gebhart/patrepeval huggingface dataset:
Letter to the Editor: Might Denosumab Fit in Primary Biliary Cholangitis Treatment? (2019)

Potential conflict of interest: Dr. Lleo is on the speakers’ bureau for Intercept, AbbVie, MSD, and Gilead. Dr. Gershwin has been an investigator to PBC trials sponsored by Arena Pharmaceuticals, Bristol‐Myers Squibb, Cymabay Pharmaceuticals, Genentech and Johnson and Johnson. Dr. Invernizzi received grants from Intercept, Gilead, and Bruschettini. TO THE EDITOR: We read with interest the recent communication1 reporting the efficacy and safety of 3‐year treatment with denosumab for osteoporosis in patients with primary biliary cholangitis (PBC). PBC is a chronic cholestatic liver disease characterized by progressive destruction of intrahepatic bile ducts, portal tract inflammation, and fibrosis that may eventually progress to end‐stage liver disease.2 Even though the exact etiology of PBC remains unknown, it is extensively accepted that development of PBC requires one or more environmental factors that initiate an autoimmune response in genetically predisposed individuals. Osteoporosis is a common extrahepatic complication in PBC patients that highly impairs quality of life. Denosumab, a fully human monoclonal antibody against the receptor activator of nuclear factor‐κB ligand (RANKL), is widely used for treatment of osteoporosis based on the fact that it increases bone mineral density by inhibiting development and activity of osteoclasts, thereby decreasing bone resorption. Accumulating evidence suggests the importance of RANKL signaling in autoimmunity, with the immune and skeletal systems being tightly interconnected. In addition, murine models lacking RANK or RANKL show defects in B‐cell number and homeostasis involving interleukin‐10 and CD40 signaling,3 and single‐nucleotide polymorphism SNP analysis has revealed that the RANKL gene is near a novel risk locus for PBC, suggesting a role of the RANKL‐RANK axis in PBC pathogenesis.4 Furthermore, our group has demonstrated that cholangiocytes from PBC patients express high levels of RANK and that the immune infiltrate within the portal areas around bile ducts in PBC are highly RANKL positive.5 Most important, hepatic level of RANKL was associated with disease severity. Our data therefore strongly suggested a role of the RANK‐RANKL axis in the innate immune activation in PBC, and we hypothesize that the damaged cholangiocytes, which express high levels of RANK, lead to the recruitment of RANKL‐positive cells and ultimately the classic portal tract infiltrates. Taken altogether, a number of old and new evidences suggests that denosumab might have a wide beneficial role in PBC treatment, besides osteoporosis.
Sequential Therapy with Nivolumab Followed by Ipilimumab Induces Complete Response in Metastatic Melanoma of the Lung but with Severe Hepatotoxicities (2016)

Since nivolumab significantly prolongs survival in patients with metastatic melanoma, the number of patients administered nivolumab is increasing, but only 30-40% of patients who received nivolumab monotherapy experienced objective tumor regression. Therefore, enhancing its anti-tumor immune response is of great interest to dermato-oncologists. In this report, we present a case of multiple metastatic melanomas in the lung successfully treated with nivolumab (2 mg/kg every 3 weeks for 12 weeks) followed by ipilimumab (3 mg/kg every 3 weeks for 9 weeks), but with severe liver dysfunction.
The ubiquitination code: a signalling problem (2007)

Ubiquitin is a highly versatile post-translational modification that controls virtually all types of cellular events. Over the past ten years we have learned that diverse forms of ubiquitin modifications and of ubiquitin binding modules co-exist in the cell, giving rise to complex networks of protein:protein interactions. A central problem that continues to puzzle ubiquitinologists is how cells translate this myriad of stimuli into highly specific responses. This is a classical signalling problem. Here, we draw parallels with the phosphorylation signalling pathway and we discuss the expanding repertoire of ubiquitin signals, signal tranducers and signalling-regulated E3 enzymes. We examine recent advances in the field, including a new mechanism of regulation of E3 ligases that relies on ubiquitination.
CASFET: A MOSFET-JFET cascode device with ultralow gate capacitance (1984)

A field-effect transistor is described that combines a short-gate MOSFET with a long-channel JFET in a cascode configuration. The composite device, a CASFET, can have a very low input capacitance due to the short gate of the MOSFET combined with the reduced Miller capacitance of the cascode. The long channel of the JFET insures that the CASFET has high output resistance. This paper discusses CASFET fabrication, performance, and modeling.
Stage 5 Retinopathy of Prematurity: Then and Now (2006)

Associated Retinal Consultants, P.C., Royal Oak, Michigan The authors have no proprietary interests in this article. Reprint requests: Antonio Capone Jr., MD, 632 Medical Office Building, 3535 West 13 Mile Road, Royal Oak, MI 48073; e-mail: [email protected].
Plasminogen Activator Inhibitor-1 Activity in Type 2 Diabetes (2008)

These data support mounting evidence that a higher PAI-1 plasma level is independently associated with a lower risk of retinopathy but a higher risk of CHD in type 2 diabetes.
Electric Field Control of Magnetic Permeability in Co-Fired Laminate Magnetoelectric Composites: A Phase-Field Study for Voltage Tunable Inductor Applications (2020)

Control of magnetic permeability through electric field in magnetoelectric materials promises to create novel voltage tunable inductors (VTIs). VTIs synthesized using co-fired ceramic processing exhibit many advantages over traditional epoxy bonding method, but the internal residual stress in co-fired VTIs resulting from thermal expansion mismatch hinders a full exploitation of the tunability of permeability. To find the optimal condition for high tunability of co-fired VTIs, domain-level phase field modeling and computer simulation are employed to study co-fired magnetoelectric composites comprising NiZn ferrite and PZT. Two key factors important toward increasing the inductor tunability are systematically investigated: intrinsic magnetocrystalline anisotropy of the ferrite material and internal residual stress caused by the co-firing process. The simulations indicate that in order to achieve a large tunability, the tuned permeability should be confined within the linear region of the reciprocal of susceptibility and stress. Additionally, both magnetocrystalline anisotropy and residual stress should be as small as possible. These results provide a design strategy for realizing high-tunability co-fired VTIs.
Type 1 Plili of Citrobacter freundii Mediate Invasion into Host Cells (2005)

Citrobacter freundii, originally designated Salmonella ballerup, are Gram-negative, motile rod-shaped bacteria of the family Enterobacteriaceae. They are wide spread in nature and can be found in the environment in soil and water as well as in foodstuffs. Citrobacter freundii was also isolated from a wide variety of animals like household pets, birds, cattle and fish. Although C. freundii is often considered a commensal of the human intestinal flora, this organism may cause urinary tract infections, diarrhea and severe cases of gastritis, wound infections and nosocomial infections like pneumonia and rarely meningitis in newborns. Several probable virulence factors have been identified in C. freundii. Citrobacter isolates are often multidrug resistant. In addition, some of the corresponding antibiotic resistance genes (e.g. tetracycline, chloramphenicol, streptomycin) are located on transferable plasmids. The production of toxins has also been reported for C. freundii strains. Isolates from humans and beef samples were positive for the production of Shiga(-like) toxin II. This toxin is much likely involved in enteropathogenicity caused by C. freundii. Futhermore, strains from patients with diarrhea produced a heat-stable enterotoxin identical to the 18-amino-acid Escherichia coli heat-stable enterotoxin STIa. Another probable virulence factor is a capsule, which is closely related to the Vi capsule of Salmonella typhi. Finally, invasion ability for several cell lines has been observed. Invasiveness in vivo would provide C. freundii with several advantages. Intracellular localization would result in protection from the host’s (humoral) immune system, from the action of many antibiotics and could therefore prolonge the infection time. Invasion ability could also
An unusual structure of the hydrated sodium chloride complex of cryptand [2.2.2] (1995)

Abstract The solid state structure of the Na[2.2.2]C1 · 3H 2 O complex has the sodium ion displaced towards one of the cryptand nitrogens and the chloride and water molecules associated by hydrogen bonds to form a pseudo cube with two chloride ions at opposite corners of the cube and water oxygens at the other six corners.
The Influence of Axial Flux Leakage from Motor Coils on the Magnetic Bearing and Shielding Measures (2023)

In the high-speed and compact magnetic levitation motor, the distance between the motor and the magnetic bearing is close. The axial flux leakage of the motor coil, introduced to the magnetic bearing easily, causes interference in the magnetic circuit of the magnetic bearing. This paper reports the crosstalk between the motor armature field and the magnetic field of the nearby magnetic bearing for the first time. The key factors affecting the magnetic field interference are explored, and the corresponding magnetic shielding measure is proposed.
A Numerical Investigation on the Influence of Lateral Boundaries in Linear Vibrating Cascades (2002)

The effect of the finite extent of linear cascades on the unsteady pressure distribution of vibrating blades is assessed by means of a numerical study. The span of a reference cascade made up of flat plates has been changed to investigate its influence on the computed influence coefficients. It is concluded that the number of passages required to match a solution obtained with a traveling-wave mode strongly depends on the inter-blade phase angle under consideration and that existing linear vibrating cascade facilities have a marginal resolution to accurately match CFD analysis that assume that the blade is vibrating in a traveling-wave mode.
Extending business objects with business rules (2002)

It is common to embed business rules within the code of distributed object systems. When business practices and/or policies change, as they often do, it is difficult if not impossible to correctly reflect those changes in the applications implementing them. The paper describes a framework that enables enterprises to develop distributed business applications that systematically externalize the time- and situation-variable parts of their business logic as externally applied entities called business rules. Decoupling business rules from the application can provide a number of advantages. Because business rules are external to the applications that depend upon them, the variable business logic contained in them can easily be changed. Because the management of the externalized business rules is done explicitly through a rule management facility, it is easy to understand what rules exist and to locate those that need to be changed. The Accessible Business Rule (ABR) framework is available as early test function in IBM Component Broker 2.0 and 3.0 (a part of WebSphere Enterprise).
3,3-Dialkyl- and 3-Alkyl-3-Benzyl-Substituted 2-Pyrrolidinones:  A New Class of Anticonvulsant Agents (1996)

A series of 3,3-dialkyl- and 3-alkyl-3-benzyl-substituted 2-pyrrolidinones (lactams) have been prepared and evaluated for their anticonvulsant activities. In the pentylenetetrazole mouse seizure model, 3,3-diethyl lactam 7c and 3-benzyl-3-ethyl lactam 7j are the most effective anticonvulsants (ED50 = 46 and 42 mg/kg, respectively) and have protective index (PI = TD50/ED50) values of 5.65 and 3.00, respectively. These protective index values compare favorably to those of the clinically used antiepileptic drugs ethosuximide (ED50 = 161 mg/kg), phenobarbital (ED50 = 22 mg/kg), and valproic acid (ED50 = 133 mg/kg), which have PI values of 2.35, 4.00, and 2.12, respectively. The benzyl compounds [3-substituents are Bn, H (7h); Bn, Me (7i); and Bn, Et (7j)] are also very effective anticonvulsants against seizures induced by maximal electroshock (ED50 = 41, 55, and 74 mg/kg, respectively) and have PI values of 3.51, 3.04, and 1.70, respectively. The corresponding PI values for phenobarbital and valproic acid are 1.37 and 5.18, respectively. As a class of anticonvulsants, the 3,3-disubstituted 2-pyrrolidinones have a broad spectrum of action and may be useful for the treatment of human epilepsies.
Progress in EUV resists for contact holes printing using EUV interference lithography (2019)

Using high-resolution extreme ultraviolet interference lithography (EUV-IL), we investigated contact hole/pillars printing performance of several EUV resist platforms for the high-NA EUV lithography. We compared the dose and local critical dimension uniformity (LCDU) of the three chemically-amplified resists (CARs) with the best performance for printing contact holes (CHs) at half pitch (HP) of 24 and 20 nm. One of the CARs showed the lowest LCDU, 2.3 and 2.2 nm with lowest dose 16.4 and 21.1 mJ/cm<sup>2</sup> for HP 24 and 20 nm, respectively. With the inorganic resist we obtained 38.8 mJ/cm<sup>2</sup> with an LCDU of 1.3 nm for HP 20 nm pillars. We have also studied the effects of the resist thickness and post-exposure baking (PEB) temperature on the dose and LCDU. These results show that there are promising CAR and non-CAR resists for CH printing towards high-NA EUVL.
Gate-Level Mitigation Techniques for Neutron-Induced Soft Error Rate (2005)

Neutron-induced single-event upsets have become increasingly problematic in aggressively scaled process technologies due to smaller nodal capacitances and reduced operating voltages. We present a probability-based analysis of neutron strikes on combinational logic chains and investigate techniques to increase circuit robustness in terms of decreasing the probability of upsetting the capturing latch given a particle strike. We show that using a technique of inserting simple cross-coupled inverter pairs on error prone sites, as well as intelligently placing lower V/sub th/ devices and readjusting device width, can increase the robustness by nearly 20% thereby increasing the mean time between soft errors by almost 25%. This technique incurs substantially less overhead than traditional redundancy approaches to mitigating soft errors.
Biosynthesis of chloramphenicol in Streptomyces sp. 3022a. Properties of an aminotransferase accepting p-aminophenylalanine as a substrate (1978)

In the presence of alpha-ketoglutarate, cell-free extracts of Streptomyces species 3022a catalysed transfer of the amino group from p-aminophenylalanine, yielding an unstable product similar to that obtained by the action of D- and L-amino acid oxidases on the amino acid. The enzyme, purified 16-fold from cell homogenates by chromatography on ion-exchange celluloses, hydroxyapatite, and cross-linked dextran gel, has a molecular weight of 90 000 and a broad pH optimum at 8.0. It is active with L-phenylalanine and L-tyrosine as well as p-amino-DL-phenylalanine as amino donors, and its relative activity towards these substrates did not change during purification. Polyacrylamide disc-gel electrophoresis of the partially purified enzyme gave single zones with identical mobility when the gels were assayed for activity with p-aminophenylalanine and tyrosine as amino donors. The results indicate that synthesis of p-aminophenylalanine en route to chloramphenicol uses a multispecific aminotransferase for aromatic amino acids. With L-phenylalanine as substrate, the preferred amino-accepting co-substrate was alpha-ketoglutarate. Some kinetic constants for the enzyme were determined, and its requirement for pyridoxal phosphate was demonstrated.
Design and Development of H∞ and μ-Synthesis Controllers for Nanorobotic Manipulation and Grasping Applications (2007)

This paper presents the development of H∞ and μ-synthesis robust controllers for nanorobotic manipulation and grasping applications. Here a 3 DOF (Degrees Of Freedom) nanomanipulator with RRP (Revolute Revolute Prismatic) actuator arrangement is considered for nanomanipulation purposes. Due to the sophisticated complexity, and expected high level of accuracy and precision (of the order of 10−7 rad in revolute actuators and 0.25 nm in the prismatic actuator) of the nanomanipulator, there is a need to design a suitable controller to guarantee an accurate manipulation process. However, structure of the nanomanipulator employed here, namely MM3A, is such that the dynamic equations of motion of the nanomanipulator are highly nonlinear and complicated. Linearizing these dynamic equations of the nanomanipulator simplifies the controller design process significantly. However, linearization could suppress some critical information about the system dynamics. In order to achieve the precise motion of the nanomanipulator utilizing the simple linearized model, H∞ and μ-synthesis robust controller design approaches are proposed. Following the development of the controllers, numerical simulations of the proposed controllers on the nanomanipulator are used to verify the positioning performance.
Variations de la composition chimique des eaux de drainage et de ruissellement, modifications des caractères agronomiques des sols après incendie de forêt dans le bassin versant du Rimbaud (Var, France)/Change of chemical composition of drainage and runoff waters and modification of soil agronomical characteristics after a forest fire in the Rimbaud catchment (Var, France) (1998)

Resume En août 1990, un incendie a ravagé plus de 8000 ha de forêt et de maquis dans la partie occidentale du massif des Maures. Les conséquences du feu sur les caractéristiques agronomiques des sols (de type ranker) et sur la composition chimique des eaux de drainage et de ruissellement ont été étudiées sur le bassin versant gneissique du Rimbaud (1,46 km2). L'exploitation d'une parcelle expérimentale (75 m2) a montré que l'influence de l'incendie sur la composition chimique des eaux de ruissellement superficiel s'est essentiellement concentrée au cours de la première année. Elle s'est notamment manifestée par une augmentation sensible des teneurs en silice, calcium, potassium et ions bicarbonates. Les valeurs maximales du pH, de la conductivité et des teneurs en silice, calcium, potassium, ions bicarbonates et ions sulfates ont nettement diminué entre 1990-1991 et les années suivantes. La baisse des teneurs s'était déjà nettement manifestée en 1990-1991. Pour les ions nitrates et l'ammonium, la combustion des végétaux n'a pas fourni des conditions favorables à des teneurs élevées (volatilisation de l'azote, modification de la micro- flore). Le passage du feu a provoqué un appauvrissement en matière organique et une diminution de la capacité d'échange cationique de l'horizon superficiel (An) des sols. La capacité d'échange, ordinairement sous-saturée, arrive à saturation tout en perdant du calcium, du magnésium et du potassium échangeables. La valeur moyenne du pH s'est élevée de 5,2 à 6,9. L'horizon A12 montre (entre 5 et 15 cm de profondeur) un enrichissement en calcium, magnésium et potassium échangeables. Des caissons lysimétriques ont été implantés en septembre 1991, en terrain incendié et sous couvert végétal. L'interprétation des données est délicate. Il semble toutefois que les effets de l'incendie se soient surtout marqués par un accroissement des exportations de calcium et de magnésium, et par une augmentation très nette de celles de silice et d'ions nitrates. Au cours de la deuxième année après le feu, les teneurs en ions nitrates se sont effondrées en terrain incendié.
Absorptionless self phase modulation in a "dark state" electromagnetically induced transparency system (2002)

Summary form only given. The field of quantum optics was greatly enriched with the discovery of dark states and electromagnetically induced transparency (EIT). Although these two processes give similar effects, they are distinctly different. Dark states (Gray et al, 1978) are quantum states created in a three-level lambda system that is decoupled from the excited state. Some of the main features are zero linear absorption, no population in the excited state and no spontaneous emission. One limiting factor of a dark state system is that self-phase modulation disappears together with absorption. EIT is a nonlinear effect that can provide transparency to a probe field in a variety of systems. Much work has been done on two-level, cascaded-three-level and even four-level systems. It has also been shown that a large third-order nonlinear susceptibility is present in the absence of absorption. However, spontaneous emission cannot be eliminated in such system, thereby limiting their applications, particularly, to squeezed light generation. Here, we combine the effects of both dark state and EIT to create a system that is suitable for squeezed light generation via self phase modulation.
Structural analysis of the role of the p3 subunit of the αVβ3 integrin in IGF-I signaling (2001)

The disintegrin echistatin inhibits ligand occupancy of the alpha V beta 3 integrin and reduces Insulin-like growth factor I (IGF-I) stimulated migration, DNA synthesis, and receptor autophosphorylation in smooth muscle cells. This suggests that ligand occupancy of the alpha V beta 3 receptor is required for full activation of the IGF-I receptor. Transfection of the full-length beta 3 subunit into CHO cells that have no endogenous beta 3 and do not migrate in response to IGF-I was sufficient for IGF-I to stimulate migration of these anchorage dependent cells. In contrast, transfection of either of two truncated mutant forms of beta 3 (terminating at W(715) or E(731)) or a mutant with substitutions for Tyr(747) Tyr(759) (YY) into either CHO or into porcine smooth muscle cells did not restore the capacity of these cells to migrate across a surface in response to IGF-I. This effect was not due to loss of IGF-I receptor autophosphorylation since the response of the receptor to IGF-I was similar in cells expressing either the full-length or any of the mutant forms of the beta 3 subunit. Echistatin reduced IGF-I receptor phosphorylation in cells expressing the full-length or the YY mutant forms of beta 3 subunit, but it had no effect in cells expressing either of two truncated forms of beta 3. A cell-permeable peptide homologous to the C-terminal region of the beta 3 subunit (amino acids 747-762) reduced IGF-I stimulated migration and receptor autophosphorylation of non-transfected porcine smooth muscle cells. These results demonstrate that the full-length beta 3 with intact tyrosines at positions 747 and 759 is required for CHO cells to migrate in response to IGF-I. Furthermore, a region of critical amino acids between residues 742-762 is required for echistatin to induce its regulatory effect on receptor phosphorylation. Since the IGF-I receptor does not bind to alpha V beta 3 the results suggest that specific but distinct regions of the beta 3 subunit interact with intermediary proteins to facilitate IGF-I stimulated cell migration and echistatin induced inhibition of IGF-I signal transduction.