gebhart/patrepeval huggingface dataset:
Mechanical Bioeffects of Ultrasound (2004)

Ultrasound is used widely in medicine as both a diagnostic and therapeutic tool. Through both thermal and nonthermal mechanisms, ultrasound can produce a variety of biological effects in tissues in vitro and in vivo. This chapter provides an overview of the fundamentals of key nonthermal mechanisms for the interaction of ultrasound with biological tissues. Several categories of mechanical bioeffects of ultrasound are then reviewed to provide insight on the range of ultrasound bioeffects in vivo, the relevance of these effects to diagnostic imaging, and the potential application of mechanical bioeffects to the design of new therapeutic applications of ultrasound in medicine.
Translationsl repression by bacteriophage MS2 coat protein does not require cysteine residues (1989)

Previous studies implicated cysteine residues in the translational repressor (i.e. RNA binding) activity of the coat protein of bacteriophage MS2. It has been proposed that a protein sulfhydryl forms a transient covalent bond with an essential pyrimidine in the translational operator by a Michael addition reaction. We have utilized codon-directed mutagenesis methods to determine the importance of each of the two coat protein cysteines for repressor function in vivo. The results indicate that cys46 can be replaced by a variety of amino acids without loss of repressor function. Cys101, on the other hand, is more sensitive to substitution. Most position 101 substitutions inactivate the repressor, but one (arginine) results in normal repressor activity. Although the possibility of a transient covalent contact between cys101 and RNA is not categorically ruled out, construction of double mutants demonstrates that cysteines are not absolutely required for translational repression by coat protein.
Oscillation Control Algorithms for Resonant Sensors with Applications to Vibratory Gyroscopes (2009)

We present two oscillation control algorithms for resonant sensors such as vibratory gyroscopes. One control algorithm tracks the resonant frequency of the resonator and the other algorithm tunes it to the specified resonant frequency by altering the resonator dynamics. Both algorithms maintain the specified amplitude of oscillations. The stability of each of the control systems is analyzed using the averaging method, and quantitative guidelines are given for selecting the control gains needed to achieve stability. The effects of displacement measurement noise on the accuracy of tracking and estimation of the resonant frequency are also analyzed. The proposed control algorithms are applied to two important problems in a vibratory gyroscope. The first is the leading-following resonator problem in the drive axis of MEMS dual-mass vibratory gyroscope where there is no mechanical linkage between the two proof-masses and the second is the on-line modal frequency matching problem in a general vibratory gyroscope. Simulation results demonstrate that the proposed control algorithms are effective. They ensure the proof-masses to oscillate in an anti-phase manner with the same resonant frequency and oscillation amplitude in a dual-mass gyroscope, and two modal frequencies to match in a general vibratory gyroscope.
Effect of fish oil on ventricular tachyarrhythmia in three studies in patients with implantable cardioverter defibrillators (2008)

These findings do not support a protective effect of omega-3 PUFAs from fish oil on cardiac arrhythmia in all patients with an ICD. Current data neither prove nor disprove a beneficial or a detrimental effect for subgroups of patients with specific underlying pathologies.
Parallel Recording of Single Ion Channels: A Heterogeneous System Approach (2010)

The convergence of integrated electronic devices with nanotechnology structures on heterogeneous systems presents promising opportunities for the development of new classes of rapid, sensitive, and reliable sensors. The main advantage of embedding microelectronic readout structures with sensing elements is twofold. On the one hand, the SNR is increased as a result of scaling. On the other, readout miniaturization allows organization of sensors into arrays. The latter point will improve sensing accuracy by using statistical methods. However, accurate interface design is required to establish efficient communication between ionic-based and electronic-based signals. This paper shows a first example of a concurrent readout system with single-ion channel resolution, using a compact and scalable architecture. An array of biological nanosensors is organized on different layers stacked together in a mixed structure: fluidics, printed circuit board, and microelectronic readout. More specifically, an array of microholes machined into a polyoxymethylene homopolymer (POMH or Delrin) device coupled with ultralow noise sigma-delta converters current amplifiers, is used to form bilayer membranes within which ion channels are embedded. It is shown how formation of multiple artificial bilayer lipid membranes (BLMs) is automatically monitored by the interface. The system is used to detect current signals in the pA range, from noncovalent binding between single, BLM-embedded ¿-hemolysin pores and ß-cyclodextrin molecules. The current signals are concurrently processed by the readout structure.
Regulation and function of the CXC chemokine ENA-78 in monocytes and its role in disease (1997)

Epithelial neutrophil-activating protein 78 (ENA-78) is a member of the CXC chemokines and acts as a potent chemoattractant and activator of neutrophil function. On stimulation in vitro, ENA-78 is highly expressed in many cell types. ENA-78 protein levels are strongly elevated in synovial fluid and blood of patients with rheumatoid arthritis. By in situ hybridization and immunofluorescence staining, ENA-78 has been recognized as a major CXC chemokine expressed in epithelial cells of the intestinal mucosa of patients with Crohn's disease, ulcerative colitis, and acute appendicitis. A high expression of ENA-78 and interleukin-8 (IL-8) was also observed in the exocrine tissue of patients with chronic pancreatitis (CP). It is interesting to note that expression of IP-10, MIP-1alpha, and MCP-1 is high in healthy pancreatic tissue but low in tissue of patients with CP, suggesting a mutually exclusive expression of the ELR-CXC vs. non-ELR-CXC/CC chemokines. High-resolution studies of intracellular chemokines has revealed specific immunoreactivity for ENA-78 associated with the endoplasmic reticulum of many cell types. In contrast, GROalpha immunoreactivity was exclusively localized in the nucleus. Despite their common effects on neutrophil functions, the differential intracellular localization of ENA-78 and GROalpha suggests additional roles for these two chemokines in normal cell biology.
Quantitation of supercoiled circular content in plasmid DNA solutions using a fluorescence-based method (2000)

A method for quantifying the proportion of supercoiled circular (SC) forms in DNA solutions is described. The method (SCFluo) takes advantage of the reversible denaturation property of SC forms and the high specificity of the PicoGreen fluorochrome for double-stranded (ds)DNA. Fluorescence values of forms capable of reversible denaturation after a 5 min heating, 2 min cooling step are normalised to fluorescence values of total dsDNA present in the preparation. For samples with a SC content >20-30%, good regression fits were obtained when values derived from densitometric scanning of an agarose gel and those derived from the SCFluo method were compared. The method represents an attractive alternative to currently established methods because it is simple, rapid and quantitative. During large-scale processing and long-term storage, enzymatic, chemical and shear degradation may substantially decrease the SC content of plasmid DNA preparations. Regulations for pharmaceutical grade products for use in gene therapy and DNA vaccination may require >90% of the plasmid to be in the SC form. In the present study the SC content of 6.9, 13 and 20 kb plasmid preparations that had been subjected to chemical and shear degradation was successfully quantified using the new method.
A Phorbol Ester-Insensitive AP-1 Motif Mediates the Stimulatory Effect of Insulin on Rat Malic Enzyme Gene Transcription (1998)

In liver, insulin stimulates the transcription of the gene encoding the cytosolic form of malic enzyme (ME) and modulates protein binding to two putative insulin response sequences (IRSs) in the ME promoter. One of these IRSs resembles that identified in the phosphoenolpyruvate carboxykinase (PEPCK) gene, whereas the other resembles that defined in the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene. To assess the functional significance of these changes in protein binding, a series of truncated ME-chloramphenicol acetyl-transferase (CAT) fusion genes were transiently transfected into rat H4IIE hepatoma cells. Deletion of the PEPCK-like IRS motif had no effect on the stimulation of CAT expression by insulin. Instead, the stimulatory effect of insulin was mediated through an AP-1 motif and an Egr-1 binding site that overlaps the GAPDH-like IRS motif. Both the ME AP-1 motif and the AP-1 motif identified in the collagenase-1 gene promoter were able to confer a stimulatory effect of insulin on the expression of a heterologous fusion gene, but surprisingly only the latter was able to confer a stimulatory effect of phorbol esters. Instead, the data suggest that AP-1 binds the ME AP-1 motif in an activated state such that phorbol ester treatment has no additional effect. The collagenase and ME AP-1 motifs were both shown to bind mainly Jun D and Fra-2, with similar affinities. However, the results of a proteolytic clipping bandshift assay suggest that these proteins bind the collagenase and ME AP-1 motifs in distinct conformations, which potentially explain the differences in phorbol ester signaling through these elements.
Dissecting the role of peptides in the immune response: theory, practice and the application to vaccine design (2003)

Analytical biochemistry and synthetic peptide based chemistry have helped to reveal the pivotal role that peptides play in determining the specificity, magnitude and quality of both humoral (antibody) and cellular (cytotoxic and helper T cell) immune responses. In addition, peptide based technologies are now at the forefront of vaccine design and medical diagnostics. The chemical technologies used to assemble peptides into immunogenic structures have made great strides over the past decade and assembly of highly pure peptides which can be incorporated into high molecular weight species, multimeric and even branched structures together with non-peptidic material is now routine. These structures have a wide range of applications in designer vaccines and diagnostic reagents. Thus the tools of the peptide chemist are exquisitely placed to answer questions about immune recognition and along the way to provide us with new and improved vaccines and diagnostics.
Touchable holography (2009)

Mid-air displays which project floating images in free space have been seen in SF movies for several decades [Rakkolainen 2007]. Recently, they are attracting a lot of attention as promising technologies in the field of digital signage and home TV, and many types of holographic displays are proposed and developed. You can see a virtual object as if it is really hovering in front of you. But that amazing experience is broken down the moment you reach for it, because you feel no sensation on your hand.
P2P networking: an information sharing alternative (2001)

Peer-to-peer networking offers unique advantages that will make it a more effective alternative to several existing client-server e-commerce applications, if it can mature into a secure and reliable technology. The paper discusses the advantages of P2P networks: load balancing; dynamic information repositories; fault tolerance; content-based addressing and improved searches. It also considers the disadvantages of P2P.
Rab GTPase–Myo5B complexes control membrane recycling and epithelial polarization (2011)

The Rab GTPases are the largest family of proteins regulating membrane traffic. Rab proteins form a nidus for the assembly of multiprotein complexes on distinct vesicle membranes to regulate particular membrane trafficking pathways. Recent investigations have demonstrated that Myosin Vb (Myo5B) is an effector for Rab8a, Rab10, and Rab11a, all of which are implicated in regulating different pathways for recycling of proteins to the plasma membrane. It remains unclear how specific interactions of Myo5B with individual Rab proteins can lead to specificity in the regulation of alternate trafficking pathways. We examined the relative contributions of Rab/Myo5B interactions with specific pathways using Myo5B mutants lacking binding to either Rab11a or Rab8a. Myo5B Q1300L and Y1307C mutations abolished Rab8a association, whereas Myo5B Y1714E and Q1748R mutations uncoupled association with Rab11a. Expression of Myo5B tails containing these mutants demonstrated that Rab11a, but not Rab8a, was required for recycling of transferrin in nonpolarized cells. In contrast, in polarized epithelial cyst cultures, Myo5B was required for apical membrane trafficking and de novo lumen formation, dependent on association with both Rab8a and Rab11a. These data demonstrate that different combinations of Rab GTPase association with Myo5B control distinct membrane trafficking pathways.
Biomimetic micro/nanostructured functional surfaces for microfluidic and tissue engineering applications (2011)

This paper reviews our work on the application of ultrafast pulsed laser micro∕nanoprocessing for the three-dimensional (3D) biomimetic modification of materials surfaces. It is shown that the artificial surfaces obtained by femtosecond-laser processing of Si in reactive gas atmosphere exhibit roughness at both micro- and nanoscales that mimics the hierarchical morphology of natural surfaces. Along with the spatial control of the topology, defining surface chemistry provides materials exhibiting notable wetting characteristics which are potentially useful for open microfluidic applications. Depending on the functional coating deposited on the laser patterned 3D structures, we can achieve artificial surfaces that are (a) of extremely low surface energy, thus water-repellent and self-cleaned, and (b) responsive, i.e., showing the ability to change their surface energy in response to different external stimuli such as light, electric field, and pH. Moreover, the behavior of different kinds of cells cultured on laser engineered substrates of various wettabilities was investigated. Experiments showed that it is possible to preferentially tune cell adhesion and growth through choosing proper combinations of surface topography and chemistry. It is concluded that the laser textured 3D micro∕nano-Si surfaces with controllability of roughness ratio and surface chemistry can advantageously serve as a novel means to elucidate the 3D cell-scaffold interactions for tissue engineering applications.
Characterization of luminal and basal cells flow-sorted from the adult rat mammary parenchyma (1991)

Differentially expressed membrane antigens have been used to flow-sort viable luminal epithelial and myoepithelial cells from freshly disaggregated adult virgin rat mammary parenchyma. Resulting cultures and clones have been characterized morphologically and by a panel of antibodies that recognise cell-type-specific cytoskeletal antigens in the intact mammary gland. Five clonal phenotypes were recognisable by morphological criteria, three (types 1-3) exclusively associated with sorted luminal epithelial (25.5-positive) cells, and two (types 4 and 5) generated from the sorted myoepithelial (CALLA/neutral endopeptidase 24.11-positive) cells. All clones derived from myoepithelial cells continued to express a basal parenchymal marker in the form of the rat equivalent of human cytokeratin 14, while smooth muscle alpha-actin was expressed by the small slowly growing type 4 clones but was found in fewer cells in rapidly proliferating type 5 myoepithelially derived clones. Two of the luminal clone types, characterized by an attenuated appearance and slow growth (types 1/2), expressed only luminal-specific markers, including the equivalent of human cytokeratins 7/18/19. Type 3 clones, by contrast, consisted of rapidly proliferating cells, many of which either co-expressed CK14 and CK18 antigens (type 3a) or were composed of a mosaic of CK14+/CK18-, CK14+/CK18+ and CK14-/CK18+ cells (type 3b). The sorted myoepithelially derived clones grew faster than clones from sorted luminal cells as evidenced by the larger fraction of cells synthesizing DNA. All types of clone could be obtained from both isolated ducts and alveoli, when these were cloned separately, although there were some differences in their relative frequency.(ABSTRACT TRUNCATED AT 250 WORDS)
HKI-272, an irreversible pan erbB receptor tyrosine kinase inhibitor: Preliminary phase 1 results in patients with solid tumors (2006)

3018 Background: HKI-272 is a potent, low molecular weight, orally active, irreversible pan erbB receptor tyrosine kinase inhibitor. It inhibits the growth of tumor cells that express erbB-1 (epidermal growth factor receptor, EGFR) and erbB-2 (HER-2) in culture and xenografts. HKI-272 also inhibits the growth of cultured cells that contain sensitizing and resistance-associated EGFR mutations (Kwak et al, Proc Natl Acad Sci USA 102:7665–70, 2005). We are conducting a phase 1 study in patients (pts) with advanced-stage tumors that express EGFR or HER-2 to assess HKI-272 for tolerability, safety, pharmacokinetics, and preliminary antitumor activity. Methods: Pts (3–6/cohort) received 40, 80, 120, 180, 240, 320, or 400 mg HKI-272 orally once on day 1 and then once daily beginning on day 8. Timed blood samples were collected on days 1 and 21 for pharmacokinetic analysis. Results: Enrollment of 73 pts is complete. Preliminary data for 51 pts as of 28 Nov 2005 are presented. Patients were a median 60 years and 26% men. The most frequently occurring tumor types at primary diagnosis were breast (23 pts), non-small cell lung (9), and colorectal, ovarian, and renal (3 pts each). Dose escalation ended when 2 pts who received 400 mg HKI-272/day had drug-related dose-limiting toxicity of grade 3 diarrhea. Thus, the maximum tolerated dose (MTD) was 320 mg HKI-272/day. HKI-272-related adverse events (AEs), any grade, that occurred in ≥10% of pts were diarrhea (84%), nausea (55%), asthenia (45%), anorexia (31%), vomiting (29%), chills (12%), and rash (10%). Grade 3 related AEs that occurred in &gt;1 pt were diarrhea (11) and asthenia (4). HKI-272 C max and AUC increased in a dose-dependent manner. At steady state at the MTD, mean values were C max : 112±58 ng/mL, AUC: 1618±930 ng.h/mL, t 1/2 : 15±2.5 h. Day 1 and 21 AUC values were comparable. Tumor assessments (modified RECIST criteria) were made at baseline and at the end of alternate cycles (28 days/cycle). Two breast cancer pts had confirmed partial responses (PRs) and 2 had unconfirmed PRs. Conclusions: When HKI-272 was administered on a continuous, once-daily, oral treatment schedule, the MTD was 320 mg/day, with diarrhea as the most frequently occurring related AE. HKI-272 has antitumor activity in HER-2-positive breast cancer. [Table: see text]
All-trans retinoic acid modulates the retinoic acid receptor-alpha in promyelocytic cells. (1991)

We have recently demonstrated that all-trans retinoic acid (RA), the active metabolite of vitamin A, is an efficient alternative to chemotherapy in the treatment of acute promyelocytic leukemia (AML3). We have further shown that, in these AML3 cells, the gene of the retinoic acid receptor-alpha (RAR alpha) is translocated from chromosome 17 to chromosome 15, and fused to a new gene, PLM. This results in the expression of both normal and chimeric RAR alpha transcripts in AML3 cells. The PLM-RAR alpha protein may account for the impairment of differentiation and thus leukemogenesis, but not for the paradoxical efficacy of RA in these cells. In an attempt to elucidate RA's differentiative effect in AML3 patients, the present work examined the in vitro and in vivo modulation of the normal RAR alpha transcripts by all-trans RA in seven cases of AML3. In all samples, Northern blot analysis revealed a low expression of the two normal RAR alpha transcripts compared with other human myeloid leukemic cells. No modulation was observed after 4-8 d of in vivo therapy with all-trans RA 45 mg/m2 per d. In vitro incubation with all-trans RA, however, increased the level of expression of the normal RAR alpha transcripts in AML3 cells but not in other AML leukemic subtypes. This modulation of the two normal RAR alpha transcripts appeared to be an early and primary event of RA's differentiating effect. We therefore suggest that up-regulation of the normal RAR alpha gene expression by pharmacological concentrations of all-trans RA may restore the normal differentiation pathway in these cells.
Cloning and characterization of CLLD6, CLLD7, and CLLD8, novel candidate genes for leukemogenesis at chromosome 13q14, a region commonly deleted in B-cell chronic lymphocytic leukemia. (2001)

Chromosome 13q14 deletions constitute the most common structural aberration in B-cell chronic lymphocytic leukemia (B-CLL). We constructed a high-resolution physical map covering the critical deleted region in B-CLL at 13q14 and flanking sequences. The order and position of both genomic markers and known genes were determined precisely. Three novel genes, CLLD6, CLLD7, and CLLD8, were isolated and characterized. The predicted protein sequence of CLLD6 revealed no homology with known proteins. However, both CLLD7 and CLLD8 predicted proteins contain known functional domains. CLLD7 has both an RCC1 and a BTB domain, and could thus be involved in cell cycle regulation by chromatin remodeling. CLLD8 contains a methyl-CpG binding, a preSET and a SET domain, suggesting that CLLD8 might be associated with methylation-mediated transcriptional repression. Mutation analysis of hematopoietic tumor cell lines and B-CLL tumor samples revealed no point mutations within the coding region of these three novel genes. The functional domains present within CLLD7 and CLLD8 suggest that the proteins may be involved in critical cellular processes such as cell cycle and transcriptional control and could therefore be directly or indirectly involved in leukemogenesis.
On the Origin of Helical Mesostructures (2006)

The investigation on the formation mechanism of helical structures and the synthesis of helical materials is attractive for scientists in different fields. Here we report the synthesis of helical mesoporous materials with chiral channels in the presence of achiral surfactants. More importantly, we suggest a simple and purely interfacial interaction mechanism to explain the spontaneous formation of helical mesostructures. Unlike the proposed model for the formation of helical molecular chains or surpramolecular packing based on the geometrically motivated model or the entropically driven model, the origin of the helical mesostructured materials may be attributed to a morphological transformation accompanied by a reduction in surface free energy. After the helical morphology is formed, the increase in bending energy together with the derivation from a perfect hexagonal mesostructure may limit the curvature of helices. Our model may be general and important in the designed synthesis of helical mesoporous materials.