gebhart/patrepeval huggingface dataset:
Measuring Real-time Drug Response in Organotypic Tumor Tissue Slices (2020)

Tumor tissues are composed of cancerous cells, infiltrated immune cells, endothelial cells, fibroblasts, and extracellular matrix. This complex milieu constitutes the tumor microenvironment (TME) and can modulate response to therapy in vivo or drug response ex vivo. Conventional cancer drug discovery screens are carried out on cells cultured in a monolayer, a system critically lacking the influence of TME. Thus, experimental systems that integrate sensitive and high-throughput assays with physiological TME will strengthen the preclinical drug discovery process. Here, we introduce ex vivo tumor tissue slice culture as a platform for medium-high-throughput drug screening. Organotypic tissue slice culture constitutes precisely-cut, thin tumor sections that are maintained with the support of a porous membrane in a liquid-air interface. In this protocol, we describe the preparation and maintenance of tissue slices prepared from mouse tumors and tumors from patient-derived xenograft (PDX) models. To assess changes in tissue viability in response to drug treatment, we leveraged a biocompatible luminescence-based viability assay that enables real-time, rapid, and sensitive measurement of viable cells in the tissue. Using this platform, we evaluated dose-dependent responses of tissue slices to the multi-kinase inhibitor, staurosporine, and cytotoxic agent, doxorubicin. Further, we demonstrate the application of tissue slices for ex vivo pharmacology by screening 17 clinical and preclinical drugs on tissue slices prepared from a single PDX tumor. Our physiologically-relevant, highly-sensitive, and robust ex vivo screening platform will greatly strengthen preclinical oncology drug discovery and treatment decision making.
Porphyrin “Flying-Saucers”:  Solid State and Solution Structure of a Novel Pentameric Array of Axially-Ligated Canted Porphyrins (1999)

The pentameric array of canted porphyrins (3‘TPyP)[Ru(TPP)(CO)]4 (1) (3‘TPyP = 5,10,15,20-tetra(3‘-pyridyl)porphyrin, TPP = meso-tetraphenylporphyrin) was synthesized by axial coordination of the 3‘N pyridyl groups of 3‘TPyP to the ruthenium core of four Ru(TPP)(CO) units; a thorough spectroscopic characterization of 1 in solution, together with a well-defined X-ray structure of the corresponding zinc derivative (Zn·3‘TPyP)[Ru(TPP)(CO)]4 (1Zn), is reported.
Enzymatic Synthesis of Cytidine 5′-Monophospho-N-acetylneuraminic Acid (2005)

We have established an efficient method for enzymatic production of cytidine 5'-monophospho-N-acetylneuraminic acid (CMP-NeuAc) from inexpensive materials, N-acetylglucosamine (GlcNAc) and cytidine 5'-monophosphate (CMP). The Haemophilus influenzae nanE gene encoding GlcNAc 6-phosphate (GlcNAc 6-P) 2-epimerase and the Campylobacter jejuni neuB1 gene encoding N-acetylneuraminic acid (NeuAc) synthetase, both of whose products are involved in NeuAc biosynthesis, were cloned and co-expressed in Escherichia coli cells. We examined the synthesis of NeuAc from GlcNAc via GlcNAc 6-P, N-acetylmannosamine (ManNAc) 6-P, and ManNAc by the use of E. coli cells producing GlcNAc 6-P 2-epimerase and NeuAc synthetase, in expectation of biological functions of E. coli such as the supply of phosphoenolpyruvate (PEP), which is an essential substrate for NeuAc synthetase, GlcNAc phospholylation by the PEP-dependent phosphotransferase system, and dephospholylation of ManNAc 6-P. Eleven mM NeuAc was synthesized from 50 mM GlcNAc by recombinant E. coli cells with the addition of glucose as an energy source. Next we attempted to synthesize CMP-NeuAc from GlcNAc and CMP using yeast cells, recombinant E. coli cells, and H. influenzae CMP-NeuAc synthetase, and succeeded in efficient production of CMP-NeuAc due to a sufficient supply of PEP and efficient conversion of CMP to cytidine 5'-triphosphate by yeast cells.
SPACE ROBOTIC MISSION CONCEPTS FOR CAPTURING STRAY OBJECTS (2002)

Abstract The capture and recovery of an expensive satellite that has lost its attitude control function can be an important class of future missions for space robots. Moreover, there are tens of thousands of pieces of debris in orbit from previous missions. These orbiting debris such as the uncontrolled pieces of booster stages and obsolete satellites are a serious hazard to future orbiting spacecrafts. Thus, the use of robotic systems to capture and de-orbit uncontrolled materials from earth orbit has the potential to be another important future class of missions for space robots which should be technically similar to satellite capture. This paper describes on-orbit service system that utilizes multiple space robots for capturing and recovering valuable satellite system and for removing and changing the orbit to avoid collision from space debris. 1. Introduction Researchers have suggested that robots will be crucial components of future orbital missions [1]. While human astronauts are invaluable for their judgment and intelligence, transporting and maintaining them in space is expensive and potentially dangerous. Robotic systems, while having many limitations, offer important advantages to augment or in some cases replace astronauts in orbit. Robots have lower cost, require minimal support infrastructure, and have an indefinite work life in orbit. This paper outlines two potential orbital space missions suited to robots, and possibly teams of robots. These missions are the capture of an uncontrolled satellite and collection or deflection of space debris. The technologies required to perform these missions are currently under study as part of a joint MIT/NASDA research program. An important issue is to identify potential tasks within these missions that are most effectively done by robots.
A MULTI-POINT DETECTION SYSTEM WITH ADDRESSABLE ELEC- TRODE ARRAY DEVICE INCORPORATED WITH IDA ELECTRODES (2010)

In this study, we developed a novel device consisting of 32 row and 32 column electrodes on a single chip for highthroughput electrochemical detection. The row and column electrodes were orthogonally arranged and connected to interdigitated array (IDA) electrodes at individual crossing points to form 1024 (32 × 32) sensor points. Electrochemical responses from each of the 1024 sensors were acquired using redox cycling at individual IDA electrodes. Alkaline phosphatase (ALP) activity were successfully detected using the device. The device is a high-throughput lab-on-a-chip tool for applications such as enzyme-linked immunosorbent assay (ELISA), reporter gene assay for monitoring gene expressions.
Evaluation of Cortical Thickness after Traumatic Brain Injury in Military Veterans (2015)

Military service members frequently sustain traumatic brain injuries (TBI) while on active duty, a majority of which are related to explosive blasts and are mild in severity. Studies evaluating the cortical gray matter in persons with injuries of this nature remain scarce. The purpose of this study was to assess cortical thickness in a sample of military veterans with chronic blast-related TBI. Thirty-eight veterans with mild TBI and 17 veterans with moderate TBI were compared with 58 demographically matched healthy civilians. All veterans with TBI sustained injuries related to a blast and were between 5 and 120 months post-injury (M = 62.08). Measures of post-traumatic stress disorder (PTSD) and depression were administered, along with a battery of neuropsychological tests to assess cognition. The Freesurfer software package was used to calculate cortical thickness of the participants. Results demonstrated significant clusters of cortical thinning in the right hemispheric insula and inferior portions of the temporal and frontal lobe in both mild and moderate TBI participants. The TBI sample from this study demonstrated a high incidence of comorbid PTSD and depression symptoms, which is consistent with the previous literature. Cortical thickness values correlated with measures of PTSD, depression, and post-concussive symptoms. This study provides evidence of cortical thinning in the context of chronic blast-related mild and moderate TBI in military veterans who have comorbid psychiatric symptoms. Our findings provide important insight into the natural progression of long-term cortical change in this population and may have implications for future clinical evaluation and treatment.
Rücktitelbild: On‐POM Ring‐Opening Polymerisation of N‐Carboxyanhydrides (Angew. Chem. 7/2021) (2021)

Nicht loslassen! POMlymere (Polyoxometallat-Peptid-Hybride) sind biozide Wirkstoffe, die die bakterielle Adhäsion und Besiedlung von Oberflächen verhindernn. In ihrer Zuschrift auf S. 3491 berichten Scott G. Mitchell, Rafael Martín-Rapún und Mitarbeiter über eine “on-POM"-Polymerisation von N-Carboxyanhydriden als innovative Plattform zum Design von Hybridmaterialien mit antimikrobiellen Eigenschaften.
Bursal origin of bone marrow cells with competence for antibody formation. (1972)

The impaired antibody response of neonatally bursectomized chickens was restored by bone marrow cells from normal—but not from bursectomized—syngeneic donors. Chimaerism of donor cells in the recipients was demonstrated using the sex chromosomal marker. Attempts to substitute autologous bursal cell suspensions for the bursa in situ were unsuccessful. It is concluded that B lymphocytes in chicken bone marrow have matured in the bursa.
Anti-kindling Induced by Two-Stage Coordinated Reset Stimulation with Weak Onset Intensity (2016)

Abnormal neuronal synchrony plays an important role in a number of brain diseases. To specifically counteract abnormal neuronal synchrony by desynchronization, Coordinated Reset (CR) stimulation, a spatiotemporally patterned stimulation technique, was designed with computational means. In neuronal networks with spike timing-dependent plasticity CR stimulation causes a decrease of synaptic weights and finally anti-kindling, i.e., unlearning of abnormally strong synaptic connectivity and abnormal neuronal synchrony. Long-lasting desynchronizing aftereffects of CR stimulation have been verified in pre-clinical and clinical proof of concept studies. In general, for different neuromodulation approaches, both invasive and non-invasive, it is desirable to enable effective stimulation at reduced stimulation intensities, thereby avoiding side effects. For the first time, we here present a two-stage CR stimulation protocol, where two qualitatively different types of CR stimulation are delivered one after another, and the first stage comes at a particularly weak stimulation intensity. Numerical simulations show that a two-stage CR stimulation can induce the same degree of anti-kindling as a single-stage CR stimulation with intermediate stimulation intensity. This stimulation approach might be clinically beneficial in patients suffering from brain diseases characterized by abnormal neuronal synchrony where a first treatment stage should be performed at particularly weak stimulation intensities in order to avoid side effects. This might, e.g., be relevant in the context of acoustic CR stimulation in tinnitus patients with hyperacusis or in the case of electrical deep brain CR stimulation with sub-optimally positioned leads or side effects caused by stimulation of the target itself. We discuss how to apply our method in first in man and proof of concept studies.
Nucleotide sequence of the tms genes of the pTiA6NC octopine Ti plasmid: two gene products involved in plant tumorigenesis. (1984)

The nucleotide sequence of the tumor morphology locus, tms, from pTiA6NC has been determined. The sequence analysis indicates that each of two polyadenylylated transcripts encoded by this locus contains an open reading frame; the predicted transcript 1 gene product has a molecular size of 83,769 daltons, and the predicted transcript 2 gene product, of 49,588 daltons. The precise start and stop positions of the transcript 2 RNA have been mapped with S1 nuclease. Several insertion mutations have been constructed. One of these localizes the transcript 2 promoter within the 72 base pairs 5' to transcription initiation. Significant homology was observed between the protein encoded by transcript 1 and the adenine binding region of p-hydroxybenzoate hydroxylase from Pseudomonas fluorescens, suggesting that the transcript 1 protein binds adenine either as substrate or cofactor.
HB11—Understanding Hydrogen-Boron Fusion as a New Clean Energy Source (2023)

Abstract HB11 Energy’s mission is to realize large-scale electricity generation from the fusion of hydrogen with boron-11 (the HB11, or “proton-boron”, reaction) without the environmental problems normally associated with nuclear energy. A non-thermal approach is taken in the initiation of the reaction using high-peak-power lasers, which was the pursuit of HB11 Energy founder Prof. Heinrich Hora’s career as a theoretical physicist. In the 1980s, the invention of Chirped Pulse Amplification (CPA) of laser pulses by Donna Strickland and Gerard Mourou (Nobel Prize 2018) enabled the possibility of experimentally validating the earlier theoretical predictions. Several experimental demonstrations of the HB11 reaction using CPA lasers inspired the establishment of HB11 Energy and with it, the possibility of realizing an aneutronic nuclear energy source with easily accessible and safe fuel resources that could last thousands of years. Like all quests for fusion energy, there are significant scientific challenges remaining. HB11 Energy Holdings Pty Ltd, an Australian company, was established as the best vehicle to co-ordinate a global collaborative research effort to address these challenges and build capacity to host large-scale public private partnerships, such as those now recommended by the US National Academies of Science, Engineering and Medicine (NASEM) (US National Academies of Sciences, Engineering and Medicine in Bringing Fusion to the U.S. Grid,: National Academies Press, Washington, D.C, 2021). If net-energy-gain can be achieved through HB11 Energy’s concepts, there are many engineering benefits over traditional DT fusion that will see a dramatically simpler and safer reactor being produced. A technoeconomic assessment of such a reactor is also discussed which presents many engineering challenges that will need to be met before commercial HB11 fusion can be deployed on a large-scale.
Postfiltering Using Log-Magnitude Spectrum for Speech and Audio Coding (2018)

Advanced coding algorithms yield high quality signals with good coding efficiency within their target bit-rate ranges, but their performance suffer outside the target range. At lower bitrates, the degradation in performance is because the decoded signals are sparse, which gives a perceptually muffled and distorted characteristic to the signal. Standard codecs reduce such distortions by applying noise filling and post-filtering methods. In this paper, we propose a post-processing method based on modeling the inherent time-frequency correlation in the log-magnitude spectrum. The goal is to improve the perceptual SNR of the decoded signals and, to reduce the distortions caused by signal sparsity. Objective measures show an average improvement of 1.5 dB for input perceptual SNR in range 4 to 18 dB. The improvement is especially prominent in components which had been quantized to zero.
Structure of Lipopolysaccharide Side-chain of Pseudomonas syringae pv. lachrymans Strain NCPPB 1096, in Relation to O-serogroup (2000)

The side-chain of lipopolysaccharide from the cucumber pathogen, Pseudomonas syringae pv. lachrymans strain NCPPB 1096, contained L- and D-rhamnose. Using Smith degradation and 1 H and 13 C nuclear magnetic resonance spectroscopy, the repeat unit was found to have the structure: 3)-α-D-Rhap(1→3)-β-L-Rhap(1→4)-α-L-Rhap(1→ The structure is correlated with a previously proposed serogrouping system.
Intellectual disability, unusual facial morphology and hand anomalies in sibs (2013)

Here we report on a Portuguese family with three sisters who shared moderate intellectual disability, unusual facial morphology (short palpebral fissures; broad nasal tip; thin upper and lower vermillion; broad and pointed chin) and hand anomalies in two of them (short left third and fifth right metacarpals in one case; marked syndactyly between the third and fourth fingers in another). One of the sisters had microcephaly and short stature, and the other two were obese. Obesity and somewhat similar facial features were also present in the otherwise healthy mother. Despite the overlap with several known syndromes (Albright osteodystrophy; Filippi syndrome; Rubinstein-Taybi syndrome; microdeletion 2q37), we suggest this condition is previously unreported, and most likely displays an autosomal recessive pattern of inheritance. © 2013 Wiley Periodicals, Inc.
Effects of Aldose Reductase Inhibition on Responses of the Corpus Cavernosum and Mesenteric Vascular Bed of Diabetic Rats (2000)

We examined the effects of 2 months of streptozotocin-induced diabetes mellitus in rats on relaxation and contraction of corpus cavernosum and the mesenteric vascular bed in vitro. A further diabetic group was treated from diabetes induction with 10 mg/kg/day of the aldose reductase inhibitor, WAY121509. For corpus cavernosum, maximal acetylcholine-induced relaxation was 35.5% reduced (p < 0.001) by diabetes, and this deficit was completely prevented by WAY121509 treatment. Neither diabetes nor treatment affected contractile responses to field stimulation of noradrenergic nerves; however, nonadrenergic noncholinergic nerve relaxation responses were 32.9% decreased by diabetes and WAY 121509 attenuated this by 84% (p < 0.001). For the mesenteric vascular bed, diabetes depressed maximal endothelium-dependent vasodilation to acetylcholine by 25.2% (p < 0.001), and this was partially (50.6%; p < 0.01) prevented by WAY121509. Nitric oxide synthase blockade revealed endothelium-derived hyperpolarising factor-mediated vasodilation to acetylcholine that was 73.5% (p < 0.001) depressed by diabetes; WAY121509 provided partial (43.4%; p < 0.001) protection. Neither diabetes nor treatment affected endothelium-independent vasorelaxation to the nitric oxide donor, sodium nitroprusside, in corpus cavernosum or mesenteric vessels. Thus the data show protective effects of WAY121509 on nitric oxide-mediated cavernosal vasorelaxation responses and on mesenteric endothelium-derived hyperpolarising factor responses. Together these findings could account for the beneficial effects of aldose reductase inhibition on diabetic complications in experimental models.
Variable annuities : a global perspective (2009)

Introduction Tigran Kalberer and Kannoo Ravindran SECTION 1: VARIABLE ANNUITY PRODUCTS 1. History and Development of the Variable Annuity Market Mike Kaster Marianne Purushotham Kaster Actuarial Watson Wyatt 2. North American Variable Annuities Hubert Mueller Tillinghast 3. Australasian Variable Annuities Michael Winkler New Re 4. European Variable Annuities Lukas Ziewer Yves Lehmann Oliver Wyman Societe Generale SECTION 2: IDENTIFYING AND QUANTIFYING RISKS UNDERLYING VARIABLE ANNUITIES 5. Risks Underlying Variable Annuities Tigran Kalberer KPMG 6. Valuation of Variable Annuity Contracts Vinay Kalro, Jay Blumenstein and Joe Zhao Swiss Re 7. Valuation of Variable Annuity Guarantees Kirk Evans Samsung Life 8. Models used to Quantify Market Risks in Guarantees Dan Heyer Nationwide 9. Models used to Quantify Actuarial/Policyholder Behavioural Risks in Guarantees Tze Ping and Matt Wion Ernst & Young SECTION 3: MANAGING RISKS IN VARIABLE ANNUITY PRODUCTS 10. Overview of Commonly Used Risk Management Strategies Rajeev Dutt Milliman 11. Using Product Development to Manage Risks Adam Stolz AXA 12. Using Reinsurance to Manage Risks Michael Winkler New Re 13. Using Capital Markets to Manage Risks Yves Lehmann Societe Generale 14. Putting it all Together - from Dynamic to Static Kannoo Ravindran Annuity Systems Inc. SECTION 4: MONITORING AND REPORTING RISKS IN A VARIABLE ANNUITY HEDGING PROGRAMME 15. Measuring and Reporting Hedge Efficiency Mark Evans Aegon 16. Measuring the Effectiveness of a Hedging Strategy Jorg Sauren ING 17. Experiences and Lessons Learnt - Does Hedging Work? Mun Kurup and Warren Manners ING 18. Issues Relating to Running A Hedging Programme Kannoo Ravindran Annuity Systems Inc SECTION 5: ACCOUNTING AND REGULATION 19. An Overview of Insurance Regulations Sam Gutterman PricewaterhouseCoopers 20. Accounting: IFRS and GAAP challenges Stefan Engelander KPMG SECTION 6: OTHER RELATED TOPICS 21. Quantifying and Managing Basis Risks Pin Chung Allianz Investment Management 22. Replication Portfolios and Hedging Tigran Kalberer KPMG 23. What do Analysts look for when Evaluating Companies Writing Variable Annuities? Darin Arita Deutsche Bank 24. What do Rating Agencies look for when Evaluating Companies Writing Variable Annuities? Scott Robinson Moody's Investors Service 25. Liquidity in Global Derivatives Markets Naveed Choudri and Edward Tom Credit Suisse
Sensorless salient‐pole PM synchronous motor drive in all speed ranges (2001)

Abstract This paper presents a position sensorless drive of salient‐pole PM synchronous motors in all speed ranges including zero speed. Two position and speed estimation algorithms using the current differences between the actual and the estimated currents are proposed. One is based on the back emf estimation in the medium‐ and high‐speed ranges. Another is based on the position dependency of the winding inductances in the low‐speed ranges including zero speed. The effectiveness of the proposed algorithm has been verified with a six‐pole, 1.5‐kW, 1500‐rpm test motor. Stable sensorless speed control from zero to 3000 rpm within ±100% load torque range was achieved. © 2001 Scripta Technica, Electr Eng Jpn, 135(3): 64–73, 2001
[Recruitment maneuver and high PEEP in a patient with severe reperfusion pulmonary edema after pulmonary thromboendarterectomy]. (2003)

Recently open lung approach such as recruitment maneuver and high PEEP has been applied in patients with acute respiratory distress syndrome. We report here a 29-year-old man with chronic pulmonary thromboembolism (CPTE). In this case, recruitment maneuver and high PEEP relieved postoperative respiratory failure. The major complications after pulmonary thromboendarterectomy (PTE) for CPTE are: reperfusion pulmonary edema (RPE), pulmonary hypertension (PH), hypoxia and bronchial bleeding, all of which the patient has demonstrated. Preoperative examination showed high pulmonary artery pressure (85/41, mean 50 mmHg), and high pulmonary vascular resistance predicted poor postoperative course. After PTE, he developed severe RPE, PH, hypoxia and bronchial bleeding, resulting in failed weaning from cardiopulmonary bypass. Therefore he required mechanical support of percutaneous cardiopulmonary support (PCPS). In ICU we repeated recruitment maneuver (PEEP: 30 cmH2O, peak inspiratory pressure: 42 cmH2O, respiratory rate; 15 breaths.min-1, for 1 min) and kept high PEEP (15 cmH2O). After initiating this ventilatory strategy, RPE was gradually relieved, followed by improvement of oxygenation and PH. We successfully weaned him from PCPS 38 hr after surgery and he was discharged alive on the 90 post-operative day. We conclude that recruitment maneuver and high PEEP may be useful for RPE developed after PTE.
RESEARCH FRONTIER: Acoustic Surface Waves in Piezoelectric Materials—A New Technology (1974)

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