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The purpose of this manuscript is to derive new convergence results for several subgradient methods applied to minimizing nonsmooth convex functions with Hölderian growth. The growth condition is satisfied in many applications and includes functions with quadratic growth and weakly sharp minima as special cases. To this end there are three main contributions. First, for a constant and sufficiently small stepsize, we show that the subgradient method achieves linear convergence up to a certain region including the optimal set, with error of the order of the stepsize. Second, if appropriate problem parameters are known, we derive a decaying stepsize which obtains a much faster convergence rate than is suggested by the classical O (1 / k) result for the subgradient method. Thirdly we develop a novel "descending stairs" stepsize which obtains this faster convergence rate and also obtains linear convergence for the special case of weakly sharp functions. We also develop an adaptive variant of the "descending stairs" stepsize which achieves the same convergence rate without requiring an error bound constant which is difficult to estimate in practice. [ABSTRACT FROM AUTHOR]

Ineffective spatial-temporal motion feature pooling has been a fundamental bottleneck for human action recognition/detection for decades. Previous pooling schemes such as global, spatial-temporal pyramid, or human and object centric pooling fail to capture discriminative motion patterns because informative movements only occur in specific regions of the human body, that depend on the type of action being performed. Global (holistic) motion feature pooling methods therefore often result in an action representation with limited discriminative capability. To address this fundamental limitation, we propose an adaptive motion feature pooling scheme that utilizes human poses as side information. Such poses can be detected for instance in assisted living and indoor smart surveillance scenarios. Taking both video sub-volumes for pooling and human pose types as hidden variables, we formulate the motion feature pooling problem as a latent structural learning problem where the relationship between the discriminative pooling video sub-volumes and the pose types is learned. The resulting pose adaptive motion feature pooling scheme is extensively tested on assisted living and smart surveillance datasets and on general action recognition benchmarks. Improved action recognition and detection performances are demonstrated. [ABSTRACT FROM AUTHOR]

Hypophosphatasia is an inheritable disorder characterised by defective bone mineralisation due to the impaired activity of tissue-non-specific alkaline phosphatase (AP). Clinical presentation ranges from stillbirth without mineralised bone to pathological fractures in late adulthood. During childhood, the main manifestations include rickets, growth delay and dental problems. Fractures and bone pain usually characterise the adult form. A 9-year-old girl was referred for repetitive fractures after minimal trauma. She had normal growth, normal sclerae, no rickets and minimal dental abnormalities. Her sister had also presented fractures. The proband, her sister and mother had low total and bone-specific AP levels and E435K mutation in exon 12 of the liver/bone/kidney AP gene. Low AP levels must lead to genetic analysis. Bone fragility and repetitive fractures may be symptoms of hypophosphatasia in childhood, which must not be neglected. Associated factors such as vitamin D or calcium deficiency must be prevented. In conclusion, hypophosphatasia must not be forgotten as an aetiological factor of repetitive fractures or bone pain in children and AP activity should be checked accurately. [ABSTRACT FROM AUTHOR]

In congenital hyperinsulinism of infancy (CHI), the loss of K-ATP channels (composed of Kir6.2 and SUR1 subunits) in β cells induces permanent insulin secretion and severe hypoglycaemia. By contrast, Sur1 −/− mice do not present such defects. We have investigated the impact of Sur1 gene inactivation on mouse islet cell morphology, structure and basic physiology. Pancreata were collected from young, adult and old wild-type (WT) and Sur1 −/− mice. After immunostaining for hormone, the total endocrine tissue, cell proportion, cell size and intra-insular distribution, hormone content and Glut-2 expression were quantified by morphometry. Basic physiological parameters were also measured. In young Sur1 −/− mice, the total endocrine tissue and proportion of β cells were higher ( P<0.05) than in WT mice, whereas the proportion of δ cells was lower ( P<0.01). In old Sur1 −/− mice, α cells were frequently located in the central regions of islets (unlike WT islets) and their proportion was increased ( P<0.05). Glut-2 protein and mRNA levels were lower in old Sur1 −/− islets ( P<0.02). Insulinaemia, fasting insulin and glucagon contents were equivalent in both groups of pancreata. Thus, the islets of Sur1 −/− mice present morphological modifications that have not been described in CHI and that might reflect an adaptive mechanism controlling insulin secretion in these mice. [ABSTRACT FROM AUTHOR]

Detecting fine-grained human action from video sequence is challenging. In this work, we propose to decompose this difficult analytic problem into two sequential tasks with increasing granularity. Firstly, we infer the coarse interaction status, i.e., which object is being manipulated and where the interaction occurs. To address the issue of frequent mutual occlusions during manipulation, we propose an interaction tracking framework in which hand (object) position and interaction status are jointly tracked by explicitly modeling the occlusion context. Secondly, for a given query sequence, the inferred interaction status is utilized to efficiently identify a small set of candidate matching sequences from the annotated training set. Frame-level action labels are then transferred to the query sequence by setting up the matching between the query and candidate sequences. Comprehensive experiments on two challenging fine-grained activity datasets show that: (1) the proposed interaction tracking approach achieves high tracking accuracy for multiple mutually occluded objects (hands) during manipulation action; and (2) the proposed multiple granularity analysis framework achieves superior action detection performance improvement over state-of-the-art methods. [ABSTRACT FROM AUTHOR]

Earlier and more reliable detection of drug-induced kidney injury would improve clinical care and help to streamline drug-development. As the current standards to monitor renal function, such as blood urea nitrogen (BUN) or serum creatinine (SCr), are late indicators of kidney injury, we conducted ten nonclinical studies to rigorously assess the potential of four previously described nephrotoxicity markers to detect drug-induced kidney and liver injury. Whereas urinary clusterin outperformed BUN and SCr for detecting proximal tubular injury, urinary total protein, cystatin C and β2-microglobulin showed a better diagnostic performance than BUN and SCr for detecting glomerular injury. Gene and protein expression analysis, in-situ hybridization and immunohistochemistry provide mechanistic evidence to support the use of these four markers for detecting kidney injury to guide regulatory decision making in drug development. The recognition of the qualification of these biomarkers by the EMEA and FDA will significantly enhance renal safety monitoring. [ABSTRACT FROM AUTHOR]

Antibodies targeting IL-17A or its receptor IL-17RA show unprecedented efficacy in the treatment of autoimmune diseases such as psoriasis. These therapies, by neutralizing critical mediators of immunity, may increase susceptibility to infections. Here, we compared the effect of antibodies neutralizing IL-17A, IL-17F or TNFα on murine host responses to Mycobacterium tuberculosis infection by evaluating lung transcriptomic, microbiological and histological analyses. Coinciding with a significant increase of mycobacterial burden and pathological changes following TNFα blockade, gene array analyses of infected lungs revealed major changes of inflammatory and immune gene expression signatures 4 weeks post-infection. Specifically, gene expression associated with host-pathogen interactions, macrophage recruitment, activation and polarization, host-antimycobacterial activities, immunomodulatory responses, as well as extracellular matrix metallopeptidases, were markedly modulated by TNFα blockade. IL-17A or IL-17F neutralization elicited only mild changes of few genes without impaired host resistance four weeks after M. tuberculosis infection. Further, the absence of both IL-17RA and IL-22 pathways in genetically deficient mice did not profoundly compromise host control of M. tuberculosis over a 6-months period, ruling out potential compensation between these two pathways, while TNFα-deficient mice succumbed rapidly. These data provide experimental confirmation of the low clinical risk of mycobacterial infection under anti-IL-17A therapy, in contrast to anti-TNFα treatment. [ABSTRACT FROM AUTHOR]