gebhart/patrepeval huggingface dataset:
TH‐E‐17A‐07: Improved Cine Four‐Dimensional Computed Tomography (4D CT) Acquisition and Processing Method (2014)

Purpose: Artifacts arising from the 4D CT acquisition and post‐processing methods add systematic uncertainty to the treatment planning process. We propose an alternate cine 4D CT acquisition and post‐processing method to consistently reduce artifacts, and explore patient parameters indicative of image quality. Methods: In an IRB‐approved protocol, 18 patients with primary thoracic malignancies received a standard cine 4D CT acquisition followed by an oversampling 4D CT that doubled the number of images acquired. A second cohort of 10 patients received the clinical 4D CT plus 3 oversampling scans for intra‐fraction reproducibility. The clinical acquisitions were processed by the standard phase sorting method. The oversampling acquisitions were processed using Dijkstras algorithm to optimize an artifact metric over available image data. Image quality was evaluated with a one‐way mixed ANOVA model using a correlation‐based artifact metric calculated from the final 4D CT image sets. Spearman correlations and a linear mixed model tested the association between breathing parameters, patient characteristics, and image quality. Results: The oversampling 4D CT scans reduced artifact presence significantly by 27% and 28%, for the first cohort and second cohort respectively. From cohort 2, the inter‐replicate deviation for the oversampling method was within approximately 13% of the cross scan average at the 0.05 significance level. Artifact presence for both clinical and oversampling methods was significantly correlated with breathing period (ρ=0.407, p‐value&lt;0.032 clinical, ρ=0.296, p‐value&lt;0.041 oversampling). Artifact presence in the oversampling method was significantly correlated with amount of data acquired, (ρ=‐0.335, p‐value&lt;0.02) indicating decreased artifact presence with increased breathing cycles per scan location. Conclusion: The 4D CT oversampling acquisition with optimized sorting reduced artifact presence significantly and reproducibly compared to the phase‐sorted clinical acquisition.
Zero Sequence Currents Externally Circulating Between the Back to Back Modular Multilevel Converters in Parallel AC-DC Distribution Links (2019)

During the operation of a three line ac link in parallel with a ac-dc-ac link system that employs Back-to-Back (B2B)Medium Voltage Modular Multilevel Converters (MMC), a path for the low frequency zero sequence currents is shown to exist. Apart from causing additional losses, these currents can result in limitations on power capacity. A detailed analysis on the influence of cell capacitance, arm inductance and link conductor length on the circulating zero sequence currents and the means to mitigate them through a simulated control strategy is investigated. The simulations show that the dc link employing B2B-MMC can successfully operate in parallel with ac link without transformer isolation by controlling the zero sequence currents.
Können wir KI vertrauen? Vergleich von KI-Software-Tools zur automatischen Erkennung, Quantifizierung und Kategorisierung von Lungenknoten in der HANSE-LCS-Studie (2023)

Zielsetzung Das Patientenmanagement in der Lungenkrebsvorsorge hängt von der Lung Imaging Reporting and Data System (Lung-RADS) – Kategorie ab. Das System basiert auf einer zuverlässigen Erkennung der Lungenknoten und akkuraten Messung deren Volumina. Ziel dieser Studie war es, die Leistung zweier KI-basierten Software-Tools zur Detektion, Quantifizierung und Kategorisierung von Lungenknoten in einem norddeutschen Lungenkrebs-Screening(LCS)-Programm (HANSE-Studie) zu evaluieren und zu vergleichen.
A phase 1b study of unesbulin (PTC596) plus dacarbazine for the treatment of patients with locally recurrent, unresectable, or metastatic relapsed/refractory leiomyosarcoma. (2022)

11507 Background: Leiomyosarcoma (LMS) is one of the most common subtypes of soft tissue sarcoma and is associated with high risk of relapse and a poor prognosis for advanced disease. In preclinical LMS models, unesbulin, a microtubule polymerization inhibitor, potentiated the activity of dacarbazine (DTIC) (Jernigan F, et al. Mol Cancer Ther. 2021;20:1846–1857). Here, we report preliminary safety and efficacy results from a Phase 1b dose escalation study evaluating the combination of unesbulin with DTIC in patients with advanced LMS (NCT03761095). Methods: In this single-arm, open-label, Phase 1b clinical trial, patients with advanced LMS received unesbulin orally at 200, 300, or 400 mg twice weekly (BIW) in combination with intravenous DTIC at 1,000 mg/m 2 once every 21 days. The primary objectives were to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of unesbulin in combination with DTIC and to characterize the safety profile of the combination. The time-to-event continual reassessment model (TITE-CRM) was used for dose finding. An expansion cohort with up to 12 additional patients is currently being enrolled. Results: As of the data cutoff on January 6, 2022, 29 LMS patients have been treated. Median prior lines of therapy were 3 (range 1–6). Of 27 evaluable patients, 12 had non-uterine and 15 had uterine LMS. The MTD/RP2D of unesbulin was determined to be 300 mg BIW with DTIC 1,000 mg/m 2 every 21 days using the TITE-CRM. At the RP2D, the most common treatment-related adverse events included fatigue, diarrhea, neutropenia, and thrombocytopenia. In the intent-to-treat population, the overall response rate (ORR) was 17.2% (5/29) and the disease control rate (DCR) (DCR = complete response + partial response + stable disease at 12 weeks) was 58.6%. At the 300 mg dose level, the ORR was 19% (4/21) and the DCR was 57.1%. Patients received a median of four cycles (range 1–12). The study is ongoing, with patients continuing to receive treatment. Conclusions: Unesbulin 300 mg BIW in combination with DTIC 1,000 mg/m 2 every 21 days was well tolerated and demonstrated promising efficacy in a heavily pre-treated patient population with advanced LMS; these results support further investigation. Updated clinical results will be presented as the data mature. A randomized, placebo-controlled, Phase 2/3 trial is planned. Clinical trial information: NCT03761095.
Abnormal activation of knee and ankle flexors-extensorsis related to altered gait in ankylosing spondilytis? (2010)

Introduction. Ankylosing Spondylitis (AS) is a rheumatic disease&#13;\nthat predominantly affects axial joints, producing a rigid spine from&#13;\nthe occiput to the sacrum. AS patients could experience a progressive&#13;\nspinal kyphosis, from a biomechanical point of view this may&#13;\ninduce a forward and downward displacement of the centre of mass&#13;\n(COM) in the sagittal plane [1]. Even though there is a clinical evidence&#13;\nof an altered posture, only one previous study involving AS&#13;\nEMG during gait, have been reported [2]. This study was aimed at&#13;\nexamining abnormal EMG patterns of AS subjects, evaluating the&#13;\nrole played in AS gait pattern alterations. Materials and methods.&#13;\nWe recruited 14 AS subjects (age: 49±1 years, BMI: 25±3 Kg). Six&#13;\ncameras BTS motion capture system (60-120 Hz) and surface EMG&#13;\n(PocketEMG, 16 channels) synchronized with 2 Bertec force plates&#13;\n(FP4060-10) were used. 3D-motion analysis of independent barefoot&#13;\nwalking was conducted. Surface electromyographic (EMG) data of&#13;\nrectus femoris (RF), tibialis anterior (TA) and gastrocnemius medialis&#13;\n(GM) muscles were collected; hips, knees and ankles flexion-extension&#13;\nmoments and ground reaction forces were evaluated. Results.&#13;\nRF signals were prolonged at initial contact and non activation was&#13;\nregistered during terminal stance and initial swing phases, TA activity&#13;\nwas delayed during swing, GM muscle always showed a&#13;\ndelayed activation during the stance phase. An increased ankle dorsiflexion&#13;\nand knee flexion, a decreased hip extension moments were&#13;\nregistered at heel strike, together with an excessive posterior and a&#13;\nlower vertical force. Conclusion. Our data confirm delays in GM&#13;\nactivation as in [3]; the presence of co-contractions in GM and TA&#13;\ncould be related to the kinetic alterations and the lack of heel&#13;\nrocker, due to difficulties in accomplishing the shock absorption.
DNA Polyplexes as Combinatory Drug Carriers of Doxorubicin and Cisplatin: An in Vitro Study (2015)

Double helix nucleic acids were used as a combination drug carrier for doxorubicin (DOX), which physically intercalates with DNA double helices, and cisplatin (CDDP), which binds to DNA without an alkylation reaction. DNA interacting with DOX, CDDP, or both was complexed with positively charged, endosomolytic polymers. Compared with the free drug, the polyplexes (100-170 nm in size) delivered more drug into the cytosol and the nucleus and demonstrated similar or superior (up to a 7-fold increase) in vitro cell-killing activity. Additionally, the gene expression activities of most of the chemical drug-loaded plasmid DNA (pDNA) polyplexes were not impaired by the physical interactions between the nucleic acid and DOX/CDDP. When a model reporter pDNA (luciferase) was employed, it expressed luciferase protein at 0.7- to 1.4-fold the amount expressed by the polyplex with no bound drugs (a control), which indicated the fast translocation of the intercalated or bound drugs from the "carrier DNA" to the "nuclear DNA" of target cells. The proposed concept may offer the possibility of versatile combination therapies of genetic materials and small molecule drugs that bind to nucleic acids to treat various diseases.
Pervasive within-Mitochondrion Single-Nucleotide Variant Heteroplasmy as Revealed by Single-Mitochondrion Sequencing (2017)

A number of mitochondrial diseases arise from single-nucleotide variant (SNV) accumulation in multiple mitochondria. Here, we present a method for identification of variants present at the single-mitochondrion level in individual mouse and human neuronal cells, allowing for extremely high-resolution study of mitochondrial mutation dynamics. We identified extensive heteroplasmy between individual mitochondrion, along with three high-confidence variants in mouse and one in human that were present in multiple mitochondria across cells. The pattern of variation revealed by single-mitochondrion data shows surprisingly pervasive levels of heteroplasmy in inbred mice. Distribution of SNV loci suggests inheritance of variants across generations, resulting in Poisson jackpot lines with large SNV load. Comparison of human and mouse variants suggests that the two species might employ distinct modes of somatic segregation. Single-mitochondrion resolution revealed mitochondria mutational dynamics that we hypothesize to affect risk probabilities for mutations reaching disease thresholds.
Direct probing characterization vehicle test chip for wafer level exploration of transistor pattern on product chips (2014)

Due to recent changes in the manufacturing of FEOL (front end of line) layers it is increasingly difficult to provide rapid learning cycles required to drive yield improvement during new product introduction (NPI). The Direct Probe Characterization Vehicle (DPCV) Test Chip presented here provides direct access to thousands of transistors on a product chip. Only two masks are needed (contact & metal 1) to provide access to the DUTs of the unchanged FEOL layers of a product chip. The DPCV test chip is capable of matching the distribution of product transistor pattern. Measurement data indicate that corrective actions to the design and/or process recipes will reduce the gap between measured product chip transistors and their expected behavior based on SPICE simulations.
Low threshold visible electron-beam-pumped-lasers (1986)

Electron-beam-pumped lasers (EBL) are small-target CRT's which are useful for projection displays, optical printing and PROMs, and optical mass-memory devices. Despite the obvious practical utility of a laser source with simple electronic scanning, applications of these devices have been held up by the high currents and, more importantly, high voltages necessary to achieve laser threshold. We have made ZnSe lasers (blue) with room temperature thresholds of 15 A/cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> at 30 kV and CdS lasers (green) with thresholds of 2.0 A/cm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> at 28 kV.
Phase I/IIb trial: In-situ vaccine for metastatic colorectal cancer. (2018)

TPS871 Background: Except for MSI-H tumors, CRC does not respond to immunotherapy. CRC does respond to the graft vs. tumor (GVT) immune effect that occurs after allogeneic stem cell transplantation. GVT is associated with GVHD toxicity which limits the clinical application. A bioengineered allograft (BAG) has been developed which can elicit host-mediated GVT-like effects without GVHD toxicity, chemotherapy conditioning or a HLA-matched donor. BAG are Th1 memory cells derived from blood of healthy donors with CD3/CD28 microbeads attached. These cells have immunomodulatory properties which enable modulation of Th1/Th2 balance and dysregulation of immunosuppressive circuits. We are evaluating the safety and efficacy of BAG in third-line mCRC. Methods: The study uses a standard 3+3 design followed by an expansion phase with the optimal dosing pattern. The protocol has four components: (A) priming; (B) in-situ vaccination; (C) extravasation and trafficking; and (D) counter immune suppression/avoidance. Priming involves intradermal injections of BAG cells which activates NK cells and develops allo-specific Th1/Tc1 immunity. In-Situ vaccination involves tumor cryoablation to release endogenous HSP which chaperone tumor neoantigens, followed immediately by the intralesional injection of BAG cells as adjuvant. Released HSP are engulfed and processed by immature dendritic cells (DC) attracted to the tissue damage. The inflammatory microenvironment created by the BAG and the subsequent allo-rejection response amplified by the priming induces DC maturation. These DC display processed tumor antigens on upregulated MHCI/II and express co-stimulatory CD80/86 enabling priming of a tumor-specific Th1/Tc1 response. CD40L and interferon-gamma expressed by BAG activates allo-specific and tumor-specific memory cells upon intravenous infusion, permitting trafficking to tumor. The host rejection of BAG releases endogenous danger signals creating a sustained systemic inflammatory cytokine release which serves to counter-regulate immunosuppressive mechanisms. Longitudinal CT scans biopsies, PBMC and serum samples are collected for analysis to verify immune events within each phase of the protocol. Clinical trial information: NCT02380443.
A macaque clonal hematopoiesis model demonstrates expansion of TET2-disrupted clones and utility for testing interventions (2022)

Individuals with age-related clonal hematopoiesis (CH) are at greater risk for hematologic malignancies and cardiovascular diseases. However, predictive preclinical animal models to recapitulate the spectrum of human CH are lacking. Through error-corrected sequencing of 56 human CH/myeloid malignancy genes, we identified natural CH driver mutations in aged rhesus macaques matching genes somatically mutated in human CH, with DNMT3A mutations being the most frequent. A CH model in young adult macaques was generated via autologous transplantation of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9-mediated gene-edited hematopoietic stem and progenitor cells (HSPCs), targeting the top human CH genes with loss-of-function (LOF) mutations. Long-term follow-up revealed reproducible and significant expansion of multiple HSPC clones with heterozygous TET2 LOF mutations, compared with minimal expansion of clones bearing other mutations. Although the blood counts of these CH macaques were normal, their bone marrows were hypercellular and myeloid-predominant. TET2-disrupted myeloid colony-forming units isolated from these animals showed a distinct hyperinflammatory gene expression profile compared with wild type. In addition, mature macrophages purified from the CH macaques showed elevated NLRP3 inflammasome activity and increased interleukin-1β (IL-1β) and IL-6 production. The model was used to test the impact of IL-6 blockage by tocilizumab, documenting a slowing of TET2-mutated expansion, suggesting that interruption of the IL-6 axis may remove the selective advantage of mutant HSPCs. These findings provide a model for examining the pathophysiology of CH and give insights into potential therapeutic interventions.
Influence of ionizing dopants on charge transport in organic semiconductors (2013)

Ionizing chemical dopants are widely used in organic semiconductors to enhance the charge transport properties by increasing the number of mobile charge carriers. However, together with mobile charges, chemical doping produces anion-cation pairs in the organic matrix. In this work we use experimental and computational analysis to study the influence of these ionic species on the charge transport. We show that the anion-cation pairs introduced upon doping have a detrimental, doping-level dependent effect on charge mobility. For doping levels of 0.02-0.05% molar ratio with respect to the molecular organic semiconductor, the increase in conductivity from the extra mobile charges is partially cancelled by a reduction in charge mobility from traps introduced by the anion-cation pairs. As the doping concentration increases, anion-cation pairs start to overlap, resulting in a comparatively smoother potential landscape, which increases the charge mobility to values closer to the undoped semiconductor. This result has a significant, practical impact, as it shows the need to dope at or slightly above a threshold level, which depends on the specific host-dopant combination.
Engineering potent long-acting variants of the Wnt inhibitor DKK2 (2017)

Wnt signaling pathways are required for a wide variety of biological processes ranging from embryonic development to tissue repair and regeneration. Dickkopf-2 (DKK2) is classically defined as a canonical Wnt inhibitor, though it may play a role in activating non-canonical Wnt pathways in the context of endothelial network formation after acute injury. Here we report the discovery of a fusion partner for a DKK2 polypeptide that significantly improves the expression, biochemical properties and pharmacokinetics (PK) of the DKK2 polypeptide. Specifically, human serum albumin (HSA) was identified as a highly effective fusion partner. Substitution of selected amino acid residues in DKK2 designed to decrease heparan sulfate binding by HSA-DKK2 variants, further improved the PK properties of the molecule in rodents. The HSA-DKK2 variants were monomeric, as thermally stable as wild type, and active as measured by their ability to bind to and prevent phosphorylation of the Wnt coreceptor LRP6. Our engineering efforts resulted in potent long-lived variants of the canonical Wnt inhibitor DKK2, applicable for Wnt pathway manipulation either by systematic delivery or focused administration at sites of tissue injury.
Slow light in fiber sensors (2012)

This paper examines the sensitivity improvements that have been achieved by making use of slow light in a variety of fiber sensors. We show in particular that slow light can have dramatically different impacts depending on its nature (material or structural) and on the parameter that is being sensed. In a fiber optic gyroscope measuring an absolute rotation for example, structural slow light does not enhance the maximum sensitivity achievable for a given loss and sensing area compared to a non-resonant structure such as a Sagnac-based fiber optic gyroscope. However, it does reduce the length of fiber required to achieve this sensitivity. For fiber sensors relying on the measurement of absorption, such as gas detectors, structural slow light improves the sensitivity because it increases the effective path length through the absorber and therefore the level of absorption. Material slow light, on the other hand, has been measured to have no impact on the sensitivity. For many other parameters besides rotation and absorption, the sensitivity is expected to be enhanced by either type of slow light, by orders of magnitude with suitable configurations. We illustrate this enormous potential with two configurations of strain sensors utilizing a fiber Bragg grating (FBG) as the sensing and slow-light medium. In properly designed FBGs supporting light with a group index in the range of 50 to 130, we measured a maximum sensitivity of 1.7-3.14 10<sup>5</sup> strain<sup>-1</sup> and a record minimum detectable strain of 820-880 f&epsilon;/&radic;Hz. This value is ~730 lower than the previous record using conventional light in a passive FBG sensor, in accord with predictions. Further enhancements are expected with straightforward improvements in FBG design.
Further Insights on the Inhibition of HIV Type 1 Infection in Vitro by CD4-Modified Synthetic Peptides Containing Phenylalanine (1996)

Phenylalanine-containing peptides from CD4 were synthesized on the basis of chemical similarity with active CD4(81-92)-benzylated peptides. Systematic replacement of amino acids of these peptides bearing the benzyl group by phenylalanine, afforded several peptides that were able to block the binding of gp120 to CD4 and to inhibit HIV-induced syncytium formation. These experiments showed that substitution of residues 81 and 85 by phenylalanine was the most important for activity. Following optimization of the length of phenylalanine-substituted peptides it was found that FYICFVED and FYICFVEDE were the most active. Their IC50 for the inhibition of syncytium formation was around 1.2-1.6 microM. This activity is at least 30 times higher than that of the parent peptide FYIFFVEDQKEEDD previously reported (Lasarte et al., J Acquir Immune Defic Syndr 1994;7:129-134). Binding competition experiments with two different anti-peptide antisera recognizing the V3 region of gp120 and FYICFVEDE, show that the active peptides bind to V3 or to a sterically near region of V3. None of the active peptides was toxic to cells in vitro. The enhanced activity and simplicity of these new phenylalanine-substituted CD4 peptides might be a good starting point for the development of mimotopes of potential use for the treatment of AIDS.
Supplementary Figrue S3 from USP9X Downregulation Renders Breast Cancer Cells Resistant to Tamoxifen (2023)

&lt;p&gt;Figure S3. Heatmap and quantifications for subsets of ChIP-seq data. (A) Heatmap visualization of ERÃŽÂ± chromatin binding events in shGFP cells, separately analyzing binding sites shared or unique for vehicle, E2 or 4-OHT conditions, as indicated in Figure 4C. All peaks were vertically aligned and centered on the top of the peak, with a window of 5 kb. Number of binding sites for each subgroup are shown. (B) Quantifications of read count at ERÃŽÂ± chromatin binding sites for different subgroups of chromatin as shown in A, with a 2.5 kb window. Y-axis shows average tag count. (C) Heatmap visualization of ERÃŽÂ± chromatin binding events in shUSP9X cells, separately analyzing binding sites shared or unique for vehicle, E2 or 4-OHT conditions, as indicated in Figure 4C. All peaks were vertically aligned and centered on the top of the peak, with a window of 5 kb. (D) Quantifications of read count at ERÃŽÂ± chromatin binding sites for different subgroups of chromatin as shown in C, with a 2.5 kb window. Y-axis shows average tag count.&lt;/p&gt;