gebhart/patrepeval huggingface dataset:
The value of animal models in the development of new drugs for the treatment of the sepsis syndrome (1998)

The sepsis syndrome has proved to be one of the most difficult clinical situations to replicate in animal models. The outcome of sepsis in patients depends not only on the pathogens, sizes of bacterial challenge and adequacy of treatment, but also on age, host defence mechanisms and individual response to septic shock and multiple organ failure. Novel immunomodulatory agents may control endotoxaemia or bacteraemia in animal models but they have not proved effective in septic patients. This article considers whether the principal problem lies in our interpretation of the data from animal studies, or whether such models are unsuitable for assessing new treatments for the sepsis syndrome.
Predicting the Activity of Phenolic Antioxidants:  Theoretical Method, Analysis of Substituent Effects, and Application to Major Families of Antioxidants (2001)

A procedure based on density functional theory is used for the calculation of the gas-phase bond dissociation enthalpy (BDE) and ionization potential for molecules belonging to the class of phenolic antioxidants. We show that use of locally dense basis sets (LDBS) vs full basis sets gives very similar results for monosubstituted phenols, and that the LDBS procedure gives good agreement with the change in experimental BDE values for highly substituted phenols in benzene solvent. Procedures for estimating the O--H BDE based on group additivity rules are given and tested. Several interesting classes of phenolic antioxidants are studied with these methods, including commercial antioxidants used as food additives, compounds related to Vitamin E, flavonoids in tea, aminophenols, stilbenes related to resveratrol, and sterically hindered phenols. On the basis of these results we are able to interpret relative rates for the reaction of antioxidants with free radicals, including a comparison of both H-atom-transfer and single-electron-transfer mechanisms, and conclude that in most cases H-atom transfer will be dominant.
Principal component analysis by gradient descent on a constrained linear Hebbian cell (1989)

The behavior of a linear computing unit is analyzed during learning by gradient descent of a cost function equal to the sum of a variance maximization and a weight normalization term. The landscape of this cost function is shown to be composed of one local maximum, a set of saddle points, and one global minimum aligned with the principal components of the input patterns. It is possible to describe the cost landscape in terms of the hyperspheres, hypercrests, and hypervalleys associated with each of these principal components. Using this description, it is possible to show that the learning trajectory will converge to the global minimum of the landscape under certain conditions of the starting weights and learning rate of the descent procedure. Furthermore, it is possible to provide a precise description of the learning trajectory in this cost landscape. Extensions and implications of the algorithm are discussed by using networks of such cells.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Variants in folate pathway genes as modulators of genetic instability and lung cancer risk (2010)

Genetic instability plays a crucial role in cancer development. The genetic stability of the cell as well as DNA methylation status could be modulated by folate levels. Several studies suggested associations between polymorphisms in folate genes and alterations in protein expression and variations in serum levels of the folate. The objective of this study was to investigate the effect of folate pathway polymorphisms on modulating genetic instability and lung cancer risk. Genotyping of 5 SNPs in folate pathway genes and cytokinesis-blocked micronucleus cytome assay analysis (to determine the genetic instability at baseline and following NNK treatment) was conducted on 180 lung cancer cases and 180 age-, gender-, and smoking-matched controls. Our results showed that individually, folate pathway SNPs were not associated with cytogenetic damage or lung cancer risk. However, in a polygenic disease such as lung cancer, gene-gene interactions are expected to play an important role in determining the phenotypic variability of the diseases. We observed that interactions between MTHFR677, MTHFR1298, and SHMT polymorphisms may have a significant impact on genetic instability in lung cancer patients. With regard to cytogenetic alterations, our results showed that lymphocytes from lung cancer patients exposed to the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone [NNK] had considerably increased frequency of cytogenetic damage in presence of MTHFR 677, MTHFR 1298, and SHMT allelic variants. These findings support the notion that significant interactions may potentially modulate the lung cancer susceptibility and alter the overall the repair abilities of lung cancer patients when exposed to tobacco carcinogens such as NNK.
Quality improvement: Managing effective school guidance and counselling service (1996)

This paper examines the management and evaluation of school guidance and counselling service in Hong Kong. A school-based model which has the potential to improve the quality of school guidance and counselling service is proposed. The model consists of a management component and an evaluation component. The school-based strategic management component is used as a mechanism to improve the quality of guidance and counselling service. The evaluation component includes curriculum and programme, personnel, and resources and policies. Evaluation is viewed as an ongoing process to improve the quality of services.\n&lt;br&gt;\n本文是探討學校輔導服務在香港之管理和評鑑。為提高輔導服務之質素，本文建議採用一個以學校為本位之模式，此模式包括管理和評鑑兩個元素，其中校本策略性管理是用作提升輔導服務質素之機制，而評鑑則包括課程與規劃，人力調配，資源和政策三方面。在此模式中，評鑑是被視為一持續不斷的過程，用以改善服務的質素。
A useful colony colour phenotype associated with the yeast selectable/counter-selectable marker MET15 (1996)

Strains of Saccharomyces cerevisiae bearing null alleles of the met15 gene are methionine auxotrophs and become darkly pigmented in the presence of Pb2+ ions (Ono et al. (1991). Appl. Env. Microbiol. 57, 3183-3186). We describe the cloning of a useful fragment of the MET15 locus which complements both the methionine requirement and the colony colour phenotype. This colony colour phenotype is very useful for genetic screens and may be applicable for use in other yeast species. The combination of the size of MET15, along with its counter-selectability and the colour of met15 mutations make this perhaps the most versatile yeast genetic marker.
Hepatitis B virus pre-S gene-encoded antigenic specificity and anti-pre-S antibody: Relationship between anti-pre-S response and recovery (1986)

A solid-phase radioimmunoassay involving specific antibody was developed for determination of the pre-S gene-encoded epitopes of hepatitis B virus and anti-pre-S antibody in sera of hepatitis B patients. The reaction for pre-S determinants associated with HBsAg was quantitatively inhibited by soluble, polymerized human serum albumin, and the lower limit of the assay was about 1.6 ng of HBsAg per ml. Continuous expression of pre-S-coded antigenic sites on HBsAg particles in chronic hepatitis B patients seropositive for HBeAg or anti-HBe shows that these determinants may be considered as a marker of chronicity during hepatitis B virus infection. The anti-pre-S antibody was determined by inhibition of the reaction for pre-S determinants. This antibody, different from anti-HBs, was detected during HBsAg antigenemia in patients recovering from acute type B hepatitis, before anti-HBs response. Kinetics of synthesis of anti-pre-S antibody in the course of acute type B hepatitis, followed by elimination of HBsAg and recovery, suggest the possible role of this antibody in the immunological clearance of infective hepatitis B virus particles.
The Treatment Challenge of Hormone-Refractory Prostate Cancer (2001)

HRPC is now regarded as a chemotherapy-sensitive tumor. The goals of chemotherapy in HRPC are to decrease PSA level and improve quality of life. New agents and combinations are needed to improve survival.
Use of a Lipid-Coated Mesoporous Silica Nanoparticle Platform for Synergistic Gemcitabine and Paclitaxel Delivery to Human Pancreatic Cancer in Mice (2015)

Recently, a commercial albumin-bound paclitaxel (PTX) nanocarrier (Abraxane) was approved as the first new drug for pancreatic ductal adenocarcinoma in almost a decade. PTX improves the pharmaceutical efficacy of the first-line pancreatic cancer drug, gemcitabine (GEM), through suppression of the tumor stroma and inhibiting the expression of the GEM-inactivating enzyme, cytidine deaminase (CDA). We asked, therefore, whether it was possible to develop a mesoporous silica nanoparticle (MSNP) carrier for pancreatic cancer to co-deliver a synergistic GEM/PTX combination. High drug loading was achieved by a custom-designed coated lipid film technique to encapsulate a calculated dose of GEM (40 wt %) by using a supported lipid bilayer (LB). The uniform coating of the 65 nm nanoparticles by a lipid membrane allowed incorporation of a sublethal amount of hydrophobic PTX, which could be co-delivered with GEM in pancreatic cells and tumors. We demonstrate that ratiometric PTX incorporation and delivery by our LB-MSNP could suppress CDA expression, contemporaneous with induction of oxidative stress as the operating principle for PTX synergy. To demonstrate the in vivo efficacy, mice carrying subcutaneous PANC-1 xenografts received intravenous (IV) injection of PTX/GEM-loaded LB-MSNP. Drug co-delivery provided more effective tumor shrinkage than GEM-loaded LB-MSNP, free GEM, or free GEM plus Abraxane. Comparable tumor shrinkage required coadministration of 12 times the amount of free Abraxane. High-performance liquid chromatography analysis of tumor-associated GEM metabolites confirmed that, compared to free GEM, MSNP co-delivery increased the phosphorylated DNA-interactive GEM metabolite 13-fold and decreased the inactivated and deaminated metabolite 4-fold. IV injection of MSNP-delivered PTX/GEM in a PANC-1 orthotopic model effectively inhibited primary tumor growth and eliminated metastatic foci. The enhanced in vivo efficacy of the dual delivery carrier could be achieved with no evidence of local or systemic toxicity. In summary, we demonstrate the development of an effective LB-MSNP nanocarrier for synergistic PTX/GEM delivery in pancreatic cancer.
Coupling of Stress in the ER to Activation of JNK Protein Kinases by Transmembrane Protein Kinase IRE1 (2000)

Malfolded proteins in the endoplasmic reticulum (ER) induce cellular stress and activate c-Jun amino-terminal kinases (JNKs or SAPKs). Mammalian homologs of yeast IRE1, which activate chaperone genes in response to ER stress, also activated JNK, and IRE1alpha-/- fibroblasts were impaired in JNK activation by ER stress. The cytoplasmic part of IRE1 bound TRAF2, an adaptor protein that couples plasma membrane receptors to JNK activation. Dominant-negative TRAF2 inhibited activation of JNK by IRE1. Activation of JNK by endogenous signals initiated in the ER proceeds by a pathway similar to that initiated by cell surface receptors in response to extracellular signals.
Deep subwavelength nanolithography using localized surface plasmon modes on planar silver mask (2005)

The development of a near-field optical lithography is presented in this paper. By accessing short modal wavelengths of localized surface plasmon modes on a planar metallic mask, the resolution can be significantly increased while using conventional UV light source. Taking into account the real material properties, numerical studies indicate that the ultimate lithographic resolution at 20nm is achievable through a silver mask by using 365nm wavelength light. The surface quality of the silver mask is improved by adding an adhesion layer of titanium during the mask fabrication. Using a two-dimensional hole array silver mask, we experimentally demonstrated nanolithography with half-pitch resolution down to 60nm, far beyond the resolution limit of conventional lithography using I-line (365nm) wavelength.
Phenotypic mixing during coinfection of cells with two strains of human rotavirus (1988)

Coinfection of MA-104 cells with serotype 1 (Wa strain) and serotype 3 (P strain) human rotaviruses resulted in progeny viruses that were phenotypically mixed in their major outer-shell structural-protein VP7 and in the genome segment that encodes this protein (segment 9). Segments from the Wa virus predominated in these progeny whether they were of parental or reassortant genotype. Neutralization with monoclonal antibodies specific for VP7 proteins of the coinfecting viruses caused an alteration in genomic distribution favoring the strain heterologous to the neutralizing monoclonal antibody. Because the percentage of change in distribution of segment 9 was similar to that of the other combined segments, there appeared to be no greater association between VP7 and segment 9 than with other segments of the homologous virus during encapsulation. From these results, it was calculated that the progeny of coinfection with P segment 9 were 77.4% mosaic structures and 14.8% pseudotypes; progeny of coinfection with Wa segment 9 were 40.2% mosaic structures and 1.3% pseudotypes. Similar determinations were made for the reassortant progeny alone.
Fungal Sphingolipids as Targets for the Development of Selective Antifungal Therapeutics (2005)

Sphingolipids are essential membrane components, present in all eukaryotic cells, but structurally distinct in mammalian and fungal cells. Therefore, they represent an attractive new target for the development of novel antimycotics. This review will briefly highlight sphingolipid biosynthesis and functions in the yeast Saccharomyces cerevisiae. In addition, naturally occurring antifungal compounds that interact with fungal-specific sphingolipids, resulting in fungal growth arrest, will be discussed regarding their mode of action, and therapeutic value. These compounds include plant and insect defensins, syringomycin E and antifungal antibodies to sphingolipids.
Keratocan, a Cornea-specific Keratan Sulfate Proteoglycan, Is Regulatedby Lumican (2005)

Lumican is an extracellular matrix glycoprotein widely distributed in mammalian connective tissues. Corneal lumican modified with keratan sulfate constitutes one of the major proteoglycans of the stroma. Lumican-null mice exhibit altered collagen fibril organization and loss of corneal transparency. A closely related protein, keratocan, carries the remaining keratan sulfate of the cornea, but keratocan-null mice exhibit a less severe corneal phenotype. In the current study, we examined the effect of lumican overexpression in corneas of wild type mice. These mice showed no alteration in collagen organization or transparency but had increased keratocan expression at both protein and mRNA levels. Corneas of lumican-null mice showed decreased keratocan. This coupling of keratocan expression with lumican also was observed after intrastromal injection of a lumican expression minigene into the corneal stroma of Lum-/- mice. Small interfering RNA knockdown of lumican in vitro reduced keratocan expression, whereas co-injection of a lumican-expressing minigene with a beta-galactosidase reporter driven by the keratocan promoter demonstrated an increase of keratocan transcriptional activity in response to lumican expression in Lum-/- corneas in vivo. These observations demonstrate that lumican has a novel regulatory role in keratocan expression at the transcriptional level. Such results help provide an explanation for the differences in severity of corneal manifestation found in Lum-/- and Kera-/- mice. The results also suggest a critical level of small proteoglycans to be essential for collagen organization but that overabundance is not detrimental to extracellular matrix morphogenesis.
CD40-mediated signaling in monocytic cells: up-regulation of tumor necrosis factor receptor-associated factor mRNAs and activation of mitogen-activated protein kinase signaling pathways (2001)

The biochemical pathways involved in CD40 signaling have been extensively studied in B cells and B cell lines, and appear to be primarily initiated by recruitment of the tumor necrosis factor (TNF) receptor-associated factor (TRAF) signaling proteins to the CD40 cytoplasmic domain. Signaling pathways activated through CD40 in monocytes/macrophages have not been characterized as well as in B cells. Using human monocytes and the human monocytic cell line THP1, we examined signal transduction events induced by CD40 engagement with its ligand, CD154. In human monocytes, all TRAF mRNAs were expressed constitutively and CD40 ligation resulted in a strong up-regulation of TRAF1 mRNA. In THP1 cells, CD40 ligation induced expression of TRAF1 and TRAF5 mRNAs. Engagement of CD40 in both monocytes and THP1 cells led to the rapid and transient activation of the extracellular signal-regulated kinases (ERK) 1 and 2, and to low levels of JNK activation. No CD40-dependent activation of p38 mitogen-activated protein kinase (MAPK) was found. In CD154-stimulated monocytes and THP1 cells the upstream ERK1/2 activator, MAPK kinase (MEK) 1/2, and downstream substrate, c-Myc, were activated. By blocking activation of ERK1/2 with a MEK-specific inhibitor, PD98059, CD40-dependent secretion of the pro-inflammatory cytokines, TNF-alpha, IL-6 and IL-8, was demonstrated to be linked to the ERK1/2 pathway. The ERK1/2 pathway did not appear to be involved in up-regulating TRAF1 and TRAF5 mRNAs in THP1 cells. Collectively, these results suggest distinct differences between B cells and monocytic cells in CD40-dependent activation of MAPK pathways.
Near optimal detection of signals in impulsive noise modeled with a symmetric /spl alpha/-stable distribution (1998)

There has been great interest in symmetric /spl alpha/-stable distributions which have proved to be very good models for impulsive noise. However, most of the classical non-Gaussian receiver design techniques cannot be extended to the symmetric /spl alpha/-stable noise case since these techniques require an explicit compact analytical form for the probability density function (PDF) of the noise distribution which /spl alpha/-stable distributions do not possess. A new analytical representation has been suggested for the symmetric /spl alpha/-stable PDF which is based on scale mixtures of Gaussians. Based on this new analytical representation, this paper introduces a novel near-optimal receiver for the detection of signals in symmetric /spl alpha/-stable noise. The performance of the new receiver is very close to the locally optimum receiver and is significantly better than the performance of previously suggested sub-optimum receivers. The new technique has important potential in radar, sonar, and other applications.
Isolation of a T-Lymphotropic Virus from Domestic Cats with an Immunodeficiency-Like Syndrome (1987)

A highly T-lymphotropic virus was isolated from cats in a cattery in which all the animals were seronegative for feline leukemia virus. A number of cats in one pen had died and several had an immunodeficiency-like syndrome. Only 1 of 18 normal cats in the cattery showed serologic evidence of infection with this new virus, whereas 10 of 25 cats with signs of ill health were seropositive for the virus. Tentatively designated feline T-lymphotropic lentivirus, this new feline retrovirus appears to be antigenically distinct from human immunodeficiency virus. There is no evidence for cat-to-human transmission of the agent. Kittens experimentally infected by way of blood or plasma from naturally infected animals developed generalized lymphadenopathy several weeks later, became transiently febrile and leukopenic, and continued to show a generalized lymphadenopathy 5 months after infection.
COG1410 Improves Cognitive Performance and Reduces Cortical Neuronal Loss in the Traumatically Injured Brain (2009)

We have previously shown that a single dose of COG1410, a small molecule ApoE-mimetic peptide derived from the apolipoprotein E (ApoE) receptor binding region, improves sensorimotor and motor outcome following cortical contusion injury (CCI). The present study evaluated a regimen of COG1410 following frontal CCI in order to examine its preclinical efficacy on cognitive recovery. Animals were prepared with a bilateral CCI of the frontal cortex. A regimen of COG1410 (0.8mg/kg intravenously [IV]) was administered twice, at 30min and again at 24h post-CCI. Starting on day 11, the animals were tested for their acquisition of a reference memory task in the Morris water maze (MWM), followed by a working memory task in the MWM on day 15. Following CCI, the animals were also tested on the bilateral tactile adhesive removal test to measure sensorimotor dysfunction. On all of the behavioral tests the COG1410 group was no different from the uninjured sham group. Administration of the regimen of COG1410 significantly improved recovery on the reference and working memory tests, as well as on the sensorimotor test. Lesion analysis revealed that COG1410 significantly reduced the size of the injury cavity. Administration of COG1410 also reduced the number of degenerating neurons, as measured by Fluoro-Jade C staining, in the frontal cortex at 48h post-CCI. These results suggest that a regimen of COG1410 appeared to block the development of significant behavioral deficits and reduced tissue loss. These combined findings suggest that COG1410 appears to have strong preclinical efficacy when administered following traumatic brain injury (TBI).
Mineral balance and whole body bone mineral content in very low‐birth‐weight infants (1994)

Fat and mineral metabolic balance studies were performed in 25 normal very low-birth-weight infants (< or = 1500 g at birth) fed either pooled pasteurized human milk supplemented with calcium, phosphorus and magnesium, or a preterm formula. Calcium, phosphorus and magnesium intake were similar in both groups and averaged 100 mg/kg/day, 72 mg/kg/day and 8 mg/kg/day, respectively. Calcium and phosphorus retention was higher in the subjects fed fortified human milk than in those receiving a preterm formula (65 +/- 14 and 62 +/- 9 mg/kg/day versus 55 +/- 12 and 47 +/- 7 mg/kg/day respectively). The difference was only significant for phosphorus. Magnesium retention was similar in the two groups and averaged 3 mg/kg/day. Fat intake and absorption was significantly higher in the preterm formula fed group than in the one fed fortified human milk (5.5 +/- 0.4 g/kg/day and 88 +/- 4% versus 4.2 +/- 1 g/kg/day, 79 +/- 6% respectively). Assessment of the whole body bone mineral content by dual energy X-ray absorptiometry was performed at 3 and 6 months of age in another group of 25 low-birth-weight infants fed either fortified human milk or a preterm formula. Whole body bone mineral content (BMCt) was low (43.3 +/- 30.8 g of hydroxyapatite) at 3 months of age (theoretical term) compared to normal full-term newborns at birth. There was no significant influence of the diet. At 6 months of age, BMCt reached 168.6 +/- 36.6 g, a value similar to that of full-term newborns, with no significant difference between the two regimen groups.(ABSTRACT TRUNCATED AT 250 WORDS)