gebhart/patrepeval huggingface dataset:
Optically Anomalous Crystals (1992)

Abstract The optical symmetry of many crystals is lower than would be expected from their external form and X‐ray diffraction data. Recently such optical anomalies have been attributed to nonequilibrium structures resulting from kinetically controlled crystal growth. Impurities are incorporated to different extents at various surface sites that would otherwise have become symmetry‐related within the bulk crystal. After their discovery by Brewster in 1815, optically anomalous crystals were the subject of lively debate throughout the 19th century among some of the most distinguished contributors to the development of crystallography including Biot, Berzelius, Herschel, Mitscherlich, Frankenheim, Pasteur, Mallard, Klein, Groth, Wyrouboff, Barlow, Brauns, Rinne, Pockels, and Friedel. From a sea of wild speculation two conflicting postulates emerged: that the symmetric form resulted from accidental twinning of segments with lower symmetry, or that the optical peculiarities resulted from stress due to impurities or external perturbations. Neither postulate expresses the present view. Interest in this research waned at the turn of the century, and after 1917 no one pursued Tammann's alternative correct insight. The problem of anomalous double refraction attracted no attention for more than half a century until its recent solution. This review discusses both mineral and organic systems with particular emphasis on the phyllosilicate apophyllite and on 1,5‐dichloro‐2,3‐dinitrobenzene. These nonequilibrium structures relate to questions of crystal order, crystal growth, molecular recognition, and the design of new materials. The review provides a reminder of the enduring value of the polarizing microscope as a research tool in chemistry.
MECHANICAL PROPERTIES OF REINFORCED MORTAR BY FLY ASH FIBER PRODUCED BY FUSING COAL ASH : Fundamental studies on utilization of coal ash for cement products (1997)

Recently, some methods to utilize the coal ash, that occurs as a waste product of thermal power plant operation, have been investigated. Fly ash fiber, that is produced by fusing coal ash and at high temperature and pulling it into fibers, exhibits high strength, thermal resistance and alkali-proof. Therefore, it was thought that if fly ash fiber could be used in the making of reinforced mortar, precast products of high strength, thermal resistance and durability would result. This report describes test results on the mechanical properties of fly ash fiber reinforced mortar. As a result, it was confirmed that the fly ash fiber reinforce mortar maintained excellent workability, high flexural strength and thermal resistance.
Cardiac regeneration based on mechanisms of cardiomyocyte proliferation and differentiation (2014)

Cardiomyocyte proliferation and progenitor differentiation are endogenous mechanisms of myocardial development. Cardiomyocytes continue to proliferate in mammals for part of post-natal development. In adult mammals under homeostatic conditions, cardiomyocytes proliferate at an extremely low rate. Because the mechanisms of cardiomyocyte generation provide potential targets for stimulating myocardial regeneration, a deep understanding is required for developing such strategies. We will discuss approaches for examining cardiomyocyte regeneration, review the specific advantages, challenges, and controversies, and recommend approaches for interpretation of results. We will also draw parallels between developmental and regenerative principles of these mechanisms and how they could be targeted for treating heart failure.
Molecular genetic and biochemical analyses of FGF23 mutations in familial tumoral calcinosis (2008)

Fibroblast growth factor 23 (FGF23) is a hormone required for normal renal phosphate reabsorption. FGF23 gain-of-function mutations result in autosomal dominant hypophosphatemic rickets (ADHR), and FGF23 loss-of-function mutations cause familial hyperphosphatemic tumoral calcinosis (TC). In this study, we identified a novel recessive FGF23 TC mutation, a lysine (K) substitution for glutamine (Q) (160 C>A) at residue 54 (Q54K). To understand the molecular consequences of all known FGF23-TC mutants (H41Q, S71G, M96T, S129F, and Q54K), these proteins were stably expressed in vitro. Western analyses revealed minimal amounts of secreted intact protein for all mutants, and ELISA analyses demonstrated high levels of secreted COOH-terminal FGF23 fragments but low amounts of intact protein, consistent with TC patients' FGF23 serum profiles. Mutant protein function was tested and showed residual, yet decreased, bioactivity compared with wild-type protein. In examining the role of the FGF23 COOH-terminal tail (residues 180-251) in protein processing and activity, truncated mutants revealed that the majority of the residues downstream from the known FGF23 SPC protease site ((176)RXXR(179)/S(180)) were not required for protein secretion. However, residues adjacent to the RXXR site (between residues 188 and 202) were required for full bioactivity. In summary, we report a novel TC mutation and demonstrate a common defect of reduced FGF23 stability for all known FGF23-TC mutants. Finally, the majority of the COOH-terminal tail of FGF23 is not required for protein secretion but is required for full bioactivity.
Toll-like receptors and their role in carcinogenesis and anti-tumor treatment (2008)

Toll-like receptors (TLRs) have been described as major components of the innate immune system, recognizing the conserved molecular structures found in the large groups of pathogens called pathogen-associated molecular patterns (PAMPs). TLR expression is ubiquitous, from epithelial to immunocompetent cells. TLR ligation triggers several adapter proteins and downstream kinases, leading to the induction of key pro-inflammatory mediators but also anti-inflammatory and anti-tumor cytokines. The result of this activation goes beyond innate immunity to shape the adaptive responses against pathogens and tumor cells, and maintains host homeostasis via cell debris utilization. TLRs have already become potent targets in infectious disease treatment and vaccine therapy and in neoplastic disease treatment, due to their ability to enhance antigen presentation. However, some studies show the dual effect of TLR stimulation on malignant cells: they can be proapoptotic or promote survival under different conditions. It is therefore crucial to design further studies assessing the biology of these receptors in normal and transformed cells. The established role of TLRs in human disease therapy is based on TLR7 and TLR4 agonists, respectively for the novel treatment of some types of skin cancer and for the anti-hepatitis B virus vaccine. Some clinical trials involving TLR agonists as potent enhancers of the anti-tumor response in solid tumors have begun.
Regulation of the membrane attack complex of complement. Evidence that C8 gamma is not the target of homologous restriction factors. (1990)

Inability of the membrane attack complex of C (C5b-9) to efficiently lyse E from the same species has been attributed to one or more membrane-associated proteins that are collectively called homologous restriction factors. These include a 65,000 Mr protein referred to as the C8 binding protein or homologous restriction factor and a 20,000 Mr protein referred to as P-18, HRF20, CD59 Ag, or MIRL. Both are found on nucleated cells as well as E and both protect against complement-mediated lysis by interfering with C8 and/or C9 function within C5b-9. The exact mechanism by which these factors restrict activity is unknown but studies with purified C8 binding protein suggest they may interact specifically with the gamma subunit of C8. To determine directly if gamma is the target of restriction factors, a derivative of human C8 lacking this subunit was evaluated for its potential to lyse homologous cells. This derivative (C8') was previously shown to be functionally equivalent to normal C8 in a heterologous sheep E system. Here, it is compared to normal C8 by using human E as target cells. Results indicate no difference between the ability of C8 and C8' to incorporate into HuEAC1-7, to mediate subsequent C9 binding and to promote hemolysis. Thus, the presence or absence of gamma has no effect on homologous restriction of C5b-9, therefore gamma cannot be the primary target of homologous restriction factors.
Automated Electronic Circuit Manufacturing Using Ink-Jet Technology (1989)

The feasibility of using ink-jet technology to write circuits on PC board material and TAB substrate has been demonstrated. Several systems were evaluated and the most successful system used paraffin as a resist material on a copper substrate. The copper was etched and the paraffin subsequently removed to form the conductive paths of the circuit. Line widths down to 100μm were achieved, and line widths of 50μm were shown feasible. The generation of the print pattern from a computer file illustrated the potential of coupling a circuit writing system to an electrical CAD system to provide rapid turnaround prototype circuits.
Isolation and characterization of a rice WUSCHEL‐type homeobox gene that is specifically expressed in the central cells of a quiescent center in the root apical meristem (2003)

The Arabidopsis WUSCHEL (WUS) protein, which plays an important role in the specification of the stem cells in the shoot apical meristem (SAM), contains an 'atypical' homeodomain (HD) with extra residues in its loop and turn regions. We speculated that a WUS-type atypical HD protein might also be involved in the specification and maintenance of the root apical meristem (RAM) stem cells of rice. To investigate this possibility, we isolated and characterized a rice WUS-type homeobox gene designated quiescent-center-specific homeobox (QHB) gene. Using transformants carrying the QHB promoter-GUS and in situ hybridization, we found that QHB was specifically expressed in the central cells of a quiescent center (QC) of the root. During embryogenesis and crown root formation, QHB expression was observed prior to the morphological differentiation of the root. However, we detected different QHB expression patterns in the process of the RAM development, specifically between radicle and crown root formation, suggesting that the cell-fate determination of the QC may be controlled by different mechanisms. We also produced transformants that overexpress QHB or Arabidopsis WUS. These transformants did not form crown roots, but developed multiple shoots from ectopic SAMs with malformed leaves. On the basis of these observations, we propose that the WUS-type homeobox gene is involved in the specification and maintenance of the stem cells (QC cells) in the RAM, by a mechanism similar to that for WUS in the SAM.
Expression of human alpha 1-antitrypsin in dogs after autologous transplantation of retroviral transduced hepatocytes. (1992)

The liver represents an excellent organ for gene therapy since many genetic disorders result from the deficiency of liver-specific gene products. We have previously demonstrated that transgenic mouse hepatocytes can be heterologously transplanted into congenic recipients where they survived indefinitely and continued to function as hepatocytes. Here we demonstrate the autologous transplantation of retrovirally transduced canine hepatocytes. At least 1 x 10(9) hepatocytes or 5% of the liver mass can be transplanted by the portal vasculature. In two animals we have transplanted hepatocytes transduced with a retroviral vector containing the human alpha 1-antitrypsin cDNA under transcriptional control of the cytomegalovirus promoter. Both animals had significant human alpha 1-antitrypsin in the serum for 1 month. Although the serum levels of human alpha 1-antitrypsin eventually fell due to inactivation of the cytomegalovirus promoter, PCR analysis demonstrated that a significant fraction of transduced hepatocytes migrated to the liver and continued to survive in vivo. The results suggest that gene therapy of hepatic deficiencies may be achieved by hepatocellular transplantation after genetic reconstitution with the use of promoters of cellular genes that are active in the normal liver.
Predictive Factors of Tumor Response and Prognostic Factors of Survival during Lung Cancer Chemotherapy (1998)

The aim of this study was (i) to determine predictive factors of a complete response to chemotherapy in small cell lung cancer (SCLC) and predictive factors of an objective response in non-small cell lung cancer (NSCLC) and (ii) to determine whether prognostic factors are different with regard to treatment response and survival. Ninety-nine patients with SCLC and two hundred and two patients with NSCLC received chemotherapy. The following variables were recorded prior to treatment: tumor, node, metastasis status, performance status, body weight loss, blood leukocyte count, serum sodium, serum albumin, lactate dehydrogenase (LDH), alkaline phosphatase, serum NSE, serum TPS, and serum CYFRA 21-1. Tumor response was analyzed at the 10th week. Analysis of survival were done using the landmark method. Hazard ratios of the significant prognostic variables of survival were calculated using the Cox's model. Odds ratios of the significant predicting factors of response were calculated by stepwise logistic regression. In SCLC, the significant determinants of poor survival were: lack of complete response (HR: 2.04), weight loss (HR: 1.76), high serum LDH level (HR: 1.64), and high serum TPS level (HR: 2.47). A high serum TPS level was the only factor among those studied able to predict lack of achievement of complete response (OR: 0.39). In NSCLC, significant determinants of poor survival were: no objective response (HR: 2.28), poor performance status (HR: 2.52), presence of metastases (HR: 1.51), and high serum CYFRA 21-1 level (HR: 1.84). On the other hand, a high serum TPS level (OR: 0.50), the presence of metastases (OR: 0.45), and a leukocyte blood count over 10,000/microl (OR: 0.43) were independent determinants for a patient not to achieve an objective response. We concluded that the predictive factors of complete response in SCLC remain to be defined. On the other hand, in NSCLC three variables contribute to the prediction of an objective response. Finally, determinants of survival differ from predictive factors of response.
Ceramide: A stress signal and mediator of growth suppression and apoptosis (1995)

A novel pathway termed the sphingomyelin cycle has been identified whereby membrane sphingomyelin is hydrolyzed in response to multiple extracellular stimuli (such as tumor necrosis factor alpha) which cause activation of regulated sphingomyelinases. The product, ceramide, has emerged as a second messenger that mediates many of the cellular effects of these extracellular stimuli. An intriguing relation exists between activation of the sphingomyelin cycle and the action of multiple stress stimuli that induce growth arrest and programmed cell death. Exogenously administered ceramide mimics these growth-suppressing effects, including the induction of apoptosis. This review will highlight the role of the sphingomyelin cycle in signal transduction and will focus on the role and function of ceramide in the regulation of cell growth in general and apoptosis specifically.
Disruption of the BCL11A Erythroid Enhancer Reactivates Fetal Hemoglobin in Erythroid Cells of Patients with β-Thalassemia Major (2018)

In the present report, we carried out clinical-scale editing in adult mobilized CD34+ hematopoietic stem and progenitor cells (HSPCs) using zinc-finger nuclease-mediated disruption of BCL11a to upregulate the expression of γ-globin (fetal hemoglobin). In these cells, disruption of the erythroid-specific enhancer of the BCL11A gene increased endogenous γ-globin expression to levels that reached or exceeded those observed following knockout of the BCL11A coding region without negatively affecting survival or <i>in vivo</i> long-term proliferation of edited HSPCs and other lineages. In addition, BCL11A enhancer modification in mobilized CD34+ cells from patients with β-thalassemia major resulted in a readily detectable γ-globin increase with a preferential increase in G-gamma, leading to an improved phenotype and, likely, a survival advantage for maturing erythroid cells after editing. Furthermore, we documented that both normal and β-thalassemia HSPCs not only can be efficiently expanded <i>ex vivo</i> after editing but can also be successfully edited post-expansion, resulting in enhanced early <i>in vivo</i> engraftment compared with unexpanded cells. Overall, this work highlights a novel and effective treatment strategy for correcting the β-thalassemia phenotype by genome editing.
Palladium-Catalyzed Synthesis of Aryl Ketones from Boronic Acids and Carboxylic Acids or Anhydrides (2001)

Mild and convenient: a palladium-catalyzed cross-coupling reaction between arylboronic acids and carboxylic anhydrides, which are generated in situ from the corresponding carboxylic acids, allows the efficient synthesis of a broad variety of functionalized aryl ketones [Eq. (1)].
Reactions of Sera from Patients with Rheumatoid Arthritis, Systemic Lupus Erythematosus and Infectious Mononucleosis to Epstein-Barr Virus-induced Polypeptides (1986)

P3HR-1 and Ramos cells induced with sodium butyrate and 12-O-tetradecanoylphorbol 13-acetate were used in the protein immunoblot technique to identify Epstein-Barr virus (EBV)-specific antibodies present in sera from clinically normal individuals and patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and infectious mononucleosis (IM). Sixteen EBV-specific polypeptides were detected ranging in mol. wt. from 22,000 (22K) to 140K. Many of the sera contained antibodies to different subsets of these antigens, and a high proportion expressed autoantibodies which reacted with cellular components from an EBV genome-negative cell line. About 50% of the sera from each category reacted with the 44K to 48K and 36K and 38K early antigen (EA) components. A high proportion of the SLE sera (64%) were found to contain anti-EA antibodies, suggesting an association between EBV and SLE. Almost all of the EBV-seropositive sera examined contained antibodies against a 22K late antigen, but none of the sera from IM patients reacted with this polypeptide.
Open study of hydroxychloroquine in the treatment of severe symptomatic or corticosteroid-dependent asthma. (1990)

To examine the possible usefulness of the immunomodulating antiinflammatory drug, hydroxychloroquine (HCQ), in the treatment of asthma, we studied the response of 11 asthmatics, four severe symptomatic nonsteroid dependent and seven steroid-dependent, in an open label 28 week trial at doses of 300 to 400 mg/d. Evaluation measures included daily symptom diary scores of six symptoms, subjective global evaluation, spirometric flow studies, and cumulative monthly steroid dosages. Baseline plasma theophylline and IgE levels were also obtained and compared with values during treatment. For the group as whole, mean FVC and FEV1 increased 10% and 17% respectively (P less than .01) and the mean of each of six symptom scores declined significantly (P less than .05). Among the nonsteroid-dependent asthmatics, the mean FVC and FEV1 rose 19% and 32% respectively (P less than .05) and mean symptom scores for five of six symptoms declined from baseline (P less than .05). Among the steroid-dependent patients, cumulative mean monthly steroid dosage required decreased 50% from 383 mg at entry to 191 mg at week 28 (P less than .01), mean FVC and FEV1 increased by 7% and 9%, although neither of these changes achieved significance, and two of six symptom scores improved (P less than .05). Comparison of pretreatment IgE levels to levels during treatment in ten patients demonstrated a fall from a mean of 645 to 339 IU/mL (P less than .05). Adverse reactions to HCQ were infrequent and did not require discontinuing therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
Neurological outcomes in late HIV infection: adverse impact of neurological impairment on survival and protective effect of antiviral therapy (1999)

Combination antiretroviral therapy can have a salutary effect on preserving or improving neurological function. Superior systemic treatments may likewise better preserve neurological function. The significant association of poor neurological performance with mortality, independent of CD4 counts and HIV-1 RNA levels indicates that neurological dysfunction is an important cause or a strong marker of poor prognosis in late HIV-1 infection. This study demonstrates the value of adjunctive neurological measures in large therapeutic trials of late HIV-1 infection.
Application of new analytical technology to the production of a "well-characterized biological". (1998)

The role of new analytical technology in the development of the concept of a "Well Characterized Biological" is to provide suitable methodology that allows the characterization of even the most complex protein sample so that a consistent manufacturing process can be established. Glycoproteins are among the most challenging of products to characterize because of extreme sample microheterogeneity due to the carbohydrate moieties. As an example of the appropriate use of new analytical technology this review will examine the steps necessary to demonstrate that a glycoprotein is a "Well Characterized Biological". The key to characterization of complex protein samples lies in the use of appropriate combinations of the different methods that analyse the sample from substantially orthogonal and independent directions. An important advantage of capillary electrophoresis (HPCE) in this application is the complementarily of the technique with reversed phase HPLC (RPLC). Thus mixtures of variants of a polypeptide that are difficult to separate by RPLC can often be readily resolved by HPCE. Both separation techniques are well suited to the analysis of peptide maps, although RPLC is particularly powerful when used in combination with on-line electrospray mass spectrometry (ESI-MS) which allows for the effective ionization and detection of even high MW glycopeptides. In this sense the ESI-MS is an ideal detector for on-line mass detection after a RPLC separation of medium MW fragments (300 to 6000 emu) that are typically present in an enzyme digest of a protein. Matrix-Assisted Laser Desorption Ionization Time-Of-Flight Mass Spectrometry (MALDI-TOFMS) is a valuable technique for off-line characterization of CE fractions due to the high sensitivity of the method and its tolerance of samples with moderate levels of salt. The development of an effective protocol for the analysis of glycoform populations of intact glycoproteins by a combination of HPCE and off-line MALDI-TOFMS wil be demonstrated by the successful analysis of two highly heterogeneous glycoproteins, ovalbumin and Desmodus Salivary Plasminogen Activator (DSPA).