gebhart/patrepeval huggingface dataset:
Standardization developments for large scale biobanks in smoking related diseases - a model system for blood sample processing and storage (2013)

This technology development allows rapid access to a given sample in the frozen archive while maintaining individual sample integrity with sample tube confinement and quality management.
Caged Single and Double Strand Breaks (1999)

Ionizing radiation and radiomimetic drugs such as bleomycin, calichieamycin, neocarzinostatin chromophore, and other synthetic agents can produce both single and double strand breaks in DNA. The ability to study the structure-activity relationships of single and double-strand break repair, lethality, and mutagenesis in vivo is complicated by the numerous types and sites of DNA cleavage products that can be induced by such agents. The ability to "cage" such breaks in DNA might help to further such studies and additionally afford a mechanism for activating and deactivating nucleic acid based drugs and probes. The major type of single strand break induced by ionizing radiation is a 3'- and 5'-phosphate terminated single nucleotide gap. Previously, a caged strand break of this type had been developed that was designed to produce the 5'-phosphate directly upon irradiation with 366 nm light, and the 3'-phosphate by a subsequent beta-elimination reaction [Ordoukhanian, P., and Taylor, J.-S. (1995) J. Am. Chem. Soc. 117, 9570]. Unfortunately, the release of the 3'-phosphate group was quite slow at pH 7. To circumvent this problem, a second caged strand break has been developed that produces the 3'-phosphate directly upon irradiation, and the 5'-phosphate by a subsequent beta-elimination reaction. When this caged strand break was used in tandem with the previous caged strand break, 5'- and 3'-phosphate terminated gaps could be directly produced by irradiation with 366 nm light. These caged single strand breaks were also incorporated in tandem into hairpin substrates to demonstrate that they could be used to cage double strand breaks. These caged single strand breaks should be generally useful for generating site-specific DNA single and double strand breaks and gaps, using wavelengths and doses of light that are nondetrimental to biological systems. Because the position of the single strand break can be varied, it should now be possible to examine the effect of the sequence context and cleavage pattern of single and double strand breaks on the lethality and mutagenicity of this important class of DNA damage.
Cytoskeletal protein kinases: titin and its relations in mechanosensing (2011)

Titin, the giant elastic ruler protein of striated muscle sarcomeres, contains a catalytic kinase domain related to a family of intrasterically regulated protein kinases. The most extensively studied member of this branch of the human kinome is the Ca(2+)-calmodulin (CaM)-regulated myosin light-chain kinases (MLCK). However, not all kinases of the MLCK branch are functional MLCKs, and about half lack a CaM binding site in their C-terminal autoinhibitory tail (AI). A unifying feature is their association with the cytoskeleton, mostly via actin and myosin filaments. Titin kinase, similar to its invertebrate analogue twitchin kinase and likely other "MLCKs", is not Ca(2+)-calmodulin-activated. Recently, local protein unfolding of the C-terminal AI has emerged as a common mechanism in the activation of CaM kinases. Single-molecule data suggested that opening of the TK active site could also be achieved by mechanical unfolding of the AI. Mechanical modulation of catalytic activity might thus allow cytoskeletal signalling proteins to act as mechanosensors, creating feedback mechanisms between cytoskeletal tension and tension generation or cellular remodelling. Similar to other MLCK-like kinases like DRAK2 and DAPK1, TK is linked to protein turnover regulation via the autophagy/lysosomal system, suggesting the MLCK-like kinases have common functions beyond contraction regulation.
Immunological Barriers to Embryonic Stem Cell-Derived Therapies (2008)

Replacement of diseased tissues with healthy cells derived from embryonic stem (ES) cells has a potential to become, in the future, a better alternative to current treatments of a number of conditions characterized by irreversible tissue injury, such as heart and liver failure, diabetes mellitus and neurodegeneration. However, several obstacles have to be overcome before this new therapeutic modality becomes part of a standard clinical practice. First of all, ethical and safety issues have to be resolved, the methodologies must be developed to enable obtaining sufficient amounts of differentiated cells, and the immune rejection of allogeneic cells must be prevented in order to ensure their long-term engraftment and function. Data on immunological properties of human and murine ES cells and their differentiated derivatives are controversial, ranging from those claiming unique immune-privileged properties for ES cells to those which refute these conclusions. This indicates that much more research is required to definitively understand the immunological features and engraftment capacity of ES cell derivatives. We review here the current state of the art in this new and exciting field of ES cell immunology and discuss the implications of these findings for the development of ES cell-based therapies.
Evidence for HSP-mediated cytoskeletal stabilization in mesothelial cells during acute experimental peritoneal dialysis (2007)

Low biocompatibility of peritoneal dialysis fluid (PDF) injures mesothelial cells and activates their stress response. In this study, we investigated the role of heat shock proteins (HSP), the main cytoprotective effectors of the stress response, in cytoskeletal stabilization of mesothelial cells in experimental peritoneal dialysis. In cultured human mesothelial cells, cytoskeletal integrity was assessed by detergent extractability of marker proteins following in vitro PDF exposure. Effects of HSP on stabilization of ezrin were evaluated by a conditioning protocol (PDF pretreatment) and repair assay, based on coincubation of cytoskeletal protein fractions with recombinant HSP-72 or HSP-72 antibodies. In the rat model, detachment of mesothelial cells from their peritoneal monolayer during in vivo PDF exposure was assessed with and without overexpression of HSP-72 (by heat conditioning). In vitro, cytoskeletal disruption on sublethal PDF exposure was demonstrated by significantly altered detergent extractability of ezrin and ZO-1. Restoration was associated with significant induction and cytoskeletal redistribution of HSP during recovery. Both the conditioning protocol and in vitro repair assay provided evidence for HSP-72-mediated cytoskeletal stabilization. In the rat model, overexpression of HSP-72 following heat conditioning resulted in significantly reduced detachment of mesothelial cells on in vivo exposure to PDF. Our results establish an essential role of HSP in repair and cytoprotection of cytoskeletal integrity in mesothelial cells following acute in vitro and in vivo exposure to PDF. Repeated exposure to PDF, as is the rule in the clinical setting, may not only cause repeat injury to mesothelial cells but rather represents a kind of inadvertent conditioning treatment.
Automated and optimal system identification by canonical variables (2005)

The completely automatic, reliable and optimal identification of linear dynamical systems has the potential to revolutionize the operation of control systems, signal processing, and system monitoring. In this paper, the theory, methods, and results of such an identification procedure are outlined. The procedure applies to a general multivariable, time-invariant linear system with stochastic disturbances that may be nonstationary and the system may be unstable and have feedback. Deterministic polynomial time functions may be present in the observations. The computation involves primarily the singular value decomposition (SVD). The model state order is automatically determined using an optimal statistical order selection procedure, a small sample version of the Akaike information criterion (AIC). A multivariable stochastic state space model of the input-output dynamics and system disturbances is computed by multivariate regression. The identified model accuracy is described by confidence bands on the transfer function and power spectrum as well as maximum singular value quantities. These can be used directly in robust control design.
In Reply (2006)

First, once a certain regimen becomes the standard of care, this implies that an alternative approach by definition is an inferior therapeutic option. We believe that the standard of care in the treatment of patients with newly diagnosed MM is to attempt attaining a remission in preparation for stem cell transplant (SCT) provided that the patient is transplant eligible. Whether the remission is achieved with singleagent D, TD, or vincristine, adriamycin, and dexamethasone is unimportant to date. There is no data to suggest that a remission achieved with TD would offer better long-term disease-free survival after SCT as opposed to D alone. It is certainly possible that this may change with long-term follow-up, but until such data is available, naming any regimen as a new standard of care seems premature. In fact, the data reported suggest that 37% of patients in the TD arm have undergone SCT, a figure comparable with patients who underwent SCT in the D arm, suggesting that single-agent D did not preclude patients from SCT. Second, one must balance therapeutic efficacy against toxicity. The data reported by Rajkumar et al 2 suggest that TD carries substantial toxicity. Peripheral neuropathy, DVT, and any grade 4 adverse event occurred at a statistically significantly higher incidence in the TD arm. These toxicities suggest that reserving the combination therapy for patients who do not respond to single-agent D is the most appropriate course of action. Since patients treated with TD are at substantial risk for DVT, it remains important to decide as to how to prevent this complication. Richardson and Anderson state in their editorial "prophylactic doses of low molecular weight heparin, full dose anticoagulation with oral warfarin, and aspirin at doses from 81 mg to 325 mg per day have all been effective." 1 This statement highlights the lack of consensus among oncologists and researchers as to how to best prevent T-induced DVT. The role of different doses of aspirin in treating and/or preventing DVTs is controversial. The suggestion that either full-dose anticoagulation or simply prophylactic doses may be effective adds to the confusion among physicians and patients and begs for researchers and investigators to conduct clinical trials in this arena. It is important to understand the mechanisms of DVTs in patients who are exposed to TD and to proceed with definitive studies that would allow for better understanding of this phenomenon and how to best prevent it. A dealer's choice approach to treat DVTs in this setting is far from science and should make all of us pause before recommending this regimen to all of our MM patients.
Burn-Induced Microglia Activation is Associated With Motor Neuron Degeneration and Muscle Wasting in Mice (2019)

BI induces microglia proliferation and activation (cytokine and chemokine release), degeneration of ventral horn motor neurons and muscle mass loss, all of which were accentuated by concomitant immobilization. The mechanisms connecting microglia activation and motor neuron degeneration to muscle mass loss require further delineation.
Flexible conflict detection and management in collaborative applications (1997)

This paper presents a comprehensive model for dealing with semantic conflicts in applications, and the implementation of this model in a toolkit for collaborative systems. Conflicts are defined purely through application semantics—the set of behaviors supported by the applications—and yet can be detected and managed by the infrastructure with minimal application code. This work describes a number of novel techniques for managing conflicts, both in the area of resolution policies and user interfaces for presenting standing conflicts in application data.
Effects of microbial invasion on cerebral hemodynamics and oxygenation monitored by near infrared spectroscopy in experimental Escherichia coli meningitis in the newborn piglet (1999)

This study was carried out to elucidate the pathophysiologic mechanism of cerebral hyperemia observed during the early phase of bacterial meningitis. We tested the hypothesis that microbial invasion through the blood-brain barrier is responsible for cerebral vasodilation and hyperemia in meningitis. Escherichia coli was given either intravenously (i.v.) or intracisternally (i.c.) to closely mimic the primary or secondary bacterial invasion occurring in meningitis and newborn piglets were grouped according to their invasion results (+ or -); 12 in the i.v. (+) group, 14 in the i.v. (-) group, 13 in the i.c. (+) group, 15 in the i.c. (-) group. The results were compared with eight animals in the control group. Near infrared spectroscopy (NIRS) was employed to monitor changes in total hemoglobin (HbT), oxygenated hemoglobin (HbO), deoxygenated hemoglobin (Hb), deduced hemoglobin (HbD), and oxidized cytochrome aa3 (Cyt aa3). HbT, as an index of cerebral blood volume, increased progressively in both i.v. (+) and i.v. (-) groups and became significantly different from control and baseline values at 2 h. Hb significantly increased only in i.v. (+) group. HbD, as an index of cerebral blood flow, decreased significantly in i.v. (+), i.v.(-) and i.c. (-) groups and this change was mitigated in i.c. (+) group, HbO was reduced in i.c. (-) group and this decrease was attenuated in i.c. (+) group. Increased Cyt aa3 was observed in all experimental groups after bacterial inoculation. Changes in ICP, blood pressure, cerebral perfusion pressure, blood or CSF glucose or lactate, CSF TNF-alpha level, or CSF leukocytes number were not associated with changes in NIRS findings. These findings suggest that primary or secondary bacterial invasion across the blood-brain barrier is primarily responsible for cerebral vasodilation and hyperemia observed during the early phase of bacterial meningitis.
CT radiation risks coming into clearer focus (2013)

As we gather more direct evidence of the dose-response curve from childhood CT

Recent attention to the cancer risks of ionizing radiation has prompted vigorous debate about how to quantify the risks of diagnostic imaging, and whether or how these risks ought to be incorporated into our decision making process as we participate in patient care.

In the past, models of the carcinogenic risks of ionizing radiation have primarily relied on long term surveillance of the Japanese atomic bomb survivors, which showed significant increases in the incidence of cancer after effective doses greater than about 50 mSv.1 2 The relative paucity of direct data in the lower dose range delivered by diagnostic imaging has led to conflicting opinions about the shape and slope of the radiation dose-response curve.

In a linked study (doi:10.1136/bmj.f2360), Mathews and colleagues present compelling data on the magnitude of the cancer risk attributable to ionizing radiation.3 This well designed study examined a cohort of nearly 11 million young patients in the Australian national Medicare system and compared subsequent incidence of cancer in the 680 000 patients exposed to …
Sterically demanding methoxy and methyl groups in ruthenium complexes lead to enhanced quantum yields for blue light triggered photodissociation (2018)

Ruthenium complexes containing a sterically congested metal center can serve as light activated prodrugs through photo-activated chemotherapy (PACT). In this work, we modified PACT agents containing 6,6'-dihydroxybipyridine (6,6'-dhbp) (Papish et al., Inorg. Chem., 2017, 56, 7519) by replacing it with a sterically bulky isoelectronic ligand, 6,6'-dimethoxybipyridine (6,6'-dmbp). The resulting complexes, [(phen)2Ru(6,6'-dmbp)]Cl2 (2OMe, phen = 1,10-phenanthroline) and [(dop)2Ru(6,6'-dmbp)]Cl2 (3OMe, dop = 2,3-dihydro-[1,4]dioxino[2,3-f][1,10]phenanthroline), have been fully characterized and display enhanced quantum yields for blue light triggered photodissociation of 0.024(6) and 0.0030(2), respectively. We have also synthesized 4OH = [(dmphen)2Ru(4,4'-dhbp)]Cl2 wherein dmphen = 2,9-dimethyl-1,10-phenanthroline and 4,4'-dhbp = 4,4'-dihydroxybipyridine. These ligands enhance steric bulk near the metal center and move the hydroxy groups further from the metal center, respectively. Complex 4OH displays a relatively low quantum yield of 0.0014(2). All of the new complexes (2OMe, 3OMe, 4OH) were tested in breast cancer cells (MDA-MB-231) and were non-toxic (IC50 > 100 μM). This has been interpreted in terms of unfavorable log(Do/w) values and furthermore photodissociation alone is insufficient for cytotoxicity. We also report the crystal structures of 4OH and 2OMe, the thermodynamic acidity of complex 4OH, and the redox potentials for all new complexes.
Mat formation and unstable flows of highly filled suspensions in capillaries and continuous processors (1989)

Abstract Suspensions, which are filled at loading levels approaching their maximum packing fractions, present special processing challenges. The flow and deformation behavior of such highly filled suspensions are dominated by strong slip effects. Furthermore, during pressure driven flows of these suspensions, the polymer matrix can filter out, giving rise to demixing and unstable flows. In this study, the capillary flow and extrusion of highly filled suspensions of ammonium sulfate and other salt fillers in a poly(butadiene acrylonitrile acrylic acid), PBAN matrix were investigated. The experimentally observed instabilities were elucidated in conjunction with a proposed mechanism, involving slip and filtration rates. This mechanism suggested greater affinity to unstable flows with relatively lower matrix shear viscosity, greater particle size of the filler, and greater convergence ratio; all of which were experimentally verified.
The Distribution of Gentamicin in the Rabbit Cornea following Iontophoresis to the Central Cornea (1999)

The purpose of this study was to evaluate the penetration of gentamicin into the central, midperipheral and peripheral cornea of rabbits following iontophoresis to the central 3 mm of the cornea. Four groups (groups 1-4) of five rabbits (one eye per rabbit) underwent corneal iontophoresis using gentamicin dissolved in agar. Low (1 mg/ml) and high (10 mg/ml) concentrations of gentamicin in agar were used for one or ten minutes. Two control groups (groups 5 and 6) of five eyes each underwent mock iontophoresis with low and high concentrations of agar-gentamicin mixture. Following sacrifice of the rabbits, the central, midperipheral and peripheral parts of each cornea were excised. Gentamicin concentration was determined in each part of every cornea. High concentrations of gentamicin (951.6 +/- 369.4 microg/ml to 26.6 +/- 41.34 microg/ml) were obtained in the central parts of all the iontophoresis-treated corneas. In each group, except group 6, central corneas had higher concentrations of gentamicin compared to midperipheral corneas (p = 0.038 to p = 0.021), and midperipheral corneas had higher levels than peripheral corneas (p = 0.038 to p = 0.021). Following iontophoresis, gentamicin is found in all portions of the corneas; however, the highest concentration of the drug remains in the central cornea.
Clozapine Treatment of Children and Adolescents with Bipolar Disorder and Schizophrenia: A Clinical Case Series (1995)

Ten consecutive severely ill child and adolescent inpatients (aged 6–15 years), who had either multiple trials of typical neuroleptics and antimanic agents with inadequate symptom remission or side effect intolerance, were treated with open-label clozapine. Five patients had bipolar mood disorder (mixed type) and four had schizophrenia; one had psychotic disorder NOS. Weekly ratings of global functioning, estimated retrospectively by the treating physicians, were obtained for the 3 weeks before and 6 weeks during clozapine treatment. The mean daily clozapine dose was 3.2 mg/kg or 128 mg (range 75–225 mg). Seven of 10 patients received concurrent lithium therapy throughout the study. All of these 10 patients had psychotic symptoms and all 9 of the male patients had aggressive symptoms that required treatment. On the Clinical Global Impression Scale (CGI), there was a 42% decrease in the Severity of Illness score during the 6-week treatment (p < 0.004). All patients were rated as "severely ill" before clozapine, but 7 of the 10 patients were rated as being "moderately ill" or better following treatment. There were also significant improvements in the CGI Improvement subscale (57% increase) and the mean CGAS score (change from 22 to 54) during the 6-week treatment. Apparent improvements were generally evident after 1–2 weeks. Clozapine also seemed particularly helpful in treating aggressive behavior and psychotic symptoms in both bipolar and schizophrenic patients. Adverse effects were common but mild. Safety and efficacy cannot be assessed without controls, but these clinical trials suggest that highly treatment-resistant patients could show clinically meaningful improvement without problematic side effects during short-term clozapine treatment. These preliminary data also suggest that clozapine might have antipsychotic/antimanic properties in some youths with early-onset bipolar disorder.
Development of a Liquid Fuel System for GE MS5002E Gas Turbine: Rig Test Validation of the Combustor Performance (2014)

Analysis of the Oil & Gas market segment showed that potential MS5002E customers could benefit from firing the gas turbine with distillate oil as a back-up fuel, mainly to provide power when the fuel gas is not available (e.g. when the plant itself is being commissioned). To address this customer need, the design of a dual fuel system for such mission should target simplicity, reliability and minimize the additional cost with respect to the single gas version. To achieve these targets, the development of the dual fuel system for the MS5002E leveraged the efforts made by GE for the design of a liquid fuel system for Frame 9F-1 series with no need of atomization air. Moreover, the emission capability during liquid fuel operation was enhanced allowing the mixing of water and fuel before injection in the combustion chamber and using of improved injection technology, thus improving the efficiency of water injection with a significant reduction in the required water flow rates; the importance of this achievement is related to both the increasingly stringent regulation on this subject and the often poor availability of water in the Oil & Gas market segment. The system is capable of continuous operation without water injection for applications where emissions are not critical; in these cases a small amount of demineralized water is employed occasionally for fuel line cooling and flushing, thus helping to guarantee constant performances of the injectors, and to maintain liquid fuel start-up capability over time. This paper presents the expected performance, in terms of ignition capability, emissions, operability and expected hardware durability on LF/water-fuel emulsion operation, based on a single can rig test campaign. The new liquid fuel cartridges were tested from ignition to base load at ISO and extreme simulated ambient conditions, both with and without water injection, showing promising performance in terms of combustor operability and emissions. All the combustor components were instrumented with thermocouples to assess variations in the hardware thermal levels with respect to the single gas conditions, and identify possible issues related to the transient and steady-state liquid fuel operation. Further development and testing will be carried out in the next phases of the development, and the performance will be confirmed by a dedicated engine test at the first commercial opportunity.