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H H Lin

Publications and source records attributed to H H Lin.

At least 19 recordsLinked to original sources
PubMed2006

PROFEAT: a web server for computing structural and physicochemical features of proteins and peptides from amino acid sequence.

Sequence-derived structural and physicochemical features have frequently been used in the development of statistical learning models for predicting proteins and peptides of different structural, functional and interaction profiles. PROFEAT (Protein Features) is a web server for computing commonly-used structural and physicochemical features of proteins and peptides from amino acid sequence. It computes six feature groups composed of ten features that include 51 descriptors and 1447 descriptor values. The computed features include amino acid composition, dipeptide composition, normalized Moreau-Broto autocorrelation, Moran autocorrelation, Geary autocorrelation, sequence-order-coupling number, quasi-sequence-order descriptors and the composition, transition and distribution of various structural and physicochemical properties. In addition, it can also compute previous autocorrelations descriptors based on user-defined properties. Our computational algorithms were extensively tested and the computed protein features have been used in a number of published works for predicting proteins of functional classes, protein-protein interactions and MHC-binding peptides. PROFEAT is accessible at http://jing.cz3.nus.edu.sg/cgi-bin/prof/prof.cgi.

Algorithms↗
PubMed2006

Prediction of MHC-binding peptides of flexible lengths from sequence-derived structural and physicochemical properties.

Peptide binding to MHC is critical for antigen recognition by T-cells. To facilitate vaccine design, computational methods have been developed for predicting MHC-binding peptides, which achieve impressive prediction accuracies of 70-90% for binders and 40-80% for non-binders. These methods have been developed for peptides of fixed lengths, for a limited number of alleles, trained from small number of non-binders, and in some cases based straightforwardly on sequence. These limit prediction coverage and accuracy particularly for non-binders. It is desirable to explore methods that predict binders of flexible lengths from sequence-derived physicochemical properties and trained from diverse sets of non-binders. This work explores support vector machines (SVM) as such a method for developing prediction systems of 18 MHC class I and 12 class II alleles by using 4208-3252 binders and 234,333-168,793 non-binders, and evaluated by an independent set of 545-476 binders and 110,564-84,430 non-binders. Binder accuracies are 86-99% for 25 and 70-80% for 5 alleles, non-binder accuracies are 96-99% for 30 alleles. Binder accuracies are comparable and non-binder accuracies substantially improved against other results. Our method correctly predicts 73.3% of the 15 newly-published epitopes in the last 4 months of 2005. Of the 251 recently-published HLA-A*0201 non-epitopes predicted as binders by other methods, 63 are predicted as binders by our method. Screening of HIV-1 genome shows that, compared to other methods, a comparable percentage (75-100%) of its known epitopes is correctly predicted, while a lower percentage (0.01-5% for 24 and 5-8% for 6 alleles) of its constituent peptides are predicted as binders. Our software can be accessed at .

Alleles↗
PubMed2006

Prediction of the functional class of lipid binding proteins from sequence-derived properties irrespective of sequence similarity.

Lipid binding proteins play important roles in signaling, regulation, membrane trafficking, immune response, lipid metabolism, and transport. Because of their functional and sequence diversity, it is desirable to explore additional methods for predicting lipid binding proteins irrespective of sequence similarity. This work explores the use of support vector machines (SVMs) as such a method. SVM prediction systems are developed using 14,776 lipid binding and 133,441 nonlipid binding proteins and are evaluated by an independent set of 6,768 lipid binding and 64,761 nonlipid binding proteins. The computed prediction accuracy is 78.9, 79.5, 82.2, 79.5, 84.4, 76.6, 90.6, 79.0, and 89.9% for lipid degradation, lipid metabolism, lipid synthesis, lipid transport, lipid binding, lipopolysaccharide biosynthesis, lipoprotein, lipoyl, and all lipid binding proteins, respectively. The accuracy for the nonmember proteins of each class is 99.9, 99.2, 99.6, 99.8, 99.9, 99.8, 98.5, 99.9, and 97.0%, respectively. Comparable accuracies are obtained when homologous proteins are considered as one, or by using a different SVM kernel function. Our method predicts 86.8% of the 76 lipid binding proteins nonhomologous to any protein in the Swiss-Prot database and 89.0% of the 73 known lipid binding domains as lipid binding. These findings suggest the usefulness of SVMs for facilitating the prediction of lipid binding proteins. Our software can be accessed at the SVMProt server (http://jing.cz3.nus.edu.sg/cgi-bin/svmprot.cgi).

Algorithms↗
PubMed2006

Prediction of transporter family from protein sequence by support vector machine approach.

Transporters play key roles in cellular transport and metabolic processes, and in facilitating drug delivery and excretion. These proteins are classified into families based on the transporter classification (TC) system. Determination of the TC family of transporters facilitates the study of their cellular and pharmacological functions. Methods for predicting TC family without sequence alignments or clustering are particularly useful for studying novel transporters whose function cannot be determined by sequence similarity. This work explores the use of a machine learning method, support vector machines (SVMs), for predicting the family of transporters from their sequence without the use of sequence similarity. A total of 10,636 transporters in 13 TC subclasses, 1914 transporters in eight TC families, and 168,341 nontransporter proteins are used to train and test the SVM prediction system. Testing results by using a separate set of 4351 transporters and 83,151 nontransporter proteins show that the overall accuracy for predicting members of these TC subclasses and families is 83.4% and 88.0%, respectively, and that of nonmembers is 99.3% and 96.6%, respectively. The accuracies for predicting members and nonmembers of individual TC subclasses are in the range of 70.7-96.1% and 97.6-99.9%, respectively, and those of individual TC families are in the range of 60.6-97.1% and 91.5-99.4%, respectively. A further test by using 26,139 transmembrane proteins outside each of the 13 TC subclasses shows that 90.4-99.6% of these are correctly predicted. Our study suggests that the SVM is potentially useful for facilitating functional study of transporters irrespective of sequence similarity.

Amino Acid Sequence↗
PubMed2005

The effect of electrical field strength on activation and development of cloned caprine embryos.

The activation procedure used in nuclear transfer (NT) is one of the critical factors affecting the efficiency of animal cloning. The purpose of this study was to compare the effect of two electrical field strengths (EFS) for activation on the developmental competence of caprine NT embryos reconstructed from ear skin fibroblasts of adult Alpine does. The NT embryos were obtained by transfer of the quiescent fibroblasts at the fourth passage into the enucleated metaphase II (M II) oocytes. Four to five hours after electrical fusion, the NT-embryos were activated by EFS either at 1.67 or at 2.33 kV/cm and immediately incubated in 6-DMAP (2 mM) for 4 h. The cleavage rate of the NT-embryos activated with 2.33 kV/cm was greater than that activated with 1.67 kV/cm after in vitro culture for 18 h (65.6% versus 19.6%, p < 0.001). No pregnancy was found in 14 recipient does after transferring 51 NT embryos at 1-2 cell stages activated with 1.67 kV/cm. In contrast, two of the seven recipients were pregnant and gave birth to three kids after transferring 61 NT embryos at 1-2 cell stages activated by 2.33 kV/cm. The birth weights of three cloned kids were within the normal range of Alpine goats. However, one kid died 1h after birth while the remaining two are still healthy. DNA analysis by polymerase chain reaction (single-strand conformation polymorphism, SSCP) confirmed that the three kids were genetically identical to the nuclear donor.

Animals↗
PubMed2005

Dyspeptic symptoms and water load test in patients with functional dyspepsia and reflux disease.

OBJECTIVE: Hypersensitivity to gastric distension has been reported in functional dyspepsia (FD). The aim of this study was to assess the perception to gastric distension and its relationship to specific symptoms using the water load test (WLT) in FD and gastroesophageal reflux disease (GERD). MATERIAL AND METHODS: A 5-min WLT was used to evaluate sensitivity of gastric distension in 47 FD and 61 GERD subjects, and 49 healthy controls (HC). A visual analogue scale (VAS) measuring symptom severity was obtained from all subjects and its relationship with the maximal ingested volume was determined. The maximal ingested volume was registered and the subjective symptoms were assessed at baseline and 30 min after the WLT. RESULTS: The maximal ingested volume by HC was 597 +/- 33 ml, which was statistically greater than that of FD (422 +/- 22 ml, p < 0.001) and GERD (504 +/- 23 ml, p < 0.02) subjects. The maximal ingested volume did not differ significantly between FD and GERD. The maximal ingested volume correlated well with nausea (r = -0.49, p < 0.01) and fullness (r = -0.33, p < 0.05) in FD. Male subjects ingested more water than females in the HC (p < 0.01) and GERD groups (p < 0.05), but not in FD (p = NS). CONCLUSIONS: Both FD and GERD subjects have altered perception to gastric fullness induced by the WLT compared to healthy controls. Good correlations have been observed between the WLT and dyspeptic symptoms such as early satiety and postprandial fullness, but not in GERD.

Adult↗
PubMed2005

Prediction of functional class of novel plant proteins by a statistical learning method.

In plant genomes, the function of a substantial percentage of the putative protein-coding open reading frames (ORFs) is unknown. These ORFs have no significant sequence similarity to known proteins, which complicates the task of functional study of these proteins. Efforts are being made to explore methods that are complementary to, or may be used in combination with, sequence alignment and clustering methods. A web-based protein functional class prediction software, SVMProt, has shown some capability for predicting functional class of distantly related proteins. Here the usefulness of SVMProt for functional study of novel plant proteins is evaluated. To test SVMProt, 49 plant proteins (without a sequence homolog in the Swiss-Prot protein database, not in the SVMProt training set, and with functional indications provided in the literature) were selected from a comprehensive search of MEDLINE abstracts and Swiss-Prot databases in 1999-2004. These represent unique proteins the function of which, at present, cannot be confidently predicted by sequence alignment and clustering methods. The predicted functional class of 31 proteins was consistent, and that of four other proteins was weakly consistent, with published functions. Overall, the functional class of 71.4% of these proteins was consistent, or weakly consistent, with functional indications described in the literature. SVMProt shows a certain level of ability to provide useful hints about the functions of novel plant proteins with no similarity to known proteins.

Artificial Intelligence↗
PubMed2004

MoViES: molecular vibrations evaluation server for analysis of fluctuational dynamics of proteins and nucleic acids.

Analysis of vibrational motions and thermal fluctuational dynamics is a widely used approach for studying structural, dynamic and functional properties of proteins and nucleic acids. Development of a freely accessible web server for computation of vibrational and thermal fluctuational dynamics of biomolecules is thus useful for facilitating the relevant studies. We have developed a computer program for computing vibrational normal modes and thermal fluctuational properties of proteins and nucleic acids and applied it in several studies. In our program, vibrational normal modes are computed by using modified AMBER molecular mechanics force fields, and thermal fluctuational properties are computed by means of a self-consistent harmonic approximation method. A web version of our program, MoViES (Molecular Vibrations Evaluation Server), was set up to facilitate the use of our program to study vibrational dynamics of proteins and nucleic acids. This software was tested on selected proteins, which show that the computed normal modes and thermal fluctuational bond disruption probabilities are consistent with experimental findings and other normal mode computations. MoViES can be accessed at http://ang.cz3.nus.edu.sg/cgi-bin/prog/norm.pl.

Computational Biology↗
PubMed2004

Transfer function analysis of heart rate variability in response to water intake: correlation with gastric myoelectrical activity.

We utilized transfer function analysis of heart rate variability (HRV) and respiration to investigate the effect of water intake on gastric myoelectrical activity and its relationship to vagal activity. The electrogastrography (EGG) and HRV were recorded simultaneously before and after drinking 500 ml of water in 10 healthy subjects. We observed good linearity between lung volumes and HRV signals at a ventilatory rate between 0.2 and 0.4 Hz before and after water intake. The EGG power of 3 cycles/min increased remarkably after the water intake. We found that there was a significant increase in the magnitude of the respiration-HRV transfer function after water intake (P < 0.05). The EGG 3 cycles/min power was positively correlated with the transfer magnitude throughout the study (r = 0.54, P = 0.01). These results confirm that transfer function analysis of HRV sensitively identifies subtle changes in the respiratory sinus arrhythmia that occurs with water intake. The present findings suggest that transfer function analysis of HRV and respiration after water intake can be used to evaluate vagal nervous activity in the human gut.

Adult↗
PubMed2004

Randomization of heavily damaged regions in annealed low energy Ge(+)-implanted (001)Si.

Apparent growth of amorphous layers during low temperature annealing was observed in low energy Ge(+)-implanted (001)Si by high-resolution transmission electron microscopy. The occurrence of abnormal growth is due to the randomization of heavily damaged regions beneath the original amorphous/crystalline interfaces. The randomization process is attributed to the strain, incurred by the presence of a high density of large Ge atoms in the heavily damaged Si substrate, relaxation to lower the free energy of the systems. The randomization upon annealing may be fruitfully applied to minimize the transient enhanced diffusion in shallow junction formation.

Journal Article↗
PubMed2004

Comparison of the severity of illness scoring systems for critically ill cirrhotic patients with renal failure.

BACKGROUND: Mortality rates of cirrhotic patients with renal failure admitted to the medical intensive care unit (ICU) are high. End-stage liver disease is frequently complicated by disturbances of renal function. This investigation is aimed to compare the predicting ability of acute physiology, age, chronic health evaluation II and III (APACHE II and III), sequential organ failure assessment (SOFA), and Child-Pugh scoring systems, obtained on the first day of ICU admission, for hospital mortality in critically ill cirrhotic patients with renal failure. METHODS: Sixty-seven patients with liver cirrhosis and renal failure were admitted to ICU from April 2001-March 2002. Information considered necessary for computing the Child-Pugh, SOFA, APACHE II and APACHE III score on the first day of ICU admission was prospectively collected. RESULTS: The overall hospital mortality rate was 86.6%. Liver disease was most commonly attributed to hepatitis B viral infection. The development of renal failure was associated with a history of gastrointestinal bleeding. Goodness-of-fit was good for SOFA, APACHE II and APACHE III scores. The APACHE III and SOFA models reported good areas under receiver operating characteristic curve (0.878 +/- 0.050 and 0.868 +/- 0.051, respectively). CONCLUSION: Renal failure is common in critically ill patients with cirrhosis. The prognosis for cirrhotic patients with renal failure is poor. APACHE III and SOFA showed excellent discrimination power in this group of patients. They are superior to APACHE II and Child-Pugh scores in this homogenous group of patients.

APACHE↗
PubMed2003

Hydrogen peroxide increases the activity of rat sympathetic preganglionic neurons in vivo and in vitro.

Reactive oxygen species (ROS) have been shown to modulate neuronal synaptic transmission and have also been implicated in cardiovascular diseases such as hypertension. The hypothesis that H(2)O(2) acting on sympathetic preganglionic neurons (SPNs) affects spinal sympathetic outflow was tested in the present study. H(2)O(2) was applied intrathecally via an implanted cannula to the T7-T9 segments of urethane-anesthetized rats. Blood pressure and heart rate were used as indices to evaluate the spinal sympathetic effects of H(2)O(2) in vivo. Intrathecal H(2)O(2) (100-1000 nmol) dose-dependently increased both the mean arterial pressure and heart rate. Reproducible pressor effects of H(2)O(2) (1000 nmol) applied consecutively at intervals of 30 min were observed. The pressor effects of intrathecal H(2)O(2) (1000 nmol) were attenuated by pretreatment with intrathecal administration of catalase (500 units), or N-acetyl-cysteine (1000 nmol). The pressor effects of intrathecal H(2)O(2) (1000 nmol) were also antagonized dose-dependently by prior intrathecal injection of AP-5 (DL-2-amino-5- phosphonovaleric acid, 10 and 30 nmol), or 6-cyano-7- nitroquinoxaline-2,3-dione, 10 and 30 nmol. In vitro electrophysiological study in spinal cord slices showed that superfusion of 1 mM H(2)O(2) for 3 min, which had no effect on membrane potential, caused an increase in amplitude of excitatory postsynaptic potentials in SPNs, but had little effect on that of inhibitory postsynaptic potentials. Taken together, these results demonstrated that oxidative stress in spinal cord may cause an increase in spinal sympathetic tone by acting on SPNs, which may contribute to ROS-induced cardiovascular dysfunction.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed2002

Structural evolution in amorphous silicon and germanium thin films.

The structural evolution in amorphous silicon and germanium thin films has been investigated by high-resolution transmission electron microscopy (HRTEM) in conjunction with autocorrelation function (ACF) analysis. The results established that the structure of as-deposited semiconductor films is of a high density of nanocrystallites embedded in the amorphous matrix. In addition, from ACF analysis, the structure of a-Ge is more ordered than that of a-Si. The density of embedded nanocrystallites in amorphous films was found to diminish with annealing temperature first, then to increase. The conclusions also corroborate well with the results of diminished medium-range order in annealed amorphous films determined previously by a variable coherence microscopy method.

Alloys↗
PubMed2002

Sympathoinhibitory action of nociceptin in the rat spinal cord.

1. Whole-cell patch recordings were made from antidromically identified sympathetic preganglionic neurons (SPN) of immature rat spinal cord slices. Bath application of nociceptin (0.1-1 micromol/L) suppressed excitatory postsynaptic potentials (EPSP) and hyperpolarized a population of SPN; these effects were naloxone (1 micromol/L) insensitive. 2. Nociceptin suppressed the amplitude of EPSP without causing a concomitant change in glutamate-induced depolarizations, suggesting a presynaptic inhibitory action. 3. Analysis of current-voltage relationships showed that nociceptin hyperpolarized SPN by increasing an inwardly rectifying K+ current. 4. Intrathecal injection of nociceptin (3, 10 and 30 nmol) to urethane-anaesthetized rats dose-dependently reduced the mean arterial pressure and heart rate; these effects were not prevented by prior intravenous injection of naloxone (1 mg/kg). 5. Results from our in vitro and in vivo experiments suggest that nociceptin suppresses spinal sympathetic outflow either by attenuating excitatory synaptic responses or hyperpolarizing SPN.

Adrenergic Fibers↗
PubMed2001

Detection of elevated serum beta-chemokine levels in seronegative Chinese individuals exposed to human immunodeficiency virus type 1.

The mutations in the CCR5 coding region, such as CCR5Delta32 and CCR5m303, that suppress the transmission of human immunodeficiency virus (HIV) type 1 do not exist in Chinese people. However, 9 Chinese subjects in Taiwan with histories of multiple sexual exposures to HIV remained uninfected, suggesting that certain anti-HIV factors do indeed exist. Experiments were therefore designed to investigate the immune mechanism that protects this cohort against HIV infection. Peripheral blood samples from these 9 subjects and 7 healthy people who had not been exposed to HIV were obtained for the quantitation of the levels for beta-chemokines and interleukin 16 (IL-16) in serum samples or secreted by peripheral blood lymphocytes. Significantly higher serum levels for nearly all 3 beta-chemokines, regulation on activation, normal T cell-expressed and secreted, macrophage inflammatory protein (MIP)-1alpha, and MIP-1beta (P<.05, P<.05, and P=.05, respectively), but not IL-16, were detected in the 9 HIV-uninfected subjects as compared with control subjects. The result suggests that among the host genes and cellular factors thus far identified, beta-chemokines are the major HIV-suppressive factors that protect Chinese people from infection with HIV.

Adult↗
PubMed2001

Requirement for high mobility group protein HMGI-C interaction with STAT3 inhibitor PIAS3 in repression of alpha-subunit of epithelial Na+ channel (alpha-ENaC) transcription by Ras activation in salivary epithelial cells.

Previously, we have demonstrated that oxidative stress or Ras/ERK activation leads to the transcriptional repression of alpha-subunit of epithelial Na(+) channel (ENaC) in lung and salivary epithelial cells. Here, we further investigated the coordinated molecular mechanisms by which alpha-ENaC expression is regulated. Using both stable and transient transfection assays, we demonstrate that the overexpression of high mobility group protein I-C (HMGI-C), a Ras/ERK-inducible HMG-I family member, represses glucocorticoid receptor (GR)/dexamethasone (Dex)-stimulated alpha-ENaC/reporter activity in salivary epithelial cells. Northern analyses further confirm that the expression of endogenous alpha-ENaC gene in salivary Pa-4 cells is suppressed by an ectopic HMGI-C overexpression. Through yeast two-hybrid screening and co-immunoprecipitation assays from eukaryotic cells, we also discovered the interaction between HMGI-C and PIAS3 (protein inhibitor of activated STAT3 (signal transducer and activator of transcription 3)). A low level of ectopically expressed PIAS3 cooperatively inhibits GR/Dex-dependent alpha-ENaC transcription in the presence of HMGI-C. Reciprocally, HMGI-C expression also coordinately enhances PIAS3-mediated repression of STAT3-dependent transactivation. Moreover, overexpression of antisense HMGI-C construct is capable of reversing the repression mediated by Ras V12 on GR- and STAT3-dependent transcriptional activation. Together, our results demonstrate that Ras/ERK-mediated induction of HMGI-C is required to effectively repress GR/Dex-stimulated transcription of alpha-ENaC gene and STAT3-mediated transactivation. These findings delineate a network of inhibitory signaling pathways that converge on HMGI-C.PIAS3 complex, causally associating Ras/ERK activation with the repression of both GR and STAT3 signaling pathways in salivary epithelial cells.

Animals↗
PubMed2001

Molecular analysis of the epidermal growth factor-like short consensus repeat domain-mediated protein-protein interactions: dissection of the CD97-CD55 complex.

Epidermal growth factor-like (EGF) and short consensus repeat (SCR) domains are commonly found in cell surface and soluble proteins that mediate specific protein-protein recognition events. Unlike the immunoglobulin (Ig) superfamily, very little is known about the general properties of intermolecular interactions encoded by these common modules, and in particular, how specificity of binding is achieved. We have dissected the binding of CD97 (a member of the EGF-TM7 family) to the complement regulator CD55, two cell surface modular proteins that contain EGF and SCR domains, respectively. We demonstrate that the interaction is mediated solely by these domains and is characterized by a low affinity (86 microm) and rapid off-rate (at least 0.6 s(-1)). The interaction is Ca(2+) -dependent but is unaffected by glycosylation of the EGF domains. Using biotinylated multimerized peptides in cell binding assays and surface plasmon resonance, we show that a CD97-related EGF-TM7 molecule (termed EMR2), differing by only three amino acids within the EGF domains, binds CD55 with a K(D) at least an order of magnitude weaker than that of CD97. These results suggest that low affinity cell-cell interactions may be a general feature of highly expressed cell surface proteins and that specificity of SCR-EGF binding can be finely tuned by a small number of amino acid changes on the EGF module surface.

Amino Acid Sequence↗