gebhart/patrepeval huggingface dataset:
The basis for a heat-induced developmental defect: defining crucial lesions. (1995)

Because lethal heat shocks perturb a multitude of cellular processes, the primary lesions responsible for death from heat stress remain to be defined. In Drosophila, sublethal heat treatments produce developmental anomalies that frequently mimic the effects of known mutations and are hence referred to as phenocopies. Mutations subject to phenocopy mimicry provide signposts to those biological processes most sensitive to heat and most important for the function and survival of the organism as a whole. We have analyzed a particular developmental defect inducible in early embryos of Drosophila melanogaster. By molecular, phenotypic, and genetic criteria, we have found extensive parallels between this phenocopy and certain dominant mutations in the segmentation gene fushi tarazu (ftz). Our analysis of this phenocopy indicates that the crucial lesion is interference with proper turnover of ftz protein, resulting in ftz overexpression. Our results provide a novel explanation for a heat-induced developmental defect. Perturbations in relative amounts of important regulatory proteins may be a common mechanism by which heat-shock phenocopies arise.
Spirobiacridine-based Host Material for Highly Efficient Blue Phosphorescent Organic Light-emitting Devices (2020)

Although spirobiacridine (SBA) derivatives show a promising potential not only for thermally activated delayed fluorescent (TADF) emitters but also as host material for blue phosphorescent emitters, only limited research has been reported in the literature. Here, we developed an SBA-based host material, mCN-SBA, which realized a blue phosphorescent OLED with an external quantum efficiency of 19.8%, and Commission Internationale de l'Éclairage (CIEx,y) of (0.16, 0.23). We developed a spirobiacridine (SBA)-based high triplet energy host material, mCN-SBA for blue phosphorescent emitter, (dfpypy)2Ir(acac). mCN-SBA realized a blue phosphorescent OLED with a maximum external quantum efficiency of 19.8%, and color coordinates of (0.16, 0.23).
Free-Standing Mechanical and Photonic Nanostructures in Single-Crystal Diamond (2012)

A variety of nanoscale photonic, mechanical, electronic, and optoelectronic devices require scalable thin film fabrication. Typically, the device layer is defined by thin film deposition on a substrate of a different material, and optical or electrical isolation is provided by the material properties of the substrate or by removal of the substrate. For a number of materials this planar approach is not feasible, and new fabrication techniques are required to realize complex nanoscale devices. Here, we report a three-dimensional fabrication technique based on anisotropic plasma etching at an oblique angle to the sample surface. As a proof of concept, this angled-etching methodology is used to fabricate free-standing nanoscale components in bulk single-crystal diamond, including nanobeam mechanical resonators, optical waveguides, and photonic crystal and microdisk cavities. Potential applications of the fabricated prototypes range from classical and quantum photonic devices to nanomechanical-based sensors and actuators.
Targeting Cathepsin E in Pancreatic Cancer by a Small Molecule Allows In Vivo Detection (2013)

When resectable, invasive pancreatic ductal adenocarcinoma (PDAC) is most commonly treated with surgery and radiochemotherapy. Given the intricate local anatomy and locoregional mode of dissemination, achieving clean surgical margins can be a significant challenge. On the basis of observations that cathepsin E (CTSE) is overexpressed in PDAC and that an United States Food and Drug Administration (FDA)-approved protease inhibitor has high affinity for CTSE, we have developed a CTSE optical imaging agent [ritonavir tetramethyl-BODIPY (RIT-TMB)] for potential intraoperative use. We show nanomolar affinity [half maximal inhibitory concentration (IC50) of 39.9 ± 1.2 nM] against CTSE of the RIT-TMB in biochemical assays and intracellular accumulation and target-to-background ratios that allow specific delineation of individual cancer cells. This approach should be useful for more refined surgical staging, planning, and resection with curative intent.
Migraine and Headache (2009)

Abstract Headaches afflict 70% of the population with 12%, or 30 million adult Americans, suffering from migraines. Due to co-morbidities, up to 30% of patients seen in primary care settings suffer from migraines. Medical care provided to these headache sufferers is often suboptimal. Part of the ‘Oxford American Pain Library,’ this concise handbook provides primary care doctors and other health care professionals with practical information about the diagnosis and management of headache in their patients. The book covers the classification of headaches and provides shortcuts to making an accurate diagnosis, along with recommendations for the proper utilization of diagnostic procedures. Common headache conditions discussed include migraine, chronic migraine, status migraine, cluster and related headaches, tension headaches, sinus headaches, cervicogenic headaches, secondary headaches, and neuralgias. The book provides a comprehensive review of pharmacological treatments such as antihypertensive agents, anticonvulsants, antidepressants, 5HT1 agonists (triptans), as well as a discussion of the scientific basis of non-drug treatments. Representative cases are presented to aid the integration of factual knowledge with practical approaches. The book is concise yet comprehensive, scientific as well as practical, filled with facts, but highly readable. The small format makes it portable as well as affordable.
Adenovirus-Mediated PD-L1 Over-Expression Has Differential Effects on Allograft Survival in Murine Islet and Heart Transplant Models. (2004)

Abstract Program death-1 (PD-1) is a negative regulator of the immune system. Blocking PD-1-mediated negative signaling accelerates autoimmune diseases, while engaging PD-1 with recombinant PD-L1Ig fusion protein potentiates the efficacy of co-stimulation blockade in prolonging allograft survival. However, soluble PD-L1Ig itself showed no graft-protecting effect, in contrast to its strong inhibition of T and B cell activation in vitro when applied in a plate-bound form. In this study, we tested the hypothesis that membrane-bound PD-L1 should prolong allograft survival due to its increased ability to crosslink PD-1 receptor. An adenovirus (Ad.PD-L1) was constructed to encode the full-length mPD-L1, followed by green fluorescent protein (GFP) gene linked by an IRES sequence. A control adenovirus (Ad.Ctrl) was similarly constructed that carries only the GFP gene. In islet transplant model, B6AF1 (H-2b/a) islets were infected with the adenoviruses, and then transplanted into C57BL/6 (H-2b) mice induced diabetic by streptozotocin. In heart transplant model, DBA/2 (H-2d) hearts were perfused with adenoviruses, and then transplanted into C57BL/6 mice. PD-L1 over-expression in islet did not prolong graft survival, but accelerated islet rejection (Ad.PD-L1: 9.0+/−3.5 days; Ad.Ctrl: 13.3+/−2.2 days). In contrast, infection with Ad.PD-L1 prolonged heart allograft survival (15.4+/−5.7 days) in C57BL/6 mice, which promptly rejected DBA/2 hearts (7.0+/−2.3 days, p&lt;0.02). Thus, over-expression of membrane-bound PD-L1 has beneficial effect in an organ/tissue specific manner. Strategies other than direct expression of PD-L1 in the islet b cells need to be devised in order to utilize this negative pathway to prevent rejection.
Mean stream coordinates structure of the Subantarctic Front: Temperature, salinity, and absolute velocity (2003)

The mean synoptic structure of the northern, strongest branch of the Antarctic Circumpolar Current southwest of Tasmania, at the Subantarctic Front (SAF), is estimated by a stream coordinates analysis of data from overlapping arrays of Inverted Echo Sounders (IESs) and Horizontal Electric Field Recorders deployed during the 1995–1997 Sub‐Antarctic Flux and Dynamics Experiment. The stream coordinates are derived from a daily objective mapping of the temperature field obtained from combining the IES travel time measurements with an empirical look‐up table constructed from the extensive hydrography acquired during WOCE. Full‐water‐column stream‐coordinates sections of temperature, Salinity, and absolute velocity are presented and compared with prior observations. The along‐stream current has a single peak with surface velocities reaching about 50 cm s −1 . The vertical structure of the along‐stream velocity is roughly consistent with a combined external and first internal normal mode description that is adapted to the buoyancy frequency as it varies across the front, although there are some significant differences. The cross‐stream structure of along‐stream velocity is very nearly symmetric about the jet axis, but the lateral shear magnitude is slightly larger on the cold side of the SAF. Separating the baroclinic and barotropic currents reveals that the SAF currents are diffluent, primarily baroclinically, in the cross‐stream direction. Baroclinic cross‐stream diffluence of approximately 0.23 Sv per km (Sv = 10 6 m 3 s −1 ), or about 16 Sv per degree of longitude at 51°S. The 2‐year mean total SAF transport is 75 Sv (for a 220 km width); the barotropic contribution is small (8 Sv) but not negligible.
Right to left differences in the ankle joint complex range of motion (1994)

Rehabilitation of the ankle joint complex after injury is often considered complete when the injured ankle has the same range of motion and strength as the uninjured contralateral limb even though this symmetry has never been quantified. The purpose of this investigation was to determine whether there were differences in the ankle joint complex range of motion between right and left legs. Total right and left ankle joint complex range of motion was measured on 18 subjects using a fixture allowing six degrees of freedom. A four-camera video system was used to record all range of motion movements. The results indicated that total dorsiflexion-plantarflexion, eversion-inversion, and abduction-adduction ranges of motion were not significantly different between right and left legs. However, separate abduction and adduction differences occurred, with the right foot tending to abduct more than the left, while the left foot tended to adduct more than the right. These differences in the abduction and adduction range of motion may be inherent in the measuring device. As a result of this study, it appears that the contralateral ankle joint complex can be used as a measure for establishing restoration of total range of motion of the ankle joint complex following injury.
Computational Tools And Resources For Metabolism-Related Property Predictions. 2. Application To Prediction Of Half-Life Time In Human Liver Microsomes (2012)

In many cases, the accuracy of prediction achieved on one external test set did not correspond to the results achieved with another test set. The most predictive models were used for predicting the metabolic stability of compounds from the open NCI database, the results of which are publicly available on the NCI/CADD Group web server ( http://cactus.nci.nih.gov ).
Oriented Attachment-Based Assembly of Dendritic Silver Nanostructures at Room Temperature (2006)

How particles aggregate into an interesting dendritic structure has been the object of research for many years because of its importance in understanding physical processes involved and in designing novel materials. In this work, we for the first time describe an oriented attachment-based assembly mechanism for formation of different types of dendritic silver nanostructures at room temperature. It is found that the concentration of both AgNO(3) and p-aminoazobenzene (PA) molecules has a significant effect on the formation and growth of these novel nanostructures. Characterization by transmission electron microscopy (TEM) clearly shows that the dendritic silver nanostructures can be obtained through the preferential oriented growth along a crystallographically special direction. Interestingly, we observe that the oriented attachment at room temperature can also take place between relatively large single-crystalline silver particles with a diameter range from 20 to 60 nm, which may provide a new possibility for the design of novel metal nanostructures by using large metal nanoparticles as building blocks at room temperature. Moreover, a surface-enhanced Raman scattering (SERS) technique is used to investigate the role of PA molecules during the growth of the dendritic silver nanostructures.
3D Characterization of the Refractive-Index and Residual-Stress Distributions in Optical Fibers (2011)

Refractive-index and residual-stress distributions of optical fibers exposed to a focused carbon-dioxide laser beam are characterized. Azimuthal and longitudinal variations are measured. Changes of 10-4 in index and 0.2 MPa in stress are resolvable.
Extended Abstract: Complex Offshore Well Intervention Now Possible by Using Thru-Tubing Bridge Plug to Produce By-Pass Zone and Isolate Lower Production Zone (2023)

Abstract Isolating lower production zone (water shut-off) and finding new perforation intervals from another reservoir zone is a typical well intervention application in mature fields. In normal conditions, legacy permanent barriers (Through Tubing Bridge Plugs -TTBP) have been used in those applications very successfully. However, challenges are posed by, well bore restrictions (passing smaller OD restrictions), rig height, reliability and setting validations with legacy tools in harsh environments and well conditions. This paper discusses the challenges during offshore well intervention operation in Indonesia due to the limited space for rig-up, limited crane lifting capability, and un-manned well platform with only daylight operation and the solutions for these challenges with new slim-sized TTBP technology and the slim-sized Pulsed Neutron tool. Critical success factors of this operation included providing valid gas saturation data by using a 1 11/16" Pulsed Neutron tool (TMD3D) to determine the remaining gas in producing interval and any bypassed opportunities; establishing enough force by using a slim size electromechanical setting tool (DPU) to set the 1 11/16" TTBP at the desired depth and establishing a mechanical barrier which can hold up to 1200 psi differential pressure until a cement cap can be established; and running a perforation simulation to select the right gun to create an effective perforation tunnel between the wellbore and the formation for optimized gas production from the bypass zone. Despite all the challenges, a good mechanical barrier was established to isolate the lower water production zone and successfully determine gas saturation in bypassed reservoirs by using the Pulsed Neutron data. Perforation intervals were selected with the pulsed neutron analysis. After perforation, significant gas production was established which was 50% higher than predicted. New slim-sized technology tools resulted in flawless job execution with their high reliability and cost-effective solutions without any service quality issues. In addition to increased gas production, efficient operation resulted by completing the job one week earlier than scheduled, which provided extra cost savings. This case study identified the challenges in complex well intervention operations and provides a valuable water shut off solution by using new 1 11/16" TTBP and 1 11/16" DPU technology. The solution has proven to provide tremendous cost saving for production enhancement activity.
Detrusor Pressure Estimation from Single-Channel Urodynamics (2022)

Urodynamics is the current gold-standard for diagnosing lower urinary tract dysfunction, but uses non-physiologically fast, retrograde cystometric filling to obtain a brief snapshot of bladder function. Ambulatory urodynamics allows physicians to evaluate bladder function during natural filling over longer periods of time, but artifacts generated from patient movement necessitate the use of an abdominal pressure sensor, which makes long-term monitoring and feedback for closed-loop treatment impractical. In this paper, we analyze the characteristics of single-channel bladder pressure signals from human and feline datasets, and present an algorithm designed to estimate detrusor pressure, which is useful for diagnosis and treatment. We utilize multiresolution analysis techniques to maximize the attenuation of probable abdominal pressure components in the vesical pressure signal. Results indicate a strong correlation, averaging 0.895 ± 0.121 (N = 40) and 0.812 ± 0.113 (N = 16) between the estimated detrusor pressure obtained by the proposed method and recorded urodynamic data from human and feline subjects, respectively. Clinical Relevance- This work establishes that signal pro-cessing techniques may be applied to vesical pressure alone to accurately reconstruct pressures generated independently by the detrusor muscle. This is relevant for emerging sensors that measure vesical pressure alone or for data analysis of bladder pressure in ambulatory subjects which contains significant abdominal pressure artifacts.
Differential activation of mitochondrial apoptotic pathways by vasculotropic amyloid‐β variants in cells composing the cerebral vessel walls (2009)

Cerebral amyloid angiopathy (CAA) is an age-associated condition and a common finding in Alzheimer's disease in which amyloid-beta (Abeta) vascular deposits are featured in >80% of the cases. Familial Abeta variants bearing substitutions at positions 21-23 are primarily associated with CAA, although they manifest with strikingly different clinical phenotypes: cerebral hemorrhage or dementia. The recently reported Piedmont L34V Abeta mutant, located outside the hot spot 21-23, shows a similar hemorrhagic phenotype, albeit less aggressive than the widely studied Dutch E22Q variant. We monitored the apoptotic events occurring after stimulation of human brain microvascular endothelial and smooth muscle cells with nonfibrillar structures of both variants and wild-type Abeta40. Induction of analogous caspase-mediated mitochondrial pathways was elicited by all peptides, although within different time frames and intensity. Activated pathways were susceptible to pharmacological modulation either through direct inhibition of mitochondrial cytochrome c release or by the action of pan- and pathway-specific caspase inhibitors, giving a clear indication of the independent or synergistic engagement of both extrinsic and intrinsic mechanisms. Structural analyses of the Abeta peptides showed that apoptosis preceded fibril formation, correlating with the presence of oligomers and/or protofibrils. The data support the notion that rare genetic mutations constitute unique paradigms to understand the molecular pathogenesis of CAA.
VB-201, an oxidized phospholipid small molecule, inhibits CD14- and Toll-like receptor-2-dependent innate cell activation and constrains atherosclerosis (2013)

Atherosclerosis is an inflammatory disease of the vascular wall. Activated monocytes and dendritic cells (DC) in the intima layer of the vasculature promote atherogenesis. Toll-like receptor (TLR)-2 and TLR-4, which are predominantly expressed on these cells and mediate their activation, are essential for atherosclerosis development. In this study we demonstrate that VB-201, an oxidized phospholipid (Ox-PL) small molecule, inhibits TLR signalling restricted to TLR-2 and TLR-4 in human and mouse monocytes and DC. Mechanistically, we show that VB-201 binds directly to TLR-2 and CD14, the TLR-4 co-receptor, to impair downstream cues and cytokine production. In a rabbit model, oral administration of VB-201 constrained atherosclerosis progression. This effect was not due to reduced cholesterol abundance, as hyperlipidaemia was sustained. We suggest that VB-201 may counter inflammation where TLR-2 and/or CD14 complicity is essential, and is therefore beneficial for the treatment of atherosclerosis.
Fosmanogepix (APX001) Is Effective in the Treatment of Pulmonary Murine Mucormycosis Due to Rhizopus arrhizus (2020)

Mucormycosis is a life-threatening infection with high mortality that occurs predominantly in immunocompromised patients. Manogepix (MGX) is a novel antifungal that targets Gwt1, a protein involved in an early step in the conserved glycosylphosphotidyl inositol (GPI) posttranslational modification pathway of surface proteins in eukaryotic cells. Inhibition of fungal inositol acylation by MGX results in pleiotropic effects, including inhibition of maturation of GPI-anchored proteins necessary for growth and virulence. MGX has been previously shown to have <i>in vitro</i> activity against some strains of Mucorales. Here, we assessed the <i>in vivo</i> activity of the prodrug fosmanogepix, currently in clinical development for the treatment of invasive fungal infections, against two <i>Rhizopus arrhizus</i> strains with high (4.0 μg/ml) and low (0.25 μg/ml) minimum effective concentration (MEC) values. In both invasive pulmonary infection models, treatment of mice with 78 mg/kg or 104 mg/kg fosmanogepix, along with 1-aminobenzotriazole to enhance the serum half-life of MGX in mice, significantly increased median survival time and prolonged overall survival by day 21 postinfection compared to placebo. In addition, administration of fosmanogepix resulted in a 1 to 2 log reduction in both lung and brain fungal burden. For the 104 mg/kg fosmanogepix dose, tissue clearance and survival were comparable to clinically relevant doses of isavuconazole (ISA), which is FDA approved for the treatment of mucormycosis. These results support continued development of fosmanogepix as a first-in-class treatment for invasive mucormycosis.
Efficacy and safety of adalimumab in Chinese patients with moderate‐to‐severe plaque psoriasis: results from a phase 3, randomized, placebo‐controlled, double‐blind study (2016)

In these Chinese patients with moderate-to-severe psoriasis, a significantly greater percentage treated with adalimumab compared with placebo achieved efficacy endpoints at week 12 and efficacy was sustained to week 24. Safety results were consistent with the known adalimumab safety profile; no new safety signals were identified in the 24 weeks of treatment.