gebhart/patrepeval huggingface dataset:
Efficient primer design algorithms (2001)

The reference point method was found to be tractable for trading-off between deviations from ideal values of all the criteria. Some criteria computations are based on dynamic programs with value iteration whose run time can be bounded by a low-degree polynomial. For designing standard PCR primers, the scheme offers in a relative gain in computing speed of up to 50: 1 over ad-hoc computational methods. Single PCR primer pairs have been used as model systems in order to simplify the quantization of the computational acceleration factors. The program has been structured so as to facilitate the analysis of large numbers of primer pairs with minor modifications. The scheme significantly increases primer design throughput which in turn facilitates the use of oligonucleotides in a wide range of applications including: multiplex PCR and other nucleic acid-based amplification systems, as well as in zip code targeting, oligonucleotide microarrays and nucleic acid-based nanoengineering.
BiolD: a multimodal biometric identification system (2000)

Biometric identification systems, which use physical features to check a person's identity, ensure much greater security than password and number systems. Biometric features such as the face or a fingerprint can be stored on a microchip in a credit card, for example. A single feature, however, sometimes fails to be exact enough for identification. Another disadvantage of using only one feature is that the chosen feature is not always readable. Dialog Communication Systems (DCS AG) developed BioID, a multimodal identification system that uses three different features-face, voice, and lip movement-to identify people. With its three modalities, BioID achieves much greater accuracy than single-feature systems. Even if one modality is somehow disturbed-for example, if a noisy environment drowns out the voice-the ether two modalities still lead to an accurate identification. This article goes into detail about the system functions, explaining the data acquisition and preprocessing techniques for voice, facial, and lip imagery data. The authors also explain the classification principles used for optical features and the sensor fusion options (the combinations of the three results-face, voice, lip movement-to obtain varying levels of security).
Activation of Ras/Erk Pathway by a Novel MET-interacting Protein RanBPM (2002)

MET is a receptor protein-tyrosine kinase (RPTK) for hepatocyte growth factor (HGF), which is a multifunctional cytokine controlling cell growth, morphogenesis, and motility. MET overexpression has been identified in a variety of human cancers. Oncogenic missense mutations of the tyrosine kinase domain of the<i>MET</i> gene have been identified in human papillary renal cell carcinomas. In this study, RanBPM, also known as RanBP9, is identified as a novel interacting protein of MET through yeast two-hybrid screen. RanBPM contains a conserved SPRY (repeats in splA andRyR) domain. We demonstrate that RanBPM can interact with MET <i>in vitro</i> and <i>in vivo</i>, and the interaction can be strengthened by HGF stimulation. RanBPM interacts with the tyrosine kinase domain of MET through its SPRY domain. We show that RanBPM can induce GTP-Ras association and Erk phosphorylation and elevate serum response element-luciferase (SRE-LUC) expression, indicating that RanBPM can activate the Ras-Erk-SRE pathway. We demonstrate that RanBPM, which itself is not a guanine exchange protein, stimulates Ras activation by recruiting Sos. On the cellular level, A704 cells, a human renal carcinoma cell line, transfected with RanBPM exhibit increased migration ability. Our data suggest that RanBPM, functioning as an adaptor protein for the MET tyrosine kinase domain, can augment the HGF-MET signaling pathway and that RanBPM overexpression may cause constitutive activation of the Ras signaling pathway.
Evaluation of Myofibroblasts By Expression of Alpha Smooth Muscle Actin: A Marker in Fibrosis, Dysplasia and Carcinoma (2014)

Myofibroblasts play a role in fibrosis, as was seen in OSMF. Activated myofibroblasts secrete proteolytic enzymes and cause matrix degradation, which is instrumental in cancer cell invasion and metastasis. Further studies in which the myofibroblasts are targetted, may help in providing therapeutic regimens in fibrosis, dysplasia and cancer.
Removing Structural Disorder from Oriented TiO2 Nanotube Arrays:  Reducing the Dimensionality of Transport and Recombination in Dye-Sensitized Solar Cells (2007)

We report on the influence of morphological disorder, arising from bundling of nanotubes (NTs) and microcracks in films of oriented TiO2 NT arrays, on charge transport and recombination in dye-sensitized solar cells (DSSCs). Capillary stress created during evaporation of liquids from the mesopores of dense TiO2 NT arrays was of sufficient magnitude to induce bundling and microcrack formation. The average lateral deflection of the NTs in the bundles increased with the surface tension of the liquids and with the film thicknesses. The supercritical CO2 drying technique was used to produce bundle-free and crack-free NT films. Charge transport and recombination properties of sensitized films were studied by frequency-resolved modulated photocurrent/photovoltage spectroscopies. Transport became significantly faster with decreased clustering of the NTs, indicating that bundling creates additional pathways via intertube contacts. Removing such contacts alters the transport mechanism from a combination of one and three dimensions to the expected one dimension and shortens the electron-transport pathway. Reducing intertube contacts also resulted in a lower density of surface recombination centers by minimizing distortion-induced surface defects in bundled NTs. A causal connection between transport and recombination is observed. The dye coverage was greater in the more aligned NT arrays, suggesting that reducing intertube contacts increases the internal surface area of the films accessible to dye molecules. The solar conversion efficiency and photocurrent density were highest for DSSCs incorporating films with more aligned NT arrays owing to an enhanced light-harvesting efficiency. Removing structural disorder from other materials and devices consisting of nominally one-dimensional architectures (e.g., nanowire arrays) should produce similar effects.
In Vivo Tumor Targeting and Imaging with Engineered Trivalent Antibody Fragments Containing Collagen-Derived Sequences (2009)

There is an urgent need to develop new and effective agents for cancer targeting. In this work, a multivalent antibody is characterized in vivo in living animals. The antibody, termed "trimerbody", comprises a single-chain antibody (scFv) fragment connected to the N-terminal trimerization subdomain of collagen XVIII NC1 by a flexible linker. As indicated by computer graphic modeling, the trimerbody has a tripod-shaped structure with three highly flexible scFv heads radially outward oriented. Trimerbodies are trimeric in solution and exhibited multivalent binding, which provides them with at least a 100-fold increase in functional affinity than the monovalent scFv. Our results also demonstrate the feasibility of producing functional bispecific trimerbodies, which concurrently bind two different ligands. A trimerbody specific for the carcinoembryonic antigen (CEA), a classic tumor-associated antigen, showed efficient tumor targeting after systemic administration in mice bearing CEA-positive tumors. Importantly, a trimerbody that recognizes an angiogenesis-associated laminin epitope, showed excellent tumor localization in several cancer types, including fibrosarcomas and carcinomas. These results illustrate the potential of this new antibody format for imaging and therapeutic applications, and suggest that some laminin epitopes might be universal targets for cancer targeting.
Towards Enforcement of the EU GDPR: Enabling Data Erasure (2018)

With the emergence of the Internet of Things (IoT), an increasing need for preserving the privacy of personal data has been realized. In this context, the EU has recently published the general data protection regulation (GDPR), which ensures strengthening of the privacy rights of the data subjects concerning their personal data. In this paper, we present the importance of having a holistic solution aimed towards the enforcement of the GDPR. As a first step towards the enforcement of the GDPR, we present the research challenges in facilitating the erasure of data as per the right to erasure. We also propose the envisaged technical solutions to work through the challenges.
Safety-modified episomal vectors for human gene therapy (1997)

The effectiveness of ongoing gene therapy trials may be limited by the expression characteristics of viral and plasmid-based vectors. To enhance levels of heterologous gene expression, we have developed a safety-modified episomal expression vector that replicates extrachromosomally in human cells. This vector system employs a simian virus 40 (SV40) large T antigen mutant (107/402-T) that is deficient in binding to human tumor suppressor gene products, including p53, retinoblastoma, and p107, yet retains replication competence. These SV40-based episomes replicate to thousands of copies by 2-4 days after gene transfer in multiple types of human cell lines, with lower activity in hamster cells, and no detectable activity in dog, rat, and murine cell lines. Importantly, 107/402-T has enhanced replication activity compared with wild-type T antigen; this finding may be due, in part, to the inability of p53 and retinoblastoma to inactivate 107/402-T function. We demonstrate that the level and duration of 107/402-T expression regulates the observed episomal copy number per cell. Compared with standard plasmid constructs, episomes encoding 107/402-T yield approximately 10- to 100-fold enhanced levels of gene expression in unselected populations of transient transfectants. To determine if 107/402-T-based episomes replicate extrachromosomally in vivo, tumor explants in nude mice were directly injected with liposome/DNA complexes. Using a PCR-based assay, we demonstrate that SV40-based episomes replicate in human cells after direct in vivo gene transfer. These data suggest that safety-modified SV40-based episomes will be effective for cancer gene therapy because high level expression of therapeutic genes in transient transfectants should yield enhanced tumor elimination.
PRELIMINARY RESULTS OF A RANDOMIZED TRIAL OF ADJUVANT IMMUNOTHERAPY IN PATIENTS WITH MALIGNANT MELANOMA WHO HAVE LYMPH NODE METASTASES (1978)

This study evaluates the effect of adjuvant immunotherapy with BCG alone, or combined with melanoma cell vaccine, on the recurrence and survival rates of patients with metastatic melanoma in the regional lymph nodes who were treated by lymphadenectomy. Patients were prospectively randomized and stratified on the basis of age, sex, site of primary tumour, and clinical estimate of the regional nodes. During the past four years, 134 patients were entered into this trial, and to date, the incidence of recurrence among the two arms mentioned and the control arm is not significantly different; however, patients receiving BCG alone had longer survival than those in either the tumour cell vaccine or control groups. The improved survival in the BCG-only group was found to be due to the fact that patients survived longer with their recurrent disease than the patients in the other two groups. At the present time, these differences do not appear to be significant enough to justify routine adjuvant immunotherapy in patients with melanoma metastatic to regional nodes. Longer follow-up will be necessary to evaluate the role of adjuvant immunotherapy of Stage II melanoma.
Ordered phase sequence testing in slm for improved blind detection (2005)

Selected mapping (SLM) is a promising technique to reduce the high peak-to-average power ratio (PAR) of orthogonal frequency division multiplexing (OFDM) signals. In this paper we present an altered form of SLM that tests phase sequences in an ordered manner and ceases testing when the PAR is below a threshold. Aside from having a reduced computational complexity compared to traditional SLM, our modification allows for maximum a posteriori (MAP) blind detection of SLM phase mappings in the receiver. MAP detection is possible because, by testing the phase sequences in an ordered way, different phase mappings have different probabilities of occurrence. We derive the MAP metric as well as a lower-complexity approximation to the MAP metric.
Analysis of Agrobacterium tumefaciens virulence mutants in leaf discs. (1986)

The leaf disc transformation system provides a simple means to score expression of various T-DNA markers within days of infection by Agrobacterium tumefaciens as well as long-term selection for growth of transformed callus and shoots. In this report, we describe the application of this system to evaluation of marker transfer and integration in a comprehensive set of defined avirulent mutants of A. tumefaciens. We conclude that virC is not essential when the T-DNA is present on a binary vector. The most likely explanation for this is that the virC gene product is involved in generation of a T-DNA intermediate.
All-optical switching of a single resonance in silicon ring resonators (2011)

We theoretically investigate a wavelength-selective all-optical switch using Raman-induced loss in a silicon resonator add-drop filter. We show that picojoule control pulses can selectively modulate and "erase" a single cavity resonance from full extinction to greater than 97% transmission while leaving adjacent resonances undisturbed. Full switching is achievable in less than 300 ps with only a few hundred femtojoule energy dissipation. This represents, to our knowledge, the first scheme for selective modulation of single resonances of an optical cavity.
Requirement for CD4+ cells in resistance to Pneumocystis carinii pneumonia in mice. (1990)

The importance of CD4+ cells in resistance to Pneumocystis carinii (PC) in PC-susceptible severe combined immunodeficient (SCID) mice that were made resistant to PC by immunocompetent spleen cell transfer, and in conventional PC-resistant mice, was investigated. SCID mice with naturally acquired PC pneumonia (PCP) were given infusions of spleen cells from immunocompetent donors. This reconstitution caused the recipients to resolve their PCP. Treatment of reconstituted SCID mice with anti-CD4 monoclonal antibodies (mAbs) to deplete them of CD4+ cells eliminated their ability to resolve PCP, whereas treating them with anti-CD8 mAb to deplete CD8+ cells had no effect. The findings indicate, therefore, that resistance to PCP in immunologically reconstituted SCID mice is dependent on CD4+ cells. To determine whether CD4+ cells enable conventional mice to resist PCP, B6D2 mice were treated with anti-CD4 mAb to deplete them of CD4+ cells in an attempt to induce PCP. After 10-11 wk of treatment, these mice developed progressive PCP. Taken together, these results indicate that loss of CD4+ cells predisposes mice to PC infection.
Dispersion polymerization of styrene in polar solvents: Effect of reaction parameters on microsphere surface composition and surface properties, size and size distribution, and molecular weight (1996)

Polystyrene microspheres were prepared by dispersion polymerization of styrene in a mixture of ethanol and 2-methoxy ethanol. Surface characterization of the formed particles was performed by x-ray photoelectron spectroscopy and critical surface tension measurements. The influence of different reaction parameters, i.e., monomer concentration, stabilizer type (polyvinylpyrrolidone, copolymers of vinylpyrrolidone and vinylacetate and polyvinylace tate), stabilizer concentration and molecular weight, and initiator type and concentration, on the molecular weight and on the size and size distribution of the formed polystyrene microspheres was investigated. The correlation between the surface composition and wett ability properties of the particles surface and their size and size distribution was also demonstrated. © 1996 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 34:1857–1871, 1996
An update on emerging drugs for Hodgkin lymphoma (2014)

Besides improving the prognosis of relapsed patients, new drugs should be used to replace the most toxic compounds in first-line therapy to reduce acute and long-term toxicities of the treatment.
Caprospinol: moving from a neuroactive steroid to a neurotropic drug (2009)

In search of new drugs for Alzheimer's disease, we departed from the classic concepts and investigated the ability of normal and Alzheimer's disease brain to convert cholesterol to steroids, otherwise known as neurosteroids. We identified 22R-hydroxycholesterol to be present in much lower levels in the hippocampus and frontal cortex of Alzheimer's disease than in tissue from age-matched controls. 22R-hydroxycholesterol was shown to protect against beta-amyloid (A beta(42))-induced neurotoxicity and block the formation of A beta oligomers. In search of a 22R-hydroxycholesterol stable analog, we identified the naturally occurring heterospirostenol, (22R,25R)-20 alpha-spirost-5-en-3beta-yl hexanoate (caprospinol). The mechanism of action underlying the neuroprotective properties of caprospinol involves, first, the ability of the compound to bind A beta(42) and, second, its interaction with components of the mitochondria respiratory chain. Samaritan Pharmaceuticals is developing caprospinol as a disease-modifying drug for the treatment of Alzheimer's disease. Samaritan Pharmaceuticals filed for an Investigational New Drug application with the FDA in 2006. The pharmacokinetic and pharmacodynamic parts of the application were found satisfactory, and the FDA has requested that additional information is submitted in support of caprospinol's safety prior to initiating the Phase I clinical study.
Codanin-1 mutations in congenital dyserythropoietic anemia type 1 affect HP1α localization in erythroblasts (2011)

Congenital dyserythropoietic anemia type 1 (CDA-1), a rare inborn anemia characterized by abnormal chromatin ultrastructure in erythroblasts, is caused by abnormalities in codanin-1, a highly conserved protein of unknown function. We have produced 3 monoclonal antibodies to codanin-1 that demonstrate its distribution in both nucleus and cytoplasm by immunofluorescence and allow quantitative measurements of patient and normal material by Western blot. A detailed analysis of chromatin structure in CDA-1 erythroblasts shows no abnormalities in overall histone composition, and the genome-wide epigenetic landscape of several histone modifications is maintained. However, immunofluorescence analysis of intermediate erythroblasts from patients with CDA-1 reveals abnormal accumulation of HP1α in the Golgi apparatus. A link between mutant codanin-1 and the aberrant localization of HP1α is supported by the finding that codanin-1 can be coimmunoprecipitated by anti-HP1α antibodies. Furthermore, we show colocalization of codanin-1 with Sec23B, the protein defective in CDA-2 suggesting that the CDAs might be linked at the molecular level. Mice containing a gene-trapped Cdan1 locus demonstrate its widespread expression during development. Cdan1(gt/gt) homozygotes die in utero before the onset of primitive erythropoiesis, suggesting that Cdan1 has other critical roles during embryogenesis.
Probiotics for the treatment ofClostridium difficileassociated disease (2013)

The purpose of this review paper is to update the current and potential future role of probiotics for Clostridium difficile-associated disease (CDAD). Included in this review, is an update on the testing of newer probiotics (e.g., Bacillus coagulans GBI-30, 6086) in animal models of CDAD. There is a focus on the modulation of signal transduction pathways (i.e., transcription factors like cAMP response element-binding, activator protein 1, and nuclear factor kappa B), as well as the inhibition of certain kinases (e.g., p38 mitogen activated protein kinases) by probiotics. Inhibition of signal transduction by probiotics, such as Saccharomyces boulardii, result in multiple effects on intestinal fluid secretion, neutrophil influx into the colon, inflammation, and colonocyte apoptosis that may positively impact CDAD. Recent clinical approaches with probiotics, for the prevention of primary and recurrent CDAD, are also summarized in this review paper. Future directions for the treatment of CDAD by probiotics are also mentioned in this review. In particular, the use of multi-strain probiotic formulations such as Ecologic(®) AAD and VSL #3(®) may represent a rationale pharmacological approach, particularly as adjunctive therapies for CDAD. Understanding the mechanistic basis of CDAD, and how probiotics interfere at ceratin steps in the pathogenic process, may also present the opportunity to design other multi-strain probiotics that could have a future impact on CDAD.
Binding of Bacterial Peptidoglycan to CD14 (1998)

The hypothesis that soluble peptidoglycan (sPGN, a macrophage-activator from Gram-positive bacteria) binds to CD14 (a lipopolysaccharide (LPS) receptor) was tested. sPGN specifically bound to CD14 in the following three assays: binding of soluble 32P-CD14 (sCD14) to agarose-immobilized sPGN, enzyme-linked immunosorbent assay, and photoaffinity cross-linking. sCD14 also specifically bound to agarose-immobilized muramyl dipeptide or GlcNAc-muramyl dipeptide but not to PGN pentapeptide. Binding of sCD14 to both sPGN and ReLPS (where ReLPS is LPS from Salmonella minnesota Re 595) was competitively inhibited by unlabeled sCD14, 1-152 N-terminal fragment of sCD14, sPGN, smooth LPS, ReLPS, lipid A, and lipoteichoic acid but not by dextran, dextran sulfate, heparin, ribitol teichoic acid, or soluble low molecular weight PGN fragments. Binding of sCD14 to sPGN was slower than to ReLPS but of higher affinity (KD = 25 nM versus 41 nM). LPS-binding protein (LBP) increased the binding of sCD14 to sPGN by adding another lower affinity KD and another higher Bmax, but for ReLPS, LBP increased the affinity of binding by yielding two KD with significantly higher affinity (7.1 and 27 nM). LBP also enhanced inhibition of sCD14 binding by LPS, ReLPS, and lipid A. Binding of sCD14 to both sPGN and ReLPS was inhibited by anti-CD14 MEM-18 mAb, but other anti-CD14 mAbs showed differential inhibition, suggesting conformational binding sites on CD14 for sPGN and LPS, that are partially identical and partially different.
Betahistine Effects on Cochlear Blood Flow: From the Laboratory to the Clinic (2000)

The development of laser Doppler flowmetry techniques has contributed greatly to the study of cochlear blood flow (CBF). In animal models, intravenous betahistine dihydrochloride clearly increased CBF in a dose-dependent manner. This effect was greater in the cochlear vasculature than in the systemic vascular bed. The effects of betahistine were blocked by the alpha 2-antagonist idazoxan, thus suggesting an interaction between histaminergic and presynaptic adrenergic receptors. This was further supported by studies investigating the effects of electrical stimulation on CBF. Local (round window membrane) application of betahistine did not affect CBF, but had a non-specific effect on cochlear electrophysiology. This indicates that the receptors for betahistine vascular effects in the inner ear are most likely located in the modiolar artery. More recently, laser Doppler flowmetry techniques have been applied to human subjects. It has been shown that intratympanic application of adrenaline affects CBF and that this blood flow is under vigorous sympathetic control. Electrical stimulation has also been used to obtain measures of dynamic responsiveness in human subjects. This results in an increase in CBF, which is dependent on the intensity of the stimulation. Preliminary evidence indicates that this procedure can provide a standardized measure of the dynamic properties of CBF and may provide a means to differentially identify patients with compromised vasculature.