gebhart/patrepeval huggingface dataset:
Differential Transformation and Its Application to Nonlinear Optimal Control (2009)

A novel numerical method based on the differential transformation is proposed for solving nonlinear optimal control problems in this paper. The differential transformation is a linear operator that transforms a function from the original time and/or space domain into another domain in order to simplify the differential calculations. The optimality conditions for the optimal control problems can be represented by algebraic and differential equations. Using the differential transformation, these algebraic and differential equations with their boundary conditions are first converted into a system of nonlinear algebraic equations. Then the numerical optimal solutions are obtained in the form of finite-term Taylor series by solving the system of nonlinear algebraic equations. The differential transformation algorithm is similar to the spectral element methods in that the computational region splits into several subregions but it uses polynomials of high degrees by keeping a small number of subregions. The differential transformation algorithm could solve the finite- (or infinite-) time horizon optimal control problems formulated as either the algebraic and ordinary differential equations using Pontryagin’s minimum principle or the Hamilton–Jacobi–Bellman partial differential equation using dynamic programming in one unified framework. In addition, the differential transformation algorithm can efficiently solve optimal control problems with the piecewise continuous dynamics and/or nonsmooth control. The performance is demonstrated through illustrative examples.
A unique case of fibrodysplasia ossificans progressiva with an ACVR1 mutation, G356D, other than the common mutation (R206H) (2008)

Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal dominant congenital disease characterized by progressive heterotopic endochondral osteogenesis with great-toe malformations. A 617G > A (R206H) mutation of the activin A type 1 receptor gene (ACVR1) has been found in all previously reported patients with FOP. Thus, this is one of the most specific of all disease-associated mutations. We report here on a 62-year-old man with slowly progressive FOP and a novel mutation in ACVR1. He developed difficulty in moving his shoulder since age 10 years due to contraction of the shoulder joint. The symptoms progressed slowly, and he could not walk at age 36 years and was bedridden at 55 years. He also showed rigid spine, baldness, sensorineural hearing loss, and hypodactyly accompanied by abnormal ectopic ossification. Analysis of ACVR1 and its cDNA revealed that the patient is heterozygous for a mutation, 1067G > A (G356D). Typing of SNPs located in the approximately 0.5-Mb region spanning ACVR1 and its neighbor genes suggested that 1067G > A is a de novo mutation. These results give a clue to better understanding of FOP as well as of the mild clinical symptoms in the patient.
LANTIBIOTICS: Biosynthesis and Biological Activities of Uniquely Modified Peptides from Gram-Positive Bacteria (1998)

A plethora of novel gene-encoded antimicrobial peptides from animals, plants and bacteria has been described during the last decade. Many of the bacterial peptides possess modified building blocks such as thioethers and thiazoles or unsaturated and stereoinverted amino acids, which are unique among ribosomally made peptides. Genetic and biochemical studies of many of these peptides, mostly the so-called lantibiotics, have revealed the degree to which cells are capable of transforming peptides by posttranslational modification. The biosynthesis follows a general scheme: Precursor peptides are first modified and then proteolytically activated; the latter may occur prior to, concomitantly with or after export from the cell. The genes for the biosynthetic machinery are organized in clusters and include information for the antibiotic prepeptide, the modification enzymes and accessory functions such as dedicated proteases and ABC transporters as well as immunity factors and regulatory proteins. These fundamental aspects are discussed along with the biotechnological potential of the peptides and of the biosynthesis enzymes, which could be used for construction of novel, peptide-based biomedical effector molecules.
TASSEL: software for association mapping of complex traits in diverse samples (2007)

Association analyses that exploit the natural diversity of a genome to map at very high resolutions are becoming increasingly important. In most studies, however, researchers must contend with the confounding effects of both population and family structure. TASSEL (Trait Analysis by aSSociation, Evolution and Linkage) implements general linear model and mixed linear model approaches for controlling population and family structure. For result interpretation, the program allows for linkage disequilibrium statistics to be calculated and visualized graphically. Database browsing and data importation is facilitated by integrated middleware. Other features include analyzing insertions/deletions, calculating diversity statistics, integration of phenotypic and genotypic data, imputing missing data and calculating principal components.
Role of lysine 173 in heparin binding to heparin cofactor II (2021)

Heparin cofactor II (HC) is a plasma serine proteinase inhibitor (serpin) that inhibits alpha-thrombin in a reaction that is dramatically enhanced by heparin and other glycosaminoglycans/polyanions. We investigated the glycosaminoglycan binding site in HC by: (i) chemical modification with pyridoxal 5'-phosphate (PLP) in the absence and presence of heparin and dermatan sulfate; (ii) molecular modeling; and (iii) site-directed oligonucleotide mutagenesis. Four lysyl residues (173, 252, 343, and 348) were protected from modification by heparin and to a lesser extent by dermatan sulfate. Heparin-protected PLPHC retained both heparin cofactor and dermatan sulfate cofactor activity while dermatan sulfate-protected PLPHC retained some dermatan sulfate cofactor activity and little heparin cofactor activity. Molecular modeling studies revealed that Lys173 and Lys252 are within a region previously shown to contain residues involved in glycosaminoglycan binding. Lys343 and Lys348 are distant from this region, but protection by heparin and dermatan sulfate might result from a conformational change following glycosaminoglycan binding to the inhibitor. Site-directed mutagenesis of Lys173 and Lys343 was performed to further dissect the role of these two regions during HC-heparin and HC-dermatan sulfate interactions. The Lys343----Asn or Thr mutants had normal or only slightly reduced heparin or dermatan sulfate cofactor activity and eluted from heparin-Sepharose at the same ionic strength as native recombinant HC. However, the Lys173----Gln or Leu mutants had greatly reduced heparin cofactor activity and eluted from heparin-Sepharose at a significantly lower ionic strength than native recombinant HC but retained normal dermatan sulfate cofactor activity. Our results demonstrate that Lys173 is involved in the interaction of HC with heparin but not with dermatan sulfate, whereas Lys343 is not critical for HC binding to either glycosaminoglycan. These data provide further evidence for the determinants required for glycosaminoglycan binding to HC.
MHC-Peptide binding prediction for epitope based vaccine design (2007)

identification of MHC binding peptides for consideration as potential T-cell epitopes has application in peptide vaccine design and immunotherapy. Determination of MHCp binding using experimental measures is time-consuming and expensive. Therefore, efficient prediction models are required that facilitate systematic computational scanning of microbial genome for candidate T cell epitopes. These prediction models are either sequence or 3D structure based. This review provides a comparative analysis on the available prediction models with specific emphasis on the salient features of each model, its prediction efficiency, and merits and demerits.
Aqueous silane modified silica sols: theory and preparation (2011)

Purpose The purpose of this paper is to study methods of reacting the surface of the particles of silica sols with silanes, primarily gamma‐glycidoxypropyltrimethoxysilane (GPTMS) and study some basic properties of the modified sols and the nature and structure of the silane groups attached to the particle surface. Design/methodology/approach The surface of the silica particles was modified by reacting the silica sols with aqueous solutions of silanes, chiefly GPTMS. The presence and structure of silane groups on the particle surface were established by Si‐NMR and C‐NMR, respectively. Findings Several silanes were studied but silica sols could be readily modified only with GPTMS and glycidoxypropylmethoxydiethoxysilane (GPMDES), most readily if the silanes were pre‐hydrolysed in water. Higher degrees of silylation were preferably done by continuous addition of silane. Lower degrees of modification can be achieved at room temperature by the stepwise addition of the silane solution. The silylation of the silica surface with GPTMS significantly reduces the number of charged surface groups and silanol groups. GPTMS binds covalently to the silica surface and the epoxy ring opens and transforms into a diol. Silica sols modified with GPTMS and GPMDES are stable toward aggregation. Research limitations/implications Only organo‐reactive silanes were studied. Originality/value This is the first work to study the modification by silanes of silica aquasols with high concentrations of silica. The silane modification can extend the use of silica to areas of applications previously inaccessible to silica sols.
Autonomic Testing (2010)

Laboratories able to test autonomic function are increasingly available and rely on batteries of well-accepted, noninvasive tests. Tests of parasympathetic cardiovagal, sympathetic vasoconstriction, and sudomotor (sweating) function are most commonly employed. Common examples include heart rate variability to various challenges, Valsalva maneuver, standing and tilt-table studies, and various sudomotor methods. New techniques and technical refinements continue to be described. Most studies rely on perturbations of complex systems and not direct assessment. Testing has helped to improve disease recognition and prompted advances in classification, pathophysiology, and treatment. Major areas impacted include hereditary and immune-mediated autonomic neuropathy, diabetic autonomic neuropathy, distal symmetric polyneuropathy, Parkinson disease and other autonomic failure syndromes, orthostatic intolerance, and unexplained syncope.
Training Perceptual Skill by Orienting Visual Attention (2006)

A major element in expert sports performance, particularly racket-and-ball games, is excellent anticipatory skill. A prestudy combined the temporal and spatial occlusion paradigms to ascertain which key stimuli badminton players use for anticipating the direction of overhead shots. The main study then evaluated a program for training anticipatory skills; 200 video clips were employed to orient attention toward these key stimuli. Participants were 63 badminton novices, 20 national league players, and 21 local league players. A transparent red patch (exogenous orienting) was used to orient attention toward the trunk up to 160 ms before racket-shuttle contact; the arm, from 160 ms to 80 ms before contact; and the racket, from 80 ms before to actual contact. Results showed that badminton novices who trained with this program significantly improved their anticipatory skill between post- and retention test compared with controls. Whereas local league players improved from pre- to posttest, training had no effect on expert national league players. It is concluded that using red transparent patches to highlight the most informative cues in perceptual training programs is a promising way to improve anticipatory skill.
BCAM and LAMA5 Mediate the Recognition between Tumor Cells and the Endothelium in the Metastatic Spreading of KRAS-Mutant Colorectal Cancer (2016)

These data show that the BCAM/LAMA5 system plays a functional role in the metastatic spreading of KRAS-mutant colorectal cancer by mediating tumor-TME interactions and as such represents a valuable therapeutic candidate for this large, currently untreatable patient group. Clin Cancer Res; 22(19); 4923-33. ©2016 AACR.
Using humanoid robots to study human behavior (2000)

Our understanding of human behavior advances as our humanoid robotics work progresses-and vice versa. This team's work focuses on trajectory formation and planning, learning from demonstration, oculomotor control and interactive behaviors. They are programming robotic behavior based on how we humans "program" behavior in-or train-each other.
Neutralizing antibody and soluble ACE2 inhibition of a replication-competent VSV-SARS-CoV-2 and a clinical isolate of SARS-CoV-2 (2020)

Antibody-based interventions against SARS-CoV-2 could limit morbidity, mortality, and possibly disrupt epidemic transmission. An anticipated correlate of such countermeasures is the level of neutralizing antibodies against the SARS-CoV-2 spike protein, yet there is no consensus as to which assay should be used for such measurements. Using an infectious molecular clone of vesicular stomatitis virus (VSV) that expresses eGFP as a marker of infection, we replaced the glycoprotein gene (G) with the spike protein of SARS-CoV-2 (VSV-eGFP-SARS-CoV-2) and developed a high-throughput imaging-based neutralization assay at biosafety level 2. We also developed a focus reduction neutralization test with a clinical isolate of SARS-CoV-2 at biosafety level 3. We compared the neutralizing activities of monoclonal and polyclonal antibody preparations, as well as ACE2-Fc soluble decoy protein in both assays and find an exceptionally high degree of concordance. The two assays will help define correlates of protection for antibody-based countermeasures including therapeutic antibodies, immune γ-globulin or plasma preparations, and vaccines against SARS-CoV-2. Replication-competent VSV-eGFP-SARS-CoV-2 provides a rapid assay for testing inhibitors of SARS-CoV-2 mediated entry that can be performed in 7.5 hours under reduced biosafety containment.
Expression of Nrf2 in Neurodegenerative Diseases (2007)

In response to oxidative stress, the nuclear factor E2-related factor 2 (Nrf2) transcription factor translocates from the cytoplasm into the nucleus and transactivates expression of genes with antioxidant activity. Despite this cellular mechanism, oxidative damage is abundant in Alzheimer and Parkinson disease (AD and PD). To investigate mechanisms by which Nrf2 activity may be aberrant or insufficient in neurodegenerative conditions, we assessed Nrf2 localization in affected brain regions of AD, Lewy body variant of AD (LBVAD), and PD. By immunohistochemistry, Nrf2 is expressed in both the nucleus and the cytoplasm of neurons in normal hippocampi with predominant expression in the nucleus. In AD and LBVAD, Nrf2 was predominantly cytoplasmic in hippocampal neurons and was not a major component of beta amyloid plaques or neurofibrillary tangles. By immunoblotting, we observed a significant decrease in nuclear Nrf2 levels in AD cases. In contrast, Nrf2 was strongly nuclear in PD nigral neurons but cytoplasmic in substantia nigra of normal, AD, and LBVAD cases. These findings suggest that Nrf2-mediated transcription is not induced in neurons in AD despite the presence of oxidative stress. In PD, nuclear localization of Nrf2 is strongly induced, but this response may be insufficient to protect neurons from degeneration.
Synthese eines GPI‐Ankers der Hefe (Saccharomyces cerevisiae) (1994)

Hochkonvergent und gleichzeitig variabel ist die hier beschriebene Synthese des GPI‐Ankers 1 aus vier Bausteinen, die alle aus einfach zugänglichen Ausgangsverbindungen in sehr guten Ausbeuten zugänglich sind. magnified image
Bacterial, Viral, and Fungal Insecticides (1983)

Microorganisms that are pathogenic to insects provide a wealth of biological material that can be exploited by humans to control insect pests. Innovative applications of a few such entomopathogens are found throughout the world, but widespread commercial production of microbial insecticides awaits further studies of the biology, ecology, and pathogenicity of the agents. Genetic engineering techniques may be used to increase the virulence of these microorganisms, as well as to make them more tolerant of physical and chemical conditions and perhaps to broaden their host ranges. The use of microbial insecticides could decrease our dependence on chemical pesticides.
Transcriptional regulation of nicotinic acetylcholine receptor genes during muscle development. (1986)

The quantities of nicotinic acetylcholine receptors measured by alpha-bungarotoxin binding on the surface of mouse skeletal muscle C2 cells increase by approximately 10- to 100-fold during their terminal differentiation in culture. By northern blot analysis, we have determined that the steady-state levels of the AChR alpha and delta subunit mRNAs increase by approximately 15-fold during differentiation of C2 cells. To determine if the differences in message levels during myogenesis are due to changes in transcriptional rates of these genes, nuclear run-on experiments were done using nuclei from 3-day-old undifferentiated cells and 7-day-old differentiated cells. The rates of transcription for both the alpha and delta subunit genes changed from levels that could not be detected over background in nuclei from undifferentiated cells to levels that were at least 8-fold over background in differentiated nuclei. As internal controls, we measured the rates of transcription of mouse actin and histone genes. The signals obtained from both undifferentiated and differentiated nuclei were approximately 50-fold over background for both genes, indicating that the absence of detectable transcription of receptor subunit genes in undifferentiated C2 is specific.
Cell Response to Surgery (2006)

Surgical trauma produces profound immunological dysfunction. Therapeutic strategies directed at restoring immune homeostasis should aim to redress the physiological proinflammatory-anti-inflammatory cell imbalance associated with major surgery.
Selective activity over a constitutively active RET‐variant of the oral multikinase inhibitor dovitinib: Results of the CNIO‐BR002 phase I‐trial (2014)

Level 1B was the RP2D as it provided adequate pharmacodynamic exposure to dovitinib. The G2071A germline variant act as a genetic modifier that renders different tumors sensitive to dovitinib.
Alanine scanning mutagenesis of human erythropoietin identifies four amino acids which are critical for biological activity (1993)

Erythropoietin regulates the growth and proliferation of red blood cell progenitors. We demonstrated previously the important structural and functional roles of the amino acid region 99-110 in the biological activity of the hormone. [Chern, Y., Chung, T. & Sytkowski, A. J. (1991) Eur. J. Biochem. 202, 225-229]. We have now performed alanine scanning mutagenesis to identify which specific residues in this region are essential for function. Four substitutions reduced the biological activity of erythropoietin. Alanine substitution of Ser104, Leu105 and Leu108 reduced activity to 16, 44, and 37% that of the wild-type protein, respectively. Most significantly, substitution of Arg103 with Ala reduced activity to undetectable levels, indicating a > 230-fold reduction in specific activity. Immunochemical analyses using anti-peptide monoclonal antibodies demonstrated that this substitution does not cause major changes in the conformation of the protein or large, localized distortions within the amino acid region 99-129 of the molecule. Heat-denaturation kinetics for the arginine mutant and wild-type erythropoietin are virtually identical, further indicating the structural similarity between these two molecules. Based upon these findings, we propose that Arg103 plays an essential role in the biological activity of erythropoietin, presumably by interacting directly with the erythropoietin receptor.
Effects of methylacetylenic putrescine, an ornithine decarboxylase inhibitor and potential novel anticancer agent, on human and mouse cancer cell lines (1999)

Sensitivity of several human and mouse cancer cell lines to methylacetylenic putrescine (MAP) was evaluated using clonogenic, sulforhodamine B and cell counting assays. The effects of MAP on cell morphology, cell cycle phase distribution and changes in polyamine metabolism of xenografted MCF-7 and MDA-MB-231 human mammary tumor cells were also investigated. On the basis of IC50 values, BHT-101 human thyroid carcinoma cells were the most sensitive (9 micrograms/ml), followed by P388 mouse lymphoma (32 micrograms/ml), MCF-7 (48 micrograms/ml) and MDA-MB-231 (110 micrograms/ml) human breast carcinoma cell lines. MAP treatment led to accumulation of P388 cells in G1 phase. At higher doses, the cytoplasm of the cells became vacuolated followed by apoptosis. The foamy cytoplasm may suggest a rare type of cell death (Clarke III type) called non-apoptotic programmed cell death. MAP treatment resulted in a total inhibition of ornithine decarboxylase (ODC) activity with a concomitant decrease of intracellular polyamine (mostly putrescine and spermidine) content in the breast cancer cells, whilst the spermine concentration was shown to increase. MAP proved at least 10 times more potent than the formerly studied DL-alpha-difluoromethylornithine making it an attractive candidate for clinical testing.
Assessment of disease-severity scoring systems for patients with sepsis in general internal medicine departments (2011)

The SCS and REMS are the most appropriate clinical scores to predict the mortality of patients with sepsis in general internal medicine departments.
Identification of fusion genes in breast cancer by paired-end RNA-sequencing (2011)

In summary, using RNA-sequencing and improved bioinformatic stratification, we have discovered a number of novel fusion genes in breast cancer, and identified VAPB-IKZF3 as a potential fusion gene with importance for the growth and survival of breast cancer cells.
Single-Molecule Detection of Nitrogen Mustards by Covalent Reaction within a Protein Nanopore (2008)

Mustards, including sulfur mustards and nitrogen mustards, form a class of cytotoxic, vesicant chemical warfare agents. Mustards have also been used to treat cancer and played a vital role in the development of chemotherapy. Additionally, because of their destructive properties, ease of synthesis, and the lack of effective antidotes, mustards are unquestionably terrorist threats. Therefore, quick and convenient detection of mustards is a critical issue. In the present study, we achieved detection of various mustards on the basis of their chemical reactivity by using engineered alpha-hemolysin (alphaHL) protein pores as sensor elements. We describe four classes of reactions for detecting mustards. These reactions occur between mustards and thiol groups contributed by cysteine side-chains within the lumen of the alphaHL pore or on an internal molecular adapter. The approach is quick and straightforward. It can confirm the existence of mustards in as little as 10 min at 50 microM or lower.