Showing papers by "University of Southern Denmark published in 2000"
TL;DR: Inherited genetic factors make a minor contribution to susceptibility to most types of neoplasms, which indicates that the environment has the principal role in causing sporadic cancer.
Abstract: Background The contribution of hereditary factors to the causation of sporadic cancer is unclear. Studies of twins make it possible to estimate the overall contribution of inherited genes to the development of malignant diseases. Methods We combined data on 44,788 pairs of twins listed in the Swedish, Danish, and Finnish twin registries in order to assess the risks of cancer at 28 anatomical sites for the twins of persons with cancer. Statistical modeling was used to estimate the relative importance of heritable and environmental factors in causing cancer at 11 of those sites. Results At least one cancer occurred in 10,803 persons among 9512 pairs of twins. An increased risk was found among the twins of affected persons for stomach, colorectal, lung, breast, and prostate cancer. Statistically significant effects of heritable factors were observed for prostate cancer (42 percent of the risk may be explained by heritable factors; 95 percent confidence interval, 29 to 50 percent), colorectal cancer (35 perce...
4,009 citations
TL;DR: Proteomics can be divided into three main areas: protein micro-characterization for large-scale identification of proteins and their post-translational modifications; ‘differential display’ proteomics for comparison of protein levels with potential application in a wide range of diseases; and studies of protein–protein interactions using techniques such as mass spectrometry or the yeast two-hybrid system.
Abstract: Proteomics, the large-scale analysis of proteins, will contribute greatly to our understanding of gene function in the post-genomic era. Proteomics can be divided into three main areas: (1) protein micro-characterization for large-scale identification of proteins and their post-translational modifications; (2) 'differential display' proteomics for comparison of protein levels with potential application in a wide range of diseases; and (3) studies of protein-protein interactions using techniques such as mass spectrometry or the yeast two-hybrid system. Because it is often difficult to predict the function of a protein based on homology to other proteins or even their three-dimensional structure, determination of components of a protein complex or of a cellular structure is central in functional analysis. This aspect of proteomic studies is perhaps the area of greatest promise. After the revolution in molecular biology exemplified by the ease of cloning by DNA methods, proteomics will add to our understanding of the biochemistry of proteins, processes and pathways for years to come.
2,345 citations
TL;DR: It is proposed that the MRE11 complex functions at telomeres, possibly by modulating t-loop formation, and is shown that RAD50 protein is present in TRF2 immunocomplexes.
Abstract: Telomeres allow cells to distinguish natural chromosome ends from damaged DNA and protect the ends from degradation and fusion In human cells, telomere protection depends on the TTAGGG repeat binding factor, TRF2 (refs 1-4), which has been proposed to remodel telomeres into large duplex loops (t-loops) Here we show by nanoelectrospray tandem mass spectrometry that RAD50 protein is present in TRF2 immunocomplexes Protein blotting showed that a small fraction of RAD50, MRE11 and the third component of the MRE11 double-strand break (DSB) repair complex, the Nijmegen breakage syndrome protein (NBS1), is associated with TRF2 Indirect immunofluorescence demonstrated the presence of RAD50 and MRE11 at interphase telomeres NBS1 was associated with TRF2 and telomeres in S phase, but not in G1 or G2 Although the MRE11 complex accumulated in irradiation-induced foci (IRIFs) in response to gamma-irradiation, TRF2 did not relocate to IRIFs and irradiation did not affect the association of TRF2 with the MRE11 complex, arguing against a role for TRF2 in DSB repair Instead, we propose that the MRE11 complex functions at telomeres, possibly by modulating t-loop formation
641 citations
TL;DR: Evaluate secular trends and provide new standards for small for gestational age for 16 to 44 weeks of gestation in Norway for the period 1967–1998 to describe birthweight by Gestational age in Norway.
Abstract: Objective. To describe birthweight by gestational age in Norway for the period 1967-1998, evaluate secular trends and provide new standards for small for gestational age for 16 to 44 weeks of gestation. Subjects and methods. The analyses were based on more than 1.8 million singleton births, covering all births in Norway for a 32 year period. Percentiles for birthweight by gestational age were estimated using smoothed means and standard deviations. In the preterm weeks, means and standard deviations were carefully screened for birthweight-gestational age consistency, adapting a method of Wilcox and Russell. Differences in birthweight by gestational age for stillbirths and livebirths in extremely preterm weeks (16-28) are presented, and the effects of cesarean section are evaluated. We observed a clear increase in birthweight by gestational age for all term weeks, but a decrease for most of the preterm weeks over the same period. This decrease was related to the increase in deliveries by cesarean section. C...
513 citations
TL;DR: Although growth rates were significantly reduced during the first years of budesonide treatment, these changes in growth rate were not significantly associated with adult height.
Abstract: Background Short-term studies have shown that inhaled corticosteroids may reduce the growth of children with asthma. However, the effect of long-term treatment on adult height is uncertain. Methods We conducted a prospective study in children with asthma to examine the effect of long-term treatment with inhaled budesonide on adult height. We report on 211 children who have attained adult height: 142 budesonide-treated children with asthma, 18 control patients with asthma who have never received inhaled corticosteroids, and 51 healthy siblings of patients in the budesonide group, who also served as controls. Results The children in the budesonide group attained adult height after a mean of 9.2 years of budesonide treatment (range, 3 to 13) at a mean daily dose of 412 μg (range, 110 to 877). The mean cumulative dose of budesonide was 1.35 g (range, 0.41 to 3.99). The mean differences between the measured and target adult heights were +0.3 cm (95 percent confidence interval, –0.6 to +1.2) for the budesonide-...
506 citations
TL;DR: It is demonstrated that Vav-2 is phosphorylated on tyrosine residues in response to EGF and associates with the EGFR in vivo, and the strategy suggested here can be used for routine identification of downstream components of cell surface receptors in mammalian cells.
Abstract: Oligomerization of receptor protein tyrosine kinases such as the epidermal growth factor receptor (EGFR) by their cognate ligands leads to activation of the receptor. Transphosphorylation of the receptor subunits is followed by the recruitment of signaling molecules containing src homology 2 (SH2) or phosphotyrosine interaction domains (PID). Additionally, several cytoplasmic proteins that may or may not associate with the receptor undergo tyrosine phosphorylation. To identify several components of the EGFR signaling pathway in a single step, we have immunoprecipitated molecules that are tyrosine phosphorylated in response to EGF and analyzed them by one-dimensional gel electrophoresis followed by mass spectrometry. Combining matrix-assisted laser desorption/ionization (MALDI) and nanoelectrospray tandem mass spectrometry (MS/MS) led to the identification of nine signaling molecules, seven of which had previously been implicated in EGFR signaling. Several of these molecules were identified from low femtomole levels of protein loaded onto the gel. We identified Vav-2, a recently discovered guanosine nucleotide exchange factor that is expressed ubiquitously, as a substrate of the EGFR. We demonstrate that Vav-2 is phosphorylated on tyrosine residues in response to EGF and associates with the EGFR in vivo. Binding of Vav-2 to the EGFR is mediated by the SH2 domain of Vav-2. In keeping with its ubiquitous expression, Vav-2 seems to be a general signaling molecule, since it also associates with the platelet-derived growth factor (PDGF) receptor and undergoes tyrosine phosphorylation in fibroblasts upon PDGF stimulation. The strategy suggested here can be used for routine identification of downstream components of cell surface receptors in mammalian cells.
416 citations
TL;DR: Two major RNA-binding proteins, nucleolin and YB-1, are identified that specifically bind to the JNK response element in the 5' untranslated region (UTR) of interleukin-2 mRNA.
Abstract: Regulated mRNA turnover is a highly important process, but its mechanism is poorly understood. Using interleukin-2 (IL-2) mRNA as a model, we described a role for the JNK-signaling pathway in stabilization of IL-2 mRNA during T-cell activation, acting via a JNK response element (JRE) in the 5' untranslated region (UTR). We have now identified two major RNA-binding proteins, nucleolin and YB-1, that specifically bind to the JRE. Binding of both proteins is required for IL-2 mRNA stabilization induced by T-cell activation signals and for JNK-induced stabilization in a cell-free system that duplicates essential features of regulated mRNA decay. Nucleolin and YB-1 are required for formation of an IL-2 mRNP complex that responds to specific mRNA stabilizing signals.
389 citations
TL;DR: A method for quantitating proteins and peptides in the low picomole and sub-picomole range has been developed using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) with internal (18)O-labeled standards.
Abstract: A method for quantitating proteins and peptides in the low picomole and sub-picomole range has been developed using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) with internal (18)O-labeled standards. A simple procedure is proposed to produce such internal standards for the tested sample by enzymatic hydrolysis of the same sample (with known concentration) in (18)O-water. A mathematical algorithm was developed which uses the isotopic patterns of the substance, the internal standard, and the substance/internal standard mixture for accurate quantitation of the substance. A great advantages of the proposed method is the absence of molecular weight limitation for the protein quantitation and the possibility of quantitation without previous fractionation of proteins and peptides. Using this strategy, the peptide angiotensinogen and two proteins, RNase and its protein inhibitor, were quantified by MALDI-time-of-flight (TOF) mass spectrometry.
387 citations
TL;DR: The localization and functions of SP-D indicate that this collectin is the counterpart in the innate immune system of IgA in the adaptive immune system.
Abstract: Lung surfactant protein-D (SP-D), a collectin mainly produced by alveolar type II cells, initiates the effector mechanisms of innate immunity on binding to microbial carbohydrates. A panel of mRNAs from human tissues was screened for SP-D mRNA by RT-PCR. The lung was the main site of synthesis, but transcripts were readily amplified from trachea, brain, testis, salivary gland, heart, prostate gland, kidney, and pancreas. Minor sites of synthesis were uterus, small intestine, placenta, mammary gland, and stomach. The sequence of SP-D derived from parotid gland mRNA was identical with that of pulmonary SP-D. mAbs were raised against SP-D, and one was used to locate SP-D in cells and tissues by immunohistochemistry. SP-D immunoreactivity was found in alveolar type II cells, Clara cells, on and within alveolar macrophages, in epithelial cells of large and small ducts of the parotid gland, sweat glands, and lachrymal glands, in epithelial cells of the gall bladder and intrahepatic bile ducts, and in exocrine pancreatic ducts. SP-D was also present in epithelial cells of the skin, esophagus, small intestine, and urinary tract, as well as in the collecting ducts of the kidney. SP-D is generally present on mucosal surfaces and not restricted to a subset of cells in the lung. The localization and functions of SP-D indicate that this collectin is the counterpart in the innate immune system of IgA in the adaptive immune system.
374 citations
TL;DR: Nano-scale Fe(III)-affinity chromatography combined with nano-electrospray FTMS/ECD facilitated phosphopeptide analysis and amino acid sequencing from crude proteolytic peptide mixtures.
Abstract: Analysis of phosphotyrosine and phosphoserine containing peptides by nano-electrospray Fouriertransform ion cyclotron resonance (FTICR) mass spectrometry established electron capture dissociation(ECD) as a viable method for phosphopeptide sequencing In general, ECD spectra of synthetic and nativephosphopeptides appeared less complex than conventional collision activated dissociation (CAD) massspectra of these species ECD of multiply protonated phosphopeptide ions generated mainly c- and z
351 citations
TL;DR: It is concluded that telomere length, which is under genetic control, might play a role in mechanisms that regulate pulse pressure, including vascular aging.
Abstract: There is evidence that telomeres, the ends of chromosomes, serve as clocks that pace cellular aging in vitro and in vivo. In industrialized nations, pulse pressure rises with age, and it might serve as a phenotype of biological aging of the vasculature. We therefore conducted a twin study to investigate the relation between telomere length in white blood cells and pulse pressure while simultaneously assessing the role of genetic factors in determining telomere length. We measured by Southern blot analysis the mean length of the terminal restriction fragments (TRF) in white blood cells of 49 twin pairs from the Danish Twin Register and assessed the relations of blood pressure parameters with TRF. TRF length showed an inverse relation with pulse pressure. Both TRF length and pulse pressure were highly familial. We conclude that telomere length, which is under genetic control, might play a role in mechanisms that regulate pulse pressure, including vascular aging.
TL;DR: Echolocation signals were recorded from big brown bats, Eptesicus fuscus, flying in the field and the laboratory, and in the terminal phase of insect capture sequences, where Fmin decreased with decreasing signal duration.
Abstract: Echolocation signals were recorded from big brown bats, Eptesicus fuscus, flying in the field and the laboratory. In open field areas the interpulse intervals (IPI) of search signals were either around 134 ms or twice that value, 270 ms. At long IPI's the signals were of long duration (14 to 18-20 ms), narrow bandwidth, and low frequency, sweeping down to a minimum frequency (Fmin) of 22-25 kHz. At short IPI's the signals were shorter (6-13 ms), of higher frequency, and broader bandwidth. In wooded areas only short (6-11 ms) relatively broadband search signals were emitted at a higher rate (avg. IPI= 122 ms) with higher Fmin (27-30 kHz). In the laboratory the IPI was even shorter (88 ms), the duration was 3-5 ms, and the Fmin 30- 35 kHz, resembling approach phase signals of field recordings. Excluding terminal phase signals, all signals from all areas showed a negative correlation between signal duration and Fmin, i.e., the shorter the signal, the higher was Fmin. This correlation was reversed in the terminal phase of insect capture sequences, where Fmin decreased with decreasing signal duration. Overall, the signals recorded in the field were longer, with longer IPI's and greater variability in bandwidth than signals recorded in the laboratory.
TL;DR: To a time-restricted microglial/macrophage production of TNF in focal cerebral ischemia in mice, nonradioactive in situ hybridization for murine TNF mRNA was performed and translation of T NF mRNA into bioactive protein was demonstrated in the neocortex of C57Bl/6 mice subjected to permanent middle cerebral artery occlusion.
Abstract: The proinflammatory cytokine tumor necrosis factor (TNF) is known to be expressed in brain ischemia; however, its cellular and temporal appearance is not fully settled. In this study, nonradioactive in situ hybridization for murine TNF mRNA was performed on brain sections from adult C57x129 mice at 6 hours, 12 hours, 24 hours, 2 days, 5 days, or 10 days (six to eight mice per group) after induction of permanent focal cerebral ischemia. Cortical infarct volumes were estimated, and TNF mRNA-expressing cells were counted within the infarct and infarct border using Cast-Grid analysis. At 12 hours, a peak of 19.2 +/- 5.1 TNF mRNA-expressing cells/mm2 was counted, contrasting two to three times lower values at 6 and 24 hours (6.4 +/- 4.6 and 9.2 +/- 3.4 cells/mm2, respectively) and <2 cells/mm2 at 48 hours and later stages. The TNF mRNA-expressing cells were distributed along the entire rostrocaudal axis of the cortical infarcts and occasionally within the caudate putamen. At all time points, TNF mRNA colocalized with Mac-1-positive microglia/macrophages but not with Ly-6G (Gr-1)-positive polymorphonuclear leukocytes. Similarly, combined in situ hybridization for TNF mRNA and immunohistochemistry for glial fibrillary acidic protein at 12 and 24 hours revealed no TNF mRNA-expressing astrocytes at these time points. Translation of TNF mRNA into bioactive protein was demonstrated in the neocortex of C57B1/6 mice subjected to permanent middle cerebral artery occlusion. In summary, this study points to a time-restricted microglial/macrophage production of TNF in focal cerebral ischemia in mice.
TL;DR: In this article, an extensive comparison of the well-known R&D models of d'Aspremont-Jacquemin and Kamien-Muller-Zang is provided, exposing full or partial conflict in key conclusions and policy prescriptions.
TL;DR: The detection of abundant NO+ and NO2- ions for HMX, RDX and CL-20, which are efficient matrices, indicates that explosive decomposition takes place in PDMS of these three substances and that a contribution from the corresponding chemical energy release is possible.
Abstract: The low-mass ions observed in both positive and negative plasma desorption mass spectrometry (PDMS) of the high explosives HMX, RDX, CL-20, NC, PETN and TNT are reported. Possible identities of the most abundant ions are suggested and their presence or absence in the different spectra is related to the properties of the explosives as matrices in PDMS. The detection of abundant NO+ and NO2- ions for HMX, RDX and CL-20, which are efficient matrices, indicates that explosive decomposition takes place in PDMS of these three substances and that a contribution from the corresponding chemical energy release is possible. The observation of abundant C2H4N+ and CH2N+ ions, which have high protonation properties, might also explain the higher protein charge states observed with these matrices. Also, the observation of NO2-, possibly formed by electron scavenging which increases the survival probability of positively charged protein molecular ions, completes the pattern. TNT does not give any of these ions and it is thereby possible to explain why it does not work as a PDMS matrix. For NC and PETN, decomposition does not seem to be as pronounced as for HMX, RDX and CL-20, and also no particularly abundant ions with high protonation properties are observed. The fact that NC works well as a matrix might be related to other properties of this compound, such as its high adsorption ability.
TL;DR: There is no evidence so far that application of ANNs represents real progress in the field of diagnosis and prognosis in oncology, according to a search in the medical literature from 1991 to 1995.
Abstract: The application of artificial neural networks (ANNs) for prognostic and diagnostic classification in clinical medicine has become very popular. In particular, feed-forward neural networks have been used extensively, often accompanied by exaggerated statements of their potential. In this paper, the essentials of feed-forward neural networks and their statistical counterparts (that is, logistic regression models) are reviewed. We point out that the uncritical use of ANNs may lead to serious problems, such as the fitting of implausible functions to describe the probability of class membership and the underestimation of misclassification probabilities. In applications of ANNs to survival data, further difficulties arise. Finally, the results of a search in the medical literature from 1991 to 1995 on applications of ANNs in oncology and some important common mistakes are reported. It is concluded that there is no evidence so far that application of ANNs represents real progress in the field of diagnosis and prognosis in oncology.
TL;DR: The role of muscle activity and mental load in the development of pain and degenerative processes on the muscle cellular level during computer work is studied.
Abstract: The role of muscle activity and mental load in the development of pain and degenerative processes on the muscle cellular level during computer work : European Journal of Applied Physiology
TL;DR: Immunolocalization experiments show that Gemin4 is colocalized with SMN in the cytoplasm and in gems, suggesting that the SMN complex may also function in preribosomal RNA processing or ribosome assembly.
Abstract: The survival of motor neurons (SMN) protein, the product of the neurodegenerative disease spinal muscular atrophy (SMA) gene, is localized both in the cytoplasm and in discrete nuclear bodies called gems. In both compartments SMN is part of a large complex that contains several proteins including Gemin2 (formerly SIP1) and the DEAD box protein Gemin3. In the cytoplasm, the SMN complex is associated with snRNP Sm core proteins and plays a critical role in spliceosomal snRNP assembly. In the nucleus, SMN is required for pre-mRNA splicing by serving in the regeneration of spliceosomes. These functions are likely impaired in cells of SMA patients because they have reduced levels of functional SMN. Here, we report the identification by nanoelectrospray mass spectrometry of a novel component of the SMN complex that we name Gemin4. Gemin4 is associated in vivo with the SMN complex through a direct interaction with Gemin3. The tight interaction of Gemin4 with Gemin3 suggests that it could serve as a cofactor of this DEAD box protein. Gemin4 also interacts directly with several of the Sm core proteins. Monoclonal antibodies against Gemin4 efficiently immunoprecipitate the spliceosomal U snRNAs U1 and U5 from Xenopus oocytes cytoplasm. Immunolocalization experiments show that Gemin4 is colocalized with SMN in the cytoplasm and in gems. Interestingly, Gemin4 is also detected in the nucleoli, suggesting that the SMN complex may also function in preribosomal RNA processing or ribosome assembly.
TL;DR: In this paper, the authors consider a two-member channel in which a manufacturer and an exclusive retailer can make advertising expenditures that have both short and long term impacts on the retailer's sales.
TL;DR: It is proposed that the exceptional stability of the LNA modified duplexes is caused by a quenching of concerted local backbone motions by the L NA nucleotides in ssLNA so as to decrease the entropy loss on duplex formation combined with a more efficient stacking of the nucleobases.
Abstract: We have used 2D NMR spectroscopy to study the sugar conformations of oligonucleotides containing a conformationally restricted nucleotide (LNA) with a 2'-O, 4'-C-methylene bridge. We have investigated a modified 9-mer single stranded oligonucleotide as well as three 9- and 10-mer modified oligonucleotides hybridized to unmodified DNA. The single-stranded LNA contained three modifications whereas the duplexes contained one, three and four modifications, respectively. The LNA:DNA duplexes have normal Watson-Crick base-pairing with all the nucleotides in anti-conformation. By use of selective DQF-COSY spectra we determined the ratio between the N-type (C3'-endo) and S-type (C2'-endo) sugar conformations of the nucleotides. In contrast to the corresponding single-stranded DNA (ssDNA), we found that the sugar conformations of the single-stranded LNA oligonucleotide (ssLNA) cannot be described by a major S-type conformer of all the nucleotides. The nucleotides flanking an LNA nucleotide have sugar conformations with a significant population of the N-type conformer. Similarly, the sugar conformations of the nucleotides in the LNA:DNA duplexes flanking a modification were also shown to have significant contributions from the N-type conformation. In all cases, the sugar conformations of the nucleotides in the complementary DNA strand in the duplex remain in the S-type conformation. We found that the locked conformation of the LNA nucleotides both in ssLNA and in the duplexes organize the phosphate backbone in such a way as to introduce higher population of the N-type conformation. These conformational changes are associated with an improved stacking of the nucleobases. Based on the results reported herein, we propose that the exceptional stability of the LNA modified duplexes is caused by a quenching of concerted local backbone motions (preorganization) by the LNA nucleotides in ssLNA so as to decrease the entropy loss on duplex formation combined with a more efficient stacking of the nucleobases.
TL;DR: Recent findings on the catalytic site, mechanism of action, substrate recognition, the linker region, the multidomain architecture, the engineering of specificity and stability, and roles of individual substrate binding subsites are focused on.
TL;DR: Introduction of a certain pattern of methyl ester distribution caused by selective removal of certain methyl Ester groups by f-PME is the most reasonable explanation for the detected differences.
TL;DR: This work demonstrates, that the use of mass spectrometry is the method of choice for analyzing cross-linking experiments aiming on nearest neighbor relationships.
Abstract: Most cellular functions are performed by multi-protein complexes. The identity of the members of such complexes can now be determined by mass spectrometry. Here we show that mass spectrometry can also be used in order to define the spatial organization of these complexes. In this approach, components of a protein complex are purified via molecular interactions using an affinity tagged member and the purified complex is then partially cross-linked. The products are separated by gel electrophoresis and their constituent components identified by mass spectrometry yielding nearest-neighbor relationships. In this study, a member of the yeast nuclear pore complex (Nup85p) was tagged and a six-member subcomplex of the pore was cross-linked and analyzed by 1D SDS−PAGE. Cross-linking reactions were optimized for yield and number of products. Analysis by MALDI mass spectrometry resulted in the identification of protein constituents in the cross-linked bands even at a level of a few hundred femtomoles. Based on thes...
TL;DR: In this article, a spectral distribution measure for non-normal elements in a finite von Neumann algebra M with respect to a fixed normal faithful tracial state τ has been proposed, expressed explicitly in terms of the S-transform of the distribution μT*T of the positive operator T*T.
TL;DR: A large scale extract of the brown alga Fucus serratus was found to contain four arsenosugars (1−4) together with traces of dimethylarsinate (DMA) and arsenate by HPLC-ICP-MS as discussed by the authors.
Abstract: A large scale extract of the brown alga Fucus serratus was found to contain four arsenosugars (1–4) together with traces of dimethylarsinate (DMA) and arsenate by HPLC-ICP-MS. The extract was divided into 1500 equal subsamples which were then freeze-dried and stored at –18°C. The homogeneity of this population of subsamples was established by random sampling and quantification of total arsenic by ICP-MS (1.22 µg As ±3.2%, mean ± RSD, n = 32) and hydride generation AAS (1.27 µg As ±2.0%, n = 32), and by quantification with HPLC-ICP-MS of the individual arsenic species in 10 subsamples: arsenosugar 1, 0.10 µg As ±3.6%; arsenosugar 2, 0.086 µg As ±2.9%; arsenosugar 3, 0.62 µg As ±3.8%; arsenosugar 4, 0.40 µg As ±3.1%; dimethylarsinate, 0.005 µg As ±20%; and arsenate ca. 0.001 µg As. The identity of the arsenosugars was confirmed by LC–electrospray (ES) MS with variable fragmenter voltage which provided simultaneous elemental and molecular detection. LC-ESMS was also used to quantify the four arsenosugars, producing values within 5% (2, 3 and 4) or 14% (1) of the ICP-MS data. The subsamples of Fucus extract provide a homogeneous source of natural material containing arsenosugars for use in arsenic speciation studies.
TL;DR: The extensive recent epidemiological literature does not support the popular opinion that sitting-while-at-work is associated with LBP, and instead finds a marginally negative association for sitting compared to diverse workplace exposures.
Abstract: Objectives: To present a critical review and evaluate recent reports investigating sitting-while-at-work as a risk factor for low back pain (LBP). Methods: The Medline, Embase and OSH-ROM databases were searched for articles dealing with sitting at work in relation to low back pain for the years 1985-97. The studies were divided into those dealing with sitting-while-working and those dealing with sedentary occupations. Each article was systematically abstracted for core items. The quality of each article was determined based on the representativeness of the study sample, the definition of LBP, and the statistical analysis. Results: Thirty-five reports were identified, 14 dealing with sitting-while-working and 21 with sedentary occupations. Eight studies were found to have a representative sample, a clear definition of LBP and a clear statistical analysis. Regardless of quality, all but one of the studies failed to find a positive association between sitting-while-working and LBP. High quality studies foun...
TL;DR: Comparative studies will continue to be required to understand the functional role of IGFs and IGFBPs in each species, and to highlight the diversity in the expression of the IGF system among placentae of man and different laboratory animals, and even between closely related species.
TL;DR: Partly modified LNA:RNA duplexes may adopt a duplex structure between the standard A and B types, thereby making the RNA strand amenable to RNase H-mediated degradation.
Abstract: We have used NMR and CD spectroscopy to study the conformations of modified oligonucleotides (locked nucleic acid, LNA) containing a conformationally restricted nucleotide (T(L)) with a 2'-O,4'-C-methylene bridge. We have investigated two LNA:RNA duplexes, d(CTGAT(L)ATGC):r(GCAUAUCAG) and d(CT(L)GAT(L)AT(L)GC):r(GCAUAUCAG), along with the unmodified DNA:RNA reference duplex. Increases in the melting temperatures of +9.6 degrees C and +8.1 degrees C per modification relative to the unmodified duplex were observed for these two LNA:RNA sequences. The three duplexes all adopt right-handed helix conformations and form normal Watson-Crick base pairs with all the bases in the anti conformation. Sugar conformations were determined from measurements of scalar coupling constants in the sugar rings and distance information derived from 1H-1H NOE measurements; all the sugars in the RNA strands of the three duplexes adopt an N-type conformation (A-type structure), whereas the sugars in the DNA strands change from an equilibrium between S- and N-type conformations in the unmodified duplex towards more of the N-type conformation when modified nucleotides are introduced. The presence of three modified T(L) nucleotides induces drastic conformational shifts of the remaining unmodified nucleotides of the DNA strand, changing all the sugar conformations except those of the terminal sugars to the N type. The CD spectra of the three duplexes confirm the structural changes described above. On the basis of the results reported herein, we suggest that the observed conformational changes can be used to tune LNA:RNA duplexes into substrates for RNase H: Partly modified LNA:RNA duplexes may adopt a duplex structure between the standard A and B types, thereby making the RNA strand amenable to RNase H-mediated degradation.
01 Jan 2000
TL;DR: An algorithm which extends the probabilistic roadmap (PRM) framework to handle manipulation planning by using a two level approach, a PRM of PRMs, made possible by the introduction of a new kind of roadmap, called the fuzzy roadmap.
Abstract: This paper presents an algorithm which extends the probabilistic roadmap (PRM) framework to handle manipulation planning. This is done by using a two level approach, a PRM of PRMs. The first level builds a manipulation graph, whose nodes represent stable placements of the manipulated objects while the edges represent transfer and transit actions. The actual motion planning for the transfer and transit paths is done by PRM planners at the second level. The approach is made possible by the introduction of a new kind of roadmap, called the fuzzy roadmap. The fuzzy roadmap contains edges which are not verified by a local planner during construction. Instead, each edge is assigned a number which represents the probability that it is feasible. Later, if the edge is part of a solution path, the edge is checked for collisions. The overall effect is that our roadmaps evolve iteratively until they contain a solution. The use of fuzzy roadmaps in both levels of our manipulation planner offers many advantages. At the first level, a fuzzy roadmap represents the manipulation graph and addresses the problem of having probabilistically complete planners at the second level. At the second level, fuzzy roadmaps drastically reduce the number of collision checks. The paper contains experimental results demonstrating the feasibility and efficiency of our scheme.
Journal Article•
TL;DR: DMBT1 is a gene that is highly unstable in cancer and encodes for a protein with at least two different functions, one in the immune defense and a second one in epithelial differentiation, according to expression analyses and studies with a monoclonal antibody against the protein.
Abstract: The gene deleted in malignant brain tumors 1
(DMBT1) has been proposed as a candidate tumor
suppressor for brain, gastrointestinal, and lung cancer. It codes for a
protein of unknown function belonging to the superfamily of scavenger
receptor cysteine-rich proteins. We aimed at getting insights into the
functions of DMBT1 by expression analyses and studies with a monoclonal
antibody against the protein. The DMBT1 mRNA is
expressed throughout the immune system, and Western blot studies
demonstrated that isoforms of DMBT1 are identical to the
collectin-binding protein gp-340, a glycoprotein that is involved in
the respiratory immune defense. Immunohistochemical analyses revealed
that DMBT1 is produced by both tumor-associated macrophages and tumor
cells and that it is deregulated in glioblastoma multiforme in
comparison to normal brain tissue. Our data further suggest that the
proteins CRP-ductin and hensin, both of which have been implicated in
epithelial differentiation, are the DMBT1 orthologs in mice and
rabbits, respectively. These findings and the spatial and temporal
distribution of DMBT1 in fetal and adult epithelia suggest that DMBT1
further plays a role in epithelial development. Rearrangements of
DMBT1 were found in 16 of 18 tumor cell lines, and
hemizygous deletions were observed in a subset of normal individuals,
indicating that the alterations in tumors may be a result of both
pre-existing deletions uncovered by a loss of heterozygosity and
secondary changes acquired during tumorigenesis. Thus,
DMBT1 is a gene that is highly unstable in cancer and
encodes for a protein with at least two different functions, one in the
immune defense and a second one in epithelial differentiation.