gebhart/patrepeval huggingface dataset:
The guidebook, the friend, and the room (2001)

In this paper, we describe an electronic guidebook prototype and report on a study of its use in a historic house. Supported by mechanisms in the guidebook, visitors constructed experiences that had a high degree of interaction with three entities: the guidebook, their companions, and the house and its contents. For example, we found that most visitors played audio descriptions through speakers (rather than using headphones or reading textual descriptions) to facilitate communication with their companions.
Small scale, big impact: the world’s thinnest and strongest free-standing carbon nanotube membrane (2021)

Sometimes the biggest impact can be made in the smallest details. Canatu pioneers the future of semiconductor manufacturing and extreme ultraviolet (EUV) lithography with its freestanding carbon nanotube (CNT) membrane pellicles that protect photomasks from particles and defects, enhancing precision, shortening processing, and increasing production efficiency per wafer. When the already remarkable 1-dimensional intrinsic properties of virtually defect-free CNTs are expanded into a 2-dimensional network, this added degree of freedom results in a membrane with an unequaled combination of optical and mechanical properties, that may truly provide solutions for the extreme physics of EUV at increasing powers. Here, we demonstrate the extensive customizability and versatility of Canatu’s CNT synthesis and freestanding network fabrication processes. For example, the fine structure and chemistry of individual tubes, as well as the mesoscopic morphology of the network can be optimized extensively. In practice, this enables precise control over the size and type of catalyst particles, as well as the diameter of the tube and the number of walls in the carbon nanotube (Single, Double, or Multi-walled). The orientation of the CNTs in the network can also be controlled, and the CNTs can be induced to form either larger or smaller bundles, resulting in dense or sparse networks with constant optical transmittance. CNT surfaces can be further treated or coated in response to specific chemical or optical requirements. In summary, this high degree of tunability is becoming increasingly critical in applications where strict particle and impurity filtering requirements must be met with minimal optical disturbances.
Management of Patients with Advanced Prostate Cancer: The Report of the Advanced Prostate Cancer Consensus Conference APCCC 2017 (2017)

The Advanced Prostate Cancer Consensus Conference provides a forum to discuss and debate current diagnostic and treatment options for patients with advanced prostate cancer. The conference, which has been held three times since 2015, aims to share the knowledge of world experts in prostate cancer management with health care providers worldwide. At the end of the conference, an expert panel discusses and votes on predefined consensus questions that target the most clinically relevant areas of advanced prostate cancer treatment. The results of the voting provide a practical guide to help clinicians discuss therapeutic options with patients as part of shared and multidisciplinary decision making.
Tracking Innate Immune Activation in a Mouse Model of Parkinson’s Disease Using TREM1 and TSPO PET Tracers (2022)

Parkinson's disease (PD) is associated with aberrant innate immune responses, including microglial activation and infiltration of peripheral myeloid cells into the central nervous system (CNS). Methods to investigate innate immune activation in PD are limited and have not yet elucidated key interactions between neuroinflammation and peripheral inflammation. Translocator protein 18 kDa (TSPO) PET is a widely evaluated imaging approach for studying activated microglia and peripheral myeloid lineage cells in vivo but has yet to be fully explored in PD. Here, we investigate the utility of TSPO PET in addition to PET imaging of triggering receptor expressed on myeloid cells 1 (TREM1)-a novel biomarker of proinflammatory innate immune cells-for detecting innate immune responses in the 6-hydroxydopamine mouse model of dopaminergic neuron degeneration. <b>Methods:</b> C57/BL6J and <i>TREM1</i> knockout mice were stereotactically injected with 6-hydroxydopamine in the left striatum; control mice were injected with saline. At day 7 or 14 after surgery, mice were administered <sup>18</sup>F-GE-180, <sup>64</sup>Cu-TREM1 monoclonal antibody (mAb), or <sup>64</sup>Cu-isotype control mAb and imaged by PET/CT. Ex vivo autoradiography was performed to obtain high-resolution images of tracer binding within the brain. Immunohistochemistry was conducted to verify myeloid cell activation and dopaminergic cell death, and quantitative polymerase chain reaction and flow cytometry were completed to assess levels of target in the brain. <b>Results:</b> PET/CT images of both tracers showed elevated signal within the striatum of 6-hydroxydopamine-injected mice compared with those injected with saline. Autoradiography afforded higher-resolution brain images and revealed significant TSPO and TREM1 tracer binding within the ipsilateral striatum of 6-hydroxydopamine mice compared with saline mice at both 7 and 14 d after toxin. Interestingly, <sup>18</sup>F-GE-180 enabled detection of inflammation in the brain and peripheral tissues (blood and spleen) of 6-hydroxydopamine mice, whereas <sup>64</sup>Cu-TREM1 mAb appeared to be more sensitive and specific for detecting neuroinflammation, in particular infiltrating myeloid cells, in these mice, as demonstrated by flow cytometry findings and higher tracer binding signal-to-background ratios in brain. <b>Conclusion:</b> TSPO and TREM1 PET tracers are promising tools for investigating different cell types involved in innate immune activation in the context of dopaminergic neurodegeneration, thus warranting further investigation in other PD rodent models and human postmortem tissue to assess their clinical potential.
Contrast Study of CdZnTe Detectors for Digital Mammography. (1997)

Experiments have been performed with the aim of optimizing the image quality parameters of CdZnTe detectors for digital mammography. A geometrical breast phantom has been designed, and the dependence of the contrast resolution of a planar CdZnTe detector on the phantom thickness has been experimentally determined. Specifically, the detected signal and noise contributions were measured and related to phantom thickness. The results of this study indicate that the CdZnTe detectors exhibit a high contrast resolution. On the other hand, the dynamic range of this detector can be improved significantly by further implementation of the data acquisition electronics.
Digital video segmentation (1994)

The data driven, bottom up approach to video segmentation has ignored the inherent structure that exists in video. This work uses the model driven approach to digital video segmentation. Mathematical models of video based on video production techniques are formulated. These models are used to classify the edit effects used in video and film production. The classes and models are used to systematically design the feature detectors for detecting edit effects in digital video. Digital video segmentation is formulated as a feature based classification problem. Experimental results from segmenting cable television programming with cuts, fades, dissolves and page translate edits are presented.
Abstract 46: Preclinical activity of novel antibody-drug conjugates with pyrrole-based kinesin spindle protein inhibitors targeting different tumor antigens (2017)

Abstract Antibody-drug conjugates (ADCs) are promising agents that are developed for targeted delivery of cytotoxic payloads to tumor cells. ADCs share a common design of antibody, linker, and cytotoxic payload. Despite significant efforts, the number of available payload classes with a differentiated mode-of-action that can successfully be employed to generate antibody-drug conjugates (ADCs) is still rather limited. So far, only ADCs with microtubule depolymerizing or DNA binding payloads have been approved. The identification of ADC payload classes with a novel mode-of-action will increase therapeutic options and potentially help to overcome resistance. Inhibitors of the kinesin spindle protein (KSP/Eg5/KIF11) have generated interest due to their high anti-tumor activity. However, the transfer of the potency of small molecule KSP inhibitors (KSPis) to highly efficient clinical regimens with a sufficient therapeutic window remains challenging. Through the conjugation of a novel pyrrole subclass of KSPis to antibodies targeting different cancer antigens, we generated a panel of ADCs and characterized them both in vitro and in vivo. ADCs targeting either EGFR or TWEAKR/Fn14 showed strong and specific internalization and displayed specific and potent anti-proliferative efficacy in vitro. In cytotoxicity assays, these ADCs exhibited sub-nanomolar potency in antigen-positive cancer cell lines (EGFR/TWEAKR-pos. NCI-H292; TWEAKR-pos. BxPC3, LoVo) and more than 100-fold selectivity versus non-targeted control-ADC containing the same linker and the same payload. Furthermore, selective anti-tumor efficacy of EGFR- and TWEAKR-KSPi-ADCs was demonstrated in vivo using both cancer cell line-derived models of NSCLC (NCI-H292), urothelial cell carcinoma (UCC) (KU-19-19), and renal cell carcinoma (A498), as well as in the TWEAKR-positive patient-derived xenograft UCC model BFX469. At doses of 5-10 mg/kg qw or bw potent anti-tumor efficacy with treated-to-control ratios (T/C) between 0.16 to 0.28 as well as complete regressions were observed. In summary, KSP inhibitors have been established as a promising new payload class allowing the generation of highly potent and selective ADCs for the treatment of solid tumors. Citation Format: Anette Sommer, Sandra Berndt, Hans-Georg Lerchen, Beatrix Stelte-Ludwig, Sven Wittrock, Anne-Sophie Rebstock, Lisa Dietz, Christoph Mahlert, Simone Greven, Nils Griebenow, Yolanda Cancho-Grande, Rolf Jautelat, Heiner Apeler, Bertolt Kreft. Preclinical activity of novel antibody-drug conjugates with pyrrole-based kinesin spindle protein inhibitors targeting different tumor antigens [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 46. doi:10.1158/1538-7445.AM2017-46
Evaluation of Two Commercial Loop-Mediated Isothermal Amplification Assays for Detection of Avian Influenza H5 and H7 Hemagglutinin Genes (2010)

Real-time reverse transcription loop-mediated isothermal amplification (real-time RT-LAMP) holds substantial potential as a highly sensitive, specific, and easy-to-perform molecular technique for pathogen detection in clinical samples. In the current study, the analytical and diagnostic performance of 2 commercial real-time RT-LAMP kits, Avian Flu H5 and Avian Flu H7, in detecting Avian influenza virus (AIV) infections were evaluated and compared with validated real-time reverse transcription polymerase chain reaction (RT-PCR) assays using RNA from reference virus isolates of subtypes H5 (n = 24) and H7 (n = 25) and of phylogenetically related subtypes (n = 20). When real-time RT-LAMP was carried out according to the recommendations of the manufacturer, 3 out of 24 H5 isolates and 8 out of 25 H7 reference strains were not detected. Prolonging the amplification phase resulted in detection of all H5 isolates but also in false positive detection of 2 non-H5 isolates. Real-time RT-LAMP specific to H7 failed to detect 2 H7 isolates after prolonged amplification. According to the examination of RNA log dilutions, the sensitivity of the real-time RT-LAMP assays, for a number of historic but also recent strains, was considerably lower compared with subtype-specific real-time RT-PCR assays. Application of the real-time RT-LAMP assays for analysis of diagnostic samples from wild birds confirmed their lower sensitivity. Commercial real-time RT-LAMP as tested in this study with a broad range of AIV H5 and H7 strains of phylogenetically diverse yet recent origin, holds some promise for routine veterinary diagnostic purposes, although real-time RT-LAMP was markedly more vulnerable to a reduction of detection limits because of strain-specific sequence variation than subtype-specific real-time RT-PCR.
Wall Teichoic Acids Facilitate the Release of Toxins from the Surface of Staphylococcus aureus (2022)

A major feature of the pathogenicity of Staphylococcus aureus is its ability to secrete cytolytic toxins. This process involves the translocation of the toxins from the cytoplasm through the bacterial membrane and the cell wall to the external environment. The process of their movement through the membrane is relatively well defined, involving both general and toxin-specific secretory systems. Movement of the toxins through the cell wall was considered to involve the passive diffusion of the proteins through the porous cell wall structures; however, recent work suggests that this is more complex, and here we demonstrate a role for the wall teichoic acids (WTA) in this process. Utilizing a genome-wide association approach, we identified a polymorphism in the locus encoding the WTA biosynthetic machinery as associated with the cytolytic activity of the bacteria. We verified this association using an isogenic mutant set and found that WTA are required for the release of several cytolytic toxins from the bacterial cells. We show that this effect is mediated by a change in the electrostatic charge across the cell envelope that results from the loss of WTA. As a major target for the development of novel therapeutics, it is important that we fully understand the entire process of cytolytic toxin production and release. These findings open up a new aspect to the process of toxin release by a major human pathogen while also demonstrating that clinical isolates can utilize WTA production to vary their cytotoxicity, thereby altering their pathogenic capabilities. <b>IMPORTANCE</b> The production and release of cytolytic toxins is a critical aspect for the pathogenicity of many bacterial pathogens. In this study, we demonstrate a role for wall teichoic acids, molecules that are anchored to the peptidoglycan of the bacterial cell wall, in the release of toxins from S. aureus cells into the extracellular environment. Our findings suggest that this effect is mediated by a gradient of electrostatic charge which the presence of the negatively charged WTA molecules create across the cell envelope. This work brings an entirely new aspect to our understanding of the cytotoxicity of S. aureus and demonstrates a further means by which this major human pathogen can adapt its pathogenic capabilities.
Three-Terminal Probe Reconfigurable Phase-Change Material Switches (2009)

We present the realization of a novel three-terminal electronic switch using phase-change (PC) chalcogenide material. This device subdivides a single PC switch into a parallel array of three-terminal subvias which are addressed with atomic-force-microscopy cantilever probes. This subdivision reduces the required switching current to acceptable levels. Vias of Ge <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">50</sub> Sb <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">50</sub> are demonstrated in this switch topology and are switched between high- and low-resistance states. The vias show an off/on resistance ratio of approximately 100×, which can be applied in radio-frequency switching applications. This dynamic range is 10× less than that observed in sheet films of this material, with the main loss being a reduction in resistivity between the sheet-film off-state and the device off-state. The device off -state resistivity is similar in the as-fabricated state and the reamorphized state.
De novo SCN8A and inherited rare CACNA1H variants associated with severe developmental and epileptic encephalopathy (2021)

Developmental and epileptic encephalopathies (DEEs) are a group of severe epilepsies that are characterized by seizures and developmental delay. DEEs are primarily attributed to genetic causes and an increasing number of cases have been correlated with variants in ion channel genes. In this study, we report a child with an early severe DEE. Whole exome sequencing showed a de novo heterozygous variant (c.4873-4881 duplication) in the SCN8A gene and an inherited heterozygous variant (c.952G > A) in the CACNA1H gene encoding for Na<sub>v</sub>1.6 voltage-gated sodium and Ca<sub>v</sub>3.2 voltage-gated calcium channels, respectively. In vitro functional analysis of human Na<sub>v</sub>1.6 and Ca<sub>v</sub>3.2 channel variants revealed mild but significant alterations of their gating properties that were in general consistent with a gain- and loss-of-channel function, respectively. Although additional studies will be required to confirm the actual pathogenic involvement of SCN8A and CACNA1H, these findings add to the notion that rare ion channel variants may contribute to the etiology of DEEs.
Characterization of Islet Health and Function Prior to Transplantation (2020)

Transplantation of Islets of Langerhans offers a cell‐based insulin replacement therapy for Type 1 diabetes but requires lifelong immunosuppression. Devices that encapsulate transplanted islets or insulin‐producing cells can isolate and protect islets from the immune system eliminating need for immunosuppression. However, the required cell density may promote a hypoxic environment with subsequent beta cell dysfunction. We investigated the effects of a hypoxic environment on unencapsulated islet insulin secretion by incubating isolated human islets at low (1%) and normal (21%) oxygen tensions. After 24 hrs, the basal secretion rate (BSR) for islets maintained at 1% O 2 (4.5 +/− 0.34 pg insulin/20min*ng DNA) was elevated compared to islets maintained in normoxic conditions (21%, 2.0 +/− 0.7 pg insulin/20min*ng DNA). For islets exposed to normoxia the stimulation index (SI) was 6.4 +/− 1.3. The SI in islets exposed to hypoxia was reduced by 50% (3.2 +/− 1.1). Thus, sufficient islet oxygenation is important for human islet function. To investigate the effect of hypoxic conditions on macroencapsulated islet function we placed a high density of rat islets, without supplemental oxygen, into a macroencapsulation device. By perifusion, we observed a delayed and decreased 1 st phase insulin secretion when compared to free islets. After 4 days of high density culture within the macroencapsulation device, macroencapsulated rat islets assayed in static assays, showed increased basal secretion, reduced GSIS, and decreased insulin content when compared to free islets. To evaluate free and macroencapsulated cellular function we recently developed perifusion chambers capable of simultaneous measurement of oxygen consumption rate (OCR) and hormone secretion. We found that GSIS was correlated with increased OCR in substrate free media demonstrating the possible utility of dynamic OCR measurements as a real time assay for islet viability and potency. Islet function is sensitive to oxygen tension and metabolic exchange, and using new technologies we are developing strategies to characterize these effects to optimize cellular health and function. Support or Funding Information Juvenile Diabetes Research Foundation Award #2‐SRA‐2018‐685‐S‐B. NIH Diabetes Impact Award #1DP3DK106933‐01
Execution-based prediction using speculative slices (2001)

A relatively small set of static instructions has significant leverage on program execution performance. These problem instructions contribute a disproportionate number of cache misses and branch mispredictions because their behavior cannot be accurately anticipated using existing prefetching or branch prediction mechanisms.
Peculiar Behavior of Azolium Azolate Energetic Ionic Liquids (2011)

We present studies of molecular dynamics and interactions in azolium azolate energetic ionic liquids (ILs) by utilizing a variety of physical methods. We observe peculiar rheological behavior for these ILs, which deviates from the one expected for molecular glass-formers. Major peculiarities include high elasticity in the low-frequency zone, peculiar van Gurp plots, and failure of time temperature superposition. We attribute these peculiarities to specific interactions in the nitrogen-rich planar rings of azolate ILs. X-ray scattering measurements reveal a “nanometer” ordered organization in azolium azolates. High values of Kamlet–Taft polarity parameters indicate high probability and strength of hydrogen bond interactions in azolate ILs. This conclusion is also supported by ab initio calculations. Our next effort is to break/enhance existing interactions in nitrogen-rich ILs by adding a “H-acceptor”. This will allow better understanding of the nature of interactions in azolium azolates and eventually their control.
The Origins of the Cultural Revolution (1984)

I: Change1. Mao in Moscow2. The Politburo Tours China3. The Chengtu Conference4. The Leap is Launched5. The Coming of the Communes6. High TideII: Retreat7. Withdrawal at Wuhan8. Mao Veers Right9. Chairman LiuIII: Clash10. High Noon at LushanIV: Defeat11. The Sino-Soviet Split Emerges12. The End of the Leap
Genetic variability of the frameshift region in IS911transposable elements fromEscherichia coliclinical isolates (2003)

The IS911 bacterial transposable element has been analyzed for its mechanism of transposition and for the way it controls the expression of its genes by programmed -1 translational frameshifting. In the present study the prevalence of IS911 has been determined in the Enterobacteriaceae family and in other Gram-negative bacilli. Three variants, found in Escherichia coli clinical isolates and having mutations in the region implicated in frameshifting, were functionally characterized. All three were altered in their frameshifting and transposition abilities, suggesting that the frameshift region of IS911 may constitute a target for mutations reducing the transposition frequency of this mobile element in natural populations of E. coli.
Supplementary Tables 1-7 from Genomic Alterations during the <i>In Situ</i> to Invasive Ductal Breast Carcinoma Transition Shaped by the Immune System (2023)

&lt;p&gt;Summary of Supplementary Tables Supplementary Table S1. Clinicopathological characteristics of patient cohort Supplementary Table S2. Antibody panel for cyclic IF Supplementary Table S3. Summary of mutations and neoantigen expression in the recurrence cohort (Related to 1C, 6A) Supplementary Table S4. Summary of altered pathways in DCIS/IDC (Fig 1F) Supplementary Table S5. Enriched gene sets between DCIS and IDC (Fig 3A) Supplementary Table S6. Identified chromosomal regions associated with immune changes (Related to Fig. 5) Supplementary Table S7. Mutational, neoantigen and rsSNP frequency of commonly mutated genes in TCGA and Abba cohorts (related to Fig 6C,E)&lt;/p&gt;
Real-Time Quantitative Polymerase Chain Reaction Assessment of Immune Reactivity in Melanoma Patients After Tumor Peptide Vaccination (2000)

Vaccination induces circulating antitumor lymphocytes, albeit in low frequencies, capable of directly reacting with tumor antigen. PBMCs of vaccinated individuals can respond to a vaccine-specific stimulus in a direct assay that does not require prolonged in vitro manipulations.