gebhart/patrepeval huggingface dataset:
Personalized DNA neoantigen vaccine in combination with plasmid IL-12 and pembrolizumab for the treatment of patients with advanced hepatocellular carcinoma. (2021)

TPS2680 Background: Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related death. Immune checkpoint inhibitors targeting PD-1 have limited activity in HCC as monotherapy, with response rates ranging from 14-17%. Tumor neoantigens derived from tumor-specific mutations can be incorporated into personalized therapeutic cancer vaccines to prime T cell responses, potentially enhancing responses to anti-PD1 therapy. DNA vaccines have been shown to elicit strong CD8 and CD4 T cell responses in preclinical and clinical trials. In preclinical studies, DNA-encoded neoantigen vaccines have shown induction of CD8 T cells against 50% of predicted high affinity epitopes with the ability to impact tumor growth. GNOS-PV02 is a personalized DNA vaccine, encoding up to 40 patient-specific neoantigens. In the GT-30 trial, it is used in combination with INO-9012 (plasmid-encoded IL-12) and pembrolizumab for the treatment of advanced HCC. Methods: The GT-30 trial (NCT04251117) is a single-arm phase I/II clinical trial to assess the safety, immunogenicity, and preliminary efficacy of GNOS-PV02 in combination with INO-9012 and pembrolizumab in patients with advanced HCC. Twenty-four patients are anticipated to be enrolled. Patients are recruited upon diagnosis or during first-line treatment with tyrosine kinase inhibitors (TKI). Tumors are biopsied for exome and transcriptome sequencing. The tumor specific vaccine is designed, optimized and manufactured during first-line therapy. Each vaccine encodes up to 40 neoantigens, which includes all detected neoantigens for the majority of HCC patients. After progression or intolerance with first-line therapy, patients can commence trial therapy with concurrent personalized vaccine and pembrolizumab. GNOS-PV02 + INO-9012 are administered Q3w for the first 4 doses and Q9w thereafter until disease progression. Pembrolizumab is delivered Q3w until disease progression. Immunogenicity of each of the vaccine epitopes will be determined by ex vivo ELISpot and flow cytometry. Clinical activity is assessed by RECIST1.1 at baseline and every 9 weeks. Serial biopsies will be obtained at 9 weeks and upon disease progression to evaluate changes in the exome, transcriptome and changes to the tumor microenvironment. Clinical trial information: NCT04251117.
Depth-Adjustable Magnetostructural Phase Transition in Fe60V40 Thin Films (2022)

Phase transitions occurring within spatially confined regions can be useful for generating nanoscale material property modulations. Here we describe a magneto-structural phase transition in a binary alloy, where a structural transition from short-range order (SRO) to body centered cubic (bcc) results in the formation of depth-adjustable ferromagnetic layers, which reveal application-relevant magnetic properties of high saturation magnetization (Ms) and low Gilbert damping (α). Here we use Fe60V40 binary alloy films which transform from initially Ms = 17 kA/m (SRO structure) to 747 kA/m (bcc structure) driven by atomic displacements caused by penetrating ions. Simulations show that an estimated ∼1 displacement per atom triggers a structural transition, forming homogeneous ferromagnetic layers. The thickness of a ferromagnetic layer increases as a step-like function of the ion fluence. Microwave excitations of the ferromagnetic/non-ferromagnetic layered system reveals an α = 0.0027 ± 0.0001. The combination of nanoscale spatial confinement, low α, and high Ms provides a pathway for the rapid patterning of magnetic and microwave device elements.
Energy efficient and ultra low voltage security circuits for nanoscale CMOS technologies (2017)

Low-area energy-efficient security primitives are key building blocks for enabling end-to-end content protection, user authentication, and consumer confidentiality in the IoT world that is estimated to surpass 50billion smart and connected devices by 2020. This paper describes design approaches that blend energy efficient circuit techniques with optimal accelerator microarchitecture datapath, and hardware friendly arithmetic to achieve ultra-low energy consumption in security platforms for seamless adoption in area/battery constrained and self-powered systems. Industry leading energy-efficiency is demonstrated with three designs, fabricated and measured in advanced process technologies : 1) A 2040-gate arithmetically optimized composite field Sbox based AES accelerator achieves 289Gbps/W peak energy-efficiency while offering 432Mbps throughput in 22nm trigate CMOS, 2) Hybrid Physically Unclonable Function (PUF) circuit leverages burn-in induced aging to reduce bit-error, followed by temporal-majority-voting, dark-bit masking, and error-correction conditioning techniques to generate a 100% stable full-entropy key with 190fJ/bit energy consumption in 22nm tri-gate CMOS. 3) A light-weight all digital TRNG uses in-line correlation suppressor and entropy-extractor circuits to achieve >0.99 min-entropy with 3pJ/bit measured energy-efficiency while operating down to 300mV in 14nm tri-gate CMOS.
Deformable MRI-Ultrasound registration using correlation-based attribute matching for brain shift correction: Accuracy and generality in multi-site data (2019)

Intraoperative tissue deformation, known as brain shift, decreases the benefit of using preoperative images to guide neurosurgery. Non-rigid registration of preoperative magnetic resonance (MR) to intraoperative ultrasound (iUS) has been proposed as a means to compensate for brain shift. We focus on the initial registration from MR to predurotomy iUS. We present a method that builds on previous work to address the need for accuracy and generality of MR-iUS registration algorithms in multi-site clinical data. High-dimensional texture attributes were used instead of image intensities for image registration and the standard difference-based attribute matching was replaced with correlation-based attribute matching. A strategy that deals explicitly with the large field-of-view mismatch between MR and iUS images was proposed. Key parameters were optimized across independent MR-iUS brain tumor datasets acquired at 3 institutions, with a total of 43 tumor patients and 758 reference landmarks for evaluating the accuracy of the proposed algorithm. Despite differences in imaging protocols, patient demographics and landmark distributions, the algorithm is able to reduce landmark errors prior to registration in three data sets (5.37±4.27, 4.18±1.97 and 6.18±3.38 mm, respectively) to a consistently low level (2.28±0.71, 2.08±0.37 and 2.24±0.78 mm, respectively). This algorithm was tested against 15 other algorithms and it is competitive with the state-of-the-art on multiple datasets. We show that the algorithm has one of the lowest errors in all datasets (accuracy), and this is achieved while sticking to a fixed set of parameters for multi-site data (generality). In contrast, other algorithms/tools of similar performance need per-dataset parameter tuning (high accuracy but lower generality), and those that stick to fixed parameters have larger errors or inconsistent performance (generality but not the top accuracy). Landmark errors were further characterized according to brain regions and tumor types, a topic so far missing in the literature.
Supplementary results from Expression of CD14, IL10, and Tolerogenic Signature in Dendritic Cells Inversely Correlate with Clinical and Immunologic Response to TARP Vaccination in Prostate Cancer Patients (2023)

&lt;p&gt;Additional Analysis not included in the main text&lt;/p&gt;
Deferoxamine-Soaked Suture Improves Angiogenesis and Repair Potential After Acute Injury of the Chicken Achilles Tendon (2018)

Stimulating angiogenesis by DFO-saturated suture may be clinically useful to improve healing of poorly vascularized tissues.
Protein Kinase A Phosphorylation of the Cardiac Calcium Release Channel (Ryanodine Receptor) in Normal and Failing Hearts (2002)

The cardiac ryanodine receptor/calcium release channel (RyR2) on the sarcoplasmic reticulum (SR) comprises a macromolecular complex that includes a kinase and two phosphatases that are bound to the channel via targeting proteins. We previously found that the RyR2 is protein kinase A (PKA)-hyperphosphorylated in end-stage human heart failure. Because heart failure is a progressive disease that often evolves from hypertrophy, we analyzed the RyR2 macromolecular complex in several animal models of cardiomyopathy that lead to heart failure, including hypertrophy, and at different stages of disease progression. We now show that RyR2 is PKA-hyperphosphorylated in diverse models of heart failure and that the degree of RyR2 PKA phosphorylation correlates with the degree of cardiac dysfunction. Interestingly, we show that RyR2 PKA hyperphosphorylation can be lost during perfusion of isolated hearts due to the activity of the endogenous phosphatases in the RyR2 macromolecular complex. Moreover, infusion of isoproterenol resulted in PKA phosphorylation of RyR2 in rat, indicating that systemic catecholamines can activate phosphorylation of RyR2 in vivo. These studies extend our previous analyses of the RyR2 macromolecular complex, show that both the kinase and phosphatase activities in the macromolecular complex are regulated physiologically in vivo, and suggest that RyR2 PKA hyperphosphorylation is likely a general feature of heart failure.
Azepino- and Diazepinoindoles: Synthesis and Dopamine Receptor Binding Profiles (2000)

Starting from the readily available building blocks 7, 10, 11, and 15, the synthesis of the fused indoles 1, 2, 5, and 6, respectively, is reported. The syntheses involved Pictet-Spengler cyclizations, Michael addition reactions, lactamization, directed metallation, and reductive amination as the key reaction steps. Radioligand displacement studies comprising the dopamine receptor subtypes D1, D2long D2short, D3, and D4.4 were performed when the diazepinoindole 6 revealed D1 and D4 affinities (Ki = 0.11 μM and 1.7 μM, respectively) which are comparable to the partial D1 agonist SKF 38393 (3b). In contrast to the benzazepine 3b, the indole based test compounds turned out less selective over the D2 and D3 receptor subtype.
New insights in acetaminophen toxicity: HMGB1 contributes by itself to amplify hepatocyte necrosis in vitro through the TLR4-TRIF-RIPK3 axis (2020)

Extracellular release of HMGB1 contributes to acetaminophen-induced liver injury. HMGB1 acts as a danger-associated molecular patterns during this toxic process but the mechanisms of action and targeted cells are incompletely defined. Here we studied, in vitro, the role of HMGB1 in amplifying the acetaminophen-induced hepatocyte necrosis process. Using cultured HepaRG cells, primary human hepatocytes and selective chemical inhibitors we evaluated acetaminophen-induced toxicity. We confirmed that addition of acetaminophen induced HepaRG cell death and HMGB1 release. We showed that inhibition of HMGB1 decreased acetaminophen-induced HepaRG cell death, suggesting a feedforward effect. We provide the first evidence that exposure of HepaRG cells to recombinant human HMGB1 (rhHMGB1) also resulted in cell death. Moreover, we found that both acetaminophen and rhHMGB1 induced programmed HepaRG cell necrosis through a RIPK3-dependent mechanism. By using TLR4 blocking antibody, we demonstrated the reduction of the HepaRG cell death induced by acetaminophen and rhHMGB1. Furthermore, inhibition of TRIF, known to induce a RIPK3-dependent cell death, reduced rhHMGB1-induced HepaRG cell death. Our data support that released HMGB1 from acetaminophen-stressed hepatocytes induced necrosis of neighboring hepatocytes by TLR4-TRIF-RIPK3- pathway. This in vitro study gives new insights in the role of HMGB1 in the amplification of acetaminophen-induced toxicity.
Electrochemical Cu Growth on MPS-Modified Au(111) Electrodes (2012)

Au(111) electrodes have been modified with self-assembled monolayers (SAM) of 3-mercapto-1-propanesulfonic acid (MPS) and used as a substrate for Cu electrodeposition. Aqueous plating solutions contained 0.1 M H2SO4, low Cu concentrations (≤80 μM), and, optionally, 1.4 mM Cl ions. The deposition process was characterized by cyclic voltammetry (CV) and in-situ scanning tunneling microscopy (STM) as a function of the electrode potential. At potentials positive of Cu growth (≥0.7 VRHE), freshly modified electrodes are covered by an ordered (5√3 × √21) MPS adlayer (α) both in Cl-free and Cl-containing electrolytes. The α adlayer becomes disordered at more negative potentials prior to the onset of Cu deposition (≤0.65 VRHE). In the potential regime of Cu underpotential deposition (UPD) (≈0.2–0.65 VRHE), the surface morphology strongly depends on the presence of Cl. In the absence of Cl, a transient, ordered Cu/MPS adlayer phase (δ) forms via 2D growth and covers the entire Au(111) surface. Subsequently, the δ phase transforms into a disordered Cu/MPS phase (σCu) with small, embedded Cu islands. In Cl-containing electrolyte, a disordered Cu/MPS/Cl phase (γ) nucleates at Au step edges or surface defects and spreads laterally. Cu islands form simultaneously within the γ phase. Two-dimensional growth of these islands results in a pure Cu-UPD layer. Overpotential deposition (OPD) proceeds via layer-by-layer mode with second layer nucleations at surprisingly small critical coverages (θC ≪ 0.5). Our observations differ significantly from those in previous studies, demonstrating that the Cu growth behavior critically depends on the concentrations of MPS, Cu, and Cl at the interface.
Supplemental Figures S7 from The BET Bromodomain Inhibitor OTX015 Affects Pathogenetic Pathways in Preclinical B-cell Tumor Models and Synergizes with Targeted Drugs (2023)

&lt;p&gt;Supplemental Figures S7. Supplemental Figures S7. Effects of JQ1 and OTX015 on BRD4 binding to MYD88 promoter region in DLBCL cell lines.&lt;/p&gt;
ChemInform Abstract: ADDITION REACTIONS OF AMINIUM RADICALS: SYNTHETIC STUDIES OF OXIDATIVE PHOTOADDITION OF N‐NITRODIMETHYLAMINE (1982)

Abstract Die Photoaddition von N‐Nitro‐dimethylamin (NNOD) an die Olefine (I) unter oxidierenden Bedingungen ergibt die unbeständigen Salpetersäureester (II), die zu den Aminoalkoholen (III) reduziert werden (diese werden von CrO 3 zu den entsprechenden Ketonen oxidiert).
Secondary metabolites in honey and their inhibitory activity on matrix metalloproteinases (2016)

Honey is a viscous, supersaturated sugar solution derived from nectar, and gathered and modified by the honeybee, Apis mellifera [1]. It has been used as a traditional medicine for centuries by different cultures. Honey possesses antimicrobial properties against a broad range of microbes, and promotes wound healing [2]. In the present study, after a first elimination of sugars, the chemical profile of 10 Greek monofloral honeys (e.g. thyme, chestnut, fir honeydew, pine, orange, heather, strawberry tree) was investigated by HPTLC, which permits the automatic, rapid and low cost evaluation of complex herbal mixtures. Furthermore, their radical scavenging activity was tested with the aid of a DPPH assay. Two honey samples, a strawberry tree and a heather honey, were further processed, and major compounds were purified by MPLC. Unedone was obtained from strawberry tree honey and the flavonoids quercitrin and naringenin from heather honey, while two isomers of abscisic acid (cis, trans-ABA and trans, trans-ABA) were isolated from both samples. Subsequently, raw honeys and pure compounds were evaluated for their ability to inhibit the matrix metalloproteinases collagenase and elastase. Both raw honey samples and pure compounds exerted moderate inhibitory activity on the tested enzymes. More specifically, strawberry tree and heather honey samples (100 µg/mL) inhibited elastase 62.4% and 56.1% and collagenase 54.3% and 50.6%, respectively. The isolated compounds tested at 100µM exerted 56.7% and 46.3% (unedone), 45.2% and 48.5% (quercitrin), 38.1% and 45.7% (naringenin) inhibitory potency against elastase and collagenase, respectively. The abscisic acid isomers didn't appear to be potent inhibitors against both enzymes. Spectrophotometric methods were used to determine the enzymatic activity. Elastase and collagenase are implicated in the wound healing process and their overexpression and activation is thought to be involved in the pathogenesis of chronic wounds. Improving basic knowledge in this area ultimately may help clarify the role of honey in the wound healing mechanism and proactively intervene in an effort to prevent normal wounds from becoming chronic [3].
Ge/SiGe asymmetric Fabry-Perot quantum well electroabsorption modulators (2012)

We demonstrate vertical-incidence electroabsorption modulators for free-space optical interconnects. The devices operate via the quantum-confined Stark effect in Ge/SiGe quantum wells grown on silicon substrates by reduced pressure chemical vapor deposition. The strong electroabsorption contrast enables use of a moderate-Q asymmetric Fabry-Perot resonant cavity, formed using a film transfer process, which allows for operation over a wide optical bandwidth without thermal tuning. Extinction ratios of 3.4 dB and 2.5 dB are obtained for 3 V and 1.5 V drive swings, respectively, with insertion loss less than 4.5 dB. For 60 ?m diameter devices, large signal modulation is demonstrated at 2 Gbps, and a 3 dB modulation bandwidth of 3.5 GHz is observed. These devices show promise for high-speed, low-energy operation given further miniaturization.
Performance Evaluation of Adapting Many-Core Processors to the Optimization of a Shaped Reflector Antenna (2014)

In the design of reflector antennas, optimization of the reflector surface requires a long computation time. To overcome this problem, we use parallel processing based on GPUs. In this paper, we present the performance of a GPU-based implementation for optimizing a shaped reflector antenna. The experimental results show that our implementation with 1-4 GPUs is about 8-20 times faster than that with a 6-threaded CPU.
Outcomes After Operative Fixation of Vancouver B2 and B3 Type Periprosthetic Fractures (2021)

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Formulation of a Criterion for Preventing Self-Loosening of Threaded Fasteners Due to Cyclic Transverse Loading (2010)

In the paper, a novel criterion is developed for preventing the self-loosening of preloaded threaded fasteners under cyclic transverse loading. For a known cyclic excitation, the system parameters are used in the formulation of a closed form solution for the minimum fastener preload required for preventing self-loosening. The effect of several key variables is investigated; this includes bearing and thread friction coefficients, bolt grip length, thread pitch, material, and the cyclic amplitude of the transverse excitation. An experimental setup and test procedure is established. Comparison between the experimental and analytical clamp load variation results shows that the proposed criterion can accurately predict the requirements for preventing self-loosening.
Experimental evaluation of nonclassical correlations between measurement outcomes and target observable in a quantum measurement (2016)

In general, it is difficult to evaluate measurement errors when the initial and final conditions of the measurement make it impossible to identify the correct value of the target observable. Ozawa proposed a solution based on the operator algebra of observables which has recently been used in experiments investigating the error-disturbance trade-off of quantum measurements. Importantly, this solution makes surprisingly detailed statements about the relations between measurement outcomes and the unknown target observable. In the present paper, we investigate this relation by performing a sequence of two measurements on the polarization of a photon, so that the first measurement commutes with the target observable and the second measurement is sensitive to a complementary observable. While the initial measurement can be evaluated using classical statistics, the second measurement introduces the effects of quantum correlations between the noncommuting physical properties. By varying the resolution of the initial measurement, we can change the relative contribution of the nonclassical correlations and identify their role in the evaluation of the quantum measurement. It is shown that the most striking deviation from classical expectations is obtained at the transition between weak and strong measurements, where the competition between different statistical effects results in measurement values well outside the range of possible eigenvalues.
Astroglia are a possible cellular substrate of angiotensin(1-7) effects in the rostral ventrolateral medulla (2010)

Astroglia are a plausible cellular target of Ang1-7 in RVLM. Our data suggest that astrocytic responsiveness to Ang1-7 is reduced in SHR. We hypothesise that Ang1-7 modulates astrocytic signalling which in vivo may affect local metabolism and microcirculation, resulting in changes in activity of RVLM pre-sympathetic neurones and hence blood pressure.
An automatic diagnosis system of nuclear cataract using slit-lamp images (2009)

An automatic diagnosis system of nuclear cataract is presented in this paper. Nuclear cataract is graded according to the severity of opacity using slit-lamp lens images. Anatomical structure in the lens image is detected using a modified active shape model (ASM). Based on the anatomical landmark, local features are extracted according to clinical grading protocol. Support vector machine (SVM) regression is employed to train a grading model for grade prediction. The system is tested using clinical images and clinical ground truth. More than five thousands slit-lamp images were tested. The success rate of feature extraction is 95% and the mean grading difference is 0.36. The automatic diagnosis system can help to improve the grading objectivity and save the workload of ophthalmologists.
Analytic model of flux distribution in linear PM synchronous machines including longitudinal end effects (2006)

This thesis studies the electric aspects of a linear synchronous permanent magnet generator. The generator is designed for use in a wave energy converter, which determines the fundamental requirements of the generator. The electromagnetic properties of the generator are investigated with a finite element based simulation tool. These simulations formed the base of the design and construction of a laboratory prototype. Several experiments where conducted on the prototype generator. The results verify at large the simulation tool. However, a difference between the measured and simulated air gap flux was discovered. This was attributed to the longitudinal ends of the generator, which are ignored in the simulation tool. Experiences from the construction, and further finite element studies, led to a significant change in the support structure of the first offshore prototype generator. A complete wave energy converter was constructed and launched, the 13th of March, on the west coast of Sweden. A study of the load resistance impact on the power absorption has been carried out. An optimal load interval, with regard to power absorption, has been identified. Furthermore, the generator has proofed to withstand short term overload several times larger than the nominal load. Finally, the longitudinal ends’ influence on the flux distribution was investigated with an analytical model, as well as finite element simulations. A possible problem with large induction of eddy currents in the actuator back steel was identified.This work is a part of a larger project, which aims do develop a viable wave energy conversion system.