gebhart/patrepeval huggingface dataset:
Vascular Endothelial Growth Factor and Vascular Endothelial Growth Factor Receptor Inhibitors as Anti-Angiogenic Agents in Cancer Therapy (2007)

New blood vessel formation (angiogenesis) is fundamental to the process of tumor growth, invasion, and metastatic dissemination. The vascular endothelial growth factor (VEGF) family of ligands and receptors are well established as key regulators of these processes. VEGF is a glycoprotein with mitogenic activity on vascular endothelial cells. Specifically, VEGF-receptor pathway activation results in signaling cascades that promote endothelial cell growth, migration, differentiation, and survival from pre-existing vasculature. Thus, the role of VEGF has been extensively studied in the pathogenesis and angiogenesis of human cancers. Recent identification of seven VEGF ligand variants (VEGF [A-F], PIGF) and three VEGF tyrosine kinase receptors (VEGFR- [1-3]) has led to the development of several novel inhibitory compounds. Clinical trials have shown inhibitors to this pathway (anti-VEGF therapies) are effective in reducing tumor size, metastasis and blood vessel formation. Clinically, this may result in increased progression free survival, overall patient survival rate and will expand the potential for combinatorial therapies. Having been first described in the 1980s, VEGF patenting activity since then has focused on anti-cancer therapeutics designed to inhibit tumoral vascular formation. This review will focus on patents which target VEGF-[A-F] and/or VEGFR-[1-3] for use in anti-cancer treatment.
Clustering Algorithm Using Hashing in Classification of Multispectral Satellite Images (2000)

Clustering is the process of partitioning a data set into meaningful clusters. As the data to process increase, a laster algorithm is required than ever. In this paper, we propose a clustering algorithm to partition a multispectral remotely sensed image data set into several clusters using a hash search algorithm. The processing time of our algorithm is compared with that of clusters algorithm using other speed-up concepts. The experiment results are compared with respect to the number of bands, the number of clusters and the size of data. It is also showed that the processing time of our algorithm is shorter than that of cluster algorithms using other speed-up concepts when the size of data is relatively large.
Ubiquitin genes in trypanosomatidae. (1988)

A ubiquitin encoding cDNA from Trypanosoma cruzi, the protozoan cause of Chagas' disease, was isolated by immunoscreening a lambda gt11 expression library with serum from a mouse chronically infected with this parasite. The cDNA encodes a precursor protein consisting of four tandem repeats of ubiquitin differing from that of Saccharomyces cerevisiae in four positions, followed by an unrelated 52-amino acid tail containing a putative metal and nucleic acid binding domain. Southern and Northern blots of DNA and RNA from various strains of T. cruzi and from several African trypanosome and Leishmania isolates revealed dramatic differences in the numbers and sizes of ubiquitin genes and transcripts. One of the T. cruzi isolates examined has as many as 10 ubiquitin genes, while a strain of Leishmania donovani appears to have only 1. Forty or more tandemly arranged ubiquitin coding repeats are present in some genes, while others have only two or three. Evidence for stage-specific expression of a ubiquitin transcript was found in one strain, but no stress-induced changes in the pattern of transcripts were detected in the one isolate examined. Thus the cellular requirements for ubiquitin in trypanosomatids can be supplied by diversely organized genes containing highly variable numbers of ubiquitin coding repeats.
Enzyme therapy for Pompe disease with recombinant human α‐glucosidase from rabbit milk (2001)

Pompe disease is a metabolic myopathy caused by deficiency of lysosomal acid alpha-glucosidase. In this report we review the first 36 weeks of a clinical study on the safety and efficacy of enzyme therapy aimed at correcting the deficiency. Four patients with infantile Pompe disease were enrolled. They received recombinant human alpha-glucosidase from transgenic rabbit milk. The product is generally well tolerated and reaches the primary target tissues. Normalization of alpha-glucosidase activity in skeletal muscle was obtained and degradation of PAS-positive material was seen in tissue sections. The clinical condition of all patients improved. The effect on heart was most significant, with an impressive reduction of the left ventricular mass index (LVMI). Motor function improved. The positive preliminary results stimulate continuation and extension of efforts towards the realization of enzyme therapy for Pompe disease.
Leukocytoclastic Vasculitis and Polyarthritis Associated with Mycoplasma pneumoniae Infection (1997)

[3] and tinea cruris In a survey of the prevalence of dermatophytes in New Zealand, E. floccosum was the second commonest 1. Demidovich CW, Kornfeld BW, Gentry RH, Fitzpatrick JE. Deep dermatocause of tinea cruris and comprised 112 (15%) of all 746 dermatophyte infection with chronic draining nodules in an immunocompromised phytes isolated
APOE4 Allele Disrupts Resting State fMRI Connectivity in the Absence of Amyloid Plaques or Decreased CSF Aβ42 (2010)

Identifying high-risk populations is an important component of disease prevention strategies. One approach for identifying at-risk populations for Alzheimer's disease (AD) is examining neuroimaging parameters that differ between patients, including functional connections known to be disrupted within the default-mode network. We have previously shown these same disruptions in cognitively normal elderly who have amyloid-β (Aβ) plaques [detected using Pittsburgh Compound B (PIB) PET imaging], suggesting neuronal toxicity of plaques. Here we sought to determine if pathological effects of apolipoprotein E ε4 (APOE4) genotype could be seen independent of Aβ plaque toxicity by examining resting state fMRI functional connectivity (fcMRI) in participants without preclinical fibrillar amyloid deposition (PIB-). Cognitively normal participants enrolled in longitudinal studies (n = 100, mean age = 62) who were PIB- were categorized into those with and without an APOE4 allele and studied using fcMRI. APOE4 allele carriers (E4+) differed significantly from E4- in functional connectivity of the precuneus to several regions previously defined as having abnormal connectivity in a group of AD participants. These effects were observed before any manifestations of cognitive changes and in the absence of brain fibrillar Aβ plaque deposition, suggesting that early manifestations of a genetic effect can be detected using fcMRI and that these changes may antedate the pathological effects of fibrillar amyloid plaque toxicity.
Structural basis for improved efficacy of therapeutic antibodies on defucosylation of their Fc glycans (2011)

Removal of the fucose residue from the N-glycans of the Fc portion of immunoglobulin G (IgG) results in a dramatic enhancement of antibody-dependent cellular cytotoxicity (ADCC) through improved affinity for Fcγ receptor IIIa (FcγRIIIa). Here, we present the 2.2-Å structure of the complex formed between nonfucosylated IgG1-Fc and a soluble form of FcγRIIIa (sFcγRIIIa) with two N-glycosylation sites. The crystal structure shows that one of the two N-glycans of sFcγRIIIa mediates the interaction with nonfucosylated Fc, thereby stabilizing the complex. However, fucosylation of the Fc N-glycans inhibits this interaction, because of steric hindrance, and furthermore, negatively affects the dynamics of the receptor binding site. Our results offer a structural basis for improvement in ADCC of therapeutic antibodies by defucosylation.
In situ SEM and ToF‐SIMS analysis of IgG conjugated gold nanoparticles at aqueous surfaces (2013)

In this study, we report new results of in situ study of 5 nm goat anti‐mouse IgG gold nanoparticles in a novel portable vacuum compatible microfluidic device using scanning electron microscope (SEM) and time‐of‐flight secondary ion mass spectrometry (ToF‐SIMS). The unique feature of the liquid flow cell is that the detection window is open to the vacuum allowing direct probing of the liquid surface. The flow cell is composed of a silicon nitride (SiN) membrane and polydimethylsiloxane (PDMS), and it is fully compatible with vacuum operations for surface analysis. The aperture can be drilled through the 100 nm SiN membrane using a focused ion beam. Characteristic signals of the conjugated gold nanoparticles were successfully observed through the aperture by both energy‐dispersive X‐ray spectroscopy (EDX) in SEM and ToF‐SIMS. Comparison was also made among wet samples, dry samples, and liquid sample in the flow cell using SEM/EDX. Stronger gold signal can be observed in our novel portable device by SEM/EDX compared with the wet or dry samples, respectively. Our results indicate that analyses of the nanoparticle components are better made in their native liquid environment. This is made possible using our unique microfluidic flow cell. Copyright © 2013 John Wiley &amp; Sons, Ltd.
Impact of moisture on thermally induced denaturation and decomposition of lyophilized bovine somatotropin (1995)

The nonisothermal transitions of lyophilized recombinant bovine somatotropin (rbSt) as seen via differential scanning calorimetry were evaluated with respect to moisture content. The transition peak temperature of rbSt decreased with increasing moisture from 161 degrees C in the dry state to a plateau of 65 degrees C at 28% moisture, which is similar to that of rbSt in solution. Using high performance liquid chromatography, this irreversible endothermic transition consisted primarily of unfolding, hydrophobic aggregation, and some covalent modifications. In the dry state, covalent modifications, including polymerization into compounds of higher molecular weight, were more prominent, while in the presence of moisture, hydrophobic aggregation was most prominent. The irreversibility and scan rate dependence of the endothermic phenomena supports the kinetic nature of the transition rather than a simple equilibrium between globular and unfolded states. The apparent activation energy for the net transition (i.e., unfolding, hydrophobic aggregation, and covalent modifications) was 57 kcal/mol for rbSt at 9.9% moisture. The observed enthalpy of the transition increased, decreased, then approximately leveled off as a function of increasing moisture content. This can be explained by the increasingly significant contribution of the exothermic aggregation at higher moisture contents.
Novel Therapies Based on Cationic Antimicrobial Peptides (2006)

Cationic antimicrobial peptides serve as critical defense molecules protecting the host from invading bacteria, viruses and fungi. These antimicrobial peptides are widely distributed in nature and in vertebrates they have been localized to numerous tissues and cells. Cationic antimicrobial peptides can be expressed constitutively or under certain circumstances they can be induced in response to infection, inflammatory mediators, and cytokines. Although, their original and primary function was believed to be antimicrobial, it is now becoming clear that these antimicrobial peptides have a wide repertoire of functions with interesting ramifications on the immune system that are not solely antimicrobial. An area of active research is the determination of the mechanism(s) of action of antimicrobial peptides which have yet to be clarified. However, current consensus is that the mechanism is sufficiently different from conventional antibiotics that the development of resistance could be remote. Their broad spectrum activity, low potential to induce resistance and diverse functions make antimicrobial peptides an attractive family of compounds that have potential to be developed as therapeutics for treating certain infections.
Steroid Receptor Regulation of Epidermal Growth Factor Signaling through Src in Breast and Prostate Cancer Cells: Steroid Antagonist Action (2005)

Under conditions of short-term hormone deprivation, epidermal growth factor (EGF) induces DNA synthesis, cytoskeletal changes, and Src activation in MCF-7 and LNCaP cells. These effects are drastically inhibited by pure estradiol or androgen antagonists, implicating a role of the steroid receptors in these findings. Interestingly, EGF triggers rapid association of Src with androgen receptor (AR) and estradiol receptor alpha (ERalpha) in MCF-7 cells or ERbeta in LNCaP cells. Here, we show that, through EGF receptor (EGFR) and erb-B2, EGF induces tyrosine phosphorylation of ER preassociated with AR, thereby triggering the assembly of ER/AR with Src and EGFR. Remarkably, experiments in Cos cells show that this complex stimulates EGF-triggered EGFR tyrosine phosphorylation. In turn, estradiol and androgen antagonists, through the Src-associated receptors, prevent Src activation by EGF and heavily reduce EGFR tyrosine phosphorylation and the subsequent multiple effects, including DNA synthesis and cytoskeletal changes in MCF-7 cells. In addition, knockdown of ERalpha or AR gene by small interfering RNA (siRNA) almost abolishes EGFR tyrosine phosphorylation and DNA synthesis in EGF-treated MCF-7 cells. The present findings reveal that steroid receptors have a key role in EGF signaling. EGFR tyrosine phosphorylation, depending on Src, is a part of this mechanism. Understanding of EGF-triggered growth and invasiveness of mammary and prostate cancer cells expressing steroid receptors is enhanced by this report, which reveals novel aspects of steroid receptor action.
The aortic valve blood supply. (2000)

The presence of a vasculature suggests that the metabolic activity of the cusp is greater than can be supported by diffusion from the cusp surface alone. The absence of functioning vessels might explain the failure associated with cryopreserved implants and may play a role in the durability problems faced by bioprosthetic valves. It will also be important to consider the role of this intrinsic circulation with the advent of tissue-engineered valves.
Synthesis and Characterization of Crosslinked Polymers for Biomedical Composites (1988)

Abstract Three kinds of low molecular weight unsaturated polyesters containing carbon-carbon double bonds were synthesized by the reaction of poly (ε-caprolactone) diol or D,L-lactide and glycolic acid with maleic anhydride or fumaric acid. These functionalized polymers were thermally crosslinked in the presence of radical initiator to prepare the crosslinked polymers available as a matrix resin for biomedical composites. Hydrolysis of the crosslinked polyesters was investigated in buffer solution at 37°C.
Recent trends in non‐viral vector‐mediated gene delivery (2009)

Nucleic acids-based next generation biopharmaceuticals (i.e., pDNA, oligonucleotides, short interfering RNA) are potential pioneering materials to cope with various incurable diseases. However, several biological barriers present a challenge for efficient gene delivery. On the other hand, developments in nanotechnology now offer numerous non-viral vectors that have been fabricated and found capable of transmitting the biopharmaceuticals into the cell and even into specific subcellular compartments like mitochondria. This overview illustrates cellular barriers and current status of non-viral gene vectors, i.e., lipoplexes, liposomes, polyplexes, and nanoparticles, to relocate therapeutic DNA-based nanomedicine into the target cell. Despite the awesome impact of physical methods (i.e., ultrasound, electroporation), chemical methods have been shown to accomplish high-level and safe transgene expression. Further comprehension of barriers and the mechanism of cellular uptake will facilitate development of nucleic acids-based nanotherapy for alleviation of various disorders.
Reducing HPV-Associated Cancer Globally (2012)

Human papillomavirus (HPV)-related cancers are a major worldwide public health concern. Virtually all cervical cancer is HPV related, with 70% caused by HPV16 and -18. Variable proportions of certain noncervical cancers (e.g., anal, vulvar, and oropharyngeal) are HPV related; more than 90% of the HPV-related ones are caused by HPV16, -18. The HPV-related cancers are dominated by cervical cancer in the developing world, where cervical cancer screening is limited. In this setting, widespread uptake of current HPV vaccines by adolescent girls could reduce this cancer's incidence and mortality by approximately two-thirds, with cost-effective screening programs of adult women having the potential to reduce mortality more rapidly. In the industrialized world, some noncervical HPV-related cancers, especially oropharyngeal, are rapidly increasing, and now rival the incidence of cervical cancer, whose rates continue to decline thanks to established cervical screening programs. Therefore, reducing HPV-associated noncervical cancers with HPV vaccination has greater importance in the industrialized world, especially because there are no approved screening programs for these cancers. Preventing the substantial number of noncervical HPV cancers in men will require either "herd" immunity through high-vaccination rates in females or male vaccination. Current HPV vaccination can complement cervical screening in protecting against cervical cancer and may permit the safe reduction of screening intensity in industrialized countries. Second-generation HPV vaccines (active against a broader array of cervical cancer-related HPV types) could prevent an even higher proportion of cervical precancer and cancer and might permit further reductions in screening intensity.
Strand-specific cleavage of mismatch-containing DNA by deoxyinosine 3'-endonuclease from Escherichia coli. (1994)

A deoxyinosine-specific endonuclease, deoxyinosine 3'-endonuclease (Yao, M., Hatahet, Z., Melamede, R. J., and Kow, Y. W. (1994) J. Biol. Chem. 269, 16260-16268), from Escherichia coli was found to recognize mismatches in DNA. Using DNA duplexes containing a unique mismatch, the enzyme was found to hydrolyze the second phosphodiester bond 3' to the mismatch. The cleavage efficiency of deoxyinosine 3'-endonuclease on mismatch-containing DNA was affected by the nature of the mismatches. The cleavage activity was also affected by the sequence context surrounding the mismatches. The presence of a G/C or C/G pair immediately 3' or 5' to the mismatch substantially reduced the ability of the enzyme to nick the mismatch-containing DNA. The presence of two G/C pairs, one 5' and the other 3' to the mismatch, abolishes the ability of the enzyme to recognize the mismatch. Interestingly, deoxyinosine 3'endonuclease showed strong strand specificity on DNA containing mismatches, and only one strand of the mismatch-containing DNA was nicked by the enzyme. This strand specificity of mismatch cleavage was not affected by the nature of the mismatch. Preliminary data suggest that the strand specificity is terminus dependent; the enzyme cleaves the strand with the mismatch closer to its 5' terminus. However, when DNA duplexes containing deoxyinosine were used as substrates, deoxyinosine 3'-endonuclease cleaved exclusively the strand containing deoxyinosine. Deoxyinosine 3'-endonuclease also cleaved single-stranded DNA containing deoxyinosine, but not DNA containing normal deoxynucleotides or deoxynebularine, suggesting the enzyme uses different mechanisms of recognition for deoxyinosine and mismatches in DNA.
Mobile-IP, ad-hoc networking, and nomadicity (2002)

Continuing advances in wireless communications and feature integration into laptop computers are creating the need to allow nomadic users to make network connections to the Internet and with each other with no loss of functionality. This requires new advances in routing protocols and application interfaces. We use Mobile-IP as the basis for providing mobility for nomadic users, and extend it to facilitate additional services for nomadic users both at the network layer and above. As an example of how Mobile-IP can be useful with other protocols at the network layer, we show how Mobile-IP can naturally extend the usefulness of ad-hoc networking. For higher level protocols, we show that, by offering a callback service, Mobile-IP can enable applications to be responsive to changing network conditions. As an example of this technique, we show how service location can benefit from interaction with Mobile-IP. We also mention some other nomadic services which will similarly benefit from a callback service from Mobile-IP.
Droplet-Based Multivolume Digital Polymerase Chain Reaction by a Surface-Assisted Multifactor Fluid Segmentation Approach (2016)

Here we developed the surface-assisted multifactor fluid segmentation (SAMFS), an automated, fast, and flexible approach for generating a two-dimensional droplet array with tunable droplet volumes, for multivolume digital polymerase chain reaction (PCR). The SAMFS was developed based on the combination of robotic liquid handling and surface-assisted droplet generation techniques, where a continuous aqueous stream that flowed out from a capillary probe was segmented and immobilized on hydrophilic micropillars of a microchip into massive oil-covered droplets with the probe rapidly scanning over the microchip. We studied various factors affecting the droplet generation process, including micropillar top area, distance between adjacent micropillars, aqueous stream flow rate, and microchip moving speed, and demonstrated a high droplet generation throughput up to 50 droplets/s and a largest droplet volume adjusting range from 0.25 to 350 nL. The SAMFS approach was adopted to form an oil-covered array of 994 droplets with four different volumes (1.2, 6, 30, and 150 nL droplets) required for multivolume digital PCR within 8 min. The droplet array system was applied in absolute quantification of plasmid DNA under the multivolume digital PCR mode with a dynamic range spanning 4 orders of magnitude, as well as measurement of HER2 expression levels in different breast cancer cell lines. The results are consistent to those obtained by quantitative real-time PCR method, while the present one has higher precision.
Temporal and Spatial Localization of Novel Nuclear Protein NP95 in Mitotic and Meiotic Cells. (2000)

Expression of novel NP95 (nuclear protein, 95 kDa), which contains a leucine zipper motif, a zinc finger motif, a putative cyclin A/E-cyclin-dependent protein kinase 2 phosphorylation site, and retinoblastoma protein-binding motifs, is associated with S-phase progression of mouse cells. It is suppressed during G1 and G2/M phases in normal thymocytes but expressed at a constantly high level irrespective of cell stage in mouse T cell lymphoma cells. NP95 was shown previously to be expressed strongly only in proliferative tissues and cells. In this immunohistochemical study, we demonstrate that NP95 is localized in S-phase nuclei as dot-like foci. Double immunostaining of NP95 and proliferating cell nuclear antigen (PCNA) showed that NP95 was co-localized with PCNA. Construction of three-dimensional images indicated that NP95 was localized with PCNA in replication sites in a somewhat distinct temporal manner. During meiosis, NP95 was present not only in proliferating spermatogonia but also in meiotic spermatocytes and differentiating spermatids which were not proliferating. The possible role of NP95 in mitotic and meiotic cells is discussed.