gebhart/patrepeval huggingface dataset:
Structural Characterization of Spo0E-like Protein-aspartic Acid Phosphatases That Regulate Sporulation in Bacilli (2006)

Spore formation is an extreme response of many bacterial species to starvation. In the case of pathogenic species of Bacillus and Clostridium, it is also a component of disease transmission. Entry into the pathway of sporulation in Bacillus subtilis and its relatives is controlled by an expanded two-component system in which starvation signals lead to the activation of sensor kinases and phosphorylation of the master sporulation response regulator Spo0A. Accumulation of threshold concentrations of Spo0A approximately P heralds the commitment to sporulation. Countering the activities of the sensor kinases are phosphatases such as Spo0E, which dephosphorylate Spo0A approximately P and inhibit sporulation. Spo0E-like protein-aspartic acid-phosphate phosphatases, consisting of 50-90 residues, are conserved in sporeforming bacteria and unrelated in sequence to proteins of known structure. Here we determined the structures of the Spo0A approximately P phosphatases BA1655 and BA5174 from Bacillus anthracis using nuclear magnetic resonance spectroscopy. Each is composed of two anti-parallel alpha-helices flanked by flexible regions at the termini. The signature SQELD motif (SRDLD in BA1655) is situated in the middle of helix alpha2 with its polar residues projecting outward. BA5174 is a monomer, whereas BA1655 is a dimer. The four-helix bundle structure in the dimer is reminiscent of the phosphotransferase Spo0B and the chemotaxis phosphatase CheZ, although in contrast to these systems, the subunits in BA1655 are in head-to-tail rather than head-to-head apposition. The implications of the structures for interactions between the phosphatases and their substrate Spo0A approximately P are discussed.
Kinetic and Structural Characterization of the Self-Labeling Protein Tags HaloTag7, SNAP-tag, and CLIP-tag (2021)

The self-labeling protein tags (SLPs) HaloTag7, SNAP-tag, and CLIP-tag allow the covalent labeling of fusion proteins with synthetic molecules for applications in bioimaging and biotechnology. To guide the selection of an SLP-substrate pair and provide guidelines for the design of substrates, we report a systematic and comparative study of the labeling kinetics and substrate specificities of HaloTag7, SNAP-tag, and CLIP-tag. HaloTag7 reaches almost diffusion-limited labeling rate constants with certain rhodamine substrates, which are more than 2 orders of magnitude higher than those of SNAP-tag for the corresponding substrates. SNAP-tag labeling rate constants, however, are less affected by the structure of the label than those of HaloTag7, which vary over 6 orders of magnitude for commonly employed substrates. Determining the crystal structures of HaloTag7 and SNAP-tag labeled with fluorescent substrates allowed us to rationalize their substrate preferences. We also demonstrate how these insights can be exploited to design substrates with improved labeling kinetics.
Directed Differentiation of Human Pluripotent Stem Cells into Radial Glia and Astrocytes Bypasses Neurogenesis (2021)

Abstract Derivation of astrocytes from human pluripotent stem cells (hPSCs) is inefficient and cumbersome, impeding their use in biomedical research. Here, we developed a highly efficient chemically defined astrocyte differentiation strategy that overcomes current limitations. This approach largely bypasses neurogenesis, which otherwise precedes astrogliogenesis during brain development and in vitro experiments. hPSCs were first differentiated into radial glial cells (RGCs) exhibiting in vivo -like radial glia signatures. Activation of NOTCH and JAK/STAT pathways in bona fide RGCs resulted in direct astrogliogenesis confirmed by expression of various glial markers (NFIA, NFIB, SOX9, CD44, S100B, GFAP). Transcriptomic and genome-wide epigenetic analyses confirmed RGC-to-astrocyte differentiation and absence of neurogenesis. The morphological and functional identity of hPSC-derived astrocytes was confirmed by using an array of methods (e.g. electron microscopy, calcium imaging, co-culture with neurons, grafting into mouse brains). Lastly, the scalable protocol was adapted to a robotic platform and used to model Alexander disease. In conclusion, our findings uncover remarkable plasticity in neural lineage progression that can be exploited to manufacture large numbers of human hPSC-derived astrocytes for drug development and regenerative medicine.
Self-increased acceptance bandwidth of second harmonic generation for high-energy light sources (2015)

We report a series of experimental results showing that the acceptance bandwidth of second harmonic generation in quadratic crystals may substantially broaden when using pumps at high intensities. We highlight the co-existence of second harmonic generation and strong unconventional spatial beam reshaping. Our experimental results are in good agreement with our numerical simulations.
Development of a method for left ventricular shape evaluation based on surfaces obtained by real-time 3D echocardiographic images (2007)

Left ventricular (LV) shape is strictly related to LV function. Previously proposed shape indexes suffer from their intrinsic 2D nature. Our aim was to develop a method to quantify directly 3D LV shape from LV surfaces semi-automatically detected from real-time 3D echocardiographic (RT3DE) images. First, a monodimensional shape descriptor has been obtained by sampling through an helical pattern the extracted endocardial surfaces. Then, four shape indexes have been defined by comparing the LV with reference shapes. The developed method was applied to RT3DE datasets obtained from 12 normal subjects, 8 patients with dilated cardiomiopathy and 7 ischemic patients. Some of the proposed shape indexes were able to follow chamber deformation throughout the cardiac cycle and to discriminate between normal and pathologic conditions.
Coordinated control of DFIG subjected to grid faults (2014)

With the interconnection requirement for wind generation to the utility power system, it is of great importance that how to enhance the fault ride-through (FRT) capability of the doubly fed induction generator (DFIG) that are nowadays widely used in wind power plants. The FRT strategies based on active crowbar have been commonly used in practical engineering, but there are two problems remain unsolved. One is how to choose the crowbar activation time, the other is how to control the rotor-side converter after the crowbar disconnection. In fact, the precondition for solving these problems is to reveal the rotor fault current characteristics. In this paper, the main frequency components and their decaying characteristics of rotor current are analyzed. Further, a coordinated control strategy between the rotor-side converters and active crowbar is proposed to enhance the FRT capability of DFIG. The main idea is utilize the time constant of high-speed decaying component of rotor current as the reference of crowbar activation time, and the low-speed decaying current component considered as the bad factor of restarting the rotor-side converter. With the proposed strategy, the fault response of DFIG can be greatly improved. The minimum operational voltage limit of the DFIG's fault ride-through is enlarged by 0.1p.u without increasing the converter rating. These performances have been demonstrated through the experimental tests based on the real time digital simulator (RTDS).
A study on the zeta potential of microcapsules during ageing (1991)

Gelatin, methylcellulose and agar microcapsules were prepared with and without suphadiazine. The zeta potential of these microcapsules was measured at regular intervals during ageing at 45 degrees C. An initial sharp rise in zeta potential is followed by a progressive decrease. Zeta potential could prove to be a useful parameter to study the changes occurring in the encapsulating material of microcapsules during ageing.
Combining Cyclostationarity and the Frequency Domain Subspace Technique for Operational Modal Analysis (2007)

This DOI is not currently attached to any metadata records. DOIs can’t actually ever be deleted (they’re persistent), but sometimes our members create DOIs in error. We do have a process to approximate deletion which we follow only in rare cases where the DOI has been genuinely created in error, and most crucially, if the DOI has never been published anywhere online or in print and never otherwise distributed to or communicated with anyone (authors, readers, reviewers, etc.
Crystal Structure of Human BCMA in complex with UniAb(TM) VH (2019)

Heavy chain-only antibodies (HCAbs) do not associate with light chains and their V(H) regions are functional as single domains, forming the smallest active antibody fragment. These V(H) regions are ideal building blocks for a variety of antibody-based biologics because they tolerate fusion to other molecules and may also be attached in series to construct multispecific antibodies without the need for protein engineering to ensure proper heavy and light chain pairing. Production of human HCAbs has been impeded by the fact that natural human V(H) regions require light chain association and display poor biophysical characteristics when expressed in the absence of light chains. Here, we present an innovative platform for the rapid development of diverse sets of human HCAbs that have been selected in vivo. Our unique approach combines antibody repertoire analysis with immunization of transgenic rats, called UniRats, that produce chimeric HCAbs with fully human V(H) domains in response to an antigen challenge. UniRats express HCAbs from large transgenic loci representing the entire productive human heavy chain V(D)J repertoire, mount robust immune responses to a wide array of antigens, exhibit diverse V gene usage and generate large panels of stable, high affinity, antigen-specific molecules.
Interconversion of the Product Specificity of Type I Eubacterial Farnesyl Diphosphate Synthase and Geranylgeranyl Diphosphate Synthase through One Amino Acid Substitution (2003)

Prenyltransferases catalyze the sequential condensation of isopentenyl diphosphate into prenyl diphosphates with specific chain lengths. Pioneering studies demonstrated that the product specificities of type I prenyltransferases were mainly determined by the amino acid residues at the 4th and 5th positions before the first aspartate-rich motif (FARM) of the prenyltransferases. We previously cloned a type I geranylgeranyl diphosphate synthase (GGDPSase) gene from Streptomyces griseolosporeus MF730-N6 [Hamano, Y., Dairi, T., Yamamoto, M., Kawasaki, T., Kaneda, K., Kuzuyama, T., Itoh, N., and Seto, H. (2001) BIOSCI: Biotechnol. Biochem. 65, 1627-1635]. In this study, a prenyltransferase gene was cloned from Streptomyces argenteolus A-2 and was confirmed to encode a type I farnesyl diphosphate synthase (FDPSase). Interestingly, the amino acid residues at the 4th and 5th positions before the FARM were the same in these two enzymes. To identify the amino acid that determines the product chain length, mutated enzymes, GGDPSase (L-50S), FDPSase (S-50L), GGDPSase (V-8A), FDPSase (A-8V), GGDPSase (A+57L), and FDPSase (L+58A), in which the amino acid residue at the -50th, -8th, and +57th (58th) position before or after the FARM was substituted with the corresponding amino acid of the other enzyme, were constructed. The GGDPSase (A+57L) and FDPSase (L+58A) produced farnesyl diphosphate and geranylgeranyl diphosphate, respectively. On the other hand, the other mutated enzymes produced prenyl diphosphates with the same chain lengths as the wild type enzymes did. These results showed that the amino acid residue at the 57th (58th) position after the FARM also played an important role in determination of the product specificity.
Optimization of Switched Reluctance Motor Drive Firing Angles Using Grey Wolf Optimizer for Torque Ripples Minimization (2018)

Switched reluctance motor (SRM) has various advantages which makes it an excellent candidate for many applications; nevertheless, its main drawback is torque ripples. This paper aims to enhance the SRM operation by reducing its torque ripples without the need for expensive and sophisticated physical changes in the motor materials or design. The SRM converter firing angles are optimized to produce the lowest possible torque ripples. The response surface method (RSM) is used to obtain the SRM optimization function that relates torque ripples with firing angles, and grey wolf optimizer (GWO) is used to minimize this function. The objective function convergence speed using the proposed GWO is compared with genetic algorithm (GA), and it is found to be faster than GA. Simulation and experimental results show the effectiveness of the proposed approach in enhancing SRM operation by providing the SRM converter firing angles that result the minimum feasible torque ripples.
ChemInform Abstract: REACTION MECHANISM OF THE SYNTHESIS OF SEYCHELLENE (1979)

Abstract Nach 15stündiger Solvolyse des Alkohols (Ia) in Acetat‐gepufferter Essigsäure werden über das Zwischenprodukt (II) die Titelverbindung (III) und das Nebenprodukt (IV) erhalten, dessen Struktur aufgeklärt wird.
High Power on-chip Integrated Laser (2022)

The lack of high power integrated lasers have been limiting silicon photonics. Despite much progress made in chip-scale laser integration, power remains below the level required for key applications. The main inhibiting factor for high power is the low energy efficiency at high pumping currents, dictated by the small size of the active device. Here we break this power limitation by demonstrating a platform that relies on the coupling of a broad-area multimode gain to a silicon-nitride feedback chip, which acts as an external cavity. The feedback provided by the silicon-nitride chip is routed through a ring resonator and a single-mode filter, thus causing the otherwise multimode-gain chip to concentrate its power into a single highly-coherent mode. Our device produces more than 150 mW of power and 400 kHz linewidth. We achieve these high-performance metrics while maintaining a small footprint of 3 mm^2.
Phase 1/2 study evaluating the safety and efficacy of DSP‐7888 dosing emulsion in myelodysplastic syndromes (2021)

DSP-7888 is an immunotherapeutic cancer vaccine derived from the Wilms' tumor gene 1 (WT1) protein. This phase 1/2 open-label study evaluated the safety and efficacy of DSP-7888 dosing emulsion in patients with myelodysplastic syndromes (MDS). DSP-7888 was administered intradermally (3.5 or 10.5 mg) every 2 weeks for 6 months and then every 2-4 weeks until lack of benefit. Twelve patients were treated in phase 1 (3.5 mg, n = 6; 10.5 mg, n = 6), with no dose-limiting toxicities reported. Thus, the 10.5 mg dose was selected as the recommended phase 2 dose, and 35 patients were treated in phase 2. Forty-seven patients received ≥1 dose of the study drug and comprised the safety analysis set. The most common adverse drug reaction (ADR) was injection site reactions (ISR; 91.5%). Grade 3 ISR were common (58.8%) in phase 1 but occurred less frequently in 2 (22.9%) following implementation of risk minimization strategies. Other common ADR were pyrexia (10.6%) and febrile neutropenia (8.5%). In the efficacy analysis set, comprising patients with higher-risk MDS after azacitidine failure in phases 1 and 2 (n = 42), the disease control rate was 19.0%, and the median overall survival (OS) was 8.6 (90% confidence interval [CI], 6.8-10.3) months. Median OS was 10.0 (90% CI, 7.6-11.4) months in patients with a WT1-specific immune response (IR; n = 33) versus 4.1 (90% CI, 2.3-8.1) months in those without a WT1-specific IR (n = 9; P = .0034). The acceptable safety and clinical activity findings observed support the continued development of DSP-7888 dosing emulsion.
Bipyrimidine-Bridged Mixed-Metal Trimetallic Complexes of Ruthenium(II) with Rhodium(III) or Iridium(III), {[(bpy)<sub>2</sub>Ru(bpm)]<sub>2</sub>MCl<sub>2</sub>}<sup>5+</sup> (1996)

Bipyrimidine-bridged trimetallic complexes of the form {[(bpy)(2)Ru(bpm)](2)MCl(2)}(5+), where M = Rh(III) or Ir(III), bpy = 2,2'-bipyridine, and bpm = 2,2'-bipyrimidine, have been synthesized and characterized. These complexes are of interest in that they couple catalytically active rhodium(III) and iridium(III) metals with light-absorbing ruthenium(II) metals within a polymetallic framework. Their molecular composition is a light absorber-electron collector-light absorber core of a photochemical molecular device (PMD) for photoinitiated electron collection. The variation of the central metal has some profound effects on the observed properties of these complexes. The electrochemical data for the title trimetallics consist of a Ru(II/III) oxidation and sequential reductions assigned to the bipyrimidine ligands, Ir or Rh metal centers, and bipyridines. In both trimetallic complexes, the first oxidation is Ru based and the bridging ligand reductions occur prior to the central metal reduction. This illustrates that the highest occupied molecular orbital (HOMO) is localized on the ruthenium metal center and the lowest unoccupied molecular orbital resides on the bpm ligand. This bpm-based LUMO in {[(bpy)(2)Ru(bpm)](2)RhCl(2)}(5+) is in contrast with that observed for the monometallic [Rh(bpm)(2)Cl(2)](+) where the Rh(III)/Rh(I) reduction occurs prior to the bpm reduction. This orbital inversion is a result of bridge formation upon construction of the trimetallic complex. Both the Ir- and Rh-based trimetallic complexes exhibit a room temperature emission centered at 800 nm with tau = 10 ns. A detailed comparison of the spectroscopic, electrochemical, and spectroelectrochemical properties of these polymetallic complexes is described herein.
Neural Encoding of Reaches in a Linear Cortical Model (2021)

To effectively control the arm, motor cortical neurons must produce complex patterns of activation that vary with the position and orientation of the arm and reach direction. In order to better understand how such a finely tuned dynamical system could arise and what its basic organizing principles are, we develop a model of the motor cortex as a linear dynamical system with feedback coupled to a two-joint model of the macaque arm. By optimizing the connections between neural populations with respect to an objective function that penalizes error between hand and target, as well as neural and muscular energy use, we show that certain properties of the motor cortex, such as muscle synergies, can naturally be obtained. We also demonstrate that the optimization process produces a stable neural system in which targets in the physical space are mapped to attracting fixed points in the neural state space. Finally, we show that this optimization process produces neural units with complex spatial and temporal activation patterns.
Deranged Calcium Signaling and Neurodegeneration in Spinocerebellar Ataxia Type 2 (2009)

Spinocerebellar ataxia type 2 (SCA2) is an autosomal dominantly inherited, neurodegenerative disease caused by an expansion of polyglutamine tracts in the cytosolic protein ataxin-2 (Atx2). Cerebellar Purkinje cells (PCs) are predominantly affected in SCA2. The cause of PC degeneration in SCA2 is unknown. Here we demonstrate that mutant Atx2-58Q, but not wild-type (WT) Atx2-22Q, specifically associates with the cytosolic C-terminal region of type 1 inositol 1,4,5-trisphosphate receptor (InsP(3)R1), an intracellular calcium (Ca(2+)) release channel. Association with Atx2-58Q increased the sensitivity of InsP(3)R1 to activation by InsP(3) in planar lipid bilayer reconstitution experiments. To validate physiological significance of these findings, we performed a series of experiments with an SCA2-58Q transgenic mouse model that expresses human full-length Atx2-58Q protein under the control of a PC-specific promoter. In Ca(2+) imaging experiments, we demonstrated that stimulation with 3,5-dihydroxyphenylglycine (DHPG) resulted in higher Ca(2+) responses in 58Q PC cultures than in WT PC cultures. DHPG-induced Ca(2+) responses in 58Q PC cultures were blocked by the addition of ryanodine, an inhibitor of the ryanodine receptor (RyanR). We further demonstrated that application of glutamate induced more pronounced cell death in 58Q PC cultures than in WT PC cultures. Glutamate-induced cell death of 58Q PC cultures was attenuated by dantrolene, a clinically relevant RyanR inhibitor and Ca(2+) stabilizer. In whole animal experiments, we demonstrated that long-term feeding of SCA1-58Q mice with dantrolene alleviated age-dependent motor deficits (quantified in beam-walk and rotarod assays) and reduced PC loss observed in untreated SCA2-58Q mice by 12 months of age (quantified by stereology). Results of our studies indicate that disturbed neuronal Ca(2+) signaling may play an important role in SCA2 pathology and also suggest that the RyanR constitutes a potential therapeutic target for treatment of SCA2 patients.
Room Temperature Consolidation of a Porous Poly(lactic-co-glycolic acid) Matrix by the Addition of Maltose to the Water-in-Oil Emulsion (2016)

In composite materials made of polymer matrices and micro-nano dispersed compartments, the morphology of the dispersed phase can strongly affect several features of the final material, including stability, loading efficiency, and kinetic release of the embedded molecules. Such a polymer matrix composite can be obtained through the consolidation of the continuous polymer phase of a water-in-oil (W/O) emulsion. Here, we show that the morphology of the dispersed phase in a poly(lactic-co-glycolic acid, PLGA) matrix can be optimized by combining an effective mild temperature drying process with the addition of maltose as a densifying compound for the water phase of the emulsion. The influence of this addition on final stability and consequent optimal pore distribution was theoretically and experimentally confirmed. Samples were analyzed in terms of morphology on dried flat substrates and in terms of rheology and interfacial tension at the liquid state. While an increase of interfacial tension was found following the addition of maltose, the lower difference in density between the two emulsion phases coming from the addition of maltose allowed us to estimate a reduced creaming tendency confirmed by the experimental observations. Rheological measurements also confirmed an improved elastic behavior for the maltose-containing emulsion.
Improved Performance of Preordered Fungal Protease‐Stearic Acid Biocomposites: Enhanced Catalytic Activity, Reusability, and Temporal Stability (2002)

In an earlier report on fungal protease (F-prot)-fatty acid biocomposite film formation [Gole et al. Anal. Chem. 2000, 72, 4301], it was observed that the biocatalytic activity of the immobilized enzyme was comparable to that of the free enzyme in solution. However, a somewhat negative aspect of the protocol was the steady loss in activity during reuse and storage of the biocomposite film. In this paper, we address the latter issues and demonstrate successful attempts toward the realization of efficient biocomposite films with enhanced biological activity, temporal stability, and excellent reusability. The improved performance of the F-prot-stearic acid biocomposite is accomplished by preordering the fatty acid film by incorporation of Pb(2+) ions into the lipid matrix prior to enzyme immobilization. The lead cation induces lamellar ordering in the lipid film and thus facilitates diffusion of the F-prot molecules into the lipid matrix and accessibility of the substrate molecules (hemoglobin, Hb) to the entrapped F-prot enzyme molecules. The preordering consequently leads to effective control of the "mass transport" problem and might be responsible for the enhanced biological activity ( approximately 36%) of the enzyme molecules in the biocomposite in comparison with the free enzyme in solution, as well the excellent reusability of the composite film. In addition to biocatalytic activity measurements, the formation and characterization of the F-prot-lead stearate biocomposite films was done by quartz crystal microgravimetry and X-ray diffraction.