Calculation of the Stability Index in Parameter-Dependent Calculus of Variations Problems: Buckling of a Twisted Elastic Strut

We consider the problem of minimizing the energy of an inextensible elastic strut with length 1 subject to an imposed twist angle and force. In a standard calculus of variations approach, one first locates equilibria by solving the Euler--Lagrange ODE with boundary conditions at arclength values 0 and 1. Then one classifies each equilibrium by counting conjugate points, with local minima corresponding to equilibria with no conjugate points. These conjugate points are arclength values $\sigma \le 1$ at which a second ODE (the Jacobi equation) has a solution vanishing at $0$ and $\sigma$. Finding conjugate points normally involves the numerical solution of a set of initial value problems for the Jacobi equation. For problems involving a parameter $\lambda$, such as the force or twist angle in the elastic strut, this computation must be repeated for every value of $\lambda$ of interest. Here we present an alternative approach that takes advantage of the presence of a parameter $\lambda$. Rather than search for conjugate points $\sigma \le 1$ at a fixed value of $\lambda$, we search for a set of special parameter values $\lambda_m$ (with corresponding Jacobi solution \bfzeta^m) for which $\sigma=1$ is a conjugate point. We show that, under appropriate assumptions, the index of an equilibrium at any $\lambda$ equals the number of these \bfzeta^m for which \langle \bfzeta^m, \Op \bfzeta^m \rangle < 0, where \Op is the Jacobi differential operator at $\lambda$. This computation is particularly simple when $\lambda$ appears linearly in \Op. We apply this approach to the elastic strut, in which the force appears linearly in \Op, and, as a result, we locate the conjugate points for any twisted unbuckled rod configuration without resorting to numerical solution of differential equations. In addition, we numerically compute two-dimensional sheets of buckled equilibria (as the two parameters of force and twist are varied) via a coordinated family of one-dimensional parameter continuation computations. Conjugate points for these buckled equilibria are determined by numerical solution of the Jacobi ODE

CATALOGUE OF PUBLICATIONS IN MAMMALOGY

The catalogue provided herein is a complete bibliography of titles relating to mammalogy published since 1946 by the Museum of Natural History. The contributions listed cover a broad spectrum; some titles are technical, whereas others are of more general interest. The catalogue is designed to provide a useful reference and to facilitate the acquisition of mammalogical publications by interested persons

Two-photon imaging of cancer cell extravasation in live mice

Abstract MDA-MB-231 breast cancer cells were engineered to express cytoplasmic paxillin-GFP and nuclear H2B-mCherry. In order to image extravasation, the cancer cells were injected in the blood stream of nude mice. Using 2-photon excitation microscopy we can simultaneously excite the two probes and also visualize the autofluorescence of tissues. A skin flap was opened to visualize blood vessels and recognize the position of the cancer cells. Two-photon imaging showed that after an initial phase in which the cells are non-adherent, some cells spread on the internal surface of the capillaries. Days later some cells started to appear on the external side of the capillary. The extravasated cells extend very long protrusions into the tissue. The goal was to determine if at the end of the long protrusion, if it is possible to observe the formation of focal adhesions by imaging paxillin-GFP. Preliminary results show that when cells start to adhere to the blood vessel wall they form focal adhesions as determined by the characteristic elongated features observed in the paxillin-GFP channel. New approaches will allow the tracking of the tip of the protrusion to determine if focal adhesions are forming there as the cells extravasate. This is important in establishing the mechanism of cell extravasation and migration in tissues. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1412. doi:10.1158/1538-7445.AM2011-141

Glycemic Variability Predicts Inflammation in Adolescents with Type 1 Diabetes

Background: Adolescents with type 1 diabetes (T1D) have increased risk of cardiovascular disease as well as elevations in biomarkers of systemic inflammation, plasma protein oxidation and vascular endothelial injury. It is unclear whether hyperglycemia itself, or variations in blood glucose are predictors of these abnormalities. Methods: This study was designed to determine the relationship of inflammatory (C-reactive protein, CRP), oxidative (total anti-oxidative capacity, TAOC) and endothelial injury (soluble intracellular adhesion molecule 1, sICAM1) markers to glycemic control measures from 3 days of continuous glucose monitoring (CGM) and to hemoglobin A1c (HbA1c), and HbA1c×duration area under the curve (A1cDur). Results: Seventeen adolescents (8 F/9M; age, 13.1±1.6 years (mean±SD); duration, 4.8±3.8 years, BMI, 20.3±3.1 kg/m2; A1c, 8.3±1.2%) were studied. Log CRP but was not related to age, duration, body mass index (BMI), HbA1c, or A1cDUR. TAOC increased as logA1cDUR increased (n=13, r=0.61, p=0.028). CRP and sICAM were not related to CGM average glucose but log CRP increased as 3 day glucose standard deviation increased (r=0.66, p=0.006). TAOC increased as glucose standard deviation increased (r=0.63, p=0.028). Conclusions: Increased glucose variability is associated with increased inflammation in adolescents withT1D. Increased TAOC with increasing variability may be an effort to compensate for the ongoing oxidative stress

Hyperglycemia Increases Muscle Blood Flow and Alters Endothelial Function in Adolescents with Type 1 Diabetes

Alterations of blood flow and endothelial function precede development of complications in type 1 diabetes. The effects of hyperglycemia on vascular function in early type 1 diabetes are poorly understood. To investigate the effect of hyperglycemia on forearm vascular resistance (FVR) and endothelial function in adolescents with type 1 diabetes, FVR was measured before and after 5 minutes of upper arm arterial occlusion using venous occlusion plethysmography in (1) fasted state, (2) euglycemic state (~90 mg/dL; using 40 mU/m2/min insulin infusion), and (3) hyperglycemic state (~200 mg/dL) in 11 adolescents with type 1 diabetes. Endothelial function was assessed by the change in FVR following occlusion. Seven subjects returned for a repeat study with hyperglycemia replaced by euglycemia. Preocclusion FVR decreased from euglycemia to hyperglycemia (P = 0.003). Postocclusion fall in FVR during hyperglycemia was less than during euglycemia (P = 0.002). These findings were not reproduced when hyperglycemia was replaced with a second euglycemia. These results demonstrate that acute hyperglycemia causes vasodilation and alters endothelial function in adolescents with type 1 diabetes. In addition they have implications for future studies of endothelial function in type 1 diabetes and provide insight into the etiology of macrovascular and microvascular complications of type 1 diabetes

Spin Forming of an Aluminum 2219-T6 Aft Bulkhead for the Orion Multi-Purpose Crew Vehicle: Phase II Supplemental Report

The principal focus of this project was to assist the Orion Multi-Purpose Crew Vehicle (MPCV) Program in developing a spin forming fabrication process for manufacture of the aft bulkhead of the pressure vessel. The spin forming process will enable a single piece aluminum (Al) 2219 aft bulkhead which will eliminate the current multiple piece welded construction, simplify fabrication, and lead to an enhanced design that will reduce vehicle weight by eliminating welds. Phase I of this assessment explored spin forming the single-piece forward pressure vessel bulkhead from aluminum-lithium 2195

Primjena intra-aortne balonske pumpe pri kardiogenom šoku uzrokovanom trovanjem aluminijevim fosfidom

Aluminium phosphide (AlP) is a highly toxic pesticide that inhibits cytochrome oxidase c and causes oxidative stress. Death results from refractory cardiogenic shock due to myocardial dysfunction. There is very little information regarding extracorporeal life support in severe AlP poisoning. Although several therapies are available, none are curative. We report on the use of an intra-aortic balloon pump (IABP) in a 24-year-old woman brought to our hospital after an intentional ingestion of a tablet of AlP (3 g), which caused refractory AlP-induced cardiogenic shock and acute respiratory distress syndrome (ARDS). The patient underwent gastric lavage with potassium permanganate, received sodium bicarbonate intravenously, and was admitted to the intensive care unit. Echocardiography at 36 h post ingestion showed a left ventricular ejection fraction (LVEF) of <20 %. An IABP was inserted and the patient’s vital signs stabilised. After eight days, the IABP was removed and on day 20, the patient’s LVEF increased to 50 %. IABP was successfully used and may improve future prognoses for severely poisoned AlP patients with refractory cardiogenic shock. We encourage clinical toxicologists to examine this new treatment.Aluminijev fosfid (AlP) visoko je toksičan pesticid koji inhibira citokrom c oksidazu i uzrokuje oksidacijski stres. Smrt nastupa nakon refraktornog kardiogenog šoka uslijed miokardijalne disfunkcije. Vrlo je malo literature o izvantjelesnim sredstvima održavanja na životu nakon otrovanja AlP-om. Iako postoji određeni broj terapija, nijedna ne vodi do potpunoga izlječenja. Prikazan je slučaj uporabe intra-aortne balonske pumpe (IABP) kod 24-godišnje žene otrovane namjernim uzimanjem AlP-a (3 g), što je uzrokovalo refraktorni kardiogeni šok i akutni respiratorni distres sindrom (ARDS). Pacijentici je želudac ispran kalijevim permanganatom, intravenozno je primila natrijev bikarbonat te je zbrinuta u jedinici za intenzivnu skrb. Ehokardiografija 36 h nakon uzimanja tablete AlP-a pokazala je ejekcijsku frakciju lijevog ventrikula (LVEF) od < 20 %. Nakon umetanja IABP-a vitalni su se znakovi su se poboljšali. Pumpa je uklonjena nakon osam dana, a dvadesetoga dana LVEF je iznosio 50 %. Naši rezultati pokazuju da bi primjena IABP-a mogla poboljšati prognoze pacijenata s refraktornim kardiogenim šokom uslijed teškog otrovanja s AlPom. Stoga preporučujemo kliničkim toksikolozima da razmotre ovaj novi tretman

Temozolomide combined with irinotecan caused regression in an adult pleomorphic rhabdomyosarcoma patient-derived orthotopic xenograft (PDOX) nude-mouse model.

Adult pleomorphic rhabdomyosarcoma (RMS) is a rare and recalcitrant, highly-malignant mesenchymal tumor in need of improved therapeutic strategies. Our laboratory pioneered the patient-derived orthotopic xenograft (PDOX) nude mouse model with the technique of surgical orthotopic implantation (SOI). We previously described the development of a PDOX model of adult pleomorphic RMS where the tumor behaved similar to the patient donor. A high-grade pleomorphic rhabdomyosarcoma from a striated muscle was previously grown orthotopically in the right biceps-femoris muscle of nude mice to establish the PDOX model. In the present study, the PDOX models were randomized into the following treatment groups when tumor volume reached 100 mm3: G1, control without treatment; G2, cyclophosphamide (CPA) 140 mg/kg, intraperitoneal (i.p.) injection, weekly, for 3 weeks; G3, temozolomide (TEM), 25 mg/kg, per oral (p.o.), daily, for 21 days; G4, temozolomide (TEM) 25 mg/kg, p.o., daily, for 21 days combined with irinotecan (IRN), 4 mg/kg, i.p., daily for 21 days. After 3 weeks, treatment of PDOX with TEM combined with IRN was so powerful that it resulted in tumor regression and the smallest tumor volume compared to other groups. The RMS PDOX model should be of use to design the treatment program for the patient and for drug discovery and evaluation for this recalcitrant tumor type

Toxicology and efficacy of tumor-targeting Salmonella typhimurium A1-R compared to VNP 20009 in a syngeneic mouse tumor model in immunocompetent mice.

Salmonella typhimurium&nbsp;A1-R (S.&nbsp;typhimurium A1-R) attenuated by leu and arg auxotrophy has been shown to target multiple types of cancer in mouse models. In the present study, toxicologic and biodistribution studies of tumor-targeting S.&nbsp;typhimurium A1-R and S.&nbsp;typhimurium VNP20009 (VNP 20009) were performed in a syngeneic tumor model growing in immunocompetent BALB/c mice. Single or multiple doses of S.&nbsp;typhimurium A1-R of 2.5 × 105 and 5 × 105 were tolerated. A single dose of 1 × 106 resulted in mouse death. S.&nbsp;typhimurium A1-R (5 × 105 CFU) was eliminated from the circulation, liver and spleen approximately 3-5 days after bacterial administration via the tail vein, but remained in the tumor in high amounts. S.&nbsp;typhimurium A1-R was cleared from other organs much more rapidly. S.&nbsp;typhimurium A1-R and VNP 20009 toxicity to the spleen and liver was minimal. S.&nbsp;typhimurium A1-R showed higher selective targeting to the necrotic areas of the tumors than VNP20009. S.&nbsp;typhimurium A1-R inhibited the growth of CT26 colon carcinoma to a greater extent at the same dose of VNP20009. In conclusion, we have determined a safe dose and schedule of S.&nbsp;typhimurium A1-R administration in BALB/c mice, which is also efficacious against tumor growth. The results of the present report indicate similar toxicity of S.&nbsp;typhimurium A1-R and VNP20009, but greater antitumor efficacy of S.&nbsp;typhimurium A1-R in an immunocompetent animal. Since VNP2009 has already proven safe in a Phase I clinical trial, the present results indicate the high clinical potential of S.&nbsp;typhimurium A1-R