gebhart/patrepeval huggingface dataset:
Light sheet luminescence imaging with Cherenkov excitation in thick scattering media (2016)

Light scattering leads to a severe loss of axial and transverse resolution with depth into tissue, limiting accuracy and value of biomedical luminescence imaging techniques. High-resolution imaging beyond a few-millimeter depth is prohibited because diffusive transport dominates beyond a few scattering distances. In this study, light sheet imaging through scattering media is demonstrated using a radiotherapy linear accelerator to deliver well-defined thin scanned sheets of x-rays. These sheets produce Cherenkov light within the medium, which in turn excites luminescence of an optical probe across the sheet plane. This luminescence can then be imaged by an intensified camera positioned perpendicular to the sheet plane. The precise knowledge of the light sheet position within the medium allowed for efficient attenuation correction of the signal with depth as well as spatial deconvolution of the excitation light. Together these methods allowed for the first time, to the best of our knowledge, high-resolution imaging of tissue-equivalent phantoms up to 3 cm thick, yielding the precise position and shape of luminescent lesions located deep in tissue without the need for nonlinear image reconstruction.
Structure–Activity relationship of tetrapeptides related to dermorphin: A 500‐MHz 1H‐nmr study (1988)

Abstract Several tetrapeptide analogs of dermorphin have been studied by means of 1 H‐nmr spectroscopy at 500 MHz in DMSO‐d 6 . In spite of the unfavorable properties of the solvent, it is possible to extract key structural information that, combined with the biological activity of the peptides, yields a structure–activity relationship that is consistent with our model of the μ receptor site. In particular, the importance of the orientation of the aromatic ring of the third residue, hypothesized in the theoretical model, is now substantiated. The shape of the P subsite of the receptor is also indirectly defined by the shape of several bulky side chains of the third residue.
OP033 Reduction of tissue pSTAT3 in Crohn's disease patients treated with filgotinib (GLPG0634, GS-6034), a JAK1-selective inhibitor (2017)

Background: Janus kinases (JAK) are a family of tyrosine kinases that play a key role in the signalling of more than 60 cytokines and growth factors. Many of these cytokines display pro-inflammatory activity in Crohn's Disease (CD). The selective JAK1 inhibitor filgotinib blocks cytokine signalling through the inhibition of STAT phosphorylation and has shown clinical efficacy in a double-blind, placebo-controlled Phase 2 study in CD (FITZROY). In order to understand the mechanism of action of filgotinib in CD patients, we measured the level of pSTAT3 in gut biopsies from this study. Methods: CD patients were randomized 3:1 to receive 200mg filgotinib or placebo QD for the first 10 weeks. Two biopsies, one each from the most and least affected mucosa, were collected during screening and at Wk 10 from each of the 6 predefined segments of the lower gastrointestinal tract. Samples from 60 patients with complete set of paired biopsies were selected. pSTAT3 was evaluated by IHC using an antibody specific to phosphorylated Y705. H-Score was quantified using Definiens Tissue Studio software. The mixed effect ANOVA method was used for evaluating the treatment effect and difference between patients achieving clinical remission (defined as CDAI <150) and those who did not. Results: Basal pSTAT3 level was comparable for the filgotinib and placebo groups. Following filgotinib treatment, pSTAT3 level was significantly reduced in the most affected mucosa from all segments combined: −36% (95% CI: −51%, −17%), whereas reduction in the placebo arm was not significant (although with less subjects): −24% (95% CI: −49%, +14%). In patients with clinical remission at Wk 10, pSTAT3 levels showed a significant reduction from baseline in each group: −62% (95% CI: −83%, −16%) with placebo, and −42% (95% CI: −57%,-21%) with filgotinib. In patients not achieving clinical remission, pSTAT3 from the placebo arm showed an average numerical increase of +12% (95% CI: −21%, +94%) whereas pSTAT3 was on average reduced with filgotinib: −28% (95% CI: −51%, +7%). Similar observations were made in the least affected mucosa of different segments. Table 1. Percent reduction of pSTAT3 at Week 10 from most affected area in all segments in CD patients Conclusions: Significant reduction of pSTAT3 by filgotinib on inflamed gut of CD patients provides direct evidence of its anti-inflammatory effect. Clinical remission status is associated with a decrease in pSTAT3. In non-remitters, the observed pSTAT3 reduction with filgotinib illustrates its pharmacodynamic effect through JAK1 inhibition. A large phase 3 program in CD and UC is ongoing.
Collaborative Multi-Agent Dialogue Model Training Via Reinforcement\n Learning (2019)

We present the first complete attempt at concurrently training conversational\nagents that communicate only via self-generated language. Using DSTC2 as seed\ndata, we trained natural language understanding (NLU) and generation (NLG)\nnetworks for each agent and let the agents interact online. We model the\ninteraction as a stochastic collaborative game where each agent (player) has a\nrole ("assistant", "tourist", "eater", etc.) and their own objectives, and can\nonly interact via natural language they generate. Each agent, therefore, needs\nto learn to operate optimally in an environment with multiple sources of\nuncertainty (its own NLU and NLG, the other agent's NLU, Policy, and NLG). In\nour evaluation, we show that the stochastic-game agents outperform deep\nlearning based supervised baselines.\n
A randomized phase 1/2 study of the safety and immunogenicity of a multivalent pneumococcal conjugate vaccine in healthy adults 50 through 85 years of age (2021)

Pneumococcal disease can be serious and debilitating in older adults. Pneumococcal conjugate vaccines (PCVs), such as the 13-valent PCV (PCV13), reduce pneumococcal disease rates caused by vaccine serotypes. Development of PCVs offering additional coverage against serotypes not contained in PCV13 can reduce disease burden further. The complementary 7-valent PCV (cPCV7) contains seven non-PCV13 serotypes (8, 10A, 11A, 12F, 15B, 22F, 33F) and can expand coverage by supplementing direct or indirect protection from existing PCVs. This phase 1/2, randomized, active-controlled, observer-blinded study evaluated cPCV7 safety and immunogenicity in healthy adults 50-85 years of age. Stage 1 randomized 66 healthy adults (50-64 years) naive to pneumococcal vaccines to receive cPCV7 or licensed tetanus, diphtheria, and acellular pertussis vaccine; Stage 2 randomized 445 healthy adults (65-85 years) previously vaccinated with PCV13 to receive cPCV7 or 23-valent polysaccharide vaccine. Local reactions and systemic events up to 14 days and adverse events (AEs) through 1 month after vaccination were assessed. Immunogenicity was evaluated by serotype-specific opsonophagocytic activity (OPA) assays before and 1 month after vaccination (and after 12 months in Stage 2). Rates of local reactions, systemic events, and AEs were generally similar after receipt of cPCV7 or control. Robust OPA responses were observed for all seven serotypes 1 month after cPCV7; titers declined yet remained above baseline 12 months after vaccination. Overall, this study found that in adults ≥50 years of age, cPCV7 was safe, well tolerated, and elicited functional immune responses to vaccine serotypes. ClinicalTrials.gov: NCT03313050.
Mass Spectrometric Data of Commonly Abused Amphetamines and Their Derivatives - Cross Contribution of Ion Intensity between the Analytes and Their Isotopically Labeled Analogs. (2005)

With GC-MS as the preferred method and isotopically labeled analogs of the analytes as the internal standards (ISs) of choice for the analysis of drugs/metabolites in biological specimens, one important aspect associated with chemical derivatization (CD) is that the CD products derived from the analyte and the selected IS must generate ions suitable for designating the analyte and the IS; these ions cannot have significant crosscontribution (CC), i.e., contribution to the intensity of the ion designated for the analyte by the IS, and vice versa. With this in mind, the authors have reviewed literature and commercial information on common CD reagents and methods and conducted a thorough search of isotopically labeled analogs of commonly abused amphetamine-type drugs/metabolites that are commercially available. These ISs and analytes were then derivatized with various derivatization groups. These CD products were then analyzed by GC-MS and the resulting MS data are presented here in two forms: (a) systematic presentation of full-scan spectra; and (b) tabulation of CC data for ions with potential for designating the ISs and analytes. Many (if not most) of these full-scan spectra are not yet available in the literature and should be of daily reference value to forensic and clinical laboratories that are engaged in the analysis of these drugs/metabolites. Full-scan MS data were further used to select ion-pairs with potential for designating the analytes and ISs in quantitative analysis protocols. The CC data of these ion-pairs were evaluated using data collected under the SIM mode and summarized in table format. These data should save enormous amounts of time and efforts for practicing laboratories in their search for this analytical parameter.
Usefulness of Oncoplastic Volume Replacement Techniques after Breast Conserving Surgery in Small to Moderate-sized Breasts (2012)

Oncoplastic volume replacement techniques can be reliable and useful for the correction of breast deformity after breast-conserving surgery, especially in patients with small to moderate-sized breasts.
A Novel NAMPT Inhibitor-Based Antibody–Drug Conjugate Payload Class for Cancer Therapy (2022)

Inhibition of intracellular nicotinamide phosphoribosyltransferase (NAMPT) represents a new mode of action for cancer-targeting antibody-drug conjugates (ADCs) with activity also in slowly proliferating cells. To extend the repertoire of available effector chemistries, we have developed a novel structural class of NAMPT inhibitors as ADC payloads. A structure-activity relationship-driven approach supported by protein structural information was pursued to identify a suitable attachment point for the linker to connect the NAMPT inhibitor with the antibody. Optimization of scaffolds and linker structures led to highly potent effector chemistries which were conjugated to antibodies targeting C4.4a (LYPD3), HER2 (c-erbB2), or B7H3 (CD276) and tested on antigen-positive and -negative cancer cell lines. Pharmacokinetic studies, including metabolite profiling, were performed to optimize the stability and selectivity of the ADCs and to evaluate potential bystander effects. Optimized NAMPTi-ADCs demonstrated potent <i>in vivo</i> antitumor efficacy in target antigen-expressing xenograft mouse models. This led to the development of highly potent NAMPT inhibitor ADCs with a very good selectivity profile compared with the corresponding isotype control ADCs. Moreover, we demonstrate─to our knowledge for the first time─the generation of NAMPTi payload metabolites from the NAMPTi-ADCs <i>in vitro</i> and <i>in vivo</i>. In conclusion, NAMPTi-ADCs represent an attractive new payload class designed for use in ADCs for the treatment of solid and hematological cancers.
An in situ analysis of the resist pattern formation process (2012)

In this paper, the 'pattern formation' characteristics of a polyhydroxystyrene (PHS)-acryl hybrid extreme ultraviolet (EUV) resist was investigated using a high speed atomic force microscope. This analysis covers the dissolution or development, rinse and drying processes that are conventionally applied after EUV exposure and post exposure bake. As a result, it was found that during the development process, the EUV-exposed resist film exhibited swelling characteristics. This was assumed to be the effect of the balance / imbalance in dissolvability introduced by the hydrophobic acryl and hydrophilic PHS components of this hybrid resist. During the rinse process with de-ionized water, the critical dimension (CD) of the resulting line pattern after development was observed to increase with rinse time. This was attributed to a possible permeation of water into the resist line pattern causing the CD to swell. Lastly, for the drying process, the same line pattern CD was found to shrink similar to pre-rinse sizes and taper at the top edges. This suggests evaporation of the rinse water imbedded into the resist line pattern.
Designing a rate-based transport protocol for wired-wireless networks (2007)

A large majority of the Internet traffic relies on TCP as its transport protocol. In future, as the edge of the Internet continues to extend over the wireless medium, TCP (or its close variants) may not prove to be appropriate. The key reason is in TCP’s inability to discriminate congestion losses from transmission losses. Since transmission losses are frequent in wireless networks, the penalty from loss misclassification can become high, leading to performance degradation. This paper presents an eXtended Rate-based Transport Protocol (XRTP), designed to support communication over lossy wireless media. We depart from the ack-based rate control paradigm. Instead, we try to estimate the network conditions by injecting probe packets at the sender, and then observing the spacing between packets that arrive at the receiver. We show that these observations can be useful indicators of available bandwidth, network congestion, and even the cause of packet loss. The inferences from the observations are utilized to regulate the transmission rate at the sender, leading to desirable properties of congestion control and loss discrimination. Simulation results show the efficacy of our proposed rate-based protocol in lossy wireless environments.
Metabolic shifts in Zymomonas mobilis in response to growth conditions (1988)

Extensive work on ethanol production with the Gram-negative bacterium Zymomonas mobilis has revealed that this is a promising microorganism for industrial use. Concise knowledge of the physiology and metabolism of this organism provides the basis for further improvements by genetic engineering and for the optimization of Zymomonas-specific fermentation processes.
Performance Analysis of Channel Extrapolation in FDD Massive MIMO Systems (2020)

Channel estimation for the downlink of frequency division duplex (FDD) massive multiple-input-multiple output (MIMO) systems is well known to generate a large overhead as the amount of training generally scales with the number of transmit antennas in a MIMO system. In this paper, we consider the solution of extrapolating the channel frequency response from uplink pilot estimates to the downlink frequency band. This drastically reduces the downlink pilot overhead and completely removes the need for a feedback from the users. The price to pay is a degradation in the quality of the channel estimates, which reduces the downlink spectral efficiency. We first show that conventional estimators fail to achieve reasonable accuracy. We propose instead to use high-resolution channel estimation. We derive the Cramer-Rao lower bound (CRLB) of the mean squared error (MSE) of the extrapolated channel. Furthermore, a relationship between the imperfect channel state information (CSI) and the downlink user performance is derived. The extrapolation-based FDD massive MIMO performance is validated through numerical simulations and compared to a corresponding time division duplex (TDD) system. Considered figures of merit for extrapolation performance include channel MSE, beamforming efficiency, extrapolation range, spectral efficiency and uncoded symbol error rate. Our main conclusion is that channel extrapolation is a viable solution for FDD massive MIMO systems.
Nutrient contents, color, texture, and sensory evaluation of 12 Arkansas grown soybean cultivars in canned products (2013)

Soybean was introduced in the U.S. in the 1800s, and it has been proven to have several health benefits. New cultivars of soybeans with varying hull colors have been developed using plantbreeding technology. Canning is one of the effective processing methods to extend the shelf life of products. However, very little information is available on canned soybeans. This research studied the composition of 12 soybean cultivars including two cultivars with brown seed coat (R08-4014 and R09-349), three cultivars with black seed coat (R07-1927, R07-10396, and R09-345), and seven regular cultivars with yellow seed coat (R05-1772, R05-4969, R07-2001, R08-4005, R08- 4006, UA Kirksey, and JYC-2) grown in Arkansas and investigated the effect of the canning process on the color, texture, and sensory properties. The data showed that the 12 soybean cultivars had lower moisture content values ranging from 6.7% to 9.1% in comparison to higher levels of moisture (13%) present in commercial lines. The protein content ranged from 40.2% to 51.0% which was higher than the expected approximate content of commercial soy (30-40%). The canning process increased the redness (+a values) of the beans but neither off-flavor nor bitterness was observed in the canned products. Among the soybean cultivars with yellow seed, the canned products of JYC-2 were the most preferred according to sensory panelists. In conclusion, canned products of soybeans can be prepared under optimized conditions to produce a product that is acceptable to consumers.
Scalable Preparation and Differential Pharmacologic and Toxicologic Profiles of Primaquine Enantiomers (2016)

Hematotoxicity in individuals genetically deficient in glucose-6-phosphate dehydrogenase (G6PD) activity is the major limitation of primaquine (PQ), the only antimalarial drug in clinical use for treatment of relapsing Plasmodium vivax malaria. PQ is currently clinically used in its racemic form. A scalable procedure was developed to resolve racemic PQ, thus providing pure enantiomers for the first time for detailed preclinical evaluation and potentially for clinical use. These enantiomers were compared for antiparasitic activity using several mouse models and also for general and hematological toxicities in mice and dogs. (+)-(S)-PQ showed better suppressive and causal prophylactic activity than (-)-(R)-PQ in mice infected with Plasmodium berghei. Similarly, (+)-(S)-PQ was a more potent suppressive agent than (-)-(R)-PQ in a mouse model of Pneumocystis carinii pneumonia. However, at higher doses, (+)-(S)-PQ also showed more systemic toxicity for mice. In beagle dogs, (+)-(S)-PQ caused more methemoglobinemia and was toxic at 5 mg/kg of body weight/day given orally for 3 days, while (-)-(R)-PQ was well tolerated. In a novel mouse model of hemolytic anemia associated with human G6PD deficiency, it was also demonstrated that (-)-(R)-PQ was less hemolytic than (+)-(S)-PQ for the G6PD-deficient human red cells engrafted in the NOD-SCID mice. All these data suggest that while (+)-(S)-PQ shows greater potency in terms of antiparasitic efficacy in rodents, it is also more hematotoxic than (-)-(R)-PQ in mice and dogs. Activity and toxicity differences of PQ enantiomers in different species can be attributed to their different pharmacokinetic and metabolic profiles. Taken together, these studies suggest that (-)-(R)-PQ may have a better safety margin than the racemate in human.
A W-Band Photonic Transmitter-Mixer Based on High-Power Near-Ballistic Uni-Traveling-Carrier Photodiode (NBUTC-PD) for 1.25-Gb/s BPSK Data Transmission under Bias Modulation (2009)

We demonstrate W-band photonic transmitters-mixers, which are composed of near-ballistic-uni-traveling-carrier-photodiodes and quasi-Yagi antennas without integrating Si-lens. By utilizing it, data-transmission at W-band can be achieved under bias modulation of 1.25-Gb/s BPSK with 5GHz IF signals.
Redistribution of Bruton's tyrosine kinase by activation of phosphatidylinositol 3-kinase and Rho-family GTPases (2000)

Bruton's tyrosine kinase (Btk) is a member of the Tec family of protein tyrosine kinases (PTK) characterized by an N-terminal pleckstrin homology domain (PH) thought to directly interact with phosphoinositides. We report here that wild-type (wt) and also a gain-of-function mutant of Btk are redistributed following a wide range of receptor-mediated stimuli through phosphatidylinositol 3-kinase (PI 3-K) activation. Employing chimeric Btk with green fluorescent protein in transient transfections resulted in Btk translocation to the cytoplasmic membrane of live cells through various forms of upstream PI 3-K activation. The redistribution was blocked by pharmacological and biological inhibitors of PI 3-K. A gain-of-function mutant of Btk was found to be a potent inducer of lamellipodia and / or membrane ruffle formation. In the presence of constitutively active forms of Rac1 and Cdc42, Btk is co-localized with actin in these regions. Formation of the membrane structures was blocked by the dominant negative form of N17-Rac1. Therefore, Btk forms a link between a vast number of cell surface receptors activating PI 3-K and certain members of the Rho-family of small GTPases. In the chicken B cell line, DT40, cells lacking Btk differed from wt cells in the actin pattern and showed decreased capacity to form aggregates, further suggesting that cytoskeletal regulation mediated by Btk may be of physiological relevance.
From TRAIL to ONC201: Case Study on the Safety Benefit of Developing Targeted Agents Against Cancer‐selective Pathways (2018)

A major goal of drug development is to end up with a safe and effective therapy for a disease such as cancer. We describe our experience with taking the small molecule ONC201/TIC10 from the lab to clinical trials. The path involved a phenotypic drug screen to identify a small molecule that activates a pathway that has been established as cancer specific – the TRAIL pathway. In vitro experiments in multiple tumor types and in normal cells led to the identification of drug candidates that have a favorable therapeutic index, a key characteristic for any successful drug. ONC201 was chosen for in vivo testing in rodent species. It was tested via different routes of administration and different frequencies, and different tissues were analyzed after varying drug-exposure times. Valuable information was gained on drug efficacy, bioavailability, and impact on non-tumor tissue. Pharmacodynamic parameters were assessed in tumor xenografts and in normal tissue to understand the drug's activity in both tumor and normal cells, and additional IND-enabling studies were performed before the drug entered into clinical trials. Ongoing efforts continue to unravel the mechanism of action of ONC201 with a goal of optimizing biomarkers of clinical response. ONC201 clinical development continues with observed single-agent safety and efficacy and with pursuit of combination therapy studies in various tumor types. Further understanding of the molecular mechanisms of ONC201 should lead to rationally designed combination therapy studies and a more comprehensive biomarker analysis that may improve patient selection and patient benefit.