gebhart/patrepeval huggingface dataset:
Different Routes of Protein Folding Contribute to Improved Protein Production in Saccharomyces cerevisiae (2020)

Protein folding is often considered the flux controlling process in protein synthesis and secretion. Here, two previously isolated <i>Saccharomyces cerevisiae</i> strains with increased α-amylase productivity were analyzed in chemostat cultures at different dilution rates using multi-omics data. Based on the analysis, we identified different routes of the protein folding pathway to improve protein production. In the first strain, the increased abundance of proteins working on the folding process, coordinated with upregulated glycogen metabolism and trehalose metabolism, helped increase α-amylase productivity 1.95-fold compared to the level in the original strain in chemostat culture at a dilution rate of 0.2/h. The second strain further strengthened the folding precision to improve protein production. More precise folding helps the cell improve protein production efficiency and reduce the expenditure of energy on the handling of misfolded proteins. As calculated using an enzyme-constrained genome-scale metabolic model, the second strain had an increased productivity of 2.36-fold with lower energy expenditure than that of the original under the same condition. Further study revealed that the regulation of <i>N</i>-glycans played an important role in the folding precision control and that overexpression of the glucosidase Cwh41p can significantly improve protein production, especially for the strains with improved folding capacity but lower folding precision. Our findings elucidated in detail the mechanisms in two strains having improved protein productivity and thereby provided novel insights for industrial recombinant protein production as well as demonstrating how multi-omics analysis can be used for identification of novel strain-engineering targets.<b>IMPORTANCE</b> Protein folding plays an important role in protein maturation and secretion. In recombinant protein production, many studies have focused on the folding pathway to improve productivity. Here, we identified two different routes for improving protein production by yeast. We found that improving folding precision is a better strategy. Dysfunction of this process is also associated with several aberrant protein-associated human diseases. Here, our findings about the role of glucosidase Cwh41p in the precision control system and the characterization of the strain with a more precise folding process could contribute to the development of novel therapeutic strategies.
Fabrication of a Second-Generation of &lt;formula formulatype="inline"&gt;&lt;tex Notation="TeX"&gt;$\hbox{Nb}_{3} \hbox{Sn}$&lt;/tex&gt;&lt;/formula&gt; Coils for the LARP HQ02 Quadrupole Magnet (2013)

In the framework of the Large Hadron Collider Luminosity upgrade (HiLumi-LHC) project, the US LHC accelerator research program is developing high-gradient, large-aperture Nb3 Sn quadrupole magnets for the LHC interaction regions. The fabrication and tests of a first series of 120-mm-aperture “HQ01” coils revealed design issues that resulted in limited performance. A second series of coils was fabricated in which a number of improved features were implemented (HQ02 coils). The improvements were partly validated with the successful test of an HQ02 coil in a mirror structure, which reached 97% of the short sample. Here, we review the modifications in the coil design and the coil fabrication process, report the issues met during the fabrication, give details of the few differences that exist within the set of HQ02 coils, and discuss a list of further improvements that will be implemented in a third series of HQ coils.
DC-Derived IL-10 Modulates Pro-inflammatory Cytokine Production and Promotes Induction of CD4+IL-10+ Regulatory T Cells during Plasmodium yoelii Infection (2017)

The cytokine IL-10 plays a crucial role during malaria infection by counteracting the pro-inflammatory immune response. We and others demonstrated that <i>Plasmodium yoelii</i> infection results in enhanced IL-10 production in CD4<sup>+</sup> T cells accompanied by the induction of an immunosuppressive phenotype. However, it is unclear whether this is a direct effect caused by the parasite or an indirect consequence due to T cell activation by IL-10-producing antigen-presenting cells. Here, we demonstrate that CD11c<sup>+</sup>CD11b<sup>+</sup>CD8<sup>-</sup> dendritic cells (DCs) produce elevated levels of IL-10 after <i>P. yoelii</i> infection of BALB/c mice. DC-specific ablation of IL-10 in <i>P. yoelii</i>-infected IL-10<sup>flox/flox</sup>/CD11c-cre mice resulted in increased IFN-γ and TNF-α production with no effect on MHC-II, CD80, or CD86 expression in CD11c<sup>+</sup> DCs. Accordingly, DC-specific ablation of IL-10 exacerbated systemic IFN-γ and IL-12 production without altering <i>P. yoelii</i> blood stage progression. Strikingly, DC-specific inactivation of IL-10 in <i>P. yoelii</i>-infected mice interfered with the induction of IL-10-producing CD4<sup>+</sup> T cells while raising the frequency of IFN-γ-secreting CD4<sup>+</sup> T cells. These results suggest that <i>P. yoelii</i> infection promotes IL-10 production in DCs, which in turn dampens secretion of pro-inflammatory cytokines and supports the induction of CD4<sup>+</sup>IL-10<sup>+</sup> T cells.
Structure-Activity Analysis of Cathepsin K/Chondroitin 4-Sulfate Interactions (2010)

In the presence of oligomeric chondroitin 4-sulfate (C4-S), cathepsin K (catK) forms a specific complex that was shown to be the source of the major collagenolytic activity in bone osteoclasts. C4-S forms multiple contacts with amino acid residues on the backside of the catK molecule that help to facilitate complex formation. As cathepsin L does not exhibit a significant collagenase activity in the presence or in the absence of C4-S, we substituted the C4-S interacting residues in catK with those of cathepsin L. Variants revealed altered collagenolytic activities with the largest inhibitory effect shown by the hexavariant M5. None of the variants showed a reduction in their gelatinolytic and peptidolytic activities when compared with wild-type catK, indicating no structural alteration within their active sites. However, the crystal structure of the M5 variant in the presence of oligomeric C4-S revealed a different binding of chondroitin 4-sulfate. C4-S is not continuously ordered as it is in the wild-type catK·C4-S complex. The orientation and the direction of the hexasaccharide on the catK surface have changed, so that the hexasaccharide is positioned between two symmetry-related molecules. Only one M5 variant molecule of the dimer that is present in the asymmetric unit interacts with C4-S. These substitutions have changed the mode of catK binding to C4-S and, as a result, have likely affected the collagenolytic potential of the variant. The data presented here support our hypothesis that distinct catK/C4-S interactions are necessary for the collagenolytic activity of the enzyme.
The effects of antihypertensive drug therapies on blood glucose levels in maturity onset diabetes patients on oral hypoglycaemic drugs: The case of selected health centres in Lesotho (2017)

Background: Antihypertensive drugs may cause changes in blood glucose levels. The concurrent use of these medications with hypoglycaemic drugs in diabetic patients may contribute to inadequate control of blood glucose levels. Objectives: To describe the effects of prescribed antihypertensive agents on fasting blood glucose levels of non-insulin dependent diabetic patients on treatment with oral hypoglycaemic medications. Method: Descriptive data on fasting blood glucose levels of diabetic patients on hypoglycaemic and antihypertensive drug treatments were collected retrospectively for a six-month period. Data sources were medical records of patients attending diabetic clinics in five health centres in the Maseru Health Service A rea of Lesotho. There cords were categorised in to two basic patient groups, namely, patient groups treated with only oral hypoglycaemic agents and patient groups treated with same agents concurrent with Anti-hypertensive agents. Differences in the means of the initial and end of six-months Period fasting blood glucose levels of patient treatment groups were determined and compared. Results: Patients who received an anti-diabetic drug regime concurrent&#13;\nwith antihypertensive medication tended to show improved fasting blood glucose levels at six months, whereas patients receiving only anti diabetic drugs did not show improvement. Partly owing to the small sample size (178patients), the differences were not&#13;\nstatistically significant. Conclusion: Hydrochlorothiazide prescribed singly or in combination with other antihypertensive drugs was implicated in increased blood glucose levels. Captopril showed better glycaemic control for patients on oral hypoglycaemic agents. Atenolol and nifedipine appeared not to have any effects on patients’ fasting&#13;\nblood glucose levels. A prospective case-control study would help clarify these findings&#13;\nin this study’s population.
High-density neural recordings from feline sacral dorsal root ganglia with thin-film array (2021)

<i>Objective</i>. Dorsal root ganglia (DRG) are promising sites for recording sensory activity. Current technologies for DRG recording are stiff and typically do not have sufficient site density for high-fidelity neural data techniques.<i>Approach</i>. In acute experiments, we demonstrate single-unit neural recordings in sacral DRG of anesthetized felines using a 4.5<i>µ</i>m thick, high-density flexible polyimide microelectrode array with 60 sites and 30-40<i>µ</i>m site spacing. We delivered arrays into DRG with ultrananocrystalline diamond shuttles designed for high stiffness affording a smaller footprint. We recorded neural activity during sensory activation, including cutaneous brushing and bladder filling, as well as during electrical stimulation of the pudendal nerve and anal sphincter. We used specialized neural signal analysis software to sort densely packed neural signals.<i>Main results</i>. We successfully delivered arrays in five of six experiments and recorded single-unit sensory activity in four experiments. The median neural signal amplitude was 55<i>μ</i>V peak-to-peak and the maximum unique units recorded at one array position was 260, with 157 driven by sensory or electrical stimulation. In one experiment, we used the neural analysis software to track eight sorted single units as the array was retracted ∼500<i>μ</i>m.<i>Significance</i>. This study is the first demonstration of ultrathin, flexible, high-density electronics delivered into DRG, with capabilities for recording and tracking sensory information that are a significant improvement over conventional DRG interfaces.
Performance Simulation and Cost Assessment of Oxy-Combustion Process for CO2 Capture from Coal-Fired Power Plants (2005)

In order to mitigate green house gas emissions, CO2 from large sources such as coal-fired power plants should be economically captured and sequestered. This paper describes the performance modeling and cost assessment of processes designed to capture and compress CO2 from sub-critical pulverized coal fired power plants (PC) and Integrated Gasification Combined Cycle (IGCC) units. Plant capacity of 533 MWe gross power output firing western PRB coal was considered. Oxy-Combustion (PC-OC) and amine scrubbing technologies (PC-MEA) are considered as technology options to capture CO2 from PC plants and Selexol process (IGCC-S) to capture CO2 from IGCC plant. Detailed results of the mass and energy balance were obtained from steady state simulations. Cost models were developed to estimate the capital, operating, electricity and the CO2 avoidance costs for each technology. The process simulations showed that, with sub-critical steam cycle, the PC-OC and PC-MEA processes with CO2 compression to 80 bars (1160 psi) decreases the net power output available by 28 % and 30 % respectively compared to PC plant with no capture. The economic analysis showed that the cost of electricity for the PC-OC plant increased by about 60%, PC-
Plasticity of Primary Somatosensory Cortex Paralleling Sensorimotor Skill Recovery From Stroke in Adult Monkeys (1998)

Adult owl and squirrel monkeys were trained to master a small-object retrieval sensorimotor skill. Behavioral observations along with positive changes in the cortical area 3b representations of specific skin surfaces implicated specific glabrous finger inputs as important contributors to skill acquisition. The area 3b zones over which behaviorally important surfaces were represented were destroyed by microlesions, which resulted in a degradation of movements that had been developed in the earlier skill acquisition. Monkeys were then retrained at the same behavioral task. They could initially perform it reasonably well using the stereotyped movements that they had learned in prelesion training, although they acted as if key finger surfaces were insensate. However, monkeys soon initiated alternative strategies for small object retrieval that resulted in a performance drop. Over several- to many-week-long period, monkeys again used the fingers for object retrieval that had been used successfully before the lesion, and reacquired the sensorimotor skill. Detailed maps of the representations of the hands in SI somatosensory cortical fields 3b, 3a, and 1 were derived after postlesion functional recovery. Control maps were derived in the same hemispheres before lesions, and in opposite hemispheres. Among other findings, these studies revealed the following 1) there was a postlesion reemergence of the representation of the fingertips engaged in the behavior in novel locations in area 3b in two of five monkeys and a less substantial change in the representation of the hand in the intact parts of area 3b in three of five monkeys. 2) There was a striking emergence of a new representation of the cutaneous fingertips in area 3a in four of five monkeys, predominantly within zones that had formerly been excited only by proprioceptive inputs. This new cutaneous fingertip representation disproportionately represented behaviorally crucial fingertips. 3) There was an approximately two times enlargement of the representation of the fingers recorded in cortical area 1 in postlesion monkeys. The specific finger surfaces employed in small-object retrieval were differentially enlarged in representation. 4) Multiple-digit receptive fields were recorded at a majority of emergent, cutaneous area 3a sites in all monkeys and at a substantial number of area 1 sites in three of five postlesion monkeys. Such fields were uncommon in area 1 in control maps. 5) Single receptive fields and the component fields of multiple-digit fields in postlesion representations were within normal receptive field size ranges. 6) No significant changes were recorded in the SI hand representations in the opposite (untrained, intact) control hemisphere. These findings are consistent with "substitution" and "vicariation" (adaptive plasticity) models of recovery from brain damage and stroke.
Pasteurella Vaccination with Metaphylaxis for Calf Health (2001)

The objective of the study was to determine the benefit of simultaneous Pasteurella/Mannheimia vaccination as an addition to metaphylaxis for the prevention of bovine respiratory disease complex (BRDC).
The IXM2 parallel associative processor for AI (1994)

Describes the IXM2 associative processor and its main application in speech-to-speech translation. The IXM2 is a semantic memory system machine that began as a faithful implementation of the NETL semantic network machine and grew into a massively parallel SIMD machine that has demonstrated the power of large associative memories. Such processors can support robust performance in speech applications. In fact, the IXM2 with 73 transputers has outperformed a Cray in some language-translation tasks. We selected speech-to-speech translation as our main application because it is one of the grand challenges of massively parallel artificial intelligence. The social implications of successful automatic translation are enormous-e.g. people who speak different languages could communicate in real time by using interpreting telephony.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Distillation with intermediate heat pumps and optimal sidestream return (1986)

Abstract The technique of distillation with intermediate heat pumps and optimal sidestream return—IHOSR distillation—is presented. IHOSR distillation allows heat to be moved between points in a distillation column with greater efficiency than several other methods of using heat pumps for distillation.
Oxa-di-π-methane Photochemical Rearrangement of Quinuclidinones. Synthesis of Pyrrolizidinones (2003)

[reaction: see text] The oxa-di-pi-methane (ODPM) photochemical rearrangement, a triplet-sensitized sigmatropic 1,2-acyl shift of beta,gamma-enones, was successful utilizing methyl and heptyl 1-aza-3-carboalkoxybicyclo[2.2.2]oct-2-en-5-ones (quinuclidinones) as the photoprecursors. The cyclopropane of the heptyl ester tricyclic photoproduct could be opened with lithium dimethylcuprate or via hydrogenolysis to produce the corresponding pyrrolizidinone skeletons.
Construction of a dual mode scanning near-field optical microscope based on a tapping mode atomic force microscope (1998)

We present the modification of a commercial tapping mode atomic force microscope into a reflection and transmission dual mode scanning near-field optical microscope. In the configuration, the normal force detection unit is replaced by a shear force detection module and an interfacing circuit. The tip-sample distance control is therefore similar to tapping mode operation. Detection of the near-field signals is based on photodiodes and the lock-in technique, and the resolutions obtained for the topography and the near-field signal are around 80 and 150 nm, respectively.
Cellular and Site-Specific Mitochondrial Characterization of Vital Human Amniotic Membrane (2018)

Over a century ago, clinicians started to use the human amniotic membrane for coverage of wounds and burn injuries. To date, literally thousands of different clinical applications exist for this biomaterial almost exclusively in a decellularized or denuded form. Recent reconsiderations for the use of vital human amniotic membrane for clinical applications would take advantage of the versatile cells of embryonic origin including the entirety of their cell organelles. Recently, more and more evidence was found, showing mitochondria to be involved in most fundamental cellular processes, such as differentiation and cell death. In this study, we focused on specific properties of mitochondria of vital human amniotic membrane and characterized bioenergetical parameters of 2 subregions of the human amniotic membrane, the placental and reflected amnion. We found significantly different levels of adenosine triphosphate (ATP) and extracellular reactive oxygen species, concentrations of succinate dehydrogenase, and lactate upon inhibition of ATP synthase in placental and reflected amnion. We also found significantly different rates of mitochondrial respiration in isolated human amniotic epithelial cells and human amniotic mesenchymal stromal cells, according to the subregions. Differences in metabolic activities were inversely related to mitochondrial DNA copy numbers in isolated cells of placental and reflected amnion. Based on significant differences of several key parameters of energy metabolism in 2 subregions of vital amnion, we propose that these metabolic differences of vital placental and reflected amnion could have critical impact on therapeutic applications. Inclusion of region-specific metabolic properties could optimize and fine-tune the clinical application of the human amniotic membrane and improve the outcome significantly.
Picosecond laser generation of ultrashort acoustic pulses in silicon (1989)

Generation and propagation characteristics of picosecond laser-generated ultrashort acoustic pulses in Si were studied by means of a ZnO piezoelectric transducer. The full width at half-maximum of the observed acoustic pulses is about 3 ns, which is determined by the response of the ZnO transducer. Under the condition of no sample ablation, the propagation velocity of laser-generated acoustic pulses agrees well with the sound velocity. In the plasma formation regime, the propagation velocity of acoustic pulses exceeds the sound velocity at the early stage of propagation. The amplitude of acoustic pulses is affected by the formation and expansion of laser-generated plasmas at the silicon surface.
Automatic Computation for Pressure Controlled Intermittent Coronary Sinus Occlusion (2010)

Pressure controlled intermittent coronary sinus occlusion (PICSO) has been found to substantially salvage ischemic myocardium. By elevating venous pressure two mechanisms are involved namely the distention of venous vessels inducing mechanotransduction as well as a redistribution of venous flow towards ischemic areas. Mechanotransduction in endothelial cells inducing changes in the ischemic heart inducing myocardial salvage as well as myocardial recovery is blunted by possible consequences of myocardial perfusion deficits by limiting coronary inflow. To limit these severe side effects we have evaluated a new mathematical model to describe the Increase (Inflation) and decrease (deflation) in coronary Sinus pressure (CSP) following pressure controlled intermittent coronary sinus occlusion (PICSO) and release. The model is evaluated and compared on the basis of dogs, pigs and sheep. The model consists of two parts with three parameter double exponential function for each, and it was fitted by using the non-linear least squares algorithms. The new model was used in implementation of automatic computing module which is responsible to compute the following quantities for Inflation and Deflation: 1. Systolic and diastolic plateau.
Solutions to security in mobile agent systems (2001)

The commercial deployment of multi-agent systems (MASs) has yet to be realised on any significant scale. One of the principle reasons for this is the poor state of agent security mechanisms. In particular, business-to-business (B2B) e-commerce, which is a favourite application domain for MASs, demands guarantees of agent behaviour and safe interaction with legacy systems. This paper outlines a design for a secure mobile agent architecture termed MATRIX (Mobile Agent Technology Robust Infrastructure eXploration), as part of a joint collaboration between BT and DERA. A highly secure cooperative MAS was the principal design objective. Static agents on each host control all data access by the mobile agents and requests for services are processed via an XML formatted agent communication language. The mobile agents&apos; access to hosts is also restricted via pre- and post-arrival authentication. This combination of features creates a robust and secure system that protects both host servers and mobile agents. The proposed architecture has been successfully tested in a prototype MAS within a distributed database application. (4 pages)
Substrate fiber alignment mediates tendon cell response to inflammatory signaling (2018)

Use of biomaterial scaffolds for tendon repair often results in tissue formation characteristic of scar tissue, rather than the highly aligned type-1 collagen matrix of healthy tendons. We hypothesized that non-optimal biomaterial surfaces may play a role in these outcomes, specifically randomly oriented biomaterial surfaces that unintentionally mimic structure of pathological tendon. We observed that disorganized scaffold surfaces do adversely affect early cell attachment and gene expression. We further identified that disorganized fiber surfaces can prime tendon cells toward pro-inflammatory signaling. These findings represent provocative evidence unstructured fiber surfaces may underlie inflammatory responses that drive aberrant collagen matrix turnover. This work could be highly relevant for the design of cell instructive biomaterial therapies that yield positive clinical outcomes.