gebhart/patrepeval huggingface dataset:
Dose escalation results from a first-in-human, phase 1 study of the glucocorticoid-induced TNF receptor-related protein (GITR) agonist AMG 228 in patients (Pts) with advanced solid tumors. (2017)

2521 Background: AMG 228 is an agonistic human IgG1 monoclonal antibody that binds to GITR (CD357), a TNFSFR costimulatory molecule expressed by effector/regulatory T cells. Dose escalation of this open label, first in human, phase 1 study evaluated the safety, pharmacokinetics (PK), pharmacodynamics, and maximum tolerated dose (MTD) and recommended phase 2 dose of AMG 228 in pts with advanced solid tumors. Methods: Pts with refractory advanced colorectal cancer (n = 13), squamous cell carcinoma of head and neck (n = 10), non–small cell lung cancer (n = 2), urothelial transitional cell carcinoma (n = 4), and melanoma (n = 1) received AMG 228 IV Q3W. Dose escalation was in two stages: single-pt cohorts until AMG 228-related grade &gt; 2 adverse events (AEs), efficacy, or 90 mg dose reached (4 cohorts: 3, 9, 30, and 90 mg), followed by rolling six design (n = 2 to 6) until MTD or highest planned dose of 1200 mg reached (5 cohorts: 180, 360, 600, 900, and 1200 mg). Primary endpoints included incidence of dose-limiting toxicities (DLTs) and AEs and PK. Additional endpoints were objective response (RECIST 1.1) and evidence of biological activity. Results: In total, 30 pts (median age 63 y) were treated (3, 9, 30, and 90 mg, n = 1; 180 mg, n = 6; 360 mg, n = 4; 600 mg, n = 6; 900 mg, n = 4; 1200 mg, n = 6). Twenty-seven (90%) pts had treatment-emergent AEs; the most common were hypophosphatemia (23%), fatigue (23%), anemia (23%), nausea (20%), and pyrexia (20%). No DLTs occurred; the MTD was not reached. AMG 228 exposure was dose-related, with PK profiles at low doses (3 to 90 mg) consistent with target mediated drug disposition; doses &gt; 360 mg achieved serum levels needed for 95% receptor occupancy on activated PBMCs. No evidence of T cell activation was observed despite complete target coverage in both tumor and peripheral blood. Among 29 evaluable pts, none had an objective response. Conclusions: In this population of pts with advanced solid tumors, AMG 228 Q3W was tolerable up to the highest tested dose (1200 mg), showing favorable PK. However, no clinical or immunological activity was observed in this limited number of pts. Clinical trial information: NCT02437916.
A study of an up‐ and a down‐pumping wide‐blade hydrofoil impeller: Part II. CFD analysis (1998)

Abstract Two different ways of using CFD to determine the flow field produced by the complex, wide‐blade hydrofoil APV‐B2 impeller are presented. The use of the “sliding mesh” approach was not successful and the reasons are discussed. Details of the numerical solution of the momentum transfer equations are described for the case of an axially‐symmetrical jet model. The flow field for the single impeller pumping either upwards or downwards at 200 rpm was simulated using the structured Fluent code. Good agreement of CFD predictions with LDA velocity data was found, though the maximum local energy dissipation rate was 2 1/2 to 5 times lower than was estimated from the experiments. The power numbers predicted by CFD were slightly higher than those obtained experimentally. The flow fields for dual and triple impellers pumping upwards were also simulated and used to guide larger scale homogenisation experiments.
Production of the cysteine proteinase inhibitor cystatin C by rat Sertoli cells (1992)

The Sertoli cells of the rat testis produce cystatin C, a cysteine proteinase inhibitor. Primary culture of Sertoli cells secreted both unglycosylated and glycosylated forms of rat cystatin C. Despite the low concentration of cystatin C in rete testis fluid, equilibrium dissociation constants (Ki) for the interaction between cystatin C and lysosomal cathepsins indicate that this molecule could be involved in the local regulation of testicular cysteine proteinase activity which may be necessary for spermatogenesis and spermiogenesis.
Electrically controlled birefringence colours in deformed helix ferroelectric liquid crystals (2008)

A short helix pitch (p 0 = 0.45 µm) ferroelectric liquid crystal (FLC) mixture was found to provide four electrically switched birefringence colours: blue, green, yellow and red. The contrast ratios of the birefringence colours were measured as functions of both driving voltage amplitude and frequency. The FLC mixture, which had a relatively high birefringence, Δn⩾0.2, was controlled by a voltage less than 5 V. A simple model is proposed, which was confirmed by experiments. A possible application is discussed in field‐sequential colour displays, where fast switching times are required.
Meeting Washington state educational goals: University of Washington's ECSEL Design Too/sup TM/ workshop (2002)

This paper is a report and discussion of the Design Too/sup TM/ workshop where K-12 educators engaged in a variety of design-based engineering projects. The intent of this workshop was to explore the role engineering design can play in meeting Washington's state-wide learning goals outlined in the Education Reform Act. We suggest engineering design is one method K-12 educators can employ to help students learn the skills to meet the state standards.
Tradies, Technology and Therapy: Towards Designing Gameful VR Environments for Burn Rehabilitation (2020)

Burn injuries are a significant public health challenge with the known consequences and long term problems including pain, permanent scarring and psychological trauma. Current available rehabilitation equipment is rudimentary, resource-intensive and lacks a human-centered design approach. Immersive Virtual Reality technologies may provide aid in this area, with prior studies showing positive effects that this technology has on reducing patient's physical pain, psychological trauma and improving movement. This study recognises the need for customised, measurable and goal-directed rehabilitation for burn patients. By conducting two ideation design sessions with health workers (session 1), and burn survivors and their carers (session 2), this study highlights the participants' perspectives on VR for burn rehabilitation such as the importance of patient agency, heat and healthy scarring. This work contributes core themes from survivors and health professionals to the field of design and computer human interaction that could inform future iterations of VR burn rehabilitation applications.
The mechanism of formation and the stereochemistry of mono- and bis-complexes of rhodium(III) with 1,10-phenanthroline (1969)

The dichlorobis-(1,10-phenanthroline)rhodium(III) cation is shown by 1H n.m.r. and vibrational (i.r. and Raman) spectroscopy to be a cis-complex. The perchlorate salt is isomorphous with cis-[Ir phen 2Cl2]ClO4(phen = 1,10-phenanthroline). Mechanistic studies with the rhodium(III) bromide–1,10-phenanthroline system show that [Rh phen Br4]– is first formed and then reacts with further phenanthroline to afford cis-[Rh phen 2Br2]+. The role of rhodium(I) intermediates is discussed. The new complexes [phen H][Rh phen X4](X = Cl, Br, or I) are reported.Electronic and vibrational spectroscopy suggest that the dichlorobis-(2,2′-bipyridyl)rhodium(III) cation has cis-stereochemistry as has the new complex dichlorobis(2,4,7,8-tetramethyl-1,10-phenanthroline)rhodium(III) chloride dihydrate.
Recognition of G-quadruplexes by Metal Complexes (2012)

‘Recognition of quadruplexes’ is a wide-ranging theme in the field of nucleic acid quadruplexes. Quadruplexes of DNA or RNA have four grooves with three distinct dimensions. They may be populated by single stranded architectures that have the potential for hydrogen bonding and base-stacking interactions. Their backbones adopts a variety of conformations characterizing greater diversity of structural motifs as compared, for example, to double-stranded DNA. Thus quadruplex nucleic acid structures are a richly provided with structural motifs that favor interactions with other molecules.In this section authors from a variety of disciplines describe a range of interactions involving quadruplex nucleic acids from a variety of perspectives. The section starts with an analysis of the selective pressure G4 motifs are associated with. It is described and contextualized in terms of specific chromosomal domains, specific regions within genes, and specific classes of genes. The current belief that quadruplex structures of DNA and RNA play roles in the regulation of gene expression is then scrutinized. There is specific emphasis on current findings and ideas on the proposed roles of quadruplex structures of DNA in the regulation of gene transcription. The section than moves into the issue of quadruplex DNA as a viable therapeutic target. Are quadruplex topologies suitable targets for the rational design and development of therapeutics? Here a discussion identifies both difficulties and opportunities in relation to this question. Next, a discussion ensues on the utility of high-throughput screening in the discovery of highly specific quadruplex ligands; including those that may not obey the rules dictated by drug design. The features that make metal complexes suitable quadruplex DNA binders are explored next. In particular the interaction of metal complex intercalators with quadruplex DNA is discussed including those complexes that have been studied as optical probes for DNA.
ChemInform Abstract: Biomimetic Oxidation of the Antimelanoma Agent 4‐S‐Cysteaminylphenol and Related Catechol Thioethers: Isolation and Reaction Behaviour of Novel Dihydrobenzothiazinequinones. (1994)

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.
A Triple‐Grid Technique for the 3D Inversion of DC Resistivity Data Incorporating Arbitrary Topography (2006)

We present a novel technique for the determination of resistivity structures associated with arbitrary surface topography. The approach represents a triple‐grid DC resistivity inversion technique which is based on unstructured tetrahedral meshes and a finite element forward operator applied to the secondary potential. We use a Gauss‐Newton method with inexact line search to fit the data within error bounds. A global regularization scheme using special smoothness constraints is applied. The regularization parameter compromising data misfit and model roughness is determined by an L‐curve method and finally evaluated by the discrepancy principle. A resolution‐dependent parameterization helps to keep the inverse problem small to cope with memory limitations of today's standard PC's. Thus, the approach can be applied to large‐scale 3D problems. As a byproduct of the primary potential calculation we obtain a quantification of the topography effect and the corresponding geometric factors. The latter are used to prevent the reconstruction process from topography induced artifacts. We first test our technique to synthetic data from a burial mound to demonstrate its functionality and efficiency. Then, we apply the method to data gathered on an abandoned mining dump.
Collagen synthesis in human skin in vivo: modulation by aging, ultraviolet B irradiation and localization. (1994)

The effect of aging, sex, skin location and a short whole body ultraviolet B (UVB) phototherapy on type I and type III skin collagen synthesis were studied by measuring carboxy- and aminoterminal propeptides of type I and aminoterminal propeptide of type III procollagens (PICP, PINP and PIIINP, respectively) in suction blister fluid (SBF). The concentrations of PICP and PIIINP correlated negatively with age in the material of 30 men and 27 women (age range 23-86 years, mean age 51 years). As the subjects were divided into 3 age groups (23-34, 35-54 and 55-86 years) and the mean concentrations of the procollagens were compared between the groups, the youngest age groups in men and in the whole material had significantly higher concentrations than the two older age groups. These results confirm the previous results, which have shown by other methods that skin collagen synthesis decreases during aging. SBF was also obtained from 4 different body regions (back, arm, abdomen and leg) of 5 young male subjects and from 2 different body regions (abdomen and thigh) of 9 older subjects. Wide individual range in the concentrations of PICP, PINP and PIIINP was noticed but, in general, none of the body regions seemed to have more excessive collagen synthesis than the other ones. SBF was further collected from abdominal skin of 8 young male dermatological patients receiving UVB phototherapy. When the concentrations of PICP and PIIINP in SBF obtained before the treatment, after the treatment and from the covered control area were compared no statistical differences were noted, suggesting that short UVB treatment has no effect on skin collagen synthesis in vivo.
Very high dilutions of dexamethasone inhibit its pharmacological effects in vivo (2001)

We evaluated the interaction of dexamethasone 10(-17) and 10(-33) M (equivalent to 7cH and 15cH) with dexamethasone in pharmacological concentrations, using as experimental models: acute inflammation induced by carrageenan, Ehrlich ascitic tumour, and migration of tumour infiltrating leukocytes (TIL). Male adult BALB/c mice (n=7 per group) were used in all experiments. Carrageenan (1%) was injected into the footpad for oedema evaluation and into the peritoneal cavity (i.p.), for differential counting of inflammatory cells. Ehrlich ascitic tumour cells (10(7) viable cells/ml) were injected i.p. and tumour cells were counted after 6 days, by the Trypan blue exclusion method. The differential TIL was counted using smears stained by hematoxylin-eosin. Treatments were made immediately after carrageenan inoculation or once a day, during Ehrlich tumour development, until the animals were killed. Animals were treated with the following preparations: (1) phosphate buffer saline (PBS) solution; (2) dexamethasone (0.5 mg/kg for inflammation model or 4mg/kg for tumour model) mixed with dexamethasone 7cH or 15cH; (3) dexamethasone (same doses) mixed in PBS. Homeopathic dexamethasone partially blocked the anti-inflammatory effect of pharmacological dexamethasone with regard to paw oedema (two-way ANOVA, P < 0.0008) and polymorphonuclear cell migration (chi2, P=0.0001). No important differences were observed between experimental and control groups, in relation to Ehrlich tumour cells viability or count, or bodyweight, but potentised dexamethasone restored control levels of TIL viability, compared to mice treated with pharmacological doses of dexamethasone (chi2, P< or = 0.001). The results demonstrate that a potentised substance may change its own pharmacological effects and suggest that ultradilutions effects act mostly on host response.
Design of Dual MCU Vehicle Control Unit Based on Electric Vehicles to Respond to Control Failure (2020)

Abstract The Vehicle Control Unit (VCU) is the core component of the entire car. It is responsible for collecting the accelerator pedal signal, brake pedal signal, gear signal and other component signals, and makes corresponding judgments based on the vehicle status to control the next controllers of each component of the layer act to drive the electric vehicle. This article introduces the overall system structure of the electric vehicle and the structural characteristics of the Vehicle Control Unit, analyzes the benefits of the dual MCU Vehicle Control Unit to the electric vehicle, and finally establishes the corresponding detection and response methods when various possible failures occur. The detection and response mechanism uses the main and auxiliary dual MCUs as the control core and cooperates in processing. When the main MCU fails, the auxiliary MCU takes over the control to avoid the uncontrollable safety problems caused by the control of the entire vehicle when the single MCU fails.The dual MCU controller uses the main and auxiliary differentiated design, and the functional design of the main and auxiliary MCUs is based on the functional modularity idea. After the main MCU meets the functions of vehicle control and other functions, the sensor signal detection and other functions are added to the auxiliary MCU. A dual MCU Vehicle Control Unit based on electric vehicle response to control failure is presented.
Reversed-Phase HPLC following Thiolysis for Quantitative Estimation and Characterization of the Four Main Classes of Phenolic Compounds in Different Tissue Zones of a French Cider Apple Variety (Malus domestica Var. Kermerrien) (1998)

Phenolic compounds, which are present in the epidermis zone, parenchyma zone, core zone, and seeds of fruit (Malus domestica var. Kermerrien), were extracted from freeze-dried material by three successive solvent extractions. The dry methanol extract and the dry aqueous acetone extracts were analyzed using reversed-phase HPLC coupled with diode array detection following thiolysis to quantify phenolic compounds according to their classes (hydroxycinnamic acid derivatives, flavan-3-ols, flavonols, and dihydrochalcones). The method is suitable for the determination of the relative proportions of the different classes of polyphenols and provided information on the constitutive units and the average degree of polymerization of oligomeric and polymeric procyanidin structures. Results showed that procyanidins are the predominant phenolic constituents in cider apple fruits, much of them corresponding to highly polymerized structures. Keywords: Apple; phenolics; procyanidins; cider; HPLC; thiolysis
Guest Editorial to the Special Issue on Automation of Software Testing (2007)

Journal Article Guest Editorial to the Special Issue on Automation of Software Testing Get access Hong Zhu, Hong Zhu 1Department of Computing, Oxford Brookes University, Oxford OX33 1HX, UK Search for other works by this author on: Oxford Academic Google Scholar S. C. Cheung, S. C. Cheung 2Department of Computer Science, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong Search for other works by this author on: Oxford Academic Google Scholar Joseph R. Horgan, Joseph R. Horgan 3Telcordia Technologies, One Telcordia Drive, RRC-1M322, Piscataway, NJ 08854, USA Search for other works by this author on: Oxford Academic Google Scholar J. Jenny Li J. Jenny Li * 4Avaya Labs, 233 Mount Airy Road, Basking Ridge, NJ 07920, USA *Corresponding author: jjli@research.avayalabs.com Search for other works by this author on: Oxford Academic Google Scholar The Computer Journal, Volume 52, Issue 5, August 2009, Page 513, https://doi.org/10.1093/comjnl/bxm077 Published: 25 September 2007
Coordination complexes of platinum as antitumor agents. (1975)

Rosenberg and VanCamp first reported the bacteriostatic and antitumor properties of certain platinum coordination compounds. This pioneering work has led to the synthesis and testing of a large number of related platinum products and the clinical use of cis-dichlorodiammineplatinum (II). This drug has proven very efficacious against a wide variety of mouse tumors when employed as the sole chemotherapeutic agent and has also been combined successfully with other antitumor agents, such as cyclophosphamide and cytosine arabinsoide. Unfortunately, cis-dichlorodiammineplatinum (II) has a low therapeutic index with renal toxicity being the principal limitation of its use. This has prompted the synthesis and testing of many related platinum compounds, of which cis-dichlorobiscyclopentylamine-platinum (II) and the "platinum blues" appear most promising. Experience in the synthesis, purification, and testing of such products will be discussed together with identification of outstanding unsolved problems in this area.
A Framework for Efficient Contract-Based Testing of Software Components (2006)

Component based frameworks become more and more state-of-the art but without verifying the components and their interaction it is nearly impossible to build correct and robust systems. Testing of such systems requires a combination of unit- and integration tests, and must deal with verifying the contracts that enables the interaction of components. In this article we present CrashIt - a test framework for component-based testing. A main concept of CrashIt is the introduction of expandable contract-checkers that verify the communication between a client and a supplier component. These checkers are able to communicate with each other and with other modules of CrashIt. Thus, CrashIt is able to check the state of each component at every time.
Activity and functions of the human gluteal muscles in walking, running, sprinting, and climbing (2013)

It has been suggested that the uniquely large gluteus maximus (GMAX) muscles were an important adaptation during hominin evolution based on numerous anatomical differences between humans and extant apes. GMAX electromyographic (EMG) signals have been quantified for numerous individual movements, but not across the range of locomotor gaits and speeds for the same subjects. Thus, comparing relative EMG amplitudes between these activities has not been possible. We assessed the EMG activity of the gluteal muscles during walking, running, sprinting, and climbing. To gain further insight into the function of the gluteal muscles during locomotion, we measured muscle activity during walking and running with external devices that increased or decreased the need to control either forward or backward trunk pitch. We hypothesized that 1) GMAX EMG activity would be greatest during sprinting and climbing and 2) GMAX EMG activity would be modulated in response to altered forward trunk pitch demands during running. We found that GMAX activity in running was greater than walking and similar to climbing. However, the activity during sprinting was much greater than during running. Further, only the inferior portion of the GMAX had a significant change with altered trunk pitch demands, suggesting that the hip extensors have a limited contribution to the control of trunk pitch movements during running. Overall, our data suggest that the large size of the GMAX reflects its multifaceted role during rapid and powerful movements rather than as a specific adaptation for a single submaximal task such as endurance running.
IL1α and IL4 signalling in human ovarian surface epithelial cells (2011)

The human ovarian surface epithelium (hOSE) is a mesothelial layer that surrounds the ovary and undergoes injury and repair cycles after ovulation-associated inflammation. We previously showed that IL4 is a key regulator of progesterone bioavailability during post-ovulatory hOSE repair as it differentially up-regulated 3β-HSD1 and 3β-HSD2 mRNA transcripts and total 3β-hydroxysteroid dehydrogenase activity whereas it inhibited androgen receptor (AR) expression. We now show that the pro-inflammatory effect of IL1α on 3β-HSD1 expression is mediated by nuclear factor-κB (NF-κB), whereas its anti-inflammatory action on 3β-HSD2 expression is exerted via p38 mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K) and NF-κB signalling pathways. The anti-inflammatory IL4 effects on 3β-HSD1 and 3β-HSD2 mRNA expression are mediated through STAT6 and PI3K signalling networks. IL4 effects on AR and 3β-HSD2 expression involve the p38 MAPK pathway. We also document that IL4 up-regulates lysyl oxidase (LOX) mRNA transcripts, a key gene for extracellular matrix (ECM) deposition and inhibits IL1α-induced expression of cyclooxygenase-2 (COX-2) mRNA, a gene involved in breakdown of ECM, showing a further role in post-ovulatory wound healing. We conclude that IL1α and IL4 actions in the post-ovulatory wound healing of hOSE cells are mediated by different signalling transduction pathways. The p38 MAPK signalling pathway may have possible therapeutic benefit in inflammation-associated disorders of the ovary, including cancer.