Conformations, hydrodynamic interactions, and instabilities of sedimenting semiflexible filaments

The conformations and dynamics of semiflexible filaments subject to a homogeneous external (gravitational) field, e.g., in a centrifuge, are studied numerically and analytically. The competition between hydrodynamic drag and bending elasticity generates new shapes and dynamical features. We show that the shape of a semiflexible filament undergoes instabilities as the external field increases. We identify two transitions that correspond to the excitation of higher bending modes. In particular, for strong fields the filament stabilizes in a non-planar shape, resulting in a sideways drift or in helical trajectories. For two interacting filaments, we find the same transitions, with the important consequence that the new non-planar shapes have an effective hydrodynamic repulsion, in contrast to the planar shapes which attract themselves even when their osculating planes are rotated with respect to each other. For the case of planar filaments, we show analytically and numerically that the relative velocity is not necessarily due to a different drag of the individual filaments, but to the hydrodynamic interactions induced by their shape asymmetry.Comment: 9 pages, 7 figures in Soft Matter (2015

Urokinase Plasminogen Activator, uPa Receptor, and Its Inhibitor in Vernal Keratoconjunctivitis

PURPOSE. Plasminogen activators play a role, not only in fibrinolysis but also in events such as chemotaxis, collagen degradation, and cell spreading. The serine protease urokinase (uPA) is a potent chemoattractant for leukocytes that may be involved in the pathogenesis of severe forms of allergic conjunctivitis such as vernal keratoconjunctivitis (VKC). METHODS. Tear and peripheral blood samples were obtained from 20 patients with active VKC and from 19 normal subjects who formed the control group. Levels of plasminogen activity, uPA, tissue plasminogen activator (tPA), and their inhibitor, plasminogen activator inhibitor type-1 (PAI-1) were measured in tears and plasma of patients with VKC. The presence of tPA, uPA, and urokinase receptor (uPAR) in conjunctival tissues were evaluated by immunohistochemistry. uPA, uPAR, and PAI-1 expression and production were measured in conjunctival epithelial cell and fibroblast cultures treated with cytokines. RESULTS. Tear levels of uPA and tPA and tear plasminogen activity levels were significantly greater in patients with VKC than in control subjects. Increased staining for uPA and uPAR was found in VKC tissues compared with normal conjunctiva. Both conjunctival epithelial cells and fibroblasts demonstrated an increased expression of uPAR after exposure to IL-4 or -13, whereas uPA was highly expressed by epithelial cells exposed to IL-4. PAI-1 levels in culture medium were increased in IL-4-exposed epithelial cells compared to nonstimulated cells and were decreased in fibroblast culture. CONCLUSIONS. Increased expression of fibrinolytic system components and imbalance between plasminogen activators and PAI may be involved in the pathogenesis of severe allergic conjunctivitis, thus contributing to inflammatory cell migration and tissue remodeling. (Invest Ophthalmol Vis Sci. 2005;46: 1364‐1370) DOI:10.1167/iovs.04-119

Galectin-3 immunodetection in follicular thyroid neoplasms: a prospective study on fine-needle aspiration samples

Fine-needle aspiration cytology, which is well established to be accurate for the diagnosis of thyroid cancer, may be inconclusive for the follicular thyroid neoplasms. As galectin-3 was suggested to be a marker of malignant thyrocytes, we investigated whether this protein might be helpful in the diagnosis of aspirates classified as undeterminate by cytology. After establishing an easy processing of aspirates for galectin-3 immunodetection, a series of aspirates categorised as benign (n=63), malignant (n=17) or undeterminate (n=34) was prospectively analysed for galectin-3. Only the patients with malignant or undeterminate lesions underwent surgery. Most lesions (86%) diagnosed as malignant by cytology or after surgery were positive for galectin-3. The majority of lesions (94%) classified as benign by cytology or after surgery was negative for galectin-3. The positive and negative predictive values were 83 and 95%, respectively. When focusing on the undeterminate lesions, the sensitivity and specificity were 75 and 90%, respectively, while the positive and negative predictive values were 82 and 87%, respectively. The specificity and the positive predictive value were higher (100%) when considering the percentage of stained cells. Altogether these results show that galectin-3 constitutes a useful marker in the diagnosis of thyroid lesions classified as undeterminate by conventional cytology

Large needle aspiration biopsy and galectin-3 determination in selected thyroid nodules with indeterminate FNA-cytology

Thyroid fine-needle aspiration biopsy (FNA)-cytology is widely used for the preoperative characterisation of thyroid nodules but this task is difficult for follicular lesions, which often remain undefined. We propose a strategy for improving the preoperative characterisation of selected follicular thyroid proliferations, which is based on large needle aspiration biopsy (LNAB) and galectin-3 expression analysis. Eighty-five thyroid specimens were obtained by LNAB (20-gauge needles) from thyroid nodules with indeterminate follicular FNA-cytology. Aspirated material was processed as a tissue microbiopsy to obtain cell blocks for both cyto/histo-morphological evaluation and galectin-3 expression analysis, by using a purified monoclonal antibody to galectin-3 and a biotin-free immunoperoxidase staining method. Preoperative diagnosis was compared to the final histology. LNAB and cell-block technique allow a preliminary distinction between nodules with a homogeneous microfollicular/trabecular structure, as frequently observed in tumours, and lesions with mixed normo–micro–macrofollicular architecture, as observed in goitre. Furthermore, LNAB provides optimal substrates for galectin-3 expression analysis. Among 85 cases tested, 14 galectin-3-positive cases were discovered preoperatively (11 thyroid cancers and three adenomas confirmed at the final histology), whereas galectin-3-negative cases were 71 (one carcinoma and 70 benign proliferations at the final histology). Sensitivity, specificity and diagnostic accuracy of this integrated morphologic and phenotypic diagnostic approach were 91.6, 97.2 and 95.3%, respectively. In conclusion, LNAB plus galectin-3 expression analysis when applied preoperatively to selected thyroid nodules candidate to surgery can potentially reduce unnecessary thyroid resections

About the role of chaos and coarse graining in statistical mechanics

We discuss the role of ergodicity and chaos for the validity of statistical laws. In particular we explore the basic aspects of chaotic systems (with emphasis on the finite-resolution) on systems composed of a huge number of particles

Human sperm steer with second harmonics of the flagellar beat

Sperm are propelled by bending waves traveling along their flagellum. For steering in gradients of sensory cues, sperm adjust the flagellar waveform. Symmetric and asymmetric waveforms result in straight and curved swimming paths, respectively. Two mechanisms causing spatially asymmetric waveforms have been proposed: an average flagellar curvature and buckling. We image flagella of human sperm tethered with the head to a surface. The waveform is characterized by a fundamental beat frequency and its second harmonic. The superposition of harmonics breaks the beat symmetry temporally rather than spatially. As a result, sperm rotate around the tethering point. The rotation velocity is determined by the second-harmonic amplitude and phase. Stimulation with the female sex hormone progesterone enhances the second-harmonic contribution and, thereby, modulates sperm rotation. Higher beat frequency components exist in other flagellated cells; therefore, this steering mechanism might be widespread and could inspire the design of synthetic microswimmers