gebhart/patrepeval huggingface dataset:
Assessing the Balance between Protein−Protein Interactions and Enzyme−Substrate Interactions in the Channeling of Intermediates between Polyketide Synthase Modules (2001)

6-Deoxyerythronolide B synthase (DEBS) is the modular polyketide synthase (PKS) that catalyzes the biosynthesis of 6-deoxyerythronolide B (6-dEB), the aglycon precursor of the antibiotic erythromycin. The biosynthesis of 6-dEB exemplifies the extraordinary substrate- and stereo-selectivity of this family of multifunctional enzymes. Paradoxically, DEBS has been shown to be an attractive scaffold for combinatorial biosynthesis, indicating that its constituent modules are also very tolerant of unnatural substrates. By interrogating individual modules of DEBS with a panel of diketides activated as N-acetylcysteamine (NAC) thioesters, it was recently shown that individual modules have a marked ability to discriminate among certain diastereomeric diketides. However, since free NAC thioesters were used as substrates in these studies, the modules were primed by a diffusive process, which precluded involvement of the covalent, substrate-channeling mechanism by which enzyme-bound intermediates are directly transferred from one module to the next in a multimodular PKS. Recent evidence pointing to a pivotal role for protein-protein interactions in the substrate-channeling mechanism has prompted us to develop novel assays to reassess the steady-state kinetic parameters of individual DEBS modules when primed in a more "natural" channeling mode by the same panel of diketide substrates used earlier. Here we describe these assays and use them to quantify the kinetic benefit of linker-mediated substrate channeling in a modular PKS. This benefit can be substantial, especially for intrinsically poor substrates. Examples are presented where the k(cat) of a module for a given diketide substrate increases >100-fold when the substrate is presented to the module in a channeling mode as opposed to a diffusive mode. However, the substrate specificity profiles for individual modules are conserved regardless of the mode of presentation. By highlighting how substrate channeling can allow PKS modules to effectively accept and process intrinsically poor substrates, these studies provide a rational basis for examining the enormous untapped potential for combinatorial biosynthesis via module rearrangement.
Biosynthetic Studies of ω-Cycloheptyl Fatty Acids in <i>Alicyclobacillus cycloheptanicus</i>. Formation of Cycloheptanecarboxylic Acid from Phenylacetic Acid (1997)

The formation of the structurally novel, mono-substituted cycloheptane ring in ω-cycloheptyl fatty acids in Alicyclobacillus cycloheptanicus (formerly Bacillus cycloheptanicus) has been examined. Feeding experiments with 13C- and 2H-labeled intermediates demonstrated that cycloheptanecarboxylic acid (3), probably as its CoA thioester, is the starter unit for ω-cycloheptyl fatty acid biosynthesis. Analysis of the resultant labeling pattern from a feeding experiment with [U-13C6]glucose suggested a shikimate pathway origin of 3 via aromatic amino acids. [1,2-13C2]Phenylacetic acid (6) was efficiently metabolized into the 3-derived moiety in a manner reminiscent of the seven-membered ring Pseudomonas metabolite thiotropocin. The fates of the aromatic and benzylic hydrogens of 6 were determined; these dictated various boundary conditions for the biosynthetic pathway from 6 to 3. Taken together with the results from feeding experiments with postulated cycloheptenylcarboxylate biosynthetic intermediates, the data lead us to propose a pathway which involves an oxidative ring-expansion of 6 to a hydroxynorcaradiene intermediate followed by a series of double bond reductions and dehydrations to the saturated 3.
A fully parallel Mandarin speech recognition system with very large vocabulary and almost unlimited texts (1991)

The authors describe a fully parallel real-time Mandarin dictation machine which recognizes Mandarin speech with almost unlimited texts and a very large vocabulary for the input of Chinese characters to computers. Isolated syllables including the tones are first recognized using specially trained hidden Markov models with special feature parameters, and the exact characters are then identified from the syllables using a Markov Chinese language model, because every syllable can represent many different homonym characters. The real-time implementation is in Occam language on a transputer system with 10 T800 processors operating in parallel. The overall correction rate for the final output characters is about 80%.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Automated registration of polarimetric imagery using Fourier transform techniques (2002)

Polarimetric imagery that is collected from time-sequential and multiple image format sensors all have potential for image misregistration. Since polarization is usually measured as small differences between radiometric measurements, it is highly sensitive to misregistration, especially at regions of high contrast. The general consensus in the polarization community is that image misregistration on the order of 1/10th of a pixel can introduce artifacts in polarization images. If the registration is not achieved and maintained to this resolution, the data must be registered in software. Typically, rotation and translation (horizontal and vertical) are the main transformations that need to be corrected. It is desirable to have a registration algorithm that determines rotations and translations to 1/10th of a pixel, does not require user intervention, takes minimal computation time, and is based on analytical (non-iterative), automated calculations. This paper details an analytical, automated registration algorithm that corrects for rotation and translations by using a Fourier transform technique. Examples of images registered with this algorithm, and estimates of residual misregistrations are presented. Typical processing times are also given.
On the Systematic Search in a Hypercube (1979)

A sequence of points has been constructed that very uniformly fill the multi-dimensional cube. These points are successfully used for systematic crude searching, as starting points for global search algorithms to optimize functions of several variables, for computer aided statement of optimum design problems.
History of surgery for the correction of spinal deformity (2003)

During the last century the technological advances in the field of spinal surgery had a dramatic impact on the treatment of spinal deformity in children and adults. Before the advent of medications and vaccines to treat and/or prevent tuberculosis and poliomyelitis, patients suffering from these disorders often became incapacitated by the resulting kyphoscoliosis. In the early 1900s Lange began to address this problem mechanically by using foreign materials to stabilize the spine internally. In the 1950s and 1960s, owing to the efforts of Harrington and others, the process evolved to create the first generation of modern spinal instrumentation. The Harrington rod was able to correct a spinal deformity primarily through distraction. In the next wave of advances, some of the shortcomings of Harrington rods were addressed. Segmental fixation involving sublaminar wires was introduced in the 1970s by Luque. Anterior approaches and instrumentation-related techniques developed by Zielke and colleagues as well as Dywer and coworkers in the late 1960s and mid-1970s allowed for better correction of deformity with immobilization of fewer motion segments compared with posterior surgery. Transpedicular fixation of the spine was popularized by Cotrel and Dubousset in the 1980s; they used the technique to perform segmental stabilization, which better reduces the rotational aspect of a deformity. Finally, in the mid-1990s, thoracoscopic techniques were developed and are currently in use for anterior release and placement of instrumentation. The authors review the major technical developments for the surgical treatment of spinal deformity.
A Multi-Element VLC Architecture for High Spatial Reuse (2015)

Visible light communication (VLC) is an emerging wireless technology that offers more capacity than legacy radio frequency (RF) communications can offer. Free-space-optical (FSO) communication is VLC's general form spanning infrared bands, and it has an upper hand on traditional RF systems due to license-free spectrum, containment of beams, inherent security, energy efficient communications, and high transmission rates. In this paper, we consider a hybrid RF/FSO mechanism to transmit multiple data streams over multi-element VLC modules. We evaluate the link quality performance of a novel multi-element hemispherical design that can simultaneously provide good lighting and communication coverage across a room.
Genes encoding proteoglycans are associated with the risk of anterior cruciate ligament ruptures (2014)

These independent associations and haplotype analyses suggest that regions within ACAN, BGN, DCN and a region spanning LUM-DCN are associated with ACL injury susceptibility. Taking into account the functions of these genes, it is reasonable to propose that genetic sequence variability within the genes encoding proteoglycans may potentially modulate the ligament fibril properties.
Retinal Arteriolar Vascular Reactivity in Untreated and Progressive Primary Open-Angle Glaucoma (2010)

Purpose. To determine (1) the magnitude of retinal arteriolar vascular reactivity to normoxic hypercapnia in patients with untreated primary open-angle glaucoma (uPOAG) or progressive (p)POAG and in control subjects and (2) the effect of treatment with 2% dorzolamide on retinal vascular reactivity in uPOAG. Methods. The sample comprised 11 patients with uPOAG (after undergoing treatment, they became treated (t)POAG), 17 patients with pPOAG (i.e., manifesting optic disc hemorrhage), and 17 age-similar control subjects. The partial pressure of end-tidal CO(2) (PetCO(2)) was stabilized at 38 mm Hg at baseline. After baseline (10 minutes), normoxic hypercapnia was then induced (15 minutes) with an automated gas flow controller. Retinal arteriolar and optic nerve head (ONH) blood hemodynamics were assessed. The procedures were repeated after treatment with 2% dorzolamide for 2 weeks in tPOAG. Results. Baseline arteriolar hemodynamics were not different across the groups. In control subjects, diameter, velocity, and flow increased (P < 0.001) in response to normoxic hypercapnia. There was no change in all three hemodynamic parameters to normoxic hypercapnia in uPOAG, whereas only blood flow increased (P = 0.030) in pPOAG. Vascular reactivity was decreased in uPOAG and pPOAG patients compared with that in control subjects. After treatment with topical 2% dorzolamide for 2 weeks, the tPOAG group showed an increase in diameter, velocity, and flow (P </= 0.04) in response to normoxic hypercapnia. Similar trends were noted for ONH vascular reactivity. Conclusions. A reduced magnitude of arteriolar vascular reactivity in response to normoxic hypercapnia was shown in uPOAG and in pPOAG. Vascular reactivity improved after dorzolamide treatment in POAG.
Handbook of Experimental Psychology (1952)

This handbook was created in response to a demand for a survey that would systematize, digest, and appraise the state of experimental psychology at the mid-century. The book is primarily for the use of graduate students, advanced scholars, and specialists, who may use it as a reference source and guide to material outside their special field of interest. It is a compilation of individual presentations by 34 outstanding contributors that covers new experimental data and theory in psychophysics, psychological mechanisms, growth and development, motivation, learning and adjustment, sensory processes, and problems of human performance. Each of the papers is fully documented, and a complete name and subject index is appended. The book should be particularly useful to specialists who do not have the time to fully cover the tremendous amount of new material that has been covered in journals in the field of psychology and related fields in recent years.
Modulation of Social Cognition via Hallucinogens and “Entactogens” (2019)

Social cognition is a fundamental ability in human everyday lives. Deficits in social functioning also represent a core aspect of many psychiatric disorders. Yet, despite its significance, deficits in social cognition skills are insufficiently targeted by current treatments. Hallucinogens and entactogens have been shown to have the potential to modulate social processing. This article reviews the literature on the influence of hallucinogens and entactogens on social processing in controlled experimental studies in humans and elucidates the underlying neurobiological and neuropharmacological mechanisms. Furthermore, it identifies current knowledge gaps and derives implications for hallucinogen-assisted treatment approaches as well as the development of novel medication for trans-diagnostic impairments in social cognition.
Homolog of tocopherol <i>C</i> methyltransferases catalyzes <i>N</i> methylation in anticancer alkaloid biosynthesis (2010)

Madagascar periwinkle (Catharanthus roseus) is the sole source of the anticancer drugs vinblastine and vincristine, bisindole alkaloids derived from the dimerization of the terpenoid indole alkaloids vindoline and catharanthine. Full elucidation of the biosynthetic pathways of these compounds is a prerequisite for metabolic engineering efforts that will improve production of these costly molecules. However, despite the medical and commercial importance of these natural products, the biosynthetic pathways remain poorly understood. Here we report the identification and characterization of a C. roseus cDNA encoding an S-adenosyl-L-methionine-dependent N methyltransferase that catalyzes a nitrogen methylation involved in vindoline biosynthesis. Recombinant enzyme produced in Escherichia coli is highly substrate specific, displaying a strict requirement for a 2,3-dihydro bond in the aspidosperma skeleton. The corresponding gene transcript is induced in methyl jasmonate-elicited seedlings, along with the other known vindoline biosynthetic transcripts. Intriguingly, this unique N methyltransferase is most similar at the amino acid level to the plastidic γ-tocopherol C methyltransferases of vitamin E biosynthesis, suggesting an evolutionary link between these two functionally disparate methyltransferases.
Applying fuzzy logic to control cycling movement induced by functional electrical stimulation (1997)

This study examines the design of a rational stimulation pattern for electrical stimulation and a robust closed-loop control scheme to improve cycling system efficacy for subjects with paraplegia. The stimulation patterns were designed by analyzing gravitation potential needed for the cycling movement of the lower limbs against a frictionless cycling ergometer and the response delay of electrically stimulated muscles. To simplify the cycling control system, the stimulation patterns were fixed and only the single gain of the stimulation patterns was adjusted via a feedback control algorithm. To circumvent the complexity involved with exactly modeling a stimulated muscle and cycling ergometer, a model-free fuzzy logic controller (FLC) was adopted herein for our control scheme. Comparison between FLC and conventional proportional-derivative (PD) controllers demonstrated that the FLC with asymmetrical membership function enabled the subject with paraplegia to maintain varied desired cycling speeds, particularly at lower cycling speed. By incorporating the rational stimulation patterns, the FLC can produce a smooth and prolonged cycling movement deemed necessary for designing various training protocols.
Blue light intensity modulation in a frequency doubledtapered amplifiermodelocked laser (1994)

Blue light, generated by frequency doubling of a modelocked compound cavity laser based on a tapered GaAlAs amplifier, is modulated by varying the RF modelocking signal amplitude. Switching times are ~20 ns.
p21-activated Kinase 1 Phosphorylates and Regulates 14-3-3 Binding to GEF-H1, a Microtubule-localized Rho Exchange Factor (2004)

GEF-H1 is a guanine nucleotide exchange factor for Rho whose activity is regulated through a cycle of microtubule binding and release. Here we identify a region in the carboxyl terminus of GEF-H1 that is important for suppression of its guanine nucleotide exchange activity by microtubules. This portion of the protein includes a coiled-coil motif, a proline-rich motif that may interact with Src homology 3 domain-containing proteins, and a potential binding site for 14-3-3 proteins. We identify GEF-H1 as a binding target and substrate for p21-activated kinase 1 (PAK1), an effector of Rac and Cdc42 GTPases, using an affinity-based screen and localize a PAK1 phosphorylation site to the inhibitory carboxyl-terminal region of GEF-H1. We show that phosphorylation of GEF-H1 at Ser(885) by PAK1 induces 14-3-3 binding to the exchange factor and relocation of 14-3-3 to microtubules. Phosphorylation of GEF-H1 by PAK may be involved in regulation of GEF-H1 activity and may serve to coordinate Rho-, Rac-, and Cdc42-mediated signaling pathways.
Relationships between Levels of Serum IgE, Cell-Bound IgE, and IgE-Receptors on Peripheral Blood Cells in a Pediatric Population (2010)

In pediatric patients, levels of age-adjusted serum IgE, cell-bound IgE, and FcepsilonRI correlate. Even in the absence of elevated levels of serum IgE, cell-bound IgE can be detected on peripheral blood cells in a subgroup of patients.
Expression and cellular localisation of renal endothelin-1 and endothelin receptor subtypes in autosomal-dominant polycystic kidney disease (2003)

The major factors influencing the rate of progression of chronic renal disease in autosomal-dominant polycystic kidney disease (ADPKD) are unknown and there are currently no effective treatments for slowing the progression of chronic renal failure in ADPKD patients. As a first step in investigating the potential role of endothelin-1 (ET1) and its receptors (ETA and ETB) in the pathophysiology of progression in ADPKD, we have studied their expression and cellular localisation in ADPKD kidney. Immunoreactive ET1 was detected in cyst epithelia, mesangial cells and vascular smooth muscle cells suggesting continuing ET1 synthesis in the cystic kidney. Compared to healthy controls, ETA mRNA was 5-10-fold higher in ADPKD cystic kidney. In cystic kidney, neoexpression of ETA receptors was found overlying glomeruli and cysts and markedly increased in medium-sized renal arteries by microautoradiography. This is the first study to demonstrate a specific upregulation of ETA receptors in human renal disease. Future studies should address whether ETA selective antagonists may be effective in slowing renal disease progression in ADPKD.
Non‐invasive visualization of sperm mitochondria behavior in transgenic mice with introduced green fluorescent protein (GFP) (2001)

Using high sensitive polymerase chain reaction (PCR), we previously demonstrated that selective elimination of sperm mitochondrial DNA occurred during early embryogenesis in mouse. To analyze the process morphologically in more detail, a non-invasive, real-time observation of sperm mitochondria was used. Transgenic mice that express green fluorescent protein (GFP) exclusively in mitochondria (mtGFP-tg mice) were generated. The fluorescence in mtGFP-tg mice was strong and stable enough to carry out repeated observations under confocal laser scanning microscopy. In these mtGFP-tg mice it was revealed that the sperm mitochondria were selectively eliminated from egg cytoplasm during the two-cell stage of early embryogenesis. Therefore, mtGFP-tg mice should contribute to studies on sequential or repeated analysis of mitochondria.
Generalized quantification of three-dimensional resolution in optical diffraction tomography using the projection of maximal spatial bandwidths (2018)

Optical diffraction tomography (ODT) is a three-dimensional (3D) quantitative phase imaging technique, which enables the reconstruction of the 3D refractive index (RI) distribution of a transparent sample. Due to its fast, non-invasive, and quantitative imaging capability, ODT has emerged as a powerful tool for various applications. However, the spatial resolution of ODT has only been quantified along the lateral and axial directions for limited conditions; it has not been investigated for arbitrary-oblique directions. In this paper, we systematically quantify the 3D spatial resolution of ODT by exploiting the spatial bandwidth of the reconstructed scattering potential. The 3D spatial resolution is calculated for various types of systems, including the illumination-scanning, sample-rotation, and hybrid scanning-rotation methods. In particular, using the calculated 3D spatial resolution, we provide the spatial resolution as well as the arbitrary sliced angle. Furthermore, to validate the present method, the point spread function of an ODT system is experimentally obtained using the deconvolution of a 3D RI distribution of a microsphere and is compared with the calculated resolution.
TRANSCRIPTION OF THE MAMMALIAN MITOCHONDRIAL GENOME (1984)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
The ontogeny of sperm specific lactate dehydrogenase in mice (1967)

Abstract Testes of sexually mature mice ( Mus musculus ) contain a unique lactate dehydrogenase isozyme associated with the spermatozoan cell. This isozyme differs in subunit composition and reactivity to the substrate DL‐α‐hydroxyvalerate when compared to the usual five isozymes found in other tissues. It has been termed LDH‐X and has the same mobility as LDH‐5 when subjected to electrophoresis on standard polyacrylamide gels. This enzyme first appears during development at the time spermatocytes first mature in the testes. From the time of birth until sexual maturity is reached the specific activity of LDH in testes extracts does not change appreciably. When the mice have reached the weight of 6.5 to 7.5 g with a testes weight of 20 mg, which is equivalent to an age of 15 to 17 days postpartum, LDH‐X appears. It is at approximately this time that the first differentiative division of the primitive germ cell, the spermatogonium, occurs. For the next period of time, 15–20 days, the testes grow and differentiate at a rapid rate and during this same period the specific activity of the sperm LDH also increses. Histochemical evidence indicated that activity of LDH‐1, 2, and 3 is highest in the interstitial cells while LDH‐X activity is restricted to the cells that are close to the lumen of the testicular tubule.
<title>Regularized multiframe myopic deconvolution from wavefront sensing</title> (1999)

Deconvolution from wavefront sensing is a powerful and low cost high resolution imaging technique designed to compensate for the image degradation due to atmospheric turbulence. It is based on a simultaneous recording of shift exposure images and wavefront sensor (WFS) data. To date, the data processing consists of a sequential estimation of the wavefronts given the WFS data and then of the object given the reconstructed wavefronts and the images. Thus, the information about the wavefronts present in the images if not used for the wavefront estimation. The aim of this communication is to propose and validate a novel method called myopic deconvolution from wavefront sensing. It is a joint estimation of the object of interest and the unknown wavefronts using all data simultaneously in a coherent Bayesian framework. It takes into account the noise in the images and in the wavefront sensor measurements, and the available a priori information on the object to be restored as well as on the wavefronts. As to the object a priori information, an edge-preserving prior is implemented and validated. This method is validated on simulations and on experimental astronomical data.