Streamflow classification by employing various machine learning models for peninsular Malaysia.

Due to excessive streamflow (SF), Peninsular Malaysia has historically experienced floods and droughts. Forecasting streamflow to mitigate municipal and environmental damage is therefore crucial. Streamflow prediction has been extensively demonstrated in the literature to estimate the continuous values of streamflow level. Prediction of continuous values of streamflow is not necessary in several applications and at the same time it is very challenging task because of uncertainty. A streamflow category prediction is more advantageous for addressing the uncertainty in numerical point forecasting, considering that its predictions are linked to a propensity to belong to the pre-defined classes. Here, we formulate streamflow prediction as a time series classification with discrete ranges of values, each representing a class to classify streamflow into five or ten, respectively, using machine learning approaches in various rivers in Malaysia. The findings reveal that several models, specifically LSTM, outperform others in predicting the following n-time steps of streamflow because LSTM is able to learn the mapping between streamflow time series of 2 or 3 days ahead more than support vector machine (SVM) and gradient boosting (GB). LSTM produces higher F1 score in various rivers (by 5% in Johor, 2% in Kelantan and Melaka and Selangor, 4% in Perlis) in 2 days ahead scenario. Furthermore, the ensemble stacking of the SVM and GB achieves high performance in terms of F1 score and quadratic weighted kappa. Ensemble stacking gives 3% higher F1 score in Perak river compared to SVM and gradient boosting.

An anaplerotic approach to correct the mitochondrial dysfunction in ataxia-telangiectasia (A-T).

BACKGROUND: ATM, the protein defective in the human genetic disorder, ataxia-telangiectasia (A-T) plays a central role in response to DNA double-strand breaks (DSBs) and in protecting the cell against oxidative stress. We showed that A-T cells are hypersensitive to metabolic stress which can be accounted for by a failure to exhibit efficient endoplasmic reticulum (ER)-mitochondrial signalling and Ca2+ transfer in response to nutrient deprivation resulting in mitochondrial dysfunction. The objective of the current study is to use an anaplerotic approach using the fatty acid, heptanoate (C7), a metabolic product of the triglyceride, triheptanoin to correct the defect in ER-mitochondrial signalling and enhance cell survival of A-T cells in response to metabolic stress. METHODS: We treated control cells and A-T cells with the anaplerotic agent, heptanoate to determine their sensitivity to metabolic stress induced by inhibition of glycolysis with 2- deoxyglucose (2DG) using live-cell imaging to monitor cell survival for 72 h using the Incucyte system. We examined ER-mitochondrial signalling in A-T cells exposed to metabolic stress using a suite of techniques including immunofluorescence staining of Grp75, ER-mitochondrial Ca2+ channel, the VAPB-PTPIP51 ER-mitochondrial tether complexes as well as proximity ligation assays between Grp75-IP3R1 and VAPB1-PTPIP51 to establish a functional interaction between ER and mitochondria. Finally, we also performed metabolomic analysis using LC-MS/MS assay to determine altered levels of TCA intermediates A-T cells compared to healthy control cells. RESULTS: We demonstrate that heptanoate corrects all aspects of the defective ER-mitochondrial signalling observed in A-T cells. Heptanoate enhances ER-mitochondrial contacts; increases the flow of calcium from the ER to the mitochondrion; restores normal mitochondrial function and mitophagy and increases the resistance of ATM-deficient cells and cells from A-T patients to metabolic stress-induced killing. The defect in mitochondrial function in ATM-deficient cells was accompanied by more reliance on aerobic glycolysis as shown by increased lactate dehydrogenase A (LDHA), accumulation of lactate, and reduced levels of both acetyl CoA and ATP which are all restored by heptanoate. CONCLUSIONS: We conclude that heptanoate corrects metabolic stress in A-T cells by restoring ER-mitochondria signalling and mitochondrial function and suggest that the parent compound, triheptanoin, has immense potential as a novel therapeutic agent for patients with A-T.

Dystrophic Scoliosis in Neurofibromatosis and Rib-head Resection: A Case Report.

Surgical management of scoliosis in Neurofibromatosis type I may be challenging at times especially when dealing with dystrophic curves. We highlight the importance of meticulous study of the radiological imaging and careful pre-operative planning in a patient with dystrophic scoliosis.

A novel genetic study of Chinese families with autosomal recessive retinitis pigmentosa.

Autosomal recessive retinitis pigmentosa (arRP) is the commonest form of RP worldwide. To date 22 loci have been implicated in the pathogenesis of this disease; however none of these loci independently account for a significant proportion of recessive RP. Linkage studies of arRP in consanguineous families have been mainly based on homozygosity mapping, but this strategy cannot be applied in the case of non-consanguineous families. Therefore, we implemented a systematic approach for identifying the disease locus in three non-consanguineous Chinese families with arRP. Initially, linkage analysis using SNPs/microsatellite markers or mutation screening of known arRP genes excluded all loci/genes except RP25 on chromosome 6. Subsequently a whole genome scan for the three families using the 10K GeneChip Mapping Array was performed, in order to identify the possible disease locus. To the best of our knowledge this is the first report on the utilisation of the 10K GeneChip to study linkage in non-consanguineous Chinese arRP. This analysis indicates that the studied families are probably linked to the RP25 locus, a well defined arRP locus in other populations. The identification of another ethnic group linked to RP25 is highly suggestive that this represents a major locus for arRP.

Initial failure of angiography to demonstrate a bleeding pancreatic cancer: a case for provocative agents.

BACKGROUND: Mesenteric angiography is commonly employed in the modern-day investigation of gastro-intestinal bleeding if the bleeding sites cannot be identified by endoscopic means. Angiography is optimally sensitive in the presence of active bleeding. However, vasospasm may occasionally account for a negative study shortly after bleeding. CASE OUTLINE: A 70-year-old lady with inoperable carcinoma of the pancreas presented with gastro-intestinal bleeding. Although upper endoscopy visualised active bleeding from the tumour, which had invaded into the duodenum, haemostasis could not be achieved endoscopically. Therefore, mesenteric angiography was arranged. RESULTS: The initial angiography failed to demonstrate the bleeding site, which only became obvious on a repeat study, when embolisation was performed to achieve haemostasis. DISCUSSION: Vasospasm probably accounted for the initial negative study, as the second angiography was able to demonstrate contrast extravasation without the use of any anticoagulant or thrombolytic agent. It is not our routine to give pharmacological agents to provoke bleeding after a negative angiography, but for selected patients this manoeuvre may turn out to be more cost-effective.

Comparison of the biochemical responses to human parathyroid hormone-(1-31)NH2 and hPTH-(1-34) in healthy humans.

The 1-31 fragment of human PTH [hPTH-(1-31)NH2] has been shown, like hPTH-(1-34), to have anabolic effects on the skeletons of ovariectomized rats when given intermittently, but, unlike hPTH-(1-34), it does so without affecting serum calcium concentrations and does not activate the protein kinase C second messenger pathway in some target cells. To investigate the biochemical responses to hPTH-(1-31) in humans, we have directly compared it to hPTH-(1-34) during the course of slow infusions of each. Ten healthy adults, five men and five women, aged 26+/-5 yr (range, 22-37), each received 8-h continuous infusions of 8 pmol/kg.h hPTH-(1-34) and hPTH-(1-31) given in random order at least 2 weeks apart. During the infusions there were significant increases in both plasma and urinary cAMP (P < 0.05), but there were no differences in the responses between the two peptides (P = 0.362 for plasma; P = 0.987 for urine). There were also significant phosphaturic and natriuretic responses to the two peptides, which again were not different between peptides. During the infusion of hPTH-(1-34) serum ionized calcium (Ca2+) increased from 1.21+/-0.033 to 1.29+/-0.046 mmol/L (P < 0.01), and endogenous hPTH-(1-84) decreased from 29.6+/-9 to 15.0+/-5.7 pg/mL (P < 0.01), such that there was a negative correlation between them (r2 = 0.45). However, when hPTH-(1-31) was infused, neither serum Ca2+ (1.24+/-0.03 vs. 1.25+/-0.03) nor hPTH-(1-84) (26.8+/-5 vs. 30.7+/-12 pg/mL) was affected. Circulating concentrations of 1,25-dihydroxyvitamin D3 increased from 92+/-42 to 131+/-63 pmol/L (P < 0.05) during infusion of hPTH-(1-34) and from 92+/-27 to 110+/-42 pmol/L (P = NS) during hPTH-(1-31) infusion. There was also a significant increase in the urinary measure of type I collagen degradation of aminoterminal telopeptides from 78+/-45 to 101+/-51 nmol/mmol creatinine (P < 0.05) when hPTH-(1-34) was infused, but it was not affected (68+/-30 vs. 66+/-24 nmol/mmol creatinine) by hPTH-(1-31). Therefore, hPTH-(1-31) appears to be equivalent and equipotent to hPTH-(1-34) in the release of cAMP from target tissues and the renal handling of phosphate and sodium. However, at the doses employed, it does not increase serum calcium, is a weaker stimulator of the 25-hydroxyvitamin D-1alpha-hydroxylase, and does not induce rapid bone resorption.

Multiple organ failure and septic shock in disseminated tuberculosis.

The diagnosis of disseminated tuberculosis should be entertained in all patients with unexplained fever associated with hepatomegaly and/or splenomegaly with or without anomalies in liver function tests and haemogram. It should be considered as a possible cause of septic shock especially in patients with typical risk factors such as advanced age, diabetes, alcoholism or immunosuppression. Prompt therapy could be life saving in an otherwise potentially fatal condition. It is therefore appropriate to initiate anti-tuberculosis treatment as soon as such a diagnosis is suspected and not await final confirmation.

Localization of the human interferon-induced, ds-RNA activated p68 kinase gene (PRKR) to chromosome 2p21-p22.

The interferon-induced dsRNA-activated protein kinase (PRKR) belongs to a subclass of serine/threonine kinases, involved in the regulation of protein synthesis by phosphorylation of the alpha subunit of initiation factor eIF2. Somatic cell hybrids segregating human chromosomes were used to assign this kinase to human chromosome 2. Fluorescence in situ hybridization confirmed this assignment and further localized the gene (PRKR) to the boundary region of bands p21 and 22.

Human p68 kinase exhibits growth suppression in yeast and homology to the translational regulator GCN2.

The human p68 kinase is an interferon-regulated enzyme that inhibits protein synthesis when activated by double-stranded RNA. We show here that when expressed in Saccharomyces cerevisiae, the p68 kinase produced a growth suppressing phenotype resulting from an inhibition of polypeptide chain initiation consistent with functional protein kinase activity. This slow growth phenotype was reverted in yeast by two different mechanisms: expression of the p68 kinase N-terminus, shown to bind double-stranded RNA in vitro and expression of a mutant form of the alpha-subunit of yeast initiation factor 2, altered at a single phosphorylatable site. These results provide the first direct in vivo evidence that the p68 kinase interacts with the alpha-subunit of eukaryotic initiation factor 2. Sequence similarity with a yeast translational regulator, GCN2, further suggests that this enzyme may be a functional homolog in higher eukaryotes, where its normal function is to regulate protein synthesis through initiation factor 2 phosphorylation.

Initial characterization of a chlamydial receptor on mammalian cells.

We have examined characteristics of the binding of eukaryotic cells to chlamydial elementary body (EB)-specific proteins. A wide variety of eukaryotic cell lines bound to representatives of both Chlamydia trachomatis lymphogranuloma venereum (LGV) and trachoma biovars and a C. psittaci strain meningopneumonitis (Mn) suggesting the presence of a common host cell receptor. Neither tunicamycin nor neuraminidase treatment of HeLa cells impaired binding to C. trachomatis EB, implying that host cell N-linked carbohydrate domains and sialic acid moieties, respectively, are not involved in attachment. However, trypsinized HeLa cells do not bind to EB, suggestive of a proteinaceous host cell receptor. The trypsin sensitivity of two EB-specific binding proteins Mr = 18,000 and 31,000) was also examined, and the finding that 125I-labeled HeLa cells bind both the 18,000 and 31,000-dalton proteins after chlamydial trypsinization corroborates our earlier observation that these EB binding proteins mediate attachment.

Sensorimotor cortical projections to the marginal zone of the trigeminal subnucleus caudalis.

An ultrastructural investigation of the marginal zone (lamina I) of the spinal trigeminal subnucleus caudalis was carried out in 7 adult cats at 30 h through 7 days after ablations of face area of the contralateral sensorimotor cortex. Corticofugal boutons were observed to undergo electron-dense degeneration in the marginal zone beginning 4 days after the cortical lesion. These boutons were small (1--2 micrometers), widely dispersed and made synaptic contacts onto small dendrites or dendritic spines. These new observations indicate that cortical inhibition and facilitation of ascending orofacial sensation may be mediated in part by a direct pathway to the marginal zone.