gebhart/patrepeval huggingface dataset:
Localization of a major receptor-binding domain for epidermal growth factor by affinity labeling. (1988)

Epidermal growth factor (EGF) receptor was affinity labeled with 125I-labeled EGF, using bifunctional covalent cross-linking agents. The affinity-labeled receptor was isolated and cleaved with CNBr to yield a single-labeled fragment, which was unequivocally identified by site-specific antibodies and other methods to encompass residues 294 to 543 of the EGF receptor. On the basis of amino acid sequence conservation, the extracellular portion of EGF receptor can be divided into four domains. The labeled CNBr fragment contains the entire sequence which is flanked by the two cysteine-rich domains of extracellular portion of the EGF receptor denoted as domain III. On the basis of these and other results, we propose that domain III contributes most of the interactions that define ligand-binding specificity of the EGF receptor.
Defective accessory genes in a human immunodeficiency virus type 1-infected long-term survivor lacking recoverable virus (1995)

We have been studying a patient who acquired human immunodeficiency virus (HIV) infection via a blood transfusion 13 years ago. She has remained asymptomatic since that time. The blood donor and two other recipients have all died of AIDS. Although this patient has shown persistently strong seroreactivity to HIV type 1 (HIV-1) antigens by Western blot (immunoblot), she has been continually HIV culture negative in results from multiple laboratories over the last 6 years and has a very low viral burden. Her CD4+ T-cell count has fluctuated around a mean of 399 cells per microliters, with little change in lymphocyte subset percentages. Strong cellular immune responses to HIV-1 epitopes by this patient have been demonstrated. We now report the results of an intensive molecular genetic analysis of the HIV-1 proviral quasispecies from this patient sampled over 5 years. Long terminal repeat region sequences supported the argument for normal basal and Tat-mediated promoter activities. Sequential sequencing of the nef gene revealed a low frequency (8.3%) of defective genes and a striking lack of sequence evolution. Functional analysis of predominant nef genes by both a cell surface CD4 downregulation and a viral infectivity complementation assay showed wild-type function. In contrast, sequential analysis of an amplicon containing the vif, vpr, vpu, tat1, and rev1 genes revealed the presence of inactivating mutations in 64% of the clones. These data suggest that this patient, initially infected with a virulent swarm of HIV-1, is presently infected with a more-attenuated viral quasispecies as a result of effective host immunity.
Selective Expansion of Human Natural Killer Cells from Peripheral Blood Mononuclear Cells by the Cell Line, HFWT (2002)

An anchorage-dependent Wilms tumor cell line HFWT was found to stimulate selective and remarkable expansion of human natural killer (NK) cells from human peripheral blood mononuclear cells (PBMC). After PBMC of healthy donors were cultured on irradiated HFWT cells for 10 - 21 days, the lymphocytes expanded 58- to 401-fold. This NK cell expansion required direct contact of PBMC with live, but not fixed, HFWT cells. The PBMC from an end-stage brain tumor patient also expanded 156-fold, whereas those cultured with irradiated NK-sensitive K562 grew only 30.5-fold. CD16+ CD56+ NK cells accounted for more than 70% of the population expanded on HFWT cells. No essential difference in expression of NK receptors was observed in the expanded NK cells on HFWT and K562 and without feeder cells. The expanded NK cells killed not only fresh HFWT cells but, unexpectedly, also MHC class I-expressing autologous brain tumor cells at an effector/target ratio of 4 for 24 h. These results will contribute to the development of a large-scale preparation method for human NK cells, which will aid studies of NK cell biology and possible treatment of brain tumors.
Use of lymphokine-activated killer cells to prevent bone marrow graft rejection and lethal graft-vs-host disease. (1989)

Prompted by our recent finding that lymphokine-activated killer (LAK) cells mediate both veto and natural suppression, we tested the ability of adoptively transferred LAK cells to block two in vivo alloreactions which complicate bone marrow transplantation: resistance to transplanted allogeneic bone marrow cells, and lethal graft-vs-host disease. Adoptive transfer of either donor type B6D2 or recipient-type B6 lymphokine-activated bone marrow cells, cells found to have strong LAK activity, abrogated or inhibited the resistance of irradiated B6 mice to both B6D2 marrow and third party-unrelated C3H marrow as measured by CFU in spleen on day 7. The ability of lymphokine-activated bone marrow cells to abrogate allogeneic resistance was eliminated by C lysis depletion of cells expressing asialo-GM1, NK1.1, and, to a variable degree, Thy-1, but not by depletion of cells expressing Lyt-2, indicating that the responsible cells had a LAK cell phenotype. Similar findings were obtained by using splenic LAK cells generated by 3 to 7 days of culture with rIL-2. Demonstration that allogeneic resistance could be blocked by a cloned LAK cell line provided direct evidence that LAK cells inhibit allogeneic resistance. In addition to inhibiting allogeneic resistance, adoptively transferred recipient-type LAK cells prevented lethal graft-vs-host disease, and permitted long term engraftment of allogeneic marrow. Irradiation prevented LAK cell inhibition of both allogeneic resistance and lethal graft-vs-host disease. These findings suggest that adoptive immunotherapy with LAK cells may prove useful in preventing graft rejection and graft-versus-host disease in human bone marrow transplant recipients.
Treatment-resistant schizophrenia: reviewing the options and identifying the way forward. (1999)

Between 20% and 40% of schizophrenic patients are thought to be resistant to conventional antipsychotic therapy, although this may be an underestimate of the scale of the problem. The causes of nonresponsiveness are likely to be multifactorial, and there have been reported associations between refractoriness and neuropsychological impairment, negative symptoms, and abnormal brain morphology. For some patients, treatment resistance may in fact represent an intrinsic part of the schizophrenic illness. Treating the refractory patient should begin with a full, preferably multidisciplinary, review of diagnosis, symptoms, and side effects. Although an increased dose of a conventional antipsychotic agent can be effective for some patients, consideration should be given to reducing the dose and combining treatment with psychosocial management, or switching to one of the newer atypical antipsychotics.
RGS4 Is Arginylated and Degraded by the N-end Rule Pathway in Vitro (2000)

The N-end rule relates the in vivo half-life of a protein to the identity of its N-terminal residue. We used an expression-cloning screen to search for mouse proteins that are degraded by the ubiquitin/proteasome-dependent N-end rule pathway in a reticulocyte lysate. One substrate thus identified was RGS4, a member of the RGS family of GTPase-activating proteins that down-regulate specific G proteins. A determinant of the RGS4 degradation signal (degron) was located at the N terminus of RGS4, because converting cysteine 2 to either glycine, alanine, or valine completely stabilized RGS4. Radiochemical sequencing indicated that the N-terminal methionine of the lysate-produced RGS4 was replaced with arginine. Since N-terminal arginine is a destabilizing residue not encoded by RGS4 mRNA, we conclude that the degron of RGS4 is generated through the removal of N-terminal methionine and enzymatic arginylation of the resulting N-terminal cysteine. RGS16, another member of the RGS family, was also found to be an N-end rule substrate. RGS4 that was transiently expressed in mouse L cells was short-lived in these cells. However, the targeting of RGS4 for degradation in this in vivo setting involved primarily another degron, because N-terminal variants of RGS4 that were stable in reticulocyte lysate remained unstable in L cells.
Electrohydrodynamic printing of silver nanoparticles by using a focused nanocolloid jet (2007)

As a direct write technology, the electrohydrodynamic printing of silver nanoparticles by using a focused nanocolloid jet is introduced. In this letter, two categorized types of examples of two-dimensional patterning were printed by using the electrohydrodynamic printing method. A spiral-type inductor was printed to demonstrate the feasibility of the electrohydrodynamic printing as a fabrication process. The printed spiral inductor produced 9.45μH and exhibited approximately five times larger resistivity (9.5μΩcm) than that of bulk silver after the sintering process. Then, complex geometries having square- and round-shape patterns were also printed.
Surfactants, Micelles and Fascinating Phenomena (1988)

Abstract In this article we shall describe processes and phenomena which may appear startling and unusual for someone who is familiar with the behavior of solutions of low molecular weight solutes. Some of these phenomena might even be surprising for someone who works with surfactants. The authors still remember their astonishment when they first became aware of a viscoelastic surfactant solution. This was many years after our group had started investigations on surfactants. But all of the solutions we had encountered until that time had behaved normally. Some of the phenomena which will be discussed are also encountered in solutions of polymers. Due to their high molecular weight one expects to find properties which are different from the properties of low molecular weight solutions and does not find them so surprising. Surfactant solutions, however, are aqueous solutions of small molecules with typical molecular weights of 200 to 400. For some of our experiments even dilute solutions were used which contained only up to one percent of surfactant.
Contribution of Antibody-based Protein Profiling to the Human Chromosome-centric Proteome Project (C-HPP) (2012)

A gene-centric Human Proteome Project has been proposed to characterize the human protein-coding genes in a chromosome-centered manner to understand human biology and disease. Here, we report on the protein evidence for all genes predicted from the genome sequence based on manual annotation from literature (UniProt), antibody-based profiling in cells, tissues and organs and analysis of the transcript profiles using next generation sequencing in human cell lines of different origins. We estimate that there is good evidence for protein existence for 69% (n = 13985) of the human protein-coding genes, while 23% have only evidence on the RNA level and 7% still lack experimental evidence. Analysis of the expression patterns shows few tissue-specific proteins and approximately half of the genes expressed in all the analyzed cells. The status for each gene with regards to protein evidence is visualized in a chromosome-centric manner as part of a new version of the Human Protein Atlas ( www.proteinatlas.org ).
Application of computer-assisted design in craniofacial reconstructive surgery using a commercial image guidance system (2006)

The technology of digital image guidance systems has transformed many aspects of neurosurgery, including intracranial tumor surgery, functional neurosurgery, and spinal surgery. Despite the central role of imaging studies in diagnosis and treatment planning, intraoperative image guidance has so far had very limited application to the surgical correction of craniofacial deformities, particularly those associated with craniosynostosis. The authors report an example of the marriage of computer-assisted design methods to a commercially available neurosurgical image-guidance system in the treatment of a case of anterior plagiocephaly due to unilateral coronal synostosis. They discuss the steps that must yet be taken to make this technology applicable to the management of craniosynostosis in infants.
Cross-cultural Adaptation and Validation of the Dutch Version of SWAL-QoL (2008)

The aim of this work was to translate the 44-item SWAL-QoL into Dutch (SWAL-QoL-NL) and compare the validity of this questionnaire against Euroqol in a Dutch population with dysphagia. SWAL-QoL was translated according to international guidelines. SWAL-QoL-NL and Euroqol were completed by 152 patients in seven diagnosis groups. Internal consistency and correlations were calculated. Scores for nine subscales (General burden, Food selection, Eating duration, Fear of eating, Sleep, Fatigue, Mental health, Social functioning and a symptom score) ranged between 0.80 and 0.92 (Cronbach's alpha). Two subscales (Eating desire and Communication scored 0.67 and 0.60, respectively, and were removed from the questionnaire. The 14-item battery on clinical symptoms showed an internal consistency of 0.80, allowing the use of a sum score on group level in clinical research. Correlation of SWAL-QoL-NL subscales with the Euroqol was negligible to low (Pearson's correlations range = 0.09-0.36). The 39-item SWAL-QoL-NL proved to be a reliable tool to examine the impact of dysphagia on quality of life in a Dutch population. Internal consistency allows the use of nine subscales of SWAL-QoL-NL for comparisons on a group level (0.80 < alpha < 0.92) only. Also a Symptom score can be derived from the raw data.
Controlling Topology and Native-like Behavior of de Novo-Designed Peptides:  Design and Characterization of Antiparallel Four-Stranded Coiled Coils (1996)

The de novo design of peptides and proteins has emerged as an attractive approach for investigating protein structure and function. Here, the design, synthesis, and characterization of a new series of alpha-helical peptides intended to form antiparallel four-stranded coiled coils is described. Computer models were generated without the use of extant protein structures and were used to refine the sequence. The peptides are of the general formula Ncap-(XaZbZcLdZeZfZg)3-Ccap, where X is either Ala, Val, Thr, or Leu, and Ncap and Ccap are sequences designed to satisfy the helices unpaired amide nitrogens and carbonyl oxygens, respectively. The hydrophobic residues (at positions a and d) were chosen so that geometric packing of large and small hydrophobes would favor an antiparallel arrangement. Special attention was also given to residues at the helix--helix interfaces. These residues were chosen to balance potential attractive and repulsive electrostatic forces so that the desired topology was favored while other possible folds were destabilized. Two of the four peptides associate under neutral conditions into the desired tetramers. One of the complexes (a = Val) behaves like a native-like protein as judged by NMR, thermodynamics, and apolar dye (ANS) binding. The other tetrameric complex (a = Leu) exhibits broader NMR resonances, diminished values of delta H and delta Cp, and tight binding of the hydrophobic dye ANS, similar to early designed proteins. These results reinforce the importance of optimizing van der Waals packing interactions in protein design but demonstrate that hydrophobic packing must be balanced with hydrogen-bonding and electrostatic interactions to produce novel native-like proteins.
A Mechanism of Drug Action Revealed by Structural Studies of Enoyl Reductase (1996)

Enoyl reductase (ENR), an enzyme involved in fatty acid biosynthesis, is the target for antibacterial diazaborines and the front-line antituberculosis drug isoniazid. Analysis of the structures of complexes of Escherichia coli ENR with nicotinamide adenine dinucleotide and either thienodiazaborine or benzodiazaborine revealed the formation of a covalent bond between the 2' hydroxyl of the nicotinamide ribose and a boron atom in the drugs to generate a tight, noncovalently bound bisubstrate analog. This analysis has implications for the structure-based design of inhibitors of ENR, and similarities to other oxidoreductases suggest that mimicking this molecular linkage may have generic applications in other areas of medicinal chemistry.
Allele‐dependent changes of olivocerebellar circuit properties in the absence of the voltage‐gated potassium channels Kv3.1 and Kv3.3 (2004)

Double-mutant mice (DKO) lacking the two voltage-gated K(+) channels Kv3.1 and Kv3.3 display a series of phenotypic alterations that include ataxia, myoclonus, tremor and alcohol hypersensitivity. The prominent cerebellar expression of mRNAs encoding Kv3.1 and Kv3.3 subunits raised the question as to whether altered electrical activity resulting from the lack of these K(+) channels might be related to the dramatic motor changes. We used the tremorogenic agent harmaline to probe mutant mice lacking different K(+) channel alleles for altered olivocerebellar circuit properties. Harmaline induced the characteristic 13-Hz tremor in wildtype mice (WT); however, no tremor was observed in DKO suggesting that the ensemble properties of the olivocerebellar circuitry are altered in the absence of Kv3.1 and Kv3.3 subunits. Harmaline induced tremor in Kv3.1-single mutants, but it was of smaller amplitude and at a lower frequency indicating the participation of Kv3.1 subunits in normal olivocerebellar system function. In contrast, harmaline tremor was virtually absent in Kv3.3-single mutants indicating an essential role for Kv3.3 subunits in tremor induction by harmaline. Immunohistochemical staining for Kv3.3 showed clear expression in the somata and proximal dendrites of Purkinje cells and in their axonal projections to the deep cerebellar nuclei (DCN). In DCN, both Kv3.1 and Kv3.3 subunits are expressed. Action potential duration is increased by approximately 100% in Purkinje cells from Kv3.3-single mutants compared to WT or Kv3.1-single mutants. We conclude that Kv3.3 channel subunits are essential for the olivocerebellar system to generate and sustain normal harmaline tremor whereas Kv3.1 subunits influence tremor amplitude and frequency.
Nanoscale study of conduction through carbon nanotube networks (2004)

We present local conductance measurements of carbon nanotube networks with nanometer scale resolution and show that there are discrete drops in conductance that correspond to junctions of metallic nanotubes and semiconducting nanotubes. The anomalies of these networks compared to thin films are shown, and a new method of discerning between semiconducting and metallic single-wall carbon nanotubes is demonstrated.
Pharmacologic approaches to cerebral aging and neuroplasticity: insights from the stroke model (2013)

Brain plasticity is an intrinsic characteristic of the nervous system that allows continuous remodeling of brain functions in pathophysiological conditions. Although normal aging is associated with morphological modifications and decline of cerebral functions, brain plasticity is at least partially preserved in elderly individuals. A growing body of evidence supports the notion that cognitive enrichment and aerobic training induce a dynamic reorganization of higher cerebral functions, thereby helping to maintain operational skills in the elderly and reducing the incidence of dementia. The stroke model clearly shows that spontaneous brain plasticity exists after a lesion, even in old patients, and that it can be modulated through external factors like rehabilitation and drugs. Whether drugs can be used with the aim of modulating the effects of physical training or cognitive stimulation in healthy aged people has not been addressed until now. The risk:benefit ratio will be the key question with regard to the ethical aspect of this challenge. We review in this article the main aspects of human brain plasticity as shown in patients with stroke, the drug modulation of brain plasticity and its consequences on recovery, and finally we address the question of the influence of aging on brain plasticity.
S100A8 Chemotactic Protein Is Abundantly Increased, but Only a Minor Contributor to LPS-Induced, Steroid Resistant Neutrophilic Lung Inflammation in Vivo (2005)

Neutrophilic lung inflammation is an essential component of host defense against diverse eukaryotic and prokaryotic pathogens, but in chronic inflammatory lung diseases, such as chronic obstructive lung disease (COPD), severe asthma, cystic fibrosis, and bronchiolitis, it may damage the host. Glucocorticosteroids are widely used in these conditions and in their infectious exacerbations; however, the clinical efficacy of steroids is disputed. In this study, we used a proteomic approach to identify molecules contributing to neutrophilic inflammation induced by transnasal administration of lipopolysaccharide (LPS) that were also resistant to the potent glucocorticosteroid dexamethasone (Dex). We confirmed that Dex was biologically active at both the transcript (suppression of GM-CSF and TNFalphatranscripts) and protein levels (induction of lipocortin) and used 2D-PAGE/MALDI-TOF to generate global expression profiles, identifying six LPS-induced proteins that were Dex resistant. Of these, S100A8, a candidate neutrophil chemotactic factor, was profiled in detail. Steroid refractory S100A8 expression was highly abundant, transcriptionally regulated, secreted into lung lavage fluid and immunohistochemically localized to tissue infiltrating neutrophils. However, in marked contrast to other vascular beds, neutralizing antibodies to S100A8 had only a weak anti-neutrophil recruitment effect and antibodies against the related S100A9 were ineffective. These data highlight the need for extensive in vivo profiling of proteomically identified candidate molecules and demonstrates that S100A8, despite its abundance, resistance to steroids and known chemotactic activity, is unlikely to be an important determinant of LPS-induced neutrophilic lung inflammation in vivo.
Fast, integrated person tracking and activity recognition with plan-view templates from a single stereo camera (2004)

Plan-view projection of real-time depth imagery can improve the statistics of its intrinsic 3D data, and allows for cleaner separation of occluding and closely-interacting people. We build a probabilistic, real-time multi-person tracking system upon a plan-view image substrate that well preserves both shape and size information of foreground objects. The tracking's robustness derives in part from its "plan-view template" person models, which capture detailed properties of people's body configurations. We demonstrate that these same person models, obtained with a single compact stereo camera unit, may also be used for fast recognition of body pose and activity. Principal components analysis is used to extract plan-view "eigenposes", onto which person models, extracted during tracking, are projected to produce a compact representation of human body configuration. We then formulate pose recognition as a classification problem, and use support vector machines (SVMs) to quickly distinguish between, for example, different directions people are facing, and different body poses such as standing, sitting, bending over, crouching, and reaching. The SVM outputs are transformed to probabilities and integrated across time in a probabilistic framework for real-time activity recognition.