gebhart/patrepeval huggingface dataset:
Induction of neonatal lupus in pups of mice immunized with synthetic peptides derived from amino acid sequences of the serotoninergic 5-HT4 receptor (2001)

We have previously suggested that the recognition of a cross-reactive epitope on the 5-HT4 receptor and the 52-kDa SSA/Ro protein by serotonin-antagonizing autoantibodies could explain the electrophysiological symptoms of congenital heart block in neonatal lupus. To confirm this hypothesis, we immunized female mice with four synthetic peptides corresponding to the recognized epitopes. All mice developed anti-peptide antibodies, which cross-reacted with the Ro52 and 5-HT4 receptor peptides and recognized both cognate proteins. Peptide-immune mice were mated. The pups from mice immunized with the Ro52 peptides had no symptoms of neonatal lupus apart from bradycardia. However, pups from mice immunized with the 5-HT4 receptor peptides and bradycardia, atrioventricular block of type I or II, longer QT intervals, skin rashes and neuromotor problems. The 5-HT4 receptor was detectable in the different fetal tissues affected (heart, skin and brain) by immunohistochemistry. Hearts from diseased pups were less developed and showed disorganized myocardial hyperplasia, compared to the normal littermates. These results demonstrate that the serotoninergic 5-HT4 receptor is the antigenic target of physiopathological autoantibodies in neonatal lupus.
Longitudinal Prospective Long-term Radiographic Follow-up After Treatment of Single-Level Cervical Disk Disease With the Bryan Cervical Disc (2010)

The device maintains preoperative motion at the index and adjacent levels, seems to protect against acceleration of adjacent-level degeneration as seen after anterior cervical discectomy and fusion, and remains securely anchored in the adjacent bone mass in the long run. Heterotopic ossification was frequently seen. The vast majority of all patients had a good to excellent clinical outcome.
J0404-4-3 Full-field monitoring of resin flow using area-sensor array in a VaRTM process (2010)

The current work investigates full-field monitoring of resin flow during a VaRTM using an area-sensor array. The squared area sensors are aligned as a matrix on a thin polyimide film without any un-sensing space; thus the film measures the full-field flow monitoring, and never misses a dry spot that may occur anywhere on the film. To identify the precise flow front and dry spots, the impregnated area is estimated by minimizing the residual sum of squares between the measured and estimated impregnated area ratios. To demonstrate the applicability of the proposed method, the area-sensor array is applied to monitoring a VaRTM resin flow on glass fiber reinforced plastic (GFRP) and foam-cored structures. As a result, the precise figurations of the flow front and the dry spot were successfully estimated in real time.
Immunological and electrophysiological characterization of T-cell subsets in inflammatory bowel diseases (2018)

Abstract Crohn’s Disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) characteristic of massive T-cell infiltration of the affected GI tract. CD is Th1-Th17 dominant whilst UC is considered as a Th2-Th17 prevailing disease. It is also known that ion channels play a crucial role in T-cell physiology and the expression profile is different among T-cell subsets. This differential expression allows ion channel-specific targeting of autoimmune diseases (e.g. psoriasis). Motivated by these findings we set out experiments to characterize the infiltration of inflamed GI tract by various T-cell subsets along with the subtype specific expression of ion channels in these cells. We isolated T-cells from biopsy specimens and blood samples of therapy naïve IBD patients (under the ethical approval of the Medical Research Council of Hungary). Following enzymatic (0.5 mg/ml collagenase IV and 250 IU/ml DNAse I) and mechanical disruption, T-cell subsets were separated using flow cytometry. Preliminary results indicate the following proportions of subsets in biopsy samples (% of CD4+ cells): 22.3% Th1, 16.0% Th2 and 25.1% Th17 in CD, while 17.0% Th1, 19.1% Th2, and 16.4% Th17 in UC. We developed electrophysiological techniques to monitor the activity of Kv1.3 and KCa3.1 channels whereas intracellular calcium imaging is used to characterize the functional expression of CRAC, TRPA1 and TRPV1 channels. Patients included in the study will be monitored for therapy follow-up: changes of T-cell subset distribution and ion channel function of subsets will be determined. Our main goal is to identify novel targets for IBD therapy that is of great importance if we consider that even the modern biological therapies often turn into ineffectiveness.
Estimating traffic density using transformer decoders (2023)

We propose a combined particle-based density prediction model consisting of three components: trajectory prediction for existing particles, entering particle prediction, and iterative sampling. At initialization, the combined model takes in a set of trajectories for trajectory prediction and a sequence of observation vectors for entering particle prediction. Then, the iterative sampling module generates the density prediction for the next time instance. It will also sample a pool of particles and pass on their trajectories to the next trajectory prediction model for future density prediction.
&lt;title&gt;Far Ultraviolet Spectroscopic Explorer optical system: lessons learned&lt;/title&gt; (2000)

The Far Ultraviolet Spectroscopic Explorer (FUSE) is a NASA astrophysics satellite designed to produce high resolution spectra in the far-ultraviolet (90.5-118.7 nm bandpass) with a high effective area (20-70 cm<SUP>2</SUP>) and low background detector. It was launched on a three-year mission in June 1999 aboard a Boeing Delta II rocket. The satellite has been performing routine science observations since December 1999. FUSE contains four co-aligned, normal incidence, off-axis parabolic primary mirrors which illuminate separate Rowland circle spectrograph channels equipped with holographically ruled diffraction gratings and microchannel plate detectors. Fine error sensors (slit jaw cameras) operating in the visible on two of the channels are used for target acquisition and guiding. The FUSE mission was first proposed in the late 1980s, and experienced several major conceptual changes prior to fabrication, assembly, and testing, which lasted from 1996 through 1999. During the program, we realized both positive and negative aspects to our design and processes that may apply to other space missions using telescopes and spectrographs. The specific topics we address are requirements, design, component specification, integration, and verification. We also discuss on-orbit alignment and focus. These activities were complicated by unexpected levels of motion between the optical elements, and the logistical problems associated with limited ground contact passes in low Earth orbit. We have developed methods to characterize the motions and mitigate their resultant effects on the science data through a combination of observing techniques and modifications to the data reduction software.
Inferring protein function in an emerging virus: detection of the nucleoprotein in Tilapia Lake Virus (2021)

Emerging viruses impose global threats to animal and human populations and may bear novel genes with limited homology to known sequences, necessitating the development of novel approaches to infer and test protein functions. This challenge is dramatically evident in tilapia lake virus (TiLV), an emerging orthomyxo-like virus that threatens the global tilapia aquaculture and food security of millions of people. The majority of TiLV proteins have no homology to known sequences, impeding functionality assessments. Using a novel bioinformatics approach, we predicted that TiLV’s Protein 4 encodes the nucleoprotein - a factor essential for viral RNA replication. Multiple methodologies revealed the expected properties of orthomyxoviral nucleoproteins. A modified yeast three-hybrid assay detected Protein 4-RNA interactions independent of the RNA sequence, and identified specific positively charged residues involved. Protein 4-RNA interactions were uncovered by R-DeeP and XRNAX methodologies. Immunoelectron microscopy found that multiple Protein 4 copies localized along enriched ribonucleoproteins. TiLV RNA from cells and virions co-immunoprecipitated with Protein 4. Immunofluorescence microscopy detected Protein 4 in the cytoplasm and nuclei, and nuclear Protein 4 increased upon CRM1 inhibition, suggesting CRM1-dependent nuclear export of TiLV RNA. Together, these data reveal TiLV’s nucleoprotein and highlight the ability to infer protein functionality, including novel RNA-binding proteins, in emerging pathogens. These are important in light of the expected discovery of many unknown viruses and the zoonotic potential of such pathogens.
Ethics and Naeopharmacy: Value Sensitive Design of New Drugs (2020)

Although applications are being developed and have reached the market, nanopharmacy to date is generally still conceived as an emerging technology. Its concept is ill-defined. Nanopharmacy can also be construed as a converging technology, which combines features of multiple technologies, ranging from nanotechnology to medicine and ICT. It is still debated whether its features give rise to new ethical issues or that issues associated with nanopharma are merely an extension of existing issues in the underlying fields. We argue here that, regardless of the alleged newness of the ethical issues involved, developments occasioned by technological advances affect the roles played by stakeholders in the field of nanopharmacy to such an extent that this calls for a different approach to responsible innovation in this field. Specific features associated with nanopharmacy itself and features introduced to the associated converging technologies- bring about a shift in the roles of stakeholders that call for a different approach to responsibility. We suggest that Value Sensitive Design is a suitable framework to involve stakeholders in addressing moral issues responsibly at an early stage of development of new nanopharmaceuticals.
Influence of areal density on the energy absorbed by thin composite plates subjected to high-velocity impacts (2012)

This work analyses the influence that the areal density of a composite thin-plate, made of glass-fibre woven laminates and subjected to high-velocity impact, exerts on perforation-threshold energy, contact time, and energy-absorption mechanisms. The perforation-threshold energy increased with the areal density. Also, the contact time increased at impact energies above the perforation-threshold energy and decreased below this threshold. The main energy-absorption mechanisms at impact energies close to that causing perforation were found to be the deformation and failure of the fibres, regardless of the areal density. For higher impact energies, the main mechanisms were fibre failure and the energy absorbed by acceleration of the laminate.
Final report of the Peña Blanca natural analogue project (2016)

The Peña Blanca region, 50 km north of Chihuahua City, Chihuahua, México, was a target of uranium exploration and mining by the Mexican government. After mining ceased in 1981, researchers became interested in this region as a study area for subsurface uranium migration with relevance to geologic disposal of nuclear waste. Many studies related to this concept were conducted at the Nopal I mine site located on a cuesta (hill) of the Sierra Peña Blanca. This site has geologic, tectonic, hydrologic, and geochemical similarities to Yucca Mountain, Nevada, a formerly proposed site for a high-level nuclear-waste repository in the unsaturated zone. The U.S. Department of Energy (U.S. DOE), Office of Civilian Radioactive Waste Management (OCRWM), sponsored studies at Nopal I in the 1990s and supported the drilling of three research wells – PB1, PB2, and PB3 – at the site in 2003. Beginning in 2004, the Peña Blanca Natural Analogue Project was undertaken by U.S. DOE, OCRWM to develop a three-dimensional conceptual model of the transport of uranium and its radiogenic daughter products at the Nopal I site.
Skill-Based Reinforcement Learning with Intrinsic Reward Matching (2022)

While unsupervised skill discovery has shown promise in autonomously acquiring behavioral primitives, there is still a large methodological disconnect between task-agnostic skill pretraining and downstream, task-aware finetuning. We present Intrinsic Reward Matching (IRM), which unifies these two phases of learning via the $\textit{skill discriminator}$, a pretraining model component often discarded during finetuning. Conventional approaches finetune pretrained agents directly at the policy level, often relying on expensive environment rollouts to empirically determine the optimal skill. However, often the most concise yet complete description of a task is the reward function itself, and skill learning methods learn an $\textit{intrinsic}$ reward function via the discriminator that corresponds to the skill policy. We propose to leverage the skill discriminator to $\textit{match}$ the intrinsic and downstream task rewards and determine the optimal skill for an unseen task without environment samples, consequently finetuning with greater sample-efficiency. Furthermore, we generalize IRM to sequence skills for complex, long-horizon tasks and demonstrate that IRM enables us to utilize pretrained skills far more effectively than previous skill selection methods on both the Fetch tabletop and Franka Kitchen robot manipulation benchmarks.
Deflexifol (a novel formulation of 5FU): Pharmacokinetics in a phase 1 trial in comparison to 5FU. (2017)

2530 Background: Simultaneous administration of 5-fluorouracil (5FU) and leucovorin (LV) is generally not feasible as 5FU and LV are chemically incompatible (CaPO4 crystals), so the maximum possible interaction for benefit is not achieved. Deflexifol, an all in one formulation of 5FU/LV with cyclodextrin (HP-β-CD 100mg/ml, 5-FU 15mg/ml &amp; LV 1mg/ml) at pH 7, was developed to overcome this problem. Methods: Limited sampling PK was done with dose 1 and 6 in a standard 3+3 phase I trial of Deflexifol given in two schedules (46-h infusion Q2W or bolus weekly x6) with no intrapatient dose escalation, at doses shown in Table. Sample times were infusion: 0, 2, 46h; bolus: 0, 0.2, 0.4, 1, 24h. 5FU and dihydroFU were measured as per Ackland et al, Anal Biochem 1997. 5FU AUC, clearance (CLR) and t1/2 were estimated for each patient to assess PK variability and adequacy of dosing compared to previous reports. Results: 40 patients were treated (21 infusion, 19 bolus, median age 67, 19 M, 21 F). The MTD(bolus) was 575 mg/m 2 , with no DLT in infusion schedule to 3600 mg/m 2 . PK showed substantial inter-patient variability – CLR(bolus) 21-900 L/h, t1/2 0.11-0.52 h, with intra-patient dose 6 CLR = 54-117% of dose 1, and a trend to increased AUC (mg/L.h) with dose (Table). Infusion CLR and AUC estimates were highly variable (CLR range 2-1200), with many cases with insufficient data. Compared to historical data with 5FU alone, AUC was likely subtherapeutic until 475mg/m 2 bolus and for many patients with infusion &lt;3000mg/m 2 . Conclusions: 5FU PK with Deflexifol is similar to 5FU alone. No evidence of saturation of kinetics over this dose range was seen, or induction of metabolism with repeated dosing. In each schedule AUC data supports the clinical impression of reduced toxicity at the same dose of 5FU. Accurate estimation of infusion PK requires more than 2 timepoints. PK in a phase II study is planned. Clinical trial information: 044867. [Table: see text]
Simulation of CVD Process by Boundary Integral Technique (1992)

The chemical vapor deposition process at atmospheric pressure has been investigated analytically and numerically with a model based on the continuum transport equation and the surface reaction kinetics. Specifically, a linear stability analysis has been carried out to find some critical parameters for the control of the deposition layer morphology, and numerical analysis based on the boundary integral technique has also been performed to understand critical factors in the step coverage control for the trenches of various geometries. From the analyses, it has been found that the ratio of gas phase diffusivity to the surface reaction rate constant (D/k) plays the most critical role in both the step coverage and morphology stability, while the surface migration and surface reaction kinetics have only minor effects on the step coverage.
N-acetylcysteine promotes long-term survival of cones in a model of retinitis pigmentosa (2010)

Retinitis pigmentosa (RP) is a major source of blindness caused by a large variety of mutations that lead to the death of rod photoreceptors. After rods die, cones gradually die from progressive oxidative damage. Several types of antioxidant formulations have been shown to reduce cone cell death over a relatively short-time frame, but in order for this strategy to be translated into a new treatment for patients with RP, prolonged effects will be needed. In this study, we determined that orally administered N-acetylcysteine (NAC) reduced cone cell death and preserved cone function by reducing oxidative damage in two models of RP, rd1(+/+) and rd10(+/+) mice. In rd10(+/+) mice, supplementation of drinking water with NAC promoted partial maintenance of cone structure and function for at least 6 months. Topical application of NAC to the cornea also reduced superoxide radicals in the retina and promoted survival and functioning of cones. Since oral and/or topical administration of NAC is feasible for long-term treatment in humans, and NAC has a good safety profile, it is reasonable to consider clinical trials to evaluate the effects of prolonged treatment with NAC in patients with RP.
Supplementary Figure S1 from BRD9 Degradation Disrupts Ribosome Biogenesis in Multiple Myeloma (2023)

&lt;p&gt;Clinical impact and biological significance of BRD9 in multiple myeloma (MM) in vitro and in vivo.&lt;/p&gt;
Resonant Raman scattering and luminescence in CuInS2 crystals (1998)

Resonant Raman scattering and luminescence have been examined for CuInS2 crystals grown by the traveling heater method (THM) and the iodine vapor transport method (IT). Resonant Raman spectra of CuInS2 have been observed, and the spectra show seven single-phonon peaks and one two-phonon peak. Among them, three single-phonon modes have been found in the low-Raman-shift region because of resonant enhancement of phonon modes. The enhancement of these phonon modes is caused by incoming resonance mediated by bound excitons on the THM crystal, while it is attributed to outgoing resonance due to intermediate states of free excitons on the IT crystal.
Modulation Detection, Modulation Masking, and Speech Understanding in Noise in the Elderly (1992)

Temporal processing of suprathreshold sounds was examined in a group of young normal-hearing subjects (mean age of 26.0 years), and in three groups of older subjects (mean ages of 54.3, 64.8, and 72.2 years) with normal hearing or mild sensorineural hearing loss. Three experiments were performed. In the first experiment (modulation detection), subjects were asked to detect sinusoidal amplitude modulation (SAM) of a broadband noise, for modulation frequencies ranging from 2-1024 Hz. In the second experiment (modulation masking), the task was to detect a SAM signal (modulation frequency of 8 Hz) in the presence of a 100%-modulated SAM masker. Masker modulation frequency ranged from 2-64 Hz. In the final experiment, speech understanding was measured as a function of signal-to-noise ratio in both an unmodulated background noise and in a SAM background noise that had a modulation frequency of 8 Hz and a modulation depth of 100%. Except for a very modest correlation between age and modulation detection sensitivity at low modulation frequencies, there were no significant effects of age once the effect of hearing loss was taken into account. The results of the experiments suggest, however, that subjects with even a mild sensorineural hearing loss may have difficulty with a modulation masking task, and may not understand speech as well as normal-hearing subjects do in a modulated noise background.
Supplementary Figure S5 from IGF2 Preserves Osteosarcoma Cell Survival by Creating an Autophagic State of Dormancy That Protects Cells against Chemotherapeutic Stress (2023)

&lt;p&gt;Supplementary Figure S5: (A,B) Viability of AXT cells was assessed after the treatment of aminooxyacetate or bafilomycin A. (C) Cell viability for AXT cells was evaluated after exposure to the indicated agents.&lt;/p&gt;
Relating Structure to Function in the Beta-Propeller Domain of Dipeptidyl Peptidase IV (2006)

Point mutations in human CD26/DP IV were analysed for adenosine deaminase (ADA) binding, monoclonal antibody (mAb) binding and DP IV enzyme activity. Point mutations at either Leu294 or Val341 ablated ADA binding. Binding by mAbs that inhibit ADA binding was found to involve both Leu340 to Arg343 and Thr440/Lys441. Glu205 and Glu206 were found to be essential for enzyme activity. All residues of interest were mapped onto a model of the beta-propeller domain of DP IV. These data led us to suggest that in DP IV and related peptidases ligand and antibody binding sites are non-linear and that enzyme activity depends on charged sidechains that surround the entrance to the central tunnel of the beta-propeller.
Author response: Olfactory connectivity mediates sleep-dependent food choices in humans (2019)

People who do not get enough sleep often start to favor sweet and fatty foods, which contributes to weight gain. While the exact mechanisms are still unknown, lack of sleep seems to change food preferences by influencing the levels of molecules that regulate food intake. In particular, it could have an effect on the endocannabinoid system, a complex network of molecules in the nervous system that controls biological processes such as appetite. The sense of smell is also tightly linked to how and what organisms choose to eat. Recent experiments indicate that in rodents, endocannabinoids enhance food intake by influencing the activity of the brain areas that process odors. However, it is still unclear whether the brain regions that process odors play a similar role in humans. To investigate, Bhutani et al. examined the impact of a four-hour night’s sleep on 25 healthy human volunteers. Blood analyses showed that after a short night, individuals had increased amounts of 2-oleoylglycerol, a molecule that is part of the endocannabinoid system. When sleep-deprived people were given the choice to eat whatever they wanted, those with greater levels of 2-oleoylglycerol preferred food higher in energy. Bhutani et al. also imaged the volunteers’ brains to examine whether these changes were connected to modifications in the way the brain processed smells. This revealed that, in people who did not sleep enough, an odor-processing region called the piriform cortex was encoding smells more strongly. The piriform cortex is connected to another region, the insula, which integrates information about the state of the body to control food intake. Lack of sleep altered this connection, and this was associated with a preference for high-energy food. In addition, further analysis showed that changes in the amounts of 2-oleoylglycerol were linked to modifications in the connection between the two brain areas. Taken together, these results suggest that sleep deprivation influences the endocannabinoid system, which in turn alters the connection between piriform and insular cortex, leading to a shift toward foods which are high in calories. In the United States alone, one in three people sleep less than six hours a night. Learning more about how sleep deprivation affects brain pathways and food choice may help scientists to develop new drugs or behavioral therapies for conditions like obesity.