Miracle-dz/UniFAR-FTUs huggingface dataset:
Enhanced sensitivity of pancreatic islets from preobese 2-week-old ob/ob mice to neurohormonal stimulation of insulin secretion.

Insulin secretion from perifused islets of preobese, 2-week-old, genetically obese (ob/ob) mice and their lean littermates was examined to identify early-onset abnormalities in regulation of insulin secretion by ob/ob mice. The ob/ob mice were slightly hyperinsulinemic (+20%) and hypoglycemic (-12%) at 2 weeks of age. Pancreatic islet size, DNA content, and insulin content were similar in ob/ob and lean mice. The responsiveness of islets to glucose, as determined by 20 mM glucose-induced insulin secretion, and the sensitivity of islets to glucose, as determined by the glucose threshold for insulin secretion, were unaffected by phenotype, but two insulin secretagogues that potentiate glucose-induced insulin secretion via activation of the phospholipase-C signal transduction pathway (i.e. acetylcholine, and cholecystokinin) were more effective in stimulating insulin secretion from islets of ob/ob mice than from islets of lean mice. Both responsiveness and sensitivity to acetylcholine and cholecystokinin potentiation of glucose-induced insulin secretion were enhanced in islets from ob/ob mice. Further, glucose-dependent insulinotropic polypeptide, which stimulates glucose-induced insulin secretion via activation of adenylate cyclase, interacted with acetylcholine to further augment differences in insulin secretion between islets from ob/ob and lean mice. The signal transduction pathway common to acetylcholine and cholecystokinin, and cross-talk between this pathway and the glucose-dependent insulinotropic polypeptide signal transduction pathway are loci for early-onset defects in control of insulin secretion from islets of ob/ob mice.
FACTORS AFFECTING THE LYTIC ACTIVITY OF LYSOZYME

Since the initial discovery of lysozyme by Fleming (1922), nuimerous attempts have been made to describe the properties of this enzyme. The absence of a reliable method for the determination of enzymatic activity, however, has contributed to the incompleteness and to the inconsistency of the facts found in the literature. The availability of crystalline, egg white lysozyme has made it possible to study quantitatively some of the factors which affect its lytic activity. The assay method reported by Smolelis and Hartsell (1949) has been found to be accurate and highly adaptable to the study of this enzyme. This report concenms its application to the effect of pH, salts, ions, temperature, and manner of preparation of the cell suspension, on the activity of lysozyme.
GABAA‐receptor expression in glioma cells is triggered by contact with neuronal cells

The expression of functional GABAA‐receptors in glioma cells correlates with low malignancy of tumours and cell lines from glioma lack these receptors. Here we show that contact with neurons induces the expression of functional GABAA‐receptors. C6 and F98 glioma cell lines were labelled by recombinant expression of enhanced green fluorescent protein injected into rat brain and studied in acute slices after two to three weeks of tumour growth. The cells responded to GABA or the specific agonist, muscimol with a current typical for GABAA‐receptors, as studied with the patch‐clamp technique. To get insight into the mechanism of GABAA receptor induction, the C6 or F98 cells were co‐cultured with neurons, astrocytes, oligodendrocytes and microglia. Glioma cells expressed functional GABAA receptors within 24 h only in cultures where physical contact to neurons occurred. Activation of GABAA‐receptors in the co‐cultures attenuated glioma cell metabolism while blockade of the receptors increased metabolism. We conclude that with this form of interaction, neurons can influence tumour behaviour in the brain.
Differentiated Products Demand Systems from a Combination of Micro and Macro Data: The New Car Market

In this paper, we consider how rich sources of information on consumer choice can help to identify demand parameters in a widely used class of differentiated products demand models. Most important, we show how to use “second‐choice” data on automotive purchases to obtain good estimates of substitution patterns in the automobile industry. We use our estimates to make out‐of‐sample predictions about important recent changes in industry structure.
Some problems with the UML V1.3 metamodel

There are several well-known problem areas in UML (Version 1.3). Although many of these have been reported to the OMG's Revisionary Task Force (RTF), that venue is highly pragmatic; the author considers the detailed "theory" relating to these problem areas. He first discusses the widely used concept of stereotypes and then concentrates on the metamodel for: WP relationships; responsibilities; and Type/Interface/Class. In addition, he identifies areas of the metamodel where UML has been used inexpertly, particularly in the incorporation of generalization to incorrectly represent implementation inheritance relationships and the use of black diamond composition for relationships that are poorly argued to be whole-part relationships. Other issues discussed include the default directionality of associations; the relationship of an association to a dependency; and the general observation that the UML uses a notation that supports expressibility but is not in itself expressive.
A hybrid method for detecting outdated information in Wikipedia infoboxes

Wikipedia has grown fast and become a major information resource for users as well as for many knowledge bases derived from it. However it is still edited manually while the world is changing rapidly. In this paper, we propose a method to detect outdated attribute values in Wikipedia infoboxes by using facts extracted from the general Web. Our proposed method extracts new information by combining pattern-based approach with entity-search-based approach to deal with the diversity of natural language presentation forms of facts on the Web. Our experimental results show that the achieved accuracies of the proposed method are 70% and 82% respectively on the chief-executive-officer attribute and the number-of-employees attribute in company infoboxes. It significantly improves the accuracy of the single pattern-based or entity-search-based method. The results also reveal the striking truth about the outdated status of Wikipedia.
A Defective Viral Superantigen-Presenting Phenotype in HLA-DR Transfectants Is Corrected by CIITA1

Activation of T lymphocytes by mouse mammary tumor virus superantigen (vSAg) requires binding to MHC class II molecules. The subcellular location where functional interactions occur between MHC class II molecules and vSAgs is still a matter of debate. To gain further insight into this issue, we have used human epithelial HeLa cells expressing HLA-DR1. Surprisingly, the human cells were unable to present transfected vSAg7 or vSAg9 to a series of murine T cell hybridomas. The defect is not related to a lack of vSAg processing, because these cells can indirectly activate T cells after coculture in the presence of B lymphocytes. However, after IFN-γ treatment, the HeLa DR1+ cells became apt at directly presenting the vSAg. Furthermore, transfection of CIITA was sufficient to restore presentation. Reconstitution experiments demonstrated the necessity of coexpressing HLA-DM and invariant chain (Ii) for efficient vSAg presentation. Interestingly, inclusion of a dileucine motif in the DRβ cytoplasmic tail bypassed the need for HLA-DM expression and allowed the efficient presentation of vSAg7 in the presence of Ii. A similar trafficking signal was included in vSAg7 by replacing its cytoplasmic tail with the one of Ii. However, sorting of this chimeric Ii/vSAg molecule to the endocytic pathway completely abolished both its indirect and direct presentation. Together, our results suggest that functional vSAgs-DR complexes form after the very late stages of class II maturation, most probably at the cell surface.
Cardiac Tissue-Specific Repression of CELF Activity Disrupts Alternative Splicing and Causes Cardiomyopathy

ABSTRACT Members of the CELF family of RNA binding proteins have been implicated in alternative splicing regulation in developing heart. Transgenic mice that express a nuclear dominant-negative CELF protein specifically in the heart (MHC-CELFΔ) develop cardiac hypertrophy and dilated cardiomyopathy with defects in alternative splicing beginning as early as 3 weeks after birth. MHC-CELFΔ mice exhibit extensive cardiac fibrosis, severe cardiac dysfunction, and premature death. Interestingly, the penetrance of the phenotype is greater in females than in males despite similar levels of dominant-negative expression, suggesting that there is sex-specific modulation of splicing activity. The cardiac defects in MHC-CELFΔ mice are directly attributable to reduced levels of CELF activity, as crossing these mice with mice overexpressing CUG-BP1, a wild-type CELF protein, rescues defects in alternative splicing, the severity and incidence of cardiac hypertrophy, and survival. We conclude that CELF protein activity is required for normal alternative splicing in the heart in vivo and that normal CELF-mediated alternative splicing regulation is in turn required for normal cardiac function.
Regulation of the Escherichia coli uvrD gene in vivo

The roles of two putative promoter sequences, P1 and P2, and a potential antiterminator sequence found in the uvrD control region were examined in vivo. Constitutive and SOS-induced levels of uvrD mRNA were determined by S1 mapping, and it was shown that the majority of uvrD transcripts are from P1, while P2 plays only a minor role. A series of increasing deletions from the 5' end of the uvrD gene was used to assay transcription in the promoterless vector pKO-1. Loss of just the -35 region of P1 was sufficient to switch off detectable transcription from both P1 and P2. Disruption of the antiterminator by site-specific mutagenesis had no effect on constitutive levels of transcription, but led to a significant increase over wild-type levels following SOS induction. This suggests that the attenuator comes into play following DNA damage to moderate the increase in UvrD protein synthesis.
Papiliotrema siamense f.a., sp. nov., a yeast species isolated from plant leaves.

Two strains representing a novel species were isolated from the external surface of a sugar cane leaf (DMKU-SP85(T)) and tissue of a rice leaf (DMKU-RE97) collected in Thailand. On the basis of morphological, biochemical, physiological and chemotaxonomic characteristics, and sequence analysis of the D1/D2 region of the large subunit (LSU) rRNA gene and the internal transcribed spacer (ITS) region, the two strains were determined to represent a novel species of the genus Papiliotrema although sexual reproduction was not observed. The sequences of the D1/D2 region of the LSU rRNA gene and ITS region of the two strains were identical, but differed from those of the type strain of Cryptococcus nemorosus by 0.6 % nucleotide substitutions (four nucleotide substitutions out of 597 nucleotides) in the D1/D2 region of the LSU rRNA gene and 1.8 % nucleotide substitutions (nine nucleotide substitutions out of 499 nucleotides) in the ITS region. The name Papiliotrema siamense f.a. , sp. nov. is proposed. The type strain is DMKU-SP85(T)( = BCC 69499(T) = CBS 13330(T)).
Isolation and characterization of polymorphic microsatellite loci for the three‐toed box turtle (Terrapene carolina triunguis) and cross‐amplification in other Terrapene species

We isolated and characterized eight polymorphic microsatellite loci for a Texas population of three‐toed box turtle, Terrapene carolina triunguis, using a refined hybridization capture procedure. All eight primer pairs amplified successfully at all loci in seven Texas ornate box turtles (T. ornata ornata). Due to the decline and conservation concerns of North American box turtles, these isolated microsatellites may be a most valuable tool for evaluating baseline population genetic structure for threatened box turtle populations.
Neuronal Necrosis Inhibition by Insulin through Protein Kinase C Activation

In the serum-free culture of rat embryonic neurons, most neurons rapidly died by necrosis, which was revealed by propidium iodide (PI)-positive staining as early as 3 h after the start of culture and by marked membrane disruption and mitochondrial swelling in transmission electron microscopic (TEM) analysis. However, neither nuclear condensation/fragmentation stained with Hoechst 33342 nor activated caspase-3-like immunoreactivity was observed. In the serum-deprived culture, on the other hand, neurons showed apoptotic features, such as caspase-3 activation and nuclear damages in TEM analysis. Insulin at relatively higher concentrations, up to 100 μg/ml, ameliorated the rapid decrease in survival activity measured with 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt WST-8 assay and PI staining in the serum-free culture, despite the fact that brain-derived neurotrophic factor and insulin-like growth factor-I had no survival effect even at concentrations up to 100 μg/ml. Insulin-induced survival effects were abolished by the protein kinase C (PKC) inhibitor calphostin C but not by the phosphatidyl inositol-3-OH-kinase inhibitor wortmannin or the mitogen-activated protein kinase inhibitors PD98059 or U0126. Insulin significantly stimulated the PKC activity in cell lysates and suppressed the mitochondrial swelling and membrane disruption in TEM analysis in a calphostin C-reversible manner. All of these findings suggest that insulin inhibited the neuronal necrosis resistant to known neurotrophic factors under the serum-free culture through PKC mechanisms.
Cytoplasmic and/or Nuclear Expression of β-Catenin Correlate with Poor Prognosis and Unfavorable Clinicopathological Factors in Hepatocellular Carcinoma: A Meta-Analysis

Background The β-catenin is an important effector in WNT/β-catenin signaling pathway, which exerts a crucial role in the development and progression of hepatocellular carcinoma (HCC). Some researchers have suggested that the overexpression of β-catenin in cytoplasm and/or nucleus was closely correlated to metastasis, poor differentiation and malignant phenotype of HCC while some other researchers hold opposite point. So far, no consensus was obtained on the prognostic and clinicopathological significance of cytoplasmic/nuclear β-catenin overexpression for HCCs. Methods Systematic strategies were applied to search eligible studies in all available databases. Subgroup analyses, sensitivity analyses and multivariate analysis were performed. In this meta-analysis, we utilized either fixed- or random-effects model to calculate the pooled odds ratios (OR) and its 95% confidence intervals (CI). Results A total of 22 studies containing 2334 cases were enrolled in this meta-analysis. Pooled data suggested that accumulation of β-catenin in cytoplasm and/or nucleus significantly correlated with poor 1-, 3- and 5-year OS and RFS. Moreover, nuclear accumulation combined with cytoplasmic accumulation of β-catenin tended to be associated with dismal metastasis and vascular invasion while cytoplasmic or nuclear expression alone showed no significant effect. Besides, no significant association was observed between cytoplasmic and/or nuclear β-catenin expression and poor differentiation grade, advanced TNM stage, liver cirrhosis, tumor size, tumor encapsulation, AFP and etiologies. Additional subgroup analysis by origin suggested that the prognostic value and clinicopathological significance of cytoplasmic and/or nuclear β-catenin expression was more validated in Asian population. Multivariate analyses of factors showed that cytoplasmic and/or nuclear β-catenin expression, as well as TNM stage, metastasis and tumor size, was an independent risk factors for OS and RFS. Conclusions Cytoplasmic and/or nuclear accumulation of β-catenin, as an independent prognostic factor, significantly associated with poor prognosis and deeper invasion of HCC, and could serve as a valuable prognostic predictor for HCC.
Plasma Cells, and Their Progenitors Survival Requirements for Memory B Cells, Deregulation of c-Myc Confers Distinct

Deregulation of the c-Myc oncogene is tightly associated with human and murine plasma cell (PC) neoplasms. Through the analysis of Ag-speciﬁc B cell responses in mice where Myc is targeted to the Igh C (cid:1) locus, we show here that c-Myc dramatically impairs the primary and secondary Ab response. This impairment is differentiation stage speciﬁc, since germinal center B cell formation, afﬁnity maturation, and class switch recombination were intact. Examination of PC viability revealed that c-Myc triggered apoptosis only upon ﬁnal maturation when Ab is secreted and is resistant to the survival factor BAFF (B cell-activating factor belonging to the TNF family). In contrast, PC precursors (PC pre ) that ultimately give rise to mature PCs survived normally and vigorously expanded with BAFF signaling. We further show that c-Myc also facilitates the apoptosis of memory B cells. Thus, C (cid:1) -Myc controls both cellular arms of long-lived B cell immunity than previously anticipated. Only when deregulation of c-Myc was combined with enforced Bcl-x L expression were mature PCs able to survive in response to BAFF. These data indicate that the survival requirements for tumor-susceptible PC pre and PCs are distinct and that tumor progression likely develops as PC pre transition to functional PCs when apoptotic pathways such as members of the Bcl-2 family are disabled. The Journal of Immunology, 2008, 181: 7537–7549. overlap and data analysis were performed using FlowJo software (Tree Star). Proﬁles are presented as 5% probability contours including outliers with gating based on ﬂuorescence-minus-one and isotype controls. Cell and nuclear morphology of apoptotic cells, as measured by 7-AAD staining of fragmented irregular-shaped nuclei, was performed using the ImageStream 100 cytometer (Amnis) as previously described (35). Brieﬂy, the instrument uses hydrodynamic focusing of cells in a core stream and illuminates cells in ﬂow for ﬂuorescence, dark ﬁeld, and bright ﬁeld image detection. All light is collected and separated by wavelength bands using a spectral decomposition optical system, resulting in six subimages being collected for each cell based on spectral properties of bright ﬁeld, dark ﬁeld, and four ﬂuorescences. Images of 10,000 cells per sample were analyzed using the IDEAS version 3.0 image analysis software (Amris). Us- ing the brightﬁeld intensity gradient feature that determines image sharp-ness, images that are considered out of focus are excluded. Spectral overlap among the four ﬂuorescences is removed by creating a compensation matrix using single-color ﬂuorescent control samples that are collected on the instrument without bright ﬁeld illumination. A matrix coefﬁcient intensity plot is generated for each ﬂuorescence, applied, and validated using control images. After compensation, images of in-focus single cells were selected on the basis of small bright ﬁeld area, high bright ﬁeld aspect ratio, and high nuclear contrast. Abs FAST 5-bromo-4-chlor-3-indolyl phosphate/NBT substrate Ab-secreting quantiﬁed direct
Mutant KRAS is a druggable target for pancreatic cancer

Significance Pancreatic cancer is still one of the major challenges in clinical oncology. Mutant KRAS is a driving oncogene in the majority of human pancreatic cancer cases. We have made an effort to meet this challenge by developing a therapeutic platform for local and prolonged delivery of siRNA. Our results show that the siRNA targeted against KRAS mutations with a local prolonged release system knocks down KRAS expression in vitro and in vivo, leading to an antitumor effect. Our report describes an applicable and efficient delivery method of siRNA that overcomes the major obstacles of toxicity and organ accessibility. Notably our approach enabled the conversion of KRAS from a nondruggable to a potentially druggable cancer target. Pancreatic ductal adenocarcinoma (PDA) represents an unmet therapeutic challenge. PDA is addicted to the activity of the mutated KRAS oncogene which is considered so far an undruggable therapeutic target. We propose an approach to target KRAS effectively in patients using RNA interference. To meet this challenge, we have developed a local prolonged siRNA delivery system (Local Drug EluteR, LODER) shedding siRNA against the mutated KRAS (siG12D LODER). The siG12D LODER was assessed for its structural, release, and delivery properties in vitro and in vivo. The effect of the siG12D LODER on tumor growth was assessed in s.c. and orthotopic mouse models. KRAS silencing effect was further assessed on the KRAS downstream signaling pathway. The LODER-encapsulated siRNA was stable and active in vivo for 155 d. Treatment of PDA cells with siG12D LODER resulted in a significant decrease in KRAS levels, leading to inhibition of proliferation and epithelial–mesenchymal transition. In vivo, siG12D LODER impeded the growth of human pancreatic tumor cells and prolonged mouse survival. We report a reproducible and safe delivery platform based on a miniature biodegradable polymeric matrix, for the controlled and prolonged delivery of siRNA. This technology provides the following advantages: (i) siRNA is protected from degradation; (ii) the siRNA is slowly released locally within the tumor for prolonged periods; and (iii) the siG12D LODER elicits a therapeutic effect, thereby demonstrating that mutated KRAS is indeed a druggable target.
Integrating microsecond circuit switching into the data center

Recent proposals have employed optical circuit switching (OCS) to reduce the cost of data center networks. However, the relatively slow switching times (10--100 ms) assumed by these approaches, and the accompanying latencies of their control planes, has limited its use to only the largest data center networks with highly aggregated and constrained workloads. As faster switch technologies become available, designing a control plane capable of supporting them becomes a key challenge. In this paper, we design and implement an OCS prototype capable of switching in 11.5 us, and we use this prototype to expose a set of challenges that arise when supporting switching at microsecond time scales. In response, we propose a microsecond-latency control plane based on a circuit scheduling approach we call Traffic Matrix Scheduling (TMS) that proactively communicates circuit assignments to communicating entities so that circuit bandwidth can be used efficiently.
A Reverse Transcriptase-Dependent Mechanism Plays Central Roles in Fundamental Biological Processes

This review summarizes emerging evidence that LINE-1 (Long Interspersed Nuclear Elements) -encoded reverse transcriptase (RT) regulates fundamental biological processes. Earlier studies showed that sperm cells can be used as vectors of both exogenous DNA and RNA molecules in sperm-mediated gene transfer assays. During these studies, a sperm endogenous RT activity was identified, which can reverse-transcribe exogenous RNA directly, or DNA molecules through sequential transcription and reverse transcription. Resulting cDNA copies generated in sperm cells can be delivered to embryos at fertilization, further propagated in tissues as low-copy extrachromosomal structures and transmitted to the progeny in a non-mendelian fashion. Being transcriptionally competent, they can induce phenotypic variations in positive tissues. An RT activity is also present in preimplantation embryos, and its inhibition causes developmental arrest in early preimplantation stages, paralleled by an extensive reprogramming of gene expression. In analogy with this, drug-mediated inhibition of RT activity, or RNA interference-mediated silencing of human LINE-1, reduce cell proliferation and induce differentiation in a variety of cancer cell lines. Furthermore, RT inhibition in vivo antagonizes the growth of human tumors in animal models. As a whole, these data implicate a RT-dependent machinery in the genesis of new genetic information in spermatozoa and in normal and pathological developmental processes.