gebhart/patrepeval huggingface dataset:
Abstract 645: IGM-55.5, a novel monoclonal human recombinant IgM antibody with potent activity against B cell leukemia and lymphoma (2014)

Abstract IGM-55.5 is an engineered monoclonal human recombinant IgM antibody that was derived from a natural monoclonal antibody 216 isolated at Stanford University from the splenocytes of a patient with Non-Hodgkin's lymphoma. HuMab 216 was previously used in a B-cell acute lymphoblastic leukemia phase I trial and was demonstrated to be well tolerated with significant decrease in peripheral blasts observed (Liedtke et al, Haematologica, 2012). IGM-55.5 has been engineered to be mono-reactive and recognizes a carbohydrate determinant as an epitope on normal human B cells as well as B-cell lymphoma and B-progenitor lymphoblasts. Here, we report new preclinical studies that describe the mechanism of action and potent activity of IGM-55.5. In-vitro analysis of IGM-55.5 was found to have high surface binding on a broad panel of B cell leukemia and lymphoma cells lines by flow cytometry. IGM-55.5 binding leads to the disruption of the plasma membrane and formation of large membrane pores resulting in cell lysis. This non-classical apoptosis occurs in the absence of complement fixation but in vitro cytotoxicity is increased in assays in the presence of human complement. Studies with aggressive disseminated tumor xenograft models (Namalwa, Granta, &amp; Nalm-6) demonstrate that IGM-55.5 significantly prolongs survival and reduces circulating tumor cells. Peripheral blood samples from chronic lymphocytic leukemia patients demonstrated the potent activity of IGM-55 in eliminating B cell lymphoblasts in comparison with Rituxan when treated in-vitro. These data taken together highlight the potent activity of IGM-55.5 as therapeutic for advanced B cell malignancies, especially indicated for Rituxan resistant or refractory patients. Citation Format: Omar Duramad, Beatrice Wang, Fen Zheng, Lena Keyt, Claire Repellin, Lucia Beviglia, Neelima Bhat, Marcia Bieber, Nelson Teng, Bruce Keyt. IGM-55.5, a novel monoclonal human recombinant IgM antibody with potent activity against B cell leukemia and lymphoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 645. doi:10.1158/1538-7445.AM2014-645
Sequence diversification of the FK506‐binding proteins in several different genomes (2000)

Sequences of FK506-binding proteins (FKBPs) from four genomes of the following organisms were compared: the prokaryote Escherichia coli, the lower eukaryote Saccharomyces cerevisiae, the plant Arabidopsis thaliana, the nematode Caenorhabditis elegans and a composite of 14 unique FKBPs from two mammalian organisms Homo sapiens (man) and Mus musculus (domestic mouse). A singular FK506-like binding domain (FKBD) has about 12 kDa and occurs in the form of archetypal FKBP-12 and as a part of different proteins ranging in size from 13 to 135 kDa. Some organisms may contain a variable number of proteins which consist from two to four consecutively fused FKBDs. In the 12-kDa subgroup of archetypal FKBPs sequence identity (ID) varies from 100 to 83% (mammalian FKBPs-12), 75-50% in mammalian vs. invertebrate FKBPs-12, and fall to about 30% for pairwise sequence comparisons of mammalian and bacterial FKBPs-12 which suggests that their sequences are divergent. Multiple sequence alignment of FKBPs from the four genomes and a set of unique mammalian FKBPs does not contain any explicit consensus sequence but certain sequence positions have conserved physico-chemical characteristics. Variations of hydrophobicity and bulkiness in the multiple sequence alignment are nonsymmetrical because the physico-chemical properties of the aligned sequences changed during evolution. These variations at the sequence positions which are crucial for binding the immunosuppressive macrolide FK506 and peptidyl-prolyl cis/trans isomerase (PPIase) activity are small.
Einleitung (2017)

In diesem Buch geht es um eine Philosophie, die aus einer unermüdlichen Kritik entstand: Die Philosophie, die ihre Konstitution überhaupt dem Verbinden der Kritiken an anderen Philosophien zu verdanken scheint. Es ist die Hegels. Hegel ist bekannt als ein Denker, der die für seine Philosophie konstitutiven und wichtigen Ansätze aus der kritischen Auseinandersetzung mit seinen Vorgängern, deren monumentale Leistungen in der Geschichte der Philosophie anerkannt wurden, gewonnen hat. Ausgehend von dieser Überzeugung rekonstruiert dieses Buch Hegels Sittlichkeitsidee durch die intensive Analyse seiner zweistelligen Kritiken an den ethischen Gesetzesmodellen (bei Kant und Antigone), neuzeitlichen Naturrechtstheorien (von Hobbes und Fichte), und politischen Regierungsformen (der antiken Ungleichheitsidee und der modernen abstrakten Gleichheitsidee).
Early-onset, rapidly progressive familial tauopathy with R406W mutation (2002)

An early-onset and rapidly progressive familial tauopathy with R406W mutation is described. The patient was a 47-year-old man who first presented with psychiatric symptoms followed by overt dementia at age 52 and died 1 year later. Postmortem study revealed tangle-associated neuronal degeneration, accentuated in the medial temporal lobe. R406W mutation was determined by sequence analysis and immunocytochemically with anti-mutant tau antibody.
A phase I dose-escalation clinical trial of a peptide-based human papillomavirus therapeutic vaccine with Candida skin test reagent as a novel vaccine adjuvant for treating women with biopsy-proven cervical intraepithelial neoplasia 2/3 (2015)

<b>PURPOSE</b>: Non-surgical treatments for cervical intraepithelial neoplasia 2/3 (CIN2/3) are needed as surgical treatments have been shown to double preterm delivery rate. The goal of this study was to demonstrate safety of a human papillomavirus (HPV) therapeutic vaccine called PepCan, which consists of four current good-manufacturing production-grade peptides covering the HPV type 16 E6 protein and <i>Candida</i> skin test reagent as a novel adjuvant. <b>PATIENTS AND METHODS</b>: The study was a single-arm, single-institution, dose-escalation phase I clinical trial, and the patients (n = 24) were women with biopsy-proven CIN2/3. Four injections were administered intradermally every 3 weeks in limbs. Loop electrical excision procedure (LEEP) was performed 12 weeks after the last injection for treatment and histological analysis. Six subjects each were enrolled (50, 100, 250, and 500 μg per peptide). <b>RESULTS</b>: The most common adverse events (AEs) were injection site reactions, and none of the patients experienced dose-limiting toxicities. The best histological response was seen at the 50 μg dose level with a regression rate of 83% (n = 6), and the overall rate was 52% (n = 23). Vaccine-induced immune responses to E6 were detected in 65% of recipients (significantly in 43%). Systemic T-helper type 1 (Th1) cells were significantly increased after four vaccinations (<i>P</i> = 0.02). <b>CONCLUSION</b>: This study demonstrated that PepCan is safe. A significantly increased systemic level of Th1 cells suggests that <i>Candida,</i> which induces interleukin-12 (IL-12) <i>in vitro</i>, may have a Th1 promoting effect. A phase II clinical trial to assess the full effect of this vaccine is warranted.
Quantitative Predictions of Peptide Binding to Any HLA-DR Molecule of Known Sequence: NetMHCIIpan (2008)

CD4 positive T helper cells control many aspects of specific immunity. These cells are specific for peptides derived from protein antigens and presented by molecules of the extremely polymorphic major histocompatibility complex (MHC) class II system. The identification of peptides that bind to MHC class II molecules is therefore of pivotal importance for rational discovery of immune epitopes. HLA-DR is a prominent example of a human MHC class II. Here, we present a method, NetMHCIIpan, that allows for pan-specific predictions of peptide binding to any HLA-DR molecule of known sequence. The method is derived from a large compilation of quantitative HLA-DR binding events covering 14 of the more than 500 known HLA-DR alleles. Taking both peptide and HLA sequence information into account, the method can generalize and predict peptide binding also for HLA-DR molecules where experimental data is absent. Validation of the method includes identification of endogenously derived HLA class II ligands, cross-validation, leave-one-molecule-out, and binding motif identification for hitherto uncharacterized HLA-DR molecules. The validation shows that the method can successfully predict binding for HLA-DR molecules-even in the absence of specific data for the particular molecule in question. Moreover, when compared to TEPITOPE, currently the only other publicly available prediction method aiming at providing broad HLA-DR allelic coverage, NetMHCIIpan performs equivalently for alleles included in the training of TEPITOPE while outperforming TEPITOPE on novel alleles. We propose that the method can be used to identify those hitherto uncharacterized alleles, which should be addressed experimentally in future updates of the method to cover the polymorphism of HLA-DR most efficiently. We thus conclude that the presented method meets the challenge of keeping up with the MHC polymorphism discovery rate and that it can be used to sample the MHC "space," enabling a highly efficient iterative process for improving MHC class II binding predictions.
CFTR nonsense mutations G542X and W1282X associated with severe reduction of CFTR mRNA in nasal epithelial cells (1992)

Journal Article CFTR nonsense mutations G542X and W1282X associated with severe reduction of CFTR mRNA in nasal epithelial cells Get access Ada Hamosh, Ada Hamosh * 1Center for Medical Genetics, the Johns Hopkins University School of MedicineBaltimore, MD 21287, USA2Departments of Pediatrics, the Johns Hopkins University School of MedicineBaltimore, MD 21287, USA *To whom correspondence should be addressed at: Blalock 1008, Johns Hopkins Hospital, 600 N. Wolfe Street, Baltimore, MD 21287-4299, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Beryl J. Rosenstein, Beryl J. Rosenstein 2Departments of Pediatrics, the Johns Hopkins University School of MedicineBaltimore, MD 21287, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Garry R. Cutting Garry R. Cutting 1Center for Medical Genetics, the Johns Hopkins University School of MedicineBaltimore, MD 21287, USA2Departments of Pediatrics, the Johns Hopkins University School of MedicineBaltimore, MD 21287, USA3Departments of Medicine, the Johns Hopkins University School of MedicineBaltimore, MD 21287, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Human Molecular Genetics, Volume 1, Issue 7, October 1992, Pages 542–544, https://doi.org/10.1093/hmg/1.7.542 Published: 01 October 1992 Article history Received: 08 July 1992 Revision received: 28 August 1992 Accepted: 28 August 1992 Published: 01 October 1992
Diabetes, fibrinogen, and risk of cardiovascular disease: The Framingham experience (1990)

The influence of fibrinogen on the risk of cardiovascular disease is examined over 16 years of follow-up in 1314 subjects who were initially free of cardiovascular disease in the Framingham Study. Of these subjects, 46 men and 43 women developed diabetes, and 56 men and 53 women had blood sugar levels that exceeded 120 mg/dl. Diabetes predisposed subjects to all of the 408 major cardiovascular disease outcomes. Diabetics had higher levels of fibrinogen, hypertension, hypertriglyceridemia, and obesity, but lower HDL cholesterol values. The influence of diabetes on cardiovascular disease was greatly dependent on these coexistent risk factors, but there was a substantial independent effect of glucose intolerance when all the standard risk factors had been taken into account. There was a rise in fibrinogen values throughout the range of blood sugar levels, which suggests a thrombogenic explanation for the unique diabetic effect. However, multivariate analysis indicates no further reduction in diabetic cardiovascular risk ratios after adjustment for fibrinogen; thus, there is a residual effect for glucose intolerance after all of the standard risk factors and fibrinogen have been taken into account.
Coordinated expression in chronically unconscious persons (1998)

The clinically described 'persistent vegetative state' (PVS), consists of wakefulness unaccompanied by any evidence of the subject's awareness of self or environment. Past studies from our own and other laboratories have used positron emission tomography (PET) to study brain metabolism in approximately 20 such patients during wakeful periods. All those efforts identified global cerebral glucose metabolism at or below levels encountered during deep barbiturate anaesthesia. Nevertheless, the clinical literature includes rare reports of relatively isolated cognitive functions expressed by PVS patients late in their course. The observation raises the question of whether such activity reflects awareness or unconscious automatic behaviour. We employed magnetometry (MEG), PET scanning, MR imaging and 24-hour EEG recordings to evaluate three patients clinically vegetative between six months and 20 years after onset. Neither meticulous clinical examinations nor 24-hour EEG and video monitoring provided any hint of cognitive interaction in any subject. Nevertheless, patient 1 uttered single words once every 48 hours or more; patient 2 frequently expressed coordinated, non-purposeful, non-dystonic movements in arms and/or legs; and, patient 3 expressed strong emotional negativity without motor responses to noxious stimuli with occasional quieting in response to prosodic stimuli. All patients had whole-brain averaged global metabolism levels below 50% of normal. Patient 1, however, demonstrated preserved islands of increased metabolism in the posterior frontal and posterior temporal lobes, as well as MEG activations of Heschl's gyrus all located in the left hemisphere. In patient 2, selected increased metabolism was confined to the frontal poles and related subcortical structures. MRI in patient 3 demonstrated severe, bilateral post-traumatic cerebral atrophy. PET metabolism was diffusely reduced to 40% of normal but MEG evoked potentials indicated early and late sensory processing with abnormal later evoked components. The correlation of fragmentary behaviour with preserved metabolic and physiologic activity in cortical and subcortical regions known to support specific modular functions is novel. The finding demonstrates the capacity of severely damaged brains to partially express surviving modular functions without evidence of integrative processes that would be necessary to produce consciousness. We conclude that the mere expression of isolated neuropsychologic activity by isolated modules is insufficient to generate consciousness in overwhelmingly damaged brains.
Zero-Gain Slow Light in Optical Fibres (2006)

Generation of optical delays with minor amplitude change are realized through the superposition of gain and loss profiles generated by stimulated Brillouin scattering. It results in synthesized spectral profiles identical to an ideal electromagnetically-induced transparency.
High‐throughput automated DNA sequencing facility with fluorescent labels at the European Molecular Biology Laboratory (1992)

One of the aims of the facility is to develop and push the automated on-line DNA sequencing gel technology to its limit in sequence throughput, which may be somewhere around 100 kilobases of sequence per device per day. Key new developments were initiated and applied in operation on the European Molecular Biology Laboratory (EMBL) automated sequencer and its commercial version A.L.F. (Pharmacia). Sequencing speed was increased by a factor of 10-20, up to 1500 bases per hour per clone on ultrathin (about 100 microns) gels, while the resolution and reading length were extended to 1000 bases on gels with 50 cm separation length, using fluorescein-15-*dATP as the internal label. With our sequencing strategy, closing about 40% of the sequence with "walking" primers and F-15-*dATP as internal label, we sequenced both strands of a cosmid insert of 38.5 kb in length, each strand twice, in only 430 sequencing reactions and with average reading of 380 bases per reaction.
Scanning thermoacoustic tomography in biological tissue (2000)

Microwave-induced thermoacoustic tomography was explored to image biological tissue. Short microwave pulses irradiated tissue to generate acoustic waves by thermoelastic expansion. The microwave-induced thermoacoustic waves were detected with a focused ultrasonic transducer. Each time-domain signal from the ultrasonic transducer represented a one-dimensional image along the acoustic axis of the ultrasonic transducer similar to an ultrasonic A-scan. Scanning the system perpendicularly to the acoustic axis of the ultrasonic transducer would generate multi-dimensional images. Two-dimensional tomographic images of biological tissue were obtained with 3-GHz microwaves. The axial and lateral resolutions were characterized. The time-domain piezo-electric signal from the ultrasonic transducer in response to the thermoacoustic signal was simulated theoretically, and the theoretical result agreed with the experimental result very well.
1,3-Dipolar Cycloaddition of Furfuryl Nitrones with Acrylates. A Convenient Approach to Protected 4-Hydroxypyroglutamic Acids (2000)

We thank the MEC (Madrid, Spain) for financial support (DGES, Project PB97-1014) and for a predoctoral fellowship to one of us (V.T.).
Tracing the evolutionary path to nitrogen-fixing crops (2015)

Nitrogen-fixing symbioses between plants and bacteria are restricted to a few plant lineages. The plant partner benefits from these associations by gaining access to the pool of atmospheric nitrogen. By contrast, other plant species, including all cereals, rely only on the scarce nitrogen present in the soil and what they can glean from associative bacteria. Global cereal yields from conventional agriculture are dependent on the application of massive levels of chemical fertilisers. Engineering nitrogen-fixing symbioses into cereal crops could in part mitigate the economic and ecological impacts caused by the overuse of fertilisers and provide better global parity in crop yields. Comparative phylogenetics and phylogenomics are powerful tools to identify genetic and genomic innovations behind key plant traits. In this review we highlight recent discoveries made using such approaches and we discuss how these approaches could be used to help direct the engineering of nitrogen-fixing symbioses into cereals.
Attachment of thioglycosides to proteins: enhancement of liver membrane binding (1976)

Thioglycosides of D-galactose, D-glucose, N-acetyl-D-glucosamine, and D-mannose were covalently attached to Aspergillus oryzae alpha-amylase, hen's eggs lysozyme, and bovine serum albumin by amidination, diazo coupling, and amide formation. The binding of the newly formed glycoproteins (neoglycoproteins) to rabbit liver membranes was measured, using asialoorosomucoid as a reference. Attachment of D-galactosides by any of the three methods enhanced binding by several orders of magnitude. Coupling of a comparable number of D-mannosides or N-acetyl-D-glucosaminides had little or no effect. Attachment of D-glucosides also enhanced binding but to a variable extent depending on the method of attachment. Thus, the behavior of neoglycoproteins toward rabbit liver membranes closely paralleled that of serum glycoproteins (Ashwell and Morell, 1974) with respect to sugar specificity.
Expression of nerve growth factor in vivo from a defective herpes simplex virus 1 vector prevents effects of axotomy on sympathetic ganglia. (1992)

Sympathetic neurons in the superior cervical ganglion (SCG) of adult rats depend on target-derived nerve growth factor (NGF) for maintenance of tyrosine hydroxylase (TH) levels and the noradrenergic neurotransmitter system. Axotomy of a SCG results in NGF deprivation, causing a decline in TH activity; continuous local application of NGF can prevent this decline in TH activity. We now report that injection of a defective herpes simplex virus 1 vector that expresses NGF (pHSVngf) into a SCG can prevent the decline in TH activity that follows axotomy. SCG of adult rats were injected with either pHSVngf virus or pNFlac virus, which expresses Escherichia coli beta-galactosidase. Analysis of RNA from pHSVngf-infected SCG indicated that the NGF gene was efficiently transcribed and processed. Furthermore, 4 days after pHSVngf injection animals underwent axotomy of the virus-injected SCG. After another 10 days, animals were sacrificed and both the injected-axotomized and contralateral control ganglia were assayed for TH activity. Axotomy of SCG injected with pNFlac virus produced a 50% decline in TH activity relative to control ganglia (P = 0.02). In contrast, SCG injected with pHSVngf virus did not show a decline in TH activity following axotomy; instead, these ganglia manifested an 18% increase in TH levels relative to control ganglia. These data demonstrate that herpes simplex virus 1 vectors can be used to modify neuronal physiology in vivo; specifically, expression of a critical gene product by neural cells that do not normally produce it has potential applications for gene therapy.
Characterization of two Rat globin cDNA Clones (1984)

The rat globin gene system is suitable for studying a coordinated regulation of seven genes from two gene families. A rat reticulocyte cDNA globin library has been constructed and two clones analyzed in detail. pBRrg 5 contains alpha while pBRrg X contains beta type sequence. These cloned cDNAs will be useful probes of structure and function of rat globin genes. The deduced amino acid sequences extend the information about the variability of rat globin chains.
Total Synthesis of the Squalene Synthase Inhibitor Zaragozic Acid C (1997)

The total synthesis of zaragozic acid C has been achieved by a convergent strategy, wherein the key feature of the construction of 2,8-dioxabicyclo[3.2.1]octane core structure is a simultaneous creation of the C4 and C5 quaternary carbon centers by Sn(OTf)2-promoted aldol coupling reaction between α-keto ester and silyl ketene thioacetal derived from L- and D-tartaric acids, respectively.
DMD transcript imbalance determines dystrophin levels (2013)

Duchenne and Becker muscular dystrophies are caused by out-of-frame and in-frame mutations, respectively, in the dystrophin encoding DMD gene. Molecular therapies targeting the precursor-mRNA are in clinical trials and show promising results. These approaches will depend on the stability and expression levels of dystrophin mRNA in skeletal muscles and heart. We report that the DMD gene is more highly expressed in heart than in skeletal muscles, in mice and humans. The transcript mutated in the mdx mouse model shows a 5' to 3' imbalance compared with that of its wild-type counterpart and reading frame restoration via antisense-mediated exon skipping does not correct this event. We also report significant transcript instability in 22 patients with Becker dystrophy, clarifying the fact that transcript imbalance is not caused by premature nonsense mutations. Finally, we demonstrate that transcript stability, rather than transcriptional rate, is an important determinant of dystrophin protein levels in patients with Becker dystrophy. We suggest that the availability of the complete transcript is a key factor to determine protein abundance and thus will influence the outcome of mRNA-targeting therapies.