron excitations in ^{207}Hg have been probed using the neutron-adding (d,p) reaction in inverse kinematics. The radioactive beam of ^{206}Hg was delivered to the new ISOLDE Solenoidal Spectrometer at an energy above the Coulomb barrier. The spectroscopy of ^{207}Hg marks a first step in improving our understanding of the relevant structural properties of nuclei involved in a key part of the path of the r process.

Probing the Single-Particle Character of Rotational States in

A beam containing a substantial component of both the J^{π}=5^{+}, T_{1/2}=162 ns isomeric state of ^{18}F and its 1^{+}, 109.77-min ground state is utilized to study members of the ground-state rotational band in ^{19}F through the neutron transfer reaction (d,p) in inverse kinematics. The resulting spectroscopic strengths confirm the single-particle nature of the 13/2^{+} band-terminating state. The agreement between shell-model calculations using an interaction constructed within the sd shell, and our experimental results reinforces the idea of a single-particle-collective duality in the descriptions of the structure of atomic nuclei.

Quenching of cross sections in nucleon transfer reactions.

Cross sections for proton knockout observed in (e,e'p) reactions are apparently quenched by a factor of ∼0.5, an effect attributed to short-range correlations between nucleons. Here we demonstrate that such quenching is not restricted to proton knockout, but a more general phenomenon associated with any nucleon transfer. Measurements of absolute cross sections on a number of targets between 16O and 208Pb were analyzed in a consistent way, with the cross sections reduced to spectroscopic factors through the distorted-wave Born approximation with global optical potentials. Across the 124 cases analyzed here, induced by various proton- and neutron-transfer reactions and with angular momentum transfer ℓ=0-7, the results are consistent with a quenching factor of 0.55. This is an apparently uniform quenching of single-particle motion in the nuclear medium. The effect is seen not only in (d,p) reactions but also in reactions with A=3 and 4 projectiles, when realistic wave functions are used for the projectiles.

Test of sum rules in nucleon transfer reactions.

The quantitative consistency of nucleon transfer reactions as a probe of the occupancy of valence orbits in nuclei is tested. Neutron-adding, neutron-removal, and proton-adding transfer reactions were measured on the four stable even Ni isotopes, with particular attention to the cross section determinations. The data were analyzed consistently in terms of the distorted wave Born approximation to yield spectroscopic factors. Valence-orbit occupancies were extracted, utilizing the Macfarlane-French sum rules. The deduced occupancies are consistent with the changing number of valence neutrons, as are the vacancies for protons, both at the level of <5%. While there has been some debate regarding the true "observability" of spectroscopic factors, the present results indicate that empirically they yield self-consistent results.

Pharmacologic control of homeostatic and antigen-driven proliferation to target HIV-1 persistence.

The presence of latent human immunodeficiency virus 1 (HIV-1) in quiescent memory CD4 + T cells represents a major barrier to viral eradication. Proliferation of memory CD4 + T cells is the primary mechanism that leads to persistence of the latent reservoir, despite effective antiretroviral therapy (ART). Memory CD4 + T cells are long-lived and can proliferate through two mechanisms: homeostatic proliferation via γc-cytokine stimulation or antigen-driven proliferation. Therefore, therapeutic modalities that perturb homeostatic and antigen-driven proliferation, combined with ART, represent promising strategies to reduce the latent reservoir. In this study, we investigated a library of FDA-approved oncology drugs to determine their ability to inhibit homeostatic and/or antigen-driven proliferation. We confirmed potential hits by evaluating their effects on proliferation in memory CD4 + T cells from people living with HIV-1 on ART (PLWH) and interrogated downstream signaling of γc-cytokine stimulation. We found that dasatinib and ponatinib, tyrosine kinase inhibitors, and trametinib, a MEK inhibitor, reduced both homeostatic and antigen-driven proliferationby >65%, with a reduction in viability <45%, ex vivo. In memory CD4 + T cells from PLWH, only dasatinib restricted both homeostatic and antigen-driven proliferation and prevented spontaneous rebound, consistent with promoting a smaller reservoir size. We show that dasatinib restricts IL-7 induced proliferation through STAT5 phosphorylation inhibition. Our results establish that the anti-cancer agent dasatinib is an exciting candidate to be used as an anti-proliferative drug in a clinical trial, since it efficiently blocks proliferation and iswell tolerated in patients with chronic myeloid leukemia (CML).

¹5C(d,p)¹6C reaction and exotic behavior in ¹6C.

We have studied the ¹5C(d,p)¹6C reaction in inverse kinematics using the Helical Orbit Spectrometer at Argonne National Laboratory. Prior studies of electromagnetic-transition rates in ¹6C suggested an exotic decoupling of the valence neutrons from the core in that nucleus. Neutron-adding spectroscopic factors give a different probe of the wave functions of the relevant states in ¹6C. Shell-model calculations reproduce both the present transfer data and the previously measured transition rates, suggesting that ¹6C may be described without invoking very exotic phenomena.

First experiment with HELIOS: the structure of 13B.

A first experiment is reported that makes use of a new kind of spectrometer uniquely suited to the study of reactions with radioactive beams in inverse kinematics, the helical orbit spectrometer, HELIOS. The properties of some low-lying states in the neutron-rich N=8 nucleus 13B were studied with good resolution. From the measured angular distributions of the (d,p) reaction and the relative spectroscopic factors, spin and configuration assignments of the first- and third-excited states of this nucleus can be constrained.

Protein design by binary patterning of polar and nonpolar amino acids.

A general strategy is described for the de novo design of proteins. In this strategy the sequence locations of hydrophobic and hydrophilic residues were specified explicitly, but the precise identities of the side chains were not constrained and varied extensively. This strategy was tested by constructing a large collection of synthetic genes whose protein products were designed to fold into four-helix bundle proteins. Each gene encoded a different amino acid sequence, but all sequences shared the same pattern of polar and nonpolar residues. Characterization of the expressed proteins indicated that most of the designed sequences folded into compact alpha-helical structures. Thus, a simple binary code of polar and nonpolar residues arranged in the appropriate order can drive polypeptide chains to collapse into globular alpha-helical folds.

Impacts of Lipase Enzyme on the Surface Properties of Marine Aerosols.

Triacylglycerol lipases have recently been shown to be transferred from the ocean to the atmosphere in atmospheric sea spray aerosol (SSA). Lipases have the potential to alter the composition of SSA; however, the structure and properties of enzymes in the high salt, high ionic strength, and low pH conditions found in SSA have never been explored. Here, we study the dynamics of Burkholderia cepacia triacylglycerol lipase (BCL) at SSA model surfaces comprised of palmitic acid and dipalmitoylphosphatidic acid (DPPA), two commonly found lipids at SSA surfaces. Surface adsorption Langmuir isotherm experiments and all-atom explicit solvent molecular dynamics simulations together illuminate how and why BCL expands the ordering of lipids at palmitic acid surfaces the most at pH < 4 and the least in DPPA surfaces at pH 6. Taken together, these results represent a first glimpse into the complex interplay between lipid surface structure and protein dynamics within enzyme-containing aerosols.

New determination of the astrophysical S factor SE1 of the 12C(alpha,gamma)16O reaction.

A new measurement of the beta-delayed alpha decay of 16N has been performed using a set of high efficiency ionization chambers. Sources were made by implantation of a 16N beam, yielding very clean alpha spectra down to energies as low as 400 keV. Our data are in good agreement with earlier results. For the S factor S(E1), we obtain a value of 74 +/- 21 keV b. In spite of improvements in the measurement, the error in S(E1) remains relatively large because of the correlations among the fit parameters and the uncertainties inherent to the extrapolation.

Cross-species prediction of human survival probabilities for accelerated anthrax vaccine absorbed (AVA) regimens and the potential for vaccine and antibiotic dose sparing.

Anthrax vaccine adsorbed (AVA, BioThrax) was recently approved by the Food and Drug Administration (FDA) for a post-exposure prophylaxis (PEP) indication in adults 18-65years of age. The schedule is three doses administered subcutaneous (SC) at 2-week intervals (0, 2, and 4weeks), in conjunction with a 60-day course of antimicrobials. The Public Health Emergency Medical Countermeasures Enterprise (PHEMCE) developed an animal model to support assessment of a shortened antimicrobial PEP duration following Bacillus anthracis exposure. A nonhuman primate (NHP) study was completed to evaluate the efficacy of a two dose anthrax vaccine absorbed (AVA) schedule (0, 2weeks) aerosol challenged with high levels of B. anthracis spores at week4- the time point at which humans would receive the third vaccination of the approved PEP schedule. Here we use logistic regression models to combine the survival data from the NHP study along with serum anthrax lethal toxin neutralizing activity (TNA) and anti-PA IgG measured by enzyme linked immunosorbent assay (ELISA) data to perform a cross-species analysis to estimate survival probabilities in vaccinated human populations at this time interval (week4 of the PEP schedule). The bridging analysis demonstrated that high levels of NHP protection also yield high predicted probability of human survival just 2weeks after the second dose of vaccine with the full or half antigen dose regimen. The absolute difference in probability of human survival between the full and half antigen dose was estimated to be at most approximately 20%, indicating that more investigation of the half-antigen dose for vaccine dose sparing strategies may be warranted.

Evaluation of early immune response-survival relationship in cynomolgus macaques after Anthrax Vaccine Adsorbed vaccination and Bacillus anthracis spore challenge.

Anthrax Vaccine Adsorbed (AVA, BioThrax) is approved by the US Food and Drug Administration for post-exposure prophylaxis (PEP) of anthrax in adults. The PEP schedule is 3 subcutaneous (SC) doses (0, 14 and 28 days), in conjunction with a 60 day course of antimicrobials. The objectives of this study were to understand the onset of protection from AVA PEP vaccination and to assess the potential for shortening the duration of antimicrobial treatment (http://www.phe.gov/Preparedness/mcm/phemce/Documents/2014-phemce-sip.pdf). We determined the efficacy against inhalation anthrax in nonhuman primates (NHP) of the first two doses of the PEP schedule by infectious challenge at the time scheduled for receipt of the third PEP dose (Day 28). Forty-eight cynomolgus macaques were randomized to five groups and vaccinated with serial dilutions of AVA on Days 0 and 14. NHP were exposed to Bacillus anthracis Ames spores on Day 28 (target dose 200 LD50 equivalents). Anti-protective antigen (PA) IgG and toxin neutralizing antibody (TNA) responses to vaccination and in post-challenge survivors were determined. Post-challenge blood and selected tissue samples were assessed for B. anthracis at necropsy or end of study (Day 56). Pre-challenge humoral immune responses correlated with survival, which ranged from 24 to 100% survival depending on vaccination group. Surviving, vaccinated animals had elevated anti-PA IgG and TNA levels for the duration of the study, were abacteremic, exhibited no apparent signs of infection, and had no gross or microscopic lesions. However, survivors had residual spores in lung tissues. We conclude that the first two doses of the PEP schedule provide high levels of protection by the scheduled timing of the third dose. These data may also support consideration of a shorter duration PEP antimicrobial regimen.

Posttraumatic meningioma.

This report concerns three patients with intracranial meningioma developing at the site of an old head injury with skull fracture. These cases, along with literature reports, suggest a causal relationship between head trauma and the subsequent development of meningioma.

Brain effect of intracarotid administration of cisplatinum.

The antitumoral effect of Cisplatinum is well known, including its effect on brain tumors. With the purpose of establishing the effect of intraarterial cis-dichlorodiammine platinum (CDDP) on the brain, Cisplatinum was injected in rabbits that were sacrificed at different intervals. The general clinical and neurological condition of the rabbits was unaffected, and histopathological examination of the rabbit's brain was normal.

Effect of high simple dose of cisplatinum and of radiation on the brain of rabbit.

In former studies of intracarotid and intravenous administration of cisplatinum, separate and combined with brain irradiation, we found no cerebral damage. In this study, gradually increasing high doses (above the therapeutic ones) of cisplatinum were administered intravenously to one series of rabbits and increasing high amounts of irradiation (above the therapeutic amounts) were given to another series. Although the rabbits that received highest doses of irradiation developed areas of alopecia and skin ulcers on the head, the general clinical and histopathologic examination of the rabbits' brains in both series was normal. The purpose of this study was to establish the effects of high doses of intravenous cisplatinum and irradiation on the rabbits brains.

Effect of the combination of cisplatinum and radiation in the rabbit's brain.

The effect of cisplatinum as a potential radiosensitizer in brain tumors is controversial. We examined the effect of the combination of cisplatinum with radiation compared to radiation alone in rabbits' brain. All rabbits were irradiated and cisplatinum was injected intravenously into part of them. Therapeutic doses of cisplatinum and irradiation were given. The rabbits were euthanised at different intervals according to protocol. The general clinical and neurological condition of the rabbits was unaffected, and histopathological examination of the rabbit's brain was normal. The purpose of this study was to establish the effect of cisplatinum followed by cranial irradiation in therapeutic doses to the normal rabbit's brain.

Effect of very high single dose of cisplatinum and of radiation on the brain of the rabbit.

The importance of chemotherapy and radiotherapy for treating brain tumors, is well established. In a previous study, a rabbit's brain was treated with doses of up to 12 mg kg-1 of cisplatinum and 4000 cGy, without any morphological or pathological changes. The purpose of this study is to establish the effect of very high single doses of cisplatinum and radiation on the rabbit's brain, applied in 12, 16 and 18 mg kg-1, and 5000, 7500 and 8000 cGy, respectively. The general clinical and neurological condition of the rabbits was unaffected, but areas of alopecia and scalp ulcers appeared. Although these are very high doses of chemotherapy and radiotherapy, the histopathological and morphological examination of the rabbit's brain remained normal.

Rapidly growing head circumference as an isolated presenting symptom of brain abscesses in an infant.

A rapid and excessive enlargement in occipito frontal circumference (OFC) as the only manifestation of multiple cerebral abscesses in infancy is extremely rare. A 2-month-old asymptomatic infant presenting with increasing OFC is described. Surgical drainage of the cerebral abscesses followed by prolonged antibiotic therapy resulted in complete recovery.