gebhart/patrepeval huggingface dataset:
Finding Chimeras: a Bioinformatics Strategy for Identification of Cross-linked Peptides (2009)

Chemical cross-linking, followed by identification of the cross-linked residues, is a powerful approach to probe the topologies and interacting surfaces of protein assemblies. In this work, we demonstrate a new bioinformatics approach using multiple program modules within the software package "Protein Prospector" that greatly facilitates the discovery of cross-linked peptides in chemical cross-linking studies. Examples are given for how this approach has been used for defining interfaces in heterodimeric and homodimeric protein complexes, both of which provide results in close agreement with crystal structures, verifying the reliability of the approach.
A Deep Reinforced Model for Abstractive Summarization (2017)

Attentional, RNN-based encoder-decoder models for abstractive summarization have achieved good performance on short input and output sequences. For longer documents and summaries however these models often include repetitive and incoherent phrases. We introduce a neural network model with a novel intra-attention that attends over the input and continuously generated output separately, and a new training method that combines standard supervised word prediction and reinforcement learning (RL). Models trained only with supervised learning often exhibit "exposure bias" - they assume ground truth is provided at each step during training. However, when standard word prediction is combined with the global sequence prediction training of RL the resulting summaries become more readable. We evaluate this model on the CNN/Daily Mail and New York Times datasets. Our model obtains a 41.16 ROUGE-1 score on the CNN/Daily Mail dataset, an improvement over previous state-of-the-art models. Human evaluation also shows that our model produces higher quality summaries.
Document analysis techniques for the infinite memory multifunction machine (1999)

A system that saves a digital copy of every document that users copy, print, or fax, without asking the user, has recently been proposed. Referred to as the Infinite Memory Multifunction Machine (IM/sup 3/), this system solves most of the problem of lost documents. However, because of the indiscriminate way it captures data, it is important that users have easy-to-use retrieval tools. Two document analysis techniques are described that simplify retrieval from large collections like the IM/sup 3/. One technique detects duplicates or versions of a document. Another method automatically files a document in a hierarchy familiar to a user. Experimental results are presented that illustrate the performance of each method.
Gender differences in gemcitabine (Gemzar) efficacy in cancer cells: effect of indole-3-carbinol. (2010)

Pancreatic cancer has a poor prognosis, mainly due to lack of effective therapies. This study demonstrated the ability of dietary agent, indole-3-carbinol (I3C), to lower the LD(50) of gemcitabine (Gemzar) in decreasing growth of both male (MiaPaca2) and female (SU86.86) pancreatic cancer cells. Female pancreatic cancer cells were more resistant to gemcitabine alone. Additionally, RT-PCR analysis of MiaPaca2 cells treated with 1, 10 or 100 μM of I3C showed that I3C reactivated the tumor suppressor gene p16INK4a in pancreatic cancer cells. Methylated-specific PCR analysis indicated that I3C demethylated the promoter region of p16 INK4a, which was methylated in the untreated cancer cells. p16INK4a inactivation through promoter hypermethylation is considered an early event in pancreatic carcinogenesis. A positive control using 5-azacytidine also reactivated p16INK4a. This study demonstrated the potential of I3C, a possible non-toxic hypomethylating agent, combined with the anticancer agent, gemcitabine, to be a powerful strategy for treating pancreatic cancer.
Engineering Carbon Nanotubes and Nanotube Circuits Using Electrical Breakdown (2001)

Carbon nanotubes display either metallic or semiconducting properties. Both large, multiwalled nanotubes (MWNTs), with many concentric carbon shells, and bundles or "ropes" of aligned single-walled nanotubes (SWNTs), are complex composite conductors that incorporate many weakly coupled nanotubes that each have a different electronic structure. Here we demonstrate a simple and reliable method for selectively removing single carbon shells from MWNTs and SWNT ropes to tailor the properties of these composite nanotubes. We can remove shells of MWNTs stepwise and individually characterize the different shells. By choosing among the shells, we can convert a MWNT into either a metallic or a semiconducting conductor, as well as directly address the issue of multiple-shell transport. With SWNT ropes, similar selectivity allows us to generate entire arrays of nanoscale field-effect transistors based solely on the fraction of semiconducting SWNTs.
Role of Bone-Type Tissue-Nonspecific Alkaline Phosphatase and PHOSPO1 in Vascular Calcification (2014)

Matrix vesicle (MV)-mediated mineralization is important for bone ossification. However, under certain circumstances such as atherosclerosis, mineralization may occur in the arterial wall. Bone-type tissue-nonspecific alkaline phosphatase (TNAP) hydrolyzes inorganic pyrophosphate (PPi) and generates inorganic phosphate (Pi), which is essential for MV-mediated hydroxyapatite formation. MVs contain another phosphatase, PHOSPHO1, that serves as an additional supplier of Pi. Activation of bone-type tissue-nonspecific alkaline phosphatase (TNAP) in vascular smooth muscle cells precedes vascular calcification. By degrading PPi, TNAP plays a procalcific role changing the Pi/PPi ratio toward mineralization. A pathologic role of bone-type TNAP and PHOSPHO1 make them to be attractive targets for cardiovascular therapy.
Biological Processes Associated with Breast Cancer Clinical Outcome Depend on the Molecular Subtypes (2008)

Although proliferation is the strongest parameter predicting clinical outcome in the ER+/HER2- subtype and the common denominator of most prognostic gene signatures, immune response and tumor invasion seem to be the main molecular processes associated with prognosis in the ER-/HER2- and HER2+ subgroups, respectively. These findings may help to define new clinicogenomic models and to identify new therapeutic strategies in the specific molecular subgroups.
Domains of the rat rDNA promoter must be aligned stereospecifically. (1992)

Efficient transcription from the rat rDNA promoter results from an undefined interaction between the core (CPE) and upstream (UPE) promoter elements or the protein complexes which form on them. These interactions were demonstrated by the behavior of promoters that contained either linker-scanning or deletion mutations of the UPE in combination with point mutations of the CPE (bidomain mutants). In vivo transcription experiments using point mutations within the CPE (G----A mutation at either -16 or -7) demonstrated that the CPE may in fact consist of two domains. Whereas both of these mutants were rescued by the addition of UBF to in vitro transcription reactions, the CPE mutant -7A/G was inactive in vivo. Experiments with these bidomain mutants demonstrated that the UPE was required for the rescue of the CPE mutants. We also examined the hypothesis that this interaction might require a stereospecific alignment of the promoter elements. Our results indicate that the promoter consists of several domains with differing responses to mutations that alter the distance between, or within, the promoter elements. For example, the insertion or deletion of half-multiples of the helical repeat distance between -167 and -147 had no significant effect on transcription. On the other hand, some sites were sensitive to deletions of any size but not to insertions of up to 20 bp. The analyses of two sites yielded results suggesting that they lay between domains of the promoter that must be on the same side of the DNA helix for promoter activity. The first of these sites mapped between -106 and -95.(ABSTRACT TRUNCATED AT 250 WORDS)
Crystallization of Calcium and Magnesium Phosphates from Solutions of Medium and Low Concentrations (1992)

Abstract Calcium phosphates are precipitated at 25 °C from solutions of medium (Ca = P = 50 mM) and low (Ca = P = 10 mM) concentrations in the presence of magnesium. Experiments are also performed with solutions in which Ca + Mg = P = 50 mM and Ca + Mg = P = 10 mM. An amorphous calcium phosphate, Ca 3 (PO 4 ) 2 · nH 2 O, and brushite, CaHPO 4 · 2 H 2 O, are the phases first nucleated. The phases occurring one year later are brushite in the more concentrated solutions, hydroxyapatite (Ca 5 OH(PO 4 ) 3 ) and whitlockite (Ca 9 MgH(PO 4 ) 7 ) in the others. Octacalciumphosphate, Ca 8 H 2 (PO 4 ) 6 · 5H 2 O, occurs as transitory phase. The effects of concentration, pH, supersaturation and magnesium on the precipitation and evolution of calcium phosphates, and the conditions for phase stability are discussed.
Aggressive Lipid-Lowering Therapy Compared with Angioplasty in Stable Coronary Artery Disease (1999)

In low-risk patients with stable coronary artery disease, aggressive lipid-lowering therapy is at least as effective as angioplasty and usual care in reducing the incidence of ischemic events.
Stability of IgG isotypes in serum (2010)

Drug development from early discovery to late stage commercialization is a long arduous process where a number of factors are taken into consideration when deciding on a particular immunoglobulin isotype for a therapeutic purpose. There are no general rules for which isotype is selected; however, prior experiences, effector function and the specific therapy targeted, as well as extensive testing early in development help in pairing the number of candidates. Over 20 monoclonal antibodies are FDA-approved, and most are IgG1 isotype, although a number of non-IgG1 molecules have been approved recently and the number in development is on the rise. Analytical techniques that examine the physicochemical properties of a molecule provide vital information on the stability and efficacy of candidate antibody therapeutics, but most of these studies are conducted using standard buffers and under well defined storage conditions. It has recently become apparent that analysis of antibody therapeutics recovered after circulation in blood show altered physicochemical characteristics, and in many instances therapeutic molecules recovered from serum show lower potency. This review examines some of these studies, with a focus on the physicochemical changes observed in the molecules. Technologies that can facilitate rapid screening of candidate antibody therapeutics directly from blood are highlighted. The facts indicate that antibody therapeutic development programs must incorporate understanding of the basic biology of the isotype and its stability in serum, which is the intended environment of the therapeutic.
Prevalence of Monoclonal Gammopathy of Undetermined Significance (2006)

Among residents of Olmsted County, Minnesota, MGUS was found in 3.2 percent of persons 50 years of age or older and 5.3 percent of persons 70 years of age or older.
Ultrasonic scattering from spherical shells including viscous and thermal effects (1993)

An analysis for sound scattering and attenuation by shell structures immersed in fluids is outlined. While the form of the analysis permits easy comparison with previous results for simple spheres, it includes novel features of viscoelasticity in the shell and core materials (which may be fluid or solid), viscosity in the suspending fluid, and thermal effects. The computational procedure adopted is outlined with particular reference to the avoidance of numerical instabilities at very low and very high values of ‘‘ka.’’ The testing of the program by comparison with previous results on simpler systems is reported, and a limited selection of numerical results is given. The program has been used successfully over the range of ka values between 10−6 and 200, its robustness needs closer definition.
Robotic Surgery in Otolaryngology and Head and Neck Surgery: A Review (2012)

Recent advancements in robotics technology have allowed more complex surgical procedures to be performed using minimally invasive approaches. In this article, we reviewed the role of robotic assistance in Otolaryngology and Head and Neck Surgery. We highlight the advantages of robot-assisted surgery and its clinical application in this field.
Identification of N‐acetylgalactosamine‐containing glycoproteins PEB3 and CgpA in Campylobacter jejuni (2002)

It was demonstrated recently that there is a system of general protein glycosylation in the human enteropathogen Campylobacter jejuni. To characterize such glycoproteins, we identified a lectin, Soybean agglutinin (SBA), which binds to multiple C. jejuni proteins on Western blots. Binding of lectin SBA was disrupted by mutagenesis of genes within the previously identified protein glycosylation locus. This lectin was used to purify putative glycoproteins selectively and, after sodium dodecyl sulphatepolyacrylamide gel electrophoresis (SDS-PAGE), Coomassie-stained bands were cut from the gels. The bands were digested with trypsin, and peptides were identified by mass spectrometry and database searching. A 28kDa band was identified as PEB3, a previously characterized immunogenic cell surface protein. Bands of 32 and 34kDa were both identified as a putative periplasmic protein encoded by the C. jejuni NCTC 11168 coding sequence Cj1670c. We have named this putative glycoprotein CgpA. We constructed insertional knockout mutants of both the peb3 and cgpA genes, and surface protein extracts from mutant and wild-type strains were analysed by one- and two-dimensional polyacrylamide gel electrophoresis (PAGE). In this way, we were able to identify the PEB3 protein as a 28 kDa SBA-reactive and immunoreactive glycoprotein. The cgpA gene encoded SBA-reactive and immunoreactive proteins of 32 and 34 kDa. By using specific exoglycosidases, we demonstrated that the SBA binding property of acid-glycine extractable C. jejuni glycoproteins, including PEB3 and CgpA, is a result of the presence of alpha-linked N-acetylgalactosamine residues. These data confirm the existence, and extend the boundaries, of the previously identified protein glycosylation locus of C. jejuni. Furthermore, we have identified two such glycoproteins, the first non-flagellin campylobacter glycoproteins to be identified, and demonstrated that their glycan components contain alpha-linked N-acetylgalactosamine residues.
Purification of the alpha 2-adrenergic receptor from porcine brain using a yohimbine-agarose affinity matrix. (1987)

A procedure has been developed for purification of the porcine brain alpha 2-adrenergic receptor to homogeneity. alpha 2-Adrenergic receptors were solubilized from porcine brain particulate preparations using sequential extraction into sodium cholate- and digitonin-containing buffers. The alpha 2-adrenergic receptors in the digitonin extract were identified using the alpha 2-adrenergic selective antagonist, [3H]yohimbine, and demonstrated the same specificity for interaction with adrenergic ligands as did the receptors in particulate preparations. Extraction into digitonin-containing buffers eliminated the modulation of receptor-agonist interactions by guanine nucleotides, but not by monovalent cations. A novel affinity resin, yohimbine-agarose, was synthesized and used for purification of alpha 2-adrenergic receptors. Using two sequential yohimbine-agarose affinity chromatography steps, digitonin-solubilized alpha 2-adrenergic receptors from porcine brain cortex were purified to homogeneity as assessed by radioiodination and silver stain analysis of these preparations on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The purified alpha 2-adrenergic receptor has an approximate Mr = 65,000, as determined by photolabeling of the adrenergic ligand-binding subunit. The yohimbine-agarose affinity resin should be useful for purifying quantities of receptor sufficient for studies of receptor structure and function.
Large scale metal-free synthesis of graphene on sapphire and transfer-free device fabrication (2012)

Metal catalyst-free growth of large scale single layer graphene film on a sapphire substrate by a chemical vapor deposition (CVD) process at 950 °C is demonstrated. A top-gated graphene field effect transistor (FET) device is successfully fabricated without any transfer process. The detailed growth process is investigated by the atomic force microscopy (AFM) studies.
Inhibition of Maize Histone Deacetylases by HC Toxin, the Host-Selective Toxin of Cochliobolus carbonum (1995)

Gerald Brosch, Richard Ransom, Thomas Lechner, Jonathan D. Walton, Peter Loidl, Inhibition of Maize Histone Deacetylases by HC Toxin, the Host-Selective Toxin of Cochliobolus carbonum, The Plant Cell, Vol. 7, No. 11 (Nov., 1995), pp. 1941-1950
Phenobarbital promotes multistage pulmonary carcinogenesis in MNU-inoculated L-W rats. (1997)

Lobund-Wistar (L-W) rats develop adenocarcinomas spontaneously in the accessory sex glands (prostate-seminal vesicles) (P-SV) in the livers and in the lungs-all after long periods of latency. This report addresses (a) the multistage pattern of induced lung carcinomas in L-W rats and (b) the role(s) of two putative promotional agents (testosterone propionate (TP) and phenobarbital (PB) in the development of carcinomas in the lungs of L-W rats. Lung cancer is a rare slow-growing spontaneous neoplasm in L-W rats. Their incidence increased from 4.4% in avg 25.6 months (spontaneously) to 23.8% in avg 19 months following a single IV inoculation of methylnitrosourea (MNU), and further increased to 57% in avg 15 months by adding phenobarbital to the diet of MNU-inoculated rats. Three stages of lung tumorigenesis were manifested in L-W rats following treatments with MNU, or MNU + PB: hyperplasia, adenoma, and carcinoma.
Generation of Human CD8 T Regulatory Cells by CD40 Ligand–activated Plasmacytoid Dendritic Cells (2002)

Although CD8 T cell-mediated immunosuppression has been a well-known phenomenon during the last three decades, the nature of primary CD8 T suppressor cells and the mechanism underlying their generation remain enigmatic. We demonstrated that naive CD8 T cells primed with allogeneic CD40 ligand-activated plasmacytoid dendritic cells (DC)2 differentiated into CD8 T cells that displayed poor secondary proliferative and cytolytic responses. By contrast, naive CD8 T cells primed with allogeneic CD40 ligand-activated monocyte-derived DCs (DC1) differentiated into CD8 T cells, which proliferated to secondary stimulation and killed allogeneic target cells. Unlike DC1-primed CD8 T cells that produced large amounts of interferon (IFN)-gamma upon restimulation, DC2-primed CD8 T cells produced significant amounts of interleukin (IL)-10, low IFN-gamma, and no IL-4, IL-5, nor transforming growth factor (TGF)-beta. The addition of anti-IL-10-neutralizing monoclonal antibodies during DC2 and CD8 T cell coculture, completely blocked the generation of IL-10-producing anergic CD8 T cells. IL-10-producing CD8 T cells strongly inhibit the allospecific proliferation of naive CD8 T cells to monocytes, and mature and immature DCs. This inhibition was mediated by IL-10, but not by TGF-beta. IL-10-producing CD8 T cells could inhibit the bystander proliferation of naive CD8 T cells, provided that they were restimulated nearby to produce IL-10. IL-10-producing CD8 T cells could not inhibit the proliferation of DC1-preactivated effector T cells. This study demonstrates that IL-10-producing CD8 T cells are regulatory T cells, which provides a cellular basis for the phenomenon of CD8 T cell-mediated immunosuppression and suggests a role for plasmacytoid DC2 in immunological tolerance.
Late resistance to imatinib therapy in a metastatic gastrointestinal stromal tumour is associated with a second KIT mutation (2004)

Currently, there are no data on the secondary resistance of gastrointestinal stromal tumours to imatinib. Here, we report a case of metastatic gastrointestinal stromal tumour that relapsed during imatinib therapy. Mutation analysis showed that the imatinib-resistant liver tumour contained two c-kit mutations.
An efficient GSC VSS-APA beamformer with integrated log-energy based VAD for noise reduction in speech reinforcement systems (2013)

This paper presents an efficient time-domain Generalized Sidelobe Canceller (GSC) with low signal distortion capabilities using the variable step size affine projection algorithm (VSS-APA) and a log-energy based voice activity detector (VAD). The performance of the proposed VSS-APA based GSC method with integrated log-energy VAD, is illustrated in the context of speech reinforcement application using different signals with low signal-to-noise ratio and different types of noise.
Effects of ionic liquids on the acetylcholinesterase – a structure–activity relationship consideration (2004)

Ionic liquids are discussed as sustainable green solvents, but toxicity and ecotoxicity data are rare. In this paper we present our results for different ionic liquids with the acetylcholinesterase inhibition assay. The results show that the acetylcholinesterase can be inhibited by ionic liquids containing a cation with a positively charged nitrogen and a certain lipophilicity. We tested imidazolium ionic liquids with different alkyl chains at R1 and R2 as well as with different anions and compared these results with our findings for other cation structures such as pyridinium ionic liquids and phosphonium ionic liquids. According to our results imidazolium and pyridinium ionic liquids inhibit the purified enzyme with EC50 values as low as 13 μM. The bulky phosphonium ionic liquids were less inhibitory. These results can be rationalized by structure–activity relationship considerations.
Direct evidence that Bcr-Abl tyrosine kinase activity disrupts normal synergistic interactions between Kit ligand and cytokines in primary primitive progenitor cells. (2003)

We previously reported that chronic myelogenous leukemia (CML) primitive granulocyte-monocyte (GM) progenitors have a greatly reduced requirement for kit ligand (KL) to achieve optimal growth with granulocyte colony-stimulating factor (G-CSF) + granulocyte-monocyte colony-stimulating factor (GM-CSF). Conversely, others have demonstrated that unlike normal, CML CD34+ progenitors can proliferate in response to KL as a sole stimulus. To address these seemingly paradoxical findings, we examined the growth responses of CML CD34+ GM progenitors to various cytokines with and without a potent inhibitor of Bcr-Abl tyrosine kinase activity, PD173955. The heightened growth responses of CML GM progenitors to KL alone and to G-CSF + GM-CSF were abrogated by 10 nM PD173955 while having no effect on normal GM progenitors. While normal GM progenitors exhibited the expected synergistic response when KL was added to G-CSF + GM-CSF, CML GM progenitors had a minimal response; however, some synergism was restored by 10 nM PD173955. Normal erythroid progenitors require the synergistic interaction between KL and a saturating amount of erythropoietin (EPO, 1 unit) for optimal growth. In contrast, CML erythroid progenitors had up to 50% of optimal growth in KL alone, and, only a subthreshold amount of EPO (0.1 unit) was needed with KL to achieve 85% of the optimal response; these heightened growth responses were largely abrogated by 10 nM PD173955. Thus, direct evidence is provided that constitutively activated Bcr-Abl kinase pathways in primitive CML progenitors cooperate with single growth factors producing a heightened growth response, and, in so doing, disrupt the normally required synergistic interactions between KL and other cytokines to achieve activation and optimal growth of primitive progenitors. Coupled with our previous findings that a larger than normal proportion of CML primitive progenitors are at a later stage of maturation, we propose that this disruption of normal synergistic responses leads to increased progenitor recruitment into a committed pool by a process of accelerated maturation.