gebhart/patrepeval huggingface dataset:
Inhibition of Megakaryocyte Differentiation by Antibody–Drug Conjugates (ADCs) is Mediated by Macropinocytosis: Implications for ADC-induced Thrombocytopenia (2017)

Thrombocytopenia is a common adverse event in cancer patients treated with antibody-drug conjugates (ADC), including AGS-16C3F, an ADC targeting ENPP3 (ectonucleotide pyrophosphatase/phosphodiesterase-3) and trastuzumab emtansine (T-DM1). This study aims to elucidate the mechanism of action of ADC-induced thrombocytopenia. ENPP3 expression in platelets and megakaryocytes (MK) was investigated and shown to be negative. The direct effect of AGS-16C3F on platelets was evaluated using platelet rich plasma following the expression of platelet activation markers. Effects of AGS-16C3F, T-DM1, and control ADCs on maturing megakaryocytes were evaluated in an <i>in vitro</i> system in which human hematopoietic stem cells (HSC) were differentiated into MKs. AGS-16C3F, like T-DM1, did not affect platelets directly, but inhibited MK differentiation by the activity of Cys-mcMMAF, its active metabolite. FcγRIIA did not appear to play an important role in ADC cytotoxicity to differentiating MKs. AGS-16C3F, cytotoxic to MKs, did not bind to FcγRIIA on MKs. Blocking the interaction of T-DM1 with FcγRIIA did not prevent the inhibition of MK differentiation and IgG1-mcMMAF was not as cytotoxic to MKs despite binding to FcγRIIA. Several lines of evidence suggest that internalization of AGS-16C3F into MKs is mediated by macropinocytosis. Macropinocytosis activity of differentiating HSCs correlated with cell sensitivity to AGS-16C3F. AGS-16C3F was colocalized with a macropinocytosis marker, dextran-Texas Red in differentiating MKs. Ethyl isopropyl amiloride (EIPA), a macropinocytosis inhibitor, blocked internalization of dextran-Texas Red and AGS-16C3F. These data support the notion that inhibition of MK differentiation via macropinocytosis-mediated internalization plays a role in ADC-induced thrombocytopenia. <i>Mol Cancer Ther; 16(9); 1877-86. ©2017 AACR</i><i>See related article by Zhao et al., p. 1866</i>.
xuv-laser spectroscopy of HD at 92–98 nm (1995)

Sub-Doppler excitation spectra of HD have been recorded in the range 92--98 nm with the use of a narrow-band and tunable extreme ultraviolet laser in combination with a molecular beam. Frequencies of 147 transitions to the B${\mathrm{}}^{1}$${\mathrm{\ensuremath{\Sigma}}}_{\mathit{u}}^{+}$, C${\mathrm{}}^{1}$${\mathrm{\ensuremath{\Pi}}}_{\mathit{u}}$, and EF${\mathrm{}}^{1}$${\mathrm{\ensuremath{\Sigma}}}_{\mathit{g}}^{+}$ states have been calibrated with an average absolute accuracy of 0.035 ${\mathrm{cm}}^{\mathrm{\ensuremath{-}}1}$. The data have been analyzed in the framework of a semiempirical deperturbation model involving mutual couplings between nearby lying levels of the B${\mathrm{}}^{1}$${\mathrm{\ensuremath{\Sigma}}}_{\mathit{u}}^{+}$ and C${\mathrm{}}^{1}$${\mathrm{\ensuremath{\Pi}}}_{\mathit{u}}$ states. Also, symmetry-breaking effects, i.e., interactions with EF${\mathrm{}}^{1}$${\mathrm{\ensuremath{\Sigma}}}_{\mathit{g}}^{+}$ gerade states, were inferred from the data.
ChemInform Abstract: Preparation of TADDOL Derivatives (I)—(III) for New Applications. (1999)

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.
PRIMATEs v2.0 (2015)

PRIMATEs are a family of permutation-based authenticated encryption algorithms for lightweight applications. They are currently under submission to the CAESAR competition. There are three PRIMATEs: the basic SpongeWrap-variant HANUMAN, GIBBON for speed-critical applications, and APE for additional security when nonces are reused or unverified plaintext is released. When resistance against hardware side-channel attacks is required, the PRIMATEs permutation has been designed to offer an efficient threshold implementation to counter first-order DPA attacks, based on glitch-free secret-sharing-based masking.
A NEW MODEL TO STUDY INTESTINAL FIBROSIS USING IPSC-DERIVED HUMAN EPITHELIAL AND MESENCHYMAL CELLS FROM CROHN’S DISEASE PATIENTS (2023)

Abstract INTRODUCTION Intestinal fibrosis is a serious complication of Crohn's disease (CD) and is caused by the excess deposition of extracellular matrix protein. There are no therapies to prevent or treat this and surgical intervention remains the only treatment option. Numerous cell types, including intestinal epithelial and mesenchymal cells, are implicated in this but research efforts are impaired by a lack of in vitro models. Human intestinal organoids (HIOs), derived from induced pluripotent stem cells (iPSCs), are comprised of both of these cell types; therefore iPSC-derived HIOs represent an approach in which an unlimited number of patient specific cells could be generated for such models. Our goal was to confirm the feasibility of using iPSC-derived epithelial and mesenchymal cells from CD patients to model intestinal fibrosis METHODS iPSCs from CD patients with and without fibrotic complications were directed to form HIOs. As iPSC-derived HIOs contain epithelial and mesenchymal cells, the organoids were dissociated to generate purified cultures of epithelial-only HIOs (eHIOs) and mesenchymal cells. Both cell types were cultured with TNFα and TGFβ, and responses were assayed after 8, 24 and 48 hrs. Further assessment on the transcriptomic profile of the cultures was conducted using the Nanostring nCounter Fibrosis Panel. RESULTS Mesenchymal cells treated with TNFα for 48 hrs showed a significant increase in MMP9 expression, whereas TGFβ elicited an upregulation in COL1A1 and COL5A1. Further analysis via Nanostring identified the upregulation of numerous other fibrosis-related genes in response to TNFα stimulation, mainly: CCL2, IL6, MMP7, and MMP9. In eHIO cultures, after 24 hrs of cytokine exposure, we detected a significant upregulation in EMT (NCAD, VIM, and SNAI2) and fibrosis genes (COL1A1, COL5A1, and MMP9), mainly in response to TGFβ and the combination TNFα/TGFβ. Nanostring further identified a total of 121 differentially expressed genes, mostly in response to these treatments, particularly: CCL2, IL11, MMP9, MMP10. Overall, Nanostring analysis found an upregulation in pathways associated with ECM production and remodeling, immunomodulation, and ligands associated with EMT and cell migration. CONCLUSION We have successfully generated a system to assay intestinal fibrosis in a patient-specific manner using iPSC-derived epithelial and mesenchymal cells from CD patients. Our model elicited a reliable and reproducible response to inflammatory and fibrogenic stimuli, measured by the differential expression of key fibrosis-associated genes. Future studies will focus on a broader analysis of these data via RNA-seq to investigate a potential fibrogenic phenotype and to identify novel genes/pathways that may play in role in the pathophysiology of intestinal fibrosis in CD.
An Ultra-Low Close-In Phase Noise Series-Resonance BAW Oscillator in a 130-nm BiCMOS process (2021)

MEMS resonators offer excellent alternatives to crystal oscillators with potential cost and area savings from silicon co-packaging/integration. Despite having lower quality factor (Q) when compared to crystals, the availability of a direct low noise high frequency reference offers wider design choices and flexibilities whether be it in addressing close-in or far out phase noise needs – long term clock stability or integrated jitter. Additionally, silicon integration aside from saving cost, dedicated pin for XO and PCB real estate, allows for on-chip thermal compensation around the resonator for superior noise and drift performance. One such promising technology is the bulk acoustic wave (BAW) oscillator [1]. This work reports an indigenous BAW resonator (BAWR) based series-resonance oscillator that provides best-in-class frequency-normalized close-in phase noise (PN) performance $(\gt5$ dB better at 1kHz and lower offsets) along with an excellent Figure-of-Merit (FoM) of -202.5dBc/Hz at 1kHz. The design addresses integrated reference needs for 100+ Gbps multi-lane wireline and multi-channel clocking applications requiring ultra-low PLL jitter for high fidelity and very low BER $(\lt1 \mathrm{x}10^{-12})$.
PRE‐TREATMENT SERUM ALBUMIN LEVEL AS A MEANS OF IMPROVING PROGNOSTIC MODELS IN PERIPHERAL T‐CELL LYMPHOMAS: A STUDY FROM THE LATIN AMERICAN GROUP OF LYMPHOMAS (GELL) (2019)

Introduction: Peripheral T-cell lymphomas (PTCL) are heterogeneous and aggressive malignancies recognized by the 2016 WHO classification. The goal of this study is to evaluate the prognostic role of pretreatment serum albumin level (PAL) in aggressive PTCL subtypeS in a cohort of patients from Peru, Argentina, Chile, and Colombia. Methods: Patients with PTCL treated between January 1991 and December 2017 were analyzed. Diagnosis of PTCL was based on histological findings. Overall survival (OS) curves were estimated using the Kaplan-Meier method and compared using the log-rank test. Uni and multivariate logistic and Cox regression analyses were performed. Results: 425 patients with PTCL met inclusion criteria; 48% were peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS),38% were adult T-cell leukemia/lymphoma (ATLL) and 18% where others (ie. anaplastic, angioimmunoblastic, NK/T cell, enteropathy-associated and hepatosplenic lymphoma). The median follow-up was 3.5 years. 54% were younger than 60 years, and 55% were men. An ECOG ≥1 was seen in 48%, B symptoms in 65%, clinical stage III-IV in 75%, and high LDH level in 55% of the patients. PAL was <3.5 g/dl in 56% of the patients. 52% were classified as high/high-intermediate IPI score (31% and 21%, respectively), and 61% as high/high-intermediate PIT score (28% and 33%, respectively).75% of patients received systemic therapy (25% best supportive care). The IPI score and PIT score were useful to discriminate the highest risk group. High/high-intermediate had worse survival than low/low-intermediate IPI score (HR 2.92, 95%CI, 2.13-4.01, p<0.001); and high/high-intermediate had worse survival than low-low intermediate PIT score (HR 2.63, 95% CI, 1.88-3.68, p<0.001). In the multivariate analysis, the ATLL group had worse survival than PTCL-NOS (HR 1.82, 95% CI, 1.32-2.50, p<0.001). PAL<3.5 had poor survival than PAL>3.5 (HR 1.82, 95% CI, 1.33-2.48, p<0.001). The median OS at 5 years was 1.5 years with Albumin >3.5 and 0.6 years with Albumin <3.5. When combining PAL<3.5 g/dl and IPI score (IPI-alb), patients were stratified in 3 risk categories: IPI-alb 0 with a median OS of 3.5 years, IPI-alb 1 with 1 year and IPI-alb 2 with 0.4 years. The IPI-alb 1 had worse survival than IPI-alb 0 (HR 2.13,95% CI 1.38-3.28, p=0.001), and IPI-alb 2 had worse survival than IPI-alb 0 (HR 3.73, 95% CI, 2.43-5.71, p<0.001). When we combine PAL<3.5 g/dl and PIT score (PIT-alb), were also stratified in 3 risk categories: PIT-alb 0 with a median OS of 3.5 years, PIT-alb 1 with 1 year and PIT-alb 2 with 0.4 years. The PIT-alb 1 had worse survival than PIT-alb 0 (HR 2.08, 95% CI 1.30-3.33, p=0.002), and PIT-alb 2 had worse survival than PIT-alb 0 (HR 3.38, 95% CI, 2.13-5.38, p<0.001). Keywords: prognostic indices; T-cell lymphoma (TCL).
cw surface-emitting grating-coupled GaAs/AlGaAs distributed feedback laser with very narrow beam divergence (1987)

Room-temperature cw operation of a GaAs/AlGaAs surface-emitting grating-coupled distributed feedback laser is reported. By using a transverse junction stripe scheme which provides a window structure for the surface-emitted light, cw surface emission having a very narrow beam divergence angle of 0.13° and an output power of more than 3 mW was observed.
Data Troubles in Sentence Level Confidence Estimation for Machine Translation (2020)

The paper investigates the feasibility of confidence estimation for neural machine translation models operating at the high end of the performance spectrum. As a side product of the data annotation process necessary for building such models we propose sentence level accuracy $SACC$ as a simple, self-explanatory evaluation metric for quality of translation. Experiments on two different annotator pools, one comprised of non-expert (crowd-sourced) and one of expert (professional) translators show that $SACC$ can vary greatly depending on the translation proficiency of the annotators, despite the fact that both pools are about equally reliable according to Krippendorff's alpha metric; the relatively low values of inter-annotator agreement confirm the expectation that sentence-level binary labeling $good$ / $needs\ work$ for translation out of context is very hard. For an English-Spanish translation model operating at $SACC = 0.89$ according to a non-expert annotator pool we can derive a confidence estimate that labels 0.5-0.6 of the $good$ translations in an "in-domain" test set with 0.95 Precision. Switching to an expert annotator pool decreases $SACC$ dramatically: $0.61$ for English-Spanish, measured on the exact same data as above. This forces us to lower the CE model operating point to 0.9 Precision while labeling correctly about 0.20-0.25 of the $good$ translations in the data. We find surprising the extent to which CE depends on the level of proficiency of the annotator pool used for labeling the data. This leads to an important recommendation we wish to make when tackling CE modeling in practice: it is critical to match the end-user expectation for translation quality in the desired domain with the demands of annotators assigning binary quality labels to CE training data.
Cellobiose dehydrogenase production by Sclerotium species pathogenic to plants (2002)

S. coffeicola and S. delphinii were identified as potent, not-yet-described producers of cellobiose dehydrogenase (CDH). The high levels of intact CDH produced by the different Sclerotium species should make them attractive producers for further studies and applications.
Active-Pixel Cosmic-Ray Sensor (1994)

In this paper, we will first introduce the notions of systematicity and combinatorial productivity and we will argue that these notions are essential for human cognition and probably for every agent that needs to be able to deal with novel, unexpected situations in a complex environment. Agents that use compositional representations are faced with the so-called binding problem and the question of how to create neural network architectures that can deal with it is essential for understanding higher level cognition. Moreover, an architecture that can solve this problem is likely to scale better with problem size than other neural network architectures. Then, we will discuss object-based attention. The influence of spatial attention is well known, but there is solid evidence for object-based attention as well. We will discuss experiments that demonstrate object-based attention and will discuss a model that can explain the data of these experiments very well. The model strongly suggests that this mode of attention provides a neural basis for parallel search. Next, we will show a model for binding in visual cortex. This model is based on a so-called neural blackboard architecture, where higher cortical areas act as processors, specialized for specific features of a visual stimulus, and lower visual areas act as a blackboard for communication between these processors. This implies that lower visual areas are involved in more than bottom-up visual processing, something which already was apparent from the large number of recurrent connections from higher to lower visual areas. This model identifies a specific role for these feedback connections. Finally, we will discuss the experimental evidence that exists for this architecture.
Improving on-product performance at litho using integrated diffraction-based metrology and computationally designed device-like targets fit for advanced technologies (incl. FinFET) (2014)

In order to meet current and future node overlay, CD and focus requirements, metrology and process control performance need to be continuously improved. In addition, more complex lithography techniques, such as double patterning, advanced device designs, such as FinFET, as well as advanced materials like hardmasks, pose new challenges for metrology and process control. In this publication several systematic steps are taken to face these challenges.
A New, Highly Conductive, Lithium Salt/Nonionic Surfactant, Lyotropic Liquid‐Crystalline Mesophase and Its Application (2012)

Salty water! Lithium salts (LiCl, LiNO3, and LiClO4) at very high concentrations in water form lyotropic liquid crystalline (LLC) mesophases with a nonionic surfactant (10-lauryl ether) and display high ionic conductivities (10−2–10−4 S cm−1) over a broad temperature range (−10 to 80 °C) with excellent behavior as gel electrolytes in electrochemical applications. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Rapid synthesis of bovine serum albumin-conjugated gold nanoparticles using pulsed laser ablation and their anticancer activity on hela cells (2022)

Nanoscience research aims to produce nanoparticles without adverse effects for medical applications. The pulsed laser ablation (PLA) technique was utilized in this study to synthesize gold nanoparticles (AuNPs) using bovine serum albumin (BSA) in simulated body fluid (SBF) at the fundamental wavelength of the Nd: YAG laser (1064 nm). BSA acted as a stabilizer, reducing and capping agent to produce spherically shaped AuNPs (diameter 3–10 nm). The successful synthesis of AuNPs was confirmed through color changes and UV–vis spectroscopy. The agglomeration and precipitation of AuNPs are attributed to the presence of BSA in the solution, and electrostatic repulsion interactions between BSA and Au nanoclusters. The effect of salt concentration of SBF on BSA stability as well as the interaction of BSA conjugated AuNPs to form complexes was studied using molecular dynamic simulations. Our results show that the stability of AuNPs-BSA conjugates increase with the salt concentration of BSA. Moreover, the synthesized AuNPs exhibit low toxicity and high biocompatibility, supporting their application in drug delivery. Investigation of the cytotoxic effect of the synthesized AuNPs show that normal fibroblast cells (L929) remain intact after treatment whereas a dose-dependent inhibition effect on the growth of cervix cancer cells (HeLa) is observed. In general, this study presents an effective, environmentally-friendly, and facile approach to the synthesis of multifunctional AuNPs using the PLA technique, as a promising efficacious therapeutic treatment of cervical cancer.
Predicting Patient Outcomes Via Neural Network Estimation of Discharge APACHE Scores for Traumatic Brain Injury (2014)

It is highly desirable to be able to predict the likely outcome of critical patients admitted to the intensive care unit (ICU) for traumatic brain injury (TBI). Vital signs, laboratory values, and clinical assessments from throughout a patient’s ICU stay were collected retrospectively in an IRB-approved protocol from a Level I Trauma-Military Medical Center in the Southwest. ICU patients were included if they had been admitted for TBI during a five-year period ending in October 2007. Data were collected for 139 ICU patients with TBI. Admission and discharge APACHE IV scores were then derived from the collected data for each patient. A static back propagation neural network was developed to predict a patient’s ICU outcome vis-a-vis discharge APACHE IV scores. The resulting network, trained using leave-one-out methodology, was able to predict the discharge APACHE score on average within 12.9% of the actual score.
Visual cortical GABA and depth of amblyopia are negatively correlated (2020)

Amblyopia is a neurodevelopmental disorder that is characterized by reduced visual acuity, atypical binocular integration, and heightened perceptual suppression. Physiology studies in animal models suggest that intracortical GABAergic inhibition might play an important role in mediating amblyopic visual deficits. Magnetic resonance spectroscopy (MRS) and fMRI findings in normally sighted persons (NSP) have demonstrated a negative correlation between occipital GABA concentration and visually evoked fMRI response amplitude. To better understand the relationships among occipital GABA, fMRI responses to visual stimulation, and perceptual suppression in human amblyopia and normal vision, we collected MRS, fMRI, and psychophysical data from both persons with amblyopia (PWA) and NSP. MR spectra that were optimized for GABA measurements were obtained from a voxel positioned bilaterally along the calcarine sulcus, and fMRI responses to checkerboard stimuli were recorded in retinotopically-defined early visual cortical areas. In PWA, we found a robust negative correlation between the depth of amblyopia (interocular difference in visual acuity) and occipital GABA concentration. This relationship was specific to visual cortex and was not observed in a sensorimotor cortical control region. Finally, our data in NSP were consistent with the negative relationship between occipital GABA and fMRI visual cortical response amplitude that has been reported in other studies. However, in PWA, the same relationship between occipital GABA and fMRI response amplitude was absent, or possibly reversed. Taken together, our findings provide evidence that intracortical GABAergic inhibition is a component of the pathology of human amblyopia. We speculate that lower levels of visual cortical GABA in individuals with deep amblyopia represent a compensatory decrease in inhibition that limits the ability of the amblyopic eye to perceptually suppress the fellow eye.
FATP4 contributes as an enzyme to the insulin mediated fatty acid uptake of C2C12 muscle cells (2010)

The function of membrane proteins in long chain fatty acid transport is controversial. The acyl‐CoA synthetase FATP4 has been suggested to facilitate fatty acid uptake by its enzymatic activity or by direct transport across the plasma membrane. Here, we investigated the role of FATP4 in C2C12 muscle cells, a model system relevant for fatty acid metabolism. Stable expression of exogenous FATP4 resulted in a twofold higher fatty acyl‐CoA synthetase activity, and uptake of radiolabeled oleate was enhanced similarly. We report for the first time that insulin increases the acyl‐CoA synthetase activity within minutes. This short term regulation offers a novel mechanistic explanation for the concomitantly observed enhanced fatty acid uptake. Confocal microscopy showed that FATP4 was localized in an intracellular ER‐like pattern clearly distinct from the plasma membrane. Neither differentiation into myotubes nor insulin treatment changed the intracellular localization of FATP4. We conclude that FATP4 functions by its intrinsic enzymatic activity. This is in line with the concept that intracellular metabolism plays a significant role in the uptake of fatty acids.