gebhart/patrepeval huggingface dataset:
Combining Histone Deacetylase Inhibitor Vorinostat with Aurora Kinase Inhibitors Enhances Lymphoma Cell Killing with Repression of c-Myc, hTERT, and microRNA Levels (2011)

MK-0457 and MK-5108 are novel aurora kinase inhibitors (AKi) leading to G(2)-M cell-cycle arrest. Growth and survival of multiple lymphoma cell lines were studied with either drug alone or in combination with vorinostat, a histone deacetylase inhibitor (HDACi), using MTS and Annexin V assays, followed by molecular studies. Either of the AKi alone at 100 to 500 nmol/L resulted in approximately 50% reduced cell growth and 10% to 40% apoptosis. Addition of vorinostat reactivated proapoptotic genes and enhanced lymphoma cell death. Quantitative PCR and immunoblotting revealed that epigenetic and protein acetylation mechanisms were responsible for this activity. The prosurvival genes Bcl-X(L) and hTERT were downregulated 5-fold by combination drug treatment, whereas the proapoptotic BAD and BID genes were upregulated 3-fold. The p53 tumor suppressor was stabilized by an increased acetylation in response to vorinostat and a reduced Ser315 phosphorylation in response to aurora kinase A. Vorinostat or trichostatin A decreased MYC mRNA and protein as well as c-Myc-regulated microRNAs. MYC is a critical gene in these responses, as MYC knockdown combined with the expression of the c-Myc antagonist MXD1 raised cell sensitivity to the effects of either AKi. Thus, the HDACi vorinostat leads to both transcriptional and posttranscriptional changes to create a proapoptotic milieu, sensitizing cells to mitosis-specific agents such as AKis.
Vorinostat, a histone deacetylase inhibitor, enhances the response of human tumor cells to ionizing radiation through prolongation of γ-H2AX foci (2006)

Vorinostat (suberoylanilide hydroxamic acid) is the prototype of a family of hybrid polar compounds that can induce growth arrest in transformed cells and shows promise for the treatment of cancer. Vorinostat specifically binds to and inhibits the activity of histone deacetylases resulting in acetylation of nucleosomal histones and an activation of gene transcription. Because histone deacetylases modulate chromatin structure and gene expression, both of which can influence radioresponse, this study was designed to examine the capacity of Vorinostat to influence radiation response in human tumor cells and investigate the mechanism underlying these interactions. Vorinostat induced hyperacetylation of histone H4 in a dose-dependent manner. We tested its ability to radiosensitize three human tumor cell lines (A375, MeWo, and A549) using clonogenic cell survival assays. Clonogenic cell survival assay showed that Vorinostat significantly radiosensitized all three tumor cell lines, substantially reducing the surviving fraction at 2 Gy. We examined potential mechanisms that may contribute to the enhanced radiation response induced by Vorinostat. Vorinostat and radiation alone did not induce apoptosis in the melanoma cell line. However, enhanced apoptosis was observed when cells were exposed to both Vorinostat and radiation, suggesting that Vorinostat renders tumor cells more susceptible to radiation-induced apoptosis. Results from DNA damage repair analysis in cultured A375 cells showed that Vorinostat had a strong inhibitory effect on the nonhomologous end joining pathway after radiation. A detailed examination of the involvement of the DNA repair pathway following Vorinostat treatment showed that Vorinostat reduced the expression of the repair-related genes Ku70, Ku80, and Rad50 in A375 cells as detected by Western blot analysis. We also examined gamma-H2AX phosphorylation as a predictive marker of radiotherapy response to Vorinostat and observed that the combination of Vorinostat and radiation caused a prolongation of expression of DNA repair proteins such as gamma-H2AX. Overall, we conclude that Vorinostat enhances tumor radioresponse by multiple mechanisms that may involve antiproliferative growth inhibition and effects on DNA repair after exposure to radiation.
in vitro Investigation of the Factors Contributing to the Unique CO2 Transport Properties of Blood in the Sea Lamprey (Petromyzon Marinus) (1994)

In vitro experiments were conducted to determine the factors contributing to the unusual distribution of CO2 in the blood of the sea lamprey. When rainbow trout red blood cells (RBCs) were equilibrated with a 3 % CO2:nitrogen mixture in either normal saline or sodium-free saline, the extracellular total carbon dioxide content (CCO2ext) was highly dependent upon the fraction of RBCs in the suspension. In contrast, when lamprey RBCs were equilibrated in normal saline, the CCO2ext decreased with increasing hematocrit. In the absence of extracellular sodium, however, the CCO2ext in the lamprey RBC suspension also became positively correlated with hematocrit. These results suggest that the membrane of sea lamprey RBCs may be somewhat permeable to bicarbonate, but that transmembrane bicarbonate movements may only be detectable in vitro when Na+/H+ exchange is inactivated. Also in contrast to the results for rainbow trout, the changes in CCO2 that occurred in lamprey RBC suspensions following a step increase in PCO2 were not associated with any change in RBC chloride concentration and were not markedly affected by the chloride/bicarbonate exchange inhibitor 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS). When lamprey RBCs in sodium-free saline were treated with an ionophore for anions, tributyl tin chloride (TBTC), however, the distribution of anions across the RBC membrane came to resemble that of the trout. Furthermore, the relationship between CCO2ext and hematocrit in suspensions of TBTC-treated lamprey RBCs also resembled that of trout in normal saline. Thus, these results demonstrate that both the presence of Na+/H+ exchange and the absence of significant anion exchange contribute to the unique CO2 transport properties of sea lamprey blood.
Rational Design of an Iron‐Based Catalyst for Suzuki–Miyaura Cross‐Couplings Involving Heteroaromatic Boronic Esters and Tertiary Alkyl Electrophiles (2020)

Abstract Suzuki–Miyaura cross‐coupling reactions between a variety of alkyl halides and unactivated aryl boronic esters using a rationally designed iron‐based catalyst supported by β‐diketiminate ligands are described. High catalyst activity resulted in a broad substrate scope that included tertiary alkyl halides and heteroaromatic boronic esters. Mechanistic experiments revealed that the iron‐based catalyst benefited from the propensity for β‐diketiminate ligands to support low‐coordinate and highly reducing iron amide intermediates, which are very efficient for effecting the transmetalation step required for the Suzuki–Miyaura cross‐coupling reaction.
Kerr imaging of a thin film magnetic transducer to measure thin film head fields (2001)

In this work, the field generated by a magnetic recording head is measured by sensing the magnetization of a transducer film, placed in proximity to the ABS of the head. The magnetization is measured by sensing Kerr rotation of a 250 nm laser spot scanned over the transducer at a step size of 55 nm. Since this measurement provides transducer normal magnetization, rather than normal field, the associated head fields are computed by iteratively solving the torque balance on the transducer magnetization and Laplace's equation. This yields a vector field consistent with the observed transducer magnetization and the transducer magnetization gradients. Using this technique the fringing fields of a head with a 0.33 /spl mu/m gap and a 2 /spl mu/m trackwidth are measured.
IL-10-driven immunoglobulin production by B lymphocytes from IgA-deficient individuals correlates to infection proneness (1996)

SUMMARY In search for a possible explanation of the phenotypic heterogeneity in IgA deficiency, we studied the function of B cells from IgA-deficient (IgAd) individuals. Two groups of IgAd individuals, one frequently infected and one clinically apparently healthy, as well as normal controls, were studied. Peripheral blood mononuclear cells (PBMC) and B cells from IgAd individuals and controls were cultured with Staphylococcus aureus Cowan I strain and with anti-CD40 MoAb presented on the CD32-transfected fibroblast cell line in the presence of IL-10. In this experimental system PBMC and B cells from the infection-prone IgAd individuals produced only minute amounts of IgA. In contrast, PBMC and B cells from healthy IgAd subjects secreted significantly more IgA1 and IgA2 in comparison with infection-prone IgAd patients (P &amp;lt; 0.05). These data suggest that the abnormalities of B cell differentiation in IgAd could be of heterogeneous origin. Thus, whereas in healthy IgAd subjects IgA production may be efficiently up-regulated in vitro by addition of IL-10 to CD40-activated B cell culture, the corresponding B cell differentiation does not occur in infection-prone IgAd patients. These observations provide a conceptual framework for phenotypic heterogeneity in IgAd subjects.
Alveolar epithelium protects macrophages from quorum sensing-induced cytotoxicity in a three-dimensional co-culture model (2010)

The quorum sensing signal N-(3-oxododecanoyl)-l-homoserine lactone (3-oxo-C(12) HSL), produced by Pseudomonas aeruginosa, exerts cytotoxic effects in macrophages in vitro, which is believed to affect host innate immunity in vivo. However, the medical significance of this finding to pulmonary disease remains unclear since the multicellular complexity of the lung was not considered in the assessment of macrophage responses to 3-oxo-C(12) HSL. We developed a novel three-dimensional co-culture model of alveolar epithelium and macrophages using the rotating wall vessel (RWV) bioreactor, by adding undifferentiated monocytes to RWV-derived alveolar epithelium. Our three-dimensional model expressed important architectural/phenotypic hallmarks of the parental tissue, as evidenced by highly differentiated epithelium, spontaneous differentiation of monocytes to functional macrophage-like cells, localization of these cells on the alveolar surface and a macrophage-to-epithelial cell ratio relevant to the in vivo situation. Co-cultivation of macrophages with alveolar epithelium counteracted 3-oxo-C(12) HSL-induced cytotoxicity via removal of quorum sensing molecules by alveolar cells. Furthermore, 3-oxo-C(12) HSL induced the intercellular adhesion molecule ICAM-1 in both alveolar epithelium and macrophages. These data stress the importance of multicellular organotypic models to integrate the role of different cell types in overall lung homeostasis and disease development in response to external factors.
MUSCLE INJURIES AND REPAIR (2002)

Johnny Huard, PhD; Yong Li, PhD, MD; Growth and Development Laboratory, Children's Hospital of Pittsburgh, 4151 Rangos Research Center, 3705 Fifth Avenue, Pittsburgh, PA 15213. E-mail address for J. Huard: [email protected] Freddie H. Fu, MD; Department of Orthopaedic Surgery, University of Pittsburgh Medical Center, Liliane S. Kaufmann Building, 3471 Fifth Avenue, Suite 1010, Pittsburgh, PA 15213
Effect of Radial Neck Length on Joint Loading (2019)

Introduction: Load transfer across the radiocapitellar joint of the elbow is poorly understood both in the setting of the native radial head and following radial head arthroplasty. The purpose of this in vitro study was to determine the effects of radial neck length, arm position, and lateral collateral ligament (LCL) repair on radial load.Methods: A uniaxial load cell was implanted into the radial neck of 8 cadaveric specimens that were mounted on an in vitro motion-control simulator and tested (in dependent, varus, and valgus arm orientations) with the native radial neck length and then −4 to +4 mm lengths. Testing was performed with the LCL intact and after sectioning and repair.Results: There was no significant difference between the 2 LCL states (P = .82), and LCL state was not protective of proximal radius overlengthening. Radial loads increased with increasing radial length (P &lt; .001).Discussion and Conclusion: Overlengthening the radial neck resulted in higher compression forces, and underlengthening produced tensile forces, demonstrating that restoration of correct radial length during radial head arthroplasty is important to restore physiologic loading. In the varus position, tensile loading occurred, which may explain clinical problems with ingrowth of uncemented radial head implant stems and dissociation of bipolar implants.
Data from Safety Run-in of Intramuscular pNGVL4a-Sig/E7(detox)/HSP70 DNA and TA-CIN Protein Vaccination as Treatment for HPV16+ ASC-US, ASC-H, or LSIL/CIN1 (2023)

&lt;div&gt;Abstract&lt;p&gt;Patients with human papillomavirus type 16 (HPV16) infection and low-grade cervical dysplasia [low-grade squamous intraepithelial lesion (LSIL)/CIN1] or atypical squamous cells [atypical squamous cells of undetermined significance (ASC-US)/atypical squamous cells- cannot exclude high-grade squamous intraepithelial lesion (ASC-H)] require active surveillance for disease progression. A safe and effective immunotherapy to clear HPV16 is an unmet medical need. The safety run-in cohort of a randomized double-blind, placebo-controlled phase II trial of PVX2 [vaccination twice with HPV16-targeting pNGVL4a-Sig/E7(detox)/HSP70 plasmid and once with the HPV16 L2E7E6 fusion protein “TA-CIN”] as immunotherapy for patients with HPV16+ ASC-US, ASC-H, or LSIL/CIN1 (NCT03911076) was recently completed. The primary objective of this cohort was to determine the safety and tolerability of PVX2 vaccination. Subjects were confirmed to have HPV16 infection and LSIL/CIN1, ASC-US, or ASC-H. Adverse events were evaluated using Common Terminology Criteria for Adverse Events v5.0. HPV typing by HPV16 18/45 Aptima Assay was done at baseline, month 6, and month 12, with simultaneous cytology analysis. Cervical biopsies and endocervical curettage were performed at baseline and month 6. In the safety run-in cohort 12 eligible patients were enrolled. Each received three monthly immunizations. One was lost to follow-up after week 12. There were no serious adverse events. A total of five adverse events were noted by 4 patients; 4 were considered not vaccine-related, and one ‘unlikely related’ by the investigator. At month 6, 45% (5/11) of participants converted to HPV16-negative and 2 others developed CIN2+ and received a loop electrosurgical excision procedure. At month 12, 64% (7/11) were HPV16-negative, including those HPV16-negative at month 6. In conclusion, PVX2 immunotherapy was well tolerated and associated with viral regression, supporting further testing.&lt;/p&gt;Prevention Relevance:&lt;p&gt;This safety run-in study cohort suggests that PVX2 immunotherapy is well tolerated in the target population and is sufficiently safe to warrant further clinical testing in a randomized study. The combined vaccines may facilitate higher-than-expected rate of human papillomavirus type 16 viral clearance 6 and 12 months after treatment, although this requires validation.&lt;/p&gt;&lt;/div&gt;
The Design Process for Google's Training Chips: TPUv2 and TPUv3 (2021)

Five years ago, few would have predicted that a software company like Google would build its own computers. Nevertheless, Google has been deploying computers for machine learning (ML) training since 2017, powering key Google services. These Tensor Processing Units (TPUs) are composed of chips, systems, and software, all co-designed in-house. In this paper, we detail the circumstances that led to this outcome, the challenges and opportunities observed, the approach taken for the chips, a quick review of performance, and finally a retrospective on the results. A companion paper describes the supercomputers built from these chips, the compiler, and a detailed performance analysis [Jou20].
Adaptive Carrier Phase Estimation in Coherent Systems (2012)

We propose an adaptive carrier-phase-estimation (CPE) technique, which automatically optimizes the block length of CPE. It is demonstrated to achieve the best performance in a long- haul 112-Gb/s PDM-QPSK system with and without 10-Gb/s OOK channels.
Light‐Directing Omnidirectional Circularly Polarized Reflection from Liquid‐Crystal Droplets (2014)

Constructing and tuning self-organized three-dimensional (3D) superstructures with tailored functionality is crucial in the nanofabrication of smart molecular devices. Herein we fabricate a self-organized, phototunable 3D photonic superstructure from monodisperse droplets of one-dimensional cholesteric liquid crystal (CLC) containing a photosensitive chiral molecular switch with high helical twisting power. The droplets are obtained by a glass capillary microfluidic technique by dispersing into PVA solution that facilitates planar anchoring of the liquid-crystal molecules at the droplet surface, as confirmed by the observation of normal incidence selective circular polarized reflection in all directions from the core of individual droplet. Photoirradiation of the droplets furnishes dynamic reflection colors without thermal relaxation, whose wavelength can be tuned reversibly by variation of the irradiation time. The results provided clear evidence on the phototunable reflection in all directions.
Trehalose hydrogels for stabilization of enzymes to heat (2015)

Enzymes can catalyze various reactions with high selectivity and are involved in many important biological processes. However, the general instability of enzymes against high temperature often limits their application. To address this, we synthesized a trehalose-based hydrogel in two steps from commercial starting materials with minimal purification procedures. Mono- and multi-functional trehalose monomers were cross-linked by redox-initiated radical polymerization to form a hydrogel. Phytase, an important enzyme utilized in animal feedstock, was employed to study the effectiveness of the trehalose hydrogel to stabilize proteins against heat. Addition of the phytase solution to the hydrogel resulted in enzyme internalization as confirmed by confocal microscopy. The phytase in the hydrogel retained 100% activity upon heating at 90 °C compared to 39% when the hydrogel was absent. The enzyme could also be recovered from the hydrogel. The trehalose hydrogel synthesis reported herein should be readily scalable for thermal stabilization of a wide variety of enzymes.
Continuous Glucose Monitoring Sensors: Past, Present and Future Algorithmic Challenges (2016)

Continuous glucose monitoring (CGM) sensors are portable devices that allow measuring and visualizing the glucose concentration in real time almost continuously for several days and are provided with hypo/hyperglycemic alerts and glucose trend information. CGM sensors have revolutionized Type 1 diabetes (T1D) management, improving glucose control when used adjunctively to self-monitoring blood glucose systems. Furthermore, CGM devices have stimulated the development of applications that were impossible to create without a continuous-time glucose signal, e.g., real-time predictive alerts of hypo/hyperglycemic episodes based on the prediction of future glucose concentration, automatic basal insulin attenuation methods for hypoglycemia prevention, and the artificial pancreas. However, CGM sensors' lack of accuracy and reliability limited their usability in the clinical practice, calling upon the academic community for the development of suitable signal processing methods to improve CGM performance. The aim of this paper is to review the past and present algorithmic challenges of CGM sensors, to show how they have been tackled by our research group, and to identify the possible future ones.
High-efficiency apodized bidirectional grating coupler for perfectly vertical coupling (2019)

We propose and experimentally demonstrate an apodized bidirectional grating coupler for high-efficiency, perfectly vertical coupling. Through grating apodization, the coupling efficiency (CE) can be notably improved, and the parasitic reflections can be minimized. For ease of fabrication, subwavelength gratings are introduced, which are also beneficial for the coupling performance. Simulation shows a record CE of 72%. We found that the coupler is quite robust to the variation of incidence mode field diameter and fiber misalignment. A CE of -1.8 dB is experimentally measured with a 1-dB bandwidth of 37 nm.
Potential-driven statistical ordering of transformations (1997)

Successive, well organized application of transformations has beenwidely recognized as an exceptionally effective, but complex anddifficult CAD task. We introduce a new potential-driven statisticalapproach for ordering transformations. Two new synthesis ideasare the backbone of the approach. The first idea is to quantifythe characteristics of all transformations and the relationship betweenthem based on their potential to reorganize a computationsuch that the complexity of the corresponding implementation isreduced. The second one is based on the observation that transformationsmay disable each other not only because they prevent theapplication of the other transformation, but also because both transformationstarget the same potential of the computation. These twoobservations drastically reduce the search space to find efficient andeffective scripts for ordering transformations. A key algorithmicnovelty is that both conceptual and optimization insights as well asall optimization algorithms are automatically derived by organizedexperimentation and statistical methods. On a large set of diversereal-life examples improvements in throughput, area, and power bylarge factors have been obtained. Both qualitative and quantitativestatistical analysis indicate effectiveness, high robustness, and consistencyof the new approach for ordering transformations.
Hydrodynamic nonadhesive cell retention in a microfluidic circuit for stressless suspension culture (2015)

Cell collection based on deterministic lateral displacement (DLD) and cell circulation with a loop channel are two component technologies for stressless cell retention which have been developed with a view to working toward suspension culture in a microfluidic channel.
Cell-free Protein Expression Using the Rapidly Growing Bacterium <em>Vibrio natriegens</em> (2019)

The marine bacterium Vibrio natriegens has garnered considerable attention as an emerging microbial host for biotechnology due to its fast growth rate. A general protocol is described for the preparation of V. natriegens crude cell extracts using common laboratory equipment. This high yielding protocol has been specifically optimized for user accessibility and reduced cost. Cell-free protein synthesis (CFPS) can be carried out in small scale 10 μL batch reactions in either a 96- or 384-well format and reproducibly yields concentrations of > 260 μg/mL super folder GFP (sfGFP) within 3 h. Overall, crude cell extract preparation and CFPS can be achieved in 1−2 full days by a single user. This protocol can be easily integrated into existing protein synthesis pipelines to facilitate advances in bio-production and synthetic biology applications.
Design of Stimuli‐Responsive Dynamic Covalent Delivery Systems for Volatile Compounds (Part 1): Controlled Hydrolysis of Micellar Amphiphilic Imines in Water (2021)

Despite their intrinsic hydrolysable character, imine bonds can become remarkably stable in water when self-assembled in amphiphilic micellar structures. In this work, we systematically studied some of these structures and the influence of various parameters that can be used to take control of their hydrolysis, including pH, concentration, the position of the imine function in the amphiphilic structure, relative lengths of the linked hydrophilic and hydrophobic moieties. Thermodynamic and kinetic data led us to the rational design of stable imines in water, partly based on the location of the imine function within the hydrophobic part of the amphiphile and on a predictable quantitative term that we define as the total hydrophilic-lipophilic balance (HLB). In addition, we show that such stable systems are also stimuli-responsive and therefore, of potential interest in trapping and releasing micellar components on demand.