gebhart/patrepeval huggingface dataset:
Evaluation of the Inhibitory Effect of Dihydropyridines on N-type Calcium Channel by Virtual Three-dimensional Pharmacophore Modeling (2011)

Currently, a new type of calcium channel blockers, which can inhibit not only L-type calcium channels abundantly expressed in vascular smooth muscles, but also N-type calcium channels that abound in the sympathetic nerve endings, have been developed. In this study, analysis on a like-for-like basis of the L- and N-type calcium channel-inhibitory activity of typical dihydropyridine-type calcium-channel blockers (DHPs) was performed. Moreover, to understand the differences of N-type calcium channel inhibition among DHPs, the binding of DHPs to the channel was investigated by means of hypothetical three-dimensional pharmacophore modeling using multiple calculated low-energy conformers of the DHPs. All of the tested compounds, i.e. cilnidipine (CAS 132203-70-4), efonidipine (CAS 111011-76-8), amlodipine (CAS 111470-99-6), benidipine (CAS 85387-35-5), azelnidipine (CAS 123524-52-7) and nifedipine (CAS 21829-25-4), potently inhibited the L-type calcium channel, whereas only cilnidipine inhibited the N-type calcium channel (IC50 value: 51.2 nM). A virtual three-dimensional structure of the N-type calcium channel was generated by using the structure of the peptide omega-conotoxin GVIA, a standard inhibitor of the channel, and cilnidipine was found to fit well into this pharmacophore model. Lipophilic potential maps of omega-conotoxin GVIA and cilnidipine supported this finding. Conformational overlay of cilnidipine and the other DHPs indicated that amlodipine and nifedipine were not compatible with the pharmacophore model because they did not contain an aromatic ring that was functionally equivalent to Tyr13 of omega-conotoxin GVIA. Azelnidipine, benidipine, and efonidipine, which have this type of aromatic ring, were not positively identified due to intrusions into the excluded volume. Estimation of virtual three-dimensional structures of proteins, such as ion channels, by using standard substrates and/or inhibitors may be a useful method to explore the mechanisms of pharmacological and toxicological effects of substrates and/or inhibitors, and to discover new drugs.
Reaction of Chick Embryo Cells Infected with Leukosis Strain MC29 Virus with Fluorescein-Labeled Antibody (1969)

Immune serum was prepared in the rabbit with BAI strain A leukosis virus isolated by centrifugal fractionation from the plasma of chickens with myeloblastic leukemia and further purified on a potassium tartrate gradient. Antibody to group-specific antigen was demonstrated in the serum by immunoelectrophoresis and immunodiffusion. Fluorescein-conjugated serum was used unabsorbed and absorbed with chick cells for study of acetone-fixed chick embryo cells uninfected or infected with strain MC29 avian leukosis virus. With unabsorbed serum, large numbers of cytoplasmic particles stained in a few cells within 2 hr after exposure to virus, and the cell number increased greatly in 24 hr. Absorption of the serum abolished the early reaction. Staining with absorbed serum was delayed until about 14 hr after culture exposure to virus, but essentially all cells were stained within 72 hr at the time when all cells were morphologically altered. Differences between the responses to unabsorbed and absorbed serum suggested cytoplasmic formation or concentration of chick tissue antigen similar to that incorporated in leukosis virus particles. The characteristics of staining with absorbed serum were similar to those observed by others in analogous studies with avian tumor viruses.
Figure S1 from HSP90 Inhibitor–SN-38 Conjugate Strategy for Targeted Delivery of Topoisomerase I Inhibitor to Tumors (2023)

&lt;p&gt;HSP90 binding promotes the intracellular retention of HSP90 inhibitor-BODIPY probes in tumor cell lines.&lt;/p&gt;
An approach to the packet scheduling with multi-users diversity in wireless CDMA systems (2003)

There have been a number of studies that investigate efficient packet scheduling schemes to support quality of service of multiple real-time data users and to increase capacity of non-real-time users sharing wireless channel. We consider the problem of scheduling transmissions of multiple data users sharing the same wireless channel so as to satisfy delay or throughput and present a packet scheduling, called MBCS (multi-users best channel scheduling) which takes advantage of the multi-users diversity of a mobile wireless system. A queueing model that represents radio resource management for supporting packet data services is developed for the purpose of evaluating the system-level performance of wireless CDMA systems. Numerical results show that the delay performance of the proposed scheduler is higher than that of the single-user best channel scheduler according to the time-varying channel condition.
Muon Tracking to Detect SNM (2017)

The Configurable Muon Tracker (CMT) is an adaptation of the existing drift tube detector commerically available from Decision Sciences International Corporation (DSIC). NSTec engineered the CMT around commercially available drift tube assemblies to make a detector that is more versatile than previous drift tube assemblies.
Uncaria rhynchophyllaUpregulates the Expression of MIF and Cyclophilin A in Kainic Acid-Induced Epilepsy Rats: A Proteomic Analysis (2010)

Uncaria rhynchophylla (Miq) Jack (UR) is a traditional Chinese herb and is used for the treatment of convulsive disorders, including epilepsy. Our previous study has shown that UR, as well as its major component rhynchophylline (RH), has an anticonvulsive effect and this effect is closely related to its scavenging activities of oxygen free radicals. The purpose of the present study was to investigate the effect of (UR) on the expression of proteins using a proteomics analysis in Sprague-Dawley (SD) rats with kainic acid (KA)-induced epileptic seizures. We profiled the differentially expressed proteins on two-dimensional electrophoresis (2-DE) maps derived from the frontal cortex and hippocampus of rat brain tissue 24 hours after KA-induced epileptic seizures. The results indicated that macrophage migration inhibitory factor (MIF) and cyclophilin A were under expressed in frontal cortex by an average of 0.19- and 0.23-fold, respectively. In the frontal cortex, MIF and cyclophilin A were significantly decreased in the KA group and these decreases were confirmed by the Western blots. However, in the hippocampus, only cyclophilin A was significantly decreased in the KA group. In addition, in real-time quantitative PCR (Q-PCR), MIF and cyclophilin A gene expressions were also significantly under expressed in the frontal cortex, and only the cyclophilin A gene was also significantly under expressed in the hippocampus in the KA group. These under expressions of MIF and cyclophilin A could be overcome by the treatment of UR and RH. In conclusion, the under expressions of MIF and cyclophilin A in the frontal cortex and hippocampus in KA-treated rats, which were overcome by both UR and UH treatment, suggesting that both MIF and cyclophilin A at least partly participate in the anticonvulsive effect of UR.
Coastal Hazards and the Global Distribution of Human Population (2000)

A frequently predicted consequence of global climate change is an increased effect of hazards on the world's human population. The impact of hazards depends on the proximity of human population to the zone. Recently compiled population estimates are combined with a new continental digital elevation model in an attempt to quantify the global distribution of human population and occupied land area with respect to elevation and proximity. The limited spatial resolution of the census data allows one to quantify some of the uncertainty in the spatial distribution of population. This provides a lower bound on the uncertainty in the resulting distributions but does not account for uncertainty in the census data or elevation data. Long-term records of relative sea level rise, tidal heights, and storm surge heights can be combined with global sea level rise estimates for a variety of climate change scenarios to estimate the approximate magnitude of vertical changes in local sea level. It is verified that large numbers of people live at low elevations near coasts but the uncertainties are too large to provide meaningful estimates of the number of people who reside in so-called coastal zones worldwide. The principal conclusion is that both the spatial distribution and the resolution of global data must be significantly improved before realistic quantitative assessments of the global impact of hazards can be made.
Investigation and appreciation of optimal output feedback. Volume 1: A convergent algorithm for the stochastic infinite-time discrete optimal output feedback problem (1984)

The stochastic, infinite time, discrete output feedback problem for time invariant linear systems is examined. Two sets of sufficient conditions for the existence of a stable, globally optimal solution are presented. An expression for the total change in the cost function due to a change in the feedback gain is obtained. This expression is used to show that a sequence of gains can be obtained by an algorithm, so that the corresponding cost sequence is monotonically decreasing and the corresponding sequence of the cost gradient converges to zero. The algorithm is guaranteed to obtain a critical point of the cost function. The computational steps necessary to implement the algorithm on a computer are presented. The results are applied to a digital outer loop flight control problem. The numerical results for this 13th order problem indicate a rate of convergence considerably faster than two other algorithms used for comparison.
Effect of annealing temperature on interrelation between the microstructural evolution and plastic deformation in polymers (2017)

The mechanical loading induced flow of glassy polymers is triggered by the nucleation of shear transformation units, and strongly depends on the initial microstructural state of the material. Therefore, investigation of the possible relationship between the microstructural state variables and plastic deformation is required for a better understanding of the macroscopic response of this class of materials during large deformation. In this study, free volume content is considered as a state variable and thermal treatment is selected as a process through which the accelerated and forced evolution of the free volume can be imposed. For two well-known glassy polymers, poly(methyl methacrylate) and polycarbonate, the free volume content alteration upon annealing is monitored via positron annihilation spectroscopy, and the changes of the micro- and macromechanical properties are also obtained by utilizing nanoindentation technique and employing the homogeneous amorphous flow theory. The correlation between the microstructural state variable, that is, free volume, and the micromechanical state variable, that is, shear activation volume, is then investigated. The results reveal opposite direction of alterations of free volume and shear activation volume with annealing temperature. Accordingly, the possibility of the existence of an interrelation between these two state variables is critically discussed. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2017, 55, 1286–1297
The molecular basis of X‐linked deafness type 3 (DFN3) in two sporadic cases: Identification of a somatic mosaicism for a POU3F4 missense mutation (1997)

We have investigated two unrelated males with X-linked deafness type 3 (DFN3) for mutations in the POU3F4 gene. In one patient, we observed a mutation that is predicted to result in an Arg330Ser amino acid substitution. In another DFN3 patient, a somatic mosaicism for an Arg323Gly amino acid substitution was found. This mosaicism was detected in two independently established EBV immortalized B cells and peripheral blood lymphocytes (PBLs). Semiquantitative analysis showed that approximately 50% of the PBLs of this patient carry the mutation. We hypothesize that the Arg323Gly mutation occurred very early in embryogenesis, before the differentiation of cells involved in hematopoiesis and inner ear development. In both patients, the missense mutations are situated in the POU homeodomain and are predicted to disrupt the DNA binding of the POU3F4 protein. All nine point mutations thus far described were found in the POU domains of POU3F4. Since these domains constitute only 35% of the open reading frame of POU3F4, there is a statistically significant preference for mutations in the POU-specific and POU homeodomain. Hum Mutat 10:207–211, 1997. © 1997 Wiley-Liss, Inc.
Multidimensional analysis and therapeutic development using patient iPSC–derived disease models of Wolfram syndrome (2022)

Wolfram syndrome is a rare genetic disorder largely caused by pathogenic variants in the WFS1 gene and manifested by diabetes mellitus, optic nerve atrophy, and progressive neurodegeneration. Recent genetic and clinical findings have revealed Wolfram syndrome as a spectrum disorder. Therefore, a genotype-phenotype correlation analysis is needed for diagnosis and therapeutic development. Here, we focus on the WFS1 c.1672C>T, p.R558C variant, which is highly prevalent in the Ashkenazi Jewish population. Clinical investigation indicated that patients carrying the homozygous WFS1 c.1672C>T, p.R558C variant showed mild forms of Wolfram syndrome phenotypes. Expression of WFS1 p.R558C was more stable compared with the other known recessive pathogenic variants associated with Wolfram syndrome. Human induced pluripotent stem cell-derived (iPSC-derived) islets (SC-islets) homozygous for WFS1 c.1672C>T variant recapitulated genotype-related Wolfram syndrome phenotypes. Enhancing residual WFS1 function through a combination treatment of chemical chaperones mitigated detrimental effects caused by the WFS1 c.1672C>T, p.R558C variant and increased insulin secretion in SC-islets. Thus, the WFS1 c.1672C>T, p.R558C variant causes a mild form of Wolfram syndrome phenotypes, which can be remitted with a combination treatment of chemical chaperones. We demonstrate that our patient iPSC-derived disease model provides a valuable platform for further genotype-phenotype analysis and therapeutic development for Wolfram syndrome.
Computational and physical analysis of active vortex generators (2002)

The objectives of this paper are to study the physics of the actuator-induced flow and to develop computational simulations of the actuator-generated flows. The vortex generator consists of a cavity with a lightweight actuator plate. The actuator plate acts like a piston pumping air out of the cavity on the down-stroke and sucking air into the cavity on the upstroke. The actuator is placed asymmetrically over the cavity opening, forming narrow and wide slots when viewed from the top. The actuator depending on amplitude, frequency, and slot spacing produces several flow fields (free jet, wall jet, vortex flow). Computational simulation of the actuator-generated flows have been developed and applied to several actuator flow modes. This work should provide an impetus for designing similar active flow control systems suitable for aircraft applications. The computational simulation uses a time-accurate full Navier-Stokes (NS) solver known as FTNS3D (a full NS version of CFL3D solver). A multi-block moving grid has been developed and used for the computational study of the flow fields produced by the vortex generator. For three-dimensional computations, ten multi-block grids are used and for two-dimensional computations, six multi-block grids are used. The grid blocks adjacent to the actuator plate move with the plate motion, and second-order interpolation is used along the block interfaces. Periodic response of the flow has been observed to develop after three cycles of the plate sinusoidal motion.
Nomogram to Predict the Long-Term Overall Survival of Early-Stage Hepatocellular Carcinoma after Radiofrequency Ablation (2023)

Our objective was to develop a predictive nomogram that could estimate the long-term survival of patients with very early/early-stage hepatocellular carcinoma (HCC) undergoing radiofrequency ablation (RFA). For this retrospective study, we enrolled 950 patients who initially received curative RFA for HCC at Barcelona Clinic Liver Cancer (BCLC) stages 0 and A between 2002 and 2016. Factors predicting poor survival after RFA were investigated through a Cox proportional hazard model. The nomogram was constructed using the investigated variables influencing overall survival (OS). After a median follow-up time of 6.25 years, 400 patients had died, and 17 patients had received liver transplantation. The 1-,3-,5-,7-, and 10-year OS rates were 94.5%, 73.5%, 57.9%, 45.7%, and 35.8%, respectively. Multivariate analysis showed that age greater than 65 years, albumin-bilirubin (ALBI) grades 2 and 3, AST-to-platelet ratio index (APRI) greater than 1, tumor size larger than 3 cm, diabetes mellitus, end-stage renal disease, and tumor number greater than 1 were significantly associated with poor OS. The nomogram was constructed using these seven variables. The validation results showed a good concordance index of 0.683. When comparing discriminative ability to tumor, node, and metastasis (TNM), BCLC, and Cancer of the Liver Italian Program (CLIP) staging systems, our nomogram had the highest C-index for predicting mortality. This nomogram provides useful information on prognosis post-RFA as a primary treatment and aids physicians in decision-making.
A scalable holographic display for interactive graphics applications (2005)

We present a scalable holographic system design targeting multi-user interactive computer graphics applications. The display device is based on back-projection technology and uses a specially arranged array of microdisplays and a holographic screen. The display is driven by DVI streams generated by multiple consumer level graphics boards and decoded in real-time by image processing units that feed the optical modules at high refresh rates. An OpenGL compliant library running on a client PC redefines the OpenGL behavior to multicast graphics commands to server PCs, where they are re-interpreted in order to implement holographic rendering. The feasibility of the approach is demonstrated with a working hardware and software 7.4M pixel prototype driven at 10-15Hz by two DVI
A modular expandable tactile sensor using flexible polymer (2005)

In this paper, we have proposed and demonstrated a modular expandable tactile sensor using PDMS elastomer. A sensor module consists of 16 /spl times/ 16 tactile cells with 1 mm spatial resolution, similar to that of human skin, and interconnection lines for expandability. Tactile response of a cell has been measured with a force gauge. Initial capacitance of each cell is about 180 fF. The fabricated cell shows a sensitivity of 3%/mN within the full scale range of 40 mN (250 kPa). Four tactile modules have been successfully attached by using ACP to demonstrate expandability. Various tactile images have been successfully captured by one sensor module as well as the expanded 32 /spl times/ 32 modular array sensors.
Energy Efficient On-Demand Dynamic Branch Prediction Models (2019)

The branch predictor unit (BPU) is among the main energy consuming components in out-of-order (OoO) processors. For integer applications, we find 16 percent of the processor energy is consumed by the BPU. BPU is accessed in parallel with the instruction cache before it is known if a fetch group contains control instructions. We find 85 percent of BPU lookups are done for non-branch operations, and of the remaining lookups, 42 percent are done for highly biased branches that can be predicted statically with high accuracy. We evaluate two variants of a branch prediction model that combines dynamic and static branch prediction to achieve energy improvements for power-constrained applications. These models, named on-demand branch prediction (ODBP) and path-based on-demand branch prediction (ODBP-PATH), are two novel prediction techniques that eliminate unnecessary BPU lookups using compiler generated hints to identify instructions that can be more accurately predicted statically. ODBP-PATH is an implementation of ODBP that combines static and dynamic branch prediction based on the program path of execution. For a 4-wide OoO processor, ODBP-PATH delivers 11 percent average energy-delay (ED) product improvement, and 9 percent core average energy saving on the SPEC Int 2006 benchmarks.
Instructed‐assembly of small peptides inhibits drug‐resistant prostate cancer cells (2019)

Abstract Despite multiple new‐drug approvals in recent years, prostate cancer remains a global health challenge because of the prostate cancers are resistant to androgen deprivation therapy. Here, we show that a small D‐phosphopeptide undergoes prostatic acid phosphatase (PAP)‐instructed self‐assembly for inhibiting castration‐resistant prostate cancer (CRPC) cells. Specifically, the installation of phosphate at the C‐terminal of a D‐tripeptide results in the D‐phosphopeptide. Dephosphorylating the D‐phosphopeptide by PAP forms uniform nanofibers that inhibit VCaP, a CRPC cell. A non‐hydrolyzable phosphate analogue of the D‐phosphopeptide, which shares similar self‐assembling properties with the D‐phosphopeptide, confirms that PAP‐instructed assembly is critical for the inhibition of VCaP. This work, for the first time, demonstrates PAP‐instructed self‐assembly of peptides for selective inhibiting CRPC cells.
A Pharmacodynamic/Pharmacokinetic Study of Ficlatuzumab in Patients with Advanced Solid Tumors and Liver Metastases (2014)

Ficlatuzumab exhibited good safety/tolerability and demonstrated ability to modulate the HGF/c-Met pathway and downstream signaling in the tumor in patients with advanced solid tumors. Safety, pharmacodynamic, and pharmacokinetic data for ficlatuzumab confirmed the recommended phase II dose of 20 mg/kg once per 14-day cycle.
Microemulsions as Nanoreactors To Produce Whey Protein Nanoparticles with Enhanced Heat Stability by Sequential Enzymatic Cross-Linking and Thermal Pretreatments (2009)

Sequential enzymatic cross-linking and heat pretreatments were used in this work to enhance the heat stability of whey protein isolate (WPI). In the first route, WPI was cross-linked by transglutaminase before incorporation in microemulsions for heat pretreatment at 90 degrees C for 20 min. In the second route, WPI was cross-linked by transglutaminase within microemulsions before thermal pretreatment. Particles produced from the two routes were different in dimension and heat stability and were also affected by the ratio of WPI and enzyme and cross-linking duration. At appropriate conditions, for example, 10 h of cross-linking by transglutaminase equivalent to 5% mass of WPI using the first route, a 5% dispersion (pH 6.8 and 100 mM NaCl) of the produced nanoparticles remained clear after heating at 90 degrees C for 20 min. In comparison, nanoparticles produced by thermal pretreatment only in a microemulsion corresponded to a translucent, flowable dispersion, whereas native WPI formed a gel. This novel approach can be used to manufacture heat-stable whey protein ingredients for clear beverage applications.