gebhart/patrepeval huggingface dataset:
COMP-16. CORRELATING MGMT PROTEIN LEVEL WITH TEMOZOLOMIDE RESPONSE IN GLIOBLASTOMA PATIENTS USING MASS SPECTROMETRY (2018)

Glioblastoma (GBM) is an aggressive primary brain tumor with median progression-free survival (PFS) of 7 months and median overall survival (OS) of 15 months. Standard treatment at diagnosis consists of surgery, radiation and temozolomide (TMZ). O-6-methylguanine DNA methyltransferase (MGMT) modulates TMZ effect and MGMT promoter methylation status is used to predict outcomes and guide treatment decisions. However, standard testing is limited by poor inter-assay reproducibility and a weak correlation between methylation status and MGMT expression. We quantitated MGMT protein by mass spectrometry in 32 GBM patients to assess its relationship to PFS and OS after upfront TMZ treatment. We obtained archived tumor samples from newly diagnosed GBM patients prior to treatment with surgery, radiation and TMZ. Tumor cells were microdissected and solubilized, and MGMT protein was quantitated using mass spectrometry. PFS (determined by RANO) and OS were assessed using the Kaplan-Meier method and log-rank test. Of the 32 patients (66% male; median age: 63 years),15 expressed MGMT protein. While methylation status agreed with absence of MGMT protein in 8/9 cases, 9/23 samples with unmethylated MGMT had undetectable MGMT protein, indicating poor agreement between methylation status and protein expression. Patients with MGMT levels below 150 amol/ug of total protein had longer PFS than those with higher MGMT levels (HR: 0.51; p=0.0399; median PFS: 303 vs. 260 days). Similarly, MGMT level below 150 amol/ug was associated with longer OS (HR: 0.49; p=0.0311; median OS: 659 vs. 534 days). Discordance between MGMT methylation status and protein expression was found in 31% of GBM samples. MGMT protein expression below 150 amol/ug correlated with longer PFS and OS in TMZ-treated patients. Mass spectrometry-based MGMT quantitation provides a direct readout of protein expression and may be more reliable than methylation testing.
Efficient Gene Replacements in <i>Toxoplasma gondii</i> Strains Deficient for Nonhomologous End Joining (2009)

A high frequency of nonhomologous recombination has hampered gene targeting approaches in the model apicomplexan parasite Toxoplasma gondii. To address whether the nonhomologous end-joining (NHEJ) DNA repair pathway could be disrupted in this obligate intracellular parasite, putative KU proteins were identified and a predicted KU80 gene was deleted. The efficiency of gene targeting via double-crossover homologous recombination at several genetic loci was found to be greater than 97% of the total transformants in KU80 knockouts. Gene replacement efficiency was markedly increased (300- to 400-fold) in KU80 knockouts compared to wild-type strains. Target DNA flanks of only approximately 500 bp were found to be sufficient for efficient gene replacements in KU80 knockouts. KU80 knockouts stably retained a normal growth rate in vitro and the high virulence phenotype of type I strains but exhibited an increased sensitivity to double-strand DNA breaks induced by treatment with phleomycin or gamma-irradiation. Collectively, these results revealed that a significant KU-dependent NHEJ DNA repair pathway is present in Toxoplasma gondii. Integration essentially occurs only at the homologous targeted sites in the KU80 knockout background, making this genetic background an efficient host for gene targeting to speed postgenome functional analysis and genetic dissection of parasite biology.
A novel assist-as-needed control method to guide pelvic trajectory for gait rehabilitation (2015)

Pelvic motion plays an important role in human locomotion. Any abnormality of the pelvic motion during walking, such as asymmetry or altered range of motion, can affect gait stability and energy consumption [1]. In this work, we propose a new control methodology to guide and correct the human pelvic motion in the transverse plane during walking. An assist-as-needed paradigm was used to generate forces on the pelvis to guide a person to follow a new pelvic trajectory. An experiment was conducted with healthy subjects to follow an extended version of their baseline pelvic trajectory using the proposed control strategy. During the experiment, a cable-driven pelvic robot was used to apply the guidance forces in the transverse plane without adding external kinematic constraints on the pelvis. Experimental results showed that the subjects adapted their pelvic motion and retained the modified pelvic trajectory after the training. These results suggest that this strategy may be explored to correct abnormal pelvic trajectory of different patient groups.
Teddy (2006)

We present a sketching interface for quickly and easily designing freeform models such as stuffed animals and other rotund objects. The user draws several 2D freeform strokes interactively on the screen and the system automatically constructs plausible 3D polygonal surfaces. Our system supports several modeling operations, including the operation to construct a 3D polygonal surface from a 2D silhouette drawn by the user: it inflates the region surrounded by the silhouette making wide areas fat, and narrow areas thin. Teddy, our prototype system, is implemented as a Java™ program, and the mesh construction is done in real-time on a standard PC. Our informal user study showed that a first-time user typically masters the operations within 10 minutes, and can construct interesting 3D models within minutes.
Field and Laboratory Testing of Approaches to Smart Whole-House Mechanical Ventilation Control (2018)

Whole-house mechanical ventilation is a critical component to a comprehensive strategy for good indoor air quality (IAQ). However, due to lack of integration with standard heating and cooling systems, and perceptions from a portion of the homebuilding industry about risks related to increased energy use, increased cost, and decreased comfort, voluntary and code-required adoption varies among regions. Smart ventilation controls (SVC) balance energy consumption, comfort, and IAQ by optimizing mechanical ventilation operation to reduce the heating and/or cooling loads, improve management of indoor moisture, and maintain IAQ equivalence according to ASHRAE 62.2.
Identification of Novel, Selective, and Stable Inhibitors of Class II Histone Deacetylases. Validation Studies of the Inhibition of the Enzymatic Activity of HDAC4 by Small Molecules as a Novel Approach for Cancer Therapy (2009)

5-Aryl-2-(trifluoroacetyl)thiophenes were identified as a new series of class II HDAC inhibitors (HDACi). Further development of this new series led to compounds such as 6h, a potent inhibitor of HDAC4 and HDAC6 (HDAC4 WT IC(50) = 310 nM, HDAC6 IC(50) = 70 nM) that displays 40-fold selectivity over HDAC1 and improved stability in HCT116 cancer cells (t(1/2) = 11 h). Compounds 6h and 2 show inhibition of alpha-tubulin deacetylation in HCT116 cells at 1 microM concentration and antiproliferation effects only at concentrations where inhibition of histone H3 deacetylation is observed.
Maximizing server utilization while meeting critical SLAs via weight-based collocation management (2013)

Abstract—Servers in most data centers are often underutilized due to concerns about SLA violations that may result from resource contention as server utilization increases. This low utilization means that neither the capital investment in the servers nor the power consumed is being used as effectively as it could be. In this paper, we present a novel method for managing the collocation of critical (e.g., user interactive) and non-critical (e.g., batch) workloads on virtualized multicore servers. Unlike previous cap-based solutions, our approach improves server utilization while meeting the SLAs of critical workloads by prioritizing resource access using Linux cgroups weights. Extensive experimental results suggest that the proposed work conserving collocation method is able to utilize a server to nearly 100 % while keeping the performance loss of critical workloads within the specified limits.
Deubiquitinase function of arterivirus papain-like protease 2 suppresses the innate immune response in infected host cells (2013)

Protein ubiquitination regulates important innate immune responses. The discovery of viruses encoding deubiquitinating enzymes (DUBs) suggests they remove ubiquitin to evade ubiquitin-dependent antiviral responses; however, this has never been conclusively demonstrated in virus-infected cells. Arteriviruses are economically important positive-stranded RNA viruses that encode an ovarian tumor (OTU) domain DUB known as papain-like protease 2 (PLP2). This enzyme is essential for arterivirus replication by cleaving a site within the viral replicase polyproteins and also removes ubiquitin from cellular proteins. To dissect this dual specificity, which relies on a single catalytic site, we determined the crystal structure of equine arteritis virus PLP2 in complex with ubiquitin (1.45 Å). PLP2 binds ubiquitin using a zinc finger that is uniquely integrated into an exceptionally compact OTU-domain fold that represents a new subclass of zinc-dependent OTU DUBs. Notably, the ubiquitin-binding surface is distant from the catalytic site, which allowed us to mutate this surface to significantly reduce DUB activity without affecting polyprotein cleavage. Viruses harboring such mutations exhibited WT replication kinetics, confirming that PLP2-mediated polyprotein cleavage was intact, but the loss of DUB activity strikingly enhanced innate immune signaling. Compared with WT virus infection, IFN-β mRNA levels in equine cells infected with PLP2 mutants were increased by nearly an order of magnitude. Our findings not only establish PLP2 DUB activity as a critical factor in arteriviral innate immune evasion, but the selective inactivation of DUB activity also opens unique possibilities for developing improved live attenuated vaccines against arteriviruses and other viruses encoding similar dual-specificity proteases.
Interferon-inducing activity of dipyridamole in mice. (1983)

The kinetics of interferon (IFN) production was studied in mice after intraperitoneal (i.p.) and oral administrations of dipyridamole. The substance showed a high IFN-inducing activity when given orally at single doses ranging from 12.5 to 100 mg/kg (1/21.5-1/172 of the single LD50 value): peak titres of 2048-4096 IU/ml in the blood serum were reached at 48 hr; elevated IFN levels persisted until day 5 after administration of the inducer. Significantly lower IFN titres were found after i.p. injection.
Rational design, synthesis, and biological evaluation of novel growth hormone releasing factor analogues (1995)

Since its initial discovery in 1982, growth hormone-releasing factor (GRF) has been the subject of intense investigation. This interest was prompted by the potential application of GRF for stimulating growth in dwarf humans and for performance enhancement in livestock. Substantial research has been focused upon the development of potent, long-acting analogs as therapeutics. Herein is described a summary of the cumulative efforts of various laboratories endeavoring in this quest. The rationale utilized in GRF analog development is discussed: 1) determination of bioactive core, 2) evaluation of secondary structure, and 3) elucidation of degradation pathways (chemical and enzymatic). Using this information, several series of linear (unnatural and natural sequence) and cyclic GRF analogs were designed, synthesized, and evaluated. Stimulated by the constraints of commercial production, innovative, alternative methods of synthesis were explored: solid-phase, solution-phase, enzymatic, and recombinant. To date, the most promising candidate for drug development is [His1, Val2, Gln8, Ala15, Leu27]-hGRF(1-32)-OH. This natural sequence analog, consisting of rodent and human sequences, incorporates the bioactive core, preferred secondary structure, resistance to chemical and enzymatic degradation; with the added benefit of amenability to large-scale recombinant synthesis.
A New Method of Measuring Static Field Distribution Using NMR Images (1985)

This paper analyzes several factors that degrade accuracy in field distributions measured using a method proposed by the authors. It is shown that phase errors resulting from a misadjusted pulse-sequence can be removed by using two sets of complex nuclear magnetic resonance(NMR) images. We also show that the distortion of a measured distribution, which can seriously affect the accuracy of the measurements in an inhomogeneous field, can be corrected, and the limitation and effectiveness of this correction are discussed. Noise transfer through the calculation of a field distribution is also analyzed. It is pointed out that the time difference, which causes phase shifts proportional to the field inhomogeneity, needs to be set at a value as large as possible, so as to obtain a maximum signal-to-noise ratio in a calculated distribution.
Terahertz Generation Setups using Segmented Tilted-Pulse-Front Excitation (2019)

Summay form only given. A very efficient way of generating high energy terahertz (THz) pulses is the tilted-pulse-front excitation in lithium niobate (LN). In the last decade drastic increase of the THz pulse energy was achieved by the continual development of this technique. However, the following factors are still strongly limit of its energy scalability and THz beam quality: limited interaction length due to angular dispersion (i), prism shape of the LN crystal (ii), and imaging errors (iii). In order to overcome (i) a setup using a reflective echelon instead of optical grating was proposed [1], in which a segmented pump pulse front with adequate average tilt angle ensures the necessary velocity matching. However, (ii) and (iii) remained unsolved. A plan parallel structured nonlinear echelon slab (NLES) [2] can solve (ii) and significantly reduce (iii) keeping the same efficiency as available with the conventional setup as shown by blue and red curves in Fig. 1(a). Advantageously this setup allows energy scalability and good focusability. Working principle and single-cycle THz waveform was demonstrated with this setup [3].
Broadly neutralizing hemagglutinin stalk-specific antibodies require FcγR interactions for protection against influenza virus in vivo (VAC6P.951) (2014)

Abstract Neutralizing antibodies (Abs) against influenza viruses have traditionally been thought to provide protection exclusively through their variable region; the contributions of mechanisms conferred by the Fc domain remain controversial. We investigated the in vivo contributions of Fc interactions with their cognate receptors for a collection of neutralizing anti-influenza Abs. Whereas five broadly neutralizing monoclonal Abs (bNAbs) targeting the conserved stalk region of hemagglutinin (HA) required interactions between the Ab Fc and Fcγ-receptors for IgG (FcγR) to confer protection from lethal H1N1 challenge, three strain-specific monoclonal Abs (mAbs) against the variable head domain of HA were equally protective in the presence or absence of FcγR interactions. Although all Abs blocked infection, only anti-stalk bNAbs were able to mediate cytotoxicity of infected cells, which accounts for their FcγR dependence. Immune complexes generated with anti-HA stalk mAb efficiently interacted with FcγRs, but anti-HA head immune complexes did not. These results suggest that FcγR binding capacity by anti-HA Ab was dependent on the interaction of the cognate Fab with antigen. We exploited these disparate mechanisms of mAb-mediated protection to reengineer an anti-stalk bNAb to selectively enhance FcγR engagement to augment its protective activity. These findings reveal a previously uncharacterized property of bNAbs and guide an approach toward enhancing mAb-mediated anti-viral therapies.
Learning with memristive devices: How should we model their behavior? (2011)

This work discusses the modeling of memristive devices, for architectures where they are used as synapses. It is shown that the most common models used in this context do not always accurately reflect the actual behavior of popular devices in pulse regime. We introduce a new behavioral model, intended towards the nanoarchitecture community. It fits the conductance evolution of Univ. Michigan's synaptic memristive devices. A variation of the model fits HP labs's memristors' behavior in the same conditions. Finally, we discuss using a simple example the importance of this type of modeling for learning architectures and how it can impact the behavior of the learning.
Stability of soliton propagation with sliding-frequency guiding filters (1994)

We report on extensive experimental measurement of the allowable range of soliton pulse energies for stable, error-free propagation with sliding-frequency guiding filters, as a function of both filter strength and sliding rate, and on interpretative numerical analysis. The most important result is our discovery of an upper bound and related optimum value for the filter strength; at the optimum, the allowed range of pulse energies is nearly two to one.
Inherently super-resolving FINCH 3D fluorescence microscopy (2014)

Progress from an idea into a high resolution microscopy application since the invention of Fresnel Incoherent Correlation Holography (FINCH) [1] will be chronicled. In its current state of development, picture perfect 3D images with resolution about two times better than the Rayleigh limit can be reconstructed from FINCH holograms acquired by fluorescence microscopy. A number of optical, electro-optical and computational advances by ours and other laboratories have made this possible. Those advances, including the introduction of liquid crystal optics [2] in place of spatial light modulators and other new approaches will be discussed.
Active Excitation Tuning for Simultaneous Transmit and Receive Antennas (2020)

We present an actively tuned balun to enable Simultaneous Transmit and Receive (STAR) antennas to achieve greater isolation. Specifically, for the first time, we propose placing an active chip into the balun feed to control the amplitude and phase of the current density. Nearly perfect balance of the feed currents enables STAR antennas to maintain strong isolation despite fabrication imperfections and unpredictable environmental reflections. Measurements demonstrate 42 dB isolation across a 250 MHz bandwidth, representing an 11 dB boost. This is the best reported transmit-receive isolation improvement to date. Notably, the balun was tuned across 1.68-1.93 GHz. A prototype was fabricated and measurements show good comparison with simulation.
DiRA: Discriminative, Restorative, and Adversarial Learning for Self-supervised Medical Image Analysis (2022)

Discriminative learning, restorative learning, and adversarial learning have proven beneficial for self-supervised learning schemes in computer vision and medical imaging. Existing efforts, however, omit their synergistic effects on each other in a ternary setup, which, we envision, can significantly benefit deep semantic representation learning. To realize this vision, we have developed <b>DiRA</b>, the first framework that unites discriminative, restorative, and adversarial learning in a unified manner to collaboratively glean complementary visual information from unlabeled medical images for fine-grained semantic representation learning. Our extensive experiments demonstrate that DiRA (1) encourages collaborative learning among three learning ingredients, resulting in more generalizable representation across organs, diseases, and modalities; (2) outperforms fully supervised ImageNet models and increases robustness in small data regimes, reducing annotation cost across multiple medical imaging applications; (3) learns fine-grained semantic representation, facilitating accurate lesion localization with only image-level annotation; and (4) enhances state-of-the-art restorative approaches, revealing that DiRA is a general mechanism for united representation learning. All code and pretrained models are available at https://github.com/JLiangLab/DiRA.
ChemInform Abstract: NEW HETEROCYCLES ‐ ACCESS TO THIENO(3,2,B)(F) AND THIENO(2,3,B)(F)BENZAZEPINE DERIVATIVES (1981)

Abstract Access to Thieno[3,2,b][f] and Thieno[2,3,b][f]Benzazepine Derivatives.
New 1α,25-Dihydroxy-19-norvitamin D<sub>3</sub> Compounds Constrained in a Single A-Ring Conformation: Synthesis of the Analogues by Ring-Closing Metathesis Route and Their Biological Evaluation (2009)

Vitamin D compounds possessing A rings prohibited from flipping to the alternative chair form (i.e., analogues 2 and 26) were synthesized. The bicyclic fragment 22 consisting of the fused cyclohexane and dihydropyran rings was constructed via the ring-closing metathesis route. Also, a homologous synthon 23 with an attached dihydropyran ring was successfully synthesized using this strategy. The carbonyl deprotection in 22 yielded cyclohexanone 5 that was subjected to Julia coupling with the anion of the phenylthiazoline sulfone 25. In the resulting isomeric 19-norvitamins 2 and 26, their A rings can exist only in the alpha- and beta-conformation. The analogue 26 was 300 times more active in binding to the vitamin D receptor protein, 30 times more effective in causing HL-60 differentiation, and 10 times more active in transcription. These results confirm that the beta-chair form of the vitamin D ring A is necessary for the binding to the receptor.
THz integrated circuits (2011)

We will review our latest efforts at making THz integrated circuits, focusing mostly on integration of a Schottky diode into the core of a quantum cascade laser to create a heterodyne receiver. We will show its capability to detect external radiation and its ability to explore the behavior of the QCL itself.
Misincorporation of Galactose by Chondroitin Synthase of Escherichia coli K4: From Traces to Synthesis of Chondbiuronan, a Novel Chondroitin-Like Polysaccharide (2020)

Chondroitin synthase KfoC is a bifunctional enzyme which polymerizes the capsular chondroitin backbone of <i>Escherichia coli</i> K4, composed of repeated β3N-acetylgalactosamine (GalNAc)-β4-glucuronic acid (GlcA) units. Sugar donors UDP-GalNAc and UDP-GlcA are the natural precursors of bacterial chondroitin synthesis. We have expressed KfoC in a recombinant strain of <i>Escherichia coli</i> deprived of 4-epimerase activity, thus incapable of supplying UDP-GalNAc in the bacterial cytoplasm. The strain was also co-expressing mammal galactose β-glucuronyltransferase, providing glucuronyl-lactose from exogenously added lactose, serving as a primer of polymerization. We show by the mean of NMR analyses that in those conditions, KfoC incorporates galactose, forming a chondroitin-like polymer composed of the repeated β3-galactose (Gal)-β4-glucuronic acid units. We also show that when UDP-GlcNAc 4-epimerase KfoA, encoded by the K4-operon, was co-expressed and produced UDP-GalNAc, a small proportion of galactose was still incorporated into the growing chain of chondroitin.