gebhart/patrepeval huggingface dataset:
Evaluation of recent Protein A stationary phase innovations for capture of biotherapeutics (2018)

We describe a comprehensive evaluation of 12 Protein A stationary phases for capture of biotherapeutics. We first examine the morphological properties of the stationary phases using a variety of orthogonal techniques including electron microscopy, particle sizing, pressure-flow behavior, and isocratic pulse response. A panel of nine proteins spanning a wide range of structures and biochemical properties was then used to assess equilibrium uptake, mass transport, dynamic binding capacity, and elution pH. Process performance and product quality were also examined under realistic bioprocess conditions using clarified mammalian cell culture broth. Equilibrium isotherms were found to be highly favorable, with equilibrium binding capacity for monoclonal and bispecific antibodies ranging from 47-100 mg/mL packed bed across all stationary phases tested. Effective pore diffusivities, D<sub>e</sub>, were obtained by fitting the chromatography general rate model to breakthrough data. The fitted D<sub>e</sub> values for monoclonal antibodies ranged from 1.1-5.7 × 10<sup>-8</sup> cm<sup>2</sup>/s. The stationary phases had high dynamic binding capacities for the model proteins. The highest dynamic capacities for monoclonal and bispecific antibodies were seen with MabSelect SuRe pcc and MabSelect PrismA, which ranged from 58-74 mg/mL packed bed at 4 min residence times. Product capture using clarified cell culture broth as a feedstock showed high yields and elution pool volumes that ranged from 2-3 column volumes in most cases. Host cell protein, DNA, and aggregate levels in the elution pool were dependent on the specific nature of protein being purified, and levels were consistent between stationary phases. Lastly, we perform an analysis of bivariate correlations and discuss considerations for process design and optimization.
Prediagnostic Serum Biomarkers as Early Detection Tools for Pancreatic Cancer in a Large Prospective Cohort Study (2014)

Most biomarkers identified in previously conducted case/control studies are ineffective in prediagnostic samples, however several biomarkers were identified as significantly altered up to 35 months prior to diagnosis. Two newly derived biomarker combinations offered advantage over CA 19-9 alone in terms of SN, particularly in samples collected >1 year prior to diagnosis. However, the efficacy of biomarker-based tools remains limited at present. Several biomarkers demonstrated significant velocity related to time to diagnosis, an observation which may offer considerable potential for enhancements in early detection.
A fast normalized cross-correlation calculation method for motion estimation (2010)

High-precision motion estimation has become essential in ultrasound-based techniques such as time-domain Doppler and elastography. Normalized cross-correlation (NCC) has been shown as one of the best motion estimators. However, a significant drawback is its associated computational cost, especially when RF signals are used. In this paper, a method based on sum tables developed elsewhere is adapted for fast NCC calculation in ultrasound-based motion estimation, and is tested with respect to the speed enhancement of the specific application of ultrasound-based motion estimation. Both the numerator and denominator in the NCC definition are obtained through pre-calculated sum tables to eliminate redundancy of repeated NCC calculations. Unlike a previously reported method, a search region following the principle of motion estimation is applied in the construction of sum tables. Because an exhaustive search and high window overlap are typically used for highest quality imaging, the computational cost of the proposed method is significantly lower than that of the direct method using the NCC definition, without increasing bias and variance characteristics of the motion estimation or sacrificing the spatial resolution. Therefore, high quality, high spatial resolution, and high calculation speed can be all simultaneously obtained using the proposed methodology. The high efficiency of this method was verified using RF signals from a human abdominal aorta in vivo. For the parameters typically used, a real-time, very high frame rate of 310 frames/s was achieved for the motion estimation. The proposed method was also extended to 2-D NCC motion estimation and motion estimation with other algorithms. The technique could thus prove very useful and flexible for real-time motion estimation as well as in other fields such as optical flow and image registration.
Structure of DNA Polymerase I Klenow Fragment Bound to Duplex DNA (1993)

Klenow fragment of Escherichia coli DNA polymerase I, which was cocrystallized with duplex DNA, positioned 11 base pairs of DNA in a groove that lies at right angles to the cleft that contains the polymerase active site and is adjacent to the 3' to 5' exonuclease domain. When the fragment bound DNA, a region previously referred to as the "disordered domain" became more ordered and moved along with two helices toward the 3' to 5' exonuclease domain to form the binding groove. A single-stranded, 3' extension of three nucleotides bound to the 3' to 5' exonuclease active site. Although this cocrystal structure appears to be an editing complex, it suggests that the primer strand approaches the catalytic site of the polymerase from the direction of the 3' to 5' exonuclease domain and that the duplex DNA product may bend to enter the cleft that contains the polymerase catalytic site.
Transmission characteristics of a power line used for data communications at high frequencies (1989)

The transmission characteristics of an installed power line used for data communication, and of a model of this actual line, were measured over the frequency range of 10 kHz-50 MHz. It was found that impedance characteristics were not greatly influenced by the working loads at high frequencies, but changed drastically at lower frequencies. For frequencies of less than 100 MHz, the transmission loss did not increase significantly with frequency. The effect of the length of the connections and variation in load impedance were both studied. It was found that for frequencies above 100 MHz, attenuation loss in the power line is divided into losses due to attenuation constant of the line and the loss occurring at wire connections located between the various wires in the wall sockets. The latter loss is proportional to the number of connections. When the transmission loss was measured by opening and closing the wire connections, the fluctuation in the loss was found to be smaller at frequencies above 1 MHz than at lower ones. The transmission loss at the higher frequency shows only fairly slight fluctuations to variations in working load on the power line. The intensity of the noise power spectrum shows a decrease of -40 B/decade. This degradation rate in the noise spectrum is greater than the rate of increase in transmission loss. The increasing transmission loss can be sufficiently compensated by amplification at the receiving end, but it is possible to keep the amplified noise below the level of disturbance.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Requirement of the Pr55gag precursor for incorporation of the Vpr product into human immunodeficiency virus type 1 viral particles (1994)

The human immunodeficiency virus type 1 (HIV-1) particles consists of two molecules of genomic RNA as well as molecules originating from gag, pol, and env products, all synthesized as precursor proteins. The 96-amino-acid Vpr protein, the only virion-associated HIV-1 regulatory protein, is not part of the virus polyprotein precursors, and its incorporation into virus particles must occur by way of an interaction with a component normally found in virions. To investigate the mechanism of incorporation of Vpr into the HIV-1 virion, Vpr- proviral DNA constructs harboring mutations or deletions in specific virion-associated gene products were cotransfected with Vpr expressor plasmids in COS cells. Virus released from the transfected cells was tested for the presence of Vpr by immunoprecipitation with Vpr-specific antibodies. The results of these experiments show that Vpr is trans-incorporated into virions but at a lower efficiency than when Vpr is expressed from a proviral construct. The minimal viral genetic information necessary for Vpr incorporation was a deleted provirus encoding only the pr55gag polyprotein precursor. Incorporation of Vpr requires the expression but not the processing of gag products and is independent of pol and env expression. Direct interaction of Vpr with the Pr55gag precursor protein was demonstrated by coprecipitation experiments with gag product-specific antibodies. Overall, these results indicate that HIV-1 Vpr is incorporated into the nascent virion through an interaction with the Gag precursor polyprotein and demonstrate a novel mechanism by which viral protein can be incorporated into virus particles.
Use of tissue-specific promoters in the regulation of aromatase cytochrome P450 gene expression in human testicular and ovarian sex cord tumors, as well as in normal fetal and adult gonads. (1993)

We have previously demonstrated that the tissue-specific regulation of human aromatase cytochrome P450 (P450arom) gene expression is, in part, the consequence of the use of tissue-specific promoters. Promoter I.1 (PI.1) and PI.2-specific transcripts are expressed in the placenta, whereas promoter II (PII) appears to be the only active promoter in the corpus luteum. Testicular and ovarian sex cord tumors with annular tubules (SCTATs) associated with gynecomastia in prepubertal boys and isosexual precocity in girls with Peutz-Jeghers syndrome (P-JS) have been previously reported. In the present study, we investigated the regulatory elements directing P450arom gene transcription in samples of SCTAT from three prepubertal boys and a girl with P-JS and an ovarian granulosa cell tumor from an adult woman, as well as in healthy fetal and adult testicular and ovarian tissues. Placental tissue was used as a control. Using polymerase chain reaction linked to reverse transcription and northern blotting, we determined the tissue-specific use of various P450arom promoters by analyzing specific 5'-termini from messenger RNA templates. Results indicate a universal gonadal promoter (PII) directs P450arom gene expression in healthy fetal and adult ovaries and testes, as well as in SCTAT of the P-JS and an adult ovarian granulosa cell tumor. These results are interpreted to mean that use of PII in human ovary and testis is preserved from the fetal period into adult life as well as in transformed neoplastic Sertoli and granulosa cells. On the other hand, transcripts from placenta are specific for PI.1 (and to a much lesser extent, PI.2). In SCTAT, immunoreactive P450arom is detected only in the cytoplasm of neoplastic cells, whereas the normal-appearing sex cords do not contain any immunoreactive P450arom. These results further suggest that the markedly increased aromatase expression of these transformed neoplastic cells is not a consequence of using different tissue-specific promoters. Rather it appears to involve activation (or failure of inhibition) of the upstream regulatory elements of the same promoter, which is normally functional in all gonadal tissues, namely the proximal PII.
Chemical State and Environment of Boron Dopant in B,N-Codoped Anatase TiO2 Nanoparticles:  An Avenue for Probing Diamagnetic Dopants in TiO2 by Electron Paramagnetic Resonance Spectroscopy (2008)

Boron is diamagnetic in B-doped anatase TiO2 nanoparticles which exhibit photocatalytic activities in the visible light range. Using N as a paramagnetic probe for the formal oxidation state of boron in N/B-codoped TiO2, with more than 90% unpaired spin density in the N2p orbital, we infer that boron enters the oxygen vacancy substitutionally in the form of B1-. Combination of spin-Hamiltonian analysis and interpretation of light dependent EPR spectra in terms of a charge compensating mechanism supports a model of [N2-B1-]+1 for the new EPR active center which acts as a trap for electrons liberated from [N1-] centers under blue light irradiation. Definite assignment of the boron oxidation state will contribute to the preparation, characterization, and understanding of B-TiO2 photoactivity under visible light which has been the subject of extensive work in the past few years.
Developmental Genes and Cancer: Role of Patched in Basal Cell Carcinoma of the Skin (1997)

Many genes originally identified because of their role in embryonic development are also important in postnatal control of cell growth and differentiation. Mutations in some of these genes have been shown to cause cancer. Basal cell carcinoma (BCC) of the skin is the most common cancer in humans. More than 750000 new cases are diagnosed annually, and the incidence is rising. BCCs are slow-growing, locally invasive tumors that rarely metastasize but can result in extensive morbidity through local recurrence and tissue destruction. Epidemiologic studies suggest that sunlight (particularly UVB radiation) is a strong risk factor for BCC formation, although other factors are also involved. The nevoid basal cell carcinoma syndrome (NBCCS), a rare genetic disorder, is characterized by predisposition to BCCs and other tumors as well as to a wide range of developmental defects. NBCCS maps to chromosome 9q22.3, and loss of heterozygosity at this site in both sporadic and hereditary BCCs suggests that it functions as a tumor suppressor. The gene for NBCCS was recently cloned and is the human homologue of the Drosophila gene "patched." Genetic studies in Drosophila show that patched is part of the hedgehog signaling pathway, which is important in determining embryonic patterning and cell fate in multiple structures of the developing embryo. Human patched is mutated in both hereditary and sporadic BCCs, and inactivation of this gene is probably a necessary, if not sufficient, step for BCC formation. Delineation of the biochemical pathway in which patched functions may lead to rational medical therapy for BCCs and possibly for other tumors associated with NBCCS.
Targeting metabolic inflammation in Parkinson’s disease: Implications for prospective therapeutic strategies (2011)

1. Parkinson's disease (PD) is one of the most common neurodegenerative disorders and is characterized by a progressive loss of dopaminergic neurons in the substantia nigra pars compacta. Although the aetiology of PD has not been clarified as yet, it is believed that ageing, diet, diabetes and adiposity are associated with PD. 2. Type 2 diabetes and lipid abnormalities share multiple common pathophysiological mechanisms with PD. In particular, inflammation plays a critical role in the destruction of both pancreatic islet β-cells and dopaminergic neurons in the substantia nigra. Emerging evidence indicates that dysfunctions of energy metabolism evoke metabolic inflammation, which differs to the narrow concept of inflammation, participating in systemic pathological processes such as neurodegenerative disease and diabetes. 3. The brain is considered an immunologically privileged organ, free from immune reactions, because it is protected by the blood-brain barrier (BBB). However, studies have shown that there is gradual impairment of neurovascular function with ageing and in neurodegenerative disorders, resulting in abnormal states, including increased BBB permeability. Consequently, harmful elements that would not normally be able to cross the BBB, such as pro-inflammatory factors, reactive oxygen species and neurotoxins, infiltrate into the brain, triggering neural injury. 4. Currently, the drugs available for the treatment of PD only ameliorate the symptoms of the disease. Therapeutic strategies aimed at stopping or modifying disease progression are still being sought. Most recent studies suggest that both central and peripheral inflammation may be dysregulated in PD. Therefore, therapeutic strategies aimed at modulating systemic inflammatory reactions or energy metabolism may represent a goal in neuroprotection in PD.
A database approach for modeling and querying video data (2000)

Indexing video data is essential for providing content-based access. In this paper, we consider how database technology can offer an integrated framework for modeling and querying video data. As many concerns in video (e.g., modeling and querying) are also found in databases, databases provide an interesting angle to attack many of the problems. From a video applications perspective, database systems provide a nice basis for future video systems. More generally, database research will provide solutions to many video issues, even if these are partial or fragmented. From a database perspective, video applications provide beautiful challenges. Next generation database systems will need to provide support for multimedia data (e.g., image, video, audio). These data types require new techniques for their management (i.e., storing, modeling, querying, etc.). Hence, new solutions are significant. This paper develops a data model and a rule-based query language for video content-based indexing and retrieval. The data model is designed around the object and constraint paradigms. A video sequence is split into a set of fragments. Each fragment can be analyzed to extract the information (symbolic descriptions) of interest that can be put into a database. This database can then be searched to find information of interest. Two types of information are considered: (1) the entities (objects) of interest in the domain of a video sequence, and (2) video frames which contain these entities.
Macromonomers and coordination polymerization (2004)

Abstract The present work discusses the synthesis of well‐defined comb‐shaped polymers or graft copolymer structures based on coordination (co)polymerization of macromonomers. Polystyrene macromonomers with various polymerizable entities were synthesized first by induced deactivation reactions. The homopolymerization of these macromonomers in the presence of selected early or late transition metal catalysts was examined. Comb‐shaped polymers could be obtained over a large range of DP values. The results were compared to those obtained by anionic homopolymerization. Some results on the copolymerization of these PS macromonomers with ethylene in the presence of VERSIPOL TM type catalysts were presented.
Intravenous administration of the natriuretic peptide urodilatin at low doses during coronary reperfusion limits infarct size in anesthetized pigs (2001)

Intravenous low-dose URO at the time of reperfusion normalizes myocardial cGMP and limits necrosis. Large doses of URO increasing myocardial cGMP well over normal values may lack this beneficial effect.
Treating haemophilia A with recombinant blood factors: a comparison (2004)

The mainstay in the treatment of haemophilia A is replacement therapy with repeated infusions of plasma-derived Factor VIII (FVIII) concentrates or recombinant FVIII products. While modern plasma-derived FVIII concentrates have an excellent safety profile, there is an inexorable shift towards the use of recombinant products, especially in affluent countries. Recombinant FVIII products have demonstrated excellent haemostatic efficacy and higher safety with regard to the transmission of blood-borne pathogens. The experience in haemophilia A treatment with five currently available recombinant FVIII products, including the first third-generation product, Advate®, which is completely free from human or animal proteins, is summarised. Some unresolved problems concerning the efficacy and assaying of recombinant factors and future perspectives of both recombinant and plasma-derived FVIII products in global haemophilia care, are also discussed.
Identification of FAZF as a novel BMP2‐induced transcription factor during osteoblastic differentiation (2006)

Bone morphogenetic protein 2 (BMP2) is a key factor in the regulation of osteoblastic differentiation; however, its downstream mediators are not fully understood. Previously, we identified and characterized transcription factor promyelocytic leukemia zinc finger protein (PLZF), composed of an N-terminal BTB/POZ and C-terminal zinc finger motifs, as an upstream factor of CBFA1 (Runx2/core-binding factor 1). PLZF was induced in an osteoblastic differentiation medium, but was not induced by BMP2. Here, we report the identification of transcription factor fanconi anemia zinc finger protein (FAZF), which is closely related to PLZF. FAZF was induced by BMP2 in human mesenchymal stem cells (hMSCs). In addition to the full-length FAZF, we also identified alternatively spliced mRNAs in which the C-terminal zinc finger motifs were deleted (designated BTB/POZ-only FAZF). Both the full-length and BTB/POZ-only FAZF mRNAs were equally expressed in BMP2-treated hMSCs. The full-length FAZF was exclusively detected in the nucleus, whereas the BTB/POZ-only FAZF protein was localized in the cytoplasm of the transfected cells. The full-length FAZF, but not the BTB/POZ-only FAZF, increased the expression of osteoblastic differentiation markers, including CBFA1, collagen 1A1, osteocalcin, and alkaline phosphatase in C2C12 cells. In conclusion, both FAZF and PLZF differentially participate in the regulation of osteoblastic differentiation via the BMP2 and CBFA1 signaling pathways, respectively.
Four-pass YAG:Nd laser amplifier with compensation for aberration and polarization distortions of the wavefront (1992)

Pulses having an energy of 1 J with an angular distribution width close to the diffraction limit were obtained at the exit of a four-pass amplifier operating at a repetition frequency of 20–25 Hz.
Active scaffolds for on-demand drug and cell delivery (2010)

Porous biomaterials have been widely used as scaffolds in tissue engineering and cell-based therapies. The release of biological agents from conventional porous scaffolds is typically governed by molecular diffusion, material degradation, and cell migration, which do not allow for dynamic external regulation. We present a new active porous scaffold that can be remotely controlled by a magnetic field to deliver various biological agents on demand. The active porous scaffold, in the form of a macroporous ferrogel, gives a large deformation and volume change of over 70% under a moderate magnetic field. The deformation and volume variation allows a new mechanism to trigger and enhance the release of various drugs including mitoxantrone, plasmid DNA, and a chemokine from the scaffold. The porous scaffold can also act as a depot of various cells, whose release can be controlled by external magnetic fields.
SIFT: predicting amino acid changes that affect protein function (2003)

Single nucleotide polymorphism (SNP) studies and random mutagenesis projects identify amino acid substitutions in protein-coding regions. Each substitution has the potential to affect protein function. SIFT (Sorting Intolerant From Tolerant) is a program that predicts whether an amino acid substitution affects protein function so that users can prioritize substitutions for further study. We have shown that SIFT can distinguish between functionally neutral and deleterious amino acid changes in mutagenesis studies and on human polymorphisms. SIFT is available at http://blocks.fhcrc.org/sift/SIFT.html.
The Enantioselective Synthesis of (+)‐Estradiol from 1,3‐Dihydrobenzo[c]thiophene‐2,2‐dioxide by Successive Thermal SO2‐Extrusion and Cycloaddition Reactions. Preliminary communication (1980)

Abstract The optically pure steroid (+)‐ 15 has been synthesized from the easily accessible (+)‐carboxylic acid 11 by a sequence of 7 steps in 50% overall yield. The key steps are the regioselective deprotonation/alkylation 7+13 → 14 and the thermal SO 2 ‐extrusion/cycloaddition 14 → 15 (Scheme 3) . The compound (+)‐ 15 has been readily converted to the naturally occurring (+)‐estradiol ( 17 ) in 60% yield.