Forecasting Proximal Femur and Wrist Fracture Caused by a Fall to the Side during Space Exploration Missions to the Moon and Mars

The possibility of bone fracture in space is a concern due to the negative impact it could have on a mission. The Bone Fracture Risk Module (BFxRM) developed at the NASA Glenn Research Center is a statistical simulation that quantifies the probability of bone fracture at specific skeletal locations for particular activities or events during space exploration missions. This paper reports fracture probability predictions for the proximal femur and wrist resulting from a fall to the side during an extravehicular activity (EVA) on specific days of lunar and Martian exploration missions. The risk of fracture at the proximal femur on any given day of the mission is small and fairly constant, although it is slightly greater towards the end of the mission, due to a reduction in proximal femur bone mineral density (BMD). The risk of wrist fracture is greater than the risk of hip fracture and there is an increased risk on Mars since it has a higher gravitational environment than the moon. The BFxRM can be used to help manage the risk of bone fracture in space as an engineering tool that is used during mission operation and resource planning

The Extravehicular Suit Impact Load Attenuation Study for Use in Astronaut Bone Fracture Prediction

The NASA Integrated Medical Model (IMM) assesses the risk, including likelihood and impact of occurrence, of all credible in-flight medical conditions. Fracture of the proximal femur is a traumatic injury that would likely result in loss of mission if it were to happen during spaceflight. The low gravity exposure causes decreases in bone mineral density which heightens the concern. Researchers at the NASA Glenn Research Center have quantified bone fracture probability during spaceflight with a probabilistic model. It was assumed that a pressurized extravehicular activity (EVA) suit would attenuate load during a fall, but no supporting data was available. The suit impact load attenuation study was performed to collect analogous data. METHODS: A pressurized EVA suit analog test bed was used to study how the offset, defined as the gap between the suit and the astronaut s body, impact load magnitude and suit operating pressure affects the attenuation of impact load. The attenuation data was incorporated into the probabilistic model of bone fracture as a function of these factors, replacing a load attenuation value based on commercial hip protectors. RESULTS: Load attenuation was more dependent on offset than on pressurization or load magnitude, especially at small offsets. Load attenuation factors for offsets between 0.1 - 1.5 cm were 0.69 +/- 0.15, 0.49 +/- 0.22 and 0.35 +/- 0.18 for mean impact forces of 4827, 6400 and 8467 N, respectively. Load attenuation factors for offsets of 2.8 - 5.3 cm were 0.93 +/- 0.2, 0.94 +/- 0.1 and 0.84 +/- 0.5, for the same mean impact forces. Reductions were observed in the 95th percentile confidence interval of the bone fracture probability predictions. CONCLUSIONS: The reduction in uncertainty and improved confidence in bone fracture predictions increased the fidelity and credibility of the fracture risk model and its benefit to mission design and operational decisions

Increased expression of leptin and the leptin receptor as a marker of breast cancer progression: possible role of obesity-related stimuli

PURPOSE: Recent in vitro studies suggested that the autocrine leptin loop might contribute to breast cancer development by enhancing cell growth and survival. To evaluate whether the leptin system could become a target in breast cancer therapy, we examined the expression of leptin and its receptor (ObR) in primary and metastatic breast cancer and noncancer mammary epithelium. We also studied whether the expression of leptin/ObR in breast cancer can be induced by obesity-related stimuli, such as elevated levels of insulin, insulin-like growth factor-I (IGF-I), estradiol, or hypoxic conditions. EXPERIMENTAL DESIGN: The expression of leptin and ObR was examined by immunohistochemistry in 148 primary breast cancers and 66 breast cancer metastases as well as in 90 benign mammary lesions. The effects of insulin, IGF-I, estradiol, and hypoxia on leptin and ObR mRNA expression were assessed by reverse transcription-PCR in MCF-7 and MDA-MB-231 breast cancer cell lines. RESULTS: Leptin and ObR were significantly overexpressed in primary and metastatic breast cancer relative to noncancer tissues. In primary tumors, leptin positively correlated with ObR, and both biomarkers were most abundant in G3 tumors. The expression of leptin mRNA was enhanced by insulin and hypoxia in MCF-7 and MDA-MB-231 cells, whereas IGF-I and estradiol stimulated leptin mRNA only in MCF-7 cells. ObR mRNA was induced by insulin, IGF-I, and estradiol in MCF-7 cells and by insulin and hypoxia in MDA-MB-231 cells. CONCLUSIONS: Leptin and ObR are overexpressed in breast cancer, possibly due to hypoxia and/or overexposure of cells to insulin, IGF-I, and/or estradiol

Instantons on ALE spaces and orbifold partitions

We consider N=4 theories on ALE spaces of $A_{k-1}$ type. As is well known, their partition functions coincide with $A_{k-1}$ affine characters. We show that these partition functions are equal to the generating functions of some peculiar classes of partitions which we introduce under the name 'orbifold partitions'. These orbifold partitions turn out to be related to the generalized Frobenius partitions introduced by G. E. Andrews some years ago. We relate the orbifold partitions to the blended partitions and interpret explicitly in terms of a free fermion system.Comment: 28 pages, 10 figures; reference adde

Penner Type Matrix Model and Seiberg-Witten Theory

We discuss the Penner type matrix model recently proposed by Dijkgraaf and Vafa for a possible explanation of the relation between four-dimensional gauge theory and Liouville theory by making use of the connection of the matrix model to two-dimensional CFT. We first consider the relation of gauge couplings defined in UV and IR regimes of N_f = 4, N = 2 supersymmetric gauge theory being related as $q_{{\rm UV}}={\vartheta_2(q_{{\rm IR}})^4/\vartheta_3(q_{{\rm IR}})^4}$. We then use this relation to discuss the action of modular transformation on the matrix model and determine its spectral curve. We also discuss the decoupling of massive flavors from the N_f = 4 matrix model and derive matrix models describing asymptotically free N = 2 gauge theories. We find that the Penner type matrix theory reproduces correctly the standard results of N = 2 supersymmetric gauge theories.Comment: 22 pages; v2: references added, typos corrected; v3: a version to appear in JHE

ABJM theory as a Fermi gas

The partition function on the three-sphere of many supersymmetric Chern-Simons-matter theories reduces, by localization, to a matrix model. We develop a new method to study these models in the M-theory limit, but at all orders in the 1/N expansion. The method is based on reformulating the matrix model as the partition function of an ideal Fermi gas with a non-trivial, one-particle quantum Hamiltonian. This new approach leads to a completely elementary derivation of the N^{3/2} behavior for ABJM theory and N=3 quiver Chern-Simons-matter theories. In addition, the full series of 1/N corrections to the original matrix integral can be simply determined by a next-to-leading calculation in the WKB or semiclassical expansion of the quantum gas, and we show that, for several quiver Chern-Simons-matter theories, it is given by an Airy function. This generalizes a recent result of Fuji, Hirano and Moriyama for ABJM theory. It turns out that the semiclassical expansion of the Fermi gas corresponds to a strong coupling expansion in type IIA theory, and it is dual to the genus expansion. This allows us to calculate explicitly non-perturbative effects due to D2-brane instantons in the AdS background.Comment: 52 pages, 11 figures. v3: references, corrections and clarifications added, plus a footnote on the relation to the recent work by Hanada et a

Quantization of Integrable Systems and a 2d/4d Duality

We present a new duality between the F-terms of supersymmetric field theories defined in two- and four-dimensions respectively. The duality relates N=2 supersymmetric gauge theories in four dimensions, deformed by an Omega-background in one plane, to N=(2,2) gauged linear sigma-models in two dimensions. On the four dimensional side, our main example is N=2 SQCD with gauge group SU(L) and 2L fundamental flavours. Using ideas of Nekrasov and Shatashvili, we argue that the Coulomb branch of this theory provides a quantization of the classical Heisenberg SL(2) spin chain. Agreement with the standard quantization via the Algebraic Bethe Ansatz implies the existence of an isomorphism between the chiral ring of the 4d theory and that of a certain two-dimensional theory. The latter can be understood as the worldvolume theory on a surface operator/vortex string probing the Higgs branch of the same 4d theory. We check the proposed duality by explicit calculation at low orders in the instanton expansion. One striking consequence is that the Seiberg-Witten solution of the 4d theory is captured by a one-loop computation in two dimensions. The duality also has interesting connections with the AGT conjecture, matrix models and topological string theory where it corresponds to a refined version of the geometric transition.Comment: 51 pages, 7 figures. Additional comments, minor improvements and references adde

Classical conformal blocks from TBA for the elliptic Calogero-Moser system

The so-called Poghossian identities connecting the toric and spherical blocks, the AGT relation on the torus and the Nekrasov-Shatashvili formula for the elliptic Calogero-Moser Yang's (eCMY) functional are used to derive certain expressions for the classical 4-point block on the sphere. The main motivation for this line of research is the longstanding open problem of uniformization of the 4-punctured Riemann sphere, where the 4-point classical block plays a crucial role. It is found that the obtained representation for certain 4-point classical blocks implies the relation between the accessory parameter of the Fuchsian uniformization of the 4-punctured sphere and the eCMY functional. Additionally, a relation between the 4-point classical block and the $N_f=4$, ${\sf SU(2)}$ twisted superpotential is found and further used to re-derive the instanton sector of the Seiberg-Witten prepotential of the $N_f=4$, ${\sf SU(2)}$ supersymmetric gauge theory from the classical block.Comment: 25 pages, no figures, latex+JHEP3, published versio

Non-compact Topological Branes on Conifold

We consider non-compact branes in topological string theories on a class of Calabi-Yau spaces including the resolved conifold and its mirror. We compute the amplitudes of the insertion of non-compact Lagrangian branes in the A-model on the resolved conifold in the context of the topological vertex as well as the melting crystal picture. They all agree with each other and also agree with the results from Chern-Simons theory, supporting the large N duality. We find that they obey the Schr\"odinger equation confirming the wavefunction behavior of the amplitudes. We also compute the amplitudes of the non-compact B-branes in the DV matrix model which arises as a B-model open string field theory on the mirror manifold of the deformed conifold. We take the large N duality to consider the B-model on the mirror of the resolved conifold and confirm the wave function behavior of this amplitude. We find appropriate descriptions of non-compact branes in each model, which give complete agreements among those amplitudes and clarify the salient features including the role of symmetries toward these agreements.Comment: 32 pages, 9 figures, a reference added, typos fixe

Absence of system xc⁻ on immune cells invading the central nervous system alleviates experimental autoimmune encephalitis

Background: Multiple sclerosis (MS) is an autoimmune demyelinating disease that affects the central nervous system (CNS), leading to neurodegeneration and chronic disability. Accumulating evidence points to a key role for neuroinflammation, oxidative stress, and excitotoxicity in this degenerative process. System x(c)- or the cystine/glutamate antiporter could tie these pathological mechanisms together: its activity is enhanced by reactive oxygen species and inflammatory stimuli, and its enhancement might lead to the release of toxic amounts of glutamate, thereby triggering excitotoxicity and neurodegeneration. Methods: Semi-quantitative Western blotting served to study protein expression of xCT, the specific subunit of system x(c)-, as well as of regulators of xCT transcription, in the normal appearing white matter (NAWM) of MS patients and in the CNS and spleen of mice exposed to experimental autoimmune encephalomyelitis (EAE), an accepted mouse model of MS. We next compared the clinical course of the EAE disease, the extent of demyelination, the infiltration of immune cells and microglial activation in xCT-knockout (xCT(-/-)) mice and irradiated mice reconstituted in xCT(-/-) bone marrow (BM), to their proper wild type (xCT(+/+)) controls. Results: xCT protein expression levels were upregulated in the NAWM of MS patients and in the brain, spinal cord, and spleen of EAE mice. The pathways involved in this upregulation in NAWM of MS patients remain unresolved. Compared to xCT(+/+) mice, xCT(-/-) mice were equally susceptible to EAE, whereas mice transplanted with xCT(-/-) BM, and as such only exhibiting loss of xCT in their immune cells, were less susceptible to EAE. In none of the above-described conditions, demyelination, microglial activation, or infiltration of immune cells were affected. Conclusions: Our findings demonstrate enhancement of xCT protein expression in MS pathology and suggest that system x(c)- on immune cells invading the CNS participates to EAE. Since a total loss of system x(c)- had no net beneficial effects, these results have important implications for targeting system x(c)- for treatment of MS