julilili42/papers huggingface dataset:
Spectroscopy
2006-06-15

Abstract Spectroscopy, the study of electromagnetic radiation and its interaction with matter as a function of frequency or wavelength, is a versatile and powerful tool for investigating atomic and molecular structure, as well as for qualitative and quantitative analysis. Optical spectroscopy is surveyed emphasizing its applicability for qualitative and quantitative laboratory and process analysis and for monitoring atmospheric pollutants. Absorption, emission (from excited samples, and radiometry of ambient thermal emission), scattering (elastic and Raman), and luminescence (fluorescence and phosphorescence) spectroscopies are discussed for the different regions of the electromagnetic spectrum: radio and microwaves, mid‐ and near‐infrared, molecular ultraviolet–visible absorption, atomic absorption and emission, and X‐ray and γ‐ray, in each case discussing instrumentation, sampling, and applications. Special techniques covered include null‐background detection, nonlinear Raman spectroscopy and other laser‐induced processes, optical activity, and Mössbauer spectroscopy. Modern ultrasensitive spectroscopies being developed for analytical use are briefly reviewed.
PCB 153, a Non-dioxin–like Tumor Promoter, Selects for β-Catenin (Catnb)–Mutated Mouse Liver Tumors
2006-06-16

Polychlorinated biphenyls (PCBs) are ubiquitous environmental toxicants which act as liver tumor promoters in rodents and can be classified as either dioxin-like or non-dioxin (phenobarbital [PB])-like inducers of cytochrome P-450. Since we have previously shown that tumor promotion by PB leads to clonal outgrowth of beta-catenin (Catnb)-mutated but not Ha-ras-mutated mouse liver tumors, we were interested to know whether the non-dioxin-like tumor promoter 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153) shows the same selective pressure during tumor promotion. Male B6129SF2/J mice were given a single injection of N-nitrosodiethylamine (90 mg/kg body weight) at 9 weeks of age, followed by 39 weeks of treatment with PCB 153 (20 biweekly ip injections of 300 mumol/kg body weight) or corn oil as a control. Animals were killed 15 weeks after the last PCB 153 injection and liver tumors were identified by immunohistochemical staining of glutamine synthetase (GS) and analyzed for Catnb, Ha-ras, and B-raf mutations. Quantitative analyses revealed that GS-positive tumors were much larger and more frequent in livers from PCB 153-treated mice than in control animals, whereas GS-negative tumors were similar in both groups. Almost 90% (34/38) of all tumors from PCB 153-treated animals contained Catnb mutations, which compares to approximately 45% (17/37) of tumors in the control group. Ha-ras- and B-raf-mutated liver tumors were rare and not significantly different between treatment groups. These results clearly indicate that PCB 153 strongly selects for Catnb-mutated, GS-positive liver tumors, which is similar to the known action of PB, a prototypical tumor promoter in rodent liver.
A functional polymorphism within plasminogen activator urokinase (PLAU) is associated with Alzheimer's disease
2006-06-16

A number of susceptibility loci for Alzheimer's disease (AD) have been identified including a region on Chromosome 10q21-q22. Within this region the plasminogen activator urokinase gene (PLAU) was considered as a reasonable candidate from its functional implication in plasmin generation, a serine protease capable of degrading beta-Amyloid (Abeta) protein. We screened 56 single nucleotide polymorphisms (SNPs) around PLAU using 1751 individuals from four independent case-control samples (Munich, N=679; Bonn N=282; Brescia (Italy) N=219; Perth (Australia) N=557 and one discordant sib-pair sample (Munich N=622). In brain tissue samples of neuropathologically confirmed cases with AD (N=33) we analyzed plaque counts according to the risk allele. We identified that one functional exonic SNP (rs2227564) is associated with development of AD using the four independent case-control samples (Munich, P=0.02; Bonn, P=0.005; Brescia (Italy), P=0.001; Perth (Australia), P=0.03) and the discordant sib-pair sample (P=0.001). In brain tissue, from neuropathologically confirmed cases with AD, we identified significantly higher plaque counts in carriers of the risk allele (N=6; 60.3+/-16.9) compared with non-carriers (N=9; 26.3+/-8.8; P=0.007). This study provides compelling evidence of a genetic and functional involvement of a common PLAU variant into the pathogenesis of AD. Further functional investigations are warranted to elucidate the specific role of PLAU, respectively, PLAU variants in the metabolism of Abeta proteins.
Theory of strong localization effects of light in disordered loss or gain media
2006-06-16

We present a systematical theory for the interplay of strong localization effects and absorption or gain of classical waves in 3-dimensional, disordered dielectrics. The theory is based on the selfconsistent Cooperon resummation, implementing the effects of energy conservation and its absorptive or emissive corrections by an exact, generalized Ward identity. Substantial renormalizations are found, depending on whether the absorption/gain occurs in the scatterers or in the background medium. We find a finite, gain-induced correlation volume which may be significantly smaller than the scale set by the scattering mean free path, even if there are no truly localized modes. Possible consequences for coherent feedback in random lasers as well as the possibility of oscillatory in time behavior induced by sufficiently strong gain are discussed.
Cytoplasmic accumulation of long‐chain coenzyme A esters activates KATP and inhibits Kir2.1 channels
2006-06-16

Long‐chain fatty acids acyl coenzyme A esters (LC‐CoA) are obligate intermediates of fatty acid metabolism and have been shown to activate K ATP channels but to inhibit most other Kir channels (e.g. Kir2.1) by direct channel binding. The activation of K ATP channels by elevated levels of LC‐CoA may be involved in the pathophysiology of type 2 diabetes, the hypothalamic sensing of circulating fatty acids and the regulation of cardiac K ATP channels. However, LC‐CoA are effectively buffered in the cytoplasm and it is currently not clear whether their free concentration can reach levels sufficient to affect Kir channels in vivo . Here, we report that extracellular oleic acid complexed with albumin at an unbound concentration of 81 ± 1 n m strongly activated K ATP channels and inhibited Kir2.1 channels in Chinese hamster ovary (CHO) cells as well as endogenous Kir currents in human embryonic kidney (HEK293) cells. These effects were only seen in the presence of a high concentration of glucose (25 m m ), a condition known to promote the accumulation of LC‐CoA by inhibiting their mitochondrial uptake via carnitine‐palmitoyl‐transferase‐1 (CPT1). Accordingly, pharmacological inhibition of CPT1 by etomoxir restored the effects of oleic acid under low glucose conditions. Finally, triacsin C, an inhibitor of the acyl‐CoA synthetase, which is necessary for LC‐CoA formation, abolished the effects of extracellular oleic acid on the various Kir channels. These results establish the direct regulation of Kir channels by the cytoplasmic accumulation of LC‐CoA, which might be of physiological and pathophysiological relevance in a variety of tissues.
Identification ofBilophila wadsworthiaby specific PCR which targets the taurine:pyruvate aminotransferase gene
2006-06-16

The bile-resistant, strictly anaerobic bacterium Bilophila wadsworthia is found in human faecal flora, in human infections and in environmental samples. A specific PCR primer set for the gene encoding the first metabolic enzyme in the degradative pathway for taurine in B. wadsworthia, taurine:pyruvate aminotransferase (tpa), was developed and tested. In addition, enrichment cultures were started from faecal samples of primates and felines and shown to contain B. wadsworthia. These were subcultured on agar media and then identified by PCR fingerprinting. PCR for tpa was successful in all positive enrichment cultures and showed no amplification signal in a variety of other bacterial species. Therefore, this PCR method could be a promising tool for rapid detection of B. wadsworthia in biological samples.
JCell—a Java-based framework for inferring regulatory networks from time series data
2006-06-16

Abstract Motivation: JCell is a Java-based application for reconstructing gene regulatory networks from experimental data. The framework provides several algorithms to identify genetic and metabolic dependencies based on experimental data conjoint with mathematical models to describe and simulate regulatory systems. Owing to the modular structure, researchers can easily implement new methods. JCell is a pure Java application with additional scripting capabilities and thus widely usable, e.g. on parallel or cluster computers. Availability: The software is freely available for download at Contact: christian.spieth@uni-tuebingen.de
Miniaturized Multiplexed Protein Binding Assays
2006-06-16

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2D or not 2D: Are two dimensions enough to accurately model convective fluid flow through faults and surrounding host rocks?
2006-06-18

In many studies of water-rock interaction, convective fluid flow has been invoked \\nto explain diagenetic processes, metamorphism, or metal precipitation. Fluid \\nconvection in faults is increasingly recognised as an important mechanism for fluid \\nflow, heat transfer, and mass transport in hydrothermal systems, particularly in \\nconsolidated and crystalline rocks. Convection is influenced not only by heat \\ntransport processes within the fault but also by lateral heat transfer to and from \\nthe surrounding rock mass. There is often a close spatial relationship between \\nmajor ore deposits and regional scale faults.\\nMost numerical studies simulate free convection in 2D only. This is because fluid \\npatterns are more easily recognised with less complicated geometries, less \\ncomputational time is required, or because some computer codes are restricted to \\ntwo dimensions.\\nUsing the finite difference simulation code SHEMAT, a series of numerical \\nsimulations of thermally driven fluid flow have been carried out to investigate the \\ndifference in the fluid flow patterns in 2D and 3D models for the same geological \\narchitecture. SHEMAT solves coupled problems involving fluid flow, heat transfer, \\nspecies transport, and chemical water-rock interaction on a Cartesian grid. In \\nSHEMAT, the different flow, transport, and reaction processes can be selectively \\ncoupled. \\nThe results of this study show that 2D and 3D models of convection in hydrothermal \\nsystems produce significantly different results. In many cases 2D models represent \\nan oversimplification, and conclusions reached from such investigations are likely \\nto be irrelevant. In the case of planar high permeability regions, such as faults \\nand permeable stratigraphic units extending along strike, 2D and 3D modelling \\noutcomes vary significantly. Hence 3D models are absolutely essential to describe \\nthe flow field in these cases. \\nAn exception is incorporation of an impermeable basement, resulting in 2D \\nconvection patterns identical to observed 3D fluid flow fields, but only if \\nvertical fault permeability equals horizontal host rock permeability. Conceptual \\nexemptions are 2D models of high permeability regions with close to radial or \\nlinear symmetries, such as damage zones between fault jogs or at fault \\nintersections, giving reasonable results in 2D.
Proteomic dissection of plant development
2006-06-19

Abstract Plant development is controlled by complex endogenous genetic programs and responses to environmental cues. Proteome analyses have recently been introduced to plant biology to identify proteins instrumental in these developmental processes. To date most plant proteome studies have been employed to generate reference maps of the most abundant soluble proteins of plant organs at a defined developmental stage. However, proteomics is now also utilized for genetic studies comparing the proteomes of different plant genotypes, for physiological studies analyzing the influences of exogenous signals on a particular plant organ, and developmental studies investigating proteome changes during development. Technical advances are now beginning to allow a proteomic dissection of individual cell types, thus greatly increasing the information revealed by proteome analyses.
Confluent and reticulated papillomatosis Gougerot‐Carteaud successfully treated with minocycline
2006-06-19

Summary Confluent and reticulated papillomatosis is a rare dermatosis of unknown etiology mostly affecting young males and females most common in adolescence. The eruption consists of confluent, flat, brown papules forming a pigmented reticulated pattern. It occurs primarily in the intermammary and epigastric regions but may spread to the axillae. A 27‐yearold patient with typical clinical and histologic features of confluent and reticulated papillomatosis responded well to oral minocycline.
Does the efficacy of supplemental oxygen for the prevention of postoperative nausea and vomiting depend on the measured outcome, observational period or site of surgery?
2006-06-20

Summary High intra‐operative oxygen concentration reportedly reduces postoperative nausea and vomiting (PONV), but recent data are conflicting. Therefore, we tested whether the effectiveness of supplemental oxygen depends on the endpoint (nausea vs. vomiting), observation interval (early vs. late) or surgical field (abdominal vs. non‐abdominal). We randomly assigned 560 adult patients undergoing various elective procedures with a PONV risk of at least 40% to intra‐operative 80% (supplemental) or 30% oxygen (control). Potential confounding factors were similar between groups. Incidences of nausea were similar in the groups during early (12% (supplemental) vs. 10% (control), p = 0.43) and late intervals, 26% vs. 20%, p = 0.09, as were the incidences of vomiting (early: 2% vs. 3%, p = 0.40; late: 8% vs. 9%, p = 0.75). Supplemental oxygen was no more effective at reducing PONV in abdominal (40% vs. 31%, p = 0.37) than in non‐abdominal surgery (25% vs. 21%, p = 0.368). Thus, supplemental oxygen was unable to reduce PONV independent of the endpoint, observational period or site of surgery.
Epirubicin/paclitaxel (EP) vs. capecitabine/paclitaxel (XP) in first-line metastatic breast cancer (MBC): A prospective, randomized multicentre phase III study of the AGO breast cancer study group
2006-06-20

517 Background: Anthracyline-taxane combinations have the highest response rates in high risk MBC. Recently, anthracyclines and taxanes have become standards for adjuvant breast cancer chemotherapy. The addition of capecitabine to docetaxel improved overall survival in MBC. This regime was associated with a high rate of side effects (actually FN was not different from Taxotere mono - it was more the addition of cape AEs to Taxotere AEs). Earlier phase II studies with XP are able to show efficacy with better tolerability including less febrile neutropenia. Methods: Our aim was to show non-inferiority of XP to EP. The primary endpoint was progression-free survival (PFS). Secondary endpoints were toxicity and overall survival (OS).Patients (pts) were treated with 6x E 60 mg/m 2 and P 175 mg/m 2 d1 q21d, or with 6× X 2×1000 mg/m 2 d1–14 q 21d and P 175 mg/m 2 d1 q21d. Results: During a period of 2.5 y the planned 340 pts (170 in each arm) in 63 centres were recruited. The median number of cycles was 6 in both arms. The median PFS for EP was 11.8 months, and 12.3 for XP (p=ns). OS also was not different between the arms. The response rate (RECIST) was 41.0% (CR 6.6%, PR 34.4%) for EP and 41.5% (CR 8.5%, PR 33.1%) for XP. The main toxicity was myelosuppression (10% of cycles grade 3/4). Febrile neutropenia was seen in 5 cases in EP and in 1 case in XP. Skin toxicity grade 3 was observed in 5 of XP pts. Two patients stopped treatment for cardiological reasons in EP, and 4 patients for GI reasons in XP. Conclusions: This first analysis shows a comparable efficacy of the non-anthracycline regimen XP to the EP combination in first-line MBC. The toxicity is relatively low compared to other non-anthracycline containing combination therapies. XP is therefore an appropriate option for pts with anthracycline pretreated first line MBC. [Table: see text]
The benefit of whole-body low-dose unenhanced multidetector computer tomography (WBLD-MDCT) for follow up and therapy response monitoring in patients with multiple myeloma: Correlation with hematologic parameters
2006-06-20

7607 Background: To assessthe value of whole-body low-dose multidetector computer tomography (WBLD-MDCT) as diagnostic and survey modality in multiple myeloma (MM), and as a one-stop alternative (Horger et al. EJR 2005;54:289–297) to established imaging techniques (e.g. x-ray and MRI). Methods: Between 7/2001 and 2/2005, WBLD-MDCT scans were obtained in 90 consecutive patients with histologically proven stage II-III MM, all patients having 2 or more scans (mean = 3,8; range = 2–6). CT-scans were performed using a standardized low-dose protocol and the number, size and density of focal or diffuse medullary (in the appendicular skeleton and pelvis) and extra-medullary lesions as well as osteolysis were analysed for each examination and at follow up. Results were correlated with current standard MM laboratory data and at follow up in order to assess correct temporal recognition of significant myeloma changes by both methods. Results: Detection and follow up of medullary and extra-medullary MM lesions and osteolysis by WBLD-MDCT resulted in a sensitivity of 92%, a specificity of 93%, a NPV of 95%, a PPV of 85% and a likelihood ratio for patients with CT-abnormalities to present changes in the course of their disease of 12. Results of radiologic and hematologic analysis showed high agreement at follow up (median, 3 mo). However, agreement of both techniques at the time of investigation was only moderate (κ = 0.629), with CT being correct in 60% of mismatching cases. Thus, CT enabled earlier detection of MM changes. WBLD-MDCT assessed correctly the course of disease in all 4 patients with nonsecretory MM. Evaluation of stability was optimal in all patients. Conclusions: WBLD-MD represents a reliable, widespread, quick (75s acquisition time), and cost-effective imaging technique in MM, allowing detection of bone marrow involvement, extra-medullary tumors and lytic bone lesions in different clinical settings (staging, follow up, therapy monitoring, evaluation of stability). WBLD-MDCT repeatedly allowed detection of changes in the course of the disease prior to laboratory data, especially in extramedullary MM relapse and nonsecretory MM. No significant financial relationships to disclose.
Combination therapy with pegylated liposomal doxorubicin and carboplatin in malignant gynecologic tumors. A prospective multicenter phase II trial of the AGO-OVAR and the AGO Kommission Uterus (AGO-K-Ut)
2006-06-20

5095 Background: To determine the toxicity and efficacy of combination therapy with pegylated liposomal doxorubicin (PLD) and carboplatin in patients with malignant gynecologic tumors. Methods: Patients with recurrent or advanced uterine sarcomas, endometrial, cervical or vaginal cancer or with recurrent platinum-sensitive ovarian cancer were treated with PLD 40mg/m 2 and carboplatin AUC 6, q28 over 6 cycles (up to 10 cycles allowed). Primary and secondary endpoints were tolerability and efficacy. Efficacy was measured according to RECIST and/or CA-125 GCIG criteria. Results: 67 pts with recurrent ovarian cancer, 11 pts with uterine sarcomas, 31 pts with endometrial cancer and 31 pts with cervical or vaginal cancer have been recruited (total 140 pts, 87 pts evaluable for response). Grade 3/4 hematologic toxicities occured in 8% for anemia, 14% for thrombocytopenia, 23% for leukopenia, and 25% for neutropenia of whom 2% developed febrile neutropenia. Non-hematologic Grade 3/4 toxicities have been observed in more than 5% of all patients for the following items: asthenia (14%), pain (10%), dyspnea (9%), palmo-plantar-erythema (7%), nausea and vomiting (7%), diarrhea (5%). The median dose intensity was 94% for PLD and 97% for carboplatin. 76% of all non-progressing patients received at least 5 cycles. The overall response rate was 56% in ovarian cancer, 43% in uterine sarcomas, 44% in endometrial cancer, and 14% in cervical and vaginal cancer. Conclusions: PLD/carboplatin was well tolerated, even in pretreated patients. The combination showed remarkable efficacy in patients with uterine sarcomas, endometrial cancer, and ovarian cancer which merits further evaluation. CA 125 response criteria in ovarian cancer are under evaluation and will be presented on ASCO. However, the regimen had limited efficacy in cervical and vaginal cancer. A prospective randomized trial in recurrent ovarian cancer patients comparing carboplatin/PLD with paclitaxel/carboplatin has already been started within the international study group network (AGO-OVAR 2.9; CALYPSO-trial). [Table: see text]
The HIV protease inhibitor ritonavir and the proteasome inhibitor bortezomib induce synergistic cytotoxicity on soft tissue sarcoma cells in vitro
2006-06-20

9566 Background: HIV-protease inhibitors like Ritonavir produces regressions in HIV-associated Kaposi‘s sarcoma, reportedly due to proteasome inhibition. We have here assessed the effect of Ritonavir and the proteasome inhibitor Bortezomib on the viability and proteasome activity of the soft tissue sarcoma cell lines RD (rhabdomyosarcoma) and A-673 (ewing‘s sarcoma) in vitro. Methods: Cytotoxixity was assessed by MTS-test. To directly dissect proteasome activity in viable sarcoma cells, we used a recently developed cell-permeable affinity label that for the first time allows to assess the individual activity profile of the different catalytically active proteasomal subunits in living cells (Berkers et al., Nature Methods, May 2005). Results: Both types of cells were resistant towards Bortezomib and Ritonavir monotherapy at therapeutic concentrations (20 nM for Bortezomib, 20μM for Ritonavir). Ritonavir induced cytotoxicity in sarcoma cell lines with an IC50 of 40μM. The combination of clinically meaningful concentrations of Ritonavir (20μM) with Bortezomib (10–20 nM) induced robust synergistic cytotoxicity in both sarcoma cell lines. Using affinity labelling of proteasome activity, we directly demonstrate that a) Botezomib abrogates beta5, but also beta1-proteosomal activity in sarcoma cells and b) that Ritonavir at 20μM does not affect proteasom activity. Conclusions: We here present the first analysis of active proteasomal subunits in living human sarcoma cell lines. Ritonavir and Velcade induce synergistic cytotoxicity at clinically meaningful concentrations in vitro, which is not mediated through a direct effect of Ritonavir on proteasome activity. Based on our data, the synergistic combination of Ritonavir and Bortezomib might warrant further clinical testing in soft tissue sarcoma in vivo. No significant financial relationships to disclose.