gebhart/patrepeval huggingface dataset:
Pain relief achieved by transcutaneous electrical nerve stimulation and/or vibratory stimulation in a case of painful legs and moving toes (1990)

A patient is described with painful legs and moving toes. The pain had been occurring for more than 15 years, and a variety of therapies had been attempted with only partial, if any, success. Only morphine had succeeded in relieving the pain, but it had to be discontinued to avoid tolerance and dependence. We devised a treatment consisting of transcutaneous electrical nerve stimulation (TENS), vibratory stimulation (VS), and a combination of the two methods (TENS + VS). TENS brought about partial pain relief, but was less effective than VS; dual stimulation (TENS + VS) led to complete alleviation of the pain. Four months later, the patient was applying dual stimulation himself at home and was thus able to maintain complete relief with 3 or 4 weekly sessions. We suggest that dual stimulation results in a large-scale recruitment of large-diameter afferent fibres and may thus set up a powerful inhibitory control of nociception in our patient.
Targeted gene repair directed by the chimeric RNA/DNA oligonucleotide in a mammalian cell-free extract (1999)

Chimeric oligonucleotides consisting of RNA and DNA residues have been shown to catalyze site-directed genetic alteration in mammalian cells both in vitro and in vivo. Since the frequency of these events appears to be logs higher than the rates of gene targeting, a process involving homologous recombination, we developed a system to study the mechanisms of chimera-directed gene conversion. Using a mammalian cell-free extract and a genetic readout in Escherichia coli, we find that point mutations and single base deletions can be corrected at frequencies of approximately 0.1% and 0.005%, respectively. The reaction depends on an accurately designed chimera and the presence of functional hMSH2 protein. The results of genetic and biochemical studies reported herein suggest that the process of mismatch repair functions in site-directed gene correction.
Primary in vivo responses to ovalbumin. Probing the predictive value of the Kb binding motif (1993)

CD8+ cytolytic T cells recognize Ag presented by MHC class I molecules on the surface of target cells. It is known that presenting cells process nascent protein into peptides of approximately eight to nine amino acids which bind to the peptide groove of MHC class I and are transported to the cell surface. Recently, several laboratories have postulated that each MHC class I haplotype has a binding motif of at least two amino acids nested within the peptide. One such motif is XXXXF/YXXL which binds to the mouse MHC class I molecule, H2-Kb, and can be found in the known antigenic peptide from OVA at amino acids 257-264. By using the motif to scan OVA five peptides were found that fit this pattern, OVA 11-18, OVA 55-62, OVA 107-114, OVA 176-183, and OVA 257-264. Binding studies revealed that three out of the five peptides (OVA 55-62, OVA 176-183, and OVA 257-264) bind to MHC class I. To test the natural antigenicity of the predicted peptides, C57BL/6 mice were immunized with OVA containing immunostimulating complexes to elicit a MHC class I-driven response to naturally processed OVA. The cytolytic potential of the responding T cell population was tested in vitro by using EL-4 cells preincubated with the predicted synthetic peptides as targets. The known antigenic peptide OVA 257-264 elicited a strong response; however, OVA 176-183 was also recognized while the remaining three were not recognized. The CTL response did not strictly correlate with the ability of the selected peptides to bind Kb, for example, OVA 55-62 was able to bind Kb efficiently, yet elicited no cytolytic response. In addition, the plasticity of the peptide-binding motif was probed by making amino acid substitutions, and as a result the motif proved to be more flexible than previously suspected. This represents the first report of a Kb-associated CTL epitope within OVA other than OVA 257-264. It also demonstrates the predictive quality of the Kb-binding motif; however, not all predicted peptides were recognized by primary OVA-induced CTL, implying more rules of processing and binding are needed.
Calhex231 Ameliorates Cardiac Hypertrophy by Inhibiting Cellular Autophagy in Vivo and in Vitro (2015)

Calhex231 ameliorates myocardial hypertrophy induced by pressure-overload or Ang II via inhibiting CaSR expression and autophagy. Our results may support the notion that Calhex231 can become a new therapeutic agent for the treatment of cardiac hypertrophy.
Surface-Confined Assemblies and Polymers for Molecular Logic (2011)

Stimuli responsive materials are capable of mimicking the operation characteristics of logic gates such as AND, OR, NOR, and even flip-flops. Since the development of molecular sensors and the introduction of the first AND gate in solution by de Silva in 1993, Molecular (Boolean) Logic and Computing (MBLC) has become increasingly popular. In this Account, we present recent research activities that focus on MBLC with electrochromic polymers and metal polypyridyl complexes on a solid support. Metal polypyridyl complexes act as useful sensors to a variety of analytes in solution (i.e., H(2)O, Fe(2+/3+), Cr(6+), NO(+)) and in the gas phase (NO(x) in air). This information transfer, whether the analyte is present, is based on the reversible redox chemistry of the metal complexes, which are stable up to 200 °C in air. The concurrent changes in the optical properties are nondestructive and fast. In such a setup, the input is directly related to the output and, therefore, can be represented by one-input logic gates. These input-output relationships are extendable for mimicking the diverse functions of essential molecular logic gates and circuits within a set of Boolean algebraic operations. Such a molecular approach towards Boolean logic has yielded a series of proof-of-concept devices: logic gates, multiplexers, half-adders, and flip-flop logic circuits. MBLC is a versatile and, potentially, a parallel approach to silicon circuits: assemblies of these molecular gates can perform a wide variety of logic tasks through reconfiguration of their inputs. Although these developments do not require a semiconductor blueprint, similar guidelines such as signal propagation, gate-to-gate communication, propagation delay, and combinatorial and sequential logic will play a critical role in allowing this field to mature. For instance, gate-to-gate communication by chemical wiring of the gates with metal ions as electron carriers results in the integration of stand-alone systems: the output of one gate is used as the input for another gate. Using the same setup, we were able to display both combinatorial and sequential logic. We have demonstrated MBLC by coupling electrochemical inputs with optical readout, which resulted in various logic architectures built on a redox-active, functionalized surface. Electrochemically operated sequential logic systems such as flip-flops, multivalued logic, and multistate memory could enhance computational power without increasing spatial requirements. Applying multivalued digits in data storage could exponentially increase memory capacity. Furthermore, we evaluate the pros and cons of MBLC and identify targets for future research in this Account.
Modeling motion blur in computer-generated images (1983)

This paper describes a procedure for modeling motion blur in computer-generated images. Motion blur in photography or cinematography is caused by the motion of objects during the finite exposure time the camera shutter remains open to record the image on film. In computer graphics, the simulation of motion blur is useful both in animated sequences where the blurring tends to remove temporal aliasing effects and in static images where it portrays the illusion of speed or movement among the objects in the scene.
A Water Extract of Artemisia capillaris Prevents 2,2'-Azobis(2-Amidinopropane) Dihydrochloride-Induced Liver Damage in Rats (2006)

A water extract of Artemisia capillaris Thunberg (Compositae) was investigated for protective effects against oxidative stress induced by 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) in Sprague-Dawley male rats. Rats were orally administered A. capillaris water extract (ACWE; 7.5 g/kg) for 7 days before AAPH treatment (60 mg/kg). AAPH intoxication significantly elevated enzyme markers of liver injury (glutamic oxaloacetic transaminase and glutamic pyruvic transaminase). The pre-administration of ACWE significantly reduced the liver-damaging effects of AAPH as indicated by the low levels of these enzymes. Moreover, the ACWE administration significantly attenuated the accumulation of thiobarbituric acid-reactive substances in both plasma and liver tissues compared with those of rats administered AAPH alone. Furthermore, ACWE administration slightly improved the liver reduced glutathione levels and enhanced the production of antioxidant enzymes like catalase. A. capillaris contained 10.1 mg of catechin in 100 g of dried sample; the high-performance liquid chromatography results showed catechin composition in the ACWE to be 28% (-)-epigallocatechin gallate, 49% (-)- epigallocatechin, and 23% other catechins. These observations clearly indicate that ACWE contains antioxidant catechins capable of ameliorating the AAPH-induced hepatic injury by virtue of its antioxidant activity.
Detailed Shape Representation with Parallax Mapping (2001)

Although texture mapping is a common technique for adding apparent surface detail to 3-D objects, it lacks the capability to represent the motion parallax effect. So the mesh to which it is applied limits its realism. In this paper, we propose Parallax Mapping, a simple method to motion parallax effects on a polygon. This method has very fast per-pixel shape representation and can be performed in real-time with current hardware.
MicroRNA miR-21 overexpression in human breast cancer is associated with advanced clinical stage, lymph node metastasis and patient poor prognosis (2008)

To investigate the global expression profile of miRNAs in primary breast cancer (BC) and normal adjacent tumor tissues (NATs) and its potential relevance to clinicopathological characteristics and patient survival, the genome-wide expression profiling of miRNAs in BC was investigated using a microarray containing 435 mature human miRNA oligonucleotide probes. Nine miRNAs of hsa-miR-21, hsa-miR-365, hsa-miR-181b, hsa-let-7f, hsa-miR-155, hsa-miR-29b, hsa-miR-181d, hsa-miR-98, and hsa-miR-29c were observed to be up-regulated greater than twofold in BC compared with NAT, whereas seven miRNAs of hsa-miR-497, hsa-miR-31, hsa-miR-355, hsa-miR-320, rno-mir-140, hsa-miR-127 and hsa-miR-30a-3p were observed to be down-regulated greater than twofold. The most significantly up-regulated miRNAs, hsa-mir-21 (miR-21), was quantitatively analyzed by TaqMan real-time PCR in 113 BC tumors. Interestingly, among the 113 BC cases, high level expression of miR-21 was significantly correlated with advanced clinical stage ( P = 0.006, Fisher's exact text), lymph node metastasis ( P = 0.007, Fisher's exact text), and shortened survival of the patients (hazard ratio [HR]=5.476, P &lt; 0.001). Multivariate Cox regression analysis revealed this prognostic impact (HR=4.133, P = 0.001) to be independent of disease stage (HR=2.226, P = 0.013) and histological grade (HR=3.681, P = 0.033). This study could identify the differentiated miRNAs expression profile in BC and reveal that miR-21 overexpression was correlated with specific breast cancer biopathologic features, such as advanced tumor stage, lymph node metastasis, and poor survival of the patients, indicating that miR-21 may serve as a molecular prognostic marker for BC and disease progression.
Interaction of the eIF4G initiation factor with the aphthovirus IRES is essential for internal translation initiation in vivo (2000)

The strategies developed by internal ribosome entry site (IRES) elements to recruit the translational machinery are poorly understood. In this study we show that protein-RNA interaction of the eIF4G translation initiation factor with sequences of the foot-and-mouth disease virus (FMDV) IRES is a key determinant of internal translation initiation in living cells. Moreover, we have identified the nucleotides required for eIF4G-RNA functional interaction, using native proteins from FMDV-susceptible cell extracts. Substitutions in the conserved internal AA loop of the base of domain 4 led to strong impairment of both eIF4G-RNA interaction in vitro and IRES-dependent translation initiation in vivo. Conversely, substitutions in the vicinity of the internal AA loop that did not impair IRES activity retained their ability to interact with eIF4G. Direct UV-crosslinking as well as competition assays indicated that domains 1-2, 3, and 5 of the IRES did not contribute to this interaction. In agreement with this, binding to domain 4 alone was as efficient as to the full-length IRES. The C-terminal fragment of eIF4G, proteolytically processed by the FMDV Lb protease, was sufficient to interact with the IRES or to its domain 4 alone. Additionally, we show here that binding of the eIF4B initiation factor to the IRES required domain 5 sequences. Moreover, eIF4G-IRES interaction was detected in the absence of eIF4B-IRES binding, suggesting that both initiation factors interact with the 3' region of the IRES but use different residues. The strong correlation found between eIF4G-RNA interaction and IRES activity in transfected cells suggests that eIF4G acts as a linker to recruit the translational machinery in IRES-dependent initiation.
BE-SONOS: A bandgap engineered SONOS with excellent performance and reliability (2006)

A bandgap engineered SONOS with greatly improved reliability properties is proposed. This concept is demonstrated by a multilayer structure of O1/N1/O2/N2/O3, where the ultra-thin "O1/N1/O2" serves as a non-trapping tunneling dielectric, N2 the high-trapping-rate charge storage layer, and O3 the blocking oxide. The ultra-thin "O1/N1/O2" provides a "modulated tunneling barrier" - it suppresses direct tunneling at low electric field during retention, while it allows efficient hole tunneling erase at high electric field due to the band offset. Therefore, this BE-SONOS offers fast hole tunneling erase, while it is immune to the retention problem of the conventional SONOS. With a N <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">+</sup> -poly gate, we achieve self-convergent erased Vt ~3 V, suitable for NOR flash application. On the other hand, by using a P <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">+</sup> -poly gate, a depletion mode device (Vt < 0) is obtained, and a very large memory window (> 6 V) is achieved, ideal for MLC-NAND application. Excellent performance and reliability for both applications are demonstrated. Furthermore, with this simple structure and no new materials BE-SONOS is readily manufacturable
Aggressive surgical management of bilateral adenocarcinoma of the kidney (1973)

A 60-year-old Caucasian woman was found to have bilateral adenocarcinoma of the kidney. A transabdominal left radical nephrectomy with right partial nephrectomy was performed as a single operation. The main advantages of this more aggressive simultaneous bilateral surgery are better exposure, the ability to rule out intra-abdominal metastasis, and the avoidance of the necessity of leaving the patient with viable malignant tissue while awaiting a second surgical procedure. The immediate postoperative course was essentially uneventful, and the patient is now over 4 years post-surgery without evidence of morbidity or tumor recurrence. A review of the literature describing similar cases and alternate methods of management is presented.
Study of strong to ultratight protein interactions using differential scanning calorimetry (1990)

Data from differential scanning calorimetry (DSC) may be used to estimate very large binding constants that cannot be conveniently measured by more conventional equilibrium techniques. Thermodynamic models have been formulated to describe interacting systems that involve either one thermal transition (protein-ligand) or two thermal transitions (protein-protein) and either 1:1 or higher binding stoichiometry. Methods are described for obtaining binding constants and heats of binding by two different methods: calculation or simulation fitting of data. Extensive DSC data on 2'CMP binding to RNase are presented and analyzed by the two methods. It is found that the methods agree when binding sites are completely saturated, but substantial errors arise in the calculation method when site saturation is incomplete and the transition of liganded molecules overlaps that of unliganded molecules. This arises primarily from an inability to determine TM (i.e., the temperature where concentrations of folded and unfolded protein are equal) under weak-binding conditions. Results from simulation show that the binding constants and heats of binding from the DSC method agree quantitatively with corresponding estimates obtained from equilibrium methods when extrapolated to the same temperature. It was also found from the DSC data that the binding constant decreases with increasing concentration of ligand, which might arise from nonideality effects associated with dimerization of 2'CMP. Simulations show that the DSC method is capable of estimating binding constants for ultratight interactions up to perhaps 10(40) M-1 or higher, while most equilibrium methods fail well below 10(10) M-1. DSC data from the literature on a number of interacting systems (trypsin-soybean trypsin inhibitor, trypsin-ovomucoid, trypsin-pancreatic trypsin inhibitor, chymotrypsin-subtilisin inhibitor, subtilisin BPN-subtilisin inhibitor, RNase S protein-RNase S peptide, avidin-biotin, ovotransferrin-Fe3+, superoxide dismutase-Zn2+, alkaline phosphatase-Zn2+, and assembly of regulatory and catalytic subunits of aspartate transcarbamoylase) were analyzed by simulation fitting or by calculation. Apparent single-site binding constants ranged from ca. 10(5) to 10(20) M-1, while the interaction constant for assembly of aspartate transcarbamoylase was estimated as 10(37) in molarity units. For most of these systems, the DSC interaction constants compared favorably with other literature estimates, for some it did not for reasons unknown, while for still others this represented the first estimate. Simulations show that for proteins having two binding sites for the same ligand within a single cooperative unit, ligand rearrangement will occur spontaneously during a DSC scan as the transition temperature of the unliganded protein is approached.(ABSTRACT TRUNCATED AT 400 WORDS)
Allosteric cofactor-mediated enzyme cooperativity: a theoretical treatment. (1983)

The situation under which substrate cooperativity is apparent only in the presence of an inhibitor has been investigated. When a substrate and an inhibitor bind independently to a cooperative enzyme that conforms to the concerted Monod-Wyman-Changeux model, each of the two ligands must induce intersubunit transitions in the protein molecule in order to have their allosteric effects coupled to one another. The inhibitor exerts a heterotropic influence on the saturation function of the substrate and enhances the otherwise recondite homotropic effect of the latter. If the ligands bind competitively to the enzyme, however, intersubunit transitions in the enzyme need be induced only by the inhibitor. A sigmoidal substrate saturation curve is then obtained as a result of displacement of the inhibitor from the enzyme by the substrate. In this mechanism, the competitive inhibitor participates as a cofactor required for the expression of substrate cooperativity and the familiar ability of regulatory enzymes to mediate homotropic interactions directly between substrate molecules is absent. Experimental tests are proposed to elucidate the nature of cooperative interactions for enzymes that appear to retain heterotropic but not homotropic effects in substrate binding.
Murine leukemia inhibitory factor enhances retroviral-vector infection efficiency of hematopoietic progenitors (1990)

We have investigated the in vitro effects of the cytokine leukemia inhibitory factor (LIF) on normal murine hematopoietic progenitors by measuring recovery and retroviral vector infection efficiency of 13-day posttransplant, spleen-colony-forming cell (CFU-S 13) in short-term culture. Up to a twofold increase in CFU-S13 recovery was observed, from 9.7 x 10(-5) cells in untreated controls to 17.8 to 19.5 x 10(-5) cells, depending on the concentration of LIF. Histologic analysis of spleen colonies from control and LIF-treated marrows demonstrated that there was no detectable alteration in the differentiative potential of CFU-S13. The efficiency of CFU-S13 infection was increased from 15% in untreated controls to 84% to 91% in LIF-treated marrows. Analysis of proviral integration sites in spleen colonies indicated that some CFU- S13 precursors were infected in the LIF-treated marrows.
P1–023: Neuronal SIRT1 activation as a novel mechanism underlying the prevention of Alzheimer's disease amyloid neuropathology by calorie restriction (2006)

In previous studies we reported that calorie restriction (CR)–treatment reduces Alzheimer's disease (AD)–type β–amyloid (Aβ) neuropathology in the brain of the Tg2576 mouse model of AD. The intent of the present study is to evaluate a possible mechanism through which CR may prevent AD–type neuropathology, specifically the involvement of the nicotinamide adenine dinucleotide (NAD)+–dependent SIRT1 mediated deacetylase activity, which has been identified to be a key regulator in the lifespan extending effects of CR in a number of species. In this study we report that CR treatment for 6 months leads to significant increase in SIRT1 protein and enhanced NAD+ /nicotinamide (NAM) ratio in the brain of the 10–month old Tg2576 mice relative to the age– and gender– matched ad–libitum fed control Tg2576 mice. We demonstrate that the predicted changes in Aβ peptide content in the brain by CR can be reproduced in embryonic Tg2576 neurons in vitro by manipulating cellular SIRT1 expression or by treatment with the SIRT1 activators NAD+ or resveratrol. Our studies, for the first time, directly link changes in neuronal SIRT1 expression/activity to changes in amyloid precursor protein (APP) processing involved in Aβ generation, specifically to increase in non–amyloidogenic α–secretase activity. The present study strongly points to SIRT1 activation and enhancement of the NAD+/NAM ratio in the brain as potential novel attractive pharmacological strategy for AD prevention or treatment.
Roscovitine-Derived, Dual-Specificity Inhibitors of Cyclin-Dependent Kinases and Casein Kinases 1 (2008)

Cyclin-dependent kinases (CDKs) and casein kinases 1 (CK1) are involved in the two key molecular features of Alzheimer's disease, production of amyloid-beta peptides (extracellular plaques) and hyper-phosphorylation of Tau (intracellular neurofibrillary tangles). A series of 2,6,9-trisubstituted purines, structurally related to the CDK inhibitor roscovitine, have been synthesized. They mainly differ by the substituent on the C-6 position. These compounds were screened for kinase inhibitory activities and antiproliferative effects. Several biaryl derivatives displayed potent inhibition of both CDKs and CK1. In particular, derivative 13a was a potent inhibitor of CDK1/cyclin B (IC 50: 220 nM), CDK5/p25 (IC 50: 80 nM), and CK1 (IC 50: 14 nM). Modeling of these molecules into the ATP-binding pocket of CK1delta provided a rationale for the increased selectivity toward this kinase. 13a was able to prevent the CK1-dependent production of amyloid-beta in a cell model. CDK/CK1 dual-specificity inhibitors may have important applications in Alzheimer's disease and cancers.