gebhart/patrepeval huggingface dataset:
Chemistry and formulations for siRNA therapeutics (2013)

Small interfering ribonucleic acids (siRNAs) form potentially the most important class of next generation therapeutics. However, achieving their efficient delivery in the correct dose, time and location in the body remains a significant challenge. Rapid developments in the chemistries of siRNA formulations are enabling new strategies to overcome the core obstacles to delivery which include poor ribonuclease (RNase) resistance, short biological half-life, lack of tissue targeting, inefficient cellular uptake and undesirable toxicity. In this review we describe these principal challenges and evaluate recent approaches proposed to overcome the chemical, biochemical and physiological barriers. The role of the specific chemical structure of siRNA is considered and an overview of selected literature-reported siRNA formulations is provided. These include chemically-modified siRNAs and analogues, aptamer-siRNA chimeras, self-assembled nanoparticles, lipid and polymer complexes, bioconjugates and fusion protein complexes. We conclude the review with an outlook for the clinical use of this highly promising, but pharmaceutically challenging biotherapeutic.
Bacteriophage Lambda as a Vehicle for Peptide and Protein Display (2002)

Bacteriophage lambda has emerged as an alternative vehicle for the surface display of peptides and proteins to the commonly used filamentous phage. There are a number of unique features that make lambda an attractive display vehicle including the ability to display multimeric proteins, no requirement for secretion of the displayed fusion protein and the means to vary the valency of the displayed fusion protein. With its increasing use for cDNA encoded display, the lambda display systems will be an important tool for functional genomics.
Methods in Protein Sequence Analysis (1982)

Methods in Protein Sequence Analysis -1986 brings together reports of the most recent methodology available to protein chemists for studying the molecular detail of proteins. The papers in this volume constitute the proceedings of the Sixth International Conference on Methods in Protein Sequence Analysis, which was held at the University of Washington in Seattle, Washington on August 17-21, 1986. This series of conferences has taken place during a period when new techniques in protein chemistry and molecular biology have enabled not only exploration of the control of protein function, but also deduction of the genetic origin of proteins, and labo- ratory generation of rare protein molecules for therapeu- tic and commercial use. The current reports are focused on the means by which experimental questions can be answered rather than on the biological implications in specific systems. The scope of the meeting was quite broad, empha- sizing microanalytical techniques and the relative merits of DNA sequencing, mass spectrometry and more tradi- tional degradation techniques. A highlight of the meeting was the Qrowing awareness of the role of mass spec- trometry In the analysis of proteins. The complementarity of protein sequencing and DNA sequencing techniques was apparent throughout the discussions and several papers dealt with the strategy of obtaining sequence in- formation from small amounts of protein in order that ap- propriate oligonucleotide probes could be constructed and the encoding nucleic acids se. quenced and manipu- lated.
Wireless Point-of-Care Diagnosis for Sleep Disorder With Dry Nanowire Electrodes (2010)

Currently, available sleep monitoring systems use electrical recording where the electrodes make contact with the patient’s skin using a conducting gel. The electrode wires are connected to a processing recording system. The subject has to be in close proximity of these machines due to the direct electrical connections with the body and the machine. The conductive gel along with many wires connected to the biopotential electrodes makes them uncomfortable for the subject, with the result that recording and monitoring of the patient’s sleep patterns can become very difficult. The patient has to be in a sleep lab and/or a hospital at all times and at least one technician needs to watch the patient’s sleep behavior via video. The patient may not experience normal sleep patterns under such environments and as such, the diagnostic results are not really very conclusive. The commonly monitored biopotential electrodes are electrocardiogram, electroencephalogram, electromyogram, and electrooculogram. The electrodes used for monitoring these signals are Ag/AgCl and gold, which require skin preparation by means of scrubbing to remove the dead cells and application of electrolytic gel to reduce the skin contact resistance. The gel takes a role of reducing skin contact impedance in the conventional Ag/AgCl electrode and its usage is directly related to the sensitivity. However, the wet conventional Ag/AgCl electrode has some drawbacks such as difficulty in long time monitoring because the gel dries out after few hours and skin irritations. Usually, physiological parameters are monitored over an extended period of time during the patient’s normal daily life to diagnose a disease. In this case, the wet conventional Ag/AgCl cannot be used because of the dry-out of gel. The dry-out of gel increases the impedance between skin and electrode and it is reflected in the poor signal sensitivity. Also noises, such as motion artifact and baseline wander, are added to the biopotential signals as the electrode floats over the electrolytic gel during monitoring. To overcome these drawbacks, dry nanoelectrodes are proposed in this paper where the electrodes are held against the skin surface to establish contact with the skin without the need for electrolytic fluids or gels. The results are presented along with a wireless communication such that the proposed system is ideal for point-of-care diagnosis of the patient at home.
Development and Implementation of Intraoperative Magnetic Resonance Imaging and Its Neurosurgical Applications (1997)

Intraoperative MRI allows lesions to be precisely localized and targeted, and the progress of a procedure can be immediately evaluated. The constantly updated images help to eliminate errors that can arise during frame-based and frameless stereotactic surgery when anatomic structures alter their position because of shifting or displacement of brain parenchyma but are correlated with images obtained preoperatively. Intraoperative MRI is particularly helpful in determining tumor margins, optimizing surgical approaches, achieving complete resection of intracerebral lesions, and monitoring potential intraoperative complications.
A novel method for angle independent ultrasonic imaging of blood flow and tissue motion (1991)

Tracking the speckle patterns produced by moving targets has been shown effective for angle independent imaging of blood flow and tissue motion. While speckle tracking overcomes major limitations of Doppler-based flow imaging, the computational complexity of commonly used cross correlation algorithms currently limits it to off-line studies. A much simpler algorithm for angle independent motion imaging is described in this paper. This method requires only one absolute difference operation per pixel, compared to eight operations for normalized cross correlation. Quantitative studies using speckle-generating targets translated by fixed amounts both axially and laterally indicate that the technique tracks moving speckle as accurately as correlation. Color flow images generated from clinical blood and liver data highlight the success of the technique for tracking both large and small motions in two dimensions. The algorithm's suitability for implementation in digital hardware makes possible the development of clinical instruments for angle independent ultrasonic imaging of blood flow and tissue motion in real time.
Acute occlusion after percutaneous transluminal coronary angioplasty--a new approach. (1983)

Between July 1980 and November 1982, there were 935 coronary angioplasties attempted at Emory University Hospital. Of these patients, 20 developed acute occlusion. Of these 20, 19 presented within 3 hr of surgery or within 3 hr after stopping a continuous heparin infusion. Five patients required emergency surgery, but in 15 nitrates, nifedipine, and/or repeat angioplasty reopened the artery and the patient could be stabilized on continuous infusions of heparin and nitroglycerin. In only one case was an occluding thrombus evident on angiographic examination. The mechanism of acute occlusion is unknown, but coronary artery spasm may play a role.
Broad Overexpression of Ribonucleotide Reductase Genes in Mice Specifically Induces Lung Neoplasms (2008)

Ribonucleotide reductase (RNR) catalyzes the rate-limiting step in nucleotide biosynthesis and plays a central role in genome maintenance. Although a number of regulatory mechanisms govern RNR activity, the physiologic effect of RNR deregulation had not previously been examined in an animal model. We show here that overexpression of the small RNR subunit potently and selectively induces lung neoplasms in transgenic mice and is mutagenic in cultured cells. Combining RNR deregulation with defects in DNA mismatch repair, the cellular mutation correction system, synergistically increased RNR-induced mutagenesis and carcinogenesis. Moreover, the proto-oncogene K-ras was identified as a frequent mutational target in RNR-induced lung neoplasms. Together, these results show that RNR deregulation promotes lung carcinogenesis through a mutagenic mechanism and establish a new oncogenic activity for a key regulator of nucleotide metabolism. Importantly, RNR-induced lung neoplasms histopathologically resemble human papillary adenocarcinomas and arise stochastically via a mutagenic mechanism, making RNR transgenic mice a valuable model for lung cancer.
ON THE OPTIMISATION, INCLUDING VISCOSITY EFFECTS, OF SHIP SCREW PROPELLERS WITH OPTIONAL END PLATES (PART II) (1991)

For ship screw propellers an optimisation theory is discussed, that can be applied to propellers with and without end plates. The method differs from the classical optimisation in that for the derivation of the optimum circulation distributions the sum of kinetic and viscous energy loss of the propeller is minimised instead of kinetic energy loss only. A criterion for the risk of cavitation, a simple strength model and an optional nonlinear correction are incorporated in the optimisation method. Hydrodynamically favourable planform shapes of screw blades and end plates are discussed. Numerical results of optimum screws are given, including a comparison between the application of different types of end plates. It is shown under what circumstances and to what extent the theory predicts a higher optimum efficiency for propellers with certain types of end plates than for propellers that have no end plates. This paper is a summary of [1], in which some topics are treated at greater length and in which more numerical results are given.
An Ankyrin-like Protein with Transmembrane Domains Is Specifically Lost after Oncogenic Transformation of Human Fibroblasts (1999)

We have identified a novel transformation-sensitive mRNA, which is present in cultured fibroblasts but is lacking in SV40 transformed cells as well as in many mesenchymal tumor cell lines. The corresponding gene is located on human chromosome 8 in band 8q13. The open reading frame of the mRNA encodes a protein of 1119 amino acids forming two distinct domains. The N-terminal domain consists of 18 repeats that are related to the cytoskeletal protein ankyrin. The C-terminal domain contains six putative transmembrane segments that resemble many ion channels. This overall structure is reminiscent of TRP-like proteins that function as store-operated calcium channels. The novel protein with an Mr of 130 kDa is expressed at a very low level in human fibroblasts and at a moderate level in liposarcoma cells. Overexpression in eukaryotic cells appears to interfere with normal growth, suggesting that it might play a direct or indirect role in signal transduction and growth control.
Thin-films field-transfer matrix theory of planar multilayer waveguides and reflection from prism-loaded waveguides (1984)

A standard 2 × 2 matrix method-used in thin-film optics is applied to planar multilayer optical waveguides. All modes are required to satisfy substrate-to-cover field-transfer equations that reduce to the equation γcm11 + γcγsm12 + m21 + γsm22 = 0 for bound modes and leaky waves. Expressions are derived for the field profiles and the power in each medium. A first-order perturbation theory is developed and applied to absorbing multilayer guides and to the reflection of plane waves from the prism-loaded lossy multilayer guide. The latter leads to experimental arrangements for measuring losses in which the gap thickness and propagation constant are accessible parameters.
Blind carrier synchronization and channel identification for OFDM communications (2002)

In OFDM communications, the loss of orthogonality due to carrier offset must be compensated before DFT-based demodulation can be performed. We present a high accuracy blind carrier offset estimation algorithm and a blind channel equalizer which exploit the intrinsic structure information of OFDM signals. The latter method allows the receiver to perform coherent demodulation in changing environments without the overhead required for additional pilots.
Design and Implementation of the System Provide of the Loyalty Service for Electronic Commerce (2000)

Loyalty is a bonus point that a customer earns in reward of purchasing goods of a shop or a manufacturer. The management of loyalty such as issuing, accounting, reimbursing is carried out by the loyalty system. Traditional loyalty systems were proprietary. As a result, the systems are not interoperable with each other. However, our loyalty system allows a group of merchants join together and use the same IC card to operate their own loyalty programs. Data and counters can be shared or totally isolated, using secret codes and keys. The loyalty pool system communicates with the loyalty service providers over the Internet and performs the management of loyalty in fully automated manner. This paper describes the functional architecture and internal behavior of the loyalty pool system along with the communication protocols.
Fractionation of mouse bone marrow by adherence separates primitive hematopoietic stem cells from in vitro colony-forming cells and spleen colony-forming cells (1991)

Fractionation of mouse bone marrow by adherence to tissue culture plastic was used to characterize the adhesive properties of hematopoietic stem (HS) cells capable of long-term reconstitution. The adherent fraction that represents approximately 13% of the total marrow population was virtually devoid of in vitro colony-forming cells and spleen colony-forming cells but did contain approximately 30% of the total HS cells recovered from the procedure. These cells could be detected by both the competitive repopulation assay and by repopulation of W/Wv recipients. In approximately 60% of the recipients from the competitive repopulation experiments, the contribution of the adherent marrow cells was relatively low early (8 to 10 weeks) after transplantation. With time, however, the hematopoietic contribution from these cells increased, reaching a stable level 20 to 30 weeks posttransplantation. In the remaining recipients (40%), the contribution from adherent cells was already significant within 8 to 10 weeks of transplantation and did not change dramatically throughout the course of the experiment. Adherent bone marrow containing significant numbers of HS cells was unable to protect mice from radiation death, indicating that these early cells in the absence of later-stage progenitors are unable to provide this function.
Key epitopes on the ESAT-6 antigen recognized in mice during the recall of protective immunity to Mycobacterium tuberculosis (1996)

The recall of long-lived immunity in a mouse model of tuberculosis (TB) is defined as an accelerated accumulation of reactive T cells in the target organs. We have recently identified Ag 85B and a 6-kilodalton early secretory antigenic target, designated ESAT-6, as key antigenic targets recognized by these cells. In the present study, preferential recognition of the ESAT-6 Ag during the recall of immunity was found to be shared by five of six genetically different strains of mice. Overlapping peptides spanning the sequence of ESAT-6 were used to map two T cell epitopes on this molecule. One epitope recognized in the context of H-2b,d was located in the N-terminal part of the molecule, whereas an epitope recognized in the context of H-2a,k covered amino acids 51 to 60. Shorter versions of the N-terminal epitope allowed the precise definition of a 13-amino acid core sequence recognized in the context of H-2b. The peptide covering the N-terminal epitope was immunogenic, and a T cell response with the same fine specificity as that induced during TB infection was generated by immunization with the peptide in IFA. In the C57BL/6j strain, this single epitope was recognized by an exceedingly high frequency of splenic T cells (approximately 1:1000), representing 25 to 35% of the total culture filtrate-reactive T cells recruited to the site of infection during the first phase of the recall response. These findings emphasize the relevance of this Ag in the immune response to TB and suggest that immunologic recognition in the first phase of infection is a highly restricted event dominated by a limited number of T cell clones.
Limiting Expert Testimony about Sexual Harassment Policies (1999)

reasonable person" standard for determining whether harassment "is sufficiently severe or pervasive to alter the conditions of the victim's employment and an abusive working environment") (internal citation and quotation marks omitted);
A Metabolic Node in Action: Chorismate-Utilizing Enzymes in Microorganisms (2001)

The shikimate pathway has been described as a metabolic tree with many branches that led to the synthesis of an extensive range of products. This pathway is present only in bacteria, fungi, and plants. While there is only little difference in the sequence of the chemical reactions of the pathway, significant differences exist in terms of organization and regulation. In the main trunk of the shikimate pathway, D-erythrose 4-phosphate and phosphoenolpyruvate are converted via shikimate to chorismate. Chorismate is the common precursor for the biosynthesis of the aromatic amino acids, phenylalanine, tyrosine, and tryptophan, but also for other products as diverse as folate cofactors, benzoid and naphthoid coenzymes, phenazines, and siderophores. Five chorismate-utilizing enzymes have been characterized in microorganisms: chorismate mutase, anthranilate synthase, aminodeoxychorismate synthase, isochorismate synthase, and chorismate pyruvate-lyase. In this review these enzymes are discussed in terms of the corresponding gene structures and regulation, nucleotide and protein sequences, protein structures, and reaction mechanisms. The main emphasis is on transcriptional and posttranslational regulatory mechanisms, in view of how a microbial cell exploits its chorismate pool in diverse anabolic pathways. Comparison of the chorismate-utilizing enzymes has shown that some of them share sequence similarity, suggesting divergent evolution and commonality in reaction mechanisms. However, other chorismate-utilizing enzymes are examples of convergent evolution toward similar reaction capabilities.
Left Ventricular Systolic Performance, Function, and Contractility in Patients With Diastolic Heart Failure (2005)

Patients with DHF had normal LV systolic performance, function, and contractility. The pathophysiology of DHF does not appear to be related to significant abnormalities in these systolic properties of the LV.
Novel mapping techniques for cardiac electrophysiology (2002)

ecause of its high success rate and low morbidity, radiofrequency (RF) catheter ablation has become first line treatment for many arrhythmias. In this procedure, one or more electrode catheters are advanced percutaneously through the vasculature to contact cardiac tissues. A diagnostic study is performed to define the arrhythmia mechanism, and subsequently an ablation catheter is positioned adjacent to the arrhythmogenic substrate. Radiofrequency energy of up to 50 W is delivered in the form of a continuous unmodulated sinusoidal waveform, typically for 60 seconds. Energy delivery is well tolerated by a mildly sedated patient, and results in a small (5 mm) well circumscribed lesion. Destruction of tissue critical for arrhythmogenesis (such as an accessory pathway) and its subsequent replacement with scar eliminates arrhythmia.
Facial emotion processing in major depression: a systematic review of neuroimaging findings (2011)

Further studies in remitted patients and high-risk samples are required to discern whether the described abnormalities represent state or trait characteristics of depression.
Synthese von selektiv N‐ funktionalisierten Polyamin‐Derivaten (1993)

Synthesis of Selectively N ‐Functionalized Polyamine Derivatives A threefold differently protected derivative 8 of the triamine spermidine ( 2 ) has been prepared in three steps starting from propane‐1,3‐diamine ( 1 ). The protected spermidine derivative 8 was converted to its spermine analogue 12 , a useful polyamine intermediate. In a convergent way, the fourfold differently protected derivative 18 of the tetraamine spermine ( 3 ) has been obtained by coupling the two different and separately prepared propane‐1,3‐diamine units 15 and 17 . Spermidine derivative 19 and spermine derivative 20 , both selectively protected at both primary amino groups, have been Prepared from the free polyamines 2 and 3 , respectively, in a direct approach.