gebhart/patrepeval huggingface dataset:
Role of CKIP-1 in suppression of osteoblast mediated bone repair in a collagen induced non-human primate arthritis model (2017)

Rheumatoid arthritis (RA) is a systemic, inflammatory disease, which predominantly affects multiple joints. RA is characterized by swollen joints and peri-articular bone erosion. Conventional RA treatments have shown to reduce inflammation and slow down bone erosion, but repair of bone erosion is limited. Additionally, failure to repair for bone erosion in rheumatoid arthritis (RA) is caused by inadequate osteoblast-mediated bone formation resulting from focal inflammatory environment. Hence, there is immediate need to facilitate greater insight and develop a new therapeutic strategy to aid osteoblast -mediated repair of bone loss in RA. CKIP-1 is an intracellular inhibitor, that can negatively regulate osteoblast lineage cells differentiation and activity. CKIP-1 levels were found to be aberrantly over expressed in bone specimens from RA patients and arthritis mice, which was associated with reduced bone formation and increased disease severity. By genetic approach, overexpressed CKIP-1 in osteoblast exacerbated bone erosion and articular inflammation in CIA mice, whereas deficiency of CKIP-1 in osteoblast alleviates bone erosion in CIA mice. By pharmacological approach, RNA interference-based silencing of osteoblastic CKIP-1 led to bone formation-mediated reparative process at erosive site and reduced articular inflammation in arthritis induced mice. To extend above findings to a more relevant species that more closely resemble humans, we aimed to investigate the role of osteoblastic Casein kinase-2 interacting protein-1 (CKIP-1) in failure to repair bone erosion in non-human primate (NHP) arthritis model in this study. We found that CKIP-1 mRNA expression in osteoblasts of arthritic NHP was significantly suppressed by CKIP-1 siRNA treatment. Moreover, silencing of CKIP-1 in osteoblast of arthritis monkey improved clinical signs such as reduction in arthritis score, joint swelling and increase in body weight. Similarly, suppression of osteoblastic CKIP-1 resulted in better organized bony and articular structure with, fewer bone erosion sites as observed in x ray and micro CT images. Moreover, we found increase in bone mass, bone formation parameters such as BFR/BS and MAR and histological examination revealed attenuation of peri articular bone erosion and intraarticular inflammation in CKIP-1 siRNA treated arthritis monkeys. Taken together, these data strongly suggest that highly expressed osteoblastic CKIP-1 plays an important role in failure to repair articular bone erosion by inhibiting bone formation in RA. Targeting osteoblastic CKIP-1 could serve as a new therapeutic strategy by bone repair augmentation in RA.
Molecular genetics: science and technology regulation (2014)

The 23rd Annual Dialogue series at the MS Swaminathan Research Foundation aimed at suggesting important inputs in the regulatory process for the approval and commercialisation of genetically modified crops.
Pharmacokinetics and Cardiovascular Effects of Ma‐Huang (Ephedra sinica) in Normotensive Adults (1997)

The purpose of this study was to evaluate heart rate and blood pressure responses to a commercially available source of ma-haung, a natural source of the sympathomimetic substance, ephedrine, and to evaluate the pharmacokinetic properties of the product in normotensive, healthy adults. On day 1, twelve study participants were monitored with an ambulatory blood pressure device between hours 7 and 20. On day 2, they ingested four capsules of powdered ma-huang at hours 8 and 17 while again wearing the monitor between hours 7 and 20. Serial plasma samples were obtained and concentrations of ephedrine were analyzed by high-performance liquid chromatography. Pharmacokinetic parameters of ephedrine were determined from plasma concentration-time profiles. The ephedrine alkaloid content of each capsule was also determined by high-performance liquid chromatography. Six participants experienced a statistically significant increase in heart rate, but the effects on blood pressure were variable. The half-life, volume of distribution, clearance, and maximum concentration in plasma of ephedrine in the ma-huang product were similar to values previously reported for a 20 mg, immediate-release ephedrine tablet. Values for the absorption rate were considerably lower and time to reach maximum concentration was longer for the capsules, compared with the standard tablet. Variability in alkaloid content of ephedrine was low and yielded a mean dose of ephedrine at 19.4 mg; pseudoephedrine at 4.9 mg; and methylephedrine at 1.2 mg for a four-capsule dose. In summary, ma-haung had variable effects on blood pressure and increased heart rate in healthy, normotensive adults. Pharmacokinetic parameters for ephedrine were in agreement with those previously reported; however, the absorption rate was much slower after ingestion of ma-huang.
An mRNA vaccine against SARS-CoV-2: Lyophilized, liposome-based vaccine candidate EG-COVID induces high levels of virus neutralizing antibodies (2021)

Abstract In addition to the traditional method of vaccine development, the mRNA coronavirus vaccine, which is attractive as a challenging vaccination, recently opened a new era in vaccinology. Here we describe the EG-COVID which is a novel liposome-based mRNA candidate vaccine that encodes the spike (S) protein of SARS-CoV-2 with 2P-3Q substitution in European variant. We developed the mRNA vaccine platform that can be lyophilized using liposome-based technology. Intramuscular injection of the EG-COVID elicited robust humoral and cellular immune response to SARS-CoV-2. Furthermore, sera obtained from mice successfully inhibited SARS-CoV-2 viral infection into Vero cells. We developed EG-COVID and found it to be effective based on in vitro data, and we plan to initiate a clinical trial soon. Since EG-COVID is a lyophilized mRNA vaccine that is convenient for transportation and storage, accessibility to vaccines will be significantly improved.
ChemInform Abstract: Synthesis of Porphyrins: Models of Natural Hemoproteins and Impressive Catalysts for Asymmetric Epoxidation of Olefins (2000)

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.
Non-fragile distributed state estimation over sensor networks subject to DoS attacks: the almost sure stability (2020)

This paper focuses on the non-fragile distributed state estimation of discrete-time nonlinear systems over sensor networks subject to DoS attacks, whose probabilistic characterisations are adopted to reflect the reality better. On the basis of considering DoS attacks and gain variations, a non-fragile distributed state estimator is designed by fusing the innovation from the adjacent estimators and itself. In light of a switching idea, an auxiliary function on the product term of attack signals is exploited to disclose the evolution of the Lyapunov function. By virtue of the limit theorem and the developed evolution rule, a sufficient condition is proposed to guarantee that the error dynamics are almost surely asymptotical stable. Furthermore, gain variations are handled by utilising the well-known S-procedure, and the desired estimator gains are designed via a set of solutions of matrix inequalities. Finally, the effectiveness of the developed results is illustrated by a numerical example.
Quantum-inspired memory-enhanced stochastic algorithms (2019)

Stochastic models are highly relevant tools in science, engineering, and society. Recent work suggests emerging quantum computing technologies can substantially decrease the memory requirements for simulating stochastic models. Here we show that some of these recent quantum memory-enhanced algorithms can be either implemented or approximated classically. In other words, we show that it is possible to develop quantum-inspired classical algorithms that require much less memory than the best classical algorithms known to date. Being classical, such algorithms could be implemented in state-of-the-art high-performance computers, which could potentially enhance the study of large-scale complex systems. Furthermore, since memory is the main bottleneck limiting the performance of classical supercomputers in one of the most promising avenues to demonstrate quantum 'supremacy', we expect adaptations of these ideas may potentially further raise the bar for near-term quantum computers to reach such a milestone.
Fast-acting and injectable cryoneurolysis device (2022)

Cryoneurolysis is an opioid-sparing therapy for long-lasting and reversible reduction of pain. We developed a nerve-selective method for cryoneurolysis by local injection of ice-slurry (- 5 to - 6 °C) that induced decrease in nocifensive response starting from about a week after treatment and lasting up to 8 weeks. In this study, we test the hypothesis that injection of colder slurry leads to faster onset of analgesia. Colder slurry (- 9ºC) was injected around the rat sciatic nerve to induce cryoneurolysis. Hematoxylin and Eosin (H&E) staining was used to examine histologic effects on surrounding tissues. Coherent anti-Stokes Raman scattering (CARS) microscopy was used to study effects on myelin sheaths. Functional tests were used to assess changes in sensory and motor function in the treated hind paw. No inflammation or scarring was detected in surrounding skin and muscle tissues at day 7 post slurry injection. Functional tests showed rapid onset reduction in mechanical pain sensitivity starting from day 1 and lasting up to day 98. CARS imaging demonstrated disintegration of myelin sheaths post treatment followed by complete recovery of nerve structure by day 140. In this study we showed that colder slurry (- 9 °C) produces more rapid onset and longer duration of analgesia, while remaining nerve-selective.
Studies on Acetylenic Compounds. LVIII. Reaction of 2-Propynyl Sulfones with Methyl Acrylate (1972)

Three 2-propynyl sulfones (VIIIa-c) reacted with methyl acrylate to give the corresponding 2-carbomethoxy-4-ethynyl-4-arylsulfonylcyclohexanones (IXa-c), respectively. Nucleophilic reaction of acetylenic sulfonyl carbanion showed ambident character depending on the nature of electrophiles which were classified into two kinds. Some discussions of the reaction and physical properties of the products are presented.
Chemical beam epitaxially grown InP/InGaAsP interference mirror for use near 1.55 μm wavelength (1987)

An interference mirror for use near 1.55 μm wavelength was constructed using InP and lattice-matched InGaAsP on an InP substrate with chemical beam epitaxy methods. The maximum reflectivity was 92.5% at 1.46 μm. The design value was 94.75% at 1.55 μm. The mirror was used as an output mirror in a synchronously pumped mode-locked Tl:KCl color center laser.
A "high-performance" 2D gel scanner. (1984)

Abstract We describe the design principles of a photometric flatbed scanner with a scan area of 250 X 250 mm2, a dynamic range of 4000 gray levels, a signal/noise ratio of 2000/1, a step size of 0.1 mm, and a step frequency of 2000 steps per second. It is controlled by a microcomputer and used to acquire data for quantitative evaluation of gels or chromatograms. The performance of the instrument is demonstrated by the data obtained by scanning gratings, gray step filters, and high-resolution electropherograms.
Fibroblast growth factor-10. A second candidate stromal to epithelial cell andromedin in prostate (1999)

Vol. 274 (1999) 12827–12834 Page 12827: The footnote “‡Contributed equally to the results of this work” should be deleted.
Computing the singular value decomposition on the Connection Machine (1990)

Consideration is given to the computation of the singular value decomposition (SVD) on the Connection Machine (CM). Brief descriptions of the Lisp language and some typical matrix manipulating functions are given. Implementation details of various Jacobi-SVD algorithms on an 8192-processor CM are presented. For n*n matrices, where n<or=64, the decomposition is computed in time O(n) per sweep.<<ETX>>
The Thrifty Barrier: Energy-Aware Synchronization in Shared-Memory Multiprocessors (2005)

Much research has been devoted to making microprocessors energy-efficient. However, little attention has been paid to multiprocessor environments where, due to the cooperative nature of the computation, the most energy-efficient execution in each processor may not translate into the most energy-efficient overall execution. We present the thrifty barrier, a hardware-software approach to saving energy in parallel applications that exhibit barrier synchronization imbalance. Threads that arrive early to a thrifty barrier pick among existing low-power processor sleep states based on predicted barrier stall time and other factors. We leverage the coherence protocol and propose small hardware extensions to achieve timely wake-up of these dormant threads, maximizing energy savings while minimizing the impact on performance.
S-Rail Sled Testing With Deceleration Sled (2005)

This paper considers the effects of rotary draw bending on structural crashworthiness. We impacted tested aluminum alloy tubes in s-rail bending, using either 2.0 mm or 3.5 mm thickness, and bend radius of either 152.4 mm or 191 mm. This report documents and summarizes the test setup using the GM R&amp;D Deceleration Sled to achieve this, with emphasis on later correlation with numerical simulation. Theoretical and numerical analyses were used to help with design setup. Forces and moments found in the tests were very consistent, suggesting good test setup design. We also found that using the longest tube section at the constrained end prevents inboard rotation and contact between the two s-rails.
Proteins that interact with Sec16p during COPII vesicle formation in Saccharomyces cerevisiae (1996)

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 1996.
Synthesis and biological activity of prostaglandin lactones (1983)

Most of the primary prostaglandins and several biologically important prostaglandin analogues were converted to 1,9-, 1,11- or 1,15-lactones, in order to investigate the biological profiles of these internal esters and to assess their potential as prodrugs for the corresponding open-chain hydroxy acids. In each case, the key lactonization step was done using Corey's "double activation" procedure (cyclization of omega-hydroxy-2-pyridinethiol esters). In general, the 1,9-lactones exhibited less than 1% of the biological activity of the parent hydroxy acids in the standard prostaglandin test systems. The 1,11- and 1,15-lactones, on the other hand, were essentially equal to the parent hydroxy acids as antifertility agents (a 4-day assay which would allow time for in vivo enzymatic lactone hydrolysis). The 1,11- and 1,15-lactones exhibited very low activity in acute or in vitro screens (e.g., rat blood pressure and gerbil colon stimulation), assays which more closely reflect the intrinsic activity of the lactones themselves. These results are consistent with the observed relative ease of enzymatic hydrolysis of the prostaglandin lactones (1,15 greater than or equal to 1,11 much greater than 1,9). Several of the lactones whose parent hydroxy acids are resistant to metabolic inactivation (e.g., 15-methyl, 16-phenoxy, and 17-phenyl) exhibited potent abortifacient activity in the hamster. These lactones, with greatly diminished activity in the blood pressure and smooth muscle assays (indicators of potential side effects), represent a therapeutically useful class of antifertility agents.
Ihh controls cartilage development by antagonizing Gli3, but requires additional effectors to regulate osteoblast and vascular development (2005)

Indian hedgehog (Ihh) controls multiple aspects of endochondral skeletal development, including proliferation and maturation of chondrocytes, osteoblast development and cartilage vascularization. Although it is known that Gli transcription factors are key effectors of hedgehog signaling, it has not been established which Gli protein mediates Ihh activity in skeletal development. Here, we show that removal of Gli3 in Ihh-null mouse embryos restored normal proliferation and maturation of chondrocytes, but only partially rescued the defects in osteoblast development and cartilage vascularization. Remarkably, in both Ihh-/- and Ihh-/-; Gli3-/- embryos, vascularization promoted osteoblast development in perichondrial progenitor cells. Our results not only establish Gli3 as a critical effector for Ihh activity in the developing skeleton, but also identify an osteogenic role for a vasculature-derived signal, which integrates with Ihh and Wnt signals to determine the osteoblast versus chondrocyte fate in the mesenchymal progenitors.
Suppression of AMPK Activation via S485 Phosphorylation by IGF-I during Hyperglycemia Is Mediated by AKT Activation in Vascular Smooth Muscle Cells (2011)

As a metabolic sensor, the serine/threonine protein kinase AMP-activated protein kinase (AMPK) promotes the adaptation of cells to signals arising from nutrients, hormones, and growth factors. The ability of IGF-I to stimulate protein synthesis is suppressed by AMPK, therefore, these studies were undertaken to determine whether IGF-I modulates AMPK activity. IGF-I dose-dependently suppressed phosphorylation of AMPK T172, and it stimulated AMPK S485 phosphorylation in vascular smooth muscle cells (VSMC). To determine whether stimulation of AMPK S485 phosphorylation was mediating this response, VSMC were transduced with a mutant AMPKα (AMPK S485A). Expression of this altered form inhibited the ability of IGF-I to suppress AMPK T172 activation, which resulted in inhibition of IGF-I-stimulated phosphorylation of P70S6 kinase. In contrast, expression of an AMPK S485D mutant resulted in constitutive suppression of AMPK activity and was associated with increased IGF-I-stimulated P70S6K phosphorylation and protein synthesis. The addition of a specific AKT inhibitor or expression of an AKT1 short hairpin RNA inhibited AMPK S485 phosphorylation, and it attenuated the IGF-I-induced decrease in AMPK T172 phosphorylation. Exposure to high glucose concentrations suppressed AMPK activity and stimulated S485 phosphorylation, and IGF-I stimulated a further increase in S485 phosphorylation and AMPK T172 suppression. We conclude that AMPK S485 phosphorylation negatively regulates AMPK activity by modulating the T172 phosphorylation response to high glucose and IGF-I. IGF-I stimulates S485 phosphorylation through AKT1. The results suggest that AMPK plays an inhibitory role in modulating IGF-I-stimulated protein synthesis and that IGF-I must down-regulate AMPK activity to induce an optimal anabolic response.
UWB wireless coexistence by fibre-based photonic ADC interference monitoring (2008)

The interference monitoring of UWB wireless picocell clusters through an in-house fibre installation is proposed and evaluated in a proof-of-concept experiment. UWB clusters enable range extension of UWB technology providing Gbit/s communications in home or office buildings. Coexistence of a large number of UWB clusters with other wireless services is guaranteed by a photonic analog-to-digital converter employing the in-house optical fiber installation.
Synthetic Analogues of Betulinic Acid as Potent Inhibitors of PS1/BACE1 Interaction to Reduce Aβ Generation (2016)

Abstract The lupane‐type triterpenoids are endowed with a wide range of biological activities such as antiviral, anti‐inflammatory and anticancer activity. We describe here its potential application in Alzheimer's disease ( AD ) treatment as an inhibitor of PS1 / BACE1 interaction. 3‐ α ‐Akebonoic acid, which emanated from a high throughput screening ( HTS ), was discovered to interfere with PS1 / BACE1 interaction and reduce amyloid β‐protein (Aβ) production. In view of the limited source, we instead used naturally rich betulinic acid (compound 2 ) as starting material for lead optimization and a focused library of its derivatives was constructed to gain a better understanding of the structure activity relationship ( SAR ) of triterpenoid‐type inhibitor of PS1 / BACE1 interaction. Compound 22 was finally chosen as the most potent PS1 / BACE1 interaction inhibitor, which reduced Aβ generation effectively.
Iterative motion compensation algorithm for heart rate detection with ultrasound data. (2011)

Noncontact active ultrasound sensors can be used to detect human physiological signals such as respiration and heart rate using Doppler processing. Target motion such as a person swaying can reduce the performance of these algorithms. To mitigate the effect of target motion or respiration on estimating the heart rate, we developed an iterative motion compensation algorithm. We low pass filter the demodulated data, estimate the motion of the target, and then compensate the data for the slow moving motion. This procedure can be repeated at different cutoff frequencies for different scenarios. Now, standard Doppler processing techniques can be used to analyze the motion compensated data. The algorithm was tested on people standing in a laboratory illuminated with a 40-KHz continuous-wave ultrasound sensor. Results for estimating the respiration rate and heart rate will be presented.
Ti/Ti-N Hf/Hf-N and W/W-N multilayer films with high mechanical hardness (1992)

Ti/Ti-N, Hf/Hf-N, and W/W-N multilayer films with very thin individual metal and metal-nitride layers were developed, with hardness of the structure much higher than that of single-layer nitride films. Hardnesses with value between 3500 and 5000 kg/mm2 or higher were observed in the multilayer films. This is an improvement over that of single-layer metal-nitride films where hardnesses between 2200 and 2800 kg/mm2 are typically achieved. The improvement is thought to be due to the fact that the grains are restricted to a very small size in the thin individual layers of the sandwich structure. The multilayer films, in general, have better adhesion and less defects than the single-layer films. These films were prepared on room-temperature substrates by a simple sputtering process and have potential applications, as in hard coatings.
The “ASQUAM” programme: improving the standards of maternity care, using democratic prioritisation, guidelines and audit (2002)

Evaluates the current success of projects within the Achieving Sustainable Quality in Maternity clinical effectiveness programme initiated in 1994 when 23 improvements in the standards of maternity care were chosen as priorities for improvement, and a further 22 added in 1996 and 1997. The interventions used to achieve improvement were guidelines, cyclical audit of cases, monthly feedback meetings, patient specific reminders and educational training sessions. The setting was North Staffordshire Maternity Acute and Community Services. Main outcome measures were measures of maternal morbidity and “near‐miss” mortality, perinatal morbidity and “near‐miss”, patients’ satisfaction, communication, staff well‐being. Presents results from the 45 audit topics. Concludes it is possible to achieve significant improvements in the quality of maternity care through the use of local guidelines, cyclical audit, monthly feedback meetings and training courses but there has not been the same success in achieving high standards in communication and informed choice.
Non‐psychoactive cannabinoids modulate the descending pathway of antinociception in anaesthetized rats through several mechanisms of action (2010)

CBD and CBC stimulated descending pathways of antinociception and caused analgesia by interacting with several target proteins involved in nociceptive control. These compounds might represent useful therapeutic agents with multiple mechanisms of action.