gebhart/patrepeval huggingface dataset:
High-efficiency recovery of functional hematopoietic progenitor and stem cells from human cord blood cryopreserved for 15 years (2003)

Transplanted cord blood (CB) hematopoietic stem cells (HSC) and progenitor cells (HPC) can treat malignant and nonmalignant disorders. Because long-term cryopreservation is critical for CB banking and transplantation, we assessed the efficiency of recovery of viable HSCHPC from individual CBs stored frozen for 15 yr. Average recoveries (+/- 1 SD) of defrosted nucleated cells, colony-forming unit-granulocyte, -macrophage (CFU-GM), burst-forming unit-erythroid (BFU-E), and colony-forming unit-granulocyte, -erythrocyte, -monocyte, and -megakaryocyte (CFU-GEMM) were, respectively, 83 +/- 12, 95 +/- 16, 84 +/- 25, and 85 +/- 25 using the same culture conditions as for prefreeze samples. Proliferative capacities of CFU-GM, BFU-E, and CFU-GEMM were intact as colonies generated respectively contained up to 22,500, 182,500, and 292,500 cells. Self-renewal of CFU-GEMM was also retained as replating efficiency of single CFU-GEMM colonies into 2 degrees dishes was >96% and yielded 2 degrees colonies of CFU-GM, BFU-E, and CFU-GEMM. Moreover, CD34(+)CD38(-) cells isolated by FACS after thawing yielded >250-fold ex vivo expansion of HPC. To assess HSC capability, defrosts from single collections were bead-separated into CD34(+) cells and infused into sublethally irradiated nonobese diabetic (NOD)severe combined immunodeficient (SCID) mice. CD45(+) human cell engraftment with multilineage phenotypes was detected in mice after 11-13 wk; engrafting levels were comparable to that reported with fresh CB. Thus, immature human CB cells with high proliferative, replating, ex vivo expansion and mouse NODSCID engrafting ability can be stored frozen for >15 yr, can be efficiently retrieved, and most likely remain effective for clinical transplantation.
Covalently immobilized enzyme gradients within three‐dimensional porous scaffolds (2006)

Horseradish peroxide (HRP) was covalently coupled to three-dimensional (3D) silk fibroin scaffolds using water-soluble carbodiimide. Stable, bilaterally symmetrical immobilized HRP gradient patterns were generated within 3D silk fibroin scaffolds using the principles of diffusion. Gradients of immobilized HRP activity were controlled using variables of volume and concentration of HRP solution activated by the carbodiimide. The method developed can be extended to immobilize a variety of proteins and small molecules on several types of porous, interconnected materials. This technique of patterning enzymes and proteins in a gradient manner offers new options in the field of chemotaxis, tissue engineering, and biosensors.
Biological factors in dental caries: role of remineralization and fluoride in the dynamic process of demineralization and remineralization (part 3) (2004)

Dental caries is a complex disease process that afflicts a large proportion of the world, regardless of gender, age and ethnicity, although it does tend to affect more with a low socioeconomic status to a greater extent. Remineralization may be enhanced by providing low levels of calcium and phosphate, in conjunction with minimal amounts of fluoride. It is truly remarkable the difference that a very small amount of fluoride (<1 ppm) has upon demineralization and remineralization. This is because fluoride acts as a catalyst and influences reaction rates with dissolution and transformation of various calcium phosphate mineral phases within tooth structure and resident within plaque adjacent to tooth surfaces. The incorporation of minimal amounts of fluoride into HAP yields FHAP that resists demineralization to similar level as FAP. New and emerging methods have been and are in the process of being developed. These hold great promise for preventing and reversing caries, especially in the one-fifth of the population that accounts for two-thirds of the caries experience. Still, the mainstay in caries prevention and remineralization is frequent exposure to low levels of fluoride. This may be accomplished with fluoridated toothpastes, supplemented with fluoride mouthrinses, CPP-ACP containing chewing gum and application of fluoride varnishes. The role of systemic fluorides appears to be limited and primarily has a topical effect.
Emerging Targeted Therapies for Breast Cancer (2010)

Increased understanding of the molecular events involved in cancer development has led to the identification of a large number of novel targets and, in parallel, to the development of multiple approaches to anticancer therapy. Targeted therapy focuses on specific molecules in the malignant cell signal transduction machinery, including crucial molecules involved in cell invasion, metastasis, apoptosis, cell-cycle control, and tumor-related angiogenesis. In breast cancer, two new targeted agents have recently been approved: lapatinib, directed against the human epidermal growth factor receptor 2 (HER2); and bevacizumab, directed against vascular endothelial growth factor (VEGF). Multiple other targeted agents are under evaluation in clinical trials, including inhibitors of the epidermal growth factor receptor (EGFR), dual EGFR and HER2 inhibitors, other VEGF or VEGF-receptor inhibitors, and agents that alter crucial signaling pathways, such as RAS/MEK/ERK; phosphatidylinositol-3-kinase/Akt/ mammalian target of rapamycin; insulin-like growth factor/insulin-like growth factor receptor; poly (ADP-ribose) polymerase 1; and others. In this review, we present the most promising studies of these new targeted therapies and novel combinations of targeted therapies with traditional cytotoxic agents.
A novel forward projection-based metal artifact reduction method for flat-detector computed tomography (2009)

Metallic implants generate streak-like artifacts in flat-detector computed tomography (FD-CT) reconstructed volumetric images. This study presents a novel method for reducing these disturbing artifacts by inserting discarded information into the original rawdata using a three-step correction procedure and working directly with each detector element. Computation times are minimized by completely implementing the correction process on graphics processing units (GPUs). First, the original volume is corrected using a three-dimensional interpolation scheme in the rawdata domain, followed by a second reconstruction. This metal artifact-reduced volume is then segmented into three materials, i.e. air, soft-tissue and bone, using a threshold-based algorithm. Subsequently, a forward projection of the obtained tissue-class model substitutes the missing or corrupted attenuation values directly for each flat detector element that contains attenuation values corresponding to metal parts, followed by a final reconstruction. Experiments using tissue-equivalent phantoms showed a significant reduction of metal artifacts (deviations of CT values after correction compared to measurements without metallic inserts reduced typically to below 20 HU, differences in image noise to below 5 HU) caused by the implants and no significant resolution losses even in areas close to the inserts. To cover a variety of different cases, cadaver measurements and clinical images in the knee, head and spine region were used to investigate the effectiveness and applicability of our method. A comparison to a three-dimensional interpolation correction showed that the new approach outperformed interpolation schemes. Correction times are minimized, and initial and corrected images are made available at almost the same time (12.7 s for the initial reconstruction, 46.2 s for the final corrected image compared to 114.1 s and 355.1 s on central processing units (CPUs)).
Ribozymes Targeted to Stearoyl-ACP D9 Desaturase mRNA Produce Heritable Increases of Stearic Acid in Transgenic Maize Leaves (1998)

Ann Owens Merlo, Neil Cowen, Tom Delate, Brent Edington, Otto Folkerts, Nicole Hopkins, Christine Lemeiux, Tom Skokut, Kelley Smith, Aaron Woosley, Yajing Yang, Scott Young, Michael Zwick, Ribozymes Targeted to Stearoyl-ACP Δ9 Desaturase mRNA Produce Heritable Increases of Stearic Acid in Transgenic Maize Leaves, The Plant Cell, Vol. 10, No. 10 (Oct., 1998), pp. 1603-1621
DMSO is a strong inducer of DNA hydroxymethylation in pre-osteoblastic MC3T3-E1 cells (2012)

Artificial induction of active DNA demethylation appears to be a possible and useful strategy in molecular biology research and therapy development. Dimethyl sulfoxide (DMSO) was shown to cause phenotypic changes in embryonic stem cells altering the genome-wide DNA methylation profiles. Here we report that DMSO increases global and gene-specific DNA hydroxymethylation levels in pre-osteoblastic MC3T3-E1 cells. After 1 day, DMSO increased the expression of genes involved in DNA hydroxymethylation (TET) and nucleotide excision repair (GADD45) and decreased the expression of genes related to DNA methylation (Dnmt1, Dnmt3b, Hells). Already 12 hours after seeding, before first replication, DMSO increased the expression of the pro-apoptotic gene Fas and of the early osteoblastic factor Dlx5, which proved to be Tet1 dependent. At this time an increase of 5-methyl-cytosine hydroxylation (5-hmC) with a concomitant loss of methyl-cytosines on Fas and Dlx5 promoters as well as an increase in global 5-hmC and loss in global DNA methylation was observed. Time course-staining of nuclei suggested euchromatic localization of DMSO induced 5-hmC. As consequence of induced Fas expression, caspase 3/7 and 8 activities were increased indicating apoptosis. After 5 days, the effect of DMSO on promoter- and global methylation as well as on gene expression of Fas and Dlx5 and on caspases activities was reduced or reversed indicating down-regulation of apoptosis. At this time, up regulation of genes important for matrix synthesis suggests that DMSO via hydroxymethylation of the Fas promoter initially stimulates apoptosis in a subpopulation of the heterogeneous MC3T3-E1 cell line, leaving a cell population of extra-cellular matrix producing osteoblasts.
Tumor necrosis factor-induced apoptosis is mediated by a CrmA-sensitive cell death pathway. (1995)

We report here that the activation of the interleukin 1 beta (IL-1 beta)-converting enzyme (ICE) family is likely to be one of the crucial events of tumor necrosis factor (TNF) cytotoxicity. The cowpox virus CrmA protein, a member of the serpin superfamily, inhibits the enzymatic activity of ICE and ICE-mediated apoptosis. HeLa cells overexpressing crmA are resistant to apoptosis induced by Ice but not by Ich-1, another member of the Ice/ced-3 family of genes. We found that the CrmA-expressing HeLa cells are resistant to TNF-alpha/cycloheximide (CHX)-induced apoptosis. Induction of apoptosis in HeLa cells by TNF-alpha/CHX is associated with secretion of mature IL-1 beta, suggesting that an IL-1 beta-processing enzyme, most likely ICE itself, is activated by TNF-alpha/CHX stimulation. These results suggest that one or more members of the ICE family sensitive to CrmA inhibition are activated and play a critical role in apoptosis induced by TNF.
Stochastic network utility maximisation—a tribute to Kelly's paper published in this journal a decade ago (2008)

Abstract Since the seminal work by Kelly on distributed network resource allocation using the language of network utility maximisation (NUM) a decade ago, there have been extensive research efforts generalising and applying NUM to model, analyse and design various network protocols and architectures. Some of these works combine the distributed optimisation approach with stochastic network models to study NUM under network dynamics occurring at the session, packet and constraint levels. We survey these works by presenting the key questions, results and methodologies in this emerging theory of stochastic network utility maximisation, followed by discussion on related work and future research challenges. Copyright © 2008 John Wiley &amp; Sons, Ltd.
Rapid Desensitization of Lipolysis in the Visceral and Subcutaneous Adipocytes of Rats (2007)

In adipocytes, short and long term stimulation of beta adrenergic receptors (beta AR) induces the desensitization to catecholamines, leading to a decrease in the intracellular accumulation of cAMP, but the roles played by this in lipolysis is not clear. In this study, we assessed the catecholamine-induced desensitization of lipolysis and compared this in adipocytes isolated from visceral and subcutaneous fat tissues of rats. When adipocytes were pretreated with isoproterenol (ISO), the norepinephrine (NE)-induced lipolysis was significantly reduced dose- and time-dependently. A similar reduction of the lipolytic response was also found in NE-, dobutamine-, terbutaline- or BRL37344-induced lipolysis. The ISO- and each beta AR agonist-induced lipolysis in the visceral fat was not only higher than in the subcutaneous fat, but also markedly reduced by ISO- or NE-pretreatment. These results showed that short-term treatment of three subtypes of beta AR by each agonist induces a rapid reduction in the lipolytic response to beta AR stimulation. This suggests some common mechanism for the rapid desensitization of beta AR-agonist-induced lipolysis, in contrast with previous reports on the characteristics of beta AR subtypes. In addition, the regional difference of adipose tissue not only in inducing lipolysis but also in rapid desensitization was also apparent.
Second-phase hepatitis C virus RNA decline during telaprevir-based therapy increases with drug effectiveness: Implications for treatment duration (2011)

Hepatitis C virus (HCV) RNA decay during antiviral therapy is characterized by a rapid first phase, followed by a slower second phase. The current understanding of viral kinetics attributes the magnitude of the first phase of decay to treatment effectiveness, whereas the second phase of decay is attributed to the progressive loss of infected cells. Here, we analyzed data from 44 patients treated with telaprevir, a potent HCV protease inhibitor. Using a viral kinetic model that accounts for the pharmacokinetics of telaprevir, we found the second-phase slope of viral decline to be strongly correlated with treatment effectiveness and to be roughly four-fold more rapid than has been reported with interferon-based therapies. Because telaprevir is not known to increase the death rate of infected cells, our results suggest that the second-phase slope of viral decline is driven not only by the death of infected cells, but may also involve other mechanisms, such as a treatment-effectiveness-dependent degradation of intracellular viral RNA. As a result of the enhanced viral decay caused by the high antiviral effectiveness of telaprevir, we predict that if drug resistance could be avoided by using an appropriate combination of antiviral agents, treatment duration needed to clear HCV might be dramatically shortened. Indeed, we predict that in 95% of fully compliant patients, the last virus particle should be eliminated by week 7 of therapy. If the remaining infected hepatocytes act as a potential reservoir for the renewal of infection, no more than 10 weeks of treatment should be sufficient to clear the infection in 95% of fully compliant patients. However, if patients miss doses, treatment duration would need to be extended.
Extracellular superoxide dismutase in the vascular system of mammals. (1988)

Plasma extracellular superoxide dismutase (EC-SOD) from the pig, cat, rabbit, guinea pig and mouse was found to be heterogeneous with regard to heparin affinity and could be separated into three fractions: A without affinity, B with weak affinity and C with relatively high affinity. Rat plasma EC-SOD was deviant and contained only A and B fractions. There were very large interspecies differences in total plasma EC-SOD activity and in division of the activity between the different fractions. Intravenous injection of heparin resulted in the pig, dog, cat, rabbit, guinea pig and mouse in a prompt increase in the plasma SOD activity. The increase was due to release of EC-SOD C to plasma, most probably from endothelial cell surfaces. In the rat, heparin induced no increase in plasma SOD activity, apparently because of the absence of EC-SOD C in this species. The relative heparin-induced increase in plasma EC-SOD C varied between 2 and 11 in the different species and was distinctly correlated with the heparin affinity of EC-SOD C in the particular species. Apparently the EC-SOD C, present in the vasculature, forms an equilibrium between plasma and endothelium, whereas EC-SOD A and B primarily exist in plasma. The wide diversity of EC-SOD in the vascular system of mammals with regard to total amount, division into fractions and distribution between plasma and endothelium indicates that the pathogenic potential of superoxide radicals in the extracellular space might vary much between species.
Thermal Lesions Induced by 480 KHz Localized Current Field in Guinea Pig and Pig Liver (1990)

We evaluated the type, dimension and histopathological evolution of thermal lesions induced in guinea pig and pig liver by radiofrequency electrode needles at various temperatures for different exposure times. The greatest useful necrosis volume was induced by a needle of 1.1 mm diameter and exposed Up 10 mm long at 90 degrees C and 120 seconds exposure time. It was an ellipsoid with the biggest diameter of about 14 mm diameter and length of about 18 mm. It seems possible that liver tumors of not more than 20 mm diameter in patients without surgical prospects could be destroyed, ultrasonography guiding the needle into the tumor and using the temperature and exposure time mentioned above.
Custodial Choices for Children at Risk: Bias, Sequentiality and the Law (1995)

Professor Davis, with Gautam Barua, analyzes the effects cognitive bias in risk assessment have on child placement decision-making.
Characterization of clocks and oscillators (1990)

This is a collection of published papers assembled as a reference for those involved in characterizing and specifying high-performance clocks and oscillators. It is an interim replacement for NBS Monograph 140, Time and Frequency: Theory and Fundamentals, an older volume of papers edited by Byron E. Blair. This current volume includes tutorial papers, papers on standards and definitions, and a collection of papers detailing specific measurement and analysis techniques. The discussion in the introduction to the volume provides a guide to the content of the papers, and tables and graphs provide further help in organizing methods described in the papers.
Embedded audio coding (EAC) with implicit auditory masking (2002)

An embedded audio coder (EAC) is proposed with compression performance rivals the best available non-scalable audio coder. The key technology that empowers the EAC with high performance is the implicit auditory masking. Unlike the common practice, where an auditory masking threshold is derived from the input audio signal, transmitted to the decoder and used to quantize (modify) the transform coefficients; the EAC integrates the auditory masking process into the embedded entropy coding. The auditory masking threshold is derived from the encoded coefficients and used to change the order of coding. There is no need to store or send the auditory masking threshold in the EAC. By eliminating the overhead of the auditory mask, EAC greatly improves the compression efficiency, especially at low bitrate. Extensive experimental results demonstrate that the EAC coder substantially outperforms existing scalable audio coders and audio compression standards (MP3 and MPEG-4), and rivals the best available commercial audio coder. Yet the EAC compressed bitstream is fully scalable, in term of the coding bitrate, number of audio channels and audio sampling rate.
A 2-V 2.5-GHz-104-dBc/Hz at 100 kHz fully integrated VCO with wide-band low-noise automatic amplitude control loop (2001)

The automatic amplitude control (AAC) loop is an indispensable element for the practical realization of VCOs embedded in a complete transceiver. Its noise however can unacceptably degrade the single-sideband-to-carrier ratio (SSCR) performance of the oscillator, this problem being even exacerbated in low-voltage circuits. This paper addresses the design issues of a low-voltage low-noise differential LC-VCO with AAC, tunable within a 2.3-2.8-GHz frequency range, fully integrated in bipolar technology with 2-V power supply. First, the mechanisms through which the AAC noise affects the output phase are identified as the poor indirect stability and the AM-to-PM conversion due to the varactors. The effect of the AAC noise is discussed and substantially reduced with suitable design choices. We show that the achievable noise-to-signal ratio is bounded by the shot noise coming from the bias source of the differential oscillator, an intrinsic limit set by the low supply voltage which does not allow for degeneration of the tail transistor. Second, the design of the AAC is discussed. A large gain-bandwidth product (GBWP), about 100 MHz, has been implemented in order to correct for the fast oscillation amplitude variations and reduce the effect of the ground line disturbances. The expected value of the phase noise level, SSCR at 100 kHz =-104 dBc/Hz, is tightly matched by the experimental results. The core oscillator dissipates 7 mA, while less than 600 /spl mu/A are drawn by the AAC circuit.
Expression of hybrid malaria antigens in insect cells and their engineering for correct folding and secretion (1990)

Hybrid proteins containing selected regions of the major surface antigens of the sporozoite and merozoite stages of Plasmodium falciparum were expressed in insect cells using baculovirus vectors. A recombinant protein containing the signal peptide from the precursor to the major merozoite surface antigens (PMMSA) fused to a fragment from the carboxy (C) terminus of the same gene was recognized by monoclonal antibodies specific for reduction-sensitive conformational epitopes within the C-terminal fragment, suggesting that correct disulphide cross-linking of cysteine residues within this region had occurred. Addition of 26 copies of the tetrapeptide repeat from the circumsporozoite protein (CSP) resulted in a protein recognized by anti-CSP antiserum as well as the conformation specific monoclonal antibodies. Deletion of the C-terminal putative anchor sequence from both proteins resulted in secretion of protein in a fully soluble form antigenically indistinguishable from the anchor containing products. Correct conformation was not observed when the proteins were expressed as polyhedrin fusions without the signal peptide. These data indicate that the PMMSA signal peptide is recognized in insect cells and that correct assembly of disulphide cross-links is dependent upon targeting the protein to the endoplasmic reticulum.