gebhart/patrepeval huggingface dataset:
Antibody modeling assessment II. Structures and models (2014)

To assess the state-of-the-art in antibody structure modeling, a blinded study was conducted. Eleven unpublished Fab crystal structures were used as a benchmark to compare Fv models generated by seven structure prediction methodologies. In the first round, each participant submitted three non-ranked complete Fv models for each target. In the second round, CDR-H3 modeling was performed in the context of the correct environment provided by the crystal structures with CDR-H3 removed. In this report we describe the reference structures and present our assessment of the models. Some of the essential sources of errors in the predictions were traced to the selection of the structure template, both in terms of the CDR canonical structures and VL/VH packing. On top of this, the errors present in the Protein Data Bank structures were sometimes propagated in the current models, which emphasized the need for the curated structural database devoid of errors. Modeling non-canonical structures, including CDR-H3, remains the biggest challenge for antibody structure prediction.
Current Evaluation and Treatment of Patients with Swallowing Disorders (1999)

To determine the varied causes of oropharyngeal dysphagia and their respective pathophysiology, a working understanding of the normal anatomy and function of the highly integrated mechanism of swallowing is outlined. This information is presented as the basis for a reasoned and detailed approach to the history, physical examination, and endoscopic evaluation of normal and altered oropharyngeal swallowing. The management of swallowing disorders depends on the nature and magnitude of the responsible clinical condition. Conservative and surgical approaches are discussed. These modalities and their indications are described in detail.
Ventroptin: A BMP-4 Antagonist Expressed in a Double-Gradient Pattern in the Retina (2001)

In the visual system, the establishment of the anteroposterior and dorsoventral axes in the retina and tectum during development is important for topographic retinotectal projection. We identified chick Ventroptin, an antagonist of bone morphogenetic protein 4 (BMP-4), which is mainly expressed in the ventral retina, not only with a ventral high-dorsal low gradient but also with a nasal high-temporal low gradient at later stages. Misexpression of Ventroptin altered expression patterns of several topographic genes in the retina and projection of the retinal axons to the tectum along both axes. Thus, the topographic retinotectal projection appears to be specified by the double-gradient molecule Ventroptin along the two axes.
ChemInform Abstract: THE CRYSTAL STRUCTURE OF SODIUM NICKEL ARSENATE, NANIASO4 (1984)

Abstract Gelbgrüne glimmer‐ ähnliche Lamellen der Titelverbindung wurden aus einer stöchiometrischen Mischung von NiCO 3 und NaH 3 AsO 4 bei IOOO°Cmit langsamer Abkühlung erhalten.
Rapamycin Inhibits Human Adipocyte Differentiation in Primary Culture (2000)

Our data indicate that rapamycin exerts important negative regulatory effects on adipogenesis in human preadipocytes, through a mechanism that does not depend on interruption of clonal expansion.
Pancreatic beta-cell-to-beta-cell interactions are required for integrated responses to nutrient stimuli: enhanced Ca2+ and insulin secretory responses of MIN6 pseudoislets. (1999)

The effect of cell-to-cell contact on Ca2+ influx and secretory responses in the beta-cell line MIN6 was studied using MIN6 pseudoislets, which are three-dimensional islet-like cell aggregates that develop when MIN6 cells are cultured for 6-8 days on gelatin. The formation of pseudoislets is dependent on the Ca2+-dependent adhesion molecule E-cadherin (E-CAD), since the process can be inhibited by incubation in the absence of Ca2+ or in the presence of an anti-E-CAD antibody. Glucose and alpha-ketoisocaproic acid (KIC) evoked a Ca2+ influx in only a small fraction of the MIN6 monolayer cells, whereas >80% of cell groups within the pseudoislets responded to both nutrients. In contrast, changes in the intracellular free Ca2+ concentration ([Ca2+]i) were observed in all or most monolayer cells or pseudoislet cell groups in response to physical or pharmacological depolarizing stimuli. No significant increase in insulin release was observed from MIN6 monolayer cells in response to nutrient or nonnutrient insulin secretagogues. Conversely, pseudoislets were found to respond significantly to both nutrients and nonnutrients. These results suggest that close cell-to-cell contact improves the functional responsiveness of MIN6 cells and that pseudoislets may therefore serve as a useful research model in the study of beta-cell function.
Compliance of hippocampal neurons to patterned substrate networks (1991)

Neuronal growth can be controlled in vitro by plating cells at low density and by differential adhesion between the cell and substrate. Primary cultures of rat hippocampal neurons were grown in serum-free culture on polylysine-coated glass coverslips patterned by selective laser ablation so as to leave grids of polylysine with varying linewidths (3, 5, and 10 microns), intersection distance (80, 120, and 160 microns), and nodal (intersection) diameter (5, 10, and 20 microns). Not only did somae strongly prefer the unablated polylysine areas, but they also migrated to loci where the local area of unablated polylysine was higher. These loci were the nodes, as opposed to the narrow connecting paths, and larger nodes, as compared with smaller nodes. Maximum migration to nodes of 88% occurred for a combination of 5-microns path width, 20-microns node diameter, and 80-microns path length. Daily observations indicated active migration to larger adhesive areas, which explains the differential compliance.
RET Genetic Screening in Patients with Medullary Thyroid Cancer and Their Relatives: Experience with 807 Individuals at One Center (2007)

In this large series of MTC, hereditary forms, mainly FMTC, were clinically unsuspected in 7.3% of apparently sporadic cases. As a consequence, the prevalence of FMTC in our series is higher than that previously reported (60 vs. 10%). In these cases, RET mutations were more prevalently located in noncysteine codons. Data derived from our series helped elucidate the role of RET genetic screening for the identification of all forms of MEN 2, and especially for FMTC, which are frequently clinically misdiagnosed as nonheritable, sporadic cases.
Chromomycin, mithramycin, and olivomycin binding sites on heterogeneous DNA. Footprinting with methidiumpropyl-EDTA•iron(II) (1983)

The DNA binding sites for the antitumor, antiviral, antibiotics chromomycin, mithramycin, and olivomycin on 70 base pairs of heterogeneous DNA have been determined by using the (methidiumpropyl-EDTA)iron(II) [MPE•Fe(II)] DNA cleavage inhibition pattern technique. Two DNA restriction fragments 117 and 168 base pairs in length containing the lactose operon promoter-operator region were prepared with complementary strands labeled with ^(32)P at the 3' end. MPE•Fe(II) was allowed to partially cleave the restriction fragment preequilibrated with either chromomycin, mithramycin, or olivomycin in the presence of Mg^(2+). The preferred binding sites for chromomycin, mithramycin, and olivomycin in the presence of Mg^(2+) appear to be a minimum of 3 base pairs in size containing at least 2 contiguous dG•dC base pairs. Many binding sites are similar for the three antibiotics; chromomycin and olivomycin binding sites are nearly identical. The number of sites protected from MPE•Fe(II) cleavage increases as the concentration of drug is raised. For chromomycin/Mg^(2+), the preferred sites on the 70 base pairs of DNA examined are (in decreasing affinity) 3'-GGG, CGA > CCG, GCC > CGA, CCT > CTG-5'. The sequence 3'-CGA-5' has different affinities, indicating the importance of either flanking sequences or a nearly bound drug.
An immunotoxin with therapeutic potential in T cell leukemia: WT1-ricin A (1984)

A conjugate of the monoclonal antibody WT1 and ricin A-chain was studied for its suitability for purging marrow of leukemic T cells for autologous transplantation in T cell acute lymphocytic leukemia (T- ALL). The conjugate was powerfully cytotoxic to the human T-ALL cell line, GH1, which expresses the WT1 antigen at a high density. Treatment of the cells with the conjugate at 10(-11) M reduced their rate of protein synthesis by 50%, and the inclusion of 6 mM ammonium chloride in the cultures enhanced the potency of cytotoxic effect by 10–100- fold. Clonogenic assays indicated that less than 0.1% of GH1 cells survived 3-hr exposure to the conjugate in ammonium chloride. WT1 alone did not react with multipotent (CFU-GEMM) hematopoietic progenitors in normal human bone marrow, as measured by fluorescence-activated cell sorting. Under conditions giving maximal killing of GH1 cells, there was no toxicity to multipotential progenitors in normal human marrow.
Design issues for interactive television systems (1995)

Computing, communication, and relevant standards are on the brink of enabling thousands of people to enjoy the services offered by large, distributed multimedia systems in their own homes. Collectively, these services will include TV (basic, subscription, and pay-per-view), service navigator, interactive entertainment, digital audio, video-on-demand, home shopping, financial transactions, interactive single- and multiuser games, digital multimedia libraries, and electronic versions of newspapers, magazines, TV program guides, and yellow pages. It is obvious that current TV systems and architectures must be redesigned to support such services. In this article, we propose potential solutions to modify existing systems to support these new functions, and we discuss related matters.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Can the life span of human marrow stromal cells be prolonged by bmi‐1, E6, E7, and/or telomerase without affecting cardiomyogenic differentiation? (2004)

The life span of hMSCs was prolonged without interfering with cardiomyogenic differentiation. hMSCs with an extended life span can be used to produce a good experimental model of cardiac cell transplantation and may serve as a highly useful cell source for cardiomyocytic transplantation.
Persistent Expression of FLAG-tagged Micro dystrophin in Nonhuman Primates Following Intramuscular and Vascular Delivery (2009)

Animal models for Duchenne muscular dystrophy (DMD) have species limitations related to assessing function, immune response, and distribution of micro- or mini-dystrophins. Nonhuman primates (NHPs) provide the ideal model to optimize vector delivery across a vascular barrier and provide accurate dose estimates for widespread transduction. To address vascular delivery and dosing in rhesus macaques, we have generated a fusion construct that encodes an eight amino-acid FLAG epitope at the C-terminus of micro-dystrophin to facilitate translational studies targeting DMD. Intramuscular (IM) injection of AAV8.MCK.micro-dys.FLAG in the tibialis anterior (TA) of macaques demonstrated robust gene expression, with muscle transduction (50-79%) persisting for up to 5 months. Success by IM injection was followed by targeted vascular delivery studies using a fluoroscopy-guided catheter threaded through the femoral artery. Three months after gene transfer, >80% of muscle fibers showed gene expression in the targeted muscle. No cellular immune response to AAV8 capsid, micro-dystrophin, or the FLAG tag was detected by interferon-gamma (IFN-gamma) enzyme-linked immunosorbent spot (ELISpot) at any time point with either route. In summary, an epitope-tagged micro-dystrophin cassette enhances the ability to evaluate site-specific localization and distribution of gene expression in the NHP in preparation for vascular delivery clinical trials.
Message from the Editors to our U.S. and International Reviewers (2006)

Neurology received 2,011 manuscripts from October 1, 2005, through March 31, 2006. In this same period the previous year, we received 1,759 manuscripts, a 14% increase. International submissions continue to constitute 65–70% of submissions. More than 90% of papers are peer-reviewed.

Neurology obtained more than 5,000 reviews from October 1, 2005, through March 31, 2006, the 6-month period that this acknowledgment includes. Reviewers are asked to complete the review in 18 days and our reviewers return them in an average of 12.3 days—a truly outstanding record. More than 25% of our reviews come from experts outside of the United States.

The readership and authors of Neurology and the Editors owe a tremendous debt to our reviewers. The reviewers’ major reward is the knowledge that they have contributed altruistically to clinical science and have worked for the benefit of authors, the readers of Neurology , and their patients.

We are especially grateful to those reviewers who review 5, 10, or 20 or more papers a year. These leaders of neurology and clinical neuroscience have been consistently generous with their time. In general, the most senior and busiest people in our field are the most frequent, the fastest, the most responsive, the most mentoring, and the most reliable reviewers.

All our reviewers have the Editors’ sincere thanks for their efficient, selfless, and responsible work. Those reviewers with one asterisk have reviewed 5 or more papers. Two asterisks indicate that the reviewer has reviewed 10 or more manuscripts. Please note this list includes those reviewers who returned a review of initial submissions (re-reviews are not included) between October 1, 2005, and March 31, 2006.

Robert C. Griggs 

Editor-in-Chief 

Robert A. Gross 

Jonathan W. Mink 

Garrett H. Riggs 

Steven R. Schwid 

Associate Editors 

Johan A. Aarli

Bassel W. Abou-Khalil

Loutfi S. Aboussouan

Sharon Abrahams …
Parathyroid hormone increases cytosolic calcium concentration in adult rat cardiac myocytes (1993)

The heart is a target organ for parathyroid hormone (PTH), and the action of this hormone on the myocardium may be mediated through the ability of PTH to increase cytosolic calcium ([Ca2+]i) in the myocardial cells. However, direct evidence for such an effect of PTH is lacking, and the mechanism(s) through which the hormone can potentially exert such an effect have not been elucidated. In the present study these questions were examined using cardiac myocytes isolated from adult rats. Both PTH-(1-34) and PTH-(1-84) produced a dose-dependent increase in [Ca2+]i of myocytes, but the effect of the latter was significantly (P < 0.01) greater than the former. This action of PTH was abolished by the inactivation of the hormone, the use of a PTH antagonist, or by verapamil. The G protein activator, guanosine 5'-O-(3-thiothriphosphate) (GTP gamma S), mimicked the effect of PTH, whereas pertussis toxin, the G protein inhibitor, guanosine 5'-O-(2-thiodiphosphate) (GDP beta S), or ryanodine significantly reduced the PTH-induced rise in [Ca2+]i. Dibutyryl- and 8-bromoadenosine-3',5'-cyclic monophosphate, forskolin, 12-O-tetradecanoylphorbol 13-acetate, and staurosporine did not increase [Ca2+]i in myocytes, and staurosporine did not alter the PTH-induced rise in [Ca2+]i. BAY K 8644 augmented the effect of PTH on [Ca2+]i. These data demonstrate that 1) PTH increases [Ca2+]i of cardiac myocytes, 2) this action is receptor mediated and is produced by activation of the L-type calcium channels following stimulation of G protein(s), and 3) the rise in [Ca2+]i is due to both augmented entry of calcium into the myocytes and mobilization of calcium from sarcoplasmic reticulum by a calcium-induced calcium release mechanism.
Parallel multiplex thermodynamic analysis of coaxial base stacking in DNA duplexes by oligodeoxyribonucleotide microchips (2001)

Parallel thermodynamic analysis of the coaxial stacking effect of two bases localized in one strand of DNA duplexes has been performed. Oligonucleotides were immobilized in an array of three-dimensional polyacrylamide gel pads of microchips (MAGIChips'). The stacking effect was studied for all combinations of two bases and assessed by measuring the increase in melting temperature and in the free energy of duplexes formed by 5mers stacked to microchip-immobilized 10mers. For any given interface, the effect was studied for perfectly paired bases, as well as terminal mismatches, single base overlaps, single and double gaps, and modified terminal bases. Thermodynamic parameters of contiguous stacking determined by using microchips closely correlated with data obtained in solution. The extension of immobilized oligonucleotides with 5,6-dihydroxyuridine, a urea derivative of deoxyribose, or by phosphate, decreased the stacking effect moderately, while extension with FITC or Texas Red virtually eliminated stacking. The extension of the immobilized oligonucleotides with either acridine or 5-nitroindole increased stacking to mispaired bases and in some GC-rich interfaces. The measurements of stacking parameters were performed in different melting buffers. Although melting temperatures of AT- and GC-rich oligonucleotides in 5 M tetramethylammonium chloride were equalized, the energy of stacking interaction was significantly diminished.
An Autoimmune Channelopathy Associated with Cancer: Lambert-Eaton Myasthenic Syndrome. (1999)

The Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disease that is often associated with lung cancer which shares a common antigenic protein with the motor nerve terminal. The myasthenic weakness is caused by an antibody-induced reduction in the release of acetylcholine from the nerve terminal. This study was undertaken to determine the target of LEMS antibodies and specify the voltage-gated calcium channel (VGCC) through which calcium influxes following the presynaptic membrane depolarization. Among the 5 types of VGCC, we found that the P/Q-type was highly recognized by LEMS antibodies. Using synthetic peptides or recombinant proteins as antigens for testing LEMS patients' sera or inducing an animal model of LEMS, we specified the S5-S6 linker regions in 3 of 4 domains constituting the alpha1 subunit of P/Q-type VGCC as immunodominant sites. Synaptotagmin, one of the functionally VGCC-associated proteins and a protein functioning as a calcium sensor for exocytosis of synaptic vesicles, was also found to be a pathogenic immunogen of LEMS when the recombinant protein for antibody assay and the synthetic peptide for the induction of animal model were used as antigens. The present study forms a united front against cancer and cancer-related myasthenic syndrome.
Premature telomeric loss in rheumatoid arthritis is genetically determined and involves both myeloid and lymphoid cell lineages (2003)

In rheumatoid arthritis, peripheral blood T cells have age-inappropriate telomeric erosion. We examined whether HLA-DRB1*04 alleles, the major susceptibility genes for this disease, confer risk for T cell senescence. In healthy individuals, HLA-DRB1*04 alleles were associated with excessive loss of telomeres in CD4+ T cells. Accelerated telomeric erosion occurred during the first two decades of life and was followed by reduced homeostatic T cell proliferation during adulthood. Premature telomeric loss also affected granulocytes, suggesting that the hematopoietic stem cell is the primary target. Telomeric repair mechanisms were intact in HLA-DRB1*04+ donors. We propose that HLA-DRB1*04 alleles or genes in linkage disequilibrium regulate stem cell replication and contribute to the accumulation of senescent and autoreactive T cells in rheumatoid arthritis.
Biochemical and functional analysis of CTR1, a protein kinase that negatively regulates ethylene signaling inArabidopsis (2003)

CTR1 encodes a negative regulator of the ethylene response pathway in Arabidopsis thaliana. The C-terminal domain of CTR1 is similar to the Raf family of protein kinases, but its first two-thirds encodes a novel protein domain. We used a variety of approaches to investigate the function of these two CTR1 domains. Recombinant CTR1 protein was purified from a baculoviral expression system, and shown to possess intrinsic Ser/Thr protein kinase activity with enzymatic properties similar to Raf-1. Deletion of the N-terminal domain did not elevate the kinase activity of CTR1, indicating that, at least in vitro, this domain does not autoinhibit kinase function. Molecular analysis of loss-of-function ctr1 alleles indicated that several mutations disrupt the kinase catalytic domain, and in vitro studies confirmed that at least one of these eliminates kinase activity, which indicates that kinase activity is required for CTR1 function. One missense mutation, ctr1-8, was found to result from an amino acid substitution within a new conserved motif within the N-terminal domain. Ctr1-8 has no detectable effect on the kinase activity of CTR1 in vitro, but rather disrupts the interaction with the ethylene receptor ETR1. This mutation also disrupts the dominant negative effect that results from overexpression of the CTR1 amino-terminal domain in transgenic Arabidopsis. These results suggest that CTR1 interacts with ETR1 in vivo, and that this association is required to turn off the ethylene-signaling pathway.
Support for the Use of Hierarchical Temporal Memory Systems in Automated Design Evaluation: A First Experiment (2009)

Computational synthesis tools that automatically generate solutions to design problems are not widely used in industry despite many years of research. This deficiency can be attributed to the lack of value that these tools provide for the user in terms of time saved in design or quality improvements in the design. In order to provide sufficient quality of solution, it is proposed that more human-like evaluation of solution quality is needed including qualitative concepts, the ability to allow for anecdotal input, and general inclusion of ambiguous information. A hierarchical temporal memory system (HTM) is proposed as a viable approach for capturing design quality from exemplars and subsequently recognizing the presence of that quality in other designs. This paper includes a first experiment in using HTMs for learning and recognizing quality in the form of the visual style characteristics of Hepplewhite, Stickley, and Greene &amp; Greene chair backs. Results show that HTMs develop a similar storage of quality to humans and are therefore a promising option for capturing and recognizing multi-modal quality information in future design automation projects.
Gemtuzumab ozogamicin in non-acute promyelocytic acute myeloid leukemia (2011)

Future challenges of personalized therapy in AML will be to integrate the signals from current subgroup analyses underlining the role of GO in genetically defined AML entities.
Cloning and developmental expression of Sna, a murine homologue of the Drosophila snail gene (1992)

The genetic analysis of dorsoventral patterning in Drosophila has identified a zinc-finger gene, snail, that is required for mesoderm formation. The cloning and nuclease protection analysis of a Xenopus homologue of this gene has suggested a possible role in the mesoderm of vertebrates. Here, we describe the cloning of a murine homologue of snail, Sna, and in situ hybridisation studies of its developmental expression. Sequence analysis reveals substantial conservation of the second to fifth zinc fingers, but not of the first zinc finger in the Sna gene. Expression occurs in the ectoplacental cone, parietal endoderm, embryonic and extraembryonic mesoderm, in neural crest and in condensing precartilage. Based on the timing and spatial restriction of expression in embryonic mesoderm, we suggest that Sna might be required for the early development of this tissue, as is the case for its Drosophila counterpart. In addition, we propose that Sna might have an analogous role in the development of neural crest. The expression in condensing precartilage indicates that this gene also has a later function in chondrogenesis.