Effects of Malformed or Absent Valves to Lymphatic Fluid Transport and Lymphedema in Vivo in Mice

Lymph is primarily composed of fluid and proteins from the blood circulatory system that drain into the space surrounding cells, interstitial space. From the interstitial space, the fluid enters and circulates in the lymphatic system until it is delivered into the venous system. In contrast to the blood circulatory system, the lymphatic system lacks a central pumping organ dictating the predominant driving pressure and velocity of lymph. Transport of lymph via capillaries, pre-collecting and collecting lymphatic vessels relies on the synergy between pressure gradients, local tissue motion, valves and lymphatic vessel contractility. The direction of lymph transport is regulated by bicuspid valves distributed throughout pre-collecting and collecting lymphatic vessels. Effective transport of lymph into the venous system is of prime importance. Disruption of lymph transport, because of impaired lymphatic function, reduced numbers of vessels or valvular insufficiencies can have severe health consequences, including lymphedema for which current clinical therapies are not curative. The lymphatic valves are usually bicuspid, however, congenital malformations in the valve such as single leaflet valve formation and arrested lymphatic valve development are observed and can cause lymphedema. Here we employ 4-week-old mice to study the effects of valves and malformed valves on lymph transport shedding light into some of the potentially underlying consequences of lymphedema. Polyethylene glycol (PEG) coated latex particles were injected into the inguinal lymph node of anesthetized mice. Particle displacement measurements through efferent lymphatic vessels yielded velocity, wall shear stress, vorticity and strain of the efferent lymph flow field carrying lymph from subdermal inguinal lymph nodes. Lymphatic vessel endothelial Prox1 green fluorescent protein (GFP) marker enabled the detection of lymphatic vessel walls and valves. Flow field, flow velocity, flow rate, velocity profiles, wall shear stress, vorticity and strain values were compared in regions downstream of normal and malformed valves in two wild type mice. A Clec2-deficient mouse, which experiences lymphatic development defects and is used as a lymphedema model, was employed to further elucidate the lymphatic valves on transport. The absence of centralized pumping yields highly variable lymphatic flow cycles varying from one to fifteen seconds. The presence of lymphatic valves introduces boundary conditions that yield spatial and temporal flow gradients increasing the degree of complexity of lymph transport. The valves dictate the trajectory of the particles and promote the formation of recirculation zones. Even in the presence of valves, lymph flow commonly reverses. Congenital defects like a single leaflet valve lowers the lymph flow efficiency and promotes higher wall shear stress regions. Furthermore, the absence of functional valves in the Clec2-deficient mouse not displaying lymphedema yielded lymph flow lacking the pulsatility that characterizes normal lymphatic flow

Deviations from Matthiessen rule and resistivity saturation effects in Gd and Fe

According to earlier first-principles calculations, the spin-disorder contribution to the resistivity of rare-earth metals in the paramagnetic state is strongly underestimated if Matthiessen's rule is assumed to hold. To understand this discrepancy, the resistivity of paramagnetic Fe and Gd is evaluated by taking into account both spin and phonon disorder. Calculations are performed using the supercell approach within the linear muffin-tin orbital method. Phonon disorder is modeled by introducing random displacements of the atomic nuclei, and the results are compared with the case of fictitious Anderson disorder. In both cases the resistivity shows a nonlinear dependence on the square of the disorder potential, which is interpreted as a resistivity saturation effect. This effect is much stronger in Gd than in Fe. The non-linearity makes the phonon and spin-disorder contributions to the resistivity non-additive, and the standard procedure of extracting the spin-disorder resistivity by extrapolation from high temperatures becomes ambiguous. An "apparent" spin-disorder resistivity obtained through such extrapolation is in much better agreement with experiment compared to the results obtained by considering only spin disorder. By analyzing the spectral function of the paramagnetic Gd in the presence of Anderson disorder, the resistivity saturation is explained by the collapse of a large area of the Fermi surface due to the disorder-induced mixing between the electronic and hole sheets.Comment: 9 pages, 7 figure

Spectral signatures of thermal spin disorder and excess Mn in half-metallic NiMnSb

Effects of thermal spin disorder and excess Mn on the electronic spectrum of half-metallic NiMnSb are studied using first-principles calculations. Temperature-dependent spin disorder, introduced within the vector disordered local moment model, causes the valence band at the $\Gamma$ point to broaden and shift upwards, crossing the Fermi level and thereby closing the half-metallic gap above room temperature. The spectroscopic signatures of excess Mn on the Ni, Sb, and empty sites (Mn$_\mathrm{Ni}$, Mn$_\mathrm{Sb}$, and Mn$_\mathrm{E}$) are analyzed. Mn$_\mathrm{Ni}$ is spectroscopically invisible. The relatively weak coupling of Mn$_\mathrm{Sb}$ and Mn$_\mathrm{E}$ spins to the host strongly deviates from the Heisenberg model, and the spin of Mn$_\mathrm{E}$ is canted in the ground state. While the half-metallic gap is preserved in the collinear ground state of Mn$_\mathrm{Sb}$, thermal spin disorder of the weakly coupled Mn$_\mathrm{Sb}$ spins destroys it at low temperatures. This property of Mn$_\mathrm{Sb}$ may be the source of the observed low-temperature transport anomalies.Comment: 5 pages, 7 figures, updated version with minor revisions and an additional figure, accepted in Phys. Rev. B (Rapid Communication

Gossip Codes for Fingerprinting: Construction, Erasure Analysis and Pirate Tracing

This work presents two new construction techniques for q-ary Gossip codes from tdesigns and Traceability schemes. These Gossip codes achieve the shortest code length specified in terms of code parameters and can withstand erasures in digital fingerprinting applications. This work presents the construction of embedded Gossip codes for extending an existing Gossip code into a bigger code. It discusses the construction of concatenated codes and realisation of erasure model through concatenated codes.Comment: 28 page

A COMPARATIVE CLINICAL STUDY ON SHARKARA MISHRITA DUGDA NASYA AND MURCHITA GHRITA NASYA ON ARDHAVABHEDAKA W.S.R. TO MIGRAINE

Ardhavabhedaka is one among the 11 types of Shirorogas described in Ayurvedic classical texts. It is a type of headache where pain is localized to one half of the head. It can be correlated with migraine based on the similarity in etiology, pathology, symptoms and treatment principles. This study is conducted with the aim to compare the effect of ‘Sharkara Mishrita Dugdha Nasya’ and ‘Murchita Gritha Nasya’ in the management of Ardhavabhedaka. Two groups of 15 patients each were administered these two types of Nasya drugs for seven days. Patients were assessed on the basis of clinical parameters. Results show good effect on all symptoms of Ardhavabhedaka in both groups but Murchita Ghrita Nasya show better effect than Sharkara Mishrita Dugdha Nasya.Among 15 patients in Group-A, 7 patients (36%) showed good response and among 20 patients in Group-B, 3 patients (16 %) showed good response after the treatment. The response obtained after 28 days of treatment and the study reveals that in Group – B Murchita Ghrita Nasya shows very good response in treating the Ardhavabhedaka. Sharkara acts as Vatapitta hara, Dugdha & Murchita Ghrita acts as Tridoshaghna