gebhart/patrepeval huggingface dataset:
Monoclonal antibody therapy for lymphomas and leukemias (2010)

Reengineered and fully human monoclonal antibodies 1501 generated by recombinant DNA techniques – better suited for humansTechnologies mimicking somatic hypermutation – 1502 potential improvement in the antigen-binding affinity of monoclonal antibodiesModifying the Fc portion of monoclonal antibodies – 1503 potential improvement in pharmacokinetics and therapeutic efficacyNext generation of monoclonal antibodies 1503 Unconjugated monoclonal antibodies 1504 Anti-CD20 (rituximab) 1504 Second-generation anti-CD20 antibodies 1507 Alemtuzumab 1508 Anti-CD22 (epratuzumab) 1509 Anti-CD23 1509 Anti-CD80 1509 Anti-CD74 1509Anti-HLA-DR 1511 Anti-CD30 1511 Anti-CD40 1511 Anti-CD19 1511 Anti-CD2 1511 Anti-CD4 1511 Anti-vascular endothelial growth factor 1512 Anti-CD47 1512 Bispecific antibodies 1512 Conjugated monoclonal antibodies 1513 Radioimmunotherapeutics 1513 Pretargeting radioimmunotherapy 1514 Drug immunoconjugates 1514 Immunotoxins 1515 Immunoliposomes 1515 Conclusions 1516 Key points 1516 References 1516Excellent target specificity and a favorable safety profile have been major underpinnings behind over three decades of intensive effort to add immunotherapy and radioimmunotherapy (RIT), novel treatments, to the cancer armamentarium. Since the introduction of the first therapeutic mouse-derived antibody in 1986, there have been major advances in the understanding of mechanism of action and safety profile of monoclonal antibodies (mAbs). In the first advancement, ‘chimerization’ and ‘humanization’ have improved safety profiles and efficacy. Development of commercial production made the antibody a serious contender in the therapeutic arena. Monoclonal antibodies, either in their native form or conjugated to therapeutic agents, have wide utilities in managing lymphoid malignancies largely because these agents have favorable pharmacokinetics (PK) in humans, are often very specific to certain cell types, andwith a broad range of chemotherapeutics to suit various clinical settings.
Light and electron microscopic immunolocalization of presenilin 1 in abnormal muscle fibers of patients with sporadic inclusion-body myositis and autosomal-recessive inclusion-body myopathy. (1998)

Sporadic inclusion-body myositis (s-IBM) is the most common progressive muscle disease of older persons. The muscle biopsy demonstrates mononuclear cell inflammation and vacuolated muscle fibers containing paired helical filaments and 6- to 10-nm fibrils, both resembling those of Alzheimer disease brain and Congo red positivity. The term hereditary inclusion-body myopathies (h-IBMs) designates autosomal-recessive or autosomal-dominant disorders with muscle biopsies cytopathologically similar to s-IBM but without inflammation. Vacuolated muscle fibers of both s-IBM and the h-IBMs contain accumulations of several "Alzheimer-characteristic proteins" including beta-amyloid protein and beta-amyloid precursor protein, and their paired helical filaments are composed of phosphorylated tau. We used six well characterized antibodies against several residues of presenilin 1 (PS1) to immunostain muscle biopsies of 12 patients with s-IBM, 5 patients with autosomal-recessive inclusion-body myopathy, and 16 normal and disease controls. Seventy to eighty percent of the vacuolated muscle fibers of both s-IBM and autosomal-recessive inclusion-body myopathy had inclusions that were strongly PS1-immunoreactive, which by immunoelectron microscopy localized mainly to paired helical filaments and 6- to 10-nm filaments. None of the control biopsies had PS1-positive inclusions characteristic of the s- and h-IBM abnormal muscle fibers. Mutations of the newly discovered PS1 gene are responsible for early-onset familial Alzheimer disease (AD), and PS1 is abnormally accumulated in sporadic and familial AD brain. Our study provides the first demonstration of PS1 abnormality in non-neural tissue and in diseases other than AD and suggests that the cytopathogenesis in AD brain and IBM muscle may share similarities.
SAIVGeM: Spreadsheet Analysis of Immunoglobulin V H Gene Mutations (2005)

The analysis of mutations in immunoglobulin heavy chain variable (IGHV) region genes is a tedious process when performed by hand on multiple sequences. This report describes a set of linked Microsoft Excel files that perform several common analyses on large numbers of IGHV sequences. The spreadsheet analysis of immunoglobulin VH gene mutations (SAIVGeM) package determines the distribution of mutations among each nucleotide, the nature of the mutation at both the nucleotide and amino acid level, the frequency of mutation in the A/G G C/T A/T (RGYW) hotspot motifs of both strand polarity, and the distribution of replacement and silent mutations among the complementarity determining regions (CDRs) and the framework regions (FRs) of the immunoglobulin gene as defined by either the Kabat or IMGT conventions. These parameters are summarized and graphically presented where appropriate. In addition, the SAIVGeM package analyzes those mutations that occur in third positions of redundant codons. Because any nucleotide change in these positions is inherently silent, these positions can be used to study the mutational spectra without biases from the selection of protein structure.
Small-molecule antagonism of the interaction of the RAGE cytoplasmic domain with DIAPH1 reduces diabetic complications in mice (2021)

The macro- and microvascular complications of type 1 and 2 diabetes lead to increased disease severity and mortality. The receptor for advanced glycation end products (RAGE) can bind AGEs and multiple proinflammatory ligands that accumulate in diabetic tissues. Preclinical studies indicate that RAGE antagonists have beneficial effects on numerous complications of diabetes. However, these antagonists target the extracellular domains of RAGE, which bind distinct RAGE ligands at diverse sites in the immunoglobulin-like variable domain and two constant domains. The cytoplasmic tail of RAGE (ctRAGE) binds to the formin, Diaphanous-1 (DIAPH1), and this interaction is important for RAGE signaling. To comprehensively capture the breadth of RAGE signaling, we developed small-molecule antagonists of ctRAGE-DIAPH1 interaction, termed RAGE229. We demonstrated that RAGE229 is effective in suppressing RAGE-DIAPH1 binding, Förster resonance energy transfer, and biological activities in cellular assays. Using solution nuclear magnetic resonance spectroscopy, we defined the molecular underpinnings of the interaction of RAGE229 with RAGE. Through in vivo experimentation, we showed that RAGE229 assuaged short- and long-term complications of diabetes in both male and female mice, without lowering blood glucose concentrations. Last, the treatment with RAGE229 reduced plasma concentrations of TNF-α, IL-6, and CCL2/JE-MCP1 in diabetic mice, in parallel with reduced pathological and functional indices of diabetes-like kidney disease. Targeting ctRAGE-DIAPH1 interaction with RAGE229 mitigated diabetic complications in rodents by attenuating inflammatory signaling.
Characterization of Ordered Mesoporous Silica Films Using Small-Angle Neutron Scattering and X-ray Porosimetry (2005)

Ordered mesoporous silica films were synthesized using pre-organized block copolymer templates in supercritical carbon dioxide. Poly(ethylene oxide-block-propylene oxide-block-ethylene oxide), PEO-b-PPO-b-PEO, films doped with p-toluenesulfonic acid (p-TSA) were infused with carbon dioxide solutions of silica precursors. Silica condensation proceeded selectively in the hydrophilic PEO domain due to selective partitioning of the acid catalyst in the template during its preparation. Removal of the organic template by calcination at 400 °C yielded robust mesoporous films. The films were characterized using X-ray diffraction (XRD), spectroscopic ellipsometry (SE), X-ray reflectivity (XR), Rutherford backscattering (RBS), forward recoil elastic spectroscopy (FRES), transmission electron microscopy (TEM), and small-angle neutron scattering (SANS). The pore structure and distribution was probed using contrast variation SANS porosimetry and X-ray porosimetry. Two distinct populations of pores are present in the films. Spherical mesopores were templated by the hydrophobic domain of the copolymer. Micropores in the pore walls are present due to removal of the hydrophilic PEO block, which forms an interpenetrating network (IPN)-like structure with the silicate network during infusion and condensation of the precursor. The wall density was determined to be (1.95 ± 0.05) g cm-3 and the overall porosity was found to be 39 vol %, with good agreement between the SANS and X-ray reflectivity results. A significant fraction of the total porosity, 44% to 53%, in these materials is attributed to the micropores in the wall structure.
Reduction of chirped fiber grating group delay ripple penalty through UV post processing (2003)

We demonstrate adiabatic UV correction of smoothed group delay ripple from /spl plusmn/10 ps to /spl plusmn/2 ps yielding reduction of OSNR penalty (40Gbit/s CSRZ) from /spl sim/ 4 dB to 0.5 dB over the tunable dispersion range of 270 to 750 ps/nm.
Small Non-Coding RNAs in Leukemia (2022)

In 2020, more than 60,500 people were diagnosed with leukemia in the USA, and more than 23,000 died. The incidence of leukemia is still rising, and drug resistance development is a serious concern for patients' wellbeing and survival. In the past two decades, small non-coding RNAs have been studied to evaluate their functions and possible role in cancer pathogenesis. Small non-coding RNAs are short RNA molecules involved in several cellular processes by regulating the expression of genes. An increasing body of evidence collected by many independent studies shows that the expression of these molecules is tissue specific, and that their dysregulation alters the expression of genes involved in tumor development, progression and drug response. Indeed, small non-coding RNAs play a pivotal role in the onset, staging, relapse and drug response of hematological malignancies and cancers in general. These findings strongly suggest that small non-coding RNAs could function as biomarkers and possible targets for therapy. Thus, in this review, we summarize the regulatory mechanisms of small non-coding RNA expression in different types of leukemia and assess their potential clinical implications.
The 2011 E. B. Hershberg Award for Important Discoveries in Medicinally Active Substances: (1S,3S)-3-Amino-4-difluoromethylenyl-1-cyclopentanoic Acid (CPP-115), a GABA Aminotransferase Inactivator and New Treatment for Drug Addiction and Infantile Spasms (2011)

ADVERTISEMENT RETURN TO ISSUEPerspectiveNEXTThe 2011 E. B. Hershberg Award for Important Discoveries in Medicinally Active Substances: (1S,3S)-3-Amino-4-difluoromethylenyl-1-cyclopentanoic Acid (CPP-115), a GABA Aminotransferase Inactivator and New Treatment for Drug Addiction and Infantile Spasms†Richard B. Silverman*View Author Information Department of Chemistry and Department of Molecular Biosciences, Chemistry of Life Processes Institute, Center for Molecular Innovation and Drug Discovery, Northwestern University, Evanston, Illinois 60208-3113, United States*Phone: 847-491-5653. Fax: 847-467-1566. E-mail: [email protected]Cite this: J. Med. Chem. 2012, 55, 2, 567–575Publication Date (Web):December 14, 2011Publication History Received6 December 2011Published online10 January 2012Published inissue 26 January 2012https://pubs.acs.org/doi/10.1021/jm201650rhttps://doi.org/10.1021/jm201650rreview-articleACS PublicationsCopyright © 2011 American Chemical SocietyRequest reuse permissionsArticle Views2144Altmetric-Citations29LEARN 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 InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Amines,Genetics,Peptides and proteins,Pharmaceuticals,Rodent models Get e-Alerts
PON Convergence (2017)

This paper discusses the concept of PON standards convergence. The history of PON standardization is reviewed in brief as a way to explain how the industry arrived at its current divergent form. The reasons why convergence is favorable are enumerated, with a focus on what has changed since the last round of standardization. Finally, some paths forward are proposed.
Ultrapotent antibodies against diverse and highly transmissible SARS-CoV-2 variants (2021)

The emergence of highly transmissible SARS-CoV-2 variants of concern (VOCs) that are resistant to therapeutic antibodies highlights the need for continuing discovery of broadly reactive antibodies. We identified four receptor binding domain-targeting antibodies from three early-outbreak convalescent donors with potent neutralizing activity against 23 variants, including the B.1.1.7, B.1.351, P.1, B.1.429, B.1.526, and B.1.617 VOCs. Two antibodies are ultrapotent, with subnanomolar neutralization titers [half-maximal inhibitory concentration (IC<sub>50</sub>) 0.3 to 11.1 nanograms per milliliter; IC<sub>80</sub> 1.5 to 34.5 nanograms per milliliter). We define the structural and functional determinants of binding for all four VOC-targeting antibodies and show that combinations of two antibodies decrease the in vitro generation of escape mutants, suggesting their potential in mitigating resistance development.
The Drug-User Husband and His Wife: Attachment Styles, Family Cohesion, and Adaptability (2003)

This study which assesses the association between the attachment styles of drug-user husbands (n = 56) and their wives (n = 56) and their perceptions of family dynamics was conducted in 1998. The population study included heroin (52.9%) and multidrug detoxified outpatients. All subjects completed the Adult Attachment Style Scale and the FACES III. Results indicated that the perceptions of family adaptability and cohesion among the drug-user husbands and their wives did not differ from the Israeli norm. Most of the drug users (60.7%) were characterized by the avoidant attachment style, followed by the secure style (26.8%), and the anxious/ambivalent style (12.5%). Half the wives (53.6%) were characterized by the secure style, followed by the avoidant style (42.9%) and the anxious/ambivalent style (3.6%). A secure style in husband and wife was associated with higher levels of family cohesion and adaptability, and the anxious/ambivalent style with a lower perception of family cohesion and adaptability. These findings have important implications for rehabilitation prospects and for planning intervention programs.
Correction to Identification of Quinoline-Based RIP2 Kinase Inhibitors with an Improved Therapeutic Index to the hERG Ion Channel (2020)

[This corrects the article DOI: 10.1021/acsmedchemlett.8b00344.].
Chapter 1. Development, Characterization, and Application of Novel High Temperature Thermoplastic and Thermosetting Dispersions (2019)

Here we discuss the theory and practice of emulsification of thermoplastic and thermosetting materials at elevated temperatures with Dow's HIPE (High Internal Phase Emulsion) process, also known as BLUEWAVE™ technology, as well as applications of these materials. First, the previous work on the effect of interfacial tension and rheology of the internal and external phases on droplet formation is described. This understanding is then expanded to enable the emulsification of thermoplastics and thermosetting materials at elevated temperatures. Specific case studies of designed particle and coating morphology that result from our dispersion process and how these influence application performance are also discussed.
Advances and Innovations in Computer-Assisted Head and Neck Oncologic Surgery (2012)

Over the past years, computer-assisted surgery has gained more importance in craniomaxillofacial surgery, especially in primary and secondary treatment of head and neck malignancies. The basis for oncologic treatment of the head and neck region requires detailed planning using computed tomography, cone-beam computed tomography, or magnetic resonance imaging in combination with computer-assisted, infrared-based navigation system. These techniques allow a preplanned image-guided path to the tumor region for taking biopsies, resection, or reconstruction. The aim of this work was to show the advances and technical benefits for tumor surgery in a daily clinical routine from the view of the craniomaxillofacial surgeon. The target of our working group was to develop and clinically evaluate a novel three-dimensional planning and navigation software solution for treatment of craniofacial tumors. This work was carried out on 5 categories for oncologic surgical procedures in which computer-assisted surgery was applied from 2005 to 2011: preplanned trajectorial-guided tumor biopsy, intraoperative image-controlled tumor resection, tumor mapping, reconstruction after tumor surgery (true to original), and oral rehabilitation (backward planning). Successful preoperative planning, import of image data suitable for navigation, and intraoperative precise infrared-based navigation were obtained for all 5 categories without any complications. Image-guided navigation technique for head and neck oncologic surgery provides a precise, safe surgical method with real-time excellent anatomic orientation. Regarding the advantages of computer-assisted surgery, this technique will play a major part in craniofacial reconstructive surgery and will address widespread general methodologic solutions that are of great interest in multidisciplinary oncologic treatment.
Characterization of soluble and insoluble fractions obtained from a commercial pea protein isolate (2022)

In this study, the characteristics of pea protein isolates after aqueous fractionization into water-soluble and water-insoluble fractions by centrifugation, decantation, and lyophilization were studied. Chemical composition and physicochemical properties upon pH changes were determined. The overall protein compositions of both soluble and insoluble pea protein fractions were similar containing albumins, globulins, and lipoxygenases, but amino acid compositions slightly varied. Distinct differences were observed in their charge properties, particle sizes, and voluminosities. The soluble pea protein fraction was free of measurable particles at pH 7, whereas the insoluble proteins contained particles with sizes of > 80 µm. Close to their respective isoelectric points, the soluble (pI = 3.9) and insoluble pea proteins (pI = 4.9) had very similar sizes of 40–50 µm. At pH 3, the particle sizes of soluble proteins did not change, however, the insoluble pea proteins had again sizes of > 80 µm. Voluminosity of the insoluble fraction was pH-dependent and had its highest voluminosity at pH 3 and 7, indicating changes in water binding as a function of pH. In contrast, the voluminosity of the soluble pea protein fraction did not change with pH. Taken together, this study showed that water-soluble and insoluble pea protein fractions of a commercial isolate may differ substantially with respect to their physicochemical properties. Observed inconsistencies in technofunctionality of various commercial preparations could thus be promoted by varying ratios between the two fractions.
Accounting for optical refractivity and turbulence effects in optical wave propagation over long distances (2018)

Propagation of optical waves in the atmosphere is influenced by refractive index spatial inhomogeneities resulting from complicated dynamics of air masses. Both large-scale deviations of refractive index (refractivity) and small-scale random refractive index inhomogeneities (turbulence) can significantly impact performance of atmospheric remote sensing systems including both imaging and laser-based electro-optics systems. Typically, in analysis of atmospheric sensing systems only turbulence effects are accounted for. This simplification is justified for only operation at relatively short distances and in absence of strong refractivity layers. In this paper we discuss more general propagation scenarios for which atmospheric refraction can play an important role and could significantly alter the major laser beam and image characteristics. Atmospheric refractivity is described by a combination of the standard MUSA76 and inverse temperature layer models, and atmospheric turbulence effects are accounted for using the classical Kolmogorov turbulence framework with HV57 model for the height profile of the refractive index structure parameter. The numerical analysis demonstrated that both refractivity and turbulence could significantly impact both laser beam propagation and image formation and lead to noticeable anisotropic effects.
Consumer Prices for Surgical Management of Ankle Arthritis: Limited Availability and Wide Variability (2019)

This study demonstrated limited availability of consumer prices for TAA and ankle arthrodesis. When comparing different institutions for surgical management of ankle arthritis, there was a wide range of quotes for both TAA and ankle arthrodesis. When comparing the choice of surgical management for ankle arthritis, no statistically significant difference was observed in price between TAA and ankle arthrodesis.
Independent association between symptom onset time and infarct size in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention (2014)

Recent studies have reported on circadian variation in infarct size in ST-elevation myocardial infarction (STEMI) patients. Controversy remains as to whether this finding indicates circadian dependence of myocardial tolerance to ischemia/reperfusion injury or that it can simply be explained by confounding factors such as baseline profile and ischemic time. We assessed the clinical impact and independent association between symptom onset time and infarct size, accounting for possible subgroup differences. From a multicenter registry, 6799 consecutive STEMI patients undergoing primary percutaneous coronary intervention (PCI) between 2004 and 2010 were included. Infarct size was measured using peak creatine kinase (CK). Infarct size exhibited circadian variation with largest infarct size in patients with symptom onset around 03:00 at night (estimated peak CK 1322 U/l; 95% confidence interval (CI): 1217-1436) and smallest infarct size around 11:00 in the morning (estimated peak CK 1071 U/l; 95% CI: 1001-1146; relative reduction 19%; p = 0.001). Circadian variation in infarct size followed an inverse pattern in patients with prior myocardial infarction (p-interaction <0.001) and prior PCI (p-interaction = 0.006), although the later did not persist in multivariable analysis. Symptom onset time remained associated with infarct size after accounting for these interactions and adjusting for baseline characteristics and ischemic time. Symptom onset time did not predict one-year mortality (p = 0.081). In conclusion, there is substantial circadian variation in infarct size, which cannot be fully explained by variations in baseline profile or ischemic time. Our results lend support to the hypothesis of circadian myocardial ischemic tolerance and suggest a different mechanism in patients with prior myocardial infarction.