gebhart/patrepeval huggingface dataset:
Long-term suspension cultures of human cord blood myeloid cells (1981)

A method is described that allows for the routine long-term (greater than 3 mo) growth of normal, immature human myeloid cells in liquid suspension culture. The techniques employ cell separation, utilization of special growth conditions (RPMI with hydrocortisone and vitamin D), and cord blood as the source of leukocytes. These cultures are composed predominantly of immature myeloid cells that have grown for over 3 mo in culture but eventually terminate as differentiated, mature granulocytes and monocyte-macrophages. Application of these techniques to other sources of fresh human leukocytes (bone marrow and adult peripheral blood) resulted in only short-term proliferation of myeloid cells. The techniques described can be used for the routine expansion of immature myeloid and monocytoid cell populations, particularly from newborns, and should be useful for systematic studies of normal myeloid-monocytoid cell growth and differentiation and providing normal control cells in studies employing human leukemic myeloid cells.
LSUN: Construction of a Large-scale Image Dataset using Deep Learning with Humans in the Loop (2015)

While there has been remarkable progress in the performance of visual recognition algorithms, the state-of-the-art models tend to be exceptionally data-hungry. Large labeled training datasets, expensive and tedious to produce, are required to optimize millions of parameters in deep network models. Lagging behind the growth in model capacity, the available datasets are quickly becoming outdated in terms of size and density. To circumvent this bottleneck, we propose to amplify human effort through a partially automated labeling scheme, leveraging deep learning with humans in the loop. Starting from a large set of candidate images for each category, we iteratively sample a subset, ask people to label them, classify the others with a trained model, split the set into positives, negatives, and unlabeled based on the classification confidence, and then iterate with the unlabeled set. To assess the effectiveness of this cascading procedure and enable further progress in visual recognition research, we construct a new image dataset, LSUN. It contains around one million labeled images for each of 10 scene categories and 20 object categories. We experiment with training popular convolutional networks and find that they achieve substantial performance gains when trained on this dataset.
Strain-driven self-rolling mechanism for anomalous coiling of multilayer nanohelices (2009)

We have proposed a comprehensive model based on a Cosserat curve to investigate the strain-driven self-rolling mechanism for anomalous coiling of multilayer nanohelices from the biaxial-torque point of view. Special attention has been paid to the edge effects, which dominate the anomalous coiling and decrease the helicity angles to as small as 0. By quantitatively explaining the experiments, we have demonstrated that the edge effects not only generate the torsion torque, together with the initial stress perpendicular to the preferential winding direction, to turn the nanobelts, but also offset part of the initial uniaxial bent torque. Our derived expressions can be used experimentally to determine the geometry of multilayer nanohelices with all helicity angles. The present work has provided useful information for the future experimental investigation on multilayer nanohelices as well as their application in meta-/quantum-devices.
Reflection on the Discovery of Carcinoembryonic Antigen, Prostate-Specific Antigen, and Cancer Antigens CA125 and CA19-9 (2012)

One of the hottest current areas of research is the discovery and validation of novel biomarkers for many diseases, including cancer. For cancers, the reality is that no new major cancer biomarkers have entered the clinic in the last 30 years. Despite the emergence of highly powerful genomic, proteomic, epigenomic, metabolomic, microarray, and other omic technologies, which have been used intensively for the discovery of novel cancer biomarkers, the yield has been poor. In previous analyses, I pinpointed the possible reasons for such failures, and I proposed remedies for avoiding common and repetitive mistakes (1–4). Other accounts have done the same, including some articles in this issue (5, 6).

It is astonishing that some of the most useful cancer biomarkers were discovered in the 1960s [e.g., carcinoembryonic antigen (CEA)8 and α-fetoprotein], the late 1970s [prostate-specific antigen (PSA)], and the early 1980s [cancer antigen 125 (CA125), CA19-9, and some others]. The discoverers of these biomarkers achieved their goals by means of classic analytical techniques, especially the more or less primitive (by today's standards) immunologic and chromatographic assays, or by taking advantage of the then new monoclonal antibody technology, which originated in 1975. If we compare the technological tools of the 1960s to the 1980s with those we have today and the volumes of data that we can generate in the same time with the new high-throughput technologies, we can conclude that contemporary technologies have not delivered the goods promised in the arena of cancer biomarker discovery, at least to date. We should admire the pioneers of cancer biomarker research, who used more ingenuity and inventiveness and less technology to reach their goals. Every major discovery, such as the 4 representative examples described below, has a story behind it, a group of characters, and, similar to a …
欧洲外景地(1):威尼斯 (2001)

神秘旖旎的威尼斯,陷落过多少荡气回肠的故事,因此有电影导演涉猎于此,是极稀松平常的事。但它似乎并不以此为荣,仍旧以它钟爱的习惯流淌着,淹没着,浮光掠影着人间一幕幕悲喜……提及威尼斯的大运河,圣·马可酒店闻名于世的回廊,以及数不尽的水路航道、小桥、舰艇,几乎可以看作威尼斯被公认为世界上最浪漫的风景地之一的代表景物。无数的制片人更是爱煞了这个迷人的水上世界——还记得1963年《来自俄罗斯的爱情》中肖恩·康纳利那艘水陆二用的多功能凤尾艇吗?或者是1979年《Moonraker》中
A strain-isolated fibre Bragg grating sensor for temperature compensation of fibre Bragg grating strain sensors (1998)

This paper describes a method of isolating a fibre Bragg grating (FBG) from strain. This strain-isolated fibre Bragg grating (SIFBG) was then used to make strain-independent temperature measurements. The SIFBG can then be used to compensate for the temperature cross sensitivity of a FBG strain sensor. Initial results using this compensation scheme are presented, demonstrating proof of the principle.
Synthesis of Soluble and Processable Rod-, Arrow-, Teardrop-, and Tetrapod-Shaped CdSe Nanocrystals (2000)

The formation of extremely high aspect ratio CdSe nanorods (30:1), as well as arrow-, teardrop-, tetrapod-, and branched tetrapod-shaped nanocrystals of CdSe, has been achieved by growth of the nanoparticles in a mixture of hexylphosphonic acid and trioctylphosphine oxide. The most influential factors in shape control are the ratio of surfactants, injection volume, and time-dependent monomer concentration.
In vivooptical characterization of human tissues from 610 to 1010 nm by time-resolved reflectance spectroscopy (2001)

A fully automated system for time-resolved reflectance spectroscopy based on tunable mode-locked laser sources and on time-correlated single-photon counting for the detection of time-resolved reflectance data was applied to the evaluation of the optical properties of biological tissues (arm, abdomen and forehead) in vivo from 610 to 1010 nm. The scattering decreases progressively with increasing wavelength, while the absorption line shapes show the typical spectral features of the principal tissue components (haemoglobin, water and lipid), with different weights depending on the tissue type. The best fit of the absorption spectra measured in vivo with the spectra of the pure constituents yielded information on the percentage composition of the different tissues. The interpretation of transport scattering spectra with Mie theory provided information on tissue structure.
Launching genomics into the cloud: deployment of Mercury, a next generation sequence analysis pipeline (2014)

By taking advantage of cloud computing and with Mercury implemented on the DNAnexus platform, we have demonstrated a powerful combination of a robust and fully validated software pipeline and a scalable computational resource that, to date, we have applied to more than 10,000 whole genome and whole exome samples.
A novel oestrogen-regulated gene in human breast cancer cells identified by differential display (1998)

Screening by differential display of oestrogen-sensitive MCF7 human breast cancer cells grown in the short-term (6 days) and long-term (70 weeks) absence of oestrogen has led to the identification of a new oestrogen-regulated mRNA. The cDNA isolated by differential display has 100% homology from nucleotides 615 to 859 of the published sequence for the mRNA for human megakaryocyte CD63 antigen but has a 3' tail extended by 23 nucleotides. Northern blotting has confirmed that this mRNA is regulated by oestrogen in both MCF7 and T47D human breast cancer cell lines.
Fjording the stream: an architecture for queries over streaming sensor data (2003)

If industry visionaries are correct, our lives will soon be full of sensors, connected together in loose conglomerations via wireless networks, each monitoring and collecting data about the environment at large. These sensors behave very differently from traditional database sources: they have intermittent connectivity, are limited by severe power constraints, and typically sample periodically and push immediately, keeping no record of historical information. These limitations make traditional database systems inappropriate for queries over sensors. We present the Fjords architecture for managing multiple queries over many sensors, and show how it can be used to limit sensor resource demands while maintaining high query throughput. We evaluate our architecture using traces from a network of traffic sensors deployed on Interstate 80 near Berkeley and present performance results that show how query throughput, communication costs and power consumption are necessarily coupled in sensor environments.
Mechanism of DNA transesterification by vaccinia topoisomerase: catalytic contributions of essential residues Arg-130, Gly-132, Tyr-136 and Lys-167 (1997)

Vaccinia topoisomerase, a eukaryotic type IB enzyme, catalyzes relaxation of supercoiled DNA by cleaving and rejoining DNA strands through a DNA- (3'-phosphotyrosyl)-enzyme intermediate. We have performed a kinetic analysis of mutational effects at four essential amino acids: Arg-130, Gly-132, Tyr-136 and Lys-167. Arg-130, Gly-132 and Lys-167 are conserved in all members of the type IB topoisomerase family. Tyr-136 is conserved in all poxvirus topoisomerases. We show that Arg-130 and Lys-167 are required for transesterification chemistry. Arg-130 enhances the rates of both cleavage and religation by 10(5). Lys-167 enhances the cleavage and religation reactions by 10(3) and 10(4), respectively. An instructive distinction between these two essential residues is that Arg-130 cannot be replaced by lysine, whereas substituting Lys-167 by arginine resulted in partial restoration of function relative to the alanine mutant. We propose that both basic residues interact directly with the scissile phosphate at the topoisomerase active site. Mutations at positions Gly-132 and Tyr-136 reduced the rate of strand cleavage by more than two orders of magnitude, but elicited only mild effects on religation rate. Gly-132 and Tyr-136 are suggested to facilitate a pre-cleavage activation step. The results of comprehensive mutagenesis of the vaccinia topoisomerase illuminate mechanistic and structural similarities to site-specific recombinases.
Three-dimensional solution structure of the extracellular region of the complement regulatory protein CD59, a new cell-surface protein domain related to snake venom neurotoxins. (1994)

The cell surface antigen CD59 is an inhibitor of complement-mediated lysis and a member of the Ly6 superfamily (Ly6SF) of cysteine-rich cell-surface molecules whose sequences are related to those of snake venom neurotoxins. The three-dimensional solution structure of a recombinant form of the extracellular region of the molecule (residues 1-70 of the mature protein; sCD59) has been solved by 2D NMR methods. sCD59 is a relatively flat, disk-shaped molecule consisting of a two-standed beta-sheet finger loosely packed against a protein core formed by a three-stranded beta-sheet and a short helix. Structure calculations allowed an unambiguous assignment of the disulfide-bonded cysteine pairs as 3-26, 6-13, 19-39, 45-63, and 64-69. The topology of sCD59 is similar to that of the snake venom neurotoxins and consistent with an evolutionary relationship existing between the Ly6SF and the neurotoxins.
Cellular Adjuvant Properties, Direct Cytotoxicity of Re-differentiated Vα24 Invariant NKT-like Cells from Human Induced Pluripotent Stem Cells (2016)

Vα24 invariant natural killer T (iNKT) cells are a subset of T lymphocytes implicated in the regulation of broad immune responses. They recognize lipid antigens presented by CD1d on antigen-presenting cells and induce both innate and adaptive immune responses, which enhance effective immunity against cancer. Conversely, reduced iNKT cell numbers and function have been observed in many patients with cancer. To recover these numbers, we reprogrammed human iNKT cells to pluripotency and then re-differentiated them into regenerated iNKT cells in vitro through an IL-7/IL-15-based optimized cytokine combination. The re-differentiated iNKT cells showed proliferation and IFN-γ production in response to α-galactosylceramide, induced dendritic cell maturation and downstream activation of both cytotoxic T lymphocytes and NK cells, and exhibited NKG2D- and DNAM-1-mediated NK cell-like cytotoxicity against cancer cell lines. The immunological features of re-differentiated iNKT cells and their unlimited availability from induced pluripotent stem cells offer a potentially effective immunotherapy against cancer.
The Marae Temple Grounds in the Society Islands, French Polynesia: A Structural Study of Spatial Relations (2002)

&lt;p&gt;In this paper we will present some of our resent research on ceremonial sites, &lt;em&gt;marae&lt;/em&gt;, in the Society Islands of French Polynesia. These islands are located in the central East Polynesia Ocean, and are divided into the Windward and the Leeward Islands. Our paper considers the structural organization of habitation and ceremonial sites in the Society Islands (cf. Kirch 1996; Ladefoged 1998), as well as relations between &lt;em&gt;marae&lt;/em&gt; and the surrounding landscape.&lt;/p&gt;
THE UBIQUITIN SYSTEM FOR PROTEIN DEGRADATION (1992)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
Short Integuments1/suspensor1/carpel Factory, a Dicer Homolog, Is a Maternal Effect Gene Required for Embryo Development in Arabidopsis (2002)

The importance of maternal cells in controlling early embryogenesis is well understood in animal development, yet in plants the precise role of maternal cells in embryogenesis is unclear. We demonstrated previously that maternal activity of the SIN1 (SHORT INTEGUMENTS1) gene of Arabidopsis is essential for embryo pattern formation and viability, and that its postembryonic activity is required for several processes in reproductive development, including flowering time control and ovule morphogenesis. Here, we report the cloning of SIN1, and demonstrate its identity to the CAF (CARPEL FACTORY) gene important for normal flower morphogenesis and to the SUS1 (SUSPENSOR1) gene essential for embryogenesis. SIN1/SUS1/CAF has sequence similarity to the Drosophila melanogaster gene Dicer, which encodes a multidomain ribonuclease specific for double-stranded RNA, first identified by its role in RNA silencing. The Dicer protein is essential for temporal control of development in animals, through the processing of small RNA hairpins that in turn inhibit the translation of target mRNAs. Structural modeling of the wild-type and sin1 mutant proteins indicates that the RNA helicase domain of SIN1/SUS1/CAF is important for function. The mRNA was detected in floral meristems, ovules, and early embryos, consistent with the mutant phenotypes. A 3.3-kb region 5' of the SIN1/SUS1/CAF gene shows asymmetric parent-of-origin activity in the embryo: It confers transcriptional activation of a reporter gene in early embryos only when transmitted through the maternal gamete. These results suggest that maternal SIN1/SUS1/CAF functions early in Arabidopsis development, presumably through posttranscriptional regulation of specific mRNA molecules.
Effect of disruption of Pichia pastoris YPS1 gene on viability and production of recombinant proteins (2013)

In the present study, we constructed a Pichia pastoris mutant strain PS111 that lacks one member of the yapsin family through disruption of the YPS1 gene coding for aspartic protease yapsin 1. Under normal growth conditions, the PS111 mutant strain did not show detectable growth defects. Unlike the S. cerevisiaeyps1 mutant, the P. pastoris PS111 strain showed no sensitivity when grown in the presence of CaCl2, elevated temperature (37 degrees C), under acid (pH 4.9) and alkaline (pH 8.3) conditions. Unlike the S. cerevisiae, the P. pastoris yps1 mutant showed decreased growth phenotype induced by cell wall-perturbing reagent sodium dodecyl sulfate (SDS) only when the concentration of SDS was increased by ten times. The use of the yps1 disruptant to produce human interferon alpha 16 (hINF-alpha 16) prevents proteolysis, which occurs in the wild-type strain. It was found that the degradation of recombinant protein Alburon composed of human serum albumin (HSA) and hINF-alpha 16 was slightly decreased in the strain lacking yapsin 1.
A Dose-Ranging Study of Pegylated Interferon Alfa-2b and Ribavirin in Chronic Hepatitis C (2000)

The objectives of this study were to assess the safety, pharmacokinetics, and efficacy of pegylated interferon alfa-2b (PEG-Intron) plus ribavirin in patients with chronic hepatitis C. A total of 72 patients (35 men/37 women, age range 20-68 years) with clinically compensated chronic hepatitis C virus (HCV) were enrolled into this open-label, randomized, active controlled study. Patients received either PEG-Intron 0.35, 0.7, or 1.4 microg/kg subcutaneously weekly for 24 weeks alone, or in combination with ribavirin 600, 800, or 1,000 to 1,200 mg orally daily. Patients were evaluated during treatment and after a 24-week follow-up period for safety and efficacy. Detailed pharmacokinetic assessments were performed at weeks 1 and 4. PEG-Intron alone produced expected dose-related reductions in white cells, neutrophils and platelets. Addition of ribavirin reduced hemoglobin levels in a dose-related manner, did not further reduce PEG-Intron-induced decreases in neutrophil or white cell count, and increased platelet counts. Neutrophil function tests (C5a and FMLP migration, killing curves) were unaltered. Reported adverse events (flu-like symptoms, asthenia) were qualitatively similar in all dose groups. Anti-HCV activity, as measured by loss of detectable serum HCV RNA (i.e. <100 copies/mL) at the end of treatment (week 24) and after 24 weeks of follow-up (week 48) showed dose-response trends for PEG-Intron. At each PEG-Intron dose level, anti-HCV activity was higher in patients coadministered ribavirin than in patients treated with PEG-Intron monotherapy. There was no evidence of pharmacokinetic interactions with either drug. We conclude that the safety and tolerability of combined PEG-Intron/ribavirin and PEG-Intron alone were comparable. Combined PEG-Intron/ribavirin showed dose-related synergistic anti-HCV effects, which were numerically superior to those obtained with PEG-Intron monotherapy.
Neonatal Encephalopathy: Treatment with Hypothermia (2009)

In this article, the role of hypothermia and neuroprotection for neonatal encephalopathy will be discussed. The incidence of encephalopathy due to hypoxia ischemia as well as the pathophysiology will be presented. The diagnosis of encephalopathy in full-term neonates will be discussed. The current management of brain injury that occurs with hypoxia ischemia and the role of hypothermia in preventing brain injury in fetal and neonatal animal models will be reviewed. The current data from randomized control trials of hypothermia as neuroprotection for full-term infants will be presented along with the results of meta-analyses of these trials. Lastly, the status of ongoing neonatal hypothermia trials will be summarized.
In Vivo Confocal Microscopy of Corneal Nerves: Analysis and Clinical Correlation (2010)

Corneal confocal microscopy is a growing technique for the study of the cornea at the cellular level, providing images comparable to ex vivo histochemical methods. In vivo confocal microscopy (IVCM) has an enormous potential, being a noninvasive procedure that images the living cornea, to study both its physiological and pathological states. Corneal nerves are of great interest to clinicians and scientists due to their important roles in regulating corneal sensation, epithelial integrity, proliferation, wound healing, and for their protective functions. IVCM enables the noninvasive examination of corneal nerves, allowing the study of nerve alterations in different ocular diseases, after corneal surgery, and in systemic diseases. To date, the correlation of sub-basal corneal nerves and their function has been studied in normal eyes, keratoconus, dry eye, contact lens wearers, and in neurotrophic keratopathy, among others. Further, the effect of corneal surgery on nerves has been studied, demonstrating the regenerative capacity of corneal nerves and the recovery of sensation. Moreover, IVCM has been applied in the diagnosis of peripheral diabetic neuropathy and the assessment of progression in this systemic disease. The purpose of this review is to describe the principles, applications, and clinical correlation of IVCM in the study of corneal nerves in different ocular and systemic diseases.
Investigating Glycol-Split-Heparin-Derived Inhibitors of Heparanase: A Study of Synthetic Trisaccharides (2016)

Heparanase is the only known endoglycosidase able to cleave heparan sulfate. Roneparstat and necuparanib, heparanase inhibitors obtained from heparin and currently being tested in man as a potential drugs against cancer, contain in their structure glycol-split uronic acid moieties probably responsible for their strong inhibitory activity. We describe here the total chemical synthesis of the trisaccharide GlcNS6S-GlcA-1,6anGlcNS (<b>1</b>) and its glycol-split (gs) counterpart GlcNS6S-gsGlcA-1,6anGlcNS (<b>2</b>) from glucose. As expected, in a heparanase inhibition assay, compound <b>2</b> is one order of magnitude more potent than <b>1</b>. Using molecular modeling techniques we have created a 3D model of <b>1</b> and <b>2</b> that has been validated by NOESY NMR experiments. The pure synthetic oligosaccharides have allowed the first in depth study of the conformation of a glycol-split glucuronic acid. Introducing a glycol-split unit in the structure of <b>1</b> increases the conformational flexibility and shortens the distance between the two glucosamine motives, thus promoting interaction with heparanase. However, comparing the relative activities of <b>2</b> and roneparstat, we can conclude that the glycol-split motive is not the only determinant of the strong inhibitory effect of roneparstat.