gebhart/patrepeval huggingface dataset:
The role of tumour‐associated macrophages in tumour progression: implications for new anticancer therapies (2002)

The role of macrophages in tumour growth and development is complex and multifaceted. Whilst there is limited evidence that tumour-associated macrophages (TAMs) can be directly tumouricidal and stimulate the anti-tumour activity of T cells, there is now contrasting evidence that tumour cells are able to block or evade the activity of TAMs at the tumour site. In some cases, tumour-derived molecules even redirect TAM activities to promote tumour survival and growth. Indeed, evidence has emerged for a symbiotic relationship between tumour cells and TAMs, in which tumour cells attract TAMs and sustain their survival, with TAMs then responding to micro-environmental factors in tumours such as hypoxia (low oxygen tension) by producing important mitogens as well as various growth factors and enzymes that stimulate tumour angiogenesis. This review presents evidence for the number and/or distribution of TAMs being linked to prognosis in different types of human malignancy. It also outlines the range of pro- and anti-tumour functions performed by TAMs, and the novel therapies recently devised using TAMs to stimulate host immune responses or deliver therapeutic gene constructs to solid tumours.
Activation of beta-isozyme of protein kinase C (PKC beta) is necessary and sufficient for phorbol ester-induced differentiation of HL-60 promyelocytes. Studies with PKC beta-defective PET mutant. (1994)

12-O-Tetradecanoylphorbol-13-acetate (TPA) induces growth arrest and differentiation of a number of leukemia cell lines including HL-60 human promyelocytic leukemia. We investigated the involvement of protein kinase C (PKC) isotypes in phorbol ester-induced differentiation using the phorbol ester-tolerant PET mutant of HL-60 cells, which (in contrast to the parent phorbol ester-sensitive (wild-type) S variant of HL-60 cells) does not growth-arrest, become adherent, or undergo apoptosis when exposed to TPA (Macfarlane, D. E., Gailani, D., and Vann, K. (1988) Br. J. Haematol. 68, 291-302). In comparison to S cells, we found that proliferating PET cells markedly underexpress mRNA for PKC beta, but do express PKC alpha and PKC delta. The PKC beta-selective activator 12-deoxyphorbol 13-phenylacetate 20-acetate induces growth arrest, adherence, surface expression of CD11a, and apoptosis in S cells, but not in PET cells. Expression of PKC beta in PET cells can be restored by exposing them to dihydroxyvitamin D3, and this treatment restores the ability of subsequently added 12-deoxyphorbol 13-phenylacetate 20-acetate or TPA to induce immediate cell adherence and growth arrest of PET cells. These data led us to conclude that activation of PKC beta is both necessary and sufficient for phorbol ester-induced growth arrest and adherence in these myeloid cells.
The significance of Ureaplasma urealyticum as a pathogenic agent in the paediatric population (2006)

This review covers recent evidence concerning the role of U. urealyticum as a pathogen during childhood. It also includes an evaluation of contemporary diagnostic techniques and optimal therapeutic approaches.
Novel 17-Azolyl Steroids, Potent Inhibitors of Human Cytochrome 17α-Hydroxylase-C17,20-lyase (P45017α):  Potential Agents for the Treatment of Prostate Cancer (1998)

A new synthetic route to a variety of novel delta 16-17-azolyl steroids is described: it involves the nucleophilic vinylic "addition-elimination" substitution reaction of 3 beta-acetoxy-17-chloro-16-formylandrosta-5,16-diene (2) and azolyl nucleophiles. Some of these novel delta 16-17-azolyl steroids, 6, 17, 19, and 27-29, prepared in good overall yields, are very potent inhibitors of human and rat testicular P450(17) alpha. They are shown to be noncompetitive and appear to be slow-binding inhibitors of human P450(17) alpha. The most potent compounds are 3 beta-hydroxy-17-(1H-imidazol-1-yl)androsta-5,16-diene (17), 3 beta-hydroxy-17-(1H-1,2,3-triazol-1-yl)androsta-5,-16-diene (19), and 17-(1H-imidazol-1-yl)androsta-4,16-dien-3-one (28), with Ki values of 1.2, 1.4, and 1.9 nM, respectively, being 20-32 times more potent than ketoconazole (Ki = 38 nM). Spectroscopic studies with a modified form of human P450(17) alpha indicate that the inhibition process involves binding of steroidal azole nitrogen to the heme iron of the enzyme. Furthermore, some of these potent P450(17) alpha inhibitors (27-29) are also powerful inhibitors of steroid 5 alpha-reductase, and others (17 and 19) appear to exhibit strong antiandrogenic activity in cultures of the LNCaP human prostatic cancer cell line. These novel compounds with impressive dual biological activities make them strong candidates for development as therapeutic agents for treatment of prostate cancer and other disease states which depend on androgens.
The influence of flanking sequence on the O-glycosylation of threonine in vitro. (1992)

To investigate the influence of flanking amino acid sequence on the O-glycosylation of a single threonine residue in vitro, we have examined a series of 52 related peptides. The substrates were based upon a sequence from human von Willebrand factor which is known to be glycosylated in vivo (-6PHMAQVTVGPGL+5). Each residue of the parent peptide was substituted, in turn, with isoleucine, alanine, proline, glutamic acid, or arginine. Peptides were glycosylated using a UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase purified 15,000-fold from bovine colostrum by chromatography on DEAE-Sephacel, SP-Sephadex, Sephacryl S-300, Affi-Gel Blue, and 5-mercuri-UDP-GalNAc thiopropyl-Sepharose. Single amino acid changes in the sequences flanking the threonine could profoundly alter the glycosylation of the substrate peptides. Substitution of any amino acid tested at positions +3, -3, and -2 markedly decreased O-glycosylation, as did the presence of a charged residue at position -1. The substitution of amino acids at the other positions of the peptide substrate had little effect on the incorporation of GalNAc. Statistical analysis of sequences flanking known glycosylated threonine and serine residues suggests that they should be glycosylated with equal efficiency in the same sequence context (O'Connell et al., 1991). However, the bovine colostrum transferase failed to glycosylate a peptide derived from human erythropoietin which contains a serine that is glycosylated in vivo (-5PPDAASAAPLR+5). When a threonine was substituted for the serine in this peptide (-5PPDAATAAPLR+5), the substrate proved to be an excellent acceptor of GalNAc. These observations indicate that although flanking amino acid sequence is important for the O-glycosylation of specific hydroxyamino acids, discrete threonine- and serine-specific transferases may exist.
Bacitracin Versus Mupirocin for Staphylococcus aureus Nasal Colonization (1999)

We performed a randomized prospective study of 5-day treatment with topical mupirocin or bacitracin for the elimination of Staphylococcus aureus nasal colonization in healthcare workers (HCWs). Nasal cultures were obtained from 141 HCWs, 37 (26%) of whom showed S. aureus. After 72 to 96 hours of treatment, the organism was eradicated in 15 (94%) of 16 by mupirocin and in 8 (44%) of 18 by bacitracin (P = .0031). Similar efficacy was demonstrated at 30 days. Mupirocin may be more effective than bacitracin for eradication of S. aureus in healthy HCWs.
Zero-interaction authentication (2002)

Laptops are vulnerable to theft, greatly increasing the likelihood of exposing sensitive files. Unfortunately, storing data in a cryptographic file system does not fully address this problem. Such systems ask the user to imbue them with long-term authority for decryption, but that authority can be used by anyone who physically possesses the machine. Forcing the user to frequently reestablish his identity is intrusive, encouraging him to disable encryption.Our solution to this problem is Zero-Interaction Authentication, or ZIA. In ZIA, a user wears a small authentication token that communicates with a laptop over a short-range, wireless link. Whenever the laptop needs decryption authority, it acquires it from the token; authority is retained only as long as necessary. With careful key management, ZIA imposes an overhead of only 9.3% for representative workloads. The largest file cache on our hardware can be re-encrypted within five seconds of the user's departure, and restored in just over six seconds after detecting the user's return. This secures the machine before an attacker can gain physical access, but recovers full performance before a returning user resumes work.
Differential Effects of HIV-1 Protease Inhibitors on Dendritic Cell Immunophenotype and Function (2001)

Recent findings show that human immunodeficiency virus (HIV)-1 protease inhibitors designed to specifically inhibit the aspartic protease of HIV-1 nonetheless exert various effects on immune cell function in vitro and in vivo. Dendritic cells (DC), central players of the immune system, express several aspartic proteases that are important for DC function. In the present study, we demonstrate that all of the HIV-1 protease inhibitors tested affect DC maturation. In addition, saquinavir had a strong inhibitory effect on the T-cell stimulatory capacity of mature DC. In contrast, indinavir had only a slight effect on DC induced T-cell proliferation and allowed efficient transduction of DC with a replication-incompetent HIV-1 vector designed for DC-based immunotherapy. HIV-1 protease inhibitors that have little or no effect on DC function may be preferable for combination with immunotherapy for HIV/AIDS.
Confidence estimation methods for neural networks: a practical comparison (2001)

Feedforward neural networks, particularly multilayer perceptrons, are widely used in regression and classification tasks. A reliable and practical measure of prediction confidence is essential. In this work three alternative approaches to prediction confidence estimation are presented and compared. The three methods are the maximum likelihood, approximate Bayesian, and the bootstrap technique. We consider prediction uncertainty owing to both data noise and model parameter misspecification. The methods are tested on a number of controlled artificial problems and a real, industrial regression application, the prediction of paper "curl". Confidence estimation performance is assessed by calculating the mean and standard deviation of the prediction interval coverage probability. We show that treating data noise variance as a function of the inputs is appropriate for the curl prediction task. Moreover, we show that the mean coverage probability can only gauge confidence estimation performance as an average over the input space, i.e., global performance and that the standard deviation of the coverage is unreliable as a measure of local performance. The approximate Bayesian approach is found to perform better in terms of global performance.
Poor Law, New (2008)

The New Poor Law refers to the system of local public assistance in England and Wales initiated by the passage of the 1834 Poor Law Amendment Act. This act attempted to restrict relief outside of workhouses for the able-bodied, but was evaded for three decades. The Crusade against Outrelief of the 1870s marked a major shift in administration and the increased use of workhouse relief. Numbers on relief fell sharply thereafter, although the elderly continued to rely heavily on the Poor Law. The Liberal welfare reforms of 1906–11 paved the way for the 1948 abolition of the Poor Law.
Aneuploidy and aneusomy of chromosome 7 detected by fluorescence in situ hybridization are markers of poor prognosis in prostate cancer. (1994)

Fluorescence in situ hybridization is a new methodology which can be used to detect cytogenetic anomalies within interphase tumor cells. We used this technique to identify nonrandom numeric chromosomal alterations in tumor specimens from the poorest prognosis patients with pathological stages T2N0M0 and T3N0M0 prostate carcinomas. Among 1368 patients treated by radical prostatectomy, 25 study patients were ascertained who died most quickly from progressive prostate carcinoma within 3 years of diagnosis and surgery. Tumors from 25 control patients who survival for more than 5 years and who were matched for age, tumor histological grade, and pathological stage also were evaluated. The tumors from all 25 (100%) poor prognosis patients and from 11 of 25 (44%) control patients were found to be aneuploid by fluorescence in situ hybridization (P < 0.0001). Alterations of chromosome 7 were observed in 24 of the tumors (96%) from the poor prognosis patients versus 3 tumors (12%) from the control group (P < 0.0001). Moreover, a characteristic aneuploidy pattern with multiple abnormal chromosomes and a hypertetrasomic population was generally found in tumors from the poor prognosis patients. This preliminary study suggests that fluorescence in situ hybridization studies of prostate cancer specimens may help to identify those patients at highest risk for early cancer death.
The C–H···Cl hydrogen bond: does it exist? (1999)

The extensive occurrence of C–H···Cl hydrogen bonds has been established through a systematic statistical analysis of the Cambridge Crystallographic Database; chloride anions are shown to be better hydrogen-bond accepor systems than neutral chloride-containing molecules, and a similar situation pertains for the other halides. As a result of this study, we propose that the conceptual van der Waals cut-off criterion be dropped for establishing the presence of weak intermolecular and intramolecular interactions, and be replaced by a distance/angle criterion determined by the empirical approach outlined here.
Bulk adhesive strength of recombinant hybrid mussel adhesive protein (2008)

Mussel adhesive proteins (MAPs) have received increased attention as potential biomedical and environmental friendly adhesives. However, practical application of MAPs has been severely limited by uneconomical extraction and unsuccessful genetic production. Developing new adhesives requires access to large quantities of material and demonstrations of bulk mechanical properties. Previously, the authors designed fp-151, a fusion protein comprised of six MAP type 1 (fp-1) decapeptide repeats at each MAP type 5 (fp-5) terminus and successfully expressed it in Escherichia coli. This recombinant hybrid protein exhibited high-level expression, a simple purification and high biocompatibility as well as strong adhesive ability on a micro-scale. In the present work, investigations on the bulk adhesive properties of semi-purified ( approximately 90% purity) fusion fp-151 were performed in air. The unmodified recombinant fp-151, as expressed, contains tyrosine residues and showed significant shear-adhesive forces ( approximately 0.33 MPa). Adhesion strength increased ( approximately 0.45 MPa) after enzymatic oxidation of tyrosine residues to l-3,4-dihydroxyphenylalanine (DOPA) groups. Addition of cross-linkers such as iron(III), manganese(III) and periodate (IO(4)(-)) generally enhanced adhesion, although too much addition decreased adhesion. Among the three cross-linking reagents examined, the non-metallic oxidant periodate showed the highest shear-adhesive forces ( approximately 0.86 MPa). In addition, it was found that adhesive strengths could be increased by adding weights to the samples. The highest adhesion strength found was that of DOPA-containing fp-151 cross-linked with periodate and having weights applied to the samples ( approximately 1.06 MPa). Taken together, the first bulk-scale adhesive force measurements are presented for an expressed recombinant hybrid mussel adhesive protein.
Growth Inhibition by Acycloguanosine of Herpesviruses Isolated from Human Infections (1979)

Inhibition by acycloguanosine (ACG) of plaque formation by harpes simplex virus types 1 and 2 (HSV-1 and HSV-2), varicella-zoster virus, and cytomegalovirus was studied. Seventeen clinical isolates of HSV-1 were inhibited by ACG at a mean 50% inhibitory dose (ID 50 ) of 0.15 ± 0.09 μM. The mean ID 50 for 10 isolates of HSV-2 was 1.62 ± 0.76 μM, and for four isolates of varicella-zoster virus it was 3.75 ± 1.30 μM. The ID 50 's for two cytomegalovirus isolates were 100 and 160 μM, and for four additional isolates of cytomegalovirus no end point (ID 50 ) was reached at 200 μM. ACG at a concentration of 200 μM had no effect on deoxyribonucleic acid synthesis in human fibroblast cells and only inhibited thymidine incorporation by Vero cells by one-third. These studies demonstrated the antiviral activity of ACG against clinical isolates of HSV-1, HSV-2, and varicella-zoster virus and the lack of toxicity to monkey or human cells in culture at concentrations which markedly inhibited these viruses. ACG had little effect on cytomegalovirus at concentrations in excess of 100 μM.
Formation of the definitive endoderm in mouse is a Smad2-dependent process (2000)

TGFbeta growth factors specify cell fate and establish the body plan during early vertebrate development. Diverse cellular responses are elicited via interactions with specific cell surface receptor kinases that in turn activate Smad effector proteins. Smad2-dependent signals arising in the extraembryonic tissues of early mouse embryos serve to restrict the site of primitive streak formation and establish anteroposterior identity in the epiblast. Here we have generated chimeric embryos using lacZ-marked Smad2-deficient ES cells. Smad2 mutant cells extensively colonize ectodermal and mesodermal populations without disturbing normal development, but are not recruited into the definitive endoderm lineage during gastrulation. These experiments provide the first evidence that TGFbeta signaling pathways are required for specification of the definitive endoderm lineage in mammals and identify Smad2 as a key mediator that directs epiblast derivatives towards an endodermal as opposed to a mesodermal fate. In largely Smad2-deficient chimeras, asymmetric nodal gene expression is maintained and expression of pitx2, a nodal target, is also unaffected. These results strongly suggest that other Smad(s) act downstream of Nodal signals in mesodermal populations. We found Smad2 and Smad3 transcripts both broadly expressed in derivatives of the epiblast. However, Smad2 and not Smad3 mRNA is expressed in the visceral endoderm, potentially explaining why the primary defect in Smad2 mutant embryos originates in this cell population.
The resonant cylindrical dielectric cavity antenna (1983)

An experimental investigation of the radiation and circuit properties of a resonant cylindrical dielectric cavity antenna has been undertaken. The radiation patterns and input impedance have been measured for structures of various geometrical aspect ratios, dielectric constants, and sizes of coaxial feed probes. A simple theory utilizing the magnetic wall boundary condition is shown to correlate well with measured results for radiation patterns and resonant frequencies.
Toward Environmental-Adaptive Visible Light Communications Receivers for Automotive Applications: A Review (2016)

Since more and more vehicles are using the transportation infrastructure, the safety and the efficiency of roads are of absolute importance. A solution to enhance the security of road transportation is by enabling wireless communications between vehicles and also with the traffic infrastructures (e.g., traffic lights, street lighting, or traffic signs). In this area, visible light communications (VLC) is considered of great perspective. A fundamental problematic in vehicular VLC is the design of a proper sensor capable to support long distance communications in dynamic traffic situations and in unfriendly atmospheric conditions. Therefore, this paper is focused on the design of the VLC sensors intended for vehicular communication applications, offering a review of the solutions found to mitigate the effect of the problematic conditions. Furthermore, this paper summarizes these solutions and proposes an environmental adaptive VLC receiver that would be capable to optimally adjust its settings in order to maximize the communication efficiency, but without affecting the communication robustness to noise.
Binding of the human retrovirus HTLV-III/LAV/ARV/HIV to the CD4 (T4) molecule: conformation dependence, epitope mapping, antibody inhibition, and potential for idiotypic mimicry. (1986)

Human immunodeficiency virus (HIV), the retrovirus that causes the acquired immunodeficiency syndrome, is cytopathic for CD4+ T cells and binds to these cells via a complex of the 110,000 m.w. viral-envelope glycoprotein, gp110, and the CD4 molecule. We treated virus with several physical, chemical, and enzymic agents to determine their effect on the capacity of HIV to bind to the CD4+ T cell line, CEM. Reduction and alkylation (but not alkylation alone) and trypsin digestion (but not glycolytic enzyme digestions) of HIV destroyed its capacity to bind. If the tertiary protein structure conferred by disulfide bonding is not disrupted, the tertiary and secondary conformations dependent on noncovalent forces appear to be thermodynamically favored, because treatment with denaturants such as sodium dodecyl sulfate, 8 M urea, alcohol, or heat (56 degrees C or 65 degrees C for 30 min) followed by removal of the denaturants did not affect binding. Irreversible denaturation and loss of binding occurred after heating at 100 degrees C for 10 min. HIV binding to CD4+ T cells was inhibited either by murine monoclonal antibodies to the CD4 molecule or by human polyclonal or murine monoclonal antibodies to the gp110 molecule. On the basis of results of binding inhibition obtained with a panel of alpha-CD4 monoclonal antibodies, the receptor site for virus on the CD4 molecule was mapped to the amino-terminal portion of the molecule. Four candidate alpha-CD4 monoclonal antibodies that were potent inhibitors of virus binding (OKT4A, OKT4D, OKT4F, and Leu-3a) were examined for the possibility that their binding sites (idiotopes) might share structural and conformational similarity with the CD4-binding site on gp110. Polyclonal human or rabbit anti-HIV sera (that reacted with gp110 and inhibited virus binding) did not react with or inhibit the binding of these four alpha-CD4 monoclonal antibodies. Conversely, rabbit anti-idiotypic sera raised against each of the four candidate CD4 monoclonal antibodies did not react with virus or inhibit virus binding to CD4+ T cells. Further search or different approaches may yet yield an idiotype that is a structural and conformational "internal image" of the CD4-binding site of virus.
Polymers of Carbonic Acid, 30 Ring-Expansion Polymerization of Trimethylene Carbonate (TMC, 1,3-Dioxanone-2) with Dibutyltin Succinate or Adipate (2001)

Macrocyclic crystalline dibutyltin succinate (Bu2SnSuc) and adipate (Bu2SnAd) were prepared in high yields from Bu2SnO and dicarboxylic acid. According to vapor pressure osmometry and MALDI-TOF mass spectrometry, Bu2SnSuc is a cyclic trimer and Bu2SnAd a cyclic dimer. These macrocycles initiate a faster polymerization of TMC at 80°C than Sn(II) octanoate or Bu2Sn octanoate. The resulting polyTMC does not contain succinate or adipate groups, and the molecular weight (Mw) is independent of the monomer to initiator ratio (M/I). Above 120°C a complete esterification and incorporation of the dicarboxylic acids takes place, and the identification of CH2OH end groups suggests that a ring-expansion polymerization via insertion of TMC into Sn—O—CH2 bonds proceeds. The number-average molecular weights increase with the M/I ratio, but do not exactly parallel it. At longer reaction times the molecular weights are affected by “back-biting” degradation.