An HDS is composed of a combination of continuous and non-ordered discrete dimensions. This combination presents new challenges in data organization and search ordering. In this paper, we present an algorithm for k -NN searches using a multidimensional index structure in hybrid data spaces.
We examine the concept of search stages and use the properties of an HDS to derive a new search heuristic that greatly reduces the number of disk accesses in the initial stage of searching. Further, we present a performance model for our algorithm that estimates the cost of performing such searches. Our experimental results demonstrate the effectiveness of our… algorithm and the accuracy of our performance estimation model.
Highlights • Developed algorithm for searching multi-dimensional hybrid data spaces. • Introduced the method of improving search performance by examining search stages. • Suggested new search heuristic to improve initial stage of searching by 33%. • Derived theoretical model accurately predicts the performance of algorithm.
It has been suggested by studies in animals and humans that substance P (SP) and its receptor neurokinin 1 (NK1R) play an important role in the pathology of depression. The pharmacological blockade or genetic deletion of the NK1 receptor, or the substance P coding gene tac1 led to a decreased emotionality and a reduction of depression-related behaviours in different animal models.
In order to characterize molecular changes associated with reduced SP-NK1 signalling in animal models of depression, we assessed the regulation of the CRH system. First, tac1(-/-) animals and tac1(+/+) controls were subjected to bulbectomy, which induces physiological and behavioural changes that are relevant to depression. We demonstrate that tac1(-/-) animals, in contrast to tac1(+/+) controls, do not show… anhedonia in the saccharine preference test after bulbectomy. Next, we studied expression levels of CRH, the receptors CRHR1 and CRHR2, and the binding protein CRHBP in the cortex and paraventricular nucleus using real-time RT-PCR.
Our results show a strong induction of CRH, CRHBP and CRHR1 expression in the cortex of tac1(-/-), but not in tac1(+/+) animals. In the PVN, bulbectomized tac1(-/-) mice showed an elevated expression of CRHR1 and CRHR2. These results show that substance P/NKA is involved in modulating CRH signalling in an animal model of depression.
The 395-residue proteolytic fragment E3, which comprises the two most C-terminal LG modules of the mouse laminin alpha1 chain, was previously shown to contain major binding sites for heparin, alpha-dystroglycan and sulfatides. The same fragment (alpha1LG4-5) and its individual alpha1LG4 and alpha1LG5 modules have now been obtained by recombinant production in mammalian cells.
These fragments were apparently folded into a native form, as shown by circular dichroism, electron microscopy and immunological assays. Fragment alpha1LG4-5 bound about five- to tenfold better to heparin, alpha-dystroglycan and sulfatides than E3. These binding activities could be exclusively localized to the alpha1LG4 module. Side-chain modifications and proteolysis demonstrated that Lys and Arg residues in the… C-terminal region of alpha1LG4 are essential for heparin binding. This was confirmed by 14 single to triple point mutations, which identified three non-contiguous basic regions (positions 2766-2770, 2791-2793, 2819-2820) as contributing to both heparin and sulfatide binding. Two of these regions were also recognized by monoclonal antibodies which have previously been shown to inhibit heparin binding.
The same three regions and a few additional basic residues also make major contributions to the binding of the cellular receptor alpha-dystroglycan, indicating a larger binding epitope. The data are also consistent with previous findings that heparin competes for alpha-dystroglycan binding.
RNA expression patterns associated with non-small cell lung cancer subclassification have been reported, but there are substantial differences in the key genes and clinical features of these subsets casting doubt on their biological significance.;;In this study, we used a training-testing approach to test the reliability of cDNA microarray-based classifications of resected human non-small cell lung cancers (NSCLCs) analyzed by cDNA microarray.
Groups of genes were identified that were able to differentiate primary tumors from normal lung and lung metastases, as well as identify known histological subgroups of NSCLCs. Groups of genes were identified to discriminate sample clusters. A blinded confirmatory set of tumors was correctly classified by using these patterns. Some histologically… diagnosed large cell tumors were clearly classified by expression profile analysis as being either adenocarcinoma or squamous cell carcinoma, indicating that this group of tumors may not be genetically homogeneous.
High alpha-actinin-4 expression was identified as highly correlated with poor prognosis.;;These results demonstrate that gene expression profiling can identify molecular classes of resected NSCLCs that correctly classifies a blinded test cohort, and correlates with and supplements standard histological evaluation.