gebhart/patrepeval huggingface dataset:
Degradation of transgenic DNA from genetically modified soya and maize in human intestinal simulations (2002)

The inclusion of genetically modified (GM) foods in the human diet has caused considerable debate. There is concern that the transfer of plant-derived transgenes to the resident intestinal microflora could have safety implications. For these gene transfer events to occur, the nucleic acid would need to survive passage through the gastrointestinal tract. The aim of the present study was to evaluate the rate at which transgenes, contained within GM soya and maize, are degraded in gastric and small bowel simulations. The data showed that 80 % of the transgene in naked GM soya DNA was degraded in the gastric simulations, while no degradation of the transgenes contained within GM soya and maize were observed in these acidic conditions. In the small intestinal simulations, transgenes in naked soya DNA were degraded at a similar rate to the material in the soya protein. After incubation for 30 min, the transgenes remaining in soya protein and naked DNA were 52 (SEM 13·1) % AND 34 (sem 17·5) %, respectively, and at the completion of the experiment (3 h) these values were 5 % and 3 %, respectively. In contrast to the soya transgene, the maize nucleic acid was hydrolysed in the small intestinal simulations in a biphasic process in which approximately 85 % was rapidly degraded, while the rest of the DNA was cleaved at a rate similar to that in the soya material. Guar gum and tannic acid, molecules that are known to inhibit digestive enzymes, did not influence the rate of transgene degradation in soya protein. In contrast guar gum reduced the rate of transgene degradation in naked soya DNA in the initial stages, but the polysaccharide did not influence the amount of nucleic acid remaining at the end of the experiment. Tannic acid reduced the rate of DNA degradation throughout the small bowel simulations, with 21 (sem 5·4) % and 2 (sem 1·8) % of the naked soya DNA remaining in the presence and absence of the phenolic acid, respectively. These data indicate that some transgenes in GM foods may survive passage through the small intestine.
Integrated multichannel microchip electrospray ionization mass spectrometry: analysis of peptides from on-chip tryptic digestion of melittin (1997)

In continuation of our work to develop an integrated multichannel microchip interfaced to electrospray mass spectrometry (ESI-MS), this paper demonstrates one of several applications of this approach in monitoring tryptic digestion products. The multichannel microchip allowed integration of sample preparation onto the microchip to facilitate the analysis process. Melittin was selected as a model oligopeptide because it possesses a cluster of four adjacent basic residues which enable probing the site specificity of trypsin as a function of digest times. Reactions were performed on-chip in different wells for specific time periods and then analyzed by infusion from the microchip by ESI-MS, using leucine enkephalin as internal standard. The rate of formation and disappearance of the molecular ion and individual fragments was followed for a melittin to trypsin concentration ratio of 300:1. The results indicate the potential of integrating enzymatic reactions with multichannel microchip ESI-MS for automated optimization of reaction condition while consuming only small amounts of sample.
Efficacy of a Tyrosine Kinase Inhibitor in Idiopathic Pulmonary Fibrosis (2011)

In patients with idiopathic pulmonary fibrosis, BIBF 1120 at a dose of 150 mg twice daily, as compared with placebo, was associated with a trend toward a reduction in the decline in lung function, with fewer acute exacerbations and preserved quality of life. (Funded by Boehringer Ingelheim; ClinicalTrials.gov number, NCT00514683 .).
A piezoresistive microcantilever array for surface stress measurement: curvature model and fabrication (2007)

This paper presents a procedure for the fabrication of a piezoresistive microcantilever array for surface-stress-based chemical and biochemical sensing applications.All existing microcantilever surface stress sensors that are based on single-crystal silicon use p-doped piezoresistors.In this work, the advantages of using n-doped silicon piezoresistors for surface stress sensing have been demonstrated.Further, a new model for surface-stress-sensitive cantilevers, based on classical laminated plate theory, is presented.This model allows for the estimation of the deformation and piezoresistive response of a multilayered microcantilever to surface stresses during analyte measurement and residual stresses in the structural layers due to fabrication processes.Also, the model accounts for bending-stretching coupling in the microcantilever response to the stresses.The utility of the model as a design tool for control of cantilever curvature during the fabrication process has been demonstrated.
Sensing Characteristics of NIR Localized Surface Plasmon Resonances in Gold Nanorings for Application as Ultrasensitive Biosensors (2007)

The optical responses of 75-150 nm diameter gold nanorings to changes in local refractive index have been quantified by near-infrared extinction spectroscopy and compared to DDA calculations and an analytical approach. The "bulk" refractive index sensitivities of gold nanorings are substantially (>5 times) larger than those of nanodisks with similar diameters. Nanorings retain a significantly larger sensitivity than nanodisks at the same spectral position, demonstrating a clear shape dependence that may correlate to a systematic difference in the influence of the dielectric substrate. The nanoring bulk refractive index sensitivity scales linearly with plasmon peak position. The spectral sensitivity to thin films of alkanethiols gave a shift of approximately 5.2 nm/CH2 unit while bulk sensitivities as high as 880 nm/RIU were observed, the highest such reported sensitivities. Both bulk and thin dielectric film sensitivities correlated well with theory. Real-time label-free monitoring of protein binding via molecular recognition was demonstrated.
Quasi-Phase-Matched Third-Harmonic Generation in a Quasi-Periodic Optical Superlattice (1997)

Quasi-periodic structure can be introduced into nonlinear optical materials such as LiTaO 3 crystals. Such structures were used for quasi–phase-matching second-harmonic generation. These materials are now shown to be able to couple second-harmonic generation and sum-frequency generation through quasi–phase-matching. The approach led to a direct third-harmonic generation with high efficiency through a coupled parametric process. The result verifies that high-order harmonics may be generated in a quadric nonlinear medium by a number of quasi–phase-matching processes, and therefore, exhibits a possible important application of quasi-periodic structure materials in nonlinear optics.
In vitro development of inner cell masses isolated immunosurgically from mouse blastocysts. II. Inner cell masses from 3.5- to 4.0-day p.c. blastocysts. (1978)

This paper describes the development in culture of inner cell masses isolated immunosurgically from C3H/He mouse blastocysts immediately after collection between 3.5 and 4.0 days p.c. By 24--48 h most of the inner cell masses isolated from half-expanded blastocysts, and about 50% of those from expanded blastocysts, regenerate an outer layer of trophectoderm-like cells and so resemble mini-blastocysts. With further in vitro culture these structures attach to the substratum and give rise to trophoblast-like giant cells, together with clusters of parietal endoderm cells or inner cell masses surrounded by visceral endoderm. Many of the inner cell masses from the remaining expanded blastocysts develop into floating structures with an outer layer of endoderm cells, and by 7 days consist of a large fluid filled cyst surrounding a collapsed vesicle of epithelial cells. Mesodermal cells line the cysts and form numerous blood islands. When mechanically disrupted, and grown as attached sheets of cells, these cystic structures give rise to patches of trophoblast-like giant cells similar to those described in the previous paper. These results suggest that the inner cell mass of normal mouse blastocysts contains cells which are capable of giving rise to trophoblast in culture.
Requirement for PAK4 in the Anchorage-independent Growth of Human Cancer Cell Lines (2002)

p21-activated protein kinase (PAK) serine/threonine kinases are important effectors of Rho family GTPases and have been implicated in the regulation of cell morphology and motility, as well as in cell transformation. To further investigate the possible involvement of PAK kinases in tumorigenesis, we analyzed the expression of several family members in tumor cell lines. Here we demonstrate that PAK4 is frequently overexpressed in human tumor cell lines of various tissue origins. We also have identified serine (Ser-474) as the likely autophosphorylation site in the kinase domain of PAK4 in vivo. Mutation of this serine to glutamic acid (S474E) results in constitutive activation of the kinase. Phosphospecific antibodies directed against serine 474 detect activated PAK4 on the Golgi membrane when PAK4 is co-expressed with activated Cdc42. Furthermore, expression of the active PAK4 (S474E) mutant has transforming potential, leading to anchorage-independent growth of NIH3T3 cells. A kinase-inactive PAK4 (K350A,K351A), on the other hand, efficiently blocks transformation by activated Ras and inhibits anchorage-independent growth of HCT116 colon cancer cells. Taken together, our data strongly implicate PAK4 in oncogenic transformation and suggest that PAK4 activity is required for Ras-driven, anchorage-independent growth.
"Sepsis/SIRS," Physiologic Classification, Severity Stratification, Relation to Cytokine Elaboration and Outcome Prediction in Posttrauma Critical Illness (1996)

PSSC allows classification of the physiologic and cytokine mediator response to trauma and permits stratification of severity in posttrauma critical illness.
The Catalytic Role of Aspartic Acid-92 in the Human Dual-Specific Protein-Tyrosine-Phosphatase Vaccinia H1-Related (1995)

The mechanism of catalysis for the human dual-specific (vaccinia H1-related) protein-tyrosine-phosphatase was investigated. The pH dependence of the kcat value is bell-shaped when p-nitrophenyl phosphate was employed as a model substrate. The kcat/Km pH profile rises with a slope of 2 and decreases with a slope of -1, indicating that two groups must be unprotonated and one group must be protonated for activity. An amino acid residue with an apparent pKa value of 5.5 +/- 0.2 must be unprotonated and a residue with a pKa value of 5.7 must be unprotonated for activity. The pKa value of the catalytic cysteine-124 (C124) was 5.6 +/- 0.1. The aspartic acid-92-asparagine (D92N) mutant enzyme was 100-fold less active than the native enzyme and exhibited the loss of the basic limb in the pH profiles, suggesting that in the native enzyme D92 must be protonated for activity. The D92 residue is conserved throughout the entire family of dual-specific phosphatases. Mutants glutamic acid-6-glutamine, glutamic acid-32-glutamine, aspartic acid-14-asparagine, and aspartic acid-110-asparagine had less than a 2-fold effect on the kinetic parameters when compared to native enzyme. Based upon the lack of a "burst" in rapid reaction kinetics, formation of the intermediate is rate-limiting with both native and D92N mutant enzymes. In agreement with rate-limiting formation of the intermediate, the pKa value of 5.5 for the group which must be unprotonated for activity was assigned to C124.(ABSTRACT TRUNCATED AT 250 WORDS)
X. The Bakerian Lecture. —Experimental relations of gold (and other metals) to light (1857)

Abstract That wonderful production of the human mind, the undulatory theory of light, with the phenomena for which it strives to account, seems to me, who am only an experimentalist, to stand midway between what we may conceive to be the coarser mechanical actions of matter, with their explanatory philosophy, and that other branch which includes, or should include, the physical idea of forces acting at a distance; and admitting for the time, the existence of the ether, I have often struggled to perceive how far that medium might account for or mingle in with such actions, generally; and to what extent experimental trials might be devised which, with their results and consequences, might contradict, confirm, enlarge, or modify the idea we form of it, always with the hope that the corrected or instructed idea would approach more and more to the truth of nature, and in the fulness of time coincide with it. The phenomena of light itself are, however, the best and closest tests at present of the undulatory theory; and if that theory is hereafter to extend to and include other actions, the most effectual means of enabling it to do so will be to render its application to its own special phenomena clear and sufficient. At present the most instructed persons are, I suppose, very far from perceiving the full and close coincidence between all the facts of fight and the physical account of them which the theory supplies. If perfect, the theory would be able to give a reason for every physical affection of fight; whilst it does not do so, the affections are in turn fitted to develope the theory, to extend and enlarge it if true, or if in error to correct it or replace it by a better. Hence my plea for the possible utility of experiments and considerations such as those I am about to advance.
Route Planning in Transportation Networks (2015)

We survey recent advances in algorithms for route planning in transportation networks. For road networks, we show that one can compute driving directions in milliseconds or less even at continental scale. A variety of techniques provide different trade-offs between preprocessing effort, space requirements, and query time. Some algorithms can answer queries in a fraction of a microsecond, while others can deal efficiently with real-time traffic. Journey planning on public transportation systems, although conceptually similar, is a significantly harder problem due to its inherent time-dependent and multicriteria nature. Although exact algorithms are fast enough for interactive queries on metropolitan transit systems, dealing with continent-sized instances requires simplifications or heavy preprocessing. The multimodal route planning problem, which seeks journeys combining schedule-based transportation (buses, trains) with unrestricted modes (walking, driving), is even harder, relying on approximate solutions even for metropolitan inputs.
Engineered binding to erythrocytes induces immunological tolerance to E. coli asparaginase (2015)

Antigen-specific immune responses to protein drugs can hinder efficacy and compromise safety because of drug neutralization and secondary clinical complications. We report a tolerance induction strategy to prevent antigen-specific humoral immune responses to therapeutic proteins. Our modular, biomolecular approach involves engineering tolerizing variants of proteins such that they bind erythrocytes in vivo upon injection, on the basis of the premise that aged erythrocytes and the payloads they carry are cleared tolerogenically, driving the deletion of antigen-specific T cells. We demonstrate that binding the clinical therapeutic enzyme Escherichia coli l-asparaginase to erythrocytes in situ antigen-specifically abrogates development of antibody titers by >1000-fold and extends the pharmacodynamic effect of the drug 10-fold in mice. Additionally, a single pretreatment dose of erythrocyte-binding asparaginase tolerized mice to multiple subsequent doses of the wild-type enzyme. This strategy for reducing antigen-specific humoral responses may enable more effective and safer treatment with therapeutic proteins and drug candidates that are hampered by immunogenicity.
Modulation of Double‐Stranded RNAs in Vivo by RNA Duplex Unwindasea (1992)

The double-stranded RNA (dsRNA) unwinding/modifying activity is a recently discovered cellular activity capable of unwinding or denaturing dsRNAs by modifying multiple adenosine residues to inosines and creating I-U mismatched base-pairings. The biological functions of this activity, which can potentially mutate the coding capacity of messenger RNAs (mRNAs), are presently not known. However, this unwinding/modifying activity is likely to affect the secondary structures, processing, and turn-over of various eukaryotic as well as viral transcripts. Although the activity was originally found and proposed as a cellular factor that interfered with the use of antisense RNA, it now appears more likely that the activity in fact may participate in antisense RNA suppression of target genes, either by altering the coding capacity of the sense mRNAs or by accelerating the degradation of duplex RNAs. Further understanding of this novel enzymatic activity, and thus, in turn, of the metabolism of dsRNAs in vivo, should allow us to derive a better strategy for designing antisense RNA.
Transparent robust image watermarking (2002)

We propose a watermarking scheme to hide copyright information in an image. The scheme employs visual masking to guarantee that the embedded watermark is invisible and to maximize the robustness of the hidden data. The watermark is constructed for arbitrary image blocks by filtering a pseudo-noise sequence (author id) with a filter that approximates the frequency masking characteristics of the visual system. The noise-like watermark is statistically invisible to deter unauthorized removal. Experimental results show that the watermark is robust to several distortions including white and colored noises, JPEG coding at different qualities, and cropping.
"Eosinophilic" peritonitis in continuous ambulatory peritoneal dialysis (CAPD). (1981)

Three cases of "sterile" peritonitis in CAPD patients are discussed, where the predominant white cell type in the peritoneal dialysis fluid was the eosinophil. No bacterial or fungal organism was isolated on repeated culture of the dialysis fluid and all had a benign course. The eosinophilic response appears to occur very soon after starting CAPD, is relatively asymptomatic and does not require antibiotic therapy. It is suggested that the eosinophilia is related to allergy to some constituent of the peritoneal dialysis system.
RET gene mutations (genotype and phenotype) of multiple endocrine neoplasia type 2 and familial medullary thyroid carcinoma (2014)

The rapid technical advances in molecular biology and accelerating improvements in genomic and proteomic diagnostics have led to increasingly personalized strategies for cancer therapy. Such an approach integrates the genomic, proteomic, and molecular information unique to the individual to provide an accurate genetic diagnosis, molecular risk assessment, informed family counseling, therapeutic profiling, and early preventative management that best fits the particular needs of each patient. The discovery of mutations in the RET proto-oncogene resulting in variable onset and severity of multiple endocrine neoplasia type 2 (MEN2) was the first step in developing direct genetic testing for at-risk individuals. Patients with germline RET mutations may undergo risk assessment and appropriate intervention based on specific mutations. Moreover, family members of affected individuals receive counseling based on understanding of the genetic transmission of the disease. Increasingly, clinicians are able to make therapeutic choices guided by an informative biomarker code. Improvements in detection and management of patients with MEN2 resulting from understanding of the RET proto-oncogene are evidence of the benefits of personalized cancer medicine. This review describes the discovery of the RET proto-oncogene, the association between genotype and phenotype, and the role of mutation analysis on diagnosis and treatment of MEN2.
1,3- -D-Glucan Antigenemia for Early Diagnosis of Invasive Fungal Infections in Neutropenic Patients with Acute Leukemia (2008)

Monitoring of BG antigenemia is a useful noninvasive method for early diagnosis of IFI in patients with acute leukemia.
Classic and alternative red blood cell storage strategies: seven years of "-omics" investigations. (2015)

significant update of all regulatory aspects concerning transfusion medicine activities in Italy, including the establishment of a nationally co-ordinated blood system consistent with the autonomy of regional authorities 1 . The aim was to identify homogeneous standards of quality and safety nationwide 1 . In this setting, the newly born Italian National Blood Centre was to be responsible for all technical and scientific aspects related to transfusion medicine issues, including (i) blood and blood product self-sufficiency; (ii) blood quality and safety; (iii) appropriate utilisation of blood resources; (iv) accreditation and funding of transfusion medicine activities; (v) a national blood information system; (vi) technology assessment; (vii) external quality assessment; (viii) a national haemovigilance network; (ix) control of medical products deriving from human plasma; (x) inspections and controls of the plasma-derivative industry; (xi) education and scientific research in transfusion medicine, and (xii) promotion of voluntary, non-remunerated, responsible and periodic blood donation 1 . In the light of such an ambitious agenda, the National Blood Centre started an extensive series of scientific initiatives, including an extensive collaboration with the laboratory of proteomics and metabolomics at Tuscia University, Viterbo, Italy. The present review summarises the main outcomes of this joint effort, while putting the results in the broader framework of laboratory research in the field of transfusion medicine, with a special focus on the storage of red blood cell (RBC) concentrates. -Omics and transfusion medicine: first contacts and rendezvous
Treatment of acute lymphoblastic leukemia in Hong Kong children: HKALL 93 study (2002)

A population-based multicentre study for childhood acute lymphoblastic leukemia (ALL) was conducted in Hong Kong from 1993 to 1997. One hundred and forty-five newly diagnosed ALL patients were treated by the HKALL 93 protocol. Patients were stratified into three risk groups according to age, presenting white cell count, immunophenotyping and cytogenetic study. The patients received the same induction and early and late intensification at week 5 and week 20. Fifty-eight standard risk (SR) patients received regular intrathecal methotrexate as CNS preventive therapy, while 49 intermediate risk (IR) patients received high dose intravenous methotrexate and regular intrathecal methotrexate. Thirty-eight high risk (HR) patients were treated with prophylactic cranial irradiation and an additional intensification block at week 35. The induction remission rate was 97.2% with 2% induction death. Two patients died during first complete remission. Relapse occurred in 20.7, 42.9 and 42.1% of SR, IR and HR patients respectively. By multivariate logistic regression, age> or =10 years and white cell count> or =100 x 10(9)/l were the two significant variables accounting for mortality. The 5-year overall and event-free survival of the whole group was 81.3 and 62.6% respectively. According to risk groups, the event-free survival was 79, 49 and 61% for SR, IR and HR patients respectively, while the overall survival was 96, 73 and 68% for SR, IR and HR patients respectively. In conclusion, the treatment protocol had low treatment-related mortality but was associated with a rather high relapse rate, especially in IR patients. Salvage therapy achieved sustained second remission in some patients. More intensive treatment especially a late intensification is required to improve the outcome.