gebhart/patrepeval huggingface dataset:
Low probability Bid-Bax reaction generates heterogeneity in apoptosis resistance of cancer and cancer stem cells (2011)

Variability in the tumorigenic potential among cancer cells within a tumor population is an unresolved fundamental issue in cancer biology. It is important to know whether cancer cells with higher tumorigenic potential, such as cancer stem cells, are only a small subpopulation. We attempt to address the question of variability in tumorigenic potential based on the heterogeneity in apoptosis resistance of cancer cells. We use stochastic differential equations and kinetic Monte Carlo simulations to explore the mechanisms that generate cell-to-cell variability in apoptosis resistance of cancer cells. In our model, a simplified scheme of apoptosis signaling reactions is developed focusing on the proapoptotic Bid-Bax reaction and its inhibition by Bcl-2 like antiapoptotic proteins. We show how a combination of low probability Bid-Bax reaction along with overexpressed reactant molecules allows specific killing of cancer cells, especially under targeted therapy such as Bcl-2 inhibition. This low probability Bid-Bax reaction protects normal cells from accidental apoptosis but generates cell-to-cell stochastic variability in apoptotic activation of cells equipped with overexpressed Bid and Bax molecules. We further demonstrate that cellular variations in Bcl-2 / Bax ratio, within a cancer cell population, can affect the intrinsic fluctuations arising from the stochastic Bid-Bax reaction and thereby provides a mechanism for origin of cells with higher tumorigenic potential. We discuss the implications of our results for cancer therapy, such as, optimal strategies to minimize stochastic fluctuations in cancer cell death.
Single-chip CMOS image sensors for a retina implant system (1999)

This work describes the architecture and realization of microelectronic components for a retina-implant system that will provide visual sensations to patients suffering from photoreceptor degeneration. Special circuitry has been developed for a fast single-chip CMOS image sensor system, which provides high dynamic range of more than seven decades (without any electronic or mechanical shutter) corresponding to the performance of the human eye. This image sensor system is directly coupled to a digital filter and a signal processor that compute the so-called receptive-field function for generation of the stimulation data. These external components are wireless, linked to an implanted flexible silicon multielectrode stimulator, which generates electrical signals for electrostimulation of the intact ganglion cells. All components, including additional hardware for digital signal processing and wireless data and power transmission, have been fabricated using in-house standard CMOS technology.
Chirp imaging vibro-acoustography for removing the ultrasound standing wave artifact (2005)

Vibro-acoustography (VA) is an imaging technique that uses the dynamic (oscillatory) radiation force of two continuous-wave (CW) ultrasound to image objects at low frequency (within the kHz range). In this technique, the dynamic radiation force is created by means of a confocused transducer emitting two ultrasound beams at slightly-shifted frequencies f1 and f2 = f1 + deltaf. It has been demonstrated previously that high-resolution images of various types of inclusions and tissues can be obtained using this technique. However, if the targeted object reflects ultrasound directly back to the transducer, standing waves are produced that result in an artifact in the VA image. The goal of this study is to remove the standing wave artifact and improve VA images by means of a new process called chirp imaging. The procedure consists of sweeping the frequencies of the primary ultrasound beams in a selected bandwidth while keeping deltaf constant during the sweep. The chirp image is produced by averaging the amplitude of the acoustic emission produced during the sweep. Vibro-acoustography chirp imaging experiments are performed on a stainless-steel sphere attached to a latex sheet in a tank of degassed water. The resulting chirp images demonstrate remarkable reduction of the standing wave artifact compared to the "fixed frequency" VA images.
Papillomavirus genomes in human cervical tumors: analysis of their transcriptional activity. (1985)

Four of six human cervical carcinoma biopsies were shown to contain the DNA of the human papillomavirus type 16 (HPV-16) covalently linked with the tumor cell DNA. HPV-16-specific mRNA species were observed in only one of the four tumors. No such sequences were found in the three other specimens in conditions that permitted the detection of less than one mRNA molecule per cell. It is concluded that maintenance of the malignant nature of these cervical tumors does not depend on the continuous transcriptional activity of HPV-16.
Electrostatic actuation of silicon optomechanical resonators (2011)

Cavity optomechanical systems offer one of the most sensitive methods for detecting mechanical motion using shifts in the optical resonance frequency of the optomechanical resonator. Presently, these systems are used for measuring mechanical thermal noise displacement or mechanical motion actuated by optical forces. Electrostatic capacitive actuation and detection have been shown previously for silicon micro electro mechanical resonators for application in filters and oscillators. Here, we demonstrate monolithic integration of electrostatic capacitive actuation with optical sensing using silicon optomechanical disk resonators and waveguides. The electrically excited mechanical motion is observed as an optical intensity modulation when the input electrical signal is at a frequency of 235 MHz corresponding to the radial vibrational mode of the silicon microdisk.
The AIDS Dementia Complex (1988)

Progressive dementia has been recognized as a complication of human immunodeficiency virus infection almost since the beginning of the epidemic. To many infectious diseases clinicians, however, the AIDS dementia complex remains ambiguous, and the clinical approach to this problem is less clearly defined than that for other infection-associated syndromes. Dr. Richard W. Price and his colleagues at Memorial Sloan-Kettering Cancer Center have, to a large extent, been responsible for defining this entity. In this AIDS Commentary they present their views of the current state of knowledge regarding the etiology, clinical presentation, and diagnostic and therapeutic approaches to the AIDS dementia complex.
Nucleosides and nucleotides. XLIII. On the stereoselectivity of alkyl addition reaction of pyrimidine 2'-ketonucleosides. (1990)

The β-face of a 2'-ketonucleoside is sterically more hindered than the α-face because of the bulky nucleobase on the β-side at the 1'-position. However, on the reaction of 4-ethoxy-1-[3, 5-O-(1, 1, 3, 3-tetraisopropyl-1, 3-disiloxanediyl)-β-D-erythro-2-pentofuranos-2-ulos-1-yl]-2(1H)-pyrimidinone (6d) with methylmagnesium bromide, the β-methyl addition product (8d) was obtained in a considerable amount. It was found that Lewis basicity of the 2-carbonyl oxygen in the pyrimidine moiety, which is influenced inductively by the substituent at the 5-position, governs the stereoselectivity of the methyl addition reaction.
EMOTION IN SPEECH: RECOGNITION AND APPLICATION TO CALL CENTERS (1999)

The paper describes two experimental studies on vocal emotion expression and recognition. The first study deals with a corpus of 700 short ut terances expressing five emotions: happiness, anger, sadness, fear, and normal (unemotional) state, which were portrayed by thirty non-professional actors. After evaluation a part of this corpus was used for extracting features and training backpropagation neural network models. Some statistics of the pitch, the first and second formants, energy and the speaking rate were selected as relevant features using feature selection techniques. Several neural network recognizers and ensembles of recognizers were created. The recognizers have demonstrated the following accuracy: normal state - 60-75%, happiness -- 6070 %, anger -- 70-80%, sadness -- 70-85%, and fear -- 35-55%. The total average accuracy is about 70%. The second study uses a corpus of 56 telephone messages of varying length (from 15 to 90 seconds) expressing mostly normal and ...
Stability of Uncertain Linear Systems with Time Delay (1991)

The control of systems with uncertain dynamics and unpredictable disturbances has raised some challenging problems. This is particularly important when high system performance is to be guaranteed at all times. Recently, Time Delay Control has been suggested as an alternative control scheme. The proposed control system does not require an explicit plant model nor does it depend on the estimation of specific plant parameters. Rather, it combines adaptation with past observations to directly estimate the effect of the plant dynamics. This paper outlines the Time Delay Control law for a class of linear dynamic systems and then presents a sufficient condition for stability of linear uncertain systems with time delay. The ideas of Nyquist and Kharitonov are used in the development of a sufficient condition, which does not resort to using approximations for time delay. Like Nyquist, the condition depends on maps of the Nyquist path and, like Kharitonov, stability depends on four functions each yielding a stable system. In this paper we combine these ideas to determine the stability of systems where the Time Delay Controller is applied to single input single output, linear time-invariant plants whose coefficients are known to vary within certain defined intervals. The development is carried out in the context of Time Delay Control but it can be applied in more general cases. Two examples will illustrate the approach and the usefulness of the technique.
Defining the clinical course of multiple sclerosis (2014)

Accurate clinical course descriptions (phenotypes) of multiple sclerosis (MS) are important for communication, prognostication, design and recruitment of clinical trials, and treatment decision-making. Standardized descriptions published in 1996 based on a survey of international MS experts provided purely clinical phenotypes based on data and consensus at that time, but imaging and biological correlates were lacking. Increased understanding of MS and its pathology, coupled with general concern that the original descriptors may not adequately reflect more recently identified clinical aspects of the disease, prompted a re-examination of MS disease phenotypes by the International Advisory Committee on Clinical Trials of MS. While imaging and biological markers that might provide objective criteria for separating clinical phenotypes are lacking, we propose refined descriptors that include consideration of disease activity (based on clinical relapse rate and imaging findings) and disease progression. Strategies for future research to better define phenotypes are also outlined.
Normal and abnormal temporomandibular joint: MR imaging with surface coil. (1986)

The normal temporomandibular joint (TMJ) was evaluated using magnetic resonance (MR) imaging with a surface coil in five subjects and compared with the abnormal joint in 37 patients (aged 14-59 years; total joints studied, 76). Multisection 3-mm-thick sagittal, coronal, and axial images were obtained with a 1.5-T MR system and 6.5-cm-diameter surface coil using both partial saturation and spin-echo sequences (TR = 1,000 msec, TE = 20 or 25 msec). A comparison with arthrography (n = 13 joints), computed tomography (CT) (n = 11), and surgical (n = 5) findings demonstrated that MR imaging with a surface coil provided an accurate depiction of both normal and abnormal TMJs. MR provided information about meniscal position, morphology, and histology that was not available with either arthrography or CT alone. The imaging potential of MR and its noninvasive characteristics warrant priority for further examination of MR as a useful modality in the diagnosis of TMJ pain and dysfunction.
Comparative antihypertensive and renoprotective effects of telmisartan and lisinopril after long-term treatment in hypertensive diabetic rats (2001)

This study compared the cardiovascular and renal effects of long-term telmisartan (3 and 10 mg/kg/day)and lisinopril (10 mg/kg/day) in an animal model combining hypertension and diabetes mellitus. It was a parallel-group study of diabetic, spontaneously hypertensive rats (SHR), treated with control or active treatment for eight months. A non-diabetic SHR control group was run in parallel. Diabetes was induced by streptozotocin (45 mg/kg i.v.) in SHRs aged 9-10 weeks. Animals were treated with telmisartan (3 or 10mg/kg/day), lisinopril (10 mg/kg/day) or vehicle. Plasma glucose levels, blood pressure (BP), and urinary protein and albumin excretion were measured monthly. Telmisartan treatment significantly reduced BP of diabetic SHRs in a dose-dependent manner (p<0.05, low-dose, n= 18; p<0.01, high-dose, n=15). The BP reduction in the lisinopril group was similar to that in the telmisartan 10 mg/kg/day group. Compared with non-diabetic SHRs, untreated diabetic SHRs developed severe proteinuria and albuminuria over the experimental period (p<0.01). In diabetic SHRs, proteinuria and albuminuria were dose-dependently and significantly attenuated by treatment with telmisartan (p<0.01 with the higher dose) and lisinopril (p<0.01). Compared with the untreated diabetic SHRs, cardiac hypertrophy was significantly reduced after treatment with both doses of telmisartan and with lisinopril. Telmisartan, 10 mg/kg/day, but not lisinopril, significantly attenuated the diabetes-induced increase in glomerular volume. In conclusion, telmisartan, 10 mg/kg/day, is at least as beneficial as lisinopril, 10 mg/kg/day, in lowering BP, reducing cardiac hypertrophy and attenuating renal excretion of protein and albumin in this model.
Antibody-Recruiting Molecules: An Emerging Paradigm for Engaging Immune Function in Treating Human Disease (2012)

Synthetic immunology, the development of synthetic systems capable of modulating and/or manipulating immunological functions, represents an emerging field of research with manifold possibilities. One focus of this area has been to create low molecular weight synthetic species, called antibody-recruiting molecules (ARMs), which are capable of enhancing antibody binding to disease-relevant cells or viruses, thus leading to their immune-mediated clearance. This article provides a thorough discussion of contributions in this area, beginning with the history of small-molecule-based technologies for modulating antibody recognition, followed by a systematic review of the various applications of ARM-based strategies. Thus, we describe ARMs capable of targeting cancer, bacteria, and viral pathogens, along with some of the scientific discoveries that have resulted from their development. Research in this area underscores the many exciting possibilities at the interface of organic chemistry and immunobiology and is positioned to advance both basic and clinical science in the years to come.
Indoleamine 2,3‐dioxygenase contributes to tumor cell evasion of T cell‐mediated rejection (2002)

The priming of an appropriate anti-tumor T cell response rarely results in the rejection of established tumors. The characteristics of tumors that allow them to evade a T cell-mediated rejection are unknown for many tumors. We report on evidence that the expression of the immunosuppressive enzyme, indoleamine 2,3-dioxygenase (IDO) by mononuclear cells that invade tumors and tumor-draining lymph nodes, is 1 mechanism that may account for this observation. Lewis lung carcinoma (LLC) cells stimulated a more robust allogeneic T cell response in vitro in the presence of a competitive inhibitor of IDO, 1-methyl tryptophan. When administered in vivo this inhibitor also resulted in delayed LLC tumor growth in syngeneic mice. Our study provides evidence for a novel mechanism whereby tumors evade rejection by the immune system, and suggests the possibility that inhibiting IDO may be developed as an anti-cancer immunotherapeutic strategy.
Modeling the dosimetry of organ‐at‐risk in head and neck IMRT planning: An intertechnique and interinstitutional study (2013)

The authors established a mathematical model to correlate the anatomical features and dosimetric indexes of OARs of HN patients in Tomotherapy plans. The model can be used for the setup of patient-specific OAR dose sparing goals and quality control of planning results.The institutional clinical experience was incorporated into the model which allows the model from one institution to generate a reference plan for another institution, or another IMRT technique.
Prediction of phenotype and gene expression for combinations of mutations (2007)

Molecular interactions provide paths for information flows. Genetic interactions reveal active information flows and reflect their functional consequences. We integrated these complementary data types to model the transcription network controlling cell differentiation in yeast. Genetic interactions were inferred from linear decomposition of gene expression data and were used to direct the construction of a molecular interaction network mediating these genetic effects. This network included both known and novel regulatory influences, and predicted genetic interactions. For corresponding combinations of mutations, the network model predicted quantitative gene expression profiles and precise phenotypic effects. Multiple predictions were tested and verified.
ARA290, a Peptide Derived from the Tertiary Structure of Erythropoietin, Produces Long-term Relief of Neuropathic Pain (2011)

ARA290 produces long-term relief of allodynia because of activation of the β-common receptor. It is argued that relief of neuropathic pain attributable to ARA290 treatment is related to its antiinflammatory properties, possibly within the central nervous system. Because ARA290, in contrast to erythropoietin, is devoid of hematopoietic and cardiovascular side effects, ARA290 is a promising new drug in the prevention of peripheral nerve injury-induced neuropathic pain in humans.
Regulation of Organelle Acidity (2001)

Intracellular organelles have characteristic pH ranges that are set and maintained by a balance between ion pumps, leaks, and internal ionic equilibria. Previously, a thermodynamic study by Rybak et al. (Rybak, S., F. Lanni, and R. Murphy. 1997. Biophys. J. 73:674-687) identified the key elements involved in pH regulation; however, recent experiments show that cellular compartments are not in thermodynamic equilibrium. We present here a nonequilibrium model of lumenal acidification based on the interplay of ion pumps and channels, the physical properties of the lumenal matrix, and the organelle geometry. The model successfully predicts experimentally measured steady-state and transient pH values and membrane potentials. We conclude that morphological differences among organelles are insufficient to explain the wide range of pHs present in the cell. Using sensitivity analysis, we quantified the influence of pH regulatory elements on the dynamics of acidification. We found that V-ATPase proton pump and proton leak densities are the two parameters that most strongly influence resting pH. Additionally, we modeled the pH response of the Golgi complex to varying external solutions, and our findings suggest that the membrane is permeable to more than one dominant counter ion. From this data, we determined a Golgi complex proton permeability of 8.1 x 10(-6) cm/s. Furthermore, we analyzed the early-to-late transition in the endosomal pathway where Na,K-ATPases have been shown to limit acidification by an entire pH unit. Our model supports the role of the Na,K-ATPase in regulating endosomal pH by affecting the membrane potential. However, experimental data can only be reproduced by (1) positing the existence of a hypothetical voltage-gated chloride channel or (2) that newly formed vesicles have especially high potassium concentrations and small chloride conductance.
SR protein-mediated inhibition of CFTR exon 9 inclusion: molecular characterization of the intronic splicing silencer (2007)

The intronic splicing silencer (ISS) of CFTR exon 9 promotes exclusion of this exon from the mature mRNA. This negative influence has important consequences with regards to human pathologic events, as lack of exon 9 correlates well with the occurrence of monosymptomatic and full forms of CF disease. We have previously shown that the ISS element interacts with members of the SR protein family. In this work, we now provide the identification of SF2/ASF and SRp40 as the specific SR proteins binding to this element and map their precise binding sites in IVS9. We have also performed a functional analysis of the ISS element using a variety of unrelated SR-binding sequences and different splicing systems. Our results suggest that SR proteins mediate CFTR exon 9 exclusion by providing a 'decoy' sequence in the vicinity of its suboptimal donor site. The results of this study give an insight on intron 'exonization' mechanisms and provide useful indications for the development of novel therapeutic strategies aimed at the recovery of exon inclusion.
Preparation and Mechanical Properties of AC8A Aluminum Alloy Composite Reinforced with Potassium Titanate Whisker (1994)

An AC8A aluminum alloy matrix composite reinforced with highly crystallized potassium titanate whisker having a crystallite size of 76 nm was fabricated by squeeze casting. Heat hardening behavior and mechanical properties were examined on the obtained composites whose Mg contents in the matrix were from 0.7 to 1.9 mass%.The Mg content and hardness of the composite were uniform at any locations. The composite whose Mg content in the matrix were 1.7 mass% solutionized at 803 K showed the highest strength value at room temperature and 573 K, respectively. And the Young’s modulus was as high as 138 GPa. The decrease in strength during exposure at up to 573 K was not observed. In particular, the properties of the obtained composite were found to be useful for the elevated temperature materials.
Effect of naltrexone on neuropathic pain in mice locally transfected with the mutantμ‐opioid receptor gene in spinal cord (2014)

This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2.
Structural Determinants of Salmon Calcitonin Bioactivity (2006)

Salmon calcitonin (sCT) forms an amphipathic helix in the region 9-19, with the C-terminal decapeptide interacting with the helix (Amodeo, P., Motta, A., Strazzullo, G., Castiglione Morelli, M. A. (1999) J. Biomol. NMR 13, 161-174). To uncover the structural requirements for the hormone bioactivity, we investigated several sCT analogs. They were designed so as to alter the length of the central helix by removal and/or replacement of flanking residues and by selectively mutating or deleting residues inside the helix. The helix content was assessed by circular dichroism and NMR spectroscopies; the receptor binding affinity in human breast cancer cell line T 47D and the in vivo hypocalcemic activity were also evaluated. In particular, by NMR spectroscopy and molecular dynamics calculations we studied Leu(23),Ala(24)-sCT in which Pro(23) and Arg(24) were replaced by helix inducing residues. Compared with sCT, it assumes a longer amphipathic alpha-helix, with decreased binding affinity and one-fifth of the hypocalcemic activity, therefore supporting the idea of a relationship between a definite helix length and bioactivity. From the analysis of other sCT mutants, we inferred that the correct helix length is located in the 9-19 region and requires long range interactions and the presence of specific regions of residues within the sequence for high binding affinity and hypocalcemic activity. Taken together, the structural and biological data identify well defined structural parameters of the helix for sCT bioactivity.