gebhart/patrepeval huggingface dataset:
Mediterranean Diet, Inflammatory and Metabolic Biomarkers, and Risk of Alzheimer's Disease (2010)

We aimed to investigate the association between adherence to the Mediterranean diet (MeDi) and Alzheimer's disease (AD) risk in a prospective study. Specifically, we analyzed reduced inflammation and improved metabolic profile as a potential medium through which the MeDi reduced the risk of AD. During a 4-year follow-up, 118 incident AD cases were identified among the 1219 non-demented elderly (age ≥ 65) subjects who provided dietary information and blood samples at baseline. We used high-sensitivity C-reactive protein (hsCRP) as an index of systemic inflammation, and fasting insulin and adiponectin as indexes of metabolic profile. We investigated whether there was a change in the association between MeDi and incident AD risk when the biomarkers were introduced into multivariable adjusted COX models. Better adherence to MeDi was associated with lower level of hsCRP (p =0.003), but not fasting insulin or adiponectin. Better adherence to MeDi was significantly associated with lower risk for AD: compared to those in the lowest tertile of MeDi, subjects in the highest tertile had a 34% less risk of developing AD (p-for-trend =0.04). Introduction of the hsCRP, fasting insulin, adiponectin, or combinations of them into the COX model did not change the magnitude of the association between MeDi and incident AD. Ultimately, the favorable association between better adherence to MeDi and lower risk of AD did not seem to be mediated by hsCRP, fasting insulin, or adiponectin. Other aspects of inflammatory and metabolic pathways not captured by these biomarkers, or non-inflammatory or non-metabolic pathways, may be relevant to the MeDi-AD association.
Overexpression of interleukin-15 in mice promotes resistance to diet-induced obesity, increased insulin sensitivity, and markers of oxidative skeletal muscle metabolism (2011)

Interleukin-15 (IL-15) is a cytokine that is highly expressed in skeletal muscle. In addition to its well-characterized effects on innate immunity, IL-15 has been proposed to modulate skeletal muscle and adipose tissue mass, as well as insulin sensitivity. In the present study, an IL-15 gain-of-function model, transgenic mice with skeletal muscle-specific oversecretion of IL-15 (IL-15 Tg mice), was utilized to test the hypotheses that IL-15 promotes insulin sensitivity and resistance to diet-induced obesity (DIO) by increasing circulating adiponectin levels, and that IL-15 regulates skeletal muscle metabolism without inducing overt muscle hypertrophy. Compared to closely related control mice, IL-15 Tg mice exhibited lower total body fat following high-fat feeding, lower intra-abdominal fat following both low- and high-fat feeding, and greater insulin sensitivity. However, this was not accompanied by increased total or high molecular weight serum adiponectin levels in IL-15 Tg mice. While overall lean body mass did not differ, IL-15 Tg mice exhibited increased mass of the oxidative soleus muscle, and increased expression of mRNA encoding the slow isoform of troponin I (TnnI 1) in the predominately glycolytic extensor digitorum longus muscle. Skeletal muscle tissue from IL-15 Tg mice also exhibited alterations in the expression of several genes associated with fatty acid metabolism, such as SIRT1, SIRT4, and uncoupling protein 2 (UCP2). These findings suggest changes in oxidative metabolism, rather than induction of adiponectin expression, appear to be responsible for the DIO-resistant and more insulin-sensitive phenotype of IL-15 Tg mice.
The expression of TIP30 in primary focus and liver metastasis of gastric cancer (2009)

Objective To detect the expression of TIP30 in primary focus and liver metastasis of gastric cancer, and approach its role in the genesis and development of gastric cancer.Methods The expression of TIP30 was detected by using immunohistoehemical staining and RT-PCR in 86 eases of gastric carcinomas and 22 cases of liver metastasis.Results (1) The positive rate of TIP30 was 60.5% and 45.5% in cancerous tissues and liver metastasis respectively,significantly higher than and normal tissues (89.5 %) (P < 0.05).(2) The expression of TIP30 in gastric cancer was correlated with lymphnode metastasis, but not with age, sex, and pathological differentiation.(3) The expression level of TIP30 was significantly lower in cancerous tissues than in the liver metastasis (P < 0.05).Conclusion The expression level of TIP30 was decreased obviously in gastric caicinoma and liver metastasis, suggesting its role in the genesis and development of gastric cancer.

Key words: 
Gastric caicinoma;  TIP30;  Metastasis
Selective Degradation of Early-Response-Gene mRNAs: Functional Analyses of Sequence Features of the AU-Rich Elements (1994)

The metabolic lifetime of mRNA can be specified by specific cis-acting elements within mRNA. One type of element is an adenylate- and uridylate-rich element (ARE) found in the 3' untranslated region of many highly unstable mRNAs for mammalian early-response genes (ERGs). Among the better-characterized members of the ERG family are certain genes encoding nuclear transcription factors. Of particular significance was the finding that their mRNAs decay rapidly with kinetics similar to those of c-fos mRNA. Our previous studies of the c-fos ARE-directed mRNA decay have revealed the existence in this ARE of two structurally distinct and functionally interdependent domains, termed domain I and domain II. We proposed that the c-fos ARE-directed decay is a two-step mechanism in which rapid shortening of the poly(A) tail leads to the decay of the mRNA body and further hypothesized that this is a general mechanism by which the ERG AREs mediate rapid mRNA degradation. To test this hypothesis and to further address the generality of the critical structural characteristics within the c-fos ARE, the RNA-destabilizing functions of more than 10 different AU-rich sequences from various nuclear transcription factor mRNAs have been tested. Consistent with the above-mentioned hypothesis is the observation that mRNAs carrying the functional AREs display a biphasic decay, which is characteristic of the proposed two-step mechanism. Our results indicated that the presence of AUUUA pentanucleotides in an AU-rich region does not always guarantee an RNA-destabilizing function for this region. Our results also led to the identification of a novel class of AU-rich destabilizing elements which contains no AUUUA pentanucleotide. The results of sequence comparison and functional tests revealed that a continuous U-rich sequence is a unique feature among the functional AREs. Finally, our experiments further showed that the c-fos ARE domain II has an RNA decay-enhancing ability upon its fusion to heterologous AU-rich regions and defined for the first time an RNA decay-enhancing element, which we termed the RDE element.
Using Deep Convolutional Neural Networks for Image Retrieval (2016)

In content-based image retrieval, the most challenging problem is the &#x201C;semantic gap&#x201D; between low-level visual features captured by machines and high-level semantic concepts perceived by human. This paper focuses on the high-level image features learning by the convolutional neural networks (CNN) in image retrieval. As a deep learning framework, CNN can extract meaningful image features in different layers, and transfer the image content into (abstract) semantic concepts. These high-level features descriptors can be better image representations than the hand-crafted feature descriptors, and further improve the image retrieval performance. The experimental results showed that layerwise learning invariant feature hierarchies in CNN is good at feature representations. Using CNN for feature extractions on CIFAR-10 and CIFAR-100 dataset, it achieved 0.707 and 0.244 of mean average precision (MAP), respectively.
Cavity-enhanced optical frequency comb spectroscopy: application to human breath analysis (2008)

Broad-bandwidth, high-spectral-resolution optical detection of human breath has identified multiple important biomarkers correlated with specific diseases and metabolic processes. This optical-frequency-comb-based breath analysis system comes with excellent performance in all criteria: high detection sensitivity, ability to identify and distinguish a large number of analytes, and simultaneous, real-time information processing. We demonstrate a minimum detectable absorption of 8 x 10(-10)cm(-1), a spectral resolution of 800 MHz, and 200 nm of spectral coverage from 1.5 to 1.7 microm where strong and unique molecular fingerprints exist for many biomarkers. We present a series of breath measurements including stable isotope ratios of CO(2), breath concentrations of CO, and the presence of trace concentrations of NH(3) in high concentrations of H(2)O.
Doxorubicin Induces Apoptosis in Normal and Tumor Cells via Distinctly Different Mechanisms (2004)

Doxorubicin (DOX), a widely used chemotherapeutic agent, exhibits cardiotoxicity as an adverse side effect in cancer patients. DOX-mediated cardiomyopathy is linked to its ability to induce apoptosis in endothelial cells and cardiomyocytes by activation of p53 protein and reactive oxygen species. We evaluated the potential roles of H(2)O(2) and p53 in DOX-induced apoptosis in normal bovine aortic endothelial cells and adult rat cardiomyocytes and in tumor cell lines PA-1 (human ovarian teratocarcinoma) and MCF-7 (human breast adenocarcinoma). Time course measurements indicated that activation of caspase-3 preceded the stimulation of p53 transcriptional activity in endothelial cells. In contrast, DOX caused early activation of p53 in tumor cells that was followed by caspase-3 activation and DNA fragmentation. These findings suggest that the transcriptional activation of p53 in DOX-induced apoptosis in endothelial cells may not be as crucial as it is in tumor cells. Further evidence was obtained using a p53 inhibitor, pifithrin-alpha. Pifithrin-alpha completely suppressed DOX-induced activation of p53 in both normal and tumor cell lines and prevented apoptosis in tumor cell lines but not in endothelial cells and cardiomyocytes. In contrast, detoxification of H(2)O(2), either by redox-active metalloporphyrin or overexpression of glutathione peroxidase, decreased DOX-induced apoptosis in endothelial cells and cardiomyocytes but not in tumor cells. This newly discovered mechanistic difference in DOX-induced apoptotic cell death in normal versus tumor cells will be useful in developing drugs that selectively mitigate the toxic side effects of DOX without affecting its antitumor action.
Site-Specific Cleavage of RNA by a Metal-Free Artificial Nuclease Attached to Antisense Oligonucleotides (2006)

RNA cleaving tris(2-aminobenzimidazoles) have been attached to DNA oligonucleotides via disulfide or amide bonds. The resulting conjugates are effective organocatalytic nucleases showing substrate and site selectivity as well as saturation kinetics. The benzimidazole conjugates also degrade enantiomeric RNA. This observation rules out contamination effects as an alternative explanation of RNA degradation. The pH dependency shows that the catalyst is most active in the deprotonated state. Typical half-lifes of RNA substrates are in the range of 12-17 h. Thus, conjugates of tris(2-aminobenzimidazoles) can compete with the majority of metal-dependent artificial nucleases.
评C.奥菲著:《福利国家的矛盾》 (1986)

在《福利国家的矛盾》一书出版之前,讲英语的读者只能在某些不知名的学术刊物中才能看到德国社会学家克劳斯·奥菲的著作(他的有关劳动组织的论文《工业与平等》是例外).对于研究奥菲著作的理论家来说,这种状况是令人遗憾的.《福利国家的矛盾》汇集了奥菲在过去十年中的主要政治论文,因而改变了这种状况.奥菲创立的福利国家的矛盾的理论,
The NeurotroDhins BDNF, NT‐3 and NT‐4/5 Promote Survival and Morphological and Biochemical Differentiation of Striatal Neurons In Vitro (1995)

The neurotrophins, brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), neurotrophin 4/5 (NT-4/5) and nerve growth factor (NGF), were compared for their effects on the survival and differentiation of embryonic rat striatal neurons grown in low-density cultures. Treatment with BDNF for 8 days resulted in a 40% increase in overall neuronal survival, a 3- to 5-fold increase in the number of calbindin-immunoreactive neurons, and an 80% increase in GABA-positive neurons. Treatment with NT-3 or NT-4/5 produced a 2- to 3-fold increase in the number of calbindin-positive neurons and an increase in GABA-positive cell number similar to that induced by BDNF, BDNF treatment produced a striking morphological differentiation of striatal GABAergic neurons, which was characterized by a doubling of the number of neurite branch points, the total area of aborization and the perikaryal area compared to control cultures. All three of these factors increased high-affinity GABA uptake 2-fold. NGF had no effect on any of the parameters examined. Our results show that BDNF, NT-3 and NT-4/5 promote the survival and/or differentiation of calbindin-immunopositive and GABAergic striatal neurons.
α1-antitrypsin gene polymorphisms are not associated with renal arterial fibromuscular dysplasia (2006)

Polymorphisms PiM1, PiZ and PiS of the AAT gene are not associated with renal FMD or infraclinical carotid lesions detected by echotracking methods. As the true prevalence of renal FMD is not precisely known and alpha1-antitrypsin deficiency is not infrequent in the general population, the association of the two may occur by chance.
Construction of aNotI linking library and isolation of new markers close to the Huntington's disease gene (1988)

Linking clones contain sequences flanking recognition sites for enzymes cutting rarely in mammalian DNA. They can be used to obtain and correlate both physical and genetic mapping information over subregions of mammalian chromosomes. We have constructed and used a NotI linking clone library representing unmethylated NotI sites from HHW693 DNA, a hamster hybrid cell line containing 4p15-4pter and a fragment of 5p as its only human chromosome contribution. Human clones were identified by hybridisation with a cloned human repeat sequence, and localised further to subregions of human chromosome 4p15-4pter using a panel of additional hybrids. Clones from the region distal to the DNA probes (D4S10, D4S43, D4S95) linked to the Huntington's disease mutation, were further analysed. Four markers close to the HD gene: D4S111, D4S113, D4S114 and clone 417 are described here. In addition to serving as markers in physical and genetic mapping experiments, these linking clones provide probes next to cleavable NotI sites, and can therefore be used to screen NotI based chromosome jumping libraries. They also provide indications for potential gene sequences, identifiable as evolutionarily conserved sequences.
Rates of Infection and Bleeding Are Not Increased in Patients with Myelodysplastic Syndromes (MDS) Treated with Azacitidine Compared with Supportive Care. (2005)

Abstract MDS are heterogeneous hematopoietic disorders characterized by dyspoiesis and cytopenias. Most patients with high-risk MDS die within 1 year from infection or hemorrhage usually attributable to bone marrow failure or progression to AML. In a phase 3, open-label, multicenter, randomized study comparing azacitidine (Vidaza®) plus supportive care (N=99) versus supportive care alone (N=91) in patients with MDS (JCO2002;20:2429), treatment with azacitidine was associated with worsening of pre-existing cytopenias in up to 78% (115/147) of patients with pre-existing cytopenias. The median time to first occurrence of any worsening cytopenia was 8 days (interquartile range: 6 to 15 days). All patients were treated with the same initial dose of azacitidine (75 mg/m2/day); no dose adjustments were made for pre-existing cytopenias despite the severity. We examined rates of infection and bleeding associated with azacitidine therapy in comparison with the rates seen with the underlying disease (supportive care). Our results are based on re-collected data from patients described in the published report; our analyses were conducted separately and independently. Total exposure for azacitidine was the cumulative time from the first dose to the end of study (30 days after last dose), and for supportive care was the cumulative time from randomization to withdrawal from study or day prior to crossover. The azacitidine group included all patients exposed to azacitidine (N=150), which included patients randomized to azacitidine (N=99) and patients after crossing over from supportive care (N=51). Similar to the rate of infections previously reported in patients with MDS (AJM1991; 90:338), infections occurred in patients in the supportive care group at nearly one per patient-year. However, infections occurred at an overall lower rate (patient-years) in the azacitidine group (0.64) compared with the supportive care group (0.95). (Table). Similarly, the overall rate (patient-years) of bleeding events was comparable between azacitidine (0.56) and supportive care (0.60). In particular, bleeding events in the gastrointestinal system occurred at a similar rate between the azacitidine group (0.26) and the supportive care group (0.25). This was also true for bleeding events in the central nervous system (azacitidine: 0.01, supportive care: 0.02). The rates of infection and bleeding were 3 to 4 times higher during cycles 1 and 2 in both treatment groups, reflecting the severity of the underlying disease at study entry. In summary, despite the potential to exacerbate pre-existing cytopenias early in therapy, treatment with azacitidine did not increase the rate of infection and bleeding above the rate due to the underlying disease. Infection Rates (Patient-Years of Exposure) in Protocol 9221
Identification and Characterization of a Sequence Motif Involved in Nonsense-Mediated mRNA Decay (1995)

In both prokaryotes and eukaryotes, nonsense mutations in a gene can enhance the decay rate or reduce the abundance of the mRNA transcribed from that gene, and we call this process nonsense-mediated mRNA decay. We have been investigating the cis-acting sequences involved in this decay pathway. Previous experiments have demonstrated that, in addition to a nonsense codon, specific sequences 3' of a nonsense mutation, which have been defined as downstream elements, are required for mRNA destabilization. The results presented here identify a sequence motif (TGYYGATGYYYYY, where Y stands for either T or C) that can predict regions in genes that, when positioned 3' of a nonsense codon, promote rapid decay of its mRNA. Sequences harboring two copies of the motif from five regions in the PGK1, ADE3, and HIS4 genes were able to function as downstream elements. In addition, four copies of this motif can function as an independent downstream element. The sequences flanking the motif played a more significant role in modulating its activity when fewer copies of the sequence motif were present. Our results indicate the sequences 5' of the motif can modulate its activity by maintaining a certain distance between the sequence motif and the termination codon. We also suggest that the sequences 3' of the motif modulate the activity of the downstream element by forming RNA secondary structures. Consistent with this view, a stem-loop structure positioned 3' of the sequence motif can enhance the activity of the downstream element. This sequence motif is one of the few elements that have been identified that can predict regions in genes that can be involved in mRNA turnover. The role of these sequences in mRNA decay is discussed.
Synthesis and biological evaluation of 1-(1,2-benzisothiazol-3-yl)- and (1,2-benzisoxazol-3-yl)piperazine derivatives as potential antipsychotic agents (1986)

Members of the series of title compounds were tested for potential antipsychotic activity in relevant receptor binding assays and behavioral screens. Structure-activity relationships within the series are discussed. Compound 24 (BMY 13859-1), a (1,2-benzisothiazol-3-yl)piperazine derivative, was selected for further study because of its potent and selective profile in primary CNS tests. It was active in the Sidman avoidance paradigm and blocked amphetamine-induced stereotyped behavior in dogs for up to 7 h. The compound's lack of typical neuroleptic-like effects in the rat catalepsy test and its failure to produce dopamine receptor supersensitivity following chronic administration indicate that it should not cause the movement disorders commonly associated with antipsychotic therapy. Although 24 has potent affinity for dopaminergic binding sites, its even greater affinity for serotonin receptors suggests that a serotonergic component may be relevant to its atypical profile. Compound 24 is currently undergoing clinical evaluation in schizophrenic patients.
Enhanced amygdala and medial prefrontal activation during nonconscious processing of fear in posttraumatic stress disorder: An fMRI study (2007)

Biological models of posttraumatic stress disorder (PTSD) suggest that patients will display heightened amygdala but decreased medial prefrontal activity during processing of fear stimuli. However, a rapid and automatic alerting mechanism for responding to nonconscious signals of fear suggests that PTSD may display heightened rather than decreased MPFC under nonconscious processing of fear stimuli. This study used functional magnetic resonance imaging to examine blood oxygenation level-dependent signal changes during nonconscious presentation (16.7 ms, masked) of fearful and neutral faces in 15 participants with PTSD and 15 age and sex-matched healthy control participants. Results indicate that PTSD participants display increased amygdala and MPFC activity during nonconscious processing of fearful faces. These data extend existing models by suggesting that the impaired MPFC activation in PTSD may be limited to conscious fear processing. Hum Brain Mapp, 2008. (c) 2007 Wiley-Liss, Inc.
Gated Luminescence Imaging of Silicon Nanoparticles (2015)

The luminescence lifetime of nanocrystalline silicon is typically on the order of microseconds, significantly longer than the nanosecond lifetimes exhibited by fluorescent molecules naturally present in cells and tissues. Time-gated imaging, where the image is acquired at a time after termination of an excitation pulse, allows discrimination of a silicon nanoparticle probe from these endogenous signals. Because of the microsecond time scale for silicon emission, time-gated imaging is relatively simple to implement for this biocompatible and nontoxic probe. Here a time-gated system with ∼10 ns resolution is described, using an intensified CCD camera and pulsed LED or laser excitation sources. The method is demonstrated by tracking the fate of mesoporous silicon nanoparticles containing the tumor-targeting peptide iRGD, administered by retro-orbital injection into live mice. Imaging of such systemically administered nanoparticles in vivo is particularly challenging because of the low concentration of probe in the targeted tissues and relatively high background signals from tissue autofluorescence. Contrast improvements of >100-fold (relative to steady-state imaging) is demonstrated in the targeted tissues.