gebhart/patrepeval huggingface dataset:
Intracellular delivery enhancement of poly(amino acid) drug carriers by oligoarginine conjugation (2007)

Poly(2-hydroxytethyl aspartamide) (PHEA) was effectively translocated in both fixed and unfixed HeLa cells, when oligoarginine (Arg(8)) known as one of the cell-penetrating peptides was conjugated via a thioether linkage. The internalization of PHEA-Arg(8) into cells was a temperature-dependent process, and the studies at endocytosis inhibition conditions suggested that an endocytosis was a key mechanism. The fluorescence spectra of PHEA-Arg(8) in liposome solutions showed that PHEA-Arg(8) was collectively adsorbed in the negative liposome membrane due to the high cationic property of a conjugated Arg(8), representing that a surface adsorption was a first step in the internalization of PHEA-Arg(8). The membrane leakage activity of PHEA-Arg(8) was much lower than that of Arg(8) own, meaning that PHEA-Arg(8) does not effectively disrupt the cell membrane integrity. The uptake of polymer conjugates increased with the incubation time and reached saturation after several hours. The increase in the number of peptide conjugated to one polymer chain could increase the collective adsorption of polymer conjugates and enhance the cellular uptake. Thus, it is believed that PHEA-Arg(8) could be internalized by an adsorptive-endocytosis. A model conjugate of PHEA-Arg(8) with methotrexate (PHEA-MTX-Arg(8)) inhibited the cell proliferation about several orders of magnitude more active than PHEA-MTX.
Co-repressor Release but Not Ligand Binding Is a Prerequisite for Transcription Activation by Human Retinoid Acid Receptor α Ligand-binding Domain (2003)

Nuclear hormone receptors coordinately regulate the activity of genetic networks through the recruitment of transcriptional co-regulators, including co-repressors and co-activators. Allosteric modulation of the ligand-binding domain by hormonal activators shifts the co-factor binding preference by defined structural changes in overlapping docking sites. We report here that mutations at conserved residues within the docking motif of the retinoic acid receptor alpha cause defects in dimerization, co-regulator association, and transcriptional regulation. Furthermore, although a minimal co-repressor receptor interaction domain is sufficient for receptor binding, flanking sequences appear to stabilize this interaction without interfering with ligand sensitivity. However, ligand sensitivity is changed by the K262A mutation, which requires much higher concentrations of all-trans-retinoic acid to promote co-repressor dissociation. Consequently, K262A functions as a dominant-negative mutant at low concentrations of all-trans-retinoic acid. As a result, transcriptional activation is mechanistically linked to co-repressor release.
Long-Term Additive Prognostic Value of Thallium-201 Myocardial Perfusion Imaging Over Clinical and Exercise Stress Test in Low to Intermediate Risk Patients (1999)

The incremental predictive value of SPECT is maintained over 6 years and is particularly relevant after positive, strongly positive, and nondiagnostic ETT.
Tethered Ligand Library for Discovery of Peptide Agonists (1995)

We exploited the mechanism underlying thrombin receptor activation to develop a novel screening method to identify peptide agonists. The thrombin receptor is activated by limited proteolysis of its amino-terminal exodomain. Thrombin cleaves this domain to unmask a new amino terminus, which then functions as a tethered peptide agonist, binding intramolecularly to the body of the receptor to trigger signaling. The thrombin receptor's amino-terminal exodomain can also donate the tethered agonist intermolecularly to activate nearby thrombin receptors. We utilized this ability by co-expressing a "tethered ligand library," which displayed the thrombin receptor's amino-terminal exodomain bearing random pentapeptides in place of the native tethered ligand together with target receptors in Xenopus oocytes. Clones that conferred thrombin-dependent signaling by intermolecular ligation of the target receptor were isolated by sib selection. Agonists for the thrombin receptor itself (GFIYF) and for the formyl peptide receptor (MMWLL) were identified. Surprisingly, the latter agonist was quite active at the formyl peptide receptor even without N-formylation, and its formylated form, fMMWLL, was more potent than the classical formyl peptide receptor agonist fMLF. In addition to identifying novel peptide agonists for targets of pharmacological interest, this method might be used to discover agonists for orphan receptors. It also suggests a possible evolutionary path from peptide to protease-activated receptors.
Exact and efficient cone-beam reconstruction algorithm for a short-scan circle combined with various lines (2005)

X-ray 3D rotational angiography based on C-arm systems has become a versatile and established tomographic imaging modality for high contrast objects in interventional environment. Improvements in data acquisition, e.g. by use of flat panel detectors, will enable C-arm systems to resolve even low-contrast details. However, further progress will be limited by the incompleteness of data acquisition on the conventional short-scan circular source trajectories. Cone artifacts, which result from that incompleteness, significantly degrade image quality by severe smearing and shading. To assure data completeness a combination of a partial circle with one or several line segments is investigated. A new and efficient reconstruction algorithm is deduced from a general inversion formula based on 3D Radon theory. The method is theoretically exact, possesses shift-invariant filtered backprojection (FBP) structure, and solves the long object problem. The algorithm is flexible in dealing with various circle and line configurations. The reconstruction method requires nothing more than the theoretically minimum length of scan trajectory. It consists of a conventional short-scan circle and a line segment approximately twice as long as the height of the region-of-interest. Geometrical deviations from the ideal source trajectory are considered in the implementation in order to handle data of real C-arm systems. Reconstruction results show excellent image quality free of cone artifacts. The proposed scan trajectory and reconstruction algorithm assure excellent image quality and allow low-contrast tomographic imaging with C-arm based cone-beam systems. The method can be implemented without any hardware modifications on systems commercially available today.
Effect of Decreasing the Affinity of the Class II-Associated Invariant Chain Peptide on the MHC Class II Peptide Repertoire in the Presence or Absence of H-2M (2004)

The class II-associated invariant chain peptide (CLIP) region of the invariant chain (Ii) directly influences MHC class II presentation by occupying the MHC class II peptide-binding groove, thereby preventing premature loading of peptides. Different MHC class II alleles exhibit distinct affinities for CLIP, and a low affinity interaction has been associated with decreased dependence upon H-2M and increased susceptibility to rheumatoid arthritis, suggesting that decreased CLIP affinity alters the MHC class II-bound peptide repertoire, thereby promoting autoimmunity. To examine the role of CLIP affinity in determining the MHC class II peptide repertoire, we generated transgenic mice expressing either wild-type human Ii or human Ii containing a CLIP region of low affinity for MHC class II. Our data indicate that although degradation intermediates of Ii containing a CLIP region with decreased affinity for MHC class II do not remain associated with I-A(b), this does not substantially alter the peptide repertoire bound by MHC class II or increase autoimmune susceptibility in the mice. This implies that the affinity of the CLIP:MHC class II interaction is not a strong contributory factor in determining the probability of developing autoimmunity. In contrast, in the absence of H-2M, MHC class II peptide repertoire diversity is enhanced by decreasing the affinity of CLIP for MHC class II, although MHC class II cell surface expression is reduced. Thus, we show clearly, in vivo, the critical chaperone function of H-2M, which preserves MHC class II molecules for high affinity peptide binding upon dissociation of Ii degradation intermediates.
Transaldolase haploinsufficiency in subjects with acetaminophen‐induced liver failure (2019)

Transaldolase (TAL) is an enzyme in the pentose phosphate pathway (PPP) that generates NADPH for protection against oxidative stress. While deficiency of other PPP enzymes, such as transketolase (TKT), are incompatible with mammalian cell survival, mice lacking TAL are viable and develop progressive liver disease attributed to oxidative stress. Mice with homozygous or heterozygous TAL deficiency are predisposed to cirrhosis, hepatocellular carcinoma (HCC) and acetaminophen (APAP)-induced liver failure. Both mice and humans with complete TAL deficiency accumulate sedoheptulose 7-phosphate (S7P). Previous human studies relied on screening patients with S7P accumulation, thus excluding potentially pathogenic haploinsufficiency. Of note, mice with TAL haploinsufficiency are also predisposed to HCC and APAP-induced liver failure which are preventable with oral N-acetylcysteine (NAC) administration. Based on TALDO1 DNA sequencing, we detected functional TAL deficiency due to novel, heterozygous variations in two of 94 healthy adults and four of 27 subjects with APAP-induced liver failure (P = .022). The functional consequences of these variations were individually validated by site-directed mutagenesis of normal cDNA and loss of activity by recombinant enzyme. All four patients with TAL haplo-insufficiency with APAP-induced liver failure were successfully treated with NAC. We also document two novel variations in two of 15 children with previously unexplained liver cirrhosis. Examination of the National Center for Biotechnology Information databases revealed 274 coding region variations have been documented in 1125 TALDO1 sequences relative to 25 variations in 2870 TKT sequences (P < .0001). These findings suggest an unexpected prevalence and variety of genetic changes in human TALDO1 with relevance for liver injury that may be preventable by treatment with NAC.
Anesthesia Management for Pulmonary Cryoablation (2013)

Lung tumors represent a major health impact globally. Pulmonary cryoablation treatment as a palliative measure for patients with non-operable pulmonary lesions has gained popularity over the last decade. With increasing case load and patients medical status becoming more complex, preparation for pulmonary cryoablation requires the implementation of an enhanced perioperative anesthetic plan. Current literature as well as our institutional experience shows that this patient population presents with multiple comorbidities raising the challenge of providing anesthetic care. These procedures are done under challenging conditions with limited resources and in remote locations in the hospital. A team approach by the anesthesiologist, thoracic surgeon, and interventional radiologist is critical to the success of this treatment. The present review examines our institution’s anesthetic management of percutaneous cryoablation treatment (PCT) in the treatment of non-operable lung cancer and metastases. The objective of this article is to review the current literature guidelines and to discuss our retrospective institutional experience in anesthesia management of PCT procedures.
Reporting Tumor Molecular Heterogeneity in Histopathological Diagnosis (2014)

TM-NGS is able to detect and quantitate multiple gene alterations from limited amounts of DNA, moving one step closer to a next-generation histopathologic diagnosis that integrates morphologic, immunophenotypic, and multigene mutational analysis on routinely processed tissues, essential for personalized cancer therapy.
Introduction (2023)

Chemical engineering as a discipline is famous for its reinvention to address problems of societal importance while leveraging new developments in surrounding fields. We are excited that this year's issue focuses on both societally important problems and new developments.
A Promising Way to Overcome Temozolomide Resistance through Inhibition of Protein Neddylation in Glioblastoma Cell Lines (2023)

There is no effective therapy for the lately increased incidence of glioblastoma multiforme (GBM)-the most common primary brain tumor characterized by a high degree of invasiveness and genetic heterogeneity. Currently, DNA alkylating agent temozolomide (TMZ) is the standard chemotherapy. Nevertheless, TMZ resistance is a major problem in the treatment of GBM due to numerous molecular mechanisms related to DNA damage repair, epigenetic alterations, cellular drug efflux, apoptosis-autophagy, and overactive protein neddylation. Low molecular weight inhibitors of NEDD8-activating enzyme (NAE), such as MLN4924, attenuate protein neddylation and present a promising low-toxicity anticancer agent. The aim of our study was to find an effective combination treatment with TMZ and MLN4924 in our TMZ-resistant GBM cell lines and study the effect of these combination treatments on different protein expressions such as O<sup>6</sup>-methylguanine methyltransferase (MGMT) and p53. The combination treatment successfully decreased cell viability and sensitized TMZ-resistant cells to TMZ, foreshadowing a new treatment strategy for GBM.
Retrogression and reaging response of 7475 aluminium alloy (1983)

AbstractAbstractThe age-hardening response of 7475 aluminium alloy has been investigated at 110°, 120°, 1400 , and 160°C, using yield-strength and electrical-conductivity measurements. Heat-treatment parameters were established to give a T6-type starting condition for specimens which were further processed by retrogression and reaging (RRA). The RRA-processed materials were further characterized by yield-strength, electrical-conductivity, and stress-corrosion-crack growth-rate measurements. The results indicate that stress-corrosion-crack growth rates can be varied independently of yield strength, and T6 strength levels can be achieved in materials having stress-corrosion resistance comparable to that of the T73 condition for alloy 7475.
Search for a trans-disulfide: structural analysis of di-tert-adamantyl disulfide by photoelectron spectroscopy, derivation of .sigma.I(t-Ad), and molecular mechanics calculations for related bulky disulfides (1980)

Photoelectron spectroscopy of t-Ad-SS-t-Ad yields an IE(n) - IE(n+) energy difference of 0.51 eV at the frontier orbital gap suggesting to an S-S dihedral angle of θ(CSSC) = 103°. Molecular mechanics calculations with Allinger's MMI yield a shallow energy minimum with respect to rotation about the S-S bond. Two conformations differing by 0.7 kcal/mol are located at θ(CSSC) = 100 and 114°. Regression analysis of dialkyl disulfide ionization energies and substituent inductive parameters (σI) leads to σ(t-Ad) = -0.089, indicating t-Ad to be a better electron donor than t-Bu. Finally force field calculations for several sterically congested disulfides suggest that trans disulfides may be realizable for very large alkyl substituents such as the (t-Bu)3C, polymethyladamantyl, and trimethylperhydrotriquinicenyl moieties.
Do nonclassical silabenzene anions exist? Synthesis and crystal structure of crown ether-stabilized lithium silacyclohexadieneides, Li(12-crown-4)2Me2SiC5H5 and Li(12-crown-4)2-tert-Bu(H)SiC5H5 (1990)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTDo nonclassical silabenzene anions exist? Synthesis and crystal structure of crown ether-stabilized lithium silacyclohexadieneides, Li(12-crown-4)2Me2SiC5H5 and Li(12-crown-4)2-tert-Bu(H)SiC5H5Peter Jutzi, Marion Meyer, H. V. Rasika Dias, and Philip P. PowerCite this: J. Am. Chem. Soc. 1990, 112, 12, 4841–4846Publication Date (Print):June 1, 1990Publication History Published online1 May 2002Published inissue 1 June 1990https://doi.org/10.1021/ja00168a031RIGHTS & PERMISSIONSArticle Views194Altmetric-Citations23LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (781 KB) Get e-AlertsSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Performance engineering of the Totem group communication system (1998)

Group communication systems simplify the development of fault-tolerant distributed applications; however, concerns exist about the performance and overheads associated with such systems. This paper presents measurements of the performance of the Totem group communication system, operating on a single local-area network (LAN) and on multiple LANs interconnected by gateways. The Totem system runs in user space with standard commercial off-the-shelf (COTS) software and hardware. For 1 kbyte messages, a throughput of over 5000 messages per second has been measured for Totem on a single LAN, and an aggregate throughput of 10 000 messages per second has been measured for Totem on three LANs. At 2000 messages per second, the message latency is less than 3 ms. The paper also discusses some of what has been learned in engineering a group communication system for high performance.
An Endogenously Tagged Fluorescent Fusion Protein Library in Mouse Embryonic Stem Cells (2017)

Embryonic stem cells (ESCs), with their dual capacity to self-renew and differentiate, are commonly used to study differentiation, epigenetic regulation, lineage choices, and more. Using non-directed retroviral integration of a YFP/Cherry exon into mouse ESCs, we generated a library of over 200 endogenously tagged fluorescent fusion proteins and present several proof-of-concept applications of this library. We show the utility of this library to track proteins in living cells; screen for pluripotency-related factors; identify heterogeneously expressing proteins; measure the dynamics of endogenously labeled proteins; track proteins recruited to sites of DNA damage; pull down tagged fluorescent fusion proteins using anti-Cherry antibodies; and test for interaction partners. Thus, this library can be used in a variety of different directions, either exploiting the fluorescent tag for imaging-based techniques or utilizing the fluorescent fusion protein for biochemical pull-down assays, including immunoprecipitation, co-immunoprecipitation, chromatin immunoprecipitation, and more.
Intermediate monocytes correlate with CXCR3+ Th17 cells but not with bone characteristics in untreated early rheumatoid arthritis (2021)

Our findings suggest that in early RA, the intermediate monocytes do not correlate with bone characteristics, despite positive correlation with circulating CXCR3+ Th17 cells. Future longitudinal studies in patients with longer disease duration are required to fully explore the potential of intermediate monocytes to drive bone loss in RA.
GEOTEXTILE AND RELIEF PILES FOR DEEP FOUNDATION IMPROVEMENT: EMBANKMENT NEAR GOETEBORG, SWEDEN (1993)

This short article describes the use of a woven multifilament polyester geotextile to carry the horizontal forces in a bridge approach embankment supported on vertically driven relief piles. The embankment was to be founded on silty clay. Brief details are provided of: a) soil condition and instrumentation; b) geotextile selection; c) construction of the piles and the placement of the geotextile; and d) performance of the geotextile. For the covering abstract see IRRD 865821.
High Expression of Micro-RNA BIC / miR155 in All Subtypes of Hodgkin Lymphoma. (2004)

Abstract We recently demonstrated that the noncoding BIC gene was highly expressed in Hodgkin Reed-Sternberg (HRS) cells of the vast majority of both classical and nodular lymphocyte predominant (NLP) Hodgkin lymphoma (HL). The BIC gene belongs to the family of noncoding mRNA-like molecules and was suggested to function through its noncoding RNA transcript. The human BIC gene shows a high degree of sequence identity to the Mouse and Gallus gallus BIC genes, which was most pronounced in a region containing a ~70 nucleotide stem-loop structure. Recently published data revealed expression of miR155 micro-RNA in murine tissue. The miR155 sequence was identical to the first 22 nucleotides of the ~70 nucleotide stem-loop structure of the BIC gene indicating that BIC is a primary micro-RNA transcript. Micro-RNAs (miRNA) are endogenous small RNAs (20–22 nucleotides) that inhibit protein translation by paring to the messages of protein-coding mRNAs. Based on recent data, it is clear that deregulation of miRNA expression, processing or stability may lead to deregulation of important cellular processes and thereby contribute to the development of cancer. In this study we analyzed the expression of miR155 in HL and NHL samples and studied the regulation of BIC/miR155 expression. Northern blot analysis revealed that HL cell lines, which all have a high level of BIC transcripts, also have high levels of the functionally mature miR155. NHL samples with low levels of BIC transcripts also have low levels of miR155. These data provide experimental support for processing of primary BIC transcripts to the functionally mature miR155 fragments and indicate that miR155 expression is specific for HL. To analyze whether BIC expression could be induced in NHL cell lines we studied several stimuli in the wild type Burkitt lymphoma derived cell line Ramos and a NF-κB deficient variant cell line. Real-time RT-PCR analysis revealed a high level of BIC and of the 70 nucleotide miR155 precursor in anti-IgM stimulated Ramos cells. Anti-IgM stimulation of the NF-κB deficient Ramos cell line revealed only low levels of BIC and pre-miR155. These data demonstrate that transactivation of NF-κB is required for continuous upregulation of BIC in Ramos cells. Stimulation of Ramos cells with PMA/calcium-ionophore, which directly activates PKC, significantly upregulated the level of BIC and pre-miR155. This suggests that activation of PKC and its downstream signaling components, including NF-κB are involved in the regulation of BIC expression. Thus, whereas HRS cells typically do not express surface immunoglobulin, upregulation of BIC in these cells may be induced by constitutively activated NF-κB.