gebhart/patrepeval huggingface dataset:
Rare functional missense variants in CACNA1H: What can we learn from Writer’s cramp? (2021)

Writer's cramp (WC) is a task-specific focal dystonia that occurs selectively in the hand and arm during writing. Previous studies have shown a role for genetics in the pathology of task-specific focal dystonia. However, to date, no causal gene has been reported for task-specific focal dystonia, including WC. In this study, we investigated the genetic background of a large Dutch family with autosomal dominant‒inherited WC that was negative for mutations in known dystonia genes. Whole exome sequencing identified 4 rare variants of unknown significance that segregated in the family. One candidate gene was selected for follow-up, Calcium Voltage-Gated Channel Subunit Alpha1 H, CACNA1H, due to its links with the known dystonia gene Potassium Channel Tetramerization Domain Containing 17, KCTD17, and with paroxysmal movement disorders. Targeted resequencing of CACNA1H in 82 WC cases identified another rare, putative damaging variant in a familial WC case that did not segregate. Using structural modelling and functional studies in vitro, we show that both the segregating p.Arg481Cys variant and the non-segregating p.Glu1881Lys variant very likely cause structural changes to the Cav3.2 protein and lead to similar gains of function, as seen in an accelerated recovery from inactivation. Both mutant channels are thus available for re-activation earlier, which may lead to an increase in intracellular calcium and increased neuronal excitability. Overall, we conclude that rare functional variants in CACNA1H need to be interpreted very carefully, and additional studies are needed to prove that the p.Arg481Cys variant is the cause of WC in the large Dutch family.
Current collection by a spherical high voltage probe: Electron trapping and collective processes (1990)

The author summarizes the results of theoretical studies of the interaction of an uninsulated, spherical, high voltage (10's of KV positive) probe with the ionospheric environment. The focus of this effort was the phenomenon of electron trapping and its implications for breakdown processes (collisional regime) and the current-voltage relationship governing current collection (collisionless regime) in space-based pulsed power systems with high voltage components exposed to space, e.g., the SPEAR I experiment.
Introduction of Strain Hardening Engineered Cementitious Composites in the Design of Reinforced Concrete Flexural Members for Improved Durability (1995)

Peer Reviewed
Pooled Genomic Screens Identify Anti-apoptotic Genes as Targetable Mediators of Chemotherapy Resistance in Ovarian Cancer (2019)

High-grade serous ovarian cancer (HGSOC) is often sensitive to initial treatment with platinum and taxane combination chemotherapy, but most patients relapse with chemotherapy-resistant disease. To systematically identify genes modulating chemotherapy response, we performed pooled functional genomic screens in HGSOC cell lines treated with cisplatin, paclitaxel, or cisplatin plus paclitaxel. Genes in the intrinsic pathway of apoptosis were among the top candidate resistance genes in both gain-of-function and loss-of-function screens. In an open reading frame overexpression screen, followed by a mini-pool secondary screen, anti-apoptotic genes including <i>BCL2L1</i> (BCL-XL) and <i>BCL2L2</i> (BCL-W) were associated with chemotherapy resistance. In a CRISPR-Cas9 knockout screen, loss of <i>BCL2L1</i> decreased cell survival whereas loss of proapoptotic genes promoted resistance. To dissect the role of individual anti-apoptotic proteins in HGSOC chemotherapy response, we evaluated overexpression or inhibition of BCL-2, BCL-XL, BCL-W, and MCL1 in HGSOC cell lines. Overexpression of anti-apoptotic proteins decreased apoptosis and modestly increased cell viability upon cisplatin or paclitaxel treatment. Conversely, specific inhibitors of BCL-XL, MCL1, or BCL-XL/BCL-2, but not BCL-2 alone, enhanced cell death when combined with cisplatin or paclitaxel. Anti-apoptotic protein inhibitors also sensitized HGSOC cells to the poly (ADP-ribose) polymerase inhibitor olaparib. These unbiased screens highlight anti-apoptotic proteins as mediators of chemotherapy resistance in HGSOC, and support inhibition of BCL-XL and MCL1, alone or combined with chemotherapy or targeted agents, in treatment of primary and recurrent HGSOC. IMPLICATIONS: Anti-apoptotic proteins modulate drug resistance in ovarian cancer, and inhibitors of BCL-XL or MCL1 promote cell death in combination with chemotherapy.
HYBRSIM—a modelling and simulation environment for hybrid bond graphs (2002)

Bond graphs are a powerful formalism to model continuous dynamics of physical systems. Hybrid bond graphs introduce an ideal switching element, the controlled junction, to approximate continuous behaviour that is too complex for numerical analysis (e.g. because of non-linearities or steep gradients). HYBRSIM is a tool for hybrid bond graph modelling and simulation implemented in Java and is documented in this paper. It performs event detection and location based on a bisectional search, handles run-time causality changes, including derivative causality, performs physically consistent (re-)initialization and supports two types of event iteration because of dynamic coupling. It exports hybrid bond graph models in Java and C/C++ code that includes discontinuities as switched equations (i.e. pre-enumeration is not required).
Activity of Sugar Esters Isolated from Leaf Trichomes of Nicotiana gossei to Pear Psylla (Homoptera: Psyllidae) (1995)

Insecticidal activity of a sugar ester fraction isolated from leaf trichomes of wild tobacco, Nicotiana gossei Domin, to egg, nymph, and adult stages of pear psylla, Cacopsylla pyricola Foerster, was determined in replicated laboratory bioassays. Aqueous solutions of sugar ester concentrations ranging from 62 to 1,000 ppm (mg/liter) were applied by an ultra-low-volume spray device to petri dishes containing eggs, nymphs, or adults. Data were recorded on nymphal mortality rates 1, 3, 5, and 7 d after treatment, on the percentage of eggs hatched 7 d after treatment, on the mortality rates of eclosed nymphs 3 dafter eclosion (10 d after treatment), and on adult mortality rates 1 d after treatment. Mortality rates did not differ significantly for sugar ester concentrations of 500 and 1,000 ppm, which both produced a mortality rate of ≥94% for nymphs and adults 1 d after treatment. Lethal concentration values for sugar esters to pear psylla nymphs and adults differed significantly 1 d after treatment for the LC50 (90 versus 200 ppm, respectively), but not for the LC90 (300 versus 400 ppm, respectively). Nymphal mortality rates for each sugar ester concentration did not increase over time significantly 1 d after application, which suggests that the sugar ester is a contact insecticide that is active mainly in the liquid state. The percentage of eggs hatched was not affected by any of the sugar ester treatments 7 d after application. In contrast, the mortality rates of newly eclosed nymphs ranged from 18.7 to 67% for sugar ester concentrations of 62- 1,000 ppm. Our data suggest that both nymphs and adults would be equally controlled with sugar ester concentrations high enough to obtain a mortality rate of >90%. These results will be useful in determining the range of sugar ester concentrations for field trials. In addition, an inexpensive ultra-low-volume spray device used in the bioassays is described that is capable of applying microliter amounts of candidate insecticidal materials to target insects.
Object-oriented modelling and simulation of a motorcycle (2008)

The design of a control oriented motorcycle model for the simulation of two-wheeled vehicles is widely recognized to be a very challenging task, as a complete analytical model is not directly available, due to its complexity and its high sensitivity to parameters' variations. Accordingly, a reliable model should be based on multibody modelling tools endowed with automated symbolic manipulation capabilities. This paper presents a simulation model for the dynamic behaviour of a motorcycle based on the object-oriented modelling paradigm developed in Modelica, within the Dymola environment. Specifically, we illustrate the modular approach to motorcycle modelling and discuss the tire-road interaction model, which is the crucial part of the proposed model. The validity of the proposed simulation model is assessed on real data, measured on an instrumented test vehicle. Further, to perform the verification phase a virtual driver model has been implemented, which allows to track both a roll angle and a target speed profile during different maneuvers. In particular, the behaviour of the driver is modelled as an inverse pendulum, with a rotational degree of freedom along the forward axis. This allows accounting for the driver lean angle, which is necessary to fully capture the real driving behaviour and its effects on the overall vehicle dynamics.
Chiral recognition of tartaric acid derivatives by a synthetic receptor (1991)

A synthetic receptor containing two acylaminopyridine groups linked through a R-(–)-binaphthyl spacer has been prepared and shown to bind to the two enantiomeric forms of diacyl tartaric acids by two very different geometries.
Correlation of Receptor Occupancy of Metabotropic Glutamate Receptor Subtype 1 (mGluR1) in Mouse Brain With In Vivo Activity of Allosteric mGluR1 Antagonists (2009)

The aim of this study was to clarify the relationship between receptor occupancy and in vivo pharmacological activity of mGluR1 antagonists. The tritiated mGluR1-selective allosteric antagonist [(3)H]FTIDC (4-[1-(2-fluoropyridin-3-yl)-5-methyl-1H-1,2,3-triazol-4-yl]-N-isopropyl-N-methyl-3,6-dihydropyridine-1(2H)-carboxamide) was identified as a radioligand having high affinity for mGluR1-expressing CHO cells (K(D) = 2.1 nM) and mouse cerebellum (K(D) = 3.7 nM). [(3)H]FTIDC bound to mGluR1 was displaced by structurally unrelated allosteric antagonists, suggesting there is a mutual binding pocket shared with different allosteric antagonists. The binding specificity of [(3)H]FTIDC for mGluR1 in brain sections was demonstrated by the lack of significant binding to brain sections prepared from mGluR1-knockout mice. Ex vivo receptor occupancy with [(3)H]FTIDC revealed that the receptor occupancy level by FTIDC correlated well with FTIDC dosage and plasma concentration. Intracerebroventricular administration of (S)-3,5-dihydroxyphenylglycine is known to elicit face washing behavior that is mainly mediated by mGluR1. Inhibition of this behavioral change by FTIDC correlated with the receptor occupancy level of mGluR1 in the brain. A linear relationship between the receptor occupancy and in vivo activity was also demonstrated using structurally diverse mGluR1 antagonists. The receptor occupancy assays could help provide guidelines for selecting appropriate doses of allosteric mGluR1 antagonist for examining the function of mGluR1 in vivo.
Augmented repair of radial meniscus tear with biomimetic electrospun scaffold: an in vitro mechanical analysis (2016)

While multilayered scaffold sheets were successfully fabricated to mimic the ultrastructure and anisotropic tensile properties of native menisci, improvements in suture retention strength or adoption of superior surgical techniques will be needed to further enhance the mechanical strength of repairs of radial meniscal tears.
Linear and nonlinear system identification of autonomic heart-rate modulation (1997)

The authors' findings show that system identification provides a useful, noninvasive, and quantitative means for evaluating cardiovascular regulatory mechanisms. With combinations of linear and nonlinear identification, new insights about the cardiovascular regulatory dynamics were obtained. System identification provides a new way of studying and monitoring cardiovascular function. Instead of just studying the signals generated by the cardiovascular regulatory system, the signals are analyzed to characterize quantitatively the mechanisms that generate them. System identification is a type of "inverse modeling"in which the physiologic signals are used to create a model of cardiovascular regulation for the specific individual from whom the data are obtained. As such, system identification would appear to be a desirable means for evaluating effects of physiologic alterations resulting from pharmacological interventions, changes in environment such as changes in gravitational field, physiologic stresses such as hypoxia and exercise, and disease processes. System identification may also prove to be an attractive means to study closed-loop regulation in other physiologic systems, ranging in size from biochemical pathways to intact multi-organ systems.
Scoliosis in Friedreich's ataxia: longitudinal characterization in a large heterogeneous cohort (2021)

Scoliosis is an important comorbidity of FRDA. Our comprehensive documentation of scoliosis progression in this natural history study provides a baseline for comparison as novel treatments become available.
Multicast beamforming with antenna selection (2012)

Multicast beamforming exploits subscriber channel state information at the base station to form multiple beams that steer radiated power towards users of interest, while minimizing leakage to other users and systems. Such functionality has been provisioned in the long-term evolution (LTE) enhanced multimedia broadcast multicast service (EMBMS). In this context, the present paper deals with joint multicast beamforming and antenna selection. Whereas this problem (and even plain multicast beamforming) is NP-hard, it is shown that using ℓ <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</sub> -norm squared (instead of ℓ <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</sub> -norm) as a surrogate for the ℓ <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">0</sub> -norm yields a natural semidefinite programming relaxation - something not obvious with the ℓ <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</sub> -norm. Simulations indicate that the proposed algorithm significantly reduces the number of antennas required to meet prescribed service levels, at a relatively small cost of excess transmission power. Furthermore, its performance is close to that attained by exhaustive search, at far lower complexity.
Decomposition-aware layout optimization for 20/14nm standard cells (2014)

Decomposition-aware layout design improvements for 8, 9, 11, and 13-track 20/14nm standard cells are presented. Using a decomposition-aware scoring methodology that quantifies the manufacturability of layouts, the Double Patterning Technology (DPT)-compliant layouts are optimized for DPT-specific metrics that include: the density difference between the two decomposition mask layers, the enclosure of stitching areas, the density of stitches, and the design regularity of stitching areas. For a 9-track standard cell, eliminating the stitches from the layout design improved the composite score from 0.53 to 0.70.
Compressive Strength Evaluation and Phase Analysis of Pulp Capping Materials Based on Carbonate Apatite-SCPC Using Different Concentration of SCPC and Calcium Hydroxide (2018)

The mechanical strength of pulp capping material based on carbonate apatite and silica calcium-phosphate composite (CO 3 Ap-SCPC) is one of the key factors for the success of the material in protecting the vitality of the pulp during the formation of apatite and dentin reparative. Modifying the material in the powder phase was known to increase the mechanical strength. The purpose of this study was to determine whether the addition of SCPC and calcium hydroxide in pulp capping materials based on CO 3 Ap-SCPC would affect the compressive strength of this pulp capping material. In this study, three cement groups were used, each group consisted of dicalcium phosphate anhydrous and vaterite which added by SCPC concentration 0%, 5% and 10% and calcium hydroxide concentration 0%, 5% and 10%, respectively. All groups were tested by a compressive strength test and X-Ray diffraction (XRD) for phase analysis. The mean value of compressive strength with addition of 0% SCPC and 10% Ca(OH) 2 was 16.54 ± 1.35 MPa, addition of 5% SCPC and 5% Ca(OH) 2 of 18.55 ± 2.81 MPa, addition of 10% SCPC and 0% Ca(OH) 2 was 9.22 ± 1.21 MPa. The addition of SCPC and Ca(OH) 2 show statistically significant difference in compressive strength (p&lt;0.05). The XRD analysis of the highest compressive strength revealed that the apatite crystal was successfully formed. It can be concluded that incorporated specific amount of SCPC and Ca(OH) 2 could improve the mechanical strength and the apatite formation of the CO 3 Ap-SCPC pulp capping material.
Hepatocyte growth factor as potential cardiovascular therapy (2005)

Hepatocyte growth factor is a mesenchyme-derived pleiotropic factor that regulates the growth, motility and morphogenesis of various types of cells, and is also a member of the angiogenic growth factors. Hepatocyte growth factor is secreted by vascular endothelial cells and smooth muscle cells, and the hepatocyte growth factor receptor, c-met, was also observed in these vascular cells. Treatment of human aortic endothelial cells with recombinant hepatocyte growth factor resulted in a significant increase in cell proliferation, accompanied by mitogen-activated protein kinase and Akt/protein kinase B phosphorylation. Recently, a novel therapeutic strategy for ischemic diseases using angiogenic growth factors to augment collateral artery development has been proposed. As preclinical study of gene therapy using hepatocyte growth factor to treat peripheral arterial disease, naked hepatocyte growth factor plasmid was intramuscularly injected into the ischemic hind limb of rabbits in order to evaluate its angiogenic activity. Intramuscular injection of hepatocyte growth factor plasmid once on day 10 following surgery, produced significant augmentation of collateral vessel development in the ischemic limb on day 30. In the clinical setting, the authors further investigated the safety and efficacy of hepatocyte growth factor plasmid DNA in patients with critical limb ischemia, in a prospective open-labeled trial. Intramuscular injection of naked plasmid DNA was performed in the ischemic limbs of six patients with critical limb ischemia with arteriosclerosis obliterans (n = 3) or Buerger disease (n = 3) graded as Fontaine III or IV. In the efficacy evaluation, a reduction of pain scale of more than 1 cm on a visual analog pain scale was observed in five out of six patients. An increase in ankle pressure index of more than 0.1 was observed in five out of five patients. The long diameter of eight out of 11 ischemic ulcers in four patients was reduced by more than 25%. Intramuscular injection of naked hepatocyte growth factor plasmid is safe, feasible and can achieve successful improvement of ischemic limbs. Although the present data were obtained to demonstrate safety in a Phase I/early Phase II trial, the initial clinical outcome with hepatocyte growth factor gene transfer seems to indicate its usefulness as sole therapy for critical limb ischemia. Randomized placebo-controlled clinical trials of alternative dosing regimens of gene therapy will be required to define the efficiency of this therapy.
Correction of Kyphotic Deformity of the Cervical Spine in Ankylosing Spondylitis Using General Anesthesia and Internal Fixation (1996)

Surgical correction of kyphotic deformity of the cervical spine caused by ankylosing spondylitis is usually done using local anesthesia to prevent undue spinal cord compression and paralysis followed by a sudden-extension maneuver. We report a case of kyphotic deformity that was corrected while the patient was under general anesthesia. To prevent cord compression and paralysis and to obtain an accurate and gradual correction, we used a Hartshill rod prebent to the desired angle, and correction was done by tightening sublaminar wires on the rod until the lamina made full contact with it. Somatosensory evoked potential and wake-up tests were also performed. Our successful result shows that correction of kyphotic deformity of the cervical spine in ankylosing spondylitis can be done more accurately and without discomfort using the present method.
Immunization With a Recombinant MAGE-A3 Protein After High-dose Therapy for Myeloma (2007)

MAGE-A3 is frequently expressed in high-risk multiple myeloma (MM). We immunized a healthy donor with MAGE-A3 protein formulated in AS02B to transfer immunity to her identical twin, diagnosed with MAGE-A3-positive MM. After a melphalan 200 mg/m syngeneic peripheral blood stem cell transplant, primed donor cells collected after immunizations were transferred and followed by repeated patient immunizations. MAGE-A3 immunizations were well tolerated. Strong MAGE-A3-specific antibody, cytotoxic T-lymphocyte (CTL), and T-helper responses were induced in both twins. A humoral response was transferred to the patient with the donor peripheral blood stem cells and increased by booster immunization. The CTL response targeted a previously undescribed HLA-A*6801 binding MAGE-A3115-123 peptide. MAGE-A3115-123 CTLs were detected in the patient more than 1 year after the last immunization. Multiple T-helper cellular responses were detected with the dominant response to an HLA-DR11 restricted MAGE-A3 epitope. The patient remains in remission 2.5 years after the second transplant. This report shows for the first time that immunization of a healthy donor with a defined cancer-testis protein induces immune responses that can be transferred and expanded posttransplant in the recipient. MAGE-A3 immunization may be a useful adjunct to high dose melphalan-based peripheral blood stem cell transplant, providing a new therapeutic option for high-risk MM.
Crystal Structure offac−Ir(ppy)3and Emission Properties under Ambient Conditions and at High Pressure (2005)

Solution and refinement of the crystal structure of fac−Ir(ppy)3 is severely hampered by systematic twinning and pseudo-symmetry. fac−Ir(ppy)3 crystallizes in the centrosymmetric space group P3̄ as has been deduced from single-crystal structure refinement and investigations of the second harmonic generation (SHG) of fac−Ir(ppy)3 powder as compared to two standard materials. The topology of the molecular packing of fac−Ir(ppy)3 is identical to the packing observed for [Ru(bpy)3]0, however, the site symmetry of all Ir(ppy)3 molecules is necessarily lowered from D3 to C3. Packing motifs with intermolecular “π−π interactions” of T-shaped and “shifted π stack” geometry are realized. The systematic twinning leads to the occurrence of crystalline domains with rigorously alternating chirality within the bulk of the domains but with homochiral fac-Ir(ppy)3 contacts at the domain interfaces. These differences in packing motifs are displayed in the emission spectra and in the high-pressure-induced shifts of the emission. The emission maximum of the bulk material at 18 350 cm-1 (545 nm) and of the domain interfaces at 19 700 cm-1 (507 nm) experience for p < 25 kbar and T = 295 K red shifts of Δν̄/Δp = −(12 ± 2) cm-1/kbar, and −(22 ± 4) cm-1/kbar, respectively.
A Review of Structural and Material Properties of Vascular Grafts (1987)

A brief review of the textile structures employed in the construction of vascular grafts is followed by a survey of the causes of failure cited in the literature. An attempt is made to determine the structural factors contributing to the failure of vascular grafts, and attention is given to material properties and methods for determining these attributes. Need for further research is emphasized.