gebhart/patrepeval huggingface dataset:
Biological correlative analyses and updated clinical data of ciltacabtagene autoleucel (cilta-cel), a BCMA-directed CAR-T cell therapy, in patients with multiple myeloma (MM) and early relapse after initial therapy: CARTITUDE-2, cohort B. (2022)

8029 Background: In cohort B of the multicohort phase 2 CARTITUDE-2 (NCT04133636) study, the efficacy and safety of cilta-cel are being evaluated in patients (pts) with MM who had early relapse after initial therapy. These pts have functionally high-risk disease, with early relapse post autologous stem cell transplantation (ASCT) being a poor prognostic factor and representing an unmet medical need. We present updated results. Methods: Eligible pts had MM, received 1 prior LOT (PI and IMiD required), had disease progression per IMWG (either ≤12 mo after ASCT or ≤12 mo after start of anti-myeloma therapy for pts who did not undergo ASCT), and were tx-naive to CAR-T/anti-BCMA therapies. A single cilta-cel infusion (target dose 0.75×10 6 CAR+ viable T cells/kg) was given post lymphodepletion. Safety and efficacy were assessed, and the primary endpoint was MRD negativity at 10 -5 . Management strategies were implemented to minimize risk of movement/neurocognitive AEs (MNTs). Pharmacokinetic (PK) analyses (C max and T max of CAR+ T-cell transgene levels in blood) are being conducted, as well as analyses of levels of CRS-related cytokines (eg, IL-6) over time, peak levels of cytokines by response and CRS, association of cytokine levels with ICANS, and CAR+ T cell CD4/CD8 ratio by response, CRS, and ICANS. Results: As of January 2022, 19 pts (median age 58.0 y [range 44–67]; 74% male; median follow-up 13.4 mo [range 5.2–21.7]) received cilta-cel. 79% of pts received prior ASCT. ORR was 100.0%, 90% achieved CR or better, and 95% achieved ≥VGPR. Median time to first response and best response were 0.95 mo (range 0.9–9.7) and 5.1 mo (range 0.9–11.8), respectively. Of pts who were MRD-evaluable (n = 15), 14 (93%) achieved MRD 10 -5 negativity during this study. Median DOR was not reached and 12-mo event-free rate was 88.9%. The 12-mo PFS rate was 90%. Median time to onset of CRS was 8 d (range 5–11) and occurred in 16 (84.2%) pts (1 gr 4). CRS resolved in all pts. ICANS (gr 1) occurred in 1 pt; MNT (gr 3) occurred in 1 pt, previously reported. 1 pt died post cilta-cel due to PD at d 158. Preliminary PK analyses indicate that peak expansion of CAR-T cells occurred on d 13.1 (range 8.96–209.9) and median persistence was 76.9 d (range 40.99–221.8). Conclusions: A single cilta-cel infusion led to deep and durable responses in a functionally high-risk pt population who experienced early clinical relapse/tx failure to initial therapy, with a manageable safety profile. In this pt population with ineffective or insufficient response to ASCT, cilta-cel led to responses. Responses continue to deepen, and follow-up is ongoing. Updated and in-depth PK, cytokine, and CAR-T subset analyses and clinical correlation will be presented and provide novel insights into biological correlates of efficacy and safety in this pt population. Clinical trial information: NCT04133636.
Group Therapy for Systems: Using Link Attestations to Manage Failures. (2006)

Managing failures and configuring systems properly are of critical importance for robust distributed services. Unfortunately, protocols offering strong fault-tolerance guarantees are generally too costly and insensitive to performance criteria. Yet, system management in practice is often ad-hoc and ill-defined, leading to under-utilized capacity or adverse effects from poorly-behaving machines. This paper proposes a new abstraction called linkattestation groups (LA-Groups) for building robust distributed systems. Developers specify application-level correctness conditions or performance requirements for nodes. Nodes vouch for each other&amp;apos;s acceptability within small groups of nodes through digitally-signed link attestations, and then apply a link-state protocol to determine these group relationships.
Development of Orally Bioavailable and CNS Penetrant Biphenylaminocyclopropane Carboxamide Bradykinin B 1 Receptor Antagonists (2006)

A series of biphenylaminocyclopropane carboxamide based bradykinin B1 receptor antagonists has been developed that possesses good pharmacokinetic properties and is CNS penetrant. Discovery that the replacement of the trifluoropropionamide in the lead structure with polyhaloacetamides, particularly a trifluoroacetamide, significantly reduced P-glycoprotein mediated efflux for the series proved essential. One of these novel bradykinin B1 antagonists (13b) also exhibited suitable pharmacokinetic properties and efficient ex vivo receptor occupancy for further development as a novel approach for the treatment of pain and inflammation.
The phase diagram of high-pressure superionic ice (2015)

Superionic ice is a special group of ice phases at high temperature and pressure, which may exist in ice-rich planets and exoplanets. In superionic ice liquid hydrogen coexists with a crystalline oxygen sublattice. At high pressures, the properties of superionic ice are largely unknown. Here we report evidence that from 280 GPa to 1.3 TPa, there are several competing phases within the close-packed oxygen sublattice. At even higher pressure, the close-packed structure of the oxygen sublattice becomes unstable to a new unusual superionic phase in which the oxygen sublattice takes the P2(1)/c symmetry. We also discover that higher pressure phases have lower transition temperatures. The diffusive hydrogen in the P2(1)/c superionic phase shows strong anisotropic behaviour and forms a quasi-two-dimensional liquid. The ionic conductivity changes abruptly in the solid to close-packed superionic phase transition, but continuously in the solid to P2(1)/c superionic phase transition.
Prompt Pulsed Neutron Activation Analysis for Detection of Fission Neutrons (2006)

A pulsed-neutron interrogation technique for detection of Special Nuclear Material (SNM) is described. The technique combines timing techniques from pulsed prompt gamma neutron activation analysis with silicon carbide (SiC) semiconductor fast neutron detector technology. SiC detectors can operate during and within nanoseconds of the end of an intense neutron pulse, providing the ability to detect the prompt neutron emissions from fission events produced by the neutrons from SNM on a much faster pulsing time scale than has been achieved by other techniques. Neutron-induced fission neutrons in <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">235</sup> U have been observed in the time intervals between pulses of 14-MeV neutrons from a deuterium-tritium electronic neutron generator. Neutron pulsing and time-sequenced neutron counts were carried out on a hundreds of microseconds time scale, enabling the observation of prompt fission neutrons induced by the die-away of thermal neutrons following the 14-MeV pulse. SNM was detected in a variety of shielded configurations, and excellent signal-to-background ratios were observed.
Controllo delle vibrazioni di strutture flessibili mediante smorzatori dinamici a correnti parassite (2001)

The objective of the paper is to present the design, the construction and the testing of an eddy current vibration absorber for the passive vibration control of flexible structures. A methodology for the design of the eddy current damper is presented in order to minimize the amount of permanent magnet used within the damper. The damper configuration is then chosen to damp the flexural behavior of very simple beam structures but it is well suited to be applied in different applications. The performances of the proposed damper are then investigated in terms of frequency response measured on an experimental test rig and compared with the performances that can be achieved with active vibration damping treatments based on the use of piezoelectric transducers.
Dynamic file-access characteristics of a production parallel scientific workload (1994)

Multiprocessors have permitted astounding increases in computational performance, but many cannot meet the intense I/O requirements of some scientific applications. An important component of any solution to this I/O bottleneck is a parallel file system that can provide high-bandwidth access to tremendous amounts of data in parallel to hundreds or thousands of processors. Most successful systems are based on a solid understanding of the expected workload, but thus far there have been no comprehensive workload characterizations of multiprocessor file systems. This paper presents the results of a three week tracing study in which all file-related activity on a massively parallel computer was recorded. Our instrumentation differs from previous efforts in that it collects information about every I/O request and about the mix of jobs running an a production environment. We also present the results of a trace-driven caching simulation and recommendations for designers of multiprocessor file systems. >
Highly reliable operation of InGaAlAs/InGaAsP integrated lasers (2007)

We present a novel concept of free integration of InGaAlAs-based and InGaAsP-based components on a single InP substrate for higher-performance long-wavelength opto-electronic devices. A butt-jointing process with in situ cleaning was used to obtain high-quality integration of InGaAlAs and InGaAsP components. Combinations of InGaAlAs lasers integrated with InGaAsP, and InGaAsP lasers integrated with InGaAlAs, were fabricated using this process. Aging tests on both types of lasers showed no significant degradation in their driving current. It can thus be concluded that the free integration of InGaAlAs and InGaAsP is promising for development of higher-performance devices for the next generation of optical communications applications.
Aluminum Nitride Out-of-Plane Piezoelectric MEMS Actuators (2023)

Integrating microelectromechanical systems (MEMS) actuators with low-loss suspended silicon nitride waveguides enables the precise alignment of these waveguides to other photonic integrated circuits (PICs). This requires both in-plane and out-of-plane actuators to ensure high-precision optical alignment. However, most current out-of-plane electrostatic actuators are bulky, while electrothermal actuators consume high power. Thus, piezoelectric actuators, thanks to their moderate actuation voltages and low power consumption, could be used as alternatives. Furthermore, piezoelectric actuators can provide displacements in two opposite directions. This study presents a novel aluminum nitride-based out-of-plane piezoelectric MEMS actuator equipped with a capacitive sensing mechanism to track its displacement. This actuator could be integrated within PICs to align different chips. Prototypes of the device were tested over the range of ±60 V, where they provided upward and downward displacements, and achieved a total average out-of-plane displacement of 1.30 ± 0.04 μm. Capacitance measurement showed a linear relation with the displacement, where at -60 V, the average change in capacitance was found to be -13.10 ± 0.89 fF, whereas at 60 V the change was 11.09 ± 0.73 fF. This study also investigates the effect of the residual stress caused by the top metal electrode, on the linearity of the displacement-voltage relation. The simulation predicts that the prototype could be modified to accommodate waveguide routing above it without affecting its performance, and it could also incorporate in-plane lateral actuators.
Plasminogen Activator Activity in Cumulus-Oocyte Complexes of Gonadotropin-Treated Rats during the Periovulatory Period1 (1987)

Two types of plasminogen activator (tissue-type, tPA; urokinase-type, uPA) have been demonstrated in ovarian granulosa cells, but only tPA activity was found in denuded oocytes. Immature rats were treated subcutaneously with 20 IU pregnant mare's serum gonadotropin (PMSG) to stimulate follicle maturation, followed 2 days later by an injection of 10 IU human chorionic gonadotropin (hCG) to induce ovulation. Cellular plasminogen activator activities were determined by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis followed by a fibrin-overlay technique. Cumulus-oocyte complexes from rats before and after PMSG treatment contained low amounts of tPA, but not uPA, activity. After hCG treatment, tPA activity showed a time-dependent increase, reaching a maximum at 24 h after injection. At 12 and 24 h after hCG treatment, uPA activity was also detected. The appearance of high molecular weight lysis zones further suggested the formation of plasminogen activator-inhibitor complexes. Morphological analysis indicated that the increases in oocyte tPA activity were correlated with the extent of cumulus cell expansion and dispersion. In denuded oocytes, tPA activity also progressively increased during the periovulatory period to a maximum at 24 h after hCG treatment. In contrast, neither uPA activity nor activator-inhibitor complex was detected. Secretion of the proteases was measured in the conditioned media of cumulus-oocyte complexes cultured for 24 h in vitro. Substantial increases in tPA release were found in complexes obtained at 8 and 12 h after hCG injection, with lower secretion from complexes obtained at 24 h after hCG treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
P4‐205: MUCOSAL IMMUNIZATION TO PREVENT CHRONIC WASTING DISEASE (CWD) IN DEER (2014)

Prionoses are transmissible, neurodegenerative disorders. Bovine spongioform encephalopathy (BSE) has crossed the species barrier to infect humans. Chronic wasting disease (CWD) infects large numbers of deer and elk, with the potential to infect humans. Currently no prionosis has an effective treatment. Previously, we have demonstrated we could prevent transmission of prions in a proportion of susceptible mice with a mucosal vaccine. Recently, we have attempted to produce an immune response in animals naturally susceptible to CWD, white tail deer, which could inhibit transmission. White tail deer (n=5) were orally inoculated with attenuated Salmonella carrying deer or mouse PrP, while control deer (n=6) were orally inoculated with vehicle attenuated Salmonella. Once a mucosal response was established, the vaccinated animals (n=5) were boosted orally and locally by application of polymerized recombinant PrP onto the tonsil and rectal mucosa. Blood, saliva and feces were collected regularly to assess IgA, IgM and IgG titers to PrP. The vaccinated (n=5) and control animals (n=6) were then challenged orally with CWD-infected brain homogenate. Tonsil and rectal biopsies plus blood, saliva, feces and urine were collected every three months post-infection to assay for PrP CWD,as an indicator of infection. All vaccinated animals produced anti-PrP IgA and IgG antibody titers of varying levels. As expected, both vaccinated and control deer produced high titers of IgA and IgG against Salmonella. Three years post CWD oral challenge all control deer developed clinical CWD (median survival 602 days), while among the vaccinated there was a prolongation of the incubation period and one deer remains CWD free clinically and by RAMALT and tonsillar biopsies (p=0.012 by Weibull regression analysis). This negative vaccinate has the highest titers of IgA in saliva and IgG systemic against PrP. Western blots showed that immunoglobulins from this vaccinate react to PrP CWD. Oral immunization can be used to overcome tolerance to self-PrP protein and produce a mucosal IgA and systemic IgG response to normal and conformational modified PrP in large mammals. We document the first partially successful vaccination for a prion disease in a species naturally at risk.
Perfusion-based high-resolution fMRI in the primate brain using a novel vertical large-bore 7 Tesla setup (2004)

Functional MR imaging in monkeys promises to build a bridge between brain research in humans and the large body of systems neuroscience work in animals. Simultaneous fMRI and electrophysiology was recently used in the anesthetized monkey to elucidate the neural activity underlying the fMRI BOLD signal [1]. Perfusion-based MRI measures cerebral blood flow (CBF) at the capillary level and can be used for functional studies based on the tight spatial coupling between brain activity and blood flow. From CBF changes and interleaved-acquired BOLD data, changes in oxygen consumption can be calculated. Obtaining functional CBF maps with high spatial resolution is a major challenge, because the CBF signal is intrinsically low and the signal-to-noise ratio is critical. In this study, high-resolution CBF maps were obtained with voxel sizes as small as 0.5 x 0.5 x 3 mm3 in the Macaca mulatta for the first time. High sensitivity was made possible by signal-to-noise gains at the high magnetic field of 7 Tesla and by using a customized RF combination coil design. In first experiments, CBF maps and functional CBF data were acquired and compared with functional BOLD data in the primary visual cortex. For CBF, large contrast-to-noise gains were obtained at high spatial resolution similar as previously reported in humans [2]. These first results demonstrate that the sensitivity gains at high field can be used to study CBF changes in primate brain with spatial dimensions well below the cortical thickness. This is significant for the understanding of localized brain function and the physiological basis of functional neuroimaging.
Imaging mass spectrometer with mass tags (2023)

A method of analyzing biological material by exposing the biological material to a recognition element, that is coupled to a mass tag element, directing an ion beam of a mass spectrometer to the biological material, interrogating at least one region of interest area from the biological material and producing data, and distributing the data in plots.
Integrated III-V/Lithium Niobate Nonlinear Laser (2022)

We demonstrate a narrow linewidth integrated nonlinear laser with both fine and coarse tunability based on electro-optic and thermo-optic effect respectively, as well as an intracavity frequency doubling capability via second-harmonic generation.
Endurance-Aware Mapping of Spiking Neural Networks to Neuromorphic\n Hardware (2021)

Neuromorphic computing systems are embracing memristors to implement high\ndensity and low power synaptic storage as crossbar arrays in hardware. These\nsystems are energy efficient in executing Spiking Neural Networks (SNNs). We\nobserve that long bitlines and wordlines in a memristive crossbar are a major\nsource of parasitic voltage drops, which create current asymmetry. Through\ncircuit simulations, we show the significant endurance variation that results\nfrom this asymmetry. Therefore, if the critical memristors (ones with lower\nendurance) are overutilized, they may lead to a reduction of the crossbar's\nlifetime. We propose eSpine, a novel technique to improve lifetime by\nincorporating the endurance variation within each crossbar in mapping machine\nlearning workloads, ensuring that synapses with higher activation are always\nimplemented on memristors with higher endurance, and vice versa. eSpine works\nin two steps. First, it uses the Kernighan-Lin Graph Partitioning algorithm to\npartition a workload into clusters of neurons and synapses, where each cluster\ncan fit in a crossbar. Second, it uses an instance of Particle Swarm\nOptimization (PSO) to map clusters to tiles, where the placement of synapses of\na cluster to memristors of a crossbar is performed by analyzing their\nactivation within the workload. We evaluate eSpine for a state-of-the-art\nneuromorphic hardware model with phase-change memory (PCM)-based memristors.\nUsing 10 SNN workloads, we demonstrate a significant improvement in the\neffective lifetime.\n
Elective percutaneous intervention for intracranial atherosclerotic stenoses by interventional cardiologists (2011)

For patients with symptomatic IC arterial stenosis who have failed medical therapy or are considered very high risk for stroke, CBT performed by experienced interventional cardiologists is safe and offers both high procedural success rates and excellent clinical outcomes at 1 year. CBT is an attractive option for this high-risk patient population considering the expected 12-15% rate of recurrent stroke at 1 year.
MicroRNA Profiling in Ovarian Cancer (2013)

The evaluation of microRNA profiles has represented one of the first approaches to investigate the aberrant microRNA expression in different human cancers, providing the first experimental evidence of the involvement of these small noncoding RNAs in the tumorigenic process. Currently, these and other methods have been applied to the search of new molecular biomarkers of diagnosis, prognosis, and response to therapy prediction. Here, we described the approach we used for the determination of a miRNA signature unique for human ovarian cancer, first performing a large-scale screening using a custom-made microarray platform, and then validating the obtained data by Northern blot or real-time PCR.
A Gaussian Mixture MRF for Model-Based Iterative Reconstruction With Applications to Low-Dose X-Ray CT (2016)

Markov random fields (MRFs) have been widely used as prior models in various inverse problems such as tomographic reconstruction. While MRFs provide a simple and often effective way to model the spatial dependencies in images, they suffer from the fact that parameter estimation is difficult. In practice, this means that MRFs typically have very simple structure that cannot completely capture the subtle characteristics of complex images. In this paper, we present a novel Gaussian mixture Markov random field model (GM-MRF) that can be used as a very expressive prior model for inverse problems such as denoising and reconstruction. The GM-MRF forms a global image model by merging together individual Gaussian-mixture models (GMMs) for image patches. In addition, we present a novel analytical framework for computing MAP estimates using the GM-MRF prior model through the construction of surrogate functions that result in a sequence of quadratic optimizations. We also introduce a simple but effective method to adjust the GM-MRF so as to control the sharpness in low- and high-contrast regions of the reconstruction separately. We demonstrate the value of the model with experiments including image denoising and low-dose CT reconstruction.
PanR1 , a Dominant Negative Missense Allele of the Gene Encoding TNF-α ( Tnf ), Does Not Impair Lymphoid Development (2006)

A dominant hypomorphic allele of Tnf, PanR1, was identified in a population of G(1) mice born to N-ethyl-N-nitrosourea-mutagenized sires. Macrophages from homozygotes produced no detectable TNF bioactivity, although normal quantities of immunoreactive TNF were secreted. The phenotype was confined to a critical region on mouse chromosome 17, and then ascribed to a C-->A transversion at position 3480 of the Tnf gene, corresponding to the amino acid substitution P138T. As a result of subunit exchange, the protein exerts a dominant-negative effect on normal TNF trimers, interfering with the trimer/receptor interaction. Homozygotes are highly susceptible to infection by Listeria monocytogenes, confirming the essential role of TNF in innate immune defense. However, PanR1 mutant mice show normal architecture of the spleen and Peyer's patches, suggesting that TNF is not essential for the formation of these lymphoid structures.
Reactive polymer fused deposition manufacturing (2023)

Methods and compositions for additive manufacturing that include reactive or thermosetting polymers, such as urethanes and epoxies. The polymers are melted, partially cross-linked prior to the depositing, deposited to form a component object, solidified, and fully cross-linked. These polymers form networks of chemical bonds that span the deposited layers. Application of a directional electromagnetic field can be applied to aromatic polymers after deposition to align the polymers for improved bonding between the deposited layers.
Introduction to Linear Systems (2017)

The fact that representation of waveforms as a sum of sine waves is useful in the elucidation of human hearing indicates that something involved in hearing is linear or nearly linear.—“The nature of musical sound,” John R. Pierce (1999)