gebhart/patrepeval huggingface dataset:
How will diagnostics create new opportunities for prophylactic and therapeutic vaccines? (2011)

The Phacilitate Vaccine Forum in Washington DC (Jan 24-26, 2011) brought together vaccine stakeholders from industry, government and non-government organizations to discuss broad current issues covering the spectrum of vaccine policy, funding, research and clinical development, manufacturing, regulatory, and post marketing safety and surveillance. While the conference is held annually and the topics generally discussed reflect the emerging trends, case studies, and best practices of current interest to the vaccine industry, this year's meeting had a new plenary session focusing on the intersection of diagnostics and vaccine development. The session was chaired by Dr. Una Ryan (President and CEO, Diagnostics for All) with the provocative title "How will diagnostics create new opportunitites for prophylactic and therapeutic vaccines?" and was followed by a panel discussion amongst industry leaders discussing the key diagnostic applications gaining interest in the vaccine industry. A common theme running through the session was the increasingly significant role of companion diagnostics and immune monitoring to facilitate and accelerate vaccine development. Indeed the recent examples from pneumococcal and meningococcal vaccine development where the developers and regulatory agencies have considered the use of diagnostic assays and immune markers to assess efficacy of the candidate vaccines in regards to licensure strategies for expanding the serotypes covered, can be considered as breakthrough events for the diagnostics developers. As such the meeting and the session was timely in presenting current progress and for soliciting a convergence of opinions amongst the vaccine industry and the regulatory agencies.
Compositional Law Parsing with Latent Random Functions (2022)

Human cognition has compositionality. We understand a scene by decomposing the scene into different concepts (e.g., shape and position of an object) and learning the respective laws of these concepts, which may be either natural (e.g., laws of motion) or man-made (e.g., laws of a game). The automatic parsing of these laws indicates the model's ability to understand the scene, which makes law parsing play a central role in many visual tasks. This paper proposes a deep latent variable model for Compositional LAw Parsing (CLAP), which achieves the human-like compositionality ability through an encoding-decoding architecture to represent concepts in the scene as latent variables. CLAP employs concept-specific latent random functions instantiated with Neural Processes to capture the law of concepts. Our experimental results demonstrate that CLAP outperforms the baseline methods in multiple visual tasks such as intuitive physics, abstract visual reasoning, and scene representation. The law manipulation experiments illustrate CLAP's interpretability by modifying specific latent random functions on samples. For example, CLAP learns the laws of position-changing and appearance constancy from the moving balls in a scene, making it possible to exchange laws between samples or compose existing laws into novel laws.
Experimental Demonstration of Training-Aided Frequency Domain Equalization in Hybrid WDM Systems with 40-Gb/s PDM-QPSK and 10-Gb/s OOK Channels (2013)

Training-aided 2×2 MIMO FDE supported by 16-symbol CAZAC sequences has been demonstrated in hybrid WDM channels transmitted over a 480-km dispersion compensated link. Performance is evaluated with respect to a commonly employed blind TDE.
ChemInform Abstract: Synthesis and Cytotoxic Activity of N‐[2‐(Dimethylamino)ethyl] Carboxamide Derivatives of Benzofuro[2,3‐b]quinoline, 6H‐Quinindoline, Indeno[2,1‐b]quinoline and [1]Benzothieno[2,3‐b]quinoline. (2000)

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.
DSHP: A “power bar” for sustained immune responses? (1998)

Primary human immunodeficiencies comprise a broad group of disorders ranging from severely impaired lymphocyte development to more subtle functional abnormalities (reviewed in ref. 1). The recent identification of the genetic basis of several of these diseases has enriched our understanding of the molecular events controlling the development and function of the immune system. These gene products fall into four major categories: enzymes regulating DNA recombination and nucleotide metabolism, cell cycle regulators, proteins involved in antigen presentation, and components of B and T cell signal transduction pathways (1). Nichols et al. (2) describe the most recent addition to the latter group in this issue of the Proceedings. DHSP encodes a single SH2 domain and is mutated in patients with X-linked lymphoproliferative syndrome (XLP). DHSP represents a new paradigm in signal transduction defects associated with immunodeficiencies. All signaling molecules previously shown to be involved in these diseases, including γc, JAK-3, and ZAP70 in severe combined immunodeficiency and Btk in X-linked agammaglobulinemia, are “hard wired” components essential for signal transmission (1). In contrast, DSHP is up-regulated late in the immune response and likely modulates signal duration or amplitude.
Location and Topology of the Fundamental Gap in Photonic Crystals (2022)

The fundamental, or first, band gap is of unmatched importance in the study of photonic crystals. Here, we address precisely where this gap can be opened in the band structure of three-dimensional photonic crystals. Although strongly constrained by symmetry, this problem cannot be addressed directly with conventional band-symmetry analysis due to the existence of a photonic polarization vortex at zero frequency. We develop an approach for overcoming the associated symmetry singularity by incorporating fictitious, auxiliary longitudinal modes. Our strategy also enables us to extend recent developments in symmetry-based topological analysis to the fundamental gap of three-dimensional photonic crystals. Exploiting this, we systematically study the topology of the minimal fundamental gaps. This reveals the existence of topological gap obstructions that push the fundamental gap higher than what a conventional analysis would suggest. Our work demonstrates that topology can play a crucial role in the opening of the fundamental photonic gap and informs future theoretical and experimental searches for conventional and topological band gaps in three-dimensional photonic crystals.
Single-Cell Transcriptomic Profiling of Pluripotent Stem Cell-Derived SCGB3A2+ Airway Epithelium (2018)

Lung epithelial lineages have been difficult to maintain in pure form in vitro, and lineage-specific reporters have proven invaluable for monitoring their emergence from cultured pluripotent stem cells (PSCs). However, reporter constructs for tracking proximal airway lineages generated from PSCs have not been previously available, limiting the characterization of these cells. Here, we engineer mouse and human PSC lines carrying airway secretory lineage reporters that facilitate the tracking, purification, and profiling of this lung subtype. Through bulk and single-cell-based global transcriptomic profiling, we find PSC-derived airway secretory cells are susceptible to phenotypic plasticity exemplified by the tendency to co-express both a proximal airway secretory program as well as an alveolar type 2 cell program, which can be minimized by inhibiting endogenous Wnt signaling. Our results provide global profiles of engineered lung cell fates, a guide for improving their directed differentiation, and a human model of the developing airway.
Cross-cohort gut microbiome associations with immune checkpoint inhibitor response in advanced melanoma (2022)

The composition of the gut microbiome has been associated with clinical responses to immune checkpoint inhibitor (ICI) treatment, but there is limited consensus on the specific microbiome characteristics linked to the clinical benefits of ICIs. We performed shotgun metagenomic sequencing of stool samples collected before ICI initiation from five observational cohorts recruiting ICI-naive patients with advanced cutaneous melanoma (n = 165). Integrating the dataset with 147 metagenomic samples from previously published studies, we found that the gut microbiome has a relevant, but cohort-dependent, association with the response to ICIs. A machine learning analysis confirmed the link between the microbiome and overall response rates (ORRs) and progression-free survival (PFS) with ICIs but also revealed limited reproducibility of microbiome-based signatures across cohorts. Accordingly, a panel of species, including Bifidobacterium pseudocatenulatum, Roseburia spp. and Akkermansia muciniphila, associated with responders was identified, but no single species could be regarded as a fully consistent biomarker across studies. Overall, the role of the human gut microbiome in ICI response appears more complex than previously thought, extending beyond differing microbial species simply present or absent in responders and nonresponders. Future studies should adopt larger sample sizes and take into account the complex interplay of clinical factors with the gut microbiome over the treatment course.
Microfluidic integration of porous photonic crystal nanolasers for chemical sensing (2005)

We have recently developed planar photonic crystal nanolasers based on porous cavity designs. High-quality factor cavities confine light within the pores of the photonic crystal and, thus, our lasers are ideally suited for the investigation of nanoscale interactions between light and matter. We have demonstrated the operation of photonic crystal lasers within different chemical solutions, embedded them into silicone microfluidic flow channels, and were able to detect refractive index changes as small as /spl Delta/n=0.005. We predict that our porous nanolasers can detect refractive index changes as small as /spl Delta/n=8.23/spl middot/10/sup -4/.
[Acquired von Willebrand syndrome with autoimmune hemolytic anemia]. (2004)

A 17-year-old female underwent examination due to the chief complaints of epistaxis and bleeding from the gums. In addition to hemolytic anemia (Coombs positivity), she was found to have a marked reduction in the von Willebrand factor antigen (vWF:Ag) and ristocetin cofactor activity (vWF:RCo). Anti vWF antibodies mainly comprised of IgG1 fractions were also detected, so acquired von Willebrand syndrome (AvWS) with autoimmune hemolytic anemia (AIHA) was diagnosed. The recovery of vWF:Ag and vWF:RCo following administration of a factor VIII concentrate containing vWF was good, but the half life was short at about two hours and the collagen binding activity and vWF:RCo in mixing tests with control plasma were only mildly inhibited. Therefore, the anti vWF antibody in the present case was thought not to inhibit vWF function but to be involved in clearance promotion. Hemostatic control during hemorrhage was performed using a factor VIII concentrate containing vWF. With the administration of prednisolone thereafter, anti vWF antibodies disappeared at the same time as there was improvement in the AIHA. Throughout the course the patient contracted acute hepatitis A, became pregnant and gave birth, but there were no clear effects on the clinical phenotype of AvWS.
Surface antigen expression on CD34+ cord blood cells: Comparative analysis by flow cytometry and limiting dilution (LD) RT-PCR of chymopapain-treated or untreated cells (1996)

Expression of antigens coexpressed on cord blood (CB) CD34+ cells was evaluated by flow cytometry analysis and reverse transcriptase polymerase chain reaction (RT-PCR). Antigen expression was also comparatively analyzed by flow cytometry and limiting dilution (LD) RT-PCR to investigate effects of chymopapain on epitopes of several cell surface markers: LD RT-PCR allows detection of the expression of antigens degraded by chymopapain which are not identified by flow cytometry. Monoclonal antibodies (MoAbs) that recognize chymopapain resistant epitopes on several coexpressed cell surface markers were identified: these included MoAbs directed against CD11a, CD13, CD18, CD38, CD45RO, CD51, HLA-DR, Thy-1, c-kit, flt-3 (STK-1), and mdr-1. Interestingly, chymopapain treatment caused enhanced staining with MoAbs against HLA-DR, Thy-1, flt-3, mdr-1, and CD51. The frequency (LD RT-PCR) of CD18, CD38, Thy-1, and c-kit RT-PCR signals on pure sorted CD34+ CD18-, CD34+ CD38-, CD34+ Thy-1-, and CD34+ c-kit- cells, respectively, was similar in corresponding subsets treated or not with chymopapain. In contrast, the frequency of CD33 RT-PCR signals on sorted CD34+ CD33- cells was higher in chymopapain-treated samples than in untreated samples and thus confirmed at the transcriptional level that the epitope recognized by anti-CD33 is chymopapain sensitive. Our findings extend data on the phenotypic profile of CB CD34+ cells and show that several key cell surface markers of hematopoietic progenitor cells are chymopapain resistant. In addition, the results of the present study demonstrate that the RT-PCR can be applied to the analysis of multiple RNA species in small numbers of hematopoietic progenitor cells and show that LD RT-PCR allows the identification and frequency determination of rare cells which are undetectable by flow cytometry.
Multi-dimensional reward volumes for sensor priority strategies (2014)

We describe a model for determining strategies for making decisions for sensor prioritization strategies. We combine operations research methods and remote sensing for decision making with several possible actions, state of the world, and a mixed probability metric. We perform data mining and discover patterns to automatically enhance situational awareness from multiple sensor inputs. Our solution has been developed for a method for determining actionable information to efficiently manage remote sensing assets and use open source information. Our tool allows for calculating optimal strategies, provides greater knowledge about the state of the world, and increases the likelihood of a decision maker making the best decision. We discuss multi-dimensional game theory using linear programming methods to solve for multiple possible strategies. We discuss a new concept of reward volumes. The decision maker's success depends upon his ability to correctly and automatically judge the multiple factors. The goal of our system, called GlobalSite, is to deliver trustworthy threat analysis systems and services that understand situations, while being a vital tool for continuing mission operations.
Percutaneous Coronary Intervention without onsite Cardiac Surgery Backup (2013)

Percutaneous coronary intervention was feasible with acceptable complications in a tertiary-level hospital without onsite cardiac surgery backup. ST-elevation myocardial infarction was the major indication and cardiogenic shock was the major complication observed, and non proximal artery stenting was more common than the proximal artery stenting.
Effects of flue-cured tobacco programs on returns to land and labor / (1968)

Excerpts from the report: This study has the following three objectives: (1) To measure returns to land and labor used in flue-cured tobacco production for selected periods of time from 1922 to 1960. (2) To determine to what extent, if any, tenure arrangements affected returns to land and labor and the distribution of benefits of the flue-cured tobacco programs. (3) To estimate the effects of the flue-cured tobacco programs on the distribution of returns to land and labor. Accomplishment of the first two objectives is necessary before the final objective can be realized. Returns to land and labor are estimated for farms operated under various tenure arrangements in two major flue-cured tobacco production areas--the Piedmont region of Virginia and the Coastal Plains of North Carolina.
Differential Expression of CD49a and CD49b Determines Localization and Function of Tumor-Infiltrating CD8+ T Cells (2021)

CD8<sup>+</sup> T-cell infiltration and effector activity in tumors are correlated with better overall survival of patients, suggesting that the ability of T cells to enter and remain in contact with tumor cells supports tumor control. CD8<sup>+</sup> T cells express the collagen-binding integrins CD49a and CD49b, but little is known about their function or how their expression is regulated in the tumor microenvironment (TME). Here, we found that tumor-infiltrating CD8<sup>+</sup> T cells initially expressed CD49b, gained CD49a, and then lost CD49b over the course of tumor outgrowth. This differentiation sequence was driven by antigen-independent elements in the TME, although T-cell receptor (TCR) stimulation further increased CD49a expression. Expression of exhaustion markers and CD49a associated temporally but not mechanistically. Intratumoral CD49a-expressing CD8<sup>+</sup> T cells failed to upregulate TCR-dependent Nur77 expression, whereas CD69 was constitutively expressed, consistent with both a lack of productive antigen engagement and a tissue-resident memory-like phenotype. Imaging T cells in live tumor slices revealed that CD49a increased their motility, especially of those in close proximity to tumor cells, suggesting that it may interfere with T-cell recognition of tumor cells by distracting them from productive engagement, although we were not able to augment productive engagement by short-term CD49a blockade. CD49b also promoted relocalization of T cells at a greater distance from tumor cells. Thus, our results demonstrate that expression of these integrins affects T-cell trafficking and localization in tumors via distinct mechanisms, and suggests a new way in which the TME, and likely collagen, could promote tumor-infiltrating CD8<sup>+</sup> T-cell dysfunction.
ImmunoMap: A Bioinformatics Tool for T-cell Repertoire Analysis (2017)

Despite a dramatic increase in T-cell receptor (TCR) sequencing, few approaches biologically parse the data in a fashion that both helps yield new information about immune responses and may guide immunotherapeutic interventions. To address this issue, we developed a method, ImmunoMap, that utilizes a sequence analysis approach inspired by phylogenetics to examine TCR repertoire relatedness. ImmunoMap analysis of the CD8 T-cell response to self-antigen (K<sup>b</sup>-TRP2) or to a model foreign antigen (K<sup>b</sup>-SIY) in naïve and tumor-bearing B6 mice showed differences in the T-cell repertoire of self- versus foreign antigen-specific responses, potentially reflecting immune pressure by the tumor, and also detected lymphoid organ-specific differences in TCR repertoires. When ImmunoMap was used to analyze clinical trial data of tumor-infiltrating lymphocytes from patients being treated with anti-PD-1, ImmunoMap, but not standard TCR sequence analyses, revealed a clinically predicative signature in pre- and posttherapy samples. <i>Cancer Immunol Res; 6(2); 151-62. ©2017 AACR</i>.
TU‐AB‐202‐09: Performance of Cross‐Modality DIR Algorithms Using Images Computed from a Novel, Tissue‐Like Phantom Capable of Reproducible Degrees of Deformation (2016)

Purpose: Develop a framework for the spatial accuracy assessment of multi‐modality deformable image registration (DIR) based on precise and reproducible deformations of a novel prostate phantom. Methods: An existing, tissue‐like prostate phantom has been adapted to allow quantifiable, reproducible, and variable degrees of volumetric deformation. This phantom is sequentially deformed into 11 stationary deformation states that can be individually imaged using CT, MRI, US and CBCT. The deformation is induced programmatically by changing the water volume of a balloon using a precise syringe pusher (5ml increments), effectively displacing and deforming the prostate and surrounding tissue. To demonstrate the phantom's utility as a DIR assessment tool, selected DIR algorithms (CT&lt;‐&gt;MR: Normalized Mutual Information, MR‐MR: Mutual Information, CT‐CT: Local Cross‐Correlation+Mutual Information) were applied to intra and cross‐imaging modalities depicting varying degrees of deformation. DIR accuracy was assessed via the DICE overlap score, calculated between the deformed prostate contour (computed by warping the manually delineated contour on the initial deformation state) and the manually delineated contour on the target deformation state. Results: DICE coefficients show excellent agreement of individual deformation states for MR and CT, hence validating the reproducibility of the induced deformation (&lt; 1.0 + 0.1 %). Intra‐modality DIR (MR‐MR, CT‐CT) shows good performance (0.93–0.98). CT‐to‐MR performance is acceptable only for the closest 5–6 deformation states (&gt; 0.94), while the DIR solutions for farthest 6 deformation states (0.78–0.92) are erroneous or artifactual. MR‐to‐CT DIR performance is demonstrably weaker (0.0–0.96) yielding asymmetrical errors w.r.t. the initial deformation state (no‐deformation vs. maxdeformation). Moreover, the first 3 deformed contours show zero overlap with the manual contours. Conclusion: We have developed a novel prostate phantom capable of gradual and reproducible deformation, and demonstrated its ability to assess multi‐modality (CT&lt;‐&gt;MR) DIR algorithm performance and range. Due to the phantom multi‐imaging capabilities, other cross‐imaging DIR algorithms can now be explored.
Fully compliant tensural bistable micromechanisms (FTBM) (2005)

A new class of bistable mechanisms, the fully compliant tensural bistable micromechanism (FTBM) class, is introduced. The class consists of linear bistable micromechanisms that undergo tension loads, in addition to the bending loads present, through their range of motion. Proof-of-concept designs fabricated in two different microelectromechanical systems (MEMS) surface micromachining processes were demonstrated. Three sets of refined designs within the FTBM class were designed using optimization methods linked with nonlinear finite element analysis (FEA), then fabricated and tested. Measured force and displacement performance are compared to values obtained by FEA. On-chip actuation of the bistable mechanisms was achieved using thermomechanical in-plane microactuators (TIMs). The FTBM class of bistable mechanisms explores a relatively new design space for fully compliant micromechanisms, and mechanisms from this class have promise in such applications as micro shutter positioning, microvalves, and electrical microrelays. [1448].
Organotemplate-free and one-pot fabrication of nano-rod assembled plate-like micro-sized mordenite crystals (2012)

Plate-like micro-sized MOR and Fe-MOR zeolite crystals assembled from highly uniform nano-rods are successfully fabricated by an organotemplate-free method during one-pot crystallization in the presence of a MOR seed solution. The seed solution rich in 4-membered rings plays a critical role for the formation of the unique nano-rod assembled structure.