gebhart/patrepeval huggingface dataset:
Drug response, dihydrofolate reductase, and cytogenetics of amethopterin-resistant Chinese hamster cells in vitro. (1972)

A graded series of amethopterin-resistant sublines maintained at concentrations varying from 0.1 to 50.0 μg/ml were selected in vitro from several parental Chinese hamster lines. Increases in resistance ranged from 45- to 108,400-fold. Dose-response data for sensitive and resistant populations demonstrated that the 3 parental lines responded identically to amethopterin and methasquin, while some but not all resistant sublines were widely divergent. Even though every resistant subline was cross-resistant to the quinazoline antifolate, methasquin was relatively effective against cells highly resistant to amethopterin and was the stronger growth inhibitor. Supplementation with thymidine (30 μm) in sensitivity assays with amethopterin did not alter response of cell lines to this agent.

Dihydrofolate reductase activity was elevated in the 9 resistant sublines. Relationships between drug response and enzyme activity appeared to differentiate cell lines into 2 groups with respect to each antifolate. The data suggest that increased levels of dihydrofolate reductase may be the primary determinant of response for some sublines whereas for others additional factors such as different enzyme form or altered transport may also influence sensitivity to drug. Disparate response of several of the sublines to the 2 agents implies separate mechanisms of uptake.

Cytogenetic analysis revealed considerable structural rearrangement of karyotype, characterizing each resistant subline. Chromosome numbers remained in the diploid range. Although there was suggestion of preferential alteration, with translocation of long chromosomal fragments, a possible association between specific karyotypic change and elevated dihydrofolate reductase level in amethopterin-resistant cells was not verified in this study.
Effect of Ionic Size on Solvate Stability of Glyme-Based Solvate Ionic Liquids (2014)

A series of binary mixtures composed of glymes (triglyme, G3; tetraglyme, G4; pentaglyme, G5) and alkali-metal bis(trifluoromethanesulfonyl)amide salts (M[TFSA]; M = Li, Na, and K) were prepared, and the correlation between the composition and solvate stability was systematically investigated. Their phase diagrams and Raman spectra suggested complexation of the glymes with M[TFSA] in 1:1 and/or 2:1 molar ratio(s). From isothermal stability measurements, it was found that the formation of structurally stable complexes in the solid state did not necessarily ensure their thermal stability in the liquid state, especially in the case of 2:1 complexes, where uncoordinating or highly exchangeable glyme ligands existed in the molten complexes. The phase-state-dependent Raman spectra also supported the presence of free glymes in certain liquid complexes. The effect of the electric field induced by the alkali-metal cations on the oxidative stability of certain glyme complexes was examined by linear sweep voltammetry and quantum chemical calculations. Although the actual oxidative stability of complexes did not necessarily reflect the calculated HOMO energy levels of the glymes, the strong electric field induced by the smaller M(+) cations and proper coordination structures impart high stability to the glyme complexes. The results of thermogravimetry of complexes with different M(+) cations revealed that a balance of competitive interactions of the M(+) ions with the glymes and [TFSA](-) anions predominates the thermal stability.
A portable device based on the interrupter technique to measure bronchodilator response in schoolchildren (1996)

A new device for measuring airway resistance following brief airflow interruption (Microlab 4000; Micromedical Ltd, UK) was evaluated in 25 asthmatic school children in comparison with well-established methods. Airway resistance was measured during brief airflow interruption (Rint), before and after administration of salbutamol 200 micrograms by metered-dose inhaler, and in the spirometric parameters, forced expiratory volume in one second (FEV1) and peak expiratory flow (PEF), and total respiratory system resistance at 6 Hz (Rrs,6) measured by the forced oscillation technique (FOT). The sensitivity index (SI) (mean change/baseline standard deviation) was calculated for each subject. At baseline, interrupter conductance, the reciprocal of Rint, correlated well with FEV1 (r = 0.837; p < 0.001) and PEF (r = 0.773; p < 0.001), and Rint correlated highly with Rrs,6 (r = 0.942; p < 0.001). The median intrasubject coefficient of variation of the interrupter method was higher than the FOT or either spirometric parameter; Rint 11%, Rrs,6 9%, FEV1 5% and PEF 5%. However, the sensitivity to detect change after bronchodilator, expressed as the median SI, did not differ significantly between measurements: Rint 3.5, Rrs,6 3.6, FEV1 2.4 and PEF 3.0. A significant response (SI > 2) was shown by the interrupter in 22 of the subjects compared with 16 by FEV1. The interrupter technique is useful for assessing changes in airway calibre in asthmatic school children, with a sensitivity at least as good as standard methods. Such a device could be of particular value in those too young to perform spirometry.
High efficiency DNA-mediated transformation of human diploid fibroblasts. (1988)

Normal human diploid fibroblasts (HDF) have only rarely been used as recipients in DNA transfection experiments even though they have the potential to add to our knowledge about the genes that control normal cell proliferation. A major impediment to the use of HDF has been their poor transfection frequency. In this paper, we show that IMR-90 human diploid fibroblasts can be stably transfected at high efficiency with pRSVneo at an average frequency of 2 x 10(-3) (0.2%) using a modified calcium phosphate-DNA coprecipitation transfection protocol. Prior to this report, the best transfection frequencies of HDF were on the order of 10(-5)-10(-4). In the present protocol it is very important to maintain relatively low cell densities, particularly during the selection process post-transfection. Using this protocol other neo-containing plasmids also yield high transfection frequencies in IMR-90. IMR-90, which are readily available from the NIH Aging Cell Repository, may be one of the best HDF to use as recipients because they are five times as efficient as are WI-38, which is another well characterized HDF.
What is going on in augmented reality simulation in laparoscopic surgery? (2008)

Several augmented reality simulators have been developed over the past few years and they are improving rapidly. We recommend the development of AR laparoscopic simulators for component tasks of procedural training. AR simulators should be implemented in current laparoscopic training curricula, in particular for laparoscopic suturing training.
Crown-Ether-Functionalized Mn(III) Salicylaldimine Complexes as Ditopic Carriers. Efficient Transport of Tryptophan and Serotonin across a CHCl3 Barrier (1998)

The crown-ether-functionalized Mn(III) salicylaldimine complexes and their alkali metal ion derivatives have been synthesized and structurally characterized, and their ability to transport zwitterionic molecules such as tryptophan and specific neurotransmitters such as serotonin and dopamine has been investigated. The complexes are effective in the efficient transport of host molecules between water compartments, across a bridging CHCl3 solution that serves as an artificial membrane.
DNA or RNA Oligonucleotide 2′-Hydrazides for Chemoselective Click-Type Ligation with Carbonyl Compounds (2011)

An efficient method for the synthesis of DNA or RNA oligonucleotide 2'-hydrazides is described. Fully deprotected oligonucleotides containing a hydrazide group at the 2'-position of a uridine residue were obtained by a novel two-step procedure: periodate cleavage of an oligonucleotide with 1,2-diol group followed by conversion of the aldehyde to hydrazide with an extended linker arm using a homobifunctional reagent succinic dihydrazide and NaBH(3)CN. The resulting oligonucleotide 2'-hydrazides were efficiently conjugated by a click-type reaction at acidic pH to aliphatic or aromatic aldehydes with or without NaBH(3)CN reduction to afford novel 2'-conjugates.
Effect of Early Referral to an Endocrinologist on Efficiency and Cost of Evaluation and Development of Treatment Plan in Patients with Thyroid Nodules (1998)

Radionuclide uptake and scan and sonogram, frequently ordered before referral to an endocrinologist, are expensive and poor predictors of thyroid nodule malignancy. We estimated costs of excessive imaging and other studies by reviewing the records of all patients (n = 70) referred to a single, consulting endocrinologist, for thyroid nodule evaluation in a 2-yr interval and subsequently, presenting only pertinent histories and results of physical examinations, thyroid function tests, and thyroid autoantibodies, to a second, reviewing endocrinologist (RE) who was blinded to diagnosis and management. Concordance in diagnosis and management between consulting endocrinologist and RE was 87.1% and 93.4%, respectively. Accuracy of diagnosis, loss of patient's time (8.7 h, average), and cost of unnecessary testing, defined as tests not required by the RE for diagnosis and management according to published guidelines, were determined. Unnecessary testing included 153 physician's office or diagnostic laboratory visits, 44 sets of thyroid function tests, 32 radionuclide uptake and scan, 39 thyroid sonograms, and 3 computed tomography scans. The total direct cost of unnecessary tests was estimated at $27,290 ($390/patient) in addition to costs of 30 unnecessary physician's office visits. Only 2 of 8 surgical referrals required surgery, whereas 6 other patients required surgery, including 3 with papillary carcinoma. We conclude that early referral to an endocrinologist of patients with suspected thyroid nodules results in significant savings in cost of evaluation, patient's time, and increased diagnostic precision. Six of the 8 patients referred for surgery before endocrine consultation had benign thyroid disease that did not require surgery. Six additional patients were referred to surgery, 3 of whom had papillary thyroid carcinoma. Early referral of patients with suspected thyroid nodules to an endocrinologist results in significant savings in both cost and patient's time as well as increased precision of diagnosis.
Automatically Extracting Structure from Free Text Addresses. (2000)

In this paper we present a novel way to automatically elementize postal addresses seen as a plain text string into atomic structured elements like ”City ” and ”Street name”. This is an essential step in all warehouse data cleaning activities. In spite of the practical importance of the problem and the technical challenges it offers, research effort on the topic has been limited. Existing commercial approaches are based on hand-tuned, rule-based approaches that are brittle and require extensive manual effort when moved to a different postal system. We present a Hidden Markov Model based approach that can work with just about any address domain when seeded with a small training data set. Experiments on real-life datasets yield accuracy of 89 % on a heterogeneous nationwide database of Indian postal addresses and 99.6 % on US addresses that tend to be more templatized. 1
Clinical perspectives of dried blood spot protein quantification using mass spectrometry methods (2017)

Although dried blood spot (DBS) sampling methods have been used since the 1960s, they have recently attracted renewed interest because of the development of new clinical applications. In addition to their other advantages, DBS methods can now be used to quantify many blood proteins using the latest highly sensitive and robust, liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) approaches such as multiple reaction monitoring. The DBS blood sampling approach could provide a useful alternative means of conducting blood sampling for routine clinical purposes and patients' follow-up. In this review, we examine the current use of DBS for LC-MS/MS protein quantification in clinical settings and discuss potential clinical applications.
A Tongue Suspension Suture for Obstructive Sleep Apnea and Snorers (2001)

A tongue suspension suture partially reduces the respiratory severity of OSA. Small changes are noted in symptoms of sleepiness, snoring, and functional outcomes. Demonstration of efficacy of the technique and device will require further controlled trials.
Glutamate transporter mRNA expression in proliferative zones of the developing and adult murine CNS (1996)

Neuronal migration, differentiation, and synapse formation are developmental processes within the CNS significantly influenced by ionotropic and metabotropic glutamate receptor activity. Extracellular glutamate concentrations mediating this activity are regulated by transport proteins localized in neuronal and glial cell membranes. We have used in situ hybridization analysis with subtype-specific antisense-oligonucleotides to study the distribution of glia-specific excitatory amino acid transporter (mEAAT1 and mEAAT2) mRNAs during the later stages of embryogenesis and postnatal CNS development. Distinct but overlapping embryonic and postnatal patterns of localization were observed for the two transporter transcripts. Both mEAAT1 and mEAAT2 mRNAs were found during the peak period of gliogenesis (E15-E19) in the telencephalic and mesencephalic CNS proliferative zones. The overall expression of mEAAT1 mRNA diminished after the completion of cell migration, whereas mEAAT2 mRNA expression increased significantly during postnatal development. Interestingly, mEAAT2 transcript expression continued in the subventricular zone postnatally and persisted in this proliferative zone in the adult brain. From PO onward, mEAAT1 mRNA was present predominantly in the cerebellar Purkinje cell layer and at a much lower abundance in the cortex, hippocampus, basal nuclei, and septum, whereas from P7 onward, mEAAT2 mRNA expression increased throughout most of the neuraxis. Postnatally, transcripts for mEAAT1 and mEAAT2 were found in cell bodies, processes, and commissural white matter tracts of the CNS. The divergent temporal and spatial expression of EAAT subtypes and their persistence in mature fiber tracts and radial glia layers reveal that specific EAATs are likely to play multiple distinct roles in the developing and adult CNS, including the regulation of cell proliferation, axon-glia interactions, and neuronal survival.
Glycogen synthase kinase 3β-dependent Snail degradation directs hepatocyte proliferation in normal liver regeneration (2011)

Liver regeneration proceeds under the well-orchestrated control of multiple transcription factors that lead hepatocytes to reenter the cell cycle, proliferate, and renew quiescence. Here, we found an important role of the zinc-finger transcription factor Snail in liver regeneration. Snail was typically expressed in quiescent adult hepatocytes, but was rapidly degraded when the liver needed to regenerate itself. Decreased levels of Snail induced DNA synthesis in hepatocytes through up-regulation of cell cycle-related proteins. Snail degradation was dependent on phosphorylation by glycogen synthase kinase (GSK)-3β, whose quantity and activity were immediately increased after loss of liver mass or hepatic injury. Inactivation of GSK-3β resulted in suppression of Snail degradation and DNA synthesis in hepatocytes, leading to impaired liver growth during regeneration. This GSK-3β-dependent Snail degradation occurred as a result of cytokine, growth factor, and bile acid signals that are known to drive liver regeneration. Thus, GSK-3β-dependent Snail degradation acts as a fundamental cue for the initiation of hepatocyte proliferation in liver regeneration.
Combination therapy in combating cancer (2017)

Combination therapy, a treatment modality that combines two or more therapeutic agents, is a cornerstone of cancer therapy. The amalgamation of anti-cancer drugs enhances efficacy compared to the mono-therapy approach because it targets key pathways in a characteristically synergistic or an additive manner. This approach potentially reduces drug resistance, while simultaneously providing therapeutic anti-cancer benefits, such as reducing tumour growth and metastatic potential, arresting mitotically active cells, reducing cancer stem cell populations, and inducing apoptosis. The 5-year survival rates for most metastatic cancers are still quite low, and the process of developing a new anti-cancer drug is costly and extremely time-consuming. Therefore, new strategies that target the survival pathways that provide efficient and effective results at an affordable cost are being considered. One such approach incorporates repurposing therapeutic agents initially used for the treatment of different diseases other than cancer. This approach is effective primarily when the FDA-approved agent targets similar pathways found in cancer. Because one of the drugs used in combination therapy is already FDA-approved, overall costs of combination therapy research are reduced. This increases cost efficiency of therapy, thereby benefiting the "medically underserved". In addition, an approach that combines repurposed pharmaceutical agents with other therapeutics has shown promising results in mitigating tumour burden. In this systematic review, we discuss important pathways commonly targeted in cancer therapy. Furthermore, we also review important repurposed or primary anti-cancer agents that have gained popularity in clinical trials and research since 2012.
Adoptive cell therapy with tumour-infiltrating lymphocytes: the emerging importance of clonal neoantigen targets for next-generation products in non-small cell lung cancer (2019)

Immune checkpoint blockade has significantly improved clinical outcomes for patients with non-small cell lung cancer (NSCLC) and other solid tumours, but many patients do not respond and acquired resistance is common. Aspects of the tumour microenvironment linked to clinical outcomes include the proportion of tumour-infiltrating lymphocytes (TIL), tumour programmed death ligand 1 ( PD-L1) score and tumour mutation burden. Adoptive cell therapy (ACT), a technique that works by infusing <i>ex vivo</i> expanded T lymphocytes to increase the effector cell pool in tumours, is anticipated to become a viable therapeutic option for patients with solid tumours, akin to chimeric antigen receptor T cell (CAR-T) therapy in haematological malignancies. TIL therapy has shown durable clinical responses in heavily pre-treated patients with melanoma and other solid tumours. We review the experience of ACT with TILs and the recent evidence that clonal neoantigens might be the most relevant immunotherapeutic targets in heterogeneous solid tumours such as NSCLC. Clonal (or truncal) neoantigens arise from the earliest mutagenic events in tumour evolution, and are retained over time in all tumour cells within a patient, making them the ideal target for T cell therapy. NSCLC has one of the highest clonal mutation burdens of all cancers through exposure to carcinogens in tobacco smoke, providing a strong rationale to develop clonal neoantigen reactive T cells (cNeT) for this indication. The first treatment modality to test this concept clinically is ATL001, a cNeT product that is derived from autologous TILs and enriched for T cells specifically recognizing clonal neoantigenic epitopes by selective expansion. Clinical studies of ATL001 will commence in 2019.
The steriochemical course of iodine–water oxidation of dinucleoside phosphite triesters (1984)

The oxidation of trialkyl phosphites, espesially dinucleoside phsphite triesters, by iodine–water and by m-chloroperbenzoic acid has been shown to occur steriospecifically with retention of configuration.
Upstream binding sequences of the XyIR activator protein and integration host factor in thexylSgene promoter region of thePseudomonasTOL plasmid (1992)

The xylR and xylS genes, which encode the positive regulators of the TOL plasmid catabolic pathways, are adjacent genes on the TOL plasmid and are transcribed from divergent promoters. Transcription from the xylS gene promoter, Ps, is positively regulated by effector-activated XylR protein and requires the specific RNA polymerase sigma 54 subunit (RpoN). Deletions and point mutations in the Ps upstream region localized the site of XylR interaction to the region between -133 bp and -207 bp (with respect to the transcriptional start of the xylS messenger), which contains an inverted sequence repeat largely homologous to the motif recognised by XylR in the XylR-regulated 'upper' catabolic pathway promoter, Pu. Gel retardation experiments showed binding of IHF to the Ps promoter region. Corresponding sequences showing good homology to the IHF-binding consensus were identified close to the Ps Promoter (between -35 bp and -47 bp, Ps proximal site) and further upstream overlapping the XylR recognition sequence (Ps distal site). In the latter case IHF recognition motifs were found well conserved on both strands at nearly the same position (between -140 bp and -152 bp on the upper and between -141 bp and -153 bp on the lower strand). Expression from Ps, either under inducing or non-inducing conditions, was, however, only slightly influenced by the absence of IHF in an IHF-deficient mutant and thus activation of Ps, like that of other sigma 54-dependent promoters which are rich in Ts, does not absolutely require IHF protein.
Conjugation of meningococcal lipopolysaccharide R-type oligosaccharides to tetanus toxoid as route to a potential vaccine against group B Neisseria meningitidis (1984)

Oligosaccharides were obtained by the mild acid hydrolysis of the lipopolysaccharides from a number of different strains of Neisseria meningitidis, serotypes L2, L3, L4, L5, and L10. The dephosphorylated oligosaccharides were conjugated to tetanus toxoid as their 2-(4-isothiocyanatophenyl)-ethylamine derivatives, which resulted in the incorporation of from 18 to 38 oligosaccharides per molecule of tetanus toxoid. When injected in rabbits, the conjugates produced oligosaccharide-specific antibodies which were predominantly serologically specific but which also exhibited some cross-reactivity. These serological results can be attributed to regions of structural dissimilarity and similarity within the oligosaccharides. The oligosaccharide-specific antibodies were also lipopolysaccharide serotype specific, thus indicating that the oligosaccharides are the determinants associated with this serotype specificity. Consistent with the serological results, the conjugate antisera were bactericidal for the homologous serotype meningococcal organisms and in some cases for heterologous serotype organisms.
Improved detection of medullary thyroid cancer with radiolabeled antibodies to carcinoembryonic antigen. (1996)

Anti-CEA MAbs are excellent agents for imaging recurrent, residual, or metastatic MTC. The high lesion sensitivity in patients with known lesions, combined with the ability to detect disease, may make these agents ideal for staging patients, monitoring disease pretherapy or posttherapy, and especially for evaluating patients with recurrent or persistent hypercalcitonemia or CEA elevations after primary surgery. Analogous to radioiodine in the evaluation of patients with differentiated thyroid cancer, radiolabeled anti-CEA MAbs may achieve a similar role in diagnosing and monitoring patients with MTC.