1,053 research outputs found
E. coli contamination of mountain springs used for drinking water and drilled well alternatives
Millions of people in developing communities drink water from springs on bedrock mountain slopes. Previous studies show E. coli causing many sampled springs on populated mountain slopes in southwest China to provide unsafe drinking water (Chitwood 2007a). Such studies are rare, but recently a reconnaissance study was initiated in a watershed in the Dominican Republic where more than 25,000 people, spread out across small communities and one town, rely on mountain springs. E. coli testing shows many of these springs to be unsafe. Water users live downslope and distant from the springs and receive spring water via pipelines. Likely, the E. coli originates from sparse livestock grazing up-slope from springs. Small wells drilled using portable rock coring machines and completed using novel continuous seals attached above the water intake zone are proposed to access safe drinking water drawn from permeable fractures tens of meters below ground, avoiding contamination near surface
Tumor-homing cytotoxic human induced neural stem cells for cancer therapy
Engineered neural stem cells (NSCs) are a promising approach to treating glioblastoma (GBM). The ideal NSC drug carrier for clinical use should be easily isolated and autologous to avoid immune rejection. We transdifferentiated (TD) human fibroblasts into tumor-homing early-stage induced NSCs (h-iNSCTE), engineered them to express optical reporters and different therapeutic gene products, and assessed the tumor-homing migration and therapeutic efficacy of cytotoxic h-iNSCTE in patient-derived GBM models of surgical and nonsurgical disease. Molecular and functional analysis revealed that our single-factor SOX2 TD strategy converted human skin fibroblasts into h-iNSCTE that were nestin+ and expressed pathways associated with tumor-homing migration in 4 days. Time-lapse motion analysis showed that h-iNSCTE rapidly migrated to human GBM cells and penetrated human GBM spheroids, a process inhibited by blockade of CXCR4. Serial imaging showed that h-iNSCTE delivery of the proapoptotic agent tumor necrosis factor-A-related apoptosis-inducing ligand (TRAIL) reduced the size of solid human GBM xenografts 250-fold in 3 weeks and prolonged median survival from 22 to 49 days. Additionally, h-iNSCTE thymidine kinase/ganciclovir enzyme/prodrug therapy (h-iNSCTE-TK) reduced the size of patient-derived GBM xenografts 20-fold and extended survival from 32 to 62 days. Mimicking clinical NSC therapy, h-iNSCTE-TK therapy delivered into the postoperative surgical resection cavity delayed the regrowth of residual GBMs threefold and prolonged survival from 46 to 60 days. These results suggest that TD of human skin into h-iNSCTE is a platform for creating tumor-homing cytotoxic cell therapies for cancer, where the potential to avoid carrier rejection could maximize treatment durability in human trials
Extension of Earth-Moon libration point orbits with solar sail propulsion
This paper presents families of libration point orbits in the Earth-Moon system that originate from complementing the classical circular restricted three-body problem with a solar sail. Through the use of a differential correction scheme in combination with a continuation on the solar sail induced acceleration, families of Lyapunov, halo, vertical Lyapunov, Earth-centred, and distant retrograde orbits are created. As the solar sail circular restricted three-body problem is non-autonomous, a constraint defined within the differential correction scheme ensures that all orbits are periodic with the Sunâs motion around the Earth-Moon system. The continuation method then starts from a classical libration point orbit with a suitable period and increases the solar sail acceleration magnitude to obtain families of orbits that are parametrised by this acceleration. Furthermore, different solar sail steering laws are considered (both in-plane and out-of-plane, and either fixed in the synodic frame or fixed with respect to the direction of sunlight), adding to the wealth of families of solar sail enabled libration point orbits presented. Finally, the linear stability properties of the generated orbits are investigated to assess the need for active orbital control. It is shown that the solar sail induced acceleration can have a positive effect on the stability of some orbit families, especially those at the L2 point, but that it most often (further) destabilises the orbit. Active control will therefore be needed to ensure long-term survivability of these orbits
Phantom Cosmology with Non-minimally Coupled Real Scalar Field
We find that the expansion of the universe is accelerating by analyzing the
recent observation data of type \textsc{I}a supernova(SN-Ia) .It indicates
that the equation of state of the dark energy might be smaller than -1,which
leads to the introduction of phantom models featured by its negative kinetic
energy to account for the regime of equation of state parameter .In this
paper the possibility of using a non-minimally coupled real scalar field as
phantom to realize the equation of state parameter is discussed.The main
equations which govern the evolution of the universe are obtained.Then we
rewrite them with the observable quantities.Comment: 12 pages, 2 figures. Accepted for publication in Gen.Rel.Gra
Combined kinase inhibitors of MEK1/2 and either PI3K or PDGFR are efficacious in intracranial triple-negative breast cancer
Background: Triple-negative breast cancer (TNBC), lacking expression of hormone and human epidermal growth factor receptor 2 receptors, is an aggressive subtype that frequently metastasizes to the brain and has no FDA-approved systemic therapies. Previous literature demonstrates mitogen-Activated protein kinase kinase (MEK) pathway activation in TNBC brain metastases. Thus, we aimed to discover rational combinatorial therapies with MEK inhibition, hypothesizing that co-inhibition using clinically available brain-penetrant inhibitors would improve survival in preclinical models of TNBC brain metastases. Methods: Using human-derived TNBC cell lines, synthetic lethal small interfering RNA kinase screens were evaluated with brain-penetrant inhibitors against MEK1/2 (selumetinib, AZD6244) or phosphatidylinositol-3 kinase (PI3K; buparlisib, BKM120). Mice bearing intracranial TNBC tumors (SUM149, MDA-MB-231Br, MDA-MB-468, or MDA-MB-436) were treated with MEK, PI3K, or platelet derived growth factor receptor (PDGFR; pazopanib) inhibitors alone or in combination. Tumors were analyzed by western blot and multiplexed kinase inhibitor beads/mass spectrometry to assess treatment effects. Results: Screens identified MEK+PI3K and MEK+PDGFR inhibitors as tractable, rational combinations. Dual treatment of selumetinib with buparlisib or pazopanib was synergistic in TNBC cells in vitro. Both combinations improved survival in intracranial SUM149 and MDA-MB-231Br, but not MDA-MB-468 or MDA-MB-436. Treatments decreased mitogen-Activated protein kinase (MAPK) and PI3K (Akt) signaling in sensitive (SUM149 and 231Br) but not resistant models (MDA-MB-468). Exploratory analysis of kinome reprogramming in SUM149 intracranial tumors after MEK PI3K inhibition demonstrates extensive kinome changes with treatment, especially in MAPK pathway members. Conclusions: Results demonstrate that rational combinations of the clinically available inhibitors selumetinib with buparlisib or pazopanib may prove to be promising therapeutic strategies for the treatment of some TNBC brain metastases. Additionally, effective combination treatments cause widespread alterations in kinase pathways, including targetable potential resistance drivers
ASTEC -- the Aarhus STellar Evolution Code
The Aarhus code is the result of a long development, starting in 1974, and
still ongoing. A novel feature is the integration of the computation of
adiabatic oscillations for specified models as part of the code. It offers
substantial flexibility in terms of microphysics and has been carefully tested
for the computation of solar models. However, considerable development is still
required in the treatment of nuclear reactions, diffusion and convective
mixing.Comment: Astrophys. Space Sci, in the pres
Schwinger Pair Production via Instantons in Strong Electric Fields
In the space-dependent gauge, each mode of the Klein-Gordon equation in a
strong electric field takes the form of a time-independent Schr\"{o}dinger
equation with a potential barrier. We propose that the single- and
multi-instantons of quantum tunneling may be related with the single- and
multi-pair production of bosons and the relative probability for the no-pair
production is determined by the total tunneling probability via instantons. In
the case of a uniform electric field, the instanton interpretation recovers
exactly the well-known pair production rate for bosons and when the Pauli
blocking is taken into account, it gives the correct fermion production rate.
The instanton is used to calculate the pair production rate even in an
inhomogeneous electric field. Furthermore, the instanton interpretation
confirms the fact that bosons and fermions can not be produced by a static
magnetic field only.Comment: RevTex 7 Pages, No figure; Formulae for the production rate in very
strong fields and references added; the final version accepted in Phys. Rev.
LCCC 1025: a phase II study of everolimus, trastuzumab, and vinorelbine to treat progressive HER2-positive breast cancer brain metastases
Purpose: HER2 + breast cancer (BC) is an aggressive subtype with high rates of brain metastases (BCBM). Two-thirds of HER2 + BCBM demonstrate activation of the PI3K/mTOR pathway driving resistance to anti-HER2 therapy. This phase II study evaluated everolimus (E), a brain-permeable mTOR inhibitor, trastuzumab (T), and vinorelbine (V) in patients with HER2 + BCBM. Patients and methods: Eligible patients had progressive HER2 + BCBM. The primary endpoint was intracranial response rate (RR); secondary objectives were CNS clinical benefit rate (CBR), extracranial RR, time to progression (TTP), overall survival (OS), and targeted sequencing of tumors from enrolled patients. A two-stage design distinguished intracranial RR of 5% versus 20%. Results: 32 patients were evaluable for toxicity, 26 for efficacy. Intracranial RR was 4% (1 PR). CNS CBR at 6 mos was 27%; at 3 mos 65%. Median intracranial TTP was 3.9 mos (95% CI 2.2â5). OS was 12.2 mos (95% CI 0.6â20.2). Grade 3â4 toxicities included neutropenia (41%), anemia (16%), and stomatitis (16%). Mutations in TP53 and PIK3CA were common in BCBM. Mutations in the PI3K/mTOR pathway were not associated with response. ERBB2 amplification was higher in BCBM compared to primary BC; ERBB2 amplification in the primary BC trended toward worse OS. Conclusion: While intracranial RR to ETV was low in HER2 + BCBM patients, one-third achieved CNS CBR; TTP/OS was similar to historical control. No new toxicity signals were observed. Further analysis of the genomic underpinnings of BCBM to identify tractable prognostic and/or predictive biomarkers is warranted. Clinical Trial: (NCT01305941)
Correlation Entropy of an Interacting Quantum Field and H-theorem for the O(N) Model
Following the paradigm of Boltzmann-BBGKY we propose a correlation entropy
(of the nth order) for an interacting quantum field, obtained by `slaving'
(truncation with causal factorization) of the higher (n+1 th) order correlation
functions in the Schwinger-Dyson system of equations. This renders an otherwise
closed system effectively open where dissipation arises. The concept of
correlation entropy is useful for addressing issues related to thermalization.
As a small yet important step in that direction we prove an H-theorem for the
correlation entropy of a quantum mechanical O(N) model with a Closed Time Path
Two Particle Irreducible Effective Action at the level of Next-to-Leading-Order
large N approximation. This model may be regarded as a field theory in
space dimensions.Comment: 22 page
Magnetic Reconnection in Extreme Astrophysical Environments
Magnetic reconnection is a basic plasma process of dramatic rearrangement of
magnetic topology, often leading to a violent release of magnetic energy. It is
important in magnetic fusion and in space and solar physics --- areas that have
so far provided the context for most of reconnection research. Importantly,
these environments consist just of electrons and ions and the dissipated energy
always stays with the plasma. In contrast, in this paper I introduce a new
direction of research, motivated by several important problems in high-energy
astrophysics --- reconnection in high energy density (HED) radiative plasmas,
where radiation pressure and radiative cooling become dominant factors in the
pressure and energy balance. I identify the key processes distinguishing HED
reconnection: special-relativistic effects; radiative effects (radiative
cooling, radiation pressure, and Compton resistivity); and, at the most extreme
end, QED effects, including pair creation. I then discuss the main
astrophysical applications --- situations with magnetar-strength fields
(exceeding the quantum critical field of about 4 x 10^13 G): giant SGR flares
and magnetically-powered central engines and jets of GRBs. Here, magnetic
energy density is so high that its dissipation heats the plasma to MeV
temperatures. Electron-positron pairs are then copiously produced, making the
reconnection layer highly collisional and dressing it in a thick pair coat that
traps radiation. The pressure is dominated by radiation and pairs. Yet,
radiation diffusion across the layer may be faster than the global Alfv\'en
transit time; then, radiative cooling governs the thermodynamics and
reconnection becomes a radiative transfer problem, greatly affected by the
ultra-strong magnetic field. This overall picture is very different from our
traditional picture of reconnection and thus represents a new frontier in
reconnection research.Comment: Accepted to Space Science Reviews (special issue on magnetic
reconnection). Article is based on an invited review talk at the
Yosemite-2010 Workshop on Magnetic Reconnection (Yosemite NP, CA, USA;
February 8-12, 2010). 30 pages, no figure
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