gebhart/patrepeval huggingface dataset:
Optimized Photoactivatable Lipid Nanoparticles Enable Red Light Triggered Drug Release (2021)

Encapsulation of small molecule drugs in long-circulating lipid nanoparticles (LNPs) can reduce toxic side effects and enhance accumulation at tumor sites. A fundamental problem, however, is the slow release of encapsulated drugs from these liposomal systems at the disease site resulting in limited therapeutic benefit. Methods to trigger release at specific sites are highly warranted. Here, it is demonstrated that incorporation of ultraviolet (UV-A) or red-light photoswitchable-phosphatidylcholine analogs (AzoPC and redAzoPC) in conventional LNPs generates photoactivatable LNPs (paLNPs) having comparable structural integrity, drug loading capacity, and size distribution to the parent DSPC-cholesterol liposomes. It is shown that 65-70% drug release (doxorubicin) can be induced from these systems by irradiation with pulsed light based on trans-to-cis azobenzene isomerization. In vitro it is confirmed that paLNPs are non-toxic in the dark but convey cytotoxicity upon irradiation in a human cancer cell line. In vivo studies in zebrafish embryos demonstrate prolonged blood circulation and extravasation of paLNPs comparable to clinically approved formulations, with enhanced drug release following irradiation with pulsed light. Conclusively, paLNPs closely mimic the properties of clinically approved LNPs with the added benefit of light-induced drug release making them promising candidates for clinical development.
Serum periostin in asthma: A potential biomarker for stratification in severe treatment-resistant asthma (2014)

Rationale: Serum periostin has been proposed as a biomarker of Th2 airway inflammation in asthma. We thus measured serum periostin in a large cohort of patients with severe asthma as well as in those with milder asthma and healthy controls, to gain insight into the value of this biomarker in asthma stratification. Methods: Serum samples from 126 healthy controls (HC), 93 non-steroid treated mild asthmatics (MA), 35 asthmatics on low dose corticosteroids +/- LABA (ModA) and 276 severe treatment-resistant asthmatics (SA) were assayed for serum periostin by ELISA (Shino-Test Corporation, Kanagawa, Japan) and the results related to clinical and inflammatory markers. Results: Group median serum periostin levels were significantly (p&lt;0.0001) lower in both the steroid treated asthma groups (ModA and SA) than the HC or MA groups, although there was greater spread in SA with 21% of values ± the normal range. Tertile analysis of the SA serum periostin identified that those in the upper tertile (≥79 ng/ml) had significantly higher sputum eosinophils (p=0.001), peripheral blood eosinophilia (p=0.002), FeNO (p=0,001) and total IgE (p=0.01) as well as lower FEV1 % predicted (p=0.02) than those in the lowest tertile (≤58ng/ml). Serum periostin measures did not appear related to age, BMI or atopic status. Conclusion: Steroid treatment in asthma is associated with significantly lower serum periostin measures than in non-steroid treated asthma, although a sub-population of severe asthmatics have levels that associate with eosinophilic inflammation. Funding: WSAC was funded by the Medical Research Council UK.
Effect of substrate doping on the capacitance-Voltage characteristics of strained-silicon pMOSFETs (2005)

The effect of substrate doping on the capacitance-voltage characteristics of a surface-channel strained-silicon p-channel MOSFET has been studied to explain a measured anomalous behavior in which a "plateau" in the accumulation region was observed. It is found that this plateau is substrate doping dependent and it switches from a plateau on the inversion side to that on the accumulation side as the substrate doping increases. The physics behind this behavior has been explained by the one-dimensional Poisson solution and validated with numerical simulations and experimental data.
Retrospective Review of 331 Consecutive Immediate Single-Stage Implant Reconstructions with Acellular Dermal Matrix (2011)

Therapeutic, III.
Development of a Renal Microchip for In Vitro Distal Tubule Models (2007)

Current developments in tissue engineering and microtechnology fields have allowed the proposal of pertinent tools, microchips, to investigate in vitro toxicity. In the framework of the proposed REACH European directive and the 3R recommendations, the purpose of these microtools is to mimic organs in vitro to refine in vitro culture models and to ultimately reduce animal testing. The microchip consists of functional living cell microchambers interconnected by a microfluidic network that allows continuous cell feeding and waste removal controls by fluid microflow. To validate this approach, Madin Darby Canine Kidney (MDCK) cells were cultivated inside a polydimethylsiloxane microchip. To assess the cell proliferation and feeding, the number of inoculated cells varied from 5 to 10 x 10(5) cells/microchip (corresponding roughly to 2.5 to 5 x 10(5) cells/cm2) and from four flow rates 0, 10, 25, and 50 microL/min were tested. Morphological observations have shown successful cell attachment and proliferation inside the microchips. The best flow rate appears to be 10 microL/min with which the cell population was multiplied by about 2.2 +/- 0.1 after 4 days of culture, including 3 days of perfusion (in comparison to 1.7 +/- 0.2 at 25 microL/min). At 10 microL/min flow rate, maximal cell population reached about 2.1 +/- 0.2 x 10(6) (corresponding to 7 +/- 0.7 x 10(7) cells/cm(3)). The viability, assessed by trypan blue and lactate deshydrogenase measurements, was found to be above 90% in all experiments. At 10 microL/min, glucose monitoring indicated a cell consumption of 16 +/- 2 microg/h/10(6) cells, whereas the glutamine metabolism was demonstrated with the production of NH3 by the cells about 0.8 +/- 0.4 micromol/day/10(6) cells. Augmentation of the flow rate appeared to increase the glucose consumption and the NH3 production by about 1.5- to 2-fold, in agreement with the tendencies reported in the literature. As a basic chronic toxicity assessment in the microchips, 5 mM and 10 mM ammonium chloride loadings, supplemented in the culture media, at 0, 10, and 25 micaroL/min flow rates were performed. At 10 microL/min, a reduction of 35% of the growth ratio with 5 mM and of 50% at 10 mM was found, whereas at 25 microL/min, a reduction of 10% with 5 mM and of 30% at 10 mM was obtained. Ammonium chloride contributed to increase the glucose consumption and to reduce the NH3 production. The microchip advantages, high surface/volume ratio, and dynamic loadings, coupled with the concordance between the present and literature results dealing with ammonia/ammonium effects on MDCK illustrate the potential of our microchip for wider in vitro chronic toxicity investigations.
Characterization of Monoclonal Antibody Specific for Human Alpha Interferon (1982)

A mouse hybridoma cell line has been isolated, which secretes a monoclonal antibody specific of human leukocyte (alpha) interferon. The antibody secreted by the hybridoma belongs to the IgG1 class. It neutralizes biological activities (cellular and antiviral) of alpha interferon. Mass production of the antibody in ascitic fluid has been obtained. A convenient method of purification of the IgG from the ascitic fluid on DEAE-Trisacryl M is described.
Experimental Generation and Time Multiplexing of Data- Carrying Nyquist Sinc Shaped Channels from a Single Microresonator-based Kerr Frequency Comb (2019)

We experimentally achieve optical time multiplexing of multiple Nyquist channels. A single microresonator Kerr comb allows the generation of multiple Nyquist sinc shaped pulse trains. TDM of pulse trains are obtained through wavelength conversion inside a PPLN.
Iterative reconstruction anti-correlated ROF model for noise reduction in dual-energy CBCT imaging (2021)

A Dual-Energy CT (DECT) with a spectral detector greatly extends the capabilities of CT by incorporating energy-dependent information of the X-ray attenuation. In order to fully exploit DECT capabilities, it is required to perform a process known as spectral decomposition. However, this process is sensitive to noise, suffers from reduced photon count per layer in DECT scans and generates anti-correlated noise in the estimated material specific images. In order to overcome these problems, the Anti-Correlated Rudin, Osher and Fatemi (AC-ROF) model is applied for noise reduction, exploiting the relationship between the material-specific images. However, this model deteriorates the structural information with intense noise. In this paper we propose to extend this method by integrating it into an iterative reconstruction procedure to improve the noise reduction performance. The resulting algorithm is called Iterative Reconstruction AC-ROF, or IR-AC-ROF. We have tested AC-ROF and IR-AC-ROF algorithms with realistic brain simulation phantoms and show encouraging results indicating that the resulting material-specific images of IR-AC-ROF can generate better mono-energetic images with improved brain structure visibility. This demonstrates the benefit of including the noise reduction constraints within the reconstruction procedure, rather than using them in a post-processing step.
Modulation of Conotoxin Structure and Function Is Achieved through a Multienzyme Complex in the Venom Glands of Cone Snails (2012)

The oxidative folding of large polypeptides has been investigated in detail; however, comparatively little is known about the enzyme-assisted folding of small, disulfide-containing peptide substrates. To investigate the concerted effect of multiple enzymes on the folding of small disulfide-rich peptides, we sequenced and expressed protein-disulfide isomerase (PDI), peptidyl-prolyl cis-trans isomerase, and immunoglobulin-binding protein (BiP) from Conus venom glands. Conus PDI was shown to catalyze the oxidation and reduction of disulfide bonds in two conotoxins, α-GI and α-ImI. Oxidative folding rates were further increased in the presence of Conus PPI with the maximum effect observed in the presence of both enzymes. In contrast, Conus BiP was only observed to assist folding in the presence of microsomes, suggesting that additional co-factors were involved. The identification of a complex between BiP, PDI, and nascent conotoxins further suggests that the folding and assembly of conotoxins is a highly regulated multienzyme-assisted process. Unexpectedly, all three enzymes contributed to the folding of the ribbon isomer of α-ImI. Here, we identify this alternative disulfide-linked species in the venom of Conus imperialis, providing the first evidence for the existence of a "non-native" peptide isomer in the venom of cone snails. Thus, ER-resident enzymes act in concert to accelerate the oxidative folding of conotoxins and modulate their conformation and function by reconfiguring disulfide connectivities. This study has evaluated the role of a number of ER-resident enzymes in the folding of conotoxins, providing novel insights into the enzyme-guided assembly of these small, disulfide-rich peptides.
Finger Ring Phased Antenna Array for 5G IoT and Sensor Networks at 28 GHz (2018)

In this paper, a circular phased antenna array has been constructed on the finger ring for the 28 GHz 5G communication systems. The antenna array has been verified in free space and with user's hand phantom on three fingers by the simulations. It has been found that such antenna structure is resilient towards the user effects and has a stable coverage efficiency characteristics. The coverage efficiency of 80 % with the realized gain of 5 dBi has been observed when the ring simulated with the user's hand. The correlation between high power loss density with antenna de-tuning has also been observed.
Self-Conscious or Self-Confident? A Diary Study Conceptualizing the Social Accessibility of Assistive Technology (2016)

With the recent influx of smartphones, tablets, and wearables such as watches and glasses, personal interactive device use is increasingly visible and commonplace in public and social spaces. Assistive Technologies (ATs) used by people with disabilities are observable to others and, as a result, can affect how AT users are perceived. This raises the possibility that what we call “social accessibility” may be as important as “functional accessibility” when considering ATs. But, to date, ATs have almost exclusively been regarded as functional aids. For example, ATs are defined by the Technical Assistance to the States Act as technologies that are “used to increase, maintain or improve functional capabilities of individuals with disabilities.” To investigate perceptions and self-perceptions of AT users, we conducted a diary study of two groups of participants: people with disabilities and people without disabilities. Our goal was to explore the types of interactions and perceptions that arise around AT use in social and public spaces. During our 4-week study, participants with sensory disabilities wrote about feeling either self-conscious or self-confident when using an assistive device in a social or public situation. Meanwhile, participants without disabilities were prompted to record their reactions and feelings whenever they saw ATs used in social or public situations. We found that AT form and function does influence social interactions by impacting self-efficacy and self-confidence. When the design of form or function is poor, or when inequality between technological accessibility exists, social inclusion is negatively affected, as are perceptions of ability. We contribute a definition for the “social accessibility” of ATs and subsequently offer Design for Social Accessibility (DSA) as a holistic design stance focused on balancing an AT user's sociotechnical identity with functional requirements.
A LEIS and in situ XAS study of supported Pd-Pt catalysts for CH4 oxidation (2016)

It is of vital importance to remove methane (CH4) from the exhausts of natural gas and biogas fueled engines as CH4 is a strong greenhouse gas. So far Pd-based catalysts have been used almost exclusively but their high sensitivity to sulfur and water pushes research to explore other materials. Among these are Pd-Pt catalysts [1-4], which exhibit a slight increase in CH4 oxidation activity with time and higher long-term stability than the Pd-only counterpart [5-7]. Still, however, little is known about the oxidation-reduction behaviour of the Pd-Pt nanoclusters and how this impacts the catalytic activity. This study aims at increase the understanding of the catalytic activity of Al2O3-supported Pd-Pt nanoclusters for low-temperature CH4 oxidation under transient, although generally lean, conditions.
Radiological diagnosis of gallbladder disease (1981)

Blunt ocular traumas include contusions and ruptures of the globe--open and closed globe injuries. Characteristic damage results in anterior and posterior segment trauma. Typical patterns of injuries are combinations of (1) hyphema grade II-IV, iris-lens injury, vitreal bleeding--choroidal rupture and increased risk of rebleeding, (2) angle recession >180 degrees--secondary open-angle glaucoma, and (3) vitreal prolapse and lens dislocation-retinal detachment. Patients with blunt eye trauma should be under steady observation by an ophthalmologist to handle late complications.
Primary Structure and Function of Three Gonadotropin-Releasing Hormones, Including a Novel Form, from an Ancient Teleost, Herring1 (2000)

The evolution of GnRH and the role of multiple forms within the brain are examined. Three forms of GnRH were purified from the brain of Pacific herring (Clupea harengus pallasi) and characterized using Edman degradation and mass spectrometry. Two forms correspond with the known structures of chicken GnRH-II and salmon GnRH that are found in many vertebrate species. The third form, designated herring GnRH (hrGnRH), has a primary structure of pGlu-His-Trp-Ser-His-Gly-Leu-Ser-Pro-Gly-NH 2 . This novel peptide is a potent stimulator of gonadotropin II and GH release from dispersed fish pituitary cells. The content of hrGnRH in the pituitary was 8-fold that of salmon GnRH and 43-fold that of chicken GnRH-II, which provides supporting evidence that hrGnRH is involved in the release of gonadotropin.
Raman spectroscopic studies of the structure of supersaturated ammonium dihydrogen phosphate solutions (1984)

Raman spectroscopic studies of quiescent under and supersaturated ammonium dihydrogen phosphate (ADP) aqueous solutions were performed on the nu //1 (totally symmetric or breathing mode) and nu //3 ...
High-Resolution Accurate-Mass Mass Spectrometry Enabling In-Depth Characterization of in Vivo Biotransformations for Intact Antibody-Drug Conjugates (2017)

Antibody-drug conjugates (ADCs) represent a promising class of therapeutics for the targeted delivery of highly potent cytotoxic drugs to tumor cells to improve bioactivity while minimizing side effects. ADCs are composed of both small and large molecules and therefore have complex molecular structures. In vivo biotransformations may further increase the complexity of ADCs, representing a unique challenge for bioanalytical assays. Quadrupole-time-of-flight mass spectrometry (Q-TOF MS) with electrospray ionization has been widely used for characterization of intact ADCs. However, interpretation of ADC biotransformations with small mass changes, for the intact molecule, remains a limitation due to the insufficient mass resolution and accuracy of Q-TOF MS. Here, we have investigated in vivo biotransformations of multiple site-specific THIOMAB antibody-drug conjugates (TDCs), in the intact form, using a high-resolution, accurate-mass (HR/AM) MS approach. Compared with conventional Q-TOF MS, HR/AM Orbitrap MS enabled more comprehensive identification of ADC biotransformations. It was particularly beneficial for characterizing ADC modifications with small mass changes such as partial drug loss and hydrolysis. This strategy has significantly enhanced our capability to elucidate ADC biotransformations and help understand ADC efficacy and safety in vivo.
The mathematics of market timing (2018)

Market timing is an investment technique that tries to continuously switch investment into assets forecast to have better returns. What is the likelihood of having a successful market timing strategy? With an emphasis on modeling simplicity, I calculate the feasible set of market timing portfolios using index mutual fund data for perfectly timed (by hindsight) all or nothing quarterly switching between two asset classes, US stocks and bonds over the time period 1993-2017. The historical optimal timing path of switches is shown to be indistinguishable from a random sequence. The key result is that the probability distribution function of market timing returns is asymmetric, that the highest probability outcome for market timing is a below median return. Put another way, simple math says market timing is more likely to lose than to win-even before accounting for costs. The median of the market timing return probability distribution can be directly calculated as a weighted average of the returns of the model assets with the weights given by the fraction of time each asset has a higher return than the other. For the time period of the data the median return was close to, but not identical with, the return of a static 60:40 stock:bond portfolio. These results are illustrated through Monte Carlo sampling of timing paths within the feasible set and by the observed return paths of several market timing mutual funds.
Clinical pharmacology of recombinant human tumor necrosis factor in patients with advanced cancer. (1987)

Twenty-six patients with advanced cancer refractory to standard therapy were treated with recombinant human tumor necrosis factor (rTNF) in a study aimed at determining the toxicity and tolerance of rTNF and at seeking evidence of antitumor activity. The study design involved two treatments per week for 4 weeks with alternating subcutaneous and intravenous (IV) administration, and weekly dose escalation through four levels in each patient. The dose range was 1 to 200 micrograms/m2 for IV bolus injection, and 5 to 250 micrograms/m2 for subcutaneous injection. Thirteen patients completed the full course. Early discontinuation of treatment was related to rTNF toxicity in seven cases. The major side effects were rigors, fever, headache, fatigue, and hypotension. Acute changes in granulocyte, lymphocyte, and monocyte counts, changes in serum zinc levels and plasma cortisol levels consistent with an acute phase response, and inflammation at the site of subcutaneous injection were also seen. At doses of 125 to 250 micrograms/m2, inflammation at the subcutaneous injection site was unacceptably severe. Minor changes were seen in hemostatic parameters. Hypotension was corrected by fluid administration and did not require treatment with vasopressors. Initial serum concentrations of rTNF were measured at five minutes after IV administration and were found to range from 2.5 ng/mL after a dose of 35 micrograms/m2 to 80 ng/mL after a dose of 200 micrograms/m2. The half-life of rTNF in the blood was 20 minutes. A decrease in lymph node size was observed in a patient with B cell lymphoma.
Use of proteomic analysis to monitor responses to biological therapies (2004)

Proteomics has the potential to revolutionise diagnosis and disease management. Serum protein pattern profiling by surface-enhanced laser desorption/ionisation time of flight (SELDI-TOF) mass spectrometry is emerging as a novel approach to discover protein patterns capable of distinguishing disease and disease-free states with high sensitivity and specificity. This method has shown great promise for early diagnosis of ovarian cancer and is being applied to a range of pathological states. Protein microarray technology is being evaluated as a new means to track biological responses to therapy. Through the measurement of key protein phosphorylation sites at different stages of disease progression or before and after treatment, protein signal pathways can be mapped and thus become the starting point for individualised therapy. Laser capture microdissection (LCM) coupled with immunostaining of protein microarrays allows isolation of pure cell populations and relative quantitation of phosphorylated and non-phosphorylated forms of the cell’s key signalling proteins. This technology is currently in use at the National Institutes of Health in Phase II clinical trials of metastatic breast and ovarian cancer. Cell survival and apoptotic protein pathways are monitored as biological markers of disease progression in these clinical trials. Proteomic technologies, such as serum protein pattern profiling, combined with protein microarray technologies, constitute a new paradigm for detecting disease and monitoring disease response to therapy. Ultimately, proteomics and genomics will become integrated into cancer patient management through the design and tracking of individualised therapy.
Performance analysis of the I-structure software cache on multi-threading systems (2002)

Non-blocking multithreaded execution models have been proposed as an effective means to overlap computation and communication in distributed memory systems without any hardware support. Even with the capability of latency tolerance in these execution models, each remote memory request still incurs the cost of communication interface overhead. We therefore designed and implemented our I-structure software cache system to further reduce communication overhead for non-blocking multithreaded execution. In this paper, we present analytical models for the performances of a multithreading system with and without I-structure software cache support. We compare our model's prediction with our experimental results on an existing multithreaded architecture platform. The analytical models allow us to predict at what ratio of communication latency/processing speed the implementation of I-structure software cache becomes profitable for applications with different characteristics.