gebhart/patrepeval huggingface dataset:
Template controlled coupling and recombination of oligonucleotide blocks containing thiophosphoryl groups (1993)

Oxidation of a pair of 3'- and 5'-thiophosphoryloligonucleotides in the presence of a complementary oligonucleotide template is shown to provide an effective means for selectively linking oligonucleotide blocks. Coupling proceeds rapidly and efficiently under mild conditions in dilute aqueous solutions (microM range for oligomers, 2-15 min at 0-4 degrees C with K3Fe(CN)6 or KI3 as oxidant). This chemistry was demonstrated by polymerization of a thymidylate decamer derivative (sTTTTTTTTTTs) in the presence of poly(dA) and by coupling oligomers possessing terminal thiophosphoryl groups (ACACCCAATTs + sCTGAAAATGG and ACACCCAATs + sCTGAAAATGG) in the presence of a template (CCATTTTCAGAATTGGGTGT). Efficient linking of 5' to 3' phosphoryl groups can be achieved under conditions where virtually no coupling takes place in absence of a template. A novel feature of the chemistry is that catalyzed recombinations of oligomers containing internal -OP(O)(O-)SSP(O)(O-)O- linkages can be directed by hydrogen bonding to a complementary oligonucleotide. Convenient procedures are reported for solid phase synthesis of the requisite oligonucleotide 3'- and 5'-phosphorothioates.
Distortionless reduction of peak power without explicit side information (2002)

Selected mapping (SLM) peak power reduction is distortionless as it selects the actual transmit signal from a set of alternative signals, which all represent the same information. Usually, the specific signal generation information needs to be transmitted and carefully protected against bit errors. Here, we propose an extension of SLM, which employs scrambling and refrains from transmitting explicit side information. Some additional complexity and nearly vanishing redundancy is introduced to achieve markedly improved transmit signal statistics. Even though SLM is applicable with any modulation, we concentrate on orthogonal frequency-division multiplexing (OFDM).
Expression of the SART‐1 Antigens in Uterine Cancers (1998)

We recently reported that the SART-1 gene, encoding the SART-1(259) tumor antigen which is recognized by HLA-A26-restricted cytotoxic T lymphocytes (CTLs), is expressed in the cytosol of squamous cell carcinomas and adenocarcinomas. The present study deals with the expression of SART-1(259) and SART-1(800) antigens in uterine cancers. The SART-1(259) antigen was detected in the cytosol fraction of 4 of 8 uterine cancer cell lines, 24 of 74 (32%) uterine cancer tissues, 0 of 7 uterine myomas, and 0 of 5 non-tumorous uterine tissues. The SART-1(800) antigen was expressed in the nuclear fraction of all the uterine cancer cell lines, 41 of 74 (55%) uterine cancer tissues, 0 of 7 myomas, and 3 of 5 non-tumorous uterine tissues. The SART-1(259)+ uterine cancer cells were recognized by HLA-A24 restricted and SART-1 specific CTLs. Therefore, SART-1(259) antigen could be an appropriate vaccine candidate for a relatively large number of uterine cancer patients.
Corticotropin-releasing factor antagonists: recent advances and exciting prospects for the treatment of human diseases. (2004)

Corticotropin-releasing factor (CRF) co-ordinates the neural, endocrine and immune responses of the body to stress. Several studies have implicated CRF in the etiology of anxiety, depression, substance abuse, stress-related gastrointestinal disorders and preterm labor, and intensive research into the design of safe and effective CRF antagonists is currently being pursued in several laboratories. Recently, improvements have been made not only in brain penetrance and in vivo activity in preclinical models for anxiety, depression and irritable bowel syndrome, but also in structural diversity for these compounds. Clinical data for R-121919 (NBI-30775; Neurocrine Biosciences Inc) raises the expectation that safe and potent CRF antagonists might be useful as drugs for the treatment of human diseases.
Obesity, autophagy and the pathogenesis of liver and pancreatic cancers (2012)

Liver and pancreatic cancers are both highly lethal diseases with limited to no therapeutic options for patients. Recent studies suggest that deregulated autophagy plays a role in the pathogenesis of these diseases by perturbing cellular homeostasis and laying the foundation for disease development. While accumulation of p62 upon impaired autophagy has been implicated in hepatocellular carcinoma, its role in pancreatic ductal adenocarcinoma remains less clear. This review will focus on recent studies illustrating the role of autophagy in liver and pancreatic cancers. The relationships between autophagy, nuclear factor-κB signaling and obesity in hepatocellular carcinoma will be discussed, as well as the dual role of autophagy in pancreatic ductal adenocarcinoma.
Cholesteryl Ester Transfer Protein Decreases High-Density Lipoprotein and Severely Aggravates Atherosclerosis in APOE*3-Leiden Mice (2006)

CETP expression in E3L mice shifts the distribution of cholesterol from HDL to VLDL/LDL, reduces plasma-mediated SR-BI-dependent cholesterol efflux, and represents a clear pro-atherogenic factor in E3L mice. We anticipate that the CETP.E3L mouse will be a valuable model for the preclinical evaluation of HDL-raising interventions on atherosclerosis development.
Smoking and Rheumatoid Arthritis (2014)

Rheumatoid arthritis (RA) is a chronic inflammatory disease caused by both genetic and environmental factors. Smoking has been implicated as one of the most important extrinsic risk factors for its development and severity. Recent developments have shed light on the pathophysiology of RA in smokers, including oxidative stress, inflammation, autoantibody formation and epigenetic changes. The association of smoking and the development of RA have been demonstrated through epidemiologic studies, as well as through in vivo and animal models of RA. With increased use of biological agents in addition to standard disease-modifying antirheumatic drugs (DMARDs), there has been interest in how smoking affects drug response in RA treatment. Recent evidence suggests the response and drug survival in people treated with anti-tumour necrosis factor (anti-TNF) therapy is poorer in heavy smokers, and possible immunological mechanisms for this effect are presented in the current paper.
A faster circular binary segmentation algorithm for the analysis of array CGH data (2007)

An R version of the CBS algorithm has been implemented in the "DNAcopy" package of the Bioconductor project. The proposed hybrid method for the P-value is available in version 1.2.1 or higher and the stopping rule for declaring a change early is available in version 1.5.1 or higher.
Enteroendocrine cells: a review of their role in brain–gut communication (2015)

This review will highlight the role played by the EECs in the complex and integrated sensory information responses, and discuss the new findings regarding EECs in the brain-gut axis bidirectional communication.
The CXXC Motif:  A Rheostat in the Active Site (1997)

The active-site CXXC motif of thiol:disulfide oxidoreductases is essential for their catalysis of redox reactions. Changing the XX residues can perturb the reduction potential of the active-site disulfide bond of the Escherichia coli enzymes thioredoxin (Trx; CGPC) and DsbA (CPHC). The reduction potential is correlated with the acidity of the N-terminal cysteine residue of the CXXC motif. As the pKa is lowered, the disulfide bond becomes more easy to reduce. A change in pKa can account fully for a change in reduction potential in well-characterized CXXC motifs of DsbA but not of Trx. Formal analysis of the Nernst equation reveals that reduction potential contains both pH-dependent and pH-independent components. Indeed, the difference between the reduction potentials of wild-type Trx and wild-type DsbA cannot be explained solely by differences in thiol pKa values. Structural data for thiol:disulfide oxidoreductases reveal no single factor that determines the pH-independent component of the reduction potential. In addition, the pH-dependent component is complex when the redox state of the CXXC motif affects the titration of residues other than the thiols. These intricacies enable CXXC motifs to vary widely in their capacity to assist electron flow, and thereby engender a family of thiol:disulfide oxidoreductases that play diverse roles in biochemistry.
Unexpected Acceleration of Type 1 Diabetes by Transgenic Expression of B7-H1 in NOD Mouse Peri-Islet Glia (2010)

In contrast with transgenic B7-H1 in NOD mouse β-cells, transgenic B7-H1 in pSC promotes rather than protects from type 1 diabetes. Here, ectopic B7-H1 enhanced the pathogenicity of effector T-cells, demonstrating that pSC can actively impact diabetes progression-likely through modification of intraislet T-cell selection. Although pSC cells emerge as a new candidate for therapeutic targets, caution is warranted with regard to the B7-H1-PD1 axis, where B7-H1 overexpression can lead to accelerated autoimmune disease.
Thalidomide treatment of prurigo nodularis (1984)

Four patients with classic recalcitrant prurigo nodularis had symptomatic and physical responses to thalidomide with remissions. Three of the four patients had increased IgE levels that decreased during therapy. In two patients, short-term treatment (2 to 3 months) was not sufficient to produce remission, but retreatment was effective. Two patients had long-term remission with more than 6 months of treatment. No significant side effects occurred.
GaAs Monolithic Direct Linear (1 - 2.8) GHz Q.P.S.K. Modulator (1989)

Monolithic 1-2.8 GHz linear "Quaternary phase Shift Keying" modulators have been designed and fabricated with the standard D07A process of the PHILIPS MICROWAVE GaAs MMIC Foundry. Output power of the modulator is a dBm with third order intermodulation signals more than 41 dBc. Carrier rejection and Band rejection of more than 45 dBc have been measured corresponding to a maximum amplitude and phase error of less than 0.12 dB and 0.8° respectively.
ATG‐saporin‐S6 immunotoxin: a new potent and selective drug to eliminate activated lymphocytes and lymphoma cells (2009)

Summary Anti‐thymocyte globulins (ATG) are currently used to prevent graft‐ versus ‐host disease in haematopoietic stem cell transplants from alternative donors and to treat and prevent acute organ rejection after transplantation. Many recent studies have demonstrated that ATG can also be beneficial in patients with myeloma, lymphoma, leukaemia and myelodysplastic syndrome. This study showed, for the first time, that the cytotoxic effect of ATG can been enhanced by conjugation with saporin‐S6, which is one of the most stable and active type‐1 ribosome‐inactivating proteins. The ATG‐saporin‐S6 immunotoxin showed a strong cytotoxic effect on five lymphoma‐ and leukaemia‐derived cell lines as well as on activated lymphocytes while sparing non‐haematological cell lines. ATG‐saporin‐S6 induced a time‐dependent activation of caspase‐3/7 in RAJI cells. The caspase inhibitor Z‐VAD‐fmk partially rescued the cells that were treated with ATG‐saporin‐S6, suggesting that multiple cell death pathways, some of which are caspase independent, play a role in ATG‐saporin‐S6 toxicity. In our experiments ATG increased the complement‐independent cytotoxicity of activated lymphocytes by a magnitude of 3–5 logs after conjugation. These findings suggest that the ATG‐saporin‐S6 immunotoxin is a promising therapeutic tool for many pathological conditions involving T lymphocytes and T and B neoplastic cells.
Service specific anomaly detection for network intrusion detection (2002)

The constant increase of attacks against networks and their resources (as recently shown by the CodeRed worm) causes a necessity to protect these valuable assets. Firewalls are now a common installation to repel intrusion attempts in the first place. Intrusion detection systems (IDS), which try to detect malicious activities instead of preventing them, offer additional protection when the first defense perimeter has been penetrated. ID systems attempt to pin down attacks by comparing collected data to predefined signatures known to be malicious (signature based) or to a model of legal behavior (anomaly based).Anomaly based systems have the advantage of being able to detect previously unknown attacks but they suffer from the difficulty to build a solid model of acceptable behavior and the high number of alarms caused by unusual but authorized activities. We present an approach that utilizes application specific knowledge of the network services that should be protected. This information helps to extend current, simple network traffic models to form an application model that allows to detect malicious content hidden in single network packets. We describe the features of our proposed model and present experimental data that underlines the efficiency of our systems.
Mast cells of two types differing in neutral protease composition in the human aortic intima. Demonstration of tryptase- and tryptase/chymase-containing mast cells in normal intimas, fatty streaks, and the shoulder region of atheromas. (1994)

Biochemical studies in vitro have demonstrated that stimulated mast cells induce macrophage foam cell formation through the synergistic action of mast cell granule neutral proteases and proteoglycans. To determine the presence and number of mast cells in human arterial intima, the site of atherogenesis, specimens of normal and atherosclerotic human aortic intima from 35 autopsies of persons ranging from 13 to 67 years old were stained with monoclonal antibodies against the two major proteases of mast cells, tryptase and chymase. All mast cells present were found to contain tryptase, and an average of 40% contained chymase as well. In sections of normal intimas, fatty streaks, and atheromas, the mast cells had average densities of 15/mm2, 15/mm2, and 3/mm2, respectively. In contrast to the normal intimas and fatty streaks, however, the atheromas had mast cells distributed unevenly in a typical pattern: 8/mm2 in the shoulder region, 1/mm2 in the fibrous cap, and none in the core region. In normal intimas, fatty streaks, and the shoulder region of atheromas, the mast cells amounted to 3% of all nucleated cells. The ratios of mast cells to T lymphocytes and to macrophages, respectively, were 2:1 and 1:4 in normal intimas, 1:3 and 1:10 in fatty streaks, and 1:5 and 1:20 in the shoulder region of atheromas. Thus, among the blood-borne cells in the human aortic intima, mast cells compose a significant cell population, and in terms of their protease content, these intimal mast cells are heterogeneous.(ABSTRACT TRUNCATED AT 250 WORDS)
Yeast m6A Methylated mRNAs Are Enriched on Translating Ribosomes during Meiosis, and under Rapamycin Treatment (2015)

Interest in mRNA methylation has exploded in recent years. The sudden interest in a 40 year old discovery was due in part to the finding of FTO's (Fat Mass Obesity) N6-methyl-adenosine (m6A) deaminase activity, thus suggesting a link between obesity-associated diseases and the presence of m6A in mRNA. Another catalyst of the sudden rise in mRNA methylation research was the release of mRNA methylomes for human, mouse and Saccharomyces cerevisiae. However, the molecular function, or functions of this mRNA 'epimark' remain to be discovered. There is supportive evidence that m6A could be a mark for mRNA degradation due to its binding to YTH domain proteins, and consequently being chaperoned to P bodies. Nonetheless, only a subpopulation of the methylome was found binding to YTHDF2 in HeLa cells.The model organism Saccharomyces cerevisiae, has only one YTH domain protein (Pho92, Mrb1), which targets PHO4 transcripts for degradation under phosphate starvation. However, mRNA methylation is only found under meiosis inducing conditions, and PHO4 transcripts are apparently non-methylated. In this paper we set out to investigate if m6A could function alternatively to being a degradation mark in S. cerevisiae; we also sought to test whether it can be induced under non-standard sporulation conditions. We find a positive association between the presence of m6A and message translatability. We also find m6A induction following prolonged rapamycin treatment.
Small Silencing RNAs in Plants Are Mobile and Direct Epigenetic Modification in Recipient Cells (2010)

A silencing signal in plants with an RNA specificity determinant moves through plasmodesmata and the phloem. To identify the mobile RNA, we grafted Arabidopsis thaliana shoots to roots that would be a recipient for the silencing signal. Using mutants that block small RNA (sRNA) biogenesis in either source or recipient tissue, we found that transgene-derived sRNA as well as a substantial proportion of the endogenous sRNA had moved across the graft union, and we provide evidence that 24-nucleotide mobile sRNAs direct epigenetic modifications in the genome of the recipient cells. Mobile sRNA thus represents a mechanism for transmitting the specification of epigenetic modification and could affect genome defense and responses to external stimuli that have persistent effects in plants.
Magnetic Stimulation in the Treatment of Partial Seizures (1991)

We have recently demonstrated that Magnetoencephalographic (MEG) brain measurements in patients with seizure disorders show significant MEG activity often in the absence of conventional EEG abnormalities. We localized foci of seizure activity using the mapping technique characterized by the ISO-Spectral Amplitude (ISO-SA) on the scalp distribution of specified spectral components or frequency bands of the emitted MEG Fourier power spectrum. In addition, using an electronic device, we utilized the above recorded activity to emit back the same intensity and frequency of magnetic field to the presumed epileptic foci. Using this method we were able, over the past two years, successfully to attenuate seizure activity in a cohort of over 100 patients with various forms of epilepsy. We now present in more detail three randomly selected patients with partial seizures in whom application of an external artificial magnetic field of low intensity produced a substantial attenuation of seizure frequency during an observation period extending from 10 to 14 months. All patients had previously obtained only partial response to conventional anticonvulsant therapy. Attenuation in seizure frequency was associated with normalization of the MEG activity. These cases demonstrate that artificial magnetic treatment may be a valuable adjunctive procedure in the management of partial seizures. The possible mechanisms underlying the anticonvulsant properties of magnetic stimulation at both cellular and systemic levels are discussed. Specifically, since the pineal gland has been shown to be a magnetosensitive organ which forms part of a combined compass-solar clock system, and since it exerts an inhibitory action on seizure activity in both experimental animals and humans, we discuss the potential pivotal role of the pineal gland in the long term anticonvulsant effects of external artificial magnetic stimulation.
Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: a prospective study (2009)

Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant plasma-cell proliferative disorder associated with a life-long risk of progression to multiple myeloma (MM). It is not known whether MM is always preceded by a premalignant asymptomatic MGUS stage. Among 77,469 healthy adults enrolled in the nationwide population-based prospective Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, we identified 71 subjects who developed MM during the course of the study in whom serially collected (up to 6) prediagnostic serum samples obtained 2 to 9.8 years prior to MM diagnosis were available. Using assays for monoclonal (M)-proteins (electrophoresis/immunofixation) and kappa-lambda free light chains (FLCs), we determined longitudinally the prevalence of MGUS and characterized patterns of monoclonal immunoglobulin abnormalities prior to MM diagnosis. MGUS was present in 100.0% (87.2%-100.0%), 98.3% (90.8%-100.0%), 97.9% (88.9%-100.0%), 94.6% (81.8%-99.3%), 100.0% (86.3%-100.0%), 93.3% (68.1%-99.8%), and 82.4% (56.6%-96.2%) at 2, 3, 4, 5, 6, 7, and 8+ years prior to MM diagnosis, respectively. In approximately half the study population, the M-protein concentration and involved FLC-ratio levels showed a yearly increase prior to MM diagnosis. In the present study, an asymptomatic MGUS stage consistently preceded MM. Novel molecular markers are needed to better predict progression to MM in patients with MGUS.
Screening of cyclic peptide phage libraries identifies ligands that bind streptavidin with high affinities (1995)

The screening of combinatorial peptide libraries has emerged as an important tool in the discovery of novel substrates or ligands for enzyme and receptor targets. For example, screening linear peptide libraries using streptavidin as a model receptor system has previously identified many low-affinity peptide ligands, all of which contain the common motif His-Pro-Gln (HPQ). We reasoned that constraining the conformational freedom of linear peptides by cyclization in a library would yield peptide ligands of increased affinity. Three different cyclic peptide libraries were constructed in an M13 phage display system as N-terminal pIII protein fusions. The random peptide sequences were flanked by two cysteine residues, which allows efficient disulfide bond formation and cyclization during phage assembly. These cyclic peptide libraries were screened with streptavidin as the model receptor system. Many sequences, all of which contained the motif His-Pro-Gln (HPQ), were discovered, and in the preceding paper, the structures of complexes of streptavidin-bound cyclic and linear peptides are described (Katz, 1995). Analysis of binding kinetics and affinities demonstrated that the conformationally constrained cyclic peptides bound streptavidin with affinities up to 3 orders of magnitude higher than linear peptides identified in previous library screens. These results demonstrate the potential of screening conformationally constrained peptide libraries for high-affinity novel receptor ligands or enzyme substrates.
Next Generation Sequencing of Prostate Cancer from a Patient Identifies a Deficiency of Methylthioadenosine Phosphorylase, an Exploitable Tumor Target (2012)

Castrate-resistant prostate cancer (CRPC) and neuroendocrine carcinoma of the prostate are invariably fatal diseases for which only palliative therapies exist. As part of a prostate tumor sequencing program, a patient tumor was analyzed using Illumina genome sequencing and a matched renal capsule tumor xenograft was generated. Both tumor and xenograft had a homozygous 9p21 deletion spanning the MTAP, CDKN2, and ARF genes. It is rare for this deletion to occur in primary prostate tumors, yet approximately 10% express decreased levels of methylthioadenosine phosphorylase (MTAP) mRNA. Decreased MTAP expression is a prognosticator for poor outcome. Moreover, it seems that this deletion is more common in CRPC than in primary prostate cancer. We show for the first time that treatment with methylthioadenosine and high dose 6-thioguanine causes marked inhibition of a patient-derived neuroendocrine xenograft growth while protecting the host from 6-thioguanine toxicity. This therapeutic approach can be applied to other MTAP-deficient human cancers as deletion or hypermethylation of the MTAP gene occurs in a broad spectrum of tumors at high frequency. The combination of genome sequencing and patient-derived xenografts can identify candidate therapeutic agents and evaluate them for personalized oncology.
Noninvasive Prediction of Ultimate Infarct Size at the Time of Acute Coronary Occlusion Based on the Extent and Magnitude of Collateral-Derived Myocardial Blood Flow (2001)

MCE can be used immediately after coronary occlusion to define ultimate IS by measuring the magnitude and spatial extent of collateral-derived residual MBF within the RA. Thus, it could help individualize risk and management in acute myocardial infarction.