gebhart/patrepeval huggingface dataset:
The Discovery of Linezolid, the First Oxazolidinone Antibacterial Agent (2001)

The emergence of new antibiotic-resistance in the significant Gram-positive pathogens in the last decade created a substantial medical need for new classes of antibacterial agents. Pharmacia Corporation scientists initiated a discovery research program in oxazolidinone chemistry and biology. Indanone-, tetralone-, and indoline-subunit oxazolidinones provided proof-of-concept interim improvements in antibacterial activity and safety SAR for the program. A method for enantiomeric enrichment of analogs was developed and intensive synthesis and evaluation efforts were undertaken with three oxazolidinone subclasses; the piperazine, indoline, and tropones. Members of the piperazinyl-phenyloxazolidinones possessed the most suitable chemical characteristics and biologic activity of the three subclasses. The monofluorophenyl congener eperezolid and the morpholino analog linezolid emerged as the first clinical candidates from the piperazine oxazolidinones. Linezolid was selected for continued human clinical evaluation based upon its' superior pharmacokinetic profile. Microbiologic testing revealed that linezolid compared very favorably against comparator antibiotics in vitro and in animal infection models. Linezolid possessed a unique mechanism of action in that it inhibited functional 70S initiation complex formation and did not cross-react with existing bacterial resistance. Oral bioavailability in humans was determined to be 100% and twice daily dosing in humans resulted in blood levels which even at trough values were in excess of the MIC90 for significant Gram-positive pathogens. The preclinical promise of linezolid was realized in human clinical trials where linezolid was highly efficacious in the treatment of medically significant Gram-positive infections.
A theoretical and experimental investigation of the systematic errors and statistical uncertainties of Time-Of-Flight-cameras (2008)

The following paper presents a model to predict the systematic errors and statistical uncertainties of Time-Of-Flight (TOF) 3D imaging systems. The experimental data obtained with a custom build test setup show that the SD of the depth signal rises approximately quadratically with the depth. The most significant systematic depth error is periodic with an amplitude of around 50mm. It is provoked by the inharmonic correlation function. The inhomogeneity in each pixel (fixed pattern) accounts for a depth error of about 20mm, while illumination and reflectivity variations cause depth errors of less than 10mm, provided that no overflows occur.
A New Approach to Manufacturing Biocomposite Sandwich Structures: Mycelium-Based Cores (2016)

A new approach to manufacturing biocomposite sandwich structures is introduced. Materials used in the biocomposite are natural textile reinforcement, mycelium-bound agricultural waste as core, and bioresin. This paper focuses on three specific steps of the seven-step manufacturing process: filling pre-stamped textile shells with core mixture; allowing the core material to grow thereby binding reinforcement particles and textile skins into a unitized preform; and oven drying said preform to drive off moisture and inactivate the mycelium. Specific process details highlighted include design and thermoforming of growth trays, tray sterilization, filling trays with mycelium-inoculated substrates filling and allowing growth to occur, and finally conduction and convection drying/inactivation of the grown parts. To study the new material’s stiffness using different materials and under different processing conditions, specimen dimensions were based on ASTM D7250 and C393 standards. All dried samples were tested in flexure by three-point bending method to determine the stiffness and strength of the resin-less preforms and to identify optimal material combinations.
Loss of aquaporin-4 expression and putative function in non-small cell lung cancer (2011)

Aquaporins (AQPs) have been recognized to promote tumor progression, invasion, and metastasis and are therefore recognized as promising targets for novel anti-cancer therapies. Potentially relevant AQPs in distinct cancer entities can be determined by a comprehensive expression analysis of the 13 human AQPs. We analyzed the presence of all AQP transcripts in 576 different normal lung and non-small cell lung cancer (NSCLC) samples using microarray data and validated our findings by qRT-PCR and immunohistochemistry. Variable expression of several AQPs (AQP1, -3, -4, and -5) was found in NSCLC and normal lung tissues. Furthermore, we identified remarkable differences between NSCLC subtypes in regard to AQP1, -3 and -4 expression. Higher transcript and protein levels of AQP4 in well-differentiated lung adenocarcinomas suggested an association with a more favourable prognosis. Beyond water transport, data mining of co-expressed genes indicated an involvement of AQP4 in cell-cell signalling, cellular movement and lipid metabolism, and underlined the association of AQP4 to important physiological functions in benign lung tissue. Our findings accentuate the need to identify functional differences and redundancies of active AQPs in normal and tumor cells in order to assess their value as promising drug targets.
Glucose metabolism in cancer cells: immunogold localization of hexokinase to the outer mitochondrial membrane (1995)

Hexokinase (ATP: D-hexose 6-phophotransferase EC 2.7.1.1) is the first enzyme of the glycolytic pathway which commits glucose to catabolism by catalyzing the phosphorylation of glucose with ATP. Previous studies have shown diat hexokinase activity is markedly elevated in rapidly growing tumor cells exhibiting high glucose catabolic rates. A large fraction (50-80%) of this enzyme activity is bound to the mitochondrial fraction (1,2) where it has preferred access to ATP (3). In contrast,the hexokinase activity of normal tissues is quite low, with one exception being brain which is a glucose-utilizing tissue (4). Biochemical evidence involving rigorous subfractionation studies have revealed striking differences between the subcellular distribution of hexokinase in normal and tumor cells [See review by Arora et al (4)]. In the present report, we have utilized immunogold labeling techniques to evaluate die subcellular localization of hexokinase in highly glycolytic AS-30D hepatoma cells and in the tissue of its origin, i.e., rat liver.
The Ca2+-dependent protein kinase CPK3 is required for MAPK-independent salt-stress acclimation in Arabidopsis (2010)

Plants use different signalling pathways to respond to external stimuli. Intracellular signalling via calcium-dependent protein kinases (CDPKs) or mitogen-activated protein kinases (MAPKs) present two major pathways that are widely used to react to a changing environment. Both CDPK and MAPK pathways are known to be involved in the signalling of abiotic and biotic stresses in animal, yeast and plant cells. Here, we show the essential function of the CDPK CPK3 (At4g23650) for salt stress acclimation in Arabidopsis thaliana, and test crosstalk between CPK3 and the major salt-stress activated MAPKs MPK4 and MPK6 in the salt stress response. CPK3 kinase activity was induced by salt and other stresses after transient overexpression in Arabidopsis protoplasts, but endogenous CPK3 appeared to be constitutively active in roots and leaves in a strictly Ca(2+) -dependent manner. cpk3 mutants show a salt-sensitive phenotype comparable with mutants in MAPK pathways. In contrast to animal cells, where crosstalk between Ca(2+) and MAPK signalling is well established, CPK3 seems to act independently of those pathways. Salt-induced transcriptional induction of known salt stress-regulated and MAPK-dependent marker genes was not altered, whereas post-translational protein phosphorylation patterns from roots of wild type and cpk3 plants revealed clear differences. A significant portion of CPK3 was found to be associated with the plasma membrane and the vacuole, both depending on its N-terminal myristoylation. An initial proteomic study led to the identification of 28 potential CPK3 targets, predominantly membrane-associated proteins.
Antigenic cross‐reactivity between the human whipworm, Trichuris trichiura, and the mouse trichuroids Trichuris muris and Trichinella spiralis (1988)

Cross-reactivity was demonstrated between circulating antibodies from Trichuris trichiura-infected humans and T. muris-infected mice for heterologous antigen preparations. Mouse immune sera raised against excretory/secretory (E/S) products and anterior end homogenate from adult T. muris showed marked affinity for T. trichiura adult homogenate in ELISA, and 35S-methionine-labelled adult T. muris E/S products were precipitated by T. trichiura infection sera. Monoclonal antibodies recognizing a 48 kD Trichinella spiralis muscle larval beta-stichocyte granule antigen also showed avidity for T. trichiura adult homogenate in ELISA, as did serum from mice with patent T. muris worm burdens. This cross-reactivity is thought to result from shared stichocyte antigens and the relevance of this observation is discussed.
Distribution of calpains and calpastatin in human blood cells. (1988)

The occurrence and molecular sizes of calpains and calpastatin in the lysates of human erythrocytes, platelets, lymphocytes/monocytes, and polymorphonuclear cells were studied by immunoelectrophoretic blot analysis. The basic uniformity among these cells of the 85-kDa and 83-kDa heavy subunits of low- and high-Ca2+-requiring calpains I and II, respectively, and of the 29-kDa light subunit was confirmed. Molecular diversity of calpastatin species, ranging from 70 kDa to 107 kDa, among different blood cells was also shown. The obtained data are consistent with those known for other animal tissues, thus settling hitherto uncertain or rather controversial issues on the distribution of calpains and calpastatin in human blood cells.
Posterior reversible encephalopathy syndrome in a postpartum woman with acute lymphoblastic leukaemia after intrathecal methotrexate (2017)

Posterior reversible encephalopathy syndrome (PRES) is the most common neurological complication occurring in children undergoing induction chemotherapy for acute lymphoblastic leukaemia (ALL) but is increasingly recognised to occur in adults as well. Here, we report a woman who presented with B-cell ALL (B-ALL) at the time of delivery and developed PRES 1 day after receiving intrathecal (IT) methotrexate (MTX) that rapidly resolved. She subsequently received IT MTX without recurrence of neurological symptoms. This case represents the first case of PRES in a postpartum B-ALL patient receiving IT MTX, demonstrates that re-treatment with MTX in this case could be done safely and highlights the risk of PRES in adults treated for B-ALL.
Commentary on prevention a possible drug-drug interaction: Is concurrent administration of orlistat and pioglitazone increase the risk of durg-induced hepatotoxicity? (2015)

Revealing the significant loss of viability of HepG2 cells in the combination use of pioglitazone and orlistat indicates these two drugs should not be administered at the same time to prevent their hepatotoxic effects especially in patients with liver dysfunction.
Site-Specific Antibody Conjugation Strategy to Functionalize Virus-Based Nanoparticles (2020)

Amine/thiol-reactive chemistries are commonly used to conjugate antibodies to pharmaceuticals or nanoparticles. Yet, these conjugation strategies often result in unfavorable outcomes such as heterogeneous antibody display with hindered biological activity or aggregation due to multivalent interactions of the antibody and nanoparticles. Here, we report the application of a site-specific and enzymatically driven antibody conjugation strategy to functionalize virus-based nanoparticles (VNPs). Specifically, an azide-handle was introduced into the Fc region of a set of immunoglobulins using a two-step enzymatic reaction: (1) cleavage of <i>N</i>-linked glycan in the Fc region by a glycosidase and (2) conjugation of a chemically reactive linker (containing an azide functional handle) using a microbial transglutaminase. Conjugation of the azide-functional antibodies to several VNPs was achieved by making use of strain-promoted azide-alkyne cycloaddition. We report the conjugation of three immunoglobulin (IgG) isotypes (human IgG from sera, anti-CD47 Rat IgG2a, κ, and Trastuzumab recombinant humanized IgG1, κ) to the plant virus cowpea mosaic virus (CPMV) and the lysine mutant of tobacco mosaic virus (TMVlys) as well as bacteriophage Qβ. Site-specific conjugation resulted in stable and functional antibody-VNP conjugates. In stark contrast, the use of heterobifunctional linkers targeting thiols and amines on the antibodies and VNPs, respectively, led to aggregation due to nonspecific and multivalent coupling between the antibodies and VNPs. We demonstrate that antibody-VNP conjugates were functional, and Trastuzumab-displaying VNPs targeted HER2-positive SKOV-3 human ovarian cancer cells. This bioconjugation strategy adds to the portfolio of methods that can be used for designing functional antibody-VNP conjugates.
Rethinking Professionalism in Early Childhood: Untested Feasibilities and Critical Ecologies (2010)

There is a lot of talk around professionalism in early childhood. Internationally, influential\ndiscourses, both scholarly and political, link ambitious goals to workforce requirements. Despite\nhuge differences between countries’ approaches to early childhood institutions, and to\nqualifications and roles of staff (Oberhuemer, 2005), there appears to be a broad consensus that the\nworkforce is central to achieving the ambitious policy goals, for example, of increasing both\nquantity and quality of provision (Siraj-Blatchford et al, 2002; Dalli, 2003; MacNaughton, 2005;\nOberhuemer, 2005; Organisation for Economic Co-operation and Development, 2006). In these\ndiscourses, the workforce and its members are regularly referred to as something that has to be\nprofessionalised, not least in order to be able to cope with the increasing challenges of the work\n(Organisation for Economic Co-operation and Development, 2001, 2006).\nThis special issue of Contemporary Issues in Early Childhood is undoubtedly placed within these\ndiscourses to further develop, rethink and re-form the early childhood profession. It does not,\nhowever, promote one particular answer; it does not attempt to offer one specific solution to the problem of early childhood professionalism. Instead, it challenges the notion that there is one\nproblem that should be dealt with by applying a specific (right) solution.
The zigzags of passion (2018)

We have been saying over the last few days that to desire means to stop looking at the stars and to put one’s feet back on the ground so as to be more able to continue on the journey. To desire where to put one’s feet and one’s eyes on Earth: in that way, the Transformation-Approach, by promoting realism, contributes to the containment of anxiety. It makes it possible, above all to see, and therefore to understand and to interpret. In this approach, regression must be considered as inevitable. In the current Italian political system, Bossi and the Lega Nord, I repeat, constitute an indispensable regression on the country’s path to Transformation, a path that is Italy’s within the rest of Europe. It was not by chance that the audience booed Bossi during a performance of a Verdi Opera in Verona’s arena. Knowing and understanding does not mean depreciating, but, on the contrary, appreciating a little bit better what is at stake. If that perception had been at work at the end of the twenties, they would have understood quicker that the regression with Mussolini was inevitable and therefore still “stoppable”. Fortunately, nowadays there are blockers: new political figures, Europe. Italy is an open system. After Moro and Mani Pulite, the country transformed and now has more vitality than France.
Decision-feedback equalization of pulse-position modulation on measured nondirected indoor infrared channels (1999)

We examine the performance of two decision-feedback equalizers (DFEs) for pulse-position modulation (PPM) on measured nondirected indoor infrared channels with intersymbol interference. PPM offers high average-power efficiency, but on ISI channels, unequalized PPM suffers severe performance penalties. We have previously examined the performance of the maximum-likelihood sequence detector (MLSD), and found that it yields significant improvements. However, the MLSD often requires such large complexity and delay that it may be impractical. We investigate suboptimal, reduced-complexity equalization techniques for PPM, providing a performance analysis of zero-forcing chip-rate and symbol-rate DFEs. Our results show that a symbol-rate DFE provides performance that closely approaches that of the optimal MLSD.
Thermogravimetric analysis of Silantek coal, Palm Kernel Shell, Palm Kernel Shell char and their blends during combustion (2011)

Preliminary thermogravimetric studies of Silantek coal (SL), Palm Kernel Shell (PKS), PKS char and their blends have been performed in a Thermogravimetry Analyser(TGA). PKS char were produced using microwave irradiation carbonization system at power of 300 Watt, with nitrogen flow rate of 150 mL/min for 30 minutes. Combustion tests of raw and blends samples were carried out in purified air atmosphere conditions at heating rates of 20 °C/min. The SL/ PKS and SL/ PKS char blends were prepared in the weight ratios of 80:20, 60:40, 50:50, 40:60 and 20:80. Derivative thermogravimetric (DTG) results which represent the decomposition of volatile matters and char showed that raw PKS has higher reactivity than SL during combustion process. The thermal profiles of the SL: PKS blends correlated with the percentage of PKS added in the blends, representing lack of synergic effect between both samples. SL and PKS char blends results in single evolution peak, indicated possibility to be used as alternative fuel for combustion. These findings may be useful for the power generation industry in the development of future co-firing plants using coal/ biomass; however, significant development work is required before large-scale implementation can be done.
Influence of melt depth in laser crystallized poly-Si thin film transistors (1997)

The influence of film thickness and incident excimer laser energy density on the properties of poly-Si thin film transistors has been investigated and a coherent pattern of behavior has been identified which establishes controlled melt-through of the film as a key condition for achieving high quality devices. The conditions were correlated with the appearance of large grains and gave consistent results from both n- and p-channel devices, with carrier mobilities of more than 150 and 80 cm2/V s, respectively, and leakage currents of less than 2×10−14 A/μm. From a study of static irradiations, using a semi-Gaussian laser beam, the results are shown to be consistent with the super lateral grain growth (SLG) model. The trailing edge of the beam, when used in a swept mode, has been demonstrated to play an important role in extending the size of the energy window for this effect by re-setting the material into the SLG regime.
Non-Medical Readiness in Pediatric Bone Marrow Transplant: Improving the Discharge Process Using a Multidisciplinary Team Approach (2015)

Pediatric patients who have undergone bone marrow transplant (BMT) are not consistently prepared (non-medical readiness) for hospital discharge at the same time they meet physiologic criteria (medical readiness). Several factors contribute to an inadequate discharge, including time constraints for education focused on complex care needs/medication management, and communication challenges among the multidisciplinary team. To improve the discharge process and increase preparedness in young BMT patients, a multidisciplinary team was created to conduct a quality improvement (QI) project. The aim of the project was to increase the percentage of BMT patients who are prepared for discharge by standardizing the time sequence of essential nonmedical/educational discharge process tasks prior to meeting criteria medical readiness. "Lean," a QI strategy focused on customers and what they value, was implemented to collect baseline data describing key process measures, and to address gaps through "Plan-Do-Study-Act" cycles. Data from a chart review across a subset of BMT patients and a staff survey supported that pediatric BMT patients had a high degree of non-medical readiness. Team members created standard assessment tools and education plans and scheduled these activities to decrease the last minute rush at time of discharge. Weekly team meetings and real-time audits allowed for individualization of the process to each patient's status, enabling the team to stay on schedule. Completed tasks were categorized according to the scheduled time sequence and were reviewed for timeliness and completion. Every three months a quarterly report was shared with staff. In the first quarter of 2014, 17% of patients met criteria for discharge preparedness and by second quarter, 30% met criteria. As real-time audits reveal tasks that fall out of the scheduled time, the process is refined to improve its efficiency. The percentage of discharge preparedness in young BMT patients continues to rise. The discharge process is continually refined and improved each quarter. In the future, the process will include follow-up with patients/families to assess their ability to care for the child outpatient.
A Practical Technique for Disinfecting Electrical Stimulation Apparatuses Used in Wound Treatment (1996)

Immersion of the electrodes and sponges for 20 minutes in the disinfectant resulted in reduction of bacteria to safe, noninfective levels. Disinfection either completely eliminated all bacteria from the sponges (in 92% of the samples) or eliminated nearly all bacteria (in the remaining 8% of the samples), compared with predisinfection samples, which contained very large numbers of bacteria. These results demonstrate that the disinfection method used in this study is efficacious, and it appears to be cost-effective, practical, and safe for clinical use.
Concept hierarchy based text database categorization in a metasearch engine environment (2002)

Document categorization, as a technique to improve the retrieval of useful documents, has been extensively investigated. One important issue in a large-scale meta-search engine is to select text databases that are likely to contain useful documents for a given query. We believe that database categorization can be a potentially effective technique for good database selection, especially in the Internet environment, where short queries are usually submitted. In this paper, we propose and evaluate several database categorization algorithms. This study indicates that, while some document categorization algorithms could be adopted for database categorization, algorithms that take into consideration the special characteristics of databases may be more effective. Preliminary experimental results are provided to compare the proposed database categorization algorithms.
Expiratory Diaphragm Activity Reduces Atelectasis Formation (2016)

Rationale. If the diaphragm, known as the major inspiratory muscle, is active also during expiration, it will limit closure of the smallairways as well as cyclic opening and closing of airways and ...