gebhart/patrepeval huggingface dataset:
Long-term safety of darolutamide in patients with metastatic castration-resistant prostate cancer. (2022)

90 Background: Darolutamide, a structurally distinct and highly potent androgen receptor inhibitor, had a consistently favorable safety and tolerability profile in patients with nonmetastatic castration-resistant prostate cancer in ARAMIS, and discontinuation rates due to adverse events (AEs) remained consistently low after longer follow-up. In previously reported phase 1/2 studies in patients with metastatic castration-resistant prostate cancer (mCRPC), darolutamide was well tolerated for up to 25 months. We report the safety and tolerability of extended treatment with darolutamide in these mCRPC studies. Methods: Data from three phase 1/2 studies (NCT02363855, NCT01317641/NCT01429064, and NCT01784757) in patients with mCRPC were pooled for analysis of long-term safety. Results are summarized descriptively. Results: Of 173 patients with mCRPC evaluable for safety in the 3 studies, 13 patients received &gt; 2 years of darolutamide treatment; median duration of treatment was 38 months (range 24–90). Six patients received &gt; 4 years of darolutamide treatment. Nine of 13 patients with &gt; 2 years of darolutamide therapy initially received 600 mg BID; others received 200 mg (n = 1), 300 mg (n = 1), or 700 mg (n = 2) BID. Median age was 68 years in the &gt; 2-years group, and most patients were white. Patients were enrolled from France (n = 4), Latvia (n = 3), United Kingdom (n = 3), Finland (n = 2), and Japan (n = 1). Most patients had normal renal function (n = 10) and hepatic function (n = 10), 12 patients had Eastern Cooperative Oncology Group performance status of 0, and 9 patients had a Gleason score ≥7. Prior systemic anticancer treatments taken by more than 1 patient were bicalutamide (n = 10); cyproterone (n = 3); and triptorelin and leuprorelin (n = 2 each). No patient received prior chemotherapy. All 13 patients reported AEs, most grade 1 or 2; 6 reported grade 3 AEs. Treatment-related AEs were reported in 5 patients, and all were grade 1 in severity. Serious AEs were reported in 6 patients, and all were judged not related to darolutamide. One patient treated with darolutamide for &gt; 2 years had an AE (new neoplasm; not related to darolutamide) that led to treatment discontinuation. Conclusions: Extended darolutamide treatment &gt; 2 years in this small group of patients with mCRPC was generally well tolerated, with safety and tolerability consistent with that previously reported. Clinical trial information: NCT02363855, NCT01317641/NCT01429064, and NCT01784757.
Transport properties and microstructures of polycrystalline In2O3–ZnO thin films (2010)

We prepared polycrystalline In2O3–ZnO films by post annealing the amorphous films (1.0 wt % ZnO) at 200 °C with various annealing times ta 0≤ta≤20 h. We have measured the electric resistivity and Hall mobility and also observed film structures by not only the x-ray diffraction but also scanning transmission electron microscopy (STEM) with electron energy-loss spectroscopy (EELS). We have found the following: (1) Hall mobility takes the maximum with respect to the carrier density and the annealed films clearly show the superconductivity of which transition temperature increases with increase in ta. (2) The data on EELS spectra mapping of indium plasmon indicate that droplets of the pure indium phase exist on grain boundaries and near the interface between the film and the glass substrate. However, it seems that these droplets do not form an electrical conducting path but contribute to the scattering centers for carrier electrons, from the dispersed distribution of these droplets in STEM-EELS spectra mapping and the relationship between the electron mean free path and the grain size.
Evaluation metrics for generation (2000)

Certain generation applications may profit from the use of stochastic methods. In developing stochastic methods, it is crucial to be able to quickly assess the relative merits of different approaches or models. In this paper, we present several types of intrinsic (system internal) metrics which we have used for baseline quantitative assessment. This quantitative assessment should then be augmented to a fuller evaluation that examines qualitative aspects. To this end, we describe an experiment that tests correlation between the quantitative metrics and human qualitative judgment. The experiment confirms that intrinsic metrics cannot replace human evaluation, but some correlate significantly with human judgments of quality and understandability and can be used for evaluation during development.
Expression of the Caldariomyces fumagoChloroperoxidase in Aspergillus niger and Characterization of the Recombinant Enzyme (2001)

The Caldariomyces fumago chloroperoxidase was successfully expressed in Aspergillus niger. The recombinant enzyme was produced in the culture medium as an active protein and could be purified by a three-step purification procedure. The catalytic behavior of recombinant chloroperoxidase (rCPO) was studied and compared with that of native CPO. The specific chlorination activity (47 units/nmol) of rCPO and its pH optimum (pH 2.75) were very similar to those of native CPO. rCPO catalyzes the oxidation of various substrates in comparable yields and selectivities to native CPO. Indole was oxidized to 2-oxindole with 99% selectivity and thioanisole to the corresponding R-sulfoxide (enantiomeric excess >98%). Incorporation of (18)O from labeled H(2)18O(2) into the oxidized products was 100% in both cases.
RF CMOS Circuits for Ad-Hoc Networks and Wearable Computing (2005)

Wireless ad-hoc networks are gaining interest for medical, sensing, wearable computing and other applications. The industry is at a critical juncture now where the maturity of RF CMOS can enable these networks. All of these applications, if deployed successfully, results in the proliferation of wireless devices like we have never seen before. The end result is that these devices need to be very low cost, which fits in well with the CMOS paradigm. The challenge going forward is how to make CMOS RF circuits that consume ultra-low power in a compact form factor.
Customisable Tablet Printing: The Development of Multimaterial Hot Melt Inkjet 3D Printing to Produce Complex and Personalised Dosage Forms (2021)

One of the most striking characteristics of 3D printing is its capability to produce multi-material objects with complex geometry. In pharmaceutics this translates to the possibility of dosage forms with multi-drug loading, tailored dosing and release. We have developed a novel dual material hot-melt inkjet 3D printing system which allows for precisely controlled multi-material solvent free inkjet printing. This reduces the need for time-consuming exchanges of printable inks and expensive post processing steps. With this printer, we show the potential for design of printed dosage forms for tailored drug release, including single and multi-material complex 3D patterns with defined localised drug loading where a drug-free ink is used as a release-retarding barrier. For this, we used Compritol HD5 ATO (matrix material) and Fenofibrate (model drug) to prepare both drug-free and drug-loaded inks with drug concentrations varying between 5% and 30% (<i>w</i>/<i>w</i>). The printed constructs demonstrated the required physical properties and displayed immediate, extended, delayed and pulsatile drug release depending on drug localisation inside of the printed formulations. For the first time, this paper demonstrates that a commonly used pharmaceutical lipid, Compritol HD5 ATO, can be printed via hot-melt inkjet printing as single ink material, or in combination with a drug, without the need for additional solvents. Concurrently, this paper demonstrates the capabilities of dual material hot-melt inkjet 3D printing system to produce multi-material personalised solid dosage forms.
Letters to the Editor (1998)

The following is an abstract of the article discussed in the subsequent letter: Finegood, Diane T., and Dan Tzur. Reduced glucose effectiveness associated with reduced insulin release: an artifact of the minimal-model method. Am. J. Physiol. 271 ( Endocrinol. Metab. 34): E485–E495, 1996.—We previously demonstrated that minimal model-derived estimates of glucose effectiveness (S G ), based on the frequently sampled intravenous glucose tolerance test (S G FSIGT ), were reduced in islet-transplanted or streptozotocin-treated dogs and in patients with insulin-dependent diabetes mellitus. To ascertain the validity of our observations, we compared S G FSIGT with estimates based on a basal hormone replacement glucose clamp (S G BRCLAMP ) and a basal hormone replacement glucose tolerance test (S G BRGTT ) in normal control (CNTL, n = 12) and streptozotocin-treated dogs with normal fasting plasma glucose (STZ-Rx, n = 9). S G FSIGT was reduced in STZ-Rx compared with CNTL ( P &lt; 0.05). However, neither S G BRCLAMP nor S G BRGTT was reduced in the STZ-Rx group ( P &gt; 0.05). Comparison of protocols for each subject indicated that S G FSIGT was greater than either S G BRCLAMP or S G BRGTT in control ( P &lt; 0.002) but not in STZ-Rx dogs ( P &gt; 0.1). The relationship of S G FSIGT to insulin secretory function suggests that our previous conclusion that S G FSIGT was reduced in subjects with limited insulin release may be an artifact of the minimal-model method. Our results suggest that caution must be exercised in the interpretation of differences in minimal-model estimates of S G between subject groups with significantly different levels of insulin secretory function.
PROLONGATION OF PRIMATE CARDIAC ALLOGRAFT SURVIVAL BY TREATMENT WITH ANTI-CD40 LIGAND (CD154) ANTIBODY1 (1999)

Anti-CD154 antibody markedly prolongs the survival of cardiac allografts in primates and is well tolerated. Sustained dosing with hu5c8 yielded improved survival and may be associated with a lower incidence of vascular pathology. We conclude that hu5c8 therapy is an effective approach for inhibiting acute cardiac allograft rejection in primates.
P858 An open-label, multi-center trial of INO-5401 and INO-9012 delivered by electroporation (EP) in combination with cemiplimab in subjects with newly-diagnosed glioblastoma (GBM) (2020)

<h3>Background</h3> GBM is one of the most deadly cancers and treatment is surgery, followed by radiation (RT) and temozolomide (TMZ) daily during RT followed by cycles of TMZ for select patients.<sup>1</sup> New immunotherapies, such as checkpoint inhibition, may benefit patients with GBM. T cell-enabling therapies, in combination with checkpoint inhibition, may improve overall survival (OS). In this study, a novel antigen-specific T cell-generating therapy, INO-5401 (synthetic DNA plasmids encoding for human telomerase [hTERT], Wilms Tumor-1 [WT-1] and prostate specific membrane antigen [PSMA]), plus INO-9012 (synthetic DNA plasmid encoding for IL-12), with the PD-1 checkpoint inhibitor, cemiplimab, was given to patients with newly-diagnosed GBM to evaluate tolerability, immunogenicity and clinical efficacy of the combination. <h3>Methods</h3> Phase I/II, single arm, two cohort study (A: MGMT Promoter Unmethylated, B: MGMT Promoter Methylated). The primary objective is to evaluate the safety of INO-5401 and INO-9012 followed by EP with CELLECTRA® 2000 in combination with cemiplimab. Secondary objectives include the evaluation of preliminary clinical efficacy and immunogenicity. Treatment is with 9 mg INO-5401 with 1 mg INO-9012 every three weeks (Q3W) for four doses, then Q9W; and cemiplimab (350 mg IV Q3W). RT is given as 40 Gy over three weeks; TMZ is given concurrent with radiation (Cohorts A and B), followed by maintenance TMZ (Cohort B). <h3>Results</h3> 52 patients were enrolled onto this study; 32 in Cohort A and 20 in Cohort B. 18 were women (35%) and 47 were white (90%). The median age was 60 years (range 19-78 years). The most common Grade ≥3 adverse events were elevations in alanine or aspartate aminotransferase (ALT/AST; 5 patients), and tumor inflammation/edema (5 patients); there was one Grade 5 unrelated event of urosepsis. The only related SAE reported in more than one patient was pyrexia. 22 patients (42%) reported immune-related AEs, with the most common being elevations in ALT or AST (8 patients), and were reported most commonly within the first nine weeks of treatment. The safety profile was consistent with that of patients with GBM and of checkpoint inhibitors. ELISpot assessments performed to date demonstrated the majority of patients have T cell responses to INO-5401. PFS6 was 75% (95% CI 56.6, 88.5) in Cohort A (preliminary; Cohort B pending). <h3>Conclusions</h3> INO-5401 + INO-9012 with cemiplimab has an acceptable safety profile, is immunogenic and is potentially efficacious in patients with newly-diagnosed GBM. This combination is promising; survival results will be updated next year. <h3>Trial Registration</h3> NCT03491683. <h3>Ethics Approval</h3> This study was approved by New York University institution’s Ethics Board; approval number i17-00764. <h3>References</h3> Stupp R, et al. (2009). <i>Lancet Oncology</i> 10(5): 459–466.
χ^2 analysis for estimating the accuracy of optical properties derived from time resolved diffuse-reflectance (2009)

Weighted residuals and the reduced chi(2) (chi(R) (2)) value are investigated with regard to their relevance for assessing optical property estimates using the diffusion equation for time-resolved measurements in turbid media. It is shown and explained, for all photon counting experiments including lifetime estimation, why chi(R) (2) increases linearly with the number of photons when there is a model bias. Only when a sufficient number of photons has been acquired, chi(R) (2) is a pertinent value for assessing the accuracy of mu(a) and mu(s)' estimates. It was concluded that chi(R) (2) is of particular interest for cases of small interfiber separation, low-level scattering, strong absorption and incorrect measurement of instrument response function. It was also found that chi(R) (2) is less pertinent for judging mu(a) in case of air boundary effects.
Purification of recombinant bacterial collagens containing structural perturbations (2023)

Streptococcus pyogenes-derived recombinant bacterial collagen-like proteins (CLPs) are emerging as a potential biomaterial for biomedical research and applications. Bacterial CLPs form stable triple helices and lack specific interactions with human cell surface receptors, thus enabling the design of novel biomaterials with specific functional attributes. Bacterial collagens have been instrumental in understanding collagen structure and function in normal and pathological conditions. These proteins can be readily produced in E. coli, purified using affinity chromatography, and subsequently isolated after cleavage of the affinity tag. Trypsin is a widely used protease during this purification step since the triple helix structure is resistant to trypsin digestion. However, the introduction of Gly→X mutations or natural interruptions within CLPs can perturb the triple helix structure, making them susceptible to trypsin digestion. Consequently, removing the affinity tag and isolating collagen-like (CL) domains containing mutations is impossible without degradation of the product. We present an alternative method to isolate CL domains containing Gly→X mutations utilizing a TEV protease cleavage site. Protein expression and purification conditions were optimized for designed protein constructs to achieve high yield and purity. Enzymatic digestion assays demonstrated that CL domains from wild-type CLPs could be isolated by digestion with either trypsin or TEV protease. In contrast, CLPs containing Gly→Arg mutations are readily digested by trypsin while digestion with TEV protease cleaved the His6-tag, enabling the isolation of mutant CL domains. The developed method can be adapted to CLPs containing various new biological sequences to develop multifunctional biomaterials for tissue engineering applications.
Integrating a critical reflection framework for experiential learning activities into a large first-year engineering course (2022)

First-year university is an ideal time for students to begin the development of critical thinking and self-directed learning skills. Structuring critical reflection with experiential learning activities can provide opportunities for students to develop and learn how to apply these skills in the future. Previous research has identified considerations for implementing critical reflection into the first-year engineering curricula in ways that students will meaningfully engage. The primary goal of this work was to integrate critical reflection learning outcomes, activities, and assessments into the first-year engineering curriculum connected to experiential learning activities.&#x0D; Critical reflection activities were scaffolded to a critical reflection framework, adapted to the first-year engineering context. Three critical reflection assessments were mapped to experiential learning activities to further the development of these skills in parallel, such as teamwork, problem solving, and communication. One assignment involved a peer review process, where students had the opportunity to learn from each other’s experiences, and give constructive feedback through learning of students’ shared university experiences.&#x0D; The benefits of developing student reflection skills are obvious, and the improvements witnessed are encouraging. However, there remain many challenges, particularly with respect to assessment methodologies, and student motivation. Meaningful integration of critical reflection remains an iterative learning experience for the instructors.
Multi-strange baryon production at mid-rapidity in Pb–Pb collisions at sNN=2.76 TeV (2013)

The production of Ξ− and Ω− baryons and their anti-particles in Pb–Pb collisions at sNN=2.76 TeV has been measured using the ALICE detector. The transverse momentum spectra at mid-rapidity (|y|<0.5) for charged Ξ and Ω hyperons have been studied in the range 0.6<pT<8.0 GeV/c and 1.2<pT<7.0 GeV/c, respectively, and in several centrality intervals (from the most central 0–10% to the most peripheral 60–80% collisions). These spectra have been compared with the predictions of recent hydrodynamic models. In particular, the Kraków and EPOS models give a satisfactory description of the data, with the latter covering a wider pT range. Mid-rapidity yields, integrated over pT, have been determined. The hyperon-to-pion ratios are similar to those at RHIC: they rise smoothly with centrality up to 〈Npart〉∼150 and saturate thereafter. The enhancements (yields per participant nucleon relative to those in pp collisions) increase both with the strangeness content of the baryon and with centrality, but are less pronounced than at lower energies.
Improved excitation model for FDTD analysis of mobile phone antennas (2002)

The practical FDTD analysis of personal communications devices requires simplified models of antenna excitation. The paper reviews the existing models and proposes a new improved one based on a thin feeding TEM line with a square cross-section and modal template termination. The new model ensures excellent accuracy of return loss extraction even at coarse discretization, and competitive speed in calculating antenna efficiency.
New Automatized Method of 3D Multiculture Viability Analysis Based on Confocal Imagery: Application to Islets and Mesenchymal Stem Cells Co-Encapsulation (2018)

Co-encapsulation of pancreatic islets with mesenchymal stem cells in a three-dimensional biomaterial's structure is a promising technique to improve transplantation efficacy and to decrease immunosuppressant therapy. Currently, evaluation of graft quality after co-encapsulation is only based on insulin secretion. Viability measurement in a 3D conformation structure involving two different cell types is complex, mainly performed manually, highly time consuming and examiner dependent. Standardization of encapsulated graft viability analysis before transplantation is a key point for the translation of the method from the bench side to clinical practice. In this study, we developed an automated analysis of islet viability based on confocal pictures processing of cells stained with three probes (Hoechst, propidium iodide, and PKH67). When compared with results obtained manually by different examiners, viability results show a high degree of similarity (under 3% of difference) and a tight correlation (<i>r</i> = 0.894; <i>p</i> < 0.001) between these two techniques. The automated technique offers the advantage of reducing the analysis time by 6 and avoids the examiner's dependent variability factor. Thus, we developed a new efficient tool to standardize the analysis of islet viability in 3D structure involving several cell types, which is a key element for encapsulated graft analysis in clinical practice.
Multifunctional nanoparticles for targeting cancer and inflammatory diseases (2013)

The interplay between cancer and inflammation has been well documented over the years and the role of nanomedical technologies for treating both these diseases has become evident over the past few decades. With the advances in nanoparticle-based imaging and therapeutic platforms that can exploit the pathological conditions of the tumor and the inflamed sites to effectively deliver drugs, genes and imaging/contrast agents; the management of such conditions with favorable therapeutic outcomes seems plausible. This review will summarize some of the latest advances in the field of targeted nanomedicine development to combat cancer and inflammation. Illustrative examples of multifunctional-targeted nanosystems are presented that highlight their potential in delivering diverse payloads, including small molecule drugs, nucleic acids and imaging agents for simultaneous theranostic interventions.
MONSTR (1994)

This paper presents a new approach to 3-dimensional thermal simulation of arbitrary electronic systems. This approach is based on the combination of numerical (finite elements and finite differences) and analytical (Fourier series) techniques which are very general and extremely efficient. Complex electronic systems (monolithic IC's, multichip modules, including their packaging) can be analyzed in minutes on PC's to produce a detailed temperature distributions within the system structure. The software system, MON-STR, has been developed and applied to several industrial examples. The results of this analysis are directly entered to the circuit simulator, HSPICE, as the actual temperature for each circuit element and thus an integrated electro-thermal simulation is performed.
A new perspective on processing-in-memory architecture design (2013)

As computation becomes increasingly limited by data movement and energy consumption, exploiting locality throughout the memory hierarchy becomes critical for maintaining the performance scaling that many have come to expect from the computing industry. Moving computation closer to main memory presents an opportunity to reduce the overheads associated with data movement. We explore the potential of using 3D die stacking to move memory-intensive computations closer to memory. This approach to processing-in-memory addresses some drawbacks of prior research on in-memory computing and appears commercially viable in the foreseeable future. We show promising early results from this approach and identify areas that are in need of research to unlock its full potential.