cssi/SciSciGPT-SciSciNet huggingface dataset:
Pharmacokinetics and toxicology of a fibroblast activation protein (FAP)-activated prodrug in murine xenograft models of human cancer.

BACKGROUND As carcinoma progresses, the stroma undergoes a variety of phenotypic changes, including the presence of carcinoma-associated fibroblasts (CAFs) that express fibroblast activation protein (FAP). FAP is a post-prolyl endopeptidase whose expression in a healthy adult is largely restricted to the cancer-associated stroma. FAP-targeted prodrugs with a 100-fold greater therapeutic window over the parent compound were previously generated. METHODS Prodrugs and non-cleavable controls were incubated in the presence of FAP. Plasma and tumor half-lives (t1/2) of the full-length and active forms of the prodrugs were determined using LCMS. Biodistribution studies of prodrug activation were performed. Histopathological analysis of tissues from treated animals were compared to vehicle-treated controls. Toxicity and efficacy studies were performed in human breast (MDA-MB-231 and MCF-7) and prostate (LNCaP) cancer xenografts models. RESULTS These FAP-activated prodrugs have a significantly slower clearance from tumor tissue than the circulation (∼12 vs. ∼4.5 hr). Micromolar concentrations of active drug persist in the tumor. Active drug is detected in non-target tissues; however, histopathologic evaluation reveals no evidence of drug-induced toxicity. A FAP-activated prodrug (ERGETGP-S12ADT) inhibits tumor growth in multiple human breast and prostate cancer xenograft models. The anti-tumor effect is comparable to that observed with docetaxel, but results in significantly less toxicity. CONCLUSION FAP-activated prodrugs are a viable strategy for the management of prostate and other cancers. These prodrugs exhibit less toxicity than a commonly used chemotherapeutic agent. Further refinement of the FAP cleavage site for greater specificity may reduce prodrug activation in non-target tissues and enhance clinical benefit. Prostate 74: 1308–1319, 2014. © 2014 Wiley Periodicals, Inc.
After Kelo, Curbing Opportunistic TIF-Driven Economic Development: Forgoing Ineffectual Blight Tests; Empowering Property Owners and School Districts

When economic development or urban redevelopment is funded by tax increment financing (TIF), local government officials, in their haste to pump up local tax receipts, may become overzealous in displacing some private land users to make way for private developers They are also tempted to hog property tax revenues collected from the project area and use it to repay redevelopment agency debt. These tax proceeds would previously have been divided among cities, counties, school districts and other taxing entities. This paper is about the legal solutions afoot to deal with these controversial aspects of TIF funded economic development - displacement of private owners for private development projects and diversion of the property tax base from other taxing entities.Most states require findings of blight as a pre-condition to economic development or redevelopment projects. They hope their blight tests will meet ‘public use’ challenges and steer local governments away from economic development projects of questionable value. But blight definitions vary greatly. Some are so expansive and vague as to be virtually meaningless as constraints. Also, the same definition of blight cannot fulfill both these functions adequately because a blight definition protective of property owners must shield unblighted properties from the threat of condemnation while a blight norm meant to limit economic development to areas that desperately need rejuvenation must be predicated on an area wide basis, and include unblighted properties necessary for a successful economic development effort.This paper recounts the measures that most states have enacted to complement or replace blight tests. Among these, states have enacted outright prohibitions on economic development takings, approved more generous compensation standards, instituted reforms in the planning process favoring citizen participation, and mandated condemnor’s to negotiate acquisition prices fairly. States have also legislated to safeguard school districts and other taxing entities from having their tax bases raided by opportunistic economic development projects. These enactments are described briefly here as well.At the same time, state courts have been responding to ‘public use’ challenges to economic development takings in the wake of Kelo v. City of New London. Local governments undertake economic development projects to spike local tax and job rolls, enhance urban infrastructure (street improvements, ball parks, affordable housing), and advance planning norms, such as those favoring increased urban densities to facilitate the use of public transit. Many courts seem sensitive to the purposes of economic development projects and are more sympathetic to projects offering traditional ‘public goods’ such as infrastructure and planning improvements than they are to projects with no apparent ‘public use’ other than to increase the redeveloping jurisdiction’s tax rolls.
Review of The Highway Revolution: 1895–1925: How the United States Got Out of the Mud by I. B. Holley, Jr.

Reluctance of elected officials to raise taxes for highways; deferred maintenance due to inadequate investment capital; holding to the promise of private investment to provide needed highway capacity; emerging technologies that make road building more efficient; and a growing national need for transportation professionals who will build and operate the future highway network. Sound familiar? As described by Professor Holley in his book on the emergence of the highway industry in the United States, these same issues that characterize today’s transportation profession were also present in the early highway years in the United States. In a remarkably detailed and comprehensive examination of the first 30 years of the highway age in America, Professor Holley convincingly describes the major factors that have led to today’s highway network and management structure. The book spans numerous topics that a transportation professional will find of interest. Chapters include financing strategies that were tried and failed in the early years, and the rationale for the financing system we have today; the evolving materials and construction technology that allowed the rapid expansion of the nation’s road network following World War II; and the information dissemination and training efforts that promoted the emergence of the transportation engineering profession. The book also describes the early efforts at highway contracting and how the process evolved as experience was gained in the best ways of
The Greeks and Greek Love by James Davidson

The first in the long series of kisses he would receive over the course of the day were from Fazio. —The Terracotta Dog, Andrea Camilleri (2002, p. 213) Male sexuality, whether in the modern Medite...
The α‐Ketoglutarate Dehydrogenase Complex

Damage from oxidative stress and mitochondrial dysfunction occur together in many common neurodegenerative diseases. The enzymes that form the mitochondrial α-ketoglutarate-dehydrogenase complex (KGDHC), a key and arguably rate-limiting enzyme system of the tricarboxylic acid cycle, might mediate the interaction of these processes. KGDHC activity is reduced in numerous age-related neurodegenerative diseases and is diminished by oxidative stress. In Alzheimer’s disease (AD), the reduction correlates highly to diminished mental performance. Thus, research has focused on the mechanisms by which select oxidants reduce KGDHC and the consequences of such a reduction. Diminished KGDHC in cells is associated with apoptosis without changes in the mitochondrial membrane potential. Studies of isolated mitochondria and of animal models suggest that a reduction in KGDHC can predispose to damage by other toxins that promote neurodegeneration. Diminished oxidative metabolism can be plausibly linked to pathological features of neurodegenerative diseases (e.g., reduced mental function, the plaques and tangles in AD). Thus, reductions in KGDHC might be central to the pathophysiology of these diseases. Studies of proteins, cells, animal models, and humans suggest that treatments to diminish, or bypass, the reduction in KGDHC might be beneficial in age-related neurodegenerative disorders.
Journalism and "The Call to Allah": Teaching Journalism in Indonesia’s Islamic Universities and State Institutes

There are 18 Islamic universities and institutes in Indonesia, and each offers some sort of journalism education. These courses are not located in the social sciences, but rather in schools of dakwah, where they are seen as key elements of Islamic propagation. This article focuses on three aspects of journalism education in Islamic Indonesia: the “vision and mission” of dakwah, the curriculum and course content, and what happens to students upon graduation. It concludes with thoughts on the similarities and differences with what has been called “prophetic journalism” in the United States, and a discussion of the overall goals of journalism in an Islamic context.
Monitoring a Nuclear Factor-κB Signature of Drug Resistance in Multiple Myeloma

The emergence of acquired drug resistance results from multiple compensatory mechanisms acting to prevent cell death. Simultaneous monitoring of proteins involved in drug resistance is a major challenge for both elucidation of the underlying biology and development of candidate biomarkers for assessment of personalized cancer therapy. Here, we have utilized an integrated analytical platform based on SDS-PAGE protein fractionation prior to liquid chromatography coupled to multiple reaction monitoring mass spectrometry, a versatile and powerful tool for targeted quantification of proteins in complex matrices, to evaluate a well-characterized model system of melphalan resistance in multiple myeloma (MM). Quantitative assays were developed to measure protein expression related to signaling events and biological processes relevant to melphalan resistance in multiple myeloma, specifically: nuclear factor-κB subunits, members of the Bcl-2 family of apoptosis-regulating proteins, and Fanconi Anemia DNA repair components. SDS-PAGE protein fractionation prior to liquid chromatography coupled to multiple reaction monitoring methods were developed for quantification of these selected target proteins in amounts of material compatible with direct translation to clinical specimens (i.e. less than 50,000 cells). As proof of principle, both relative and absolute quantification were performed on cell line models of MM to compare protein expression before and after drug treatment in naive cells and in drug resistant cells; these liquid chromatography-multiple reaction monitoring results are compared with existing literature and Western blots. The initial stage of a systems biology platform for examining drug resistance in MM has been implemented in cell line models and has been translated to MM cells isolated from a patient. The ultimate application of this platform could assist in clinical decision-making for individualized patient treatment. Although these specific assays have been developed to monitor MM, these techniques are expected to have broad applicability in cancer and other types of disease.
Urinary tuberculosis: Modern issues

Tuberculosis remains an epidemic that affects one third of the world’s population. The persistence of this disease is caused by a large pool of immunecompromised and lower socioeconomic populations. The advent of rapid transportation and migration has contributed to the persistence of this disease in developed and less developed nations. The emergence of drug-resistant strains has added an additional factor for the pervasiveness of tuberculosis. The genitourinary system is a primary target for hematogenous infections. This article reviews the contemporary issues that affect the diagnosis and treatment of urinary tuberculosis.
Black Psychiatric Nurses: Historical Perspectives, 1964 to 1984

During the 1960s, many significant changes affecting Blacks occurred in the United States in the social, education, and political spheres. Harris (1983, p. 107) discussed three major developments occurring during the 1960s that influenced interest in the writing of Afro-American history. These developments included the civil rights struggle, urban uprisings, and the Black consciousness movement. As a result of the Black consciousness movement, Blacks and others realized that there was a lack of written information about Blacks and their contributions to American society. Black historians, therefore, began to write Afro-American history. The purpose of Afro-American historiography was to broaden the knowledge of Americans, as a whole, about Black people in the United States by presenting their activities overtime and place. Harris (p. 108) stated that as a result of this publicity, Americans became concerned that Black people were now demanding equality, when previously they were apparently passive.
Undrained Displacement Behavior of Spread Footings in Clay

The analytical and experimental undrained displacement behavior of spread footings in clay is investigated in this study. Three spread footings ranging in size from 0.76 to 2.74 m were loaded and displaced up to 130 mm into medium stiff to stiff Beaumont clay. Load-displacement curves were determined, and soil displacements below the edge of the largest instrumented footing were measured. The footing displacements were modeled using linear elastic stress distributions and a nonlinear constitutive model calibrated with common in-situ and laboratory tests results. The effect of soil nonlinearity and footing rigidity on soil displacement behavior was also investigated. Results show that the linear elastic stress distributions used in a nonlinear constitutive setting resulted in very good prediction of undrained displacements at the footing center. Displacements at the edge of the footing were less well predicted. Regardless of the assumption of footing rigidity, when nonlinear, in-situ stress-dependent behavior is modeled, realistic concentrations of displacement towards the footing boundaries are observed.
Associations of dietary phosphorus intake, urinary phosphate excretion, and fibroblast growth factor 23 with vascular stiffness in chronic kidney disease.

Objective Elevated serum phosphate concentrations are established risk factors for cardiovascular disease and mortality in chronic kidney disease (CKD). Independent associations of other indices of phosphorus metabolism, such as phosphorus intake, urinary phosphate excretion, or hormones that regulate these systems, like fibroblast growth factor 23 (FGF23), with markers of cardiovascular disease in CKD, have been studied in less detail. Design Cross-sectional study. Participants Seventy-four adult CKD patients with mean creatinine clearance of 51 ± 19 mL/minute. Outcome Augmentation index (AI)—a surrogate marker of arterial stiffness. Results Although serum phosphate varied little across quartiles of creatinine clearance, average daily phosphorus intake and 24-hour urinary phosphate excretion decreased from highest to lowest quartile (by 31% and 60%, respectively, P for trend P = .03) and creatinine clearance (r = −0.4, P = .001), but not with dietary phosphorus or 24-hour urinary phosphate excretion ( P > .05 for both). Older age, higher systolic blood pressure, female gender, and black race were independently associated with increased AI. In contrast, there were no associations of serum phosphate, dietary phosphorus intake, urinary phosphate excretion, or FGF23 with AI in multivariate-adjusted models. Conclusions In this sample of patients with CKD, established risk factors for arterial stiffness, but not mediators of phosphorus metabolism, were associated with increased AI. In addition, there were no significant associations between FGF23 and dietary phosphorus or urinary phosphate excretion. Future studies are needed to determine the main factors associated with elevations in FGF23 in CKD and to further assess the association of disordered phosphorus metabolism with subclinical markers of vascular disease.
Engineered measles virus as a novel oncolytic viral therapy system for hepatocellular carcinoma

The oncolytic measles virus Edmonston strain (MV-Edm), a nonpathogenic virus targeting cells expressing abundant CD46, selectively destroys neoplastic tissue. Clinical development of MV-Edm would benefit from noninvasive monitoring strategies to determine the speed and extent of the spread of the virus in treated patients and the location of virus-infected cells. We evaluated recombinant MV-Edm expressing carcinoembryonic antigen (CEA) or the human sodium iodide symporter (hNIS) for oncolytic potential in hepatocellular carcinoma (HCC) and efficiency in tracking viruses in vivo by noninvasive monitoring. CD46 expression in human HCC and primary hepatocytes was assessed by flow cytometry and immunohistochemistry. Infectivity, syncytium formation, and cytotoxicity of recombinant MV-Edm in HCC cell lines were evaluated by fluorescence microscopy, crystal violet staining, and the MTS assay. Transgene expression in HCC cell lines after infection with recombinant MV-Edm in vitro and in vivo was assessed by CEA concentration, 125I-uptake, and 123I-imaging studies. Toxicology studies were performed in Ifnar(KO)xCD46 transgenic mice. The CD46 receptor was highly expressed in HCC compared to nonmalignant hepatic tissue. Recombinant MV-Edm efficiently infected HCC cell lines, resulting in extensive syncytium formation followed by cell death. Transduction of HCC cell lines and subcutaneous HCC xenografts with recombinant MV-Edm resulted in high-level expression of transgenes in vitro and in vivo. MV-Edm was nontoxic in susceptible mice. Intratumoral and intravenous therapy with recombinant MV-Edm resulted in inhibition of tumor growth and prolongation of survival with complete tumor regression in up to one third of animals. In conclusion, engineered MV-Edm may be a potent and novel cancer gene therapy system for HCC. MV-Edm expressing CEA or hNIS elicited oncolytic effects in human HCC cell lines in vitro and in vivo, enabling the spread of the virus to be monitored in a noninvasive manner.
State of the Art Reviews: Male Menopause: Fact or Fiction?

The possible existence of a menopause-like process in aging men has been speculated, given certain age-related hormonal and other biological changes noted to occur. Specifically, a slow decline in serum testosterone levels has been reported to occur with normal male aging. Androgen deficiency, which may result from this process, could have an effect on various systems and physiologic parameters, including bone density, body composition, sexual function, and the cardiovascular system, thus significantly affecting health and quality-of-life issues in older men. There has been an increasing interest in evaluating the possible use of testosterone replacement in preventing some detrimental aspects of aging and age-related hypogonadism, as well as in the investigation of the potential adverse effects of this therapy on different target organs. It is the purpose of this review to summarize currently available information with regard to the changes in testosterone and other hormones in older men, discuss their po...
Total Synthesis of N-Acetylglucosamine-1,6-anhydro-N-acetylmuramylpentapeptide and Evaluation of Its Turnover by AmpD from Escherichia coli

The bacterial cell wall is recycled extensively during the course of cell growth. The first recycling event involves the catalytic action of the lytic transglycosylase enzymes, which produce an uncommon 1,6-anhydropyranose moiety during separation of the muramyl residues from the peptidoglycan, the major constituent of the cell wall. This product, an N-acetyl-β-d-glucosamine-(1→4)-1,6-anhydro-N-acetyl-β-d-muramylpeptide, is either internalized to initiate the recycling process or diffuses into the milieu to cause stimulation of the pro-inflammatory responses by the host. We report the total syntheses of N-acetyl-β-d-glucosamine-(1→4)-1,6-anhydro-N-acetyl-β-d-muramyl-l-Ala-γ-d-Glu-meso-DAP-d-Ala-d-Ala (compound 1, the product of lytic transglycosylase action on the cell wall of Gram-negative bacteria) and N-acetyl-β-d-glucosamine-(1→4)-1,6-anhydro-N-acetyl-β-d-muramyl-l-Ala-γ-d-Glu-l-Lys-d-Ala-d-Ala (compound 2, from lytic transglycosylase action on the cell wall of Gram-positive bacteria). The syntheses w...
A statistical procedure for determining the best performing air quality simulation model

Abstract Air quality simulation models have been the subject of extensive evaluations to determine their performance under a variety of environmental and meteorological conditions. While much information has been gathered, no clearly defined methodology exists for comparing the performance of two or more models. The purpose of this paper is to present a statistically oriented procedure to test if the performance of one model is superior to others using a composite performance index involving the bootstrap resampling technique.
Generation of voluminous silicic magmas and formation of mid-Cenozoic crust beneath north-central Mexico: evidence from ignimbrites, associated lavas, deep crustal granulites, and mantle pyroxenites

Isotopic and trace element data from mantle and granulite xenoliths are used to estimate the relative contributions of mantle and crustal components to a large ignimbrite, referred to as the upper ignimbrite, that is representative of the voluminous mid-Cenozoic rhyolites of northwestern Mexico. The study also uses data from the volcanic rocks to identify deep crustal xenoliths that are samples of new crust created by the Tertiary magmatism. The isotopic composition of the mantle component is defined by mantle-derived pyroxenites that are interpreted to have precipitated from mid-Cenozoic basaltic magmas. This component has ɛNd≈+1.5, 87Sr/86Sr≈0.7043 and 206Pb/204Pb≈18.6. Within the upper ignimbrite and associated andesitic and dacitic lavas, initial 87Sr/86Sr is positively correlated with SiO2, reaching 0.7164 in the ignimbrite. Initial 206Pb/204Pb ratios also show a positive correlation with silica, whereas ɛNd values have a crude negative correlation, reaching values as low as −2. Of the four isotopically distinct crustal components identified from studies of granulite xenoliths, only the sedimentary protolith of the paragneiss xenoliths can be responsible for the high initial 87Sr/86Sr of the upper ignimbrite. The Nd, Sr, and Pb isotopic compositions of the upper ignimbrite can be modeled with relatively modest assimilation (≤20%) of the sedimentary component ± Proterozoic granulite. Gabbroic composition granulite xenoliths have distinctive Nd, Sr, and Pb isotope ratios that cluster closely within the range of compositions found in the andesitic and dacitic lavas. These mafic granulites are cumulates, and their protoliths are interpreted to have precipitated from the intermediate to silicic magmas at 32–31 Ma. These mafic cumulate rocks are probably representative of much of the deep crust that formed during mid-Cenozoic magmatism in Mexico. Worldwide xenolith studies suggest that the relatively great depth (≤20 km) at which assimilation-fractional crystallization took place in the intermediate to silicic magma systems of the La Olivina region is the rule rather than the exception. Oligocene ignimbrites of the southwestern United States (SWUS) have substantially lower ɛNd values (e.g. <−6) than the upper ignimbrite and other rhyolites from Mexico. This difference appears to reflect a greater crustal contribution to ignimbrites of the SWUS, perhaps due to a higher temperature of the lower crust prior to the emplacement of the Oligocene basaltic magmas.
Mutation eliminating mitochondrial leader sequence of methylmalonyl-CoA mutase causes muto methylmalonic acidemia.

Abstract Methylmalonyl-CoA mutase (EC 5.4.99.2) is a mitochondrial matrix enzyme whose activity is deficient in the inherited disorder methylmalonic acidemia. Previous studies on primary fibroblast cell lines from patients with methylmalonic acidemia have delineated a variety of biochemical phenotypes underlying this disorder. One cell line with primary mutase apoenzyme deficiency exhibited a particularly unusual phenotype; it expressed an abnormally small and unstable immunoreactive protein, which was not imported by mitochondria. We now report cloning and sequencing of the cDNA encoding this mutant protein. The mutation is a single base change, a cytosine----thymine transition, which introduces an amber termination codon at position 17 within the mitochondrial leader sequence. The immunoreactive protein produced by these cells reflects translation from AUG codons downstream from this termination codon and, hence, lacks a mitochondrial leader peptide. This mutation represents a complex prototype for a class of mutations in which absence of the mitochondrial targeting sequence leads to absence of a functioning gene product.
Public opinion and SETI: a mathematical approach?

Abstract Since the goals of SETI concern eventually all humanity, public opinion about SETI is crucially important. Formation of public opinion can be modeled with the aid of stochastic equations. This method, developed by specialists in statistical physics and poorly known by sociologists and the SETI community, gives new insight into the old problem of how to influence public opinion. A popular introduction to this method and some suggestions of how to apply it to SETI will be given.
Distribution of Radioactive Carbon Administered as Carbonate in the Body and Excreta of Mature Rat

SummaryRadioactive carbon was administered to unfasted mature rats either by intraperitoneal injection of Na2C14O3 or by implantation in the peritoneal cavity of CaC14O3. Quantitative studies were made of the relative amounts of C14 excreted in the urine, the feces, expired air and incorporated by the tissues and derived components. A significant incorporation of C14 was found in the inorganic carbonate fraction of bone and in bone protein, the dentin, and enamel of the teeth, fatty acids, glycerol, hemin, red cell protein, plasma proteins, central nervous system protein, liver and muscle glycogen, muscle protein, and in the proteins of the testes and of the thoracic and abdominal viscera.
Delivery of endothelial cells to balloon-dilated rabbit arteries with use of a local delivery catheter.

PURPOSE Experiments were performed to determine if a local delivery catheter could deliver endothelial cells that would be retained on the luminal surface of balloon-dilated arteries. MATERIALS AND METHODS Six New Zealand White rabbits underwent carotid catheterization, arteriography, and balloon angioplasty of an external iliac artery. A local delivery catheter (Dispatch) was then positioned at the site of angioplasty and the 3-mm balloon was inflated. Cultured rabbit endothelial cells (1.26 ± 0.3 × 10 6 ), previously stained with fluorescent dye PKH26, were delivered to the artery in three infusions separated by 10 minutes. The delivery balloon was deflated and removed 25 minutes after the last delivery. The arteries were then perfusion-fixed in situ at physiologic pressure, removed, and divided into four segments, and the segments were rapidly frozen and cryosectioned. Eight sections from each arterial segment were examined by means of epifluorescence microscopy. The luminal surface of each artery was visually divided into eight sectors of equal length and each sector was assigned a score based on the degree of endothelial coverage (0 = no coverage, 1= 50% coverage). RESULTS The endothelial coverage score for the six arteries averaged 0.40 ± 0.46 (SD; range, 0.04–1.24). Areas of each artery receiving scores of 0, 1, and 2 averaged 68%, 25%, and 7%, respectively. Average coverage scores were 0.42, 0.38, 0.51, and 0.28 for individual segments along the length of the artery. CONCLUSIONS The Dispatch local delivery catheter is able to deliver endothelial cells that adhere to balloondilated arteries. Although the magnitude of cellular retention was modest and varied among arteries, the retention along the length of each artery was constant.
Quantitative Proteomic Analysis of Niemann-Pick Disease, Type C1 Cerebellum Identifies Protein Biomarkers and Provides Pathological Insight

Niemann-Pick disease, type C1 (NPC1) is a fatal, neurodegenerative disorder for which there is no definitive therapy. In NPC1, a pathological cascade including neuroinflammation, oxidative stress and neuronal apoptosis likely contribute to the clinical phenotype. While the genetic cause of NPC1 is known, we sought to gain a further understanding into the pathophysiology by identifying differentially expressed proteins in Npc1 mutant mouse cerebella. Using two-dimensional gel electrophoresis and mass spectrometry, 77 differentially expressed proteins were identified in Npc1 mutant mice cerebella compared to controls. These include proteins involved in glucose metabolism, detoxification/oxidative stress and Alzheimer disease-related proteins. Furthermore, members of the fatty acid binding protein family, including FABP3, FABP5 and FABP7, were found to have altered expression in the Npc1 mutant cerebellum relative to control. Translating our findings from the murine model to patients, we confirm altered expression of glutathione s-transferase α, superoxide dismutase, and FABP3 in cerebrospinal fluid of NPC1 patients relative to pediatric controls. A subset of NPC1 patients on miglustat, a glycosphingolipid synthesis inhibitor, showed significantly decreased levels of FABP3 compared to patients not on miglustat therapy. This study provides an initial report of dysregulated proteins in NPC1 which will assist with further investigation of NPC1 pathology and facilitate implementation of therapeutic trials.
Towards multi-lingual adaptability of subjective logic based document summarization: A case study with Chinese documents

Due to the rapid advancement of the internet technology, there is proliferation of textual data, as a result of which automatic summarization has become one of the useful means of coping with the problem of information overload. These textual data are not just in English; thus researchers started focusing on multilingual summarization platforms, so that single framework can be used to cope with different languages. Chinese being another widely spoken language, in this paper, we present an extension of Subjective Logic summarization framework (SubSum) [1], for Chinese. SubSum extracts significant sentences from documents to form extractive summaries. Quantifying uncertainty is the key advantage of SubSum over commonly used summarization methods. The main aim of this work is to show how well SubSum can be adapted to a completely different language, without making changes to the core framework. Moreover, extensive experiments on benchmark datasets demonstrate the effectiveness of SubSum applied for Chinese summarization.
Benthic foraminifera of dysoxic sediments: chloroplast sequestration and functional morphology

Abstract Our recent surveys of dysoxic and anoxic sites reveal that many of the common foraminiferal inhabitants sequester chloroplasts. Such species include: Nonionella stella , which dominates the laminated sediments of the silled Santa Barbara Basin and comprises up to 82% of the living assemblage when [O 2 ] is below 2 μM (∼0.04 ml/l); the closely related species Nonionellina labradorica , which occurs in oxygen-depleted, silled fjords of Sweden; Stainforthia fusiformis , which dominates dysoxic sediments of Norwegian fjords; and Bulimina elegantissima , which is abundant in a shallow-water oil seep site supporting the filamentous, sulfide-oxidizing bacteria Beggiatoa . The literature contains examples of at least eight Elphidium species and one species from each of three other foraminiferal genera (i.e., Haynesina , Nonion , Reophax ) that are known to sequester chloroplasts. These foraminifera are typically infaunal and/or may live under dysoxic conditions. Photosynthetic activity of the sequestered chloroplasts might provide oxygen to the host foraminifera, thereby enabling them to inhabit anoxic pore waters. However, given that most of the surveyed sites occur in the aphotic zone where light levels are too low to fuel photosynthesis, it is more likely that the host employs an as yet unidentified biochemical pathway associated with the sequestered chloroplasts. Additionally, these foraminifera have external test ornamentations that may facilitate separation of the chloroplasts from their algal prey. We discuss potential uses for these morphological features in interpreting the fossil record.
FLX1 codes for a carrier protein involved in maintaining a proper balance of flavin nucleotides in yeast mitochondria.

Respiratory defective mutants of Saccharomyces cerevisiae previously assigned to complementation group G178 are characterized by an abnormally low ratio of FAD/FMN in mitochondria. A nuclear gene, designated FLX1, was selected from a yeast genomic library, based on its ability to confer wild-type growth properties to a representative G178 mutant. Genetic evidence has confirmed that the flavin nucleotide imbalance of G178 mutants is caused by mutations in FLX1. The sequence of FLX1 is identical to a reading frame recently reported to be present on yeast chromosome IX (GenBankTM Z47047). The sequence and tripartite repeat structure of the FLX1 product (Flx1p) indicate it is a member of a protein family consisting of mitochondrial substrate and nucleotide carriers. In yeast, FAD synthetase is present in the soluble cytoplasmic protein fraction but not in mitochondria. Riboflavin kinase, the preceding enzyme in flavin biosynthesis, is present in both subcellular fractions. The absence of FAD synthetase in mitochondria implies that FAD is imported from the cytoplasm. The lower concentration of mitochondrial FAD in flx1 mutants suggests that Flx1p is involved in flavin transport, a role that is also supported by biochemical evidence indicating more efficient flux of FAD across mitochondrial membrane vesicles prepared from wild-type strains than membrane vesicles from flx1 mutants.
Single-atom spintronics

Abstract Recent work on magnetic quantum point contacts (QPCs) was discussed. Complete magnetoresistance loops across Co QPCs as small as a single atom was measured. The remarkable feature of these QPCs is the rapid oscillatory decay in magnetoresistance with the increase of contact size. In addition, stepwise or quantum magnetoresistance loops are observed, resulting from varying transmission probability of the available discrete conductance channels because the sample is cycled between the ferromagnetic (F) and antiferromagnetic (AF) aligned states. Quantized conductance combined with spin dependent transmission of electron waves gives rise to a multi-channel system with a quantum domain wall acting as a valve, i.e., a quantum spin-valve. Behavior of a few-atom QPC is built on the behavior of a single-atom QPC and hence the summarization of results as ‘single-atom spintronics’. An evolutionary trace of spin-dependent electron transmission from a single atom to bulk is provided, the requisite hallmarks of artefact-free magnetoresistance is established across a QPC – stepwise or quantum magnetoresistance loops and size dependent oscillatory magnetoresistance.
Electrophysiological Properties of Motor Neurons in a Mouse Model of Severe Spinal Muscular Atrophy: In Vitro versus In Vivo Development

We examined the electrophysiological activity of motor neurons from the mouse model of severe spinal muscular atrophy (SMA) using two different methods: whole cell patch clamp of neurons cultured from day 13 embryos; and multi-electrode recording of ventral horns in spinal cord slices from pups on post-natal days 5 and 6. We used the MED64 multi-electrode array to record electrophysiological activity from motor neurons in slices from the lumbar spinal cord of SMA pups and their unaffected littermates. Recording simultaneously from up to 32 sites across the ventral horn, we observed a significant decrease in the number of active neurons in 5–6 day-old SMA pups compared to littermates. Ventral horn activity in control pups is significantly activated by serotonin and depressed by GABA, while these agents had much less effect on SMA slices. In contrast to the large differences observed in spinal cord, neurons cultured from SMA embryos for up to 21 days showed no significant differences in electrophysiological activity compared to littermates. No differences were observed in membrane potential, frequency of spiking and synaptic activity in cells from SMA embryos compared to controls. In addition, we observed no difference in cell survival between cells from SMA embryos and their unaffected littermates. Our results represent the first report on the electrophysiology of SMN-deficient motor neurons, and suggest that motor neuron development in vitro follows a different path than in vivo development, a path in which loss of SMN expression has little effect on motor neuron function and survival.
Systems Approaches to Establishing the Relationship Between Protein Modification and Cellular Responses by Lipid Electrophiles

P14 systeMs aPProacHes to estaBlisHing tHe relationsHiP Between Protein ModiFication and cellUlar resPonses By liPid electroPHiles Lawrence J. Marnett1, Aaron Jacobs2, Andrew Vila1, Colleen McGrath1, Mariana Boiani3, Jody Ullery3, Keri Tallman3, Ned A. Porter1, Bing Zhang1, and Daniel C. Liebler1 1Vanderbilt University School of Medicine, 2University of Hawaii, 3Vanderbilt University, USA Electrophilic products of lipid peroxidation form covalent adducts with proteins and DNA that lead to alterations in cell signaling. We compared the ability of 4-hydroxynonenal (HNE), 4-oxononeal (ONE) and several oxidative metabolites to induce apoptosis and cell signaling in a human colon cancer cell line, RKO, and to inhibit cytokine synthesis in a human macrophage cell line, THP-1. To explore the molecular basis of electrophile signaling, we developed a strategy for post-hoc tagging of modified proteins that enables a comprehensive determination of their identities. HNE was substituted at its ω-termini with azido or alkynyl groups, which enabled derivatization via Click chemistry to attach biotin moieties. Exposed cells are lysed, protein extracts treated to attach biotin moieties, then tagged proteins adsorbed to streptavidin beads for affinity purification. Adsorbed proteins were digested to peptides that were identified by liquid chromatography/ mass spectrometry. In parallel, RNA was prepared from exposed cells and the pattern of gene expression determined by microarray analysis. These two datasets the identity of modified proteins and the transcriptional changes induced were generated for each electrophile exposure. Informatic analysis enabled linkages of these two datasets and generation of testable hypotheses regarding the transcriptional consequences of protein modification. This analysis led to the identification of several important cellular responses to electrophile damage resulting from the activation of fourteen and inhibition of four transcriptional pathways. An important activated pathway was the heat-shock response. siRNA-mediated knockdown of the transcription factor, Hsf1, eliminated HNE induction of heat-shock gene expression and increased the sensitivity of cells to its toxicity. Increased sensitivity was due to reduction in the levels of the anti-apoptotic proteins, Bcl-XL, Mcl-1, and to some extent, Bcl-2. The reduced levels of the Bcl-2 family members were due to the inability of the Hsf1-knocked-down cells to express the co-chaperone, Bag3. Additional studies revealed that Bag3 plays an important role in controlling the turnover of the anti-apoptotic Bcl-2 family proteins. Systems level integration of protein modification and transcriptional regulation enables elucidation of the biological consequences of individual protein modification by electrophilic products of lipid peroxidation. Supported by P01ES013125.
Decomposition of H2O on Si(111)7×7 studied using laser-induced thermal desorption

Abstract The decomposition of water on Si(111)7 × 7 was studied using laser-induced thermal desorption (LITD), temperature programmed desorption (TPD) and Auger electron spectroscopy (AES). Product yields versus H 2 O exposure were determined using TPD measurements. The only TPD reaction products were H 2 and SiO which desorbed at approximately 800 and 950 K, respectively. The LITD yield from H 2 O on Si(111)7 × 7 also produced H 2 and SiO desorption products. Moreover, H 2 O and SiOH were detected in the LITD yield after larger water exposures at temperatures above the H 2 O multilayer desorption at 160 K. The LITD desorption yield for H 2 O persisted until 550 K, whereas the SiOH LITD signals were observed up to 600 K. These H 2 O and SiOH LITD signals were associated with reaction intermediates on Si(111)7 × 7 because neither H 2 O nor SiOH was observed in the TPD yield above 160 K. Isothermal LITD experiments were performed to measure the disappearance of SiOH and H 2 O LITD signals from Si(111)7 × 7. The results for the isothermal decay were consistent with self-poisoning of the H 2 O decomposition caused by site-blocking by the reaction products. In addition, the effects of preadsorbed hydrogen on the H 2 O decomposition reaction were investigated. Hydrogen was observed to decrease the H 2 O decomposition reaction on Si(111)7 × 7 nearly linearly with hydrogen coverage.
Hypertension after Kidney Transplantation: A Pathophysiologic Approach

Post-transplant hypertension is associated with decreased graft and patient survival and cardiovascular morbidity. Unfortunately, post-transplant hypertension is often poorly controlled. Important risk factors include immunosuppressive medications, complications of the transplant surgery, delayed graft function, rejection, and donor and recipient risk factors. The effects of immunosuppressive medications are multifactorial including increased vascular and sympathetic tone and salt and fluid retention. The immunosuppressive agents most commonly associated with hypertension are glucocorticoids and calcineurin inhibitors. Drug therapy for hypertension should be based on the comorbidities and pathophysiology. Evidence-based approaches to defining and treating hypertension in renal transplant recipients are predominantly extrapolated from large-scale studies performed in the general population. Thus, there continues to be a need for larger studies examining the pathophysiology, diagnosis and treatment of hypertension in renal transplant recipients.
Explanation, Entailment, and Leibnizian Cosmological Arguments

I argue that there are Leibnizian-style cosmological arguments for the existence of God which start from very mild premises which affirm the mere possibility of a principle of sufficient reason. The utilization of such premises gives a great deal of plausibility to such types of argumentation. I spend the majority of the paper defending three major objections to such “mild” premises viz., a reductio argument from Peter van Inwagen and William Rowe, which proffers and defends the idea that a necessary proposition cannot explain a contingent one. I, then, turn to an amelioration of the Rowe/van Inwagen argument which attempts to appeal to an entailment relation between explanans and explanandum that is fettered out in terms of relevance logic. Subsequent to dispelling with that worry, I tackle objections to the utilization of weak principles of sufficient reason that depend essentially upon agglomerative accounts of explanation.
An intracellular conformational sensor assay for Abl T315I.

Abstract Conformational change is a common molecular mechanism for the regulation of kinase activities. Small molecule modulators of protein conformations, including allosteric kinase inhibitors, are highly wanted as tools for the interrogation of kinase biology and as selective therapeutic agents. However, straightforward cellular assays monitoring kinase conformations in a manner conducive to high-throughput screening (HTS) are not readily available. Here we describe such an HTS-compatible conformational sensor assay for Abl based on a split luciferase construct. The Abl sensor responds to intramolecular structural rearrangements associated with intracellular Abl deactivation and small molecule inhibition. The intact regulatory CAP–SH3–SH2 domain is required for the full functionality of the sensor. Moreover, a T334I Abl mutant (T315I in Abl1a) was found to be particularly well suited for HTS purposes and mechanistic intracellular studies of T334I mutant inhibitors. We expect that the split luciferase-based conformational sensor approach might be more broadly useful to probe the intracellular activation of other kinases and enzymes in general.
GABA actions on the excitability of cultured CNS neurons.

Abstract The membrane mechanisms associated with Cl − conductance activated by GABA in spinal and hippocampal neurons cultured from the embryonic mouse and rat have been studied with voltage- and patch-clamp techniques. The elementary mechanism underlying the conductance response is predominantly all-or-none with both similar and different kinetics in different assays. β-Alanine and glycine also alter conductance via a similar mechanism, but the electrical properties associated with each transmitter are unique. Clinically important drugs modulate GABA-mediated responses by altering the kinetics of ion channel activity. Inhibitory synaptic currents whose time constant of decay coincides with the common, slower phase of channel kinetics in pharmacological experiments are altered in amplitude and/or time course by the same drugs. The results strongly suggest that the synaptic events reflect the activation of 1700 channels whose open-time distribution describes the time constant of decay.
Self-concept, money beliefs and values

Abstract The psychology of money includes such domains as self-concept (status-seeker, distrustful, prudent …), and money attitudes. Money attitudes include beliefs (e.g., rich people are vulgar; hard work is the key to success), and values (e.g., expensive clothes are important; spend and enjoy now). This research explores through canonical analysis the interrelations of broad dimensions and specific variables in a comprehensive set of money psychology test items. Self-concept variables are related to two money attitude components. Specifically, the self-concept of money envy is found to be linked to negative beliefs about other people and their money, as well as to personal values expressing norms of possessiveness.
Systems for KDD: From concepts to practice

Abstract The considerable interest in knowledge discovery in databases (KDD) has led to several techniques and tools for the automated extraction of useful information from large data repositories. In order to use these developments in practical settings, there is need to consider the computing systems that would support the complete KDD process. In this regard, we identify and discuss important computing systems issues, and we compare and contrast some available research and commercial efforts. We suggest several enhancements to the underlying database systems that may significantly benefit the KDD process. We indicate why it is important that tools to handle different aspects of the KDD effort need to be integrated. Finally, we briefly describe our experience in implementing a prototype KDD system for a large corporate environment.