Identifying and attacking the saddle point problem in high-dimensional non-convex optimization

A central challenge to many fields of science and engineering involves minimizing non-convex error functions over continuous, high dimensional spaces. Gradient descent or quasi-Newton methods are almost ubiquitously used to perform such minimizations, and it is often thought that a main source of difficulty for these local methods to find the global minimum is the proliferation of local minima with much higher error than the global minimum. Here we argue, based on results from statistical physics, random matrix theory, neural network theory, and empirical evidence, that a deeper and more profound difficulty originates from the proliferation of saddle points, not local minima, especially in high dimensional problems of practical interest. Such saddle points are surrounded by high error plateaus that can dramatically slow down learning, and give the illusory impression of the existence of a local minimum. Motivated by these arguments, we propose a new approach to second-order optimization, the saddle-free Newton method, that can rapidly escape high dimensional saddle points, unlike gradient descent and quasi-Newton methods. We apply this algorithm to deep or recurrent neural network training, and provide numerical evidence for its superior optimization performance.Comment: The theoretical review and analysis in this article draw heavily from arXiv:1405.4604 [cs.LG

Golden Horn Estuary: Description of the ecosystem and an attempt to assess its ecological quality status using various classification metrics

In this paper, we describe the pelagic and benthic ecosystem of the Golden Horn  estuary opening into the Marmara Sea. To improve the water quality of the estuary, which had long been subject to severe anthropogenic pollution (industrial, chemical, shipping),  industrial facilities were moved from the estuary in the 1980s, followed by a rehabilitation plan in the 1990s. Our results, based on chemical parameters and phytoplankton showed some signs of improvement of water conditions in the upper layer. However, macrozoobenthic findings of this study did not reflect such a recovery in bottom life.An approach to the Ecological Quality Status (EQS) assessment was performed by applying the biotic indices BENTIX, AMBI, BOPA, BO2A. Our final assessment was based on 'expert-judgements' and revealed a very disturbed overall ecosystem with 'bad' EQS for the station at the head of the estuary,  'poor' in the rest of the estuary and 'moderate' EQS only in the middle station

Engineered Protein Polymer-Gold Nanoparticle Hybrid Materials for Small Molecule Delivery

We have fabricated protein polymer-gold nanoparticle (P-GNP) nanocomposites that exhibit enhanced binding and delivery properties of the small hydrophobic molecule drug, curcumin, to the model breast cancer cell line, MCF-7. These hybrid biomaterials are constructed via in situ GNP templated-synthesis with genetically engineered histidine tags. The P-GNP nanocomposites exhibit enhanced small molecule loading, sustained release and increased uptake by MCF-7 cells. When compared to the proteins polymers alone, the P-GNPs demonstrate a greater than 7-fold increase in curcumin binding, a nearly 50% slower release profile and more than 2-fold increase in cellular uptake of curcumin. These results suggest that P-GNP nanocomposites serve as promising candidates for drug delivery vehicles

Role of a Novel Heparanase Inhibitor on the Balance between Apoptosis and Autophagy in U87 Human Glioblastoma Cells

Background: Heparanase (HPSE) is an endo-& beta;-glucuronidase that cleaves heparan sulfate side chains, leading to the disassembly of the extracellular matrix, facilitating cell invasion and metastasis dissemination. In this research, we investigated the role of a new HPSE inhibitor, RDS 3337, in the regulation of the autophagic process and the balance between apoptosis and autophagy in U87 glioblastoma cells. Methods: After treatment with RDS 3337, cell lysates were analyzed for autophagy and apoptosis-related proteins by Western blot. Results: We observed, firstly, that LC3II expression increased in U87 cells incubated with RDS 3337, together with a significant increase of p62/SQSTM1 levels, indicating that RDS 3337 could act through the inhibition of autophagic-lysosomal flux of LC3-II, thereby leading to accumulation of lipidated LC3-II form. Conversely, the suppression of autophagic flux could activate apoptosis mechanisms, as revealed by the activation of caspase 3, the increased level of cleaved Parp1, and DNA fragmentation. Conclusions: These findings support the notion that HPSE promotes autophagy, providing evidence that RDS 3337 blocks autophagic flux. It indicates a role for HPSE inhibitors in the balance between apoptosis and autophagy in U87 human glioblastoma cells, suggesting a potential role for this new class of compounds in the control of tumor growth progression

Development and Validation of the Parent-Initiated Motivational Climate in Individual Sport Competition Questionnaire

This paper presents a series of studies that progresses the development and validation of the Parent-Initiated Motivational Climate in Individual Sport Competition Questionnaire (MCISCQ-Parent). Study 1 examined the face and content validity of an initial pool of 26 items based on the principles of achievement goal theory and prior research. In Study 2, data from an adolescent sample of individual sport athletes was subjected to an exploratory factor analysis (EFA) of items pertaining to the perceived task and ego involving characteristics of fathers and mothers in the competition setting. Study 3 tested the factor structure of the MCISCQ-Parent through confirmatory factor analysis (CFA) in a further youth athlete sample. Following appropriate CFA-related modifications, good goodness of fit indices emerged for the father- (three factor-model) and mother-related (two factor-model) dimensions of motivational climate. In Study 4, a further CFA was conducted and provided additional evidence for the revised factor structure of the MCISCQ-Parent, convergent and discriminant validity, and internal consistency. Finally, Study 5 provided support for the concurrent validity of the MCISCQ-Parent by demonstrating significant relationships between MCISCQ-Parent subscales and task and ego orientation, athlete engagement, and perceived social support. In sum, we present the MCISCQ-Parent as a measure with promising psychometric properties, and specifically to those applied researchers interested in assessing the quality of motivation-related parental involvement perceived by young athletes in the competition setting

LOFAR discovery of a double radio halo system in Abell 1758 and radio/X-ray study of the cluster pair

Radio halos and radio relics are diffuse synchrotron sources that extend over Mpc-scales and are found in a number of merger galaxy clusters. They are believed to form as a consequence of the energy that is dissipated by turbulence and shocks in the intra-cluster medium (ICM). However, the precise physical processes that generate these steep synchrotron spectrum sources are still poorly constrained. We present a new LOFAR observation of the double galaxy cluster Abell 1758. This system is composed of A1758N, a massive cluster hosting a known giant radio halo, and A1758S, which is a less massive cluster whose diffuse radio emission is confirmed here for the first time. Our observations have revealed a radio halo and a candidate radio relic in A1758S, and a suggestion of emission along the bridge connecting the two systems which deserves confirmation. We combined the LOFAR data with archival VLA and GMRT observations to constrain the spectral properties of the diffuse emission. We also analyzed a deep archival Chandra observation and used this to provide evidence that A1758N and A1758S are in a pre-merger phase. The ICM temperature across the bridge that connects the two systems shows a jump which might indicate the presence of a transversal shock generated in the initial stage of the merger

CLP1 Founder Mutation Links tRNA Splicing and Maturation to Cerebellar Development and Neurodegeneration

SummaryNeurodegenerative diseases can occur so early as to affect neurodevelopment. From a cohort of more than 2,000 consanguineous families with childhood neurological disease, we identified a founder mutation in four independent pedigrees in cleavage and polyadenylation factor I subunit 1 (CLP1). CLP1 is a multifunctional kinase implicated in tRNA, mRNA, and siRNA maturation. Kinase activity of the CLP1 mutant protein was defective, and the tRNA endonuclease complex (TSEN) was destabilized, resulting in impaired pre-tRNA cleavage. Germline clp1 null zebrafish showed cerebellar neurodegeneration that was rescued by wild-type, but not mutant, human CLP1 expression. Patient-derived induced neurons displayed both depletion of mature tRNAs and accumulation of unspliced pre-tRNAs. Transfection of partially processed tRNA fragments into patient cells exacerbated an oxidative stress-induced reduction in cell survival. Our data link tRNA maturation to neuronal development and neurodegeneration through defective CLP1 function in humans