gebhart/patrepeval huggingface dataset:
Age at menarche, probability of ovulation and breast cancer risk (1982)

An analysis is undertaken of the frequency of ovulation in 17 groups of women aged 15 to 19 who had been the subjects of other studies. A urine specimen of at least 8 h accumulation had been provided on the 20th or 21st day of a menstrual cycle by 681 women. Analysis is restricted to 431 specimens which had been collected between 11 and 3 days prior to the onset of the subsequent menstrual period. A pregnanediol concentration of less than 1 mg per litre in such a specimen was taken as evidence that the cycle was anovular. The probability of a cycle being anovular was inversely and significantly related to the number of years since menarche, and, with years since menarche held constant, was positively but not significantly associated with age at menarche. This observation indicates that women with early menarche do not have a longer duration of exposure to anovular cycles than do those whose menarche is delayed, and that variation in the duration of exposure to post-menarcheal anovular cycles does not explain the association of breast cancer risk with early age at menarche. The 17 groups of women were classified into four categories according to ethnic origin and breast cancer incidence in the populations from which they derived. Anovular cycles were not more common in the high-risk groups; indeed, the two centers in the lowest risk category had the highest proportion of anovular cycles.
Metal-free aqueous redox capacitor via proton rocking-chair system in an organic-based couple (2014)

Safe and inexpensive energy storage devices with long cycle lifetimes and high power and energy densities are mandatory for the development of electrical power grids that connect with renewable energy sources. In this study, we demonstrated metal-free aqueous redox capacitors using couples comprising low-molecular-weight organic compounds. In addition to the electric double layer formation, proton insertion/extraction reactions between a couple consisting of inexpensive quinones/hydroquinones contributed to the energy storage. This energy storage mechanism, in which protons are shuttled back and forth between two electrodes upon charge and discharge, can be regarded as a proton rocking-chair system. The fabricated capacitor showed a large capacity (>20 Wh/kg), even in the applied potential range between 0-1 V, and high power capability (>5 A/g). The support of the organic compounds in nanoporous carbon facilitated the efficient use of the organic compounds with a lifetime of thousands of cycles.
Selective Nucleophilic Replacement of the Benzylsulfanyl Group in 2,4‐Disulfanyl‐substituted Thieno[2,3‐d]pyrimidin‐6‐carboxylic Acid Derivatives by Secondary Amines. (2005)

Abstract For Abstract see ChemInform Abstract in Full Text.
Host Intraspatial Selection of Infectious Bronchitis Virus Populations (2010)

Arkansas (Ark)-type infectious bronchitis virus (IBV) subpopulations with an S gene sequence distinct from the vaccine predominant consensus were previously found in the upper respiratory tract of chickens within 3 days after inoculation. This finding indicated that a distinct virus subpopulation was rapidly positively selected by the chicken upper respiratory tract. We hypothesized that during host invasion, the replicating IBV population further changes as it confronts the distinct environments of different tissues, leading to selection of the most fit population. We inoculated 15-day-old chickens with 10(4) 50% embryo infective doses of an Ark-type IBV commercial vaccine via the ocular and nasal routes and characterized the sequences of the S1 gene of IBV contained in tear fluid, trachea, and reproductive tract of individual chickens at different times postinoculation. The predominant IBV phenotype contained in the vaccine (before inoculation) became a minor or nondetectable population at all times in all tissues after replication in the majority of the chickens, corroborating our previous findings. Five new predominant populations designated component (C) 1 through C5, showing distinct nonsynonymous changes, i.e., nucleotide changes resulting in different amino acids encoded and thus in a phenotypic change of the predominant virus population, were detected in the tissues or fluids of individual vaccinated chickens. Due to the different biochemical properties of some amino acids that changed in the S1 glycoprotein, we anticipate that phenotypic shift occurred during the invasion process. Significant differences were detected in the incidence of some distinct IBV predominant populations in tissues and fluids; e.g., phenotype C1 showed the highest incidence in the reproductive tract of the chickens, achieving a significant difference versus its incidence in the trachea (P < 0.05). These results indicate for the first time that IBV undergoes intraspatial variation during host invasion, i.e., the dominant genotype/phenotype further changes during host invasion as the microenvironment of distinct tissues exerts selective pressure on the replicating virus population.
Continuous separation of microparticles by size with Direct current‐dielectrophoresis (2005)

Direct current-dielectrophoresis (DC-DEP), the induced motion of the dielectric particles in a spatially nonuniform DC electric field, is demonstrated to be a highly efficient method to separate the microparticles by size. The locally nonuniform electric field is generated by an insulating block fabricated inside a polydimethylsiloxane microchannel. The particle experiences a negative DEP (accordingly a repulsive force) at the corners of the block, where the local electric-field strength is the strongest. Thus, the particle deviates from the streamline and the degree of deviation is dependent on the DEP force (i.e., the particle size). Combined with the electrokinetic flow, mixed polystyrene particles of a few micrometers difference in diameter can be continuously separated into distinct reservoirs. For separating target particles of a specific size, it is required to simply adjust the voltage outputs of the electrodes. A numerical model based on the Lagrangian tracking method is developed to simulate the particle motion and the results showed a reasonable agreement with the experimental data.
Efficient construction of producer cell lines for a SIN lentiviral vector for SCID-X1 gene therapy by concatemeric array transfection (2009)

Retroviral vectors containing internal promoters, chromatin insulators, and self-inactivating (SIN) long terminal repeats (LTRs) may have significantly reduced genotoxicity relative to the conventional retroviral vectors used in recent, otherwise successful clinical trials. Large-scale production of such vectors is problematic, however, as the introduction of SIN vectors into packaging cells cannot be accomplished with the traditional method of viral transduction. We have derived a set of packaging cell lines for HIV-based lentiviral vectors and developed a novel concatemeric array transfection technique for the introduction of SIN vector genomes devoid of enhancer and promoter sequences in the LTR. We used this method to derive a producer cell clone for a SIN lentiviral vector expressing green fluorescent protein, which when grown in a bioreactor generated more than 20 L of supernatant with titers above 10(7) transducing units (TU) per milliliter. Further refinement of our technique enabled the rapid generation of whole populations of stably transformed cells that produced similar titers. Finally, we describe the construction of an insulated, SIN lentiviral vector encoding the human interleukin 2 receptor common gamma chain (IL2RG) gene and the efficient derivation of cloned producer cells that generate supernatants with titers greater than 5 x 10(7) TU/mL and that are suitable for use in a clinical trial for X-linked severe combined immunodeficiency (SCID-X1).
Massive and Reproducible Production of Liver Buds Entirely from Human Pluripotent Stem Cells (2017)

Organoid technology provides a revolutionary paradigm toward therapy but has yet to be applied in humans, mainly because of reproducibility and scalability challenges. Here, we overcome these limitations by evolving a scalable organ bud production platform entirely from human induced pluripotent stem cells (iPSC). By conducting massive "reverse" screen experiments, we identified three progenitor populations that can effectively generate liver buds in a highly reproducible manner: hepatic endoderm, endothelium, and septum mesenchyme. Furthermore, we achieved human scalability by developing an omni-well-array culture platform for mass producing homogeneous and miniaturized liver buds on a clinically relevant large scale (>10<sup>8</sup>). Vascularized and functional liver tissues generated entirely from iPSCs significantly improved subsequent hepatic functionalization potentiated by stage-matched developmental progenitor interactions, enabling functional rescue against acute liver failure via transplantation. Overall, our study provides a stringent manufacturing platform for multicellular organoid supply, thus facilitating clinical and pharmaceutical applications especially for the treatment of liver diseases through multi-industrial collaborations.
Human Islet Separation Utilizing a Closed Automated Purification System (2008)

A central step within the human islet isolation process is the separation of islets from contaminating exocrine tissue utilizing linear, continuous density gradients manufactured by means of manually controlled standard gradient makers (SGM). The present study was performed to develop a closed, automated purification system (APS) that customizes density gradient profiles aiming to standardize and optimize human islet purification. Digested human pancreata were pooled, split evenly, and incubated in UW solution according to our standard protocol (n = 11). Continuous density gradient centrifugation was performed in parallel in two refrigerated COBE 2991 cell separators loaded with light (1.076 g/ml) and heavy (1.097 g/ml) Ficoll utilizing either an SGM or two computer-controlled pumps connected to Ficoll-containing bags. Quality control included islet equivalent (IE) yield, purity, in vitro function, and islet cytokine expression. Gradient profiles demonstrated that the APS readily customizes linear and nonlinear gradients. In comparison to the SGM, the APS recovered a higher percentage of the expected volume of continuous gradients (90.0 +/- 1.1% vs. 98.2 +/- 2.0%, p < 0.05). Islet yield (120,468 +/- 15,970 vs. 114,570 +/- 15,313 IE, NS) and purity (51.7 +/- 4.8% vs. 54.4 +/- 4.9%, NS) were nearly identical utilizing the SGM or APS. Decreased MCP-1, IL-6, and IL-8 expression indicated that APS-purified islets were possibly exposed to less proinflammatory stress. Compared to standard procedures, similar success and gentle continuous density gradient separation of human islets is feasible utilizing the APS. The APS facilitates the standardization of this complex procedure according to cGMP standards.
Appearance compression and synthesis based on 3D model for mixed reality (1999)

Rendering photorealistic virtual objects from their real images is one of the main research issues in mixed reality systems. We previously proposed the Eigen-Texture method (K. Nishino et al., 1999), a new rendering method for generating virtual images of objects from their real images to deal with the problems posed by past work in image based methods and model based methods. Eigen-Texture method samples appearances of a real object under various illumination and viewing conditions, and compresses them in the 2D coordinate system defined on the 3D model surface. However, we had a serious limitation in our system, due to the alignment problem of the 3D model and color images. We deal with this limitation by solving the alignment problem; we do this by using the method originally designed by P. Viola (1995). The paper describes the method and reports on how we implement it.
HPV16 E6 and E7 proteins induce a chronic oxidative stress response via NOX2 that causes genomic instability and increased susceptibility to DNA damage in head and neck cancer cells (2015)

Human papillomavirus (HPV) is the causative agent of a subgroup of head and neck cancer characterized by an intrinsic radiosensitivity. HPV initiates cellular transformation through the activity of E6 and E7 proteins. E6 and E7 expression is necessary but not sufficient to transform the host cell, as genomic instability is required to acquire the malignant phenotype in HPV-initiated cells. This study reveals a key role played by oxidative stress in promoting genomic instability and radiosensitivity in HPV-positive head and neck cancer. By employing an isogenic human cell model, we observed that expression of E6 and E7 is sufficient to induce reactive oxygen species (ROS) generation in head and neck cancer cells. E6/E7-induced oxidative stress is mediated by nicotinamide adenine dinucleotide phosphate oxidases (NOXs) and causes DNA damage and chromosomal aberrations. This mechanism for genomic instability distinguishes HPV-positive from HPV-negative tumors, as we observed NOX-induced oxidative stress in HPV-positive but not HPV-negative head and neck cancer cells. We identified NOX2 as the source of HPV-induced oxidative stress as NOX2 silencing significantly reduced ROS generation, DNA damage and chromosomal aberrations in HPV-positive cells. Due to their state of chronic oxidative stress, HPV-positive cells are more susceptible to DNA damage induced by ROS and ionizing radiation (IR). Furthermore, exposure to IR results in the formation of complex lesions in HPV-positive cells as indicated by the higher amount of chromosomal breakage observed in this group of cells. These results reveal a novel mechanism for sustaining genomic instability in HPV-positive head and neck tumors and elucidate its contribution to their intrinsic radiosensitivity.
Parallel Computation in Econometrics: A Simplified Approach (2004)

Parallel computation has a long history in econometric computing, but is not at all wide spread. We believe that a major impediment is the labour cost of coding for parallel architectures. Moreover, programs for specific hardware often become obsolete quite quickly. Our approach is to take a popular matrix programming language (Ox), and implement a message-passing interface using MPI. Next, object-oriented programming allows us to hide the specific parallelization code, so that a program does not need to be rewritten when it is ported from the desktop to a distributed network of computers. Our focus is on so-called embarrassingly parallel computations, and we address the issue of parallel random number generation.
Role of the phosphoryl group of .BETA.-casein in milk curdling. (1982)

β-Casein was modified by trypsin, chymosin or phosphoprotein phosphatase. Each modified β-casein was fortified to the test-milk which was pretreated at 10°C by immobilized thermolysin to curdle non-enzymatically at 35°C. Fortification with chymosin-modified β-casein, devoid of the hydrophobic moiety near the C-terminus, increased the curd tension as did native β-casein. The test-milk fortified with trypsin-modified β-casein, which has been deleted some part of the hydrophilic region near the N-terminus, had similar curd tension to unfortified test-milk. The test-milk fortified with dephosphorylated β-casein, formed a softer curd than that with native β-casein. Trypsin-modified β-casein or dephosphorylated β-casein retained its associative ability, but chymosin-modified β-casein revealed negligible ability to associate. These results led to the conclusion that the phosphoryl group on the hydrophilic moiety of β-casein contributes to the increase in curd tension, while the hydrophobic moiety is responsible for the association of β-casein.
Officers and Arms: The 1843 General Return of the Nauvoo Legion's Second Cohort (1995)

The Nauvoo Legion was probably more a skeleton organization than the fully manned and impressively equipped force memorialized by popular artists and writers.
Cloning, Expression, and Chromosomal Localization of the Human Uridine Nucleotide Receptor Gene (1995)

Extracellular ATP and ADP mediate diverse physiological responses in mammalian cells, in part through the activation of G protein-coupled P2 purinoceptors. The cloning and expression of cDNAs encoding several P2 purinoceptor subtypes have enabled rapid advances in our understanding of the structural and functional properties of these receptors. The current report describes the isolation of a gene from a human genomic library that encodes a protein with the greatest similarity to the human P2U purinoceptor, a subtype that is distinguished by its ability to be activated by uridine nucleotides as well as adenine nucleotides. When expressed in a mammalian cell line, this novel receptor is activated specifically by UTP and UDP but not by ATP and ADP. Activation of this uridine nucleotide receptor resulted in increased inositol phosphate formation and calcium mobilization. Fluorescence in situ hybridization revealed that the gene encoding the uridine nucleotide receptor is located in region q13 of the X chromosome. Dendrogram analysis of the G protein-coupled P2 purinoceptors and the uridine nucleotide receptor indicates that these receptors belong to a family that may be more aptly named nucleotide receptors.
EphA2 overexpression correlates with poor prognosis in esophageal squamous cell carcinoma (2002)

EphA2 is a member of the Eph family of receptor tyrosine kinases, which interact with cell-bound ligands known as ephrins. EphA2 expression was investigated by immunohistochemistry with an anti-EphA2 monoclonal antibody in 80 patients with esophageal squamous cell carcinoma (ESCC) who had undergone surgery. EphA2 overexpression was positive in 40 of the 80 patients (50%). A significant correlation was observed between EphA2 expression and regional lymph node metastasis (p=0.023), number of lymph node metastases (p=0.011) and poor degree of tumor differentiation (p=0.004). The survival rates of EphA2-positive patients were poorer than those of EphA2-negative patients (p=0.014). The 5-year survival rate of patients without EphA2 overexpression was 68%, whereas that of patients with EphA2 overexpression was 29%. EphA2 expression was also investigated in 7 ESCC cell lines (TE-1, -2, -8, -13, -15, TT and TTn) and 1 immortalized human esophageal keratinocyte cell line (CHEK-1). Western blotting revealed different levels of EphA2 expression in the 8 cell lines. EphA2 was expressed at a high level in the ESCC cell lines compared to CHEK-1. EphA2 phosphorylation was demonstrated in all cell lines. Northern blot analysis showed that EphA2 mRNA expression in TE-1 was greater than that in the other ESCC cell lines. The observation of small gaps on Western blot analysis of the ESCC cell lines suggests that there may be a mechanism for EphA2 regulation at the point of translation. In conclusion, EphA2 overexpression appears to be related to poor degree of tumor differentiation and lymph node metastasis in ESCC. Consequently, patients with EphA2 overexpression have a poorer prognosis than those without. EphA2 is a potential target to prevent ESCC cells spreading into the lymphatic drainage.
T‐DM1, a novel antibody–drug conjugate, is highly effective against primary HER2 overexpressing uterine serous carcinoma in vitro and in vivo (2014)

Amplification of c-erbB2 has been reported in over 30% of uterine serous carcinoma (USC) and found to confer poor survival because of high proliferation and increased resistance to therapy. In this study, we evaluated for the first time Trastuzumab emtansine (T-DM1), a novel antibody-drug conjugate, against multiple epidermal growth factor receptor-2 (HER2)-positive USC cells in vitro followed by developing a supportive in vivo model. Fifteen primary USC cell lines were assessed by immunohistochemistry (IHC) and flow cytometry for HER2 protein expression. C-erbB2 gene amplification was evaluated using fluorescent in situ hybridization. Sensitivity to T-DM1 and trastuzumab (T)-induced antibody-dependent cell-mediated cytotoxicity was evaluated in 5-h chromium release assays. T-DM1 and T cytostatic and apoptotic activities were evaluated using flow-cytometry-based proliferation assays. In vivo activity of T-DM1 versus T in USC xenografts in SCID mice was also evaluated. High levels of HER2 protein overexpression and HER2 gene amplification were detected in 33% of USC cell lines. T-DM1 was considerably more effective than trastuzumab in inhibiting cell proliferation and in causing apoptosis (P = 0.004) of USC showing HER2 overexpression. Importantly, T-DM1 was highly active at reducing tumor formation in vivo in USC xenografts overexpressing HER2 (P = 0.04) and mice treated with TDM-1 had significantly longer survival when compared to T-treated mice and control mice (P ≤ 0.0001). T-DM1 shows promising antitumor effect in HER2-positive USC cell lines and USC xenografts and its activity is significantly higher when compared to T. T-DM1 may represent a novel treatment option for HER2-positive USC patients with disease refractory to trastuzumab and traditional chemotherapy.
The p110δ subunit of phosphoinositide 3-kinase is required for the lipopolysaccharide response of mouse B cells (2004)

PI3K (phosphoinositide 3-kinase) I(A) family members contain a regulatory subunit and a catalytic subunit. The p110delta catalytic subunit is expressed predominantly in haematopoietic cells. There, among other functions, it regulates antigen receptor-mediated responses. Using mice deficient in the p110delta subunit of PI3K, we investigated the role of this subunit in LPS (lipopolysaccharide)-induced B cell responses, which are mediated by Toll-like receptor 4 and RP105. After injection of DNP-LPS (where DNP stands for 2,4-dinitrophenol), p110delta(-/-) mice produced reduced levels of DNP-specific IgM and IgG when compared with wild-type mice. In vitro, the proliferation and up-regulation of surface activation markers such as CD86 and CD25 induced by LPS and an antibody against RP105 were decreased. We analysed the activation state of key components of the LPS pathway in B cells to determine whether there was a defect in signalling in p110delta(-/-) B cells. They showed normal extracellular-signal-regulated kinase phosphorylation, but anti-RP105-induced protein kinase B, IkappaB (inhibitor of nuclear factor kappaB) and c-Jun N-terminal kinase activation was severely reduced. This demonstrates that the p110delta subunit of PI3K is involved in the LPS response in B cells and may represent a link between the innate and the adaptive immune system.
Ferric carboxymaltose: A revolution in the treatment of postpartum anemia in Indian women (2015)

Ferric carboxymaltose elevates Hb level and restores iron stores faster than IV iron sucrose and oral iron, without any severe adverse reactions. There was better overall satisfaction reported by the patients who received FCM treatment.