gebhart/patrepeval huggingface dataset:
Tenascin-C modulates tumor stroma and monocyte/macrophage recruitment but not tumor growth or metastasis in a mouse strain with spontaneous mammary cancer (1999)

The local growth of tumors and their ability to metastasize are crucially dependent on their interactions with the surrounding extracellular matrix. Tenascin-C (TNC) is an extracellular matrix protein which is highly expressed during development, tissue repair and cancer. Despite the high levels of TNC in the stroma of primary and metastatic tumors, the function of TNC is not known. In the present study we have crossed TNC-null mice with a mouse strain where both female and male mice spontaneously develop mammary tumors followed by metastatic disease in the lungs. We report that the absence of TNC had no effect on the temporal occurrence of mammary tumors and their metastatic dissemination in lungs. Furthermore, the number and size of tumors, the number and size of metastatic foci in the lungs, the proliferation rate and apoptosis of tumor cells and tumor angiogenesis were not altered in the absence of TNC. Histological examination revealed that the tumor organisation, however, was modulated by TNC. In the presence of TNC both primary as well as metastatic tumors were organised in large tumor cell nests surrounded by thick layers of extracellular matrix proteins. In the absence of TNC these tumor cell nests were smaller but still separated from each other by extracellular matrix proteins. In addition, the TNC-null stromal compartment contained significantly more monocytes/macrophages than tumor stroma from TNC wild-type mice. Using in vitro coculture experiments we show that TNC-null tumor cells were still able to activate the TNC gene in fibroblasts which express low basal levels of TNC. Altogether these data indicate that TNC has a very limited role during the spontaneous development and growth of mamary tumors and their metastasis to the lungs.
Mass, mobility and MSn measurements of single ions using charge detection mass spectrometry (2017)

Charge detection mass spectrometry is used to measure the mass, charge, MS<sup>n</sup> and mobility of an individual ion produced by electrospray ionization of a 8 MDa polyethylene glycol sample. The charge detection mass spectrometer is an electrostatic ion trap that uses cone electrodes and a single tube detector and can detect ions for up to the full trapping time of 4.0 s. The time-domain signal induced on the detector tube by a single multiply charged ion can be complex owing to sequential fragmentation of the original precursor ion as well as increasing oscillation frequencies of the single ion owing to collisions with background gas that reduce the kinetic energy of the ion inside the trap. Simulations show that the ratio of the time for the ion to turn around inside the cone region of the trap to the time for the ion to travel through the detector tube is constant with m/z and increases with the ion energy per charge. By measuring this ratio, the kinetic energy of an ion can be obtained with good precision (∼1%) and this method to measure ion kinetic energies eliminates the necessity of ion energy selection prior to trapping for high precision mass measurement of large molecules in complex mixtures. This method also makes it possible to measure the masses of each sequential fragment ion formed from the original precursor ion. MS<sup>7</sup> of a single multiply charged PEG molecule is demonstrated, and from these ion energy measurements and effects of collisions on the ion motion inside the trap, information about the ion mobility of the precursor ion and its fragments is obtained.
[Active derivatives of oligonucleotides with a zwitterionic terminal phosphate group for design of affinity reagents and probes]. (1989)

Method of synthesis and isolation of oligonucleotide derivatives with a zwitterionic terminal phosphate group, containing N-methylimidazole (MeIm), 4-dimethylaminopyridine (DMAP) or 4-dimethylaminopyridine 1-oxide (DMAPO) residues has been developed. Mononucleotide derivatives were used to study the reactivity of these compounds to various nucleophiles and the dependence of hydrolysis rate on pH of solution. These compounds interact rapidly and quantitatively with aliphatic amines and much slower with water, aniline and methanol. MeIm derivatives are most active to nucleophiles, whereas the reactivity of DMAP derivatives is ca. 5 times lower and that of DMAPO derivatives is lower by 2 order of magnitude. This method of activating terminal phosphate group is promising for synthesis of various oligonucleotide phosphoramidates.
Protein topology prediction through parallel constraint logic programming. (1993)

In this paper, two programs are described (CBS1e and CBS2e). These are implemented in the parallel constraint logic programming language ElipSys. These predict protein alpha/beta-sheet and beta-sheet topologies from secondary structure assignments and topological folding rules (constraints). These programs illustrate how recent developments in logic programming environments can be applied to solve large-scale combinatorial problems in molecular biology. We demonstrate that parallel constraint logic programming is able to overcome some of the important limitations of more established logic programming languages i.e. Prolog. This is particularly the case in providing features that enhance the declarative nature of the program and also in addressing directly the problems of scaling-up logic programs to solve scientifically realistic problems. Moreover, we show that for large topological problems CBS1e was approximately 60 times faster than an equivalent Prolog implementation (CBS1) on a sequential device with further performance enhancements possible on parallel computer architectures. CBS2e is an extension of CBS1e that addresses the important problem of integrating the use of uncertain (weighted) protein folding constraints with categorical ones, through the use of a cost function that is minimized. CBS2e achieves this with a relatively minor reduction of performance. These results significantly extend the range and complexity of protein structure prediction methods that can reasonably be addressed using AI languages.
Thin film magnetoresistive vector sensors with submicron gap width (1984)

The size of gap between adjacent conducting strips In the folded resistor track of a thin film magnetoresistive sensor element has an important effect on its performance. Pattern fabrication methods using electron-beam lithography enable conductor spacings in the submicron range to be used. Sensors with smaller conductor spacing have an enhanced sensitivity and require a much smaller orthogonal bias field than devices made using conventional photolithography. The parameters for optimum linearity of the signal are considered in terms of the amount of harmonic distortion introduced by the sensor when its working range of ±1 oersted is swept by an input field of sinusoidal form. The distortion values are extremely low and the orthogonal field for best linearity is established to be close to that for peak sensitivity. immunity to fields at right angles to the measurement vector is also a function of the bias field: the optimum value in this case is about 75% of that for peak sensitivity. Noise measurements indicate that levels are sufficiently low to permit magnetic signals of less than one gamma to be detected.
A study of mefloquine treatment for progressive multifocal leukoencephalopathy: results and exploration of predictors of PML outcomes (2013)

Immune reconstitution has improved outcomes for progressive multifocal leukoencephalopathy (PML), a potentially lethal brain disease caused by JC virus (JCV). However, an antiviral treatment to control JCV is needed when immune reconstitution is delayed or not possible. On the basis of in vitro efficacy, this study evaluated the effect of mefloquine on PML and factors that may predict PML outcomes. This 38-week, open-label, randomized, parallel-group, proof-of-concept study compared patients with PML who received standard of care (SOC) with those who received SOC plus mefloquine (250 mg for 3 days, then 250 mg weekly). Patients randomized to SOC could add mefloquine treatment at week 4. The primary endpoint was change from baseline to weeks 4 and 8 in JCV DNA copy number (load) in cerebrospinal fluid (CSF). Exploratory analyses evaluated factors that might correlate with clinical outcome. The majority of enrolled patients were HIV positive. Preplanned interim data analyses suggested that the study was unlikely to successfully demonstrate a significant difference between groups; therefore, the study was terminated prematurely. There was no significant difference between groups in CSF JCV DNA loads or clinical/MRI findings. Decrease in CSF JCV DNA load from baseline to week 4 was associated with a better clinical outcome at 16 weeks, as measured by Karnofsky scores. This study found no evidence of anti-JCV activity by mefloquine. An early decrease of CSF JCV DNA load appears to be associated with a better clinical outcome.
An insight into molecular mechanisms of human T helper cell differentiation (2008)

Selective activation of T helper (Th) cell subsets plays an important role in immune response to pathogens as well as in the pathogenesis of human allergy and inflammatory diseases. Th1 cells along with the recently discovered Th17 cells play a role in the pathogenesis of autoimmune diseases. Th2 cytokines lead to series of inflammatory processes characteristic for asthma and other atopic diseases. To understand the pathogenesis of immune-mediated diseases it is crucial to dissect pathways and regulatory networks leading to the development of distinct Th subsets. Such knowledge may lead to better strategies for developing diagnostics and therapies for these diseases. The differentiation of Th1, Th2, and Th17 effector cells is driven by signals originating from T cell and costimulatory receptors as well as cytokines in the surroundings of activated naive T helper cells. There are several proteins involved in the regulation of this differentiation process. Most of the data on T helper cell differentiation have been acquired using mouse. In this review, we have summarized what is known about human T helper differentiation. In addition, selected differences between human and mouse will be discussed.
Measurement Site and Applied Pressure Consideration in Wrist Photoplethysmography (2008)

The objective of this study is to describe preliminary evaluation of a new optical reflectance sensor module with air pressure cuff. In order to improve PPG signals from the wrist as an example of wearable PPG, the optical reflectance sensor module includes two identical photodiodes and a pair of red and infrared LED. The sensor module was packaged inside of a cuff to demonstrate the effects of pressure applied to reflectance probe at the radial artery in the wrist. PPG signals with large amplitude were measured when the induced cuff pressure was close to mean blood pressure. This result will be applied to development of a wrist type healthcare device.
Placental methylation markers in normal and trisomy 21 tissues (2013)

The MS-MLPA is an effective alternative to bisulfite sequencing in assessing placental MR. CGI149 is a potential marker for the noninvasive diagnosis of Down syndrome.
Immortalization of chicken preadipocytes by retroviral transduction of chicken TERT and TR (2017)

The chicken is an important agricultural animal and model for developmental biology, immunology and virology. Excess fat accumulation continues to be a serious problem for the chicken industry. However, chicken adipogenesis and obesity have not been well investigated, because no chicken preadipocyte cell lines have been generated thus far. Here, we successfully generated two immortalized chicken preadipocyte cell lines through transduction of either chicken telomerase reverse transcriptase (chTERT) alone or in combination with chicken telomerase RNA (chTR). Both of these cell lines have survived >100 population doublings in vitro, display high telomerase activity and have no sign of replicative senescence. Similar to primary chicken preadipocytes, these two cell lines display a fibroblast-like morphology, retain the capacity to differentiate into adipocytes, and do not display any signs of malignant transformation. Isoenzyme analysis and PCR-based analysis confirmed that these two cell lines are of chicken origin and are free from inter-species contamination. To our knowledge, this is the first report demonstrating the generation of immortal chicken cells by introduction of chTERT and chTR. Our established chicken preadipocyte cell lines show great promise as an in vitro model for the investigation of chicken adipogenesis, lipid metabolism, and obesity and its related diseases, and our results also provide clues for immortalizing other avian cell types.
New Antithrombotic Drugs (2009)

Thrombosis, both venous and arterial, is a major cause of morbidity and mortality worldwide. Consequently, there is an ongoing search for new antithrombotic drugs, particularly novel antiplatelet agents and anticoagulants. A better understanding of the biochemical pathways involved in platelet activation and coagulation and of the links between these systems and the impact of thrombosis on inflammation has led to the identification of new targets for antithrombotic drugs. This paper focuses on these new targets and new antiplatelet drugs and anticoagulants and describes the major advances in the continuing search for more potent antithrombotic drugs that have limited effects on hemostasis.
Characterization of Irreversible Kinase Inhibitors by Directly Detecting Covalent Bond Formation: A Tool for Dissecting Kinase Drug Resistance (2010)

Targeting protein kinases in cancer therapy with irreversible small-molecule inhibitors is moving to the forefront of kinase-inhibitor research and is thought to be an effective means of overcoming mutation-associated drug resistance in epidermal growth factor receptor kinase (EGFR). We generated a detection technique that allows direct measurements of covalent bond formation without relying on kinase activity, thereby allowing the straightforward investigation of the influence of steric clashes on covalent inhibitors in different resistant kinase mutants. The obtained results are discussed together with structural biology and biochemical studies of catalytic activity in both wild-type and gatekeeper mutated kinase variants to draw conclusions about the impact of steric hindrance and increased catalytic activity in drug-resistant kinase variants.
New and Old Monoclonal Antibodies for the Treatment of Chronic Lymphocytic Leukemia (2011)

Over the last few years, several new agents have been under evaluation in preclinical studies and clinical trials, showing promise in treating chronic lymphocytic leukemia (CLL). Among these agents, monoclonal antibodies (mAbs) such as rituximab and alemtuzumab have changed the natural course of the disease. Nowadays there are several new promising monoclonal antibodies under investigation against the CD20, CD23, CD37 and CD40 molecules. Application of newer monoclonal antibodies represents an area of ongoing clinical research in CLL.
Human Gut Microbiota Changes Reveal the Progression of Glucose Intolerance (2013)

To explore the relationship of gut microbiota with the development of type 2 diabetes (T2DM), we analyzed 121 subjects who were divided into 3 groups based on their glucose intolerance status: normal glucose tolerance (NGT; n = 44), prediabetes (Pre-DM; n = 64), or newly diagnosed T2DM (n = 13). Gut microbiota characterizations were determined with 16S rDNA-based high-throughput sequencing. T2DM-related dysbiosis was observed, including the separation of microbial communities and a change of alpha diversity between the different glucose intolerance statuses. To assess the correlation between metabolic parameters and microbiota diversity, clinical characteristics were also measured and a significant association between metabolic parameters (FPG, CRP) and gut microbiota was found. In addition, a total of 28 operational taxonomic units (OTUs) were found to be related to T2DM status by the Kruskal-Wallis H test, most of which were enriched in the T2DM group. Butyrate-producing bacteria (e.g. Akkermansia muciniphila ATCCBAA-835, and Faecalibacterium prausnitzii L2-6) had a higher abundance in the NGT group than in the pre-DM group. At genus level, the abundance of Bacteroides in the T2DM group was only half that of the NGT and Pre-DM groups. Previously reported T2DM-related markers were also compared with the data in this study, and some inconsistencies were noted. We found that Verrucomicrobiae may be a potential marker of T2DM as it had a significantly lower abundance in both the pre-DM and T2DM groups. In conclusion, this research provides further evidence of the structural modulation of gut microbiota in the pathogenesis of diabetes.
The A–Z of bacterial translation inhibitors (2009)

Protein synthesis is one of the major targets in the cell for antibiotics. This review endeavors to provide a comprehensive "post-ribosome structure" A-Z of the huge diversity of antibiotics that target the bacterial translation apparatus, with an emphasis on correlating the vast wealth of biochemical data with more recently available ribosome structures, in order to understand function. The binding site, mechanism of action, and modes of resistance for 26 different classes of protein synthesis inhibitors are presented, ranging from ABT-773 to Zyvox. In addition to improving our understanding of the process of translation, insight into the mechanism of action of antibiotics is essential to the development of novel and more effective antimicrobial agents to combat emerging bacterial resistance to many clinically-relevant drugs.
Perceptions of the effects of exercise on joint health in rheumatoid arthritis patients (2010)

RA patients demonstrated awareness of the advantages of exercise for their joints, both experientially and through education. However, they perceived that health professionals lacked certainty and clarity regarding specific exercise recommendations and the occurrence of joint damage. Thus, to enhance patient-centred exercise prescription in the RA population, uncertainties surrounding joint health, pain symptoms and exercise specificity need to be addressed, alongside continual emphasis of exercise benefits.
Applications and Technical Issues of Wavelength-Division Multiplexing Passive Optical Networks With Colorless Optical Network Units [Invited] (2009)

We review our recent research activities on the applications and technical issues of WDM passive optical networks (WDM-PONs). First, we describe our focus on two candidate applications of WDM-PON: one is a long-reach WDM-PON based on wavelength routing for metro–access integration, and the other is a short-reach WDM-PON for coexistence with current PON systems. We identify that the realization of colorless optical network units (ONUs) is an important technical issue for both applications, and an effective protection function is another important issue, especially for the long-reach WDM-PON. We compare several colorless-ONU approaches as well as introduce our recent research results to resolve the issues raised by some colorless-ONU approaches. We also describe two demonstrations: one is the long-reach WDM-PON with a wavelength-shifted protection scheme as well as loop-back-type colorless ONUs, and the other is a WDM-PON coexisting with a current PON system with tunable-type colorless ONUs.
PhaseLift: Exact and Stable Signal Recovery from Magnitude Measurements via Convex Programming (2011)

Suppose we wish to recover a signal x in C^n from m intensity measurements of the form ||^2, i = 1, 2,..., m; that is, from data in which phase information is missing. We prove that if the vectors z_i are sampled independently and uniformly at random on the unit sphere, then the signal x can be recovered exactly (up to a global phase factor) by solving a convenient semidefinite program---a trace-norm minimization problem; this holds with large probability provided that m is on the order of n log n, and without any assumption about the signal whatsoever. This novel result demonstrates that in some instances, the combinatorial phase retrieval problem can be solved by convex programming techniques. Finally, we also prove that our methodology is robust vis a vis additive noise.
Comprehensive Molecular Analysis of Mismatch Repair Gene Defects in Suspected Lynch Syndrome (Hereditary Nonpolyposis Colorectal Cancer) Cases (2009)

An accurate algorithm is essential for effective molecular diagnosis of hereditary colorectal cancer (CRC). Here, we have extended the analysis of 71 CRC cases suspected to be Lynch syndrome cases for MSH2, MLH1, MSH6, and PMS2 gene defects. All cases were screened for mutations in MSH2, MLH1, and MSH6, and all cases where tumors were available were screened for microsatellite instability (MSI) and expression of MSH2 and MLH1. Subsequently, mutation-negative cases were screened for MLH1 methylation and mutations in PMS2. Of the MSI-high (MSI-H) cases, 96% had a mismatch repair (MMR) gene defect, mostly involving MSH2 or MLH1; one PMS2 mutation, one MLH1 epimutation, and no MSH6 mutations were found. Four of the 28 MSI-H cases, including one Amsterdam criteria case, had biallelic tumor MLH1 methylation, indicating that sporadic cases can be admixed in with Lynch syndrome cases, even those meeting the strongest criteria for Lynch syndrome. MMR gene defects were found in similar frequency in cases where tumors were and were not available. One MLH1 and one MSH2 deletion mutation were found in MSI-stable/low cases, indicating that MSI testing can exclude cases with pathogenic mutations. Our analysis supports a diagnostic algorithm where cases are selected for analysis based on clinical criteria or prediction models; isolated sporadic young-onset cases can be prescreened by tumor testing, whereas familial cases may be directly subjected to molecular analysis for mutations in MMR genes followed by MSI, protein expression, and DNA methylation analysis to aid in the resolution of mutation-negative cases.
FGFR2 exon IIIa and IIIc mutations in Crouzon, Jackson-Weiss, and Pfeiffer syndromes: evidence for missense changes, insertions, and a deletion due to alternative RNA splicing. (1996)

Fibroblast growth factor receptor 2 (FGFR2) mutations have been associated with the craniosynostotic conditions Crouzon, Jackson-Weiss, and Pfeiffer syndromes. Previously, mutations were described in the exons IIIa and IIIc, which form the extracellular, third immunoglobulin-like domain (IgIII) and adjacent linker regions, both of which are normally involved in ligand binding. For all three conditions, mutations were found in exon IIIc. Only in Crouzon syndrome were mutations identified in exon IIIa. In this study, 39 cases with one of these three conditions were screened for exon IIIa or IIIc mutations. Eleven mutations are reported in 17 unrelated cases. Mutations in exon IIIa are identified for not only Crouzon but also Jackson-Weiss and Pfeiffer syndromes. Four mutations in either exon IIIa or exon IIIc reported only in Crouzon syndrome are present also in one of the other two syndromes. Two insertions, one in exon IIIa in a Crouzon syndrome patient and the other in exon IIIc in a Pfeiffer syndrome patient, were observed. The latter mutation has the same alternative RNA splicing effect as a reported synonymous mutation for Crouzon syndrome. A missense mutation was detected in one Pfeiffer syndrome family in which two members had craniosynostosis without limb anomalies. The inter- and intrafamilial variability in expression of FGFR2 mutations suggests that these three syndromes, presumed to be clinically distinct, are instead representative of a spectrum of related craniosynostotic and digital disorders.