gebhart/patrepeval huggingface dataset:
Altered interactions between circulating and tissue-resident CD8 T cells with the colonic mucosa define colitis associated with immune checkpoint inhibitors (2021)

Abstract Therapeutic blockade of co-inhibitory immune receptors PD-1 and CTLA-4 has revolutionized oncology, but treatments are limited by immune-related adverse events (IRAEs). IRAE Colitis (irColitis) is the most common, severe IRAE affecting up to 25% of patients on dual PD-1 and CTLA-4 inhibition. Here, we present a systems biology approach to define the cell populations and transcriptional programs driving irColitis. We collected paired colon mucosal biopsy and blood specimens from 13 patients with irColitis, 8 healthy individuals, and 8 controls on immune checkpoint inhibitors (ICIs), and analyzed them with single-cell/nuclei RNA sequencing with paired TCR and BCR sequencing, multispectral fluorescence microscopy, and secreted factor analysis (Luminex). We profiled 299,407 cells from tissue and blood and identified 105 cell subsets that revealed significant tissue remodeling in active disease. Colon mucosal immune populations were dominated by tissue-resident memory (T RM ) ITGAE -expressing CD8 T cells representing a phenotypic spectrum defined by gene programs associated with T cell activation, cytotoxicity, cycling, and exhaustion. CD8 T RM and effector CD4 T cells upregulated type 17 immune programs ( IL17A, IL26 ) and Tfh-like programs ( CXCL13, PDCD1 ). We also identified for the first time an increased abundance of two KLRG1 and ITGB2 -expressing CD8 T cell populations with circulatory cell markers, including a GZMK T RM -like population and a CX3CR1 population that is predicted to be intravascular. These two populations were more abundant in irColitis patients treated with dual PD-1/CTLA-4 inhibition than those receiving anti-PD-1 monotherapy. They also had significant TCR sharing with PBMCs, suggesting a circulatory origin. In irColitis we observed significant epithelial turnover marked by fewer LGR5 -expressing stem cells, more transit amplifying cells, and upregulation of apoptotic and DNA-sensing programs such as the cGAS-STING pathway. Mature epithelial cells with top crypt genes upregulated interferon-stimulated pathways, CD274 (PD-L1), anti-microbial genes, and MHC-class II genes, and downregulated aquaporin and solute-carrier gene families, likely contributing to epithelial cell damage and absorptive dysfunction. Mesenchymal remodeling was defined by increased endothelial cells, both in irColitis patients and specifically in patients on dual PD-1/CTLA-4 blockade. Cell-cell communication analysis identified putative receptor-ligand pairs that recruit CD8 T cells from blood to inflamed endothelium and positive feedback loops such as the CXCR3 chemokine system that retain cells in tissue. This study highlights the cellular and molecular drivers underlying irColitis and provides new insights into the role of CTLA-4 and PD-1 signaling in maintaining CD8 T RM homeostasis, regulating CD8 T recruitment from blood, and promoting epithelial-immune crosstalk critical to gastrointestinal immune tolerance and intestinal barrier function.
Selective Permeabilization of Gram-Negative Bacterial Membranes Using Multivalent Peptide Constructs for Antibiotic Sensitization (2021)

The drug-impermeable bacterial membrane in Gram-negative pathogens limits antibiotic access to intracellular drug targets. To expand our rapidly waning antibiotic arsenal, one approach is to improve the intracellular delivery of drugs with historically poor accumulation in Gram-negative bacteria. To do so, we engineered macromolecular potentiators to permeabilize the Gram-negative membrane to facilitate drug influx. Potentiators, known as WD40, were synthesized by grafting multiple copies of a cationic α-helical antimicrobial peptide, WLBU2, onto a dextran polymer scaffold. WD40 enabled drug uptake in the model pathogen <i>P. aeruginosa</i>, a capability that was not observed with unmodified WLBU2 peptide. WD40 was able to reduce minimum inhibitory concentrations of a drug panel by up to 3 orders of magnitude. Hydrophobic and highly three-dimensional antibiotics exhibited the greatest potentiation. Antibiotic activity was potentiated in several clinical strains and resulted in sensitization of drug-resistant strains to rifampin, a drug not previously used for Gram-negative infections.
Looking Backwards (and Forwards): NSF Secure and Trustworthy Computing 20-Year Retrospective Panel Transcription (2023)

The U.S. National Science Foundation (NSF) celebrated the 20th anniversary of its research funding programs in cybersecurity, and more generally, secure and trustworthy computing, with a panel session at its conference held in June, 2022. The panel members, distinguished researchers in different research areas of trustworthy computing, were asked to comment on what has been learned, what perhaps should be “unlearned,” what still needs to be learned, and the status of education and training in their respective areas of expertise. Laurie Williams covered enterprise security and measuring security, Gene Tsudik commented on cryptographic security, Trent Jaeger addressed computing infrastructure security, Tadayoshi Kohno reviewed security in cyberphysical systems, and Apu Kapadia provided insights on human-centered security. Michael K. Reiter chaired the panel and moderated questions from the audience. This report provides a brief summary of NSF’s research programs in the area and an edited transcript of the panel discussion.
Regioselective Synthesis of Highly Aryl‐Substituted Pyrrole Carboxylates as Useful Medicinal Chemistry Leads (2007)

Abstract The regioselective syntheses of two pharmaceutically relevant pyrrole scaffolds are described. A synthetic route for the preparation of differentially substituted pyrrole‐3,4‐dicarboxylates is presented and exemplified. This route circumvents some of the problems and limitations associated with previous butynedioic diester condensations and 1,3‐dipolar cycloaddition reactions. A route to the related 4,5‐diarylpyrrole‐2‐carboxylic acid scaffold is also presented. Both routes allow for the regiocontrolled preparation of highly substituted pyrrole pharmacophore cores.
Evaluation of a Pediatric Facial Paralysis Education and Family Support Day (2020)

The needs assessment demonstrated that families were most interested in advances in medicine, therapy and coping sessions and meeting other families. The post-event evaluation questionnaire indicated that attendees enjoyed the event, would attend again and found it highly valuable connecting and networking other families. It also indicated that key needs identified were addressed, with excellent ratings for the presentation discussing advances in medicine (100% rated "good" or "very good"), the therapy sessions (92% rated "good" or "very good") and the presentations by patients and their families (100% rated "good" or "very good.") DISCUSSION:: Two areas of improvement highlighted were elaborating further on medical advances and facilitating interactions between families. Overall, this event was well regarded and will likely be repeated at our institution and serve as a valuable resource for other hospitals planning to organize a similar event.
Data for: On the Modeling of a Contact-Aided Cross-Axis Flexural Pivot (2019)

The folder contains files for a multi-software automatic framework, capable of analyzing the performances of a Contact-Aided Cross-Axis pivot. Chained-Beam-Constraint Model and batch 1D FEA are launched from Matlab environment.
Temperature Sensing in Cells Using Polymeric Upconversion Nanocapsules (2020)

Monitoring local temperature inside cells is crucial when interpreting biological activities as enhanced cellular metabolism leads to higher heat production and is commonly correlated with the presence of diseases such as cancer. In this study, we report on polymeric upconversion nanocapsules for potential use as local nanothermometers in cells by exploiting the temperature dependence of the triplet-triplet annihilation upconversion phenomenon. Nanocapsules synthesized by the miniemulsion solvent evaporation technique are composed of a polymer shell and a liquid core of rice bran oil, hosting triplet-triplet annihilation upconversion active dyes as sensitizer and emitter molecules. The sensitivity of the triplet-triplet annihilation upconversion to the local oxygen concentration was overcome by the oxygen reduction ability of the rice bran oil core. The triplet-triplet annihilation upconversion process could thus successfully be applied at different levels of oxygen presence including at ambient conditions. Using this method, the local temperature within a range of 22 to 40 °C could be determined when the upconversion nanocapsules were taken up by HeLa cells with good cellular viability. Thus, the higher cell temperatures where the cells show enhanced metabolic activity led to a significant increase in the delayed fluorescence spectrum of the upconversion nanocapsules. These findings are promising for further development of novel treatment and diagnostic tools in medicine.
ChemInform Abstract: Cycloadditions. Part 52. Utilization of L‐Serine in an Oxime Olefin Cycloaddition Route to a Functionalized Asymmetric Pyrrolidine, a Selective α‐Glucosidase Inhibitor. (1994)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Applications of SNMP in Ubiquitous Environment (2006)

Ubiquitous computing is fast becoming a reality. Several ubiquitous devices compliant with the service discoveries like UPnP and JINI are available now. Individually, managing the ubiquitous devices with UPnP is not a problem. But, it is quite cumbersome to manage these devices in the large scale environment especially when the management issues like performance, fault and security management have to be considered. SNMP is a standard for network management and widely deployed. A majority of SNMP compliant devices are already present. We propose that by integrating SNMP with service discovery protocols like UPnP, we could leverage the use of management factors in the business, organizations, and other multi-user ubiquitous environments, while providing a uniform interface to an administrator for the management of UPnP and SNMP based devices. 1.
Regioisomeric and Substituent Effects upon the Outcome of the Reaction of 1-Borodienes with Nitrosoarene Compounds (2015)

A study of the reactivity of 1-borodienes with nitrosoarene compounds has been carried out showing an outcome that differs according to the hybridization state of the boron moiety. Using an sp(2) boron substituent, a one-pot hetero-Diels-Alder/ring contraction cascade occurred to afford N-arylpyrroles with low to good yields depending on the electronic properties of the substituents on the borodiene, whereas an sp(3) boron substituent led to the formation of stable boro-oxazines with high regioselectivity in most of the cases, in moderate to good yields. (1)H and (11)B NMR studies on two boro-oxazine regioisomers showed that selective deprotection can be performed. Formation of either the pyrrole or the furan derivative is pH- and regioisomer-structure-dependent. The results obtained, together with previous B3LYP calculations, support mechanistic proposals which suggest that pyrrole, or furan, formation proceeds via oxazine formation, followed by a boryl rearrangement and an intramolecular addition-elimination sequence.
Data from Tumor- and Neoantigen-Reactive T-cell Receptors Can Be Identified Based on Their Frequency in Fresh Tumor (2023)

&lt;div&gt;Abstract&lt;p&gt;Adoptive transfer of T cells with engineered T-cell receptor (TCR) genes that target tumor-specific antigens can mediate cancer regression. Accumulating evidence suggests that the clinical success of many immunotherapies is mediated by T cells targeting mutated neoantigens unique to the patient. We hypothesized that the most frequent TCR clonotypes infiltrating the tumor were reactive against tumor antigens. To test this hypothesis, we developed a multistep strategy that involved TCRB deep sequencing of the CD8&lt;sup&gt;+&lt;/sup&gt;PD-1&lt;sup&gt;+&lt;/sup&gt; T-cell subset, matching of TCRA–TCRB pairs by pairSEQ and single-cell RT-PCR, followed by testing of the TCRs for tumor-antigen specificity. Analysis of 12 fresh metastatic melanomas revealed that in 11 samples, up to 5 tumor-reactive TCRs were present in the 5 most frequently occurring clonotypes, which included reactivity against neoantigens. These data show the feasibility of developing a rapid, personalized TCR-gene therapy approach that targets the unique set of antigens presented by the autologous tumor without the need to identify their immunologic reactivity. &lt;i&gt;Cancer Immunol Res; 4(9); 734–43. ©2016 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
Copper Deposition in the Presence of Surface‐Confined Additives (1997)

The galvanostatic deposition of Cu from sulfuric acid solutions onto evaporated (111) Au electrodes bearing alkanethiol monolayers (SAMs) was studied with a combination of cyclic voltammetry, in situ atomic force microscopy, and x‐ray photoelectron spectroscopy. The morphology of the electrodeposit was found to depend on the chain length of the alkanethiol used to form the SAM and the applied current density. It was found that short chain length (n = 4) thiols and high current densities (j ⩾ 1.67 mA/cm2) promote the formation of smooth deposits. We attribute this effect to the overpotential‐driven activation of numerous monolayer defects that play the role of nucleation centers. The passage of the current was found to cause a change in the monolayer defect density. X‐ray photoelectron spectroscopic analysis showed that deposition occurred on top of the monolayer in a completely reversible manner and that the deposition and subsequent stripping did not affect the S‒Au bond of most thiolate moieties contained in the SAM. The implications of these results for additive‐based electrodeposition are discussed.
Reduction of aldehydes and ketones by sodium dithionite (1980)

Conditions have been developed for the effective reduction of aldehydes and ketones by sodium dithionite, Na2S2O4. Complete reduction of simple aldehydes and ketones can be achieved with excess Na2S2O4 in H2O/dioxane mixtures at reflux temperature. Some aliphatic ketones, for example, pentanone and 4-heptanone, are reduced only sluggishly under these conditions. Good conversions can be achieved, however, by adding dimethylformamide to the reaction mixture, again held at reflux. The reductions of 17 compounds are described and the scope of the reaction is discussed. α-Hydroxy sulfinates are suggested as probable intermediates in these reductions.
Efficient generation of infrared light in LiNbO3 waveguides with integrated coupling structures (1998)

Difference-frequency mixing (DFM), in which a pump at frequency ω p is mixed with a signal at frequency ω s to generate an idler at frequency ω i = ω p - ω s , is useful for generating infrared radiation. By mixing the outputs of two infrared lasers, one can generate coherent infrared radiation 1 , 2 for spectroscopic applications such as molecular sensing 3 ; one can also apply DFM to wavelength conversion in wavelength-division-multiplexed (WDM) communication systems. 4 , 5 Optical parametric generation (OPG) and optical parametric oscillation (OPO) 6 , in which a strong pump is mixed with vacuum noise input, are useful for generating widely tunable infrared radiation from a single pump laser. DFM in bulk nonlinear crystals has been demonstrated with AgGaS 2 and AgGaSe 2 7 and with periodically-poled LiNbO 3 (PPLN) 3 , but with low conversion efficiencies. Waveguide confinement has been shown to increase single-pass conversion efficiencies for second harmonic generation by factors up to 1000, as compared with bulk. However guided-wave DFM has, to date, failed to demonstrate comparable improvements to the bulk, primarily because of difficulties in coupling of the pump radiation. In this paper, we address the mode launching problem using integrated mode coupling structures, including mode filters, adiabatic tapers and directional couplers. Using these coupling components, we have demonstrated efficient guided-wave DFM in periodically-poled LiNbO 3 and guided-wave OPG.
Gold nanoring as a sensitive plasmonic biosensor for on-chip DNA detection (2012)

We report an on-chip nanosensor based on the localized surface plasmon resonance (LSPR) property of gold nanorings. The fabricated nanorings using nanosphere lithography showed highly tunable optical properties and were optimized to boost LSPR-based biosensing. The LSPR extinction spectra of the nanosensor agreed well with the theoretical calculations using a finite-difference time-domain model. Such an on-chip nanoring-based biosensor showed a refractive index sensitivity of 350 nm/refractive index unit with a figure of merit of 3.1 and was utilized to detect DNA in a real-time and label-free manner.
Acoustic high-frequency effects inside the package of capacitive silicon microphones and their impact on the device performance (2015)

We present investigations on acoustic effects occurring inside the sound port of capacitive silicon microphones, which exert additional frequency-dependent damping forces on the sensing membrane and, thus, affect the overall performance of the microphone. Extensive FE simulations have been carried out in order to study the airflow inside the package, to identify relevant impact factors, and to optimize an existing acoustic network model intended for implementation in a fully coupled, multi-energy domain system-level model of the device.
Oxidation Kinetics of Waveguide Roughness Minimization in Silicon Microphotonics (2003)

Waveguide roughness at the core/cladding interface causes severe signal attenuation in silicon waveguide systems. In this study, the smoothing kinetics of the roughness are simulated using TSUPREME4 and measured by AFM. As anticipated, we find that small period roughness is reduced faster than long period roughness. Simultaneously, we unexpectedly observe saturation in the oxidation smoothing kinetics.
Utilizing Two-Dimensional Photonic Crystals to Investigate the Correlation between the Air Duty Cycle and the Light Extraction Efficiency of InGaN-Based Light-Emitting Diodes (2014)

By incorporating two-dimensional photonic crystals into the surface of InGaN-based LEDs, the strong correlation between the air duty cycle and the light extraction efficiency of LEDs was demonstrated by optical and electrical measurement results.
Recognizing and Splitting Conditional Sentences for Automation of Business Processes Management (2021)

Business Process Management (BPM) is the discipline which is responsible for management of discovering, analyzing, redesigning, monitoring, and controlling business processes. One of the most crucial tasks of BPM is discovering and modelling business processes from text documents. In this paper, we present our system that resolves an end-to-end problem consisting of 1) recognizing conditional sentences from technical documents, 2) finding boundaries to extract conditional and resultant clauses from each conditional sentence, and 3) categorizing resultant clause as Action or Consequence which later helps to generate new steps in our business process model automatically. We created a new dataset and three models solve this problem. Our best model achieved very promising results of 83.82, 87.84, and 85.75 for Precision, Recall, and F1, respectively, for extracting Condition, Action, and Consequence clauses using Exact Match metric.
Use of an optical technique to evaluate the cerebral vascular effects of alcohol (A): Effects on deoxyhemoglobin (DH) and levels of reduced cytochrome oxidase (rCO) (1992)

The dose-response effects of acute A infusion were studied to examine the suggestion that A can induce stroke-like events as a consequence of cerebral vasospasm. By employing a single sending and receiving fiber, an optical backscatter measurement was employed to monitor the levels in DH and rCO in a closed cranium preparation. Anesthetized rats were prepared by cannulating a branch of the internal carotid artery and subjected to either a bolus infusion (BI) or to a constant infusion (CI) of 5 or 10% A at various rates. Results showed that low BI doses of A typically produced a slight increase in the oxyhemoglobin signal indicating that vasodilation had probably occurred. Higher BI doses, however, produced a prompt and significant reduction in the hemoglobin signal with a rise in rCO suggesting a vasoconstrictor response leading to ischemia, followed by recovery within 3-5 min. CI of A produced a similar cerebral vascular response, in a dose-related manner, but of a more sustained nature. At 30-50% of the BI dose levels, a global blanching of the brain surface occurred; rCO levels increased by 50-90% with a corresponding decline in levels of oxyhemoglobin. Control experiments using identical volumes/flow rates of Ringers solution failed tomore » produce any alterations in the optical spectrum. Overall, these data indicate that, depending on dose, (a) A can induce vasodilatory or vasoconstrictor effects in the intact brain; (b) the more pronounced effects involve vasospasm in the cortical microcirculation leading to global ischemia as determined by elevated levels of rCO and DH; (c) optical measurements permit direct noninvasive assessment of the cerebral vascular effects of substances of abuse.« less
Synthesis, assembly and reaction of a nanocatalyst in microfluidic systems: a general platform (2012)

We present a successive microfluidic approach to create and characterize hierarchical catalyst structures consisting of metal-decorated nanoparticles that are assembled into porous microparticles ("supraball" catalysts). First, using a silicon microreactor, platinum nanoparticles with a very narrow size distribution are grown and immobilized uniformly onto iron oxide/silica core-shell nanospheres. The Pt-decorated silica nanospheres are then assembled into uniform, spherical, micron-sized particles by using emulsion templates generated with a microfluidic drop generator. Finally, the assembled supraballs are loaded into a packed-bed microreactor for characterization of the catalytic reactivity. The prepared material showed excellent catalytic activity for the oxidation of aldehyde with only ~1 mg of material (containing ~50 μg of platinum nanoparticles). After the reactions, all the supraball catalysts are recovered by using the magnetic property of the underlying iron oxide/silica core-shell nanospheres.
Synthesizing Programs for Images using Reinforced Adversarial Learning (2018)

Advances in deep generative networks have led to impressive results in recent years. Nevertheless, such models can often waste their capacity on the minutiae of datasets, presumably due to weak inductive biases in their decoders. This is where graphics engines may come in handy since they abstract away low-level details and represent images as high-level programs. Current methods that combine deep learning and renderers are limited by hand-crafted likelihood or distance functions, a need for large amounts of supervision, or difficulties in scaling their inference algorithms to richer datasets. To mitigate these issues, we present SPIRAL, an adversarially trained agent that generates a program which is executed by a graphics engine to interpret and sample images. The goal of this agent is to fool a discriminator network that distinguishes between real and rendered data, trained with a distributed reinforcement learning setup without any supervision. A surprising finding is that using the discriminator's output as a reward signal is the key to allow the agent to make meaningful progress at matching the desired output rendering. To the best of our knowledge, this is the first demonstration of an end-to-end, unsupervised and adversarial inverse graphics agent on challenging real world (MNIST, Omniglot, CelebA) and synthetic 3D datasets.