gebhart/patrepeval huggingface dataset:
Imaging brain tumors by targeting peptide radiopharmaceuticals through the blood-brain barrier. (1999)

Present day imaging of brain tumors requires a disrupted blood-brain barrier (BBB). However, the BBB is intact in the early stages of brain tumor growth, when diagnosis is most critical. Relative to normal brain, brain tumor cells frequently overexpress peptide receptors, such as the receptor for epidermal growth factor (EGF). Peptide radiopharmaceuticals such as radiolabeled EGF could be used to image early brain tumors, should these radiopharmaceuticals be made transportable through the BBB. The present studies describe a bifunctional molecule that contains both biologically active human EGF radiolabeled with 111In and an anti-transferrin receptor monoclonal antibody that undergoes transcytosis through the BBB via the endogenous transferrin transport system. The two domains of the bifunctional conjugate are separated by a Mr 3400 polyethyleneglycol linker, which releases steric hindrance and allows the conjugate to bind to both the EGF receptor, to image the brain tumor, and to the transferrin receptor, to enable transport through the BBB. Successful imaging of experimental brain tumors with this system is demonstrated in nude rats bearing cerebral implants of human U87 glioma.
Maxmargin min-entropy models (2012)

We propose a new family of latent variable models called max-margin min-entropy (m3e) models, which define a distribution over the output and the hidden variables conditioned on the input. Given an input, an m3e model predicts the output with the smallest corresponding Rényi entropy of generalized distribution. This is equivalent to minimizing a score that consists of two terms: (i) the negative log-likelihood of the output, ensuring that the output has a high probability; and (ii) a measure of uncertainty over the distribution of the hidden variables conditioned on the input and the output, ensuring that there is little confusion in the values of the hidden variables. Given a training dataset, the parameters of an m3e model are learned by maximizing the margin between the Rényi entropies of the ground-truth output and all other incorrect outputs. Training an m3e can be viewed as minimizing an upper bound on a user-defined loss, and includes, as a special case, the latent support vector machine framework. We demonstrate the efficacy of m3e models on two standard machine learning applications, discriminative motif finding and image classification, using publicly available datasets. 1
Chimaerism shown by cytogenetics and DNA polymorphism analysis. (1994)

A child with ambiguous genitalia, brought up phenotypically male, had a 46,XX/46,XY karyotype. At laparotomy, he had a left sided ovary and uterus, and a right sided scrotal testis. The 46,XX line made up 50% of cells in the blood and 90% of cells in a skin biopsy. There were no cytogenetic polymorphisms. Analysis of lymphocyte DNA with seven polymorphic DNA markers showed him to be chimaeric, with four, three, and two parental alleles at different loci. He had one paternal and one maternal X chromosome at the marker DXS1053. Based on our data, we would suggest that chimaerism arose as a result of postzygotic fusion of two embryos. We have shown by DNA polymorphisms the presence of autosomal chimaerism in a case of sex chromosome chimaerism, and indicated the usefulness of DNA polymorphisms in determining the origin of chimaerism.
novoSNP, a novel computational tool for sequence variation discovery (2005)

Technological improvements shifted sequencing from low-throughput, work-intensive, gel-based systems to high-throughput capillary systems. This resulted in a broad use of genomic resequencing to identify sequence variations in genes and regulatory, as well as extended genomic regions. We describe a software package, novoSNP, that conscientiously discovers single nucleotide polymorphisms (SNPs) and insertion-deletion polymorphisms (INDELs) in sequence trace files in a fast, reliable, and user-friendly way. We compared the performance of novoSNP with that of PolyPhred and PolyBayes on two data sets. The first data set comprised 1028 sequence trace files obtained from diagnostic mutation analyses of SCN1A (neuronal voltage-gated sodium channel alpha-subunit type I gene). The second data set comprised 9062 sequence trace files from a genomic resequencing project aiming at the construction of a high-density SNP map of MAPT (microtubule-associated protein tau gene). Visual inspection of these data sets had identified 38 sequence variations for SCN1A and 488 for MAPT. novoSNP automatically identified all 38 SCN1A variations including five INDELs, while for MAPT only 15 of the 488 variations were not correctly marked. PolyPhred detected far fewer SNPs as compared to novoSNP and missed nearly all INDELs. PolyBayes, designed for the sequence analysis of cloned templates, detected only a limited number of the variations present in the data set. Besides the significant improvement in the automated detection of sequence variations both in diagnostic mutation analyses and in SNP discovery projects, novoSNP also offers a user-friendly interface for inspecting possible genetic variations.
The repeat domain of the type III effector protein PthA shows a TPR‐like structure and undergoes conformational changes upon DNA interaction (2010)

Many plant pathogenic bacteria rely on effector proteins to suppress defense and manipulate host cell mechanisms to cause disease. The effector protein PthA modulates the host transcriptome to promote citrus canker. PthA possesses unusual protein architecture with an internal region encompassing variable numbers of near-identical tandem repeats of 34 amino acids termed the repeat domain. This domain mediates protein-protein and protein-DNA interactions, and two polymorphic residues in each repeat unit determine DNA specificity. To gain insights into how the repeat domain promotes protein-protein and protein-DNA contacts, we have solved the structure of a peptide corresponding to 1.5 units of the PthA repeat domain by nuclear magnetic resonance (NMR) and carried out small-angle X-ray scattering (SAXS) and spectroscopic studies on the entire 15.5-repeat domain of PthA2 (RD2). Consistent with secondary structure predictions and circular dichroism data, the NMR structure of the 1.5-repeat peptide reveals three α-helices connected by two turns that fold into a tetratricopeptide repeat (TPR)-like domain. The NMR structure corroborates the theoretical TPR superhelix predicted for RD2, which is also in agreement with the elongated shape of RD2 determined by SAXS. Furthermore, RD2 undergoes conformational changes in a pH-dependent manner and upon DNA interaction, and shows sequence similarities to pentatricopeptide repeat (PPR), a nucleic acid-binding motif structurally related to TPR. The results point to a model in which the RD2 structure changes its compactness as it embraces the DNA with the polymorphic diresidues facing the interior of the superhelix oriented toward the nucleotide bases.
Syntheses of Substituted Trifluorophenyl Isocyanates (1967)

クロル, ニトロ, トリフルオルメチル, メトキシ置換のトリフルオルメチルアニリンをエチレングリコールジメチルエーテルに溶解し,ホスゲンを導入して加熱反応させることによって新しい対応する11種のクロル,ニトロ,トリフルオルメチルまたはメトキシ基の置換したトリフルオルメチルフェニルイソシアナートを合成し,さらに水との反応により対応する対称型尿素誘導体を得た。これらの反応条件,物理的性質を明らかにするとともに,各種の置換基のイソシアナート基におよぼす影響を検討するためベンゼン中でのm-ニトロアニリン,アセトン中での水との反応を行ないイソシアナート類の相対的反応性を明らかにした。その結果, 電子吸引性の強い置換基を有するイソシアナートが最も反応性が大であった。
Hepatic Clearance of Tissue-Type Plasminogen Activator in Rats (1985)

The clearance of tissue-type plasminogen activator (t-PA) was studied, in rats, by use of a functional assay for t-PA. Half-lives in the circulation were about one minute both for human (melanoma cell-derived) t-PA and for the rat's own t-PA. The clearance of t-PA required an intact liver blood flow. In isolated liver perfusion experiments the hepatic extraction of t-PA did not require any plasma proteins, including fast-acting t-PA inhibitor. Competition experiments, using monosaccharides, suggested that known hepatic glycoprotein receptors were not involved in hepatic t-PA extraction.
Autoinducer-2 Plays a Crucial Role in Gut Colonization and Probiotic Functionality of Bifidobacterium breve UCC2003 (2014)

In the present study we show that luxS of Bifidobacterium breve UCC2003 is involved in the production of the interspecies signaling molecule autoinducer-2 (AI-2), and that this gene is essential for gastrointestinal colonization of a murine host, while it is also involved in providing protection against Salmonella infection in Caenorhabditis elegans. We demonstrate that a B. breve luxS-insertion mutant is significantly more susceptible to iron chelators than the WT strain and that this sensitivity can be partially reverted in the presence of the AI-2 precursor DPD. Furthermore, we show that several genes of an iron starvation-induced gene cluster, which are downregulated in the luxS-insertion mutant and which encodes a presumed iron-uptake system, are transcriptionally upregulated under in vivo conditions. Mutation of two genes of this cluster in B. breve UCC2003 renders the derived mutant strains sensitive to iron chelators while deficient in their ability to confer gut pathogen protection to Salmonella-infected nematodes. Since a functional luxS gene is present in all tested members of the genus Bifidobacterium, we conclude that bifidobacteria operate a LuxS-mediated system for gut colonization and pathogen protection that is correlated with iron acquisition.
Semisynthetic Maytansine Analogues for the Targeted Treatment of Cancer (2006)

Maytansine, a highly cytotoxic natural product, failed as an anticancer agent in human clinical trials because of unacceptable systemic toxicity. The potent cell killing ability of maytansine can be used in a targeted delivery approach for the selective destruction of cancer cells. A series of new maytansinoids, bearing a disulfide or thiol substituent were synthesized. The chain length of the ester side chain and the degree of steric hindrance on the carbon atom bearing the thiol substituent were varied. Several of these maytansinoids were found to be even more potent in vitro than maytansine. The targeted delivery of these maytansinoids, using monoclonal antibodies, resulted in a high, specific killing of the targeted cells in vitro and remarkable antitumor activity in vivo.
The 67-kDa Laminin-binding Protein Is Involved in Shear Stress-dependent Endothelial Nitric-oxide Synthase Expression (1999)

It has been suggested that the mechanical forces acting on endothelial cells may be sensed in part by cell-matrix connections. We therefore studied the role of different matrix proteins, in particular laminin I, on a shear stress-dependent endothelial response, namely nitric-oxide synthase (eNOS) expression. Primary porcine aortic endothelial cells were seeded onto glass plates either noncoated (NC cells) or precoated with fibronectin (FN cells), laminin (LN cells), or collagen I (CN cells). Western blots were used to detect differences in the final matrix composition of these cells. A shear stress of 16 dyn/cm2 was applied for 6 h. Only LN cells showed detectable amounts of laminin I in their underlying matrix when they reached confluence. They reacted with a 2-fold increase of eNOS expression (n = 16, p < 0.001) to the exposure of shear stress, which went along with enhanced eNOS protein and NO release. In contrast, neither FN cells (n = 9) nor NC cells (n = 13) showed a significant increase of eNOS expression under shear stress. The increase in CN cells was borderline (1.4-fold; n = 9, p < 0.05) and was not associated with an increase of eNOS protein. The shear-induced increase in eNOS expression of LN cells was abolished by the peptide YIGSR, which blocks the cellular binding to laminin I via a 67-kDa laminin-binding protein, whereas a control peptide (YIGSK) had no effect. The induction of eNOS expression by shear stress is stimulated by an interaction of endothelial cells with laminin which is, at least in part, mediated by a 67-kDa laminin-binding protein.
The biology of neoadjuvant chemotherapy for breast cancer. (2002)

Neoadjuvant/pre-surgical medical therapy of breast cancer provides a unique opportunity to derive biological information related to tumour response. Large clinical trials of neoadjuvant chemotherapy have established that pathological complete remission is an independent predictor of improved disease-free survival. Clinical response has been found to parallel substantial reductions in the proliferation of breast cancer cells. Increased apoptosis also occurs, but it is not closely associated with response. Numerous biological markers such as p53, bcl-2, oestrogen receptor (ER) and HER2 have been assessed for their possible role in chemoresistance/response, but the data are not clear at this stage. Continuing work using cDNA microarrays may yield new, more reliable indices of likely response and an improved insight into biological processes related to chemotherapeutic response.
Smart Reply: Automated Response Suggestion for Email (2016)

In this paper we propose and investigate a novel end-to-end method for automatically generating short email responses, called Smart Reply. It generates semantically diverse suggestions that can be used as complete email responses with just one tap on mobile. The system is currently used in Inbox by Gmail and is responsible for assisting with 10% of all mobile responses. It is designed to work at very high throughput and process hundreds of millions of messages daily. The system exploits state-of-the-art, large-scale deep learning. We describe the architecture of the system as well as the challenges that we faced while building it, like response diversity and scalability. We also introduce a new method for semantic clustering of user-generated content that requires only a modest amount of explicitly labeled data.
Comparative proteomic analysis of human mesenchymal and embryonic stem cells: Towards the definition of a mesenchymal stem cell proteomic signature (2009)

Mesenchymal stem cells (MSC) are adult multipotential progenitors which have a high potential in regenerative medicine. They can be isolated from different tissues throughout the body and their homogeneity in terms of phenotype and differentiation capacities is a real concern. To address this issue, we conducted a 2-DE gel analysis of mesenchymal stem cells isolated from bone marrow (BM), adipose tissue, synovial membrane and umbilical vein wall. We confirmed that BM and adipose tissue derived cells were very similar, which argue for their interchangeable use for cell therapy. We also compared human mesenchymal to embryonic stem cells and showed that umbilical vein wall stem cells, a neo-natal cell type, were closer to BM cells than to embryonic stem cells. Based on these proteomic data, we could propose a panel of proteins which were the basis for the definition of a mesenchymal stem cell proteomic signature.
Erythropoietin Improved Neurologic Outcomes in Newborns With Hypoxic-Ischemic Encephalopathy (2009)

Repeated, low-dose, recombinant human erythropoietin treatment reduced the risk of disability for infants with moderate HIE, without apparent side effects.
Channel formation by antiapoptotic protein Bcl-2 (1997)

Bcl-2 is the prototypical member of a large family of apoptosis-regulating proteins, consisting of blockers and promoters of cell death. The three-dimensional structure of a Bcl-2 homologue, Bcl-XL, suggests striking similarity to the pore-forming domains of diphtheria toxin and the bacterial colicins, prompting exploration of whether Bcl-2 is capable of forming pores in lipid membranes. Using chloride efflux from KCl-loaded unilamellar lipid vesicles as an assay, purified recombinant Bcl-2 protein exhibited pore-forming activity with properties similar to those of the bacterial toxins, diphtheria toxin, and colicins, i.e., dependence on low pH and acidic lipid membranes. In contrast, a mutant of Bcl-2 lacking the two core hydrophobic alpha-helices (helices 5 and 6), predicted to be required for membrane insertion and channel formation, produced only nonspecific effects. In planar lipid bilayers, where detection of single channels is possible, Bcl-2 formed discrete ion-conducting, cation-selective channels, whereas the Bcl-2 (Deltah5, 6) mutant did not. The most frequent conductance observed (18 +/- 2 pS in 0.5 M KCl at pH 7.4) is consistent with a four-helix bundle structure arising from Bcl-2 dimers. However, larger channel conductances (41 +/- 2 pS and 90 +/- 10 pS) also were detected with progressively lower occurrence, implying the step-wise formation of larger oligomers of Bcl-2 in membranes. These findings thus provide biophysical evidence that Bcl-2 forms channels in lipid membranes, suggesting a novel function for this antiapoptotic protein.
Prevention of Epstein-Barr (EB) Virus-induced Lymphoma in Cottontop Tamarins by Vaccination with the EB Virus Envelope Glycoprotein gp340 Incorporated into Immune-stimulating Complexes (1988)

Experimental induction of malignant lymphomas can be achieved in the cottontop tamarin by inoculation with Epstein-Barr (EB) virus. This system provides an animal model for assessing the efficacy of vaccine protection against the virus which is intended to reduce the incidence of human tumours associated with EB virus infection, namely endemic Burkitt's lymphoma and undifferentiated nasopharyngeal carcinoma. Cottontop tamarins have been vaccinated with the major envelope glycoprotein of EB virus, gp340, incorporated into immune-stimulating complexes (iscoms) and were thereby protected against a 100% lymphomagenic dose of virus. The gp340 iscoms are highly immunogenic, requiring only a few micrograms of immunogen to induce protective immunity and thus would be a strong candidate for further development as an EB virus vaccine for use in man.
Nano Graphene Application Improving Drilling Fluids Performance (2015)

Abstract Scomi together with the technical partner had developed series of nano graphene engineered product in mass production scale, one of the latest product that had been field trial successfully in the region is a graphene enhanced product that provides superior lubricity and thermal stability to the water based drilling fluids. It is a blend of proprietary surfactants engineered with nano graphene, where graphenes will penetrates into microscopic pores of the tubular metal, crystalized in layers under high pressure, forming a protective film to improve lubricity, prevent bit balling, improve BHA's life span, improve ROP, and most important of all improving fluids' thermal stability. Laboratory performance test with EP/Lubricity Tester indicated 70–80% torque reduction on a water based salt polymer mud system, compared to conventional lubricants of only 30–40% reduction. The product had been field trial in a HTHP onshore well with temperature up to 176°C (349°F), and hard formation reducing the bits' life span to only 2–3 days. During the field trial, it's agreed that 2–3% of the product had improved ROP 125%, actual reaming torque reduction of 20%, bit's life span increased &amp;gt;75%, also noticed by the fluids company Scomi that fluids loss reduction of 30% with 40% polymers concentration reduction compared to planned mud formulation, which are additional benefits observed and yet to be continously monitor in future subsequent field trials. The improvement in drilling performance and bits' life span had reduced operator's operational time and cost. With the success of the first field trial on nano graphene engineered drilling fluids, Company is in the midst of developing series of graphene enhanced product to cater more challenging drilling and production conditions.
Technology Update: Seismic Stimulation: An Eco-Friendly, Effective EOR Alternative (2018)

Technology Update Environmental and economic concerns have led to an increased interest in seismic stimulation as an alternative enhanced oil recovery (EOR) methodology. Seismic stimulation, achievable with the implementation of a single tool, requires significantly lower investments than gas, thermal, and chemical injection methods, while making minimal environmental impact. Applied Seismic Research (ASR), based in McKinney, Texas, has placed more than 200 of its proprietary seismic stimulation tools in more than 50 locations, including fields in Arkansas, California, Canada, Egypt, Kansas, Mexico, Oklahoma, Oman, and Texas. This article will examine the operation of the tool and highlight the EOR results achieved in a variety of formations. What is Seismic Stimulation? Seismic stimulation is the harnessing of low-frequency, high-energy elastic waves to mobilize oil. The method’s origins trace back to the 1950s when it was noticed that natural earthquakes could increase oil production by up to 45%. Attempts in the 1980s to duplicate earthquake effects by the use of surface vibrators above a targeted zone were largely unsuccessful and commercially unviable. Later development of tools that generate subsurface shockwaves proved more promising. ASR received the first patent for its technology in 2000. A “Greener” EOR Method In-situ seismic stimulation may be one of the greenest EOR options available. The method doesn’t involve injecting any amount of potentially harmful fluids or chemicals into the earth or dealing with the byproducts created by other EOR methods. In fact, it is implemented in a completely closed wellbore having no hydraulic communication with the formation. It can offer a measure of relief to field operators grappling with issues including managing groundwater contamination from harmful chemicals; dealing with the treatment, transport, and disposal of high volumes of contaminated wastewater; and/or handling the environmental consequences of the intense energy and carbon use occasioned by thermal injections. How the Tool Works The seismic stimulation tool (Fig. 1), which has a lifespan of up to 1.5 years and typically requires no maintenance, is powered by a conventional pumping unit and can be installed in abandoned wells at depths from 700 to 10,000 ft. It is relatively easy to transport to wellsites, coming in three preassembled segments in a single crate. The tool is installed into an abandoned wellbore, connected to a rod string and then to a pumping unit. The pumping unit drives movement of three plungers within the tool in unison. The lowest plunger contains a traveling valve to bring in fluids. When the plunger reaches the top of its stroke, it exits the lower barrel to release highly compressed fluids, creating the elastic waves.
The role of IL-7 in Immunity and Cancer (2017)

Interleukin-7 (IL-7) is a cytokine that has been known since long in immunology, mainly regarding its effects on T-cells and B-cells. IL-7 has been demonstrated to be necessary for both B-cell and T-cell proliferation and lack of IL-7 causes immature immune cell arrest. Interestingly, in recent years, certain studies have strongly suggested that the role of IL-7 is far beyond the field of immunology, it might have direct or indirect effect on cancer. This review aims to summarize the role of IL-7 in immunity and its role in the pathogenesis of neoplasia.
Energetic Nanoporous Silicon Devices (2009)

Nanoporous energetic silicon is a promising new material for on-chip integration of energetic materials. We demonstrate several advances in the integration of nanoporous energetic silicon, including monolithic integration of a hotwire initiator on nanoporous energetic silicon, with 2.8-V ignition. We also demonstrate lithographically patterned arrays of energetic devices that are independently addressable through integrated initiators with no sympathetic ignition. Monolithic integration of the energetic material with a surface micromachined microelectromechanical systems sensor is also shown. The performance and failure mechanisms of the hotwire initiator are examined, and preliminary measurements of the thrust and propagation velocity are reported.