gebhart/patrepeval huggingface dataset:
Sequence preferences in cleavage of dsDNA and ssDNA by the extracellular Serratia marcescens endonuclease (1995)

The preferred cleavage sites in dsDNA and ssDNA for the extracellular Serratia marcescens endonuclease (commercially available as BENZONASE) were identified by limited digestion of PCR-generated substrates. Two different dsDNA substrates were synthesized by using either radioactively or fluorescent dye labeled primers. ssDNA of identical sequence to one of the fluorescent dye labeled duplex strands was prepared by affinity chromatography. Cleavage experiments carried out under single hit conditions demonstrate that the enzyme shows preferences for GC-rich regions in dsDNA, in particular d(G).d(C)-tracts, and avoids cleavage of d(A).d(T)-tracts. There is a correlation between cleavage at a given position in one strand with cleavage at the same position in the other strand of the duplex. ssDNA cleavage occurs at somewhat different preferred sites than observed in dsDNA. On dsDNA, the Serratia nuclease produces a very different cleavage pattern compared to bovine pancreatic DNase I, with the notable exception that both enzymes avoid d(A).d(T)-tracts. In general, the Serratia nuclease compared to DNase I is a slightly more nonspecific endonuclease that attacks a particular substrate more evenly under standard reaction conditions. At high ionic strength or in the presence of DMSO, it becomes more nonspecific. Addition of urea, however, makes the enzyme more selective than observed under standard conditions. From these results which were confirmed by the results of cleavage experiments with synthetic oligodeoxynucleotides, we conclude that the Serratia nuclease like DNase I is sensitive to global features of the DNA, for example, the width of the minor groove. In addition, localized sequence-dependent interactions between substrate and nuclease determine whether a site is cleaved preferentially. Some of these interactions seem to be the same for ds- and ssDNA.
Chromosome deletion in a case of retinoblastoma (1963)

SUMMARY In the course of an investigation of karyotypes in patients with retinoblastoma, one was found in whom all cells showed a deletion in the longer arm of one of the large acrocentric chromosomes. Five other patients had normal karyotypes. The writers wish to thank Dr White Franklin for drawing attention to case no. 1 and arranging for the biopsy, Dr Joy D. A. Delhanty for the fibroblast culture in case no. 1, Dr R. G. Chitham for the culture in case no. 6, Dr Sylvia D. Lawler for suggestions and Miss Dorothy Newlyn for family history investigations. The work was carried out with the aid of a grant RG‐6984 from the United States Public Health Service.
Guidelines for energy-efficient coils: coils designed for magnetic stimulation of the heart. (1991)

Magnetic stimulation of the heart requires high magnetic field energy and results in considerable Joulean dissipation. Energetically efficient and mechanically robust coils were designed for magnetic stimulation of the canine heart. Circular coils with rectangular cross section oriented either parallel or perpendicular to the skin were employed. A reasonable compromise between coil size and energy efficiency is achieved when the outer radius is twice the target depth. Nearly optimal efficiency is obtained by coils with annular width and height of 60% and 20% of the radius, respectively. A coplanar pair of coils parallel to the skin surface requires less energy and provides a more localized stimulus than a single coil. Placing a single coil perpendicular to the skin provides stimulus localization comparable to that of a coplanar pair; however, a single coil requires approximately 4 times the energy. The large coil currents required for cardiac stimulation exert Lorentz forces on the conductors that may exceed their tensile strength, emphasizing the need for an adequate support structure. Coils fabricated along the preceding guidelines were used to stimulate dog hearts repeatedly, requiring magnetic fields with energy greater than 12,000 J, without coil failure. Although the principles for coil design described herein were applied to a cardiac stimulator, they can also be applied to coils for other tissues, resulting in less coil heating, better stimulus localization and less power consumption.
GMP-140, a platelet alpha-granule membrane protein, is also synthesized by vascular endothelial cells and is localized in Weibel-Palade bodies. (1989)

We used an immunoperoxidase procedure to examine the tissue distribution of the platelet alpha-granule membrane protein, GMP-140. In addition to its presence in megakaryocytes and platelets, GMP-140 antigen was found in vascular endothelial cells of diverse human organs, but it was not detected in other types of secretory cells. [35S]Cysteine-labeled human umbilical vein endothelial cells synthesized a GMP-140 molecule containing complex N-linked oligosaccharides similar to those previously demonstrated in platelets and the megakaryocytic HEL cell line. Using an immunogold procedure on frozen thin sections of endothelial cells, we found GMP-140 antigen to be localized to membranes of electron-dense storage granules. In double-label experiments there was colocalization of GMP-140 with vWf, indicating that these granules are Weibel-Palade bodies. When endothelial cells were stimulated with histamine, GMP-140 rapidly redistributed to the plasma membrane. Immunoassays of cell lysates indicated that, relative to total cell protein, less GMP-140 is present in human umbilical vein endothelial cells than in platelets. The restricted expression of GMP-140 in secretory granules of platelets and endothelium suggests that it has a specific function in the vascular system rather than a general role related to inducible secretion.
Cardiovascular safety with linagliptin in patients with type 2 diabetes mellitus: a pre-specified, prospective, and adjudicated meta-analysis of a phase 3 programme (2012)

These results from a large Phase 3 programme support the hypothesis that linagliptin may have CV benefits in patients with T2DM.
Biodegradable PLGA Microcarriers for Injectable Delivery of Chondrocytes: Effect of Surface Modification on Cell Attachment and Function (2004)

Poly(D,L-lactic-co-glycolic acid) (PLGA) microspheres were prepared by an oil/water emulsion solvent evaporation method to use as an injectable microcarrier for cell delivery. Three different kinds of PLGA microspheres having hydrophobic, negatively charged, and positively charged surfaces were prepared. Hydrophobic and negatively charged PLGA microspheres were prepared by using terminally capped and uncapped PLGA polymer, respectively. Positively charged PLGA microspheres were prepared by blending PLGA with PLGA-g-poly(L-lysine) graft copolymer as a surface modifying agent. Bovine chondrocytes were cultured on the three PLGA microspheres under serum conditions to comparatively evaluate cell attachment, cell proliferation, and cell function with respect to surface properties. Positively charged PLGA microspheres showed the highest cell attachment, growth, and function compared to hydrophobic and negatively charged microspheres. Surface-modified PLGA microspheres can potentially be used as an injectable delivery system for cells into a tissue defect site.
Transformation of meta-stable calcium silicate hydrates to tobermorite: reaction kinetics and molecular structure from XRD and NMR spectroscopy (2009)

Understanding the integrity of well-bore systems that are lined with Portland-based cements is critical to the successful storage of sequestered CO2 in gas and oil reservoirs. As a first step, we investigate reaction rates and mechanistic pathways for cement mineral growth in the absence of CO2 by coupling water chemistry with XRD and NMR spectroscopic data. We find that semi-crystalline calcium (alumino-)silicate hydrate (Al-CSH) forms as a precursor solid to the cement mineral tobermorite. Rate constants for tobermorite growth were found to be k = 0.6 (+/- 0.1) x 10(-5) s(-1) for a solution:solid of 10:1 and 1.6 (+/- 0.8) x 10(-4) s(-1) for a solution:solid of 5:1 (batch mode; T = 150 degrees C). This data indicates that reaction rates for tobermorite growth are faster when the solution volume is reduced by half, suggesting that rates are dependent on solution saturation and that the Gibbs free energy is the reaction driver. However, calculated solution saturation indexes for Al-CSH and tobermorite differ by less than one log unit, which is within the measured uncertainty. Based on this data, we consider both heterogeneous nucleation as the thermodynamic driver and internal restructuring as possible mechanistic pathways for growth. We also use NMR spectroscopy to characterize the site symmetry and bonding environment of Al and Si in a reacted tobermorite sample. We find two [4]Al coordination structures at delta iso = 59.9 ppm and 66.3 ppm with quadrupolar product parameters (PQ) of 0.21 MHz and 0.10 MHz (+/- 0.08) from 27Al 3Q-MAS NMR and speculate on the Al occupancy of framework sites by probing the protonation environment of Al metal centers using 27Al{1H}CP-MAS NMR.
[Etiology of Kii ALS/PDC, featuring a mineral hypothesis]. (2007)

In 1960s, epidemiological surveys in both Kozagawa and Hobara foci revealed the characteristics of Kii ALS as follows: younger age at onset. M/F ratio of 1.5-1.8:1, familial clustering and presence of Alzheimer's neurofibrillary tangles (NFTs). The segregation ratio of six families in Hobara was estimated 0.304 +/- 0.096 ( p +/- 95% confidence level), suggesting a multifactorial inheritance. Kii environmental studies showed that extremely low contents of calcium (Ca) and magnesium (Mg) in the birthplace's rivers of ALS patients inversely and significanthy correlated with high mortality rates, aluminum (Al) contents, and densities of hipocampal NFTs. In experimental animals, a low Ca and Mg, and high Al content diet led to a neuronal loss with axonal swellings and chromatolysis, and positive staining of cortical neurons with anti-PHF antibodies. Recently, a significant loss of dopaminergic neurons was identified exclusively in the substantia nigra in 1-year-old rat fed under a low Mg intake over two generations. Kii people may have a predisposition to develop ALS/PDC precipitated by their environmental status, suggesting gene-environmental interactions.
EFFECT OF HEAT TREATMENT ON THE STRUCTURE OF SiC−Si3N4 COMPOSITE ULTRAFINE POWDER (1996)

Effect of heat treatment on the structure of SiC−Si 3 N 4 composite ultrafine powder was studied. SiC-Si 3 N 4 composite ultrafine powder synthesized by laser-induced gas-phase reaction was heat-treated at various temperatures below 1773 K in 99% Ar +1% H 2 gas mixture. The change of the structure was studied by chemical analysis, x-ray diffraction (XRD), and transmission electron microscope (TEM). The structure of the powder did not change significantly in lattice constant, particle size, and composition by the treatment up to 1573 K . The structure of the powder changed drastically by the treatment above 1673 K . The broad XRD pattern due to β- Si for the original powder changed to the four phases of β- SiC , Si and α, β- Si 3 N 4 by the treatment at 1773 K , accompanied by large increases in particle size and lattice parameter, and decreases in nitrogen content and specific surface area.
A Passive Radio-Frequency pH-Sensing Tag for Wireless Food-Quality Monitoring (2011)

We present a new method, suitable for food quality management by wirelessly monitoring pH level changes in food with a flexible pH sensor embedded in a batteryless radio-frequency (RF) transponder. The wireless sensor tag includes a flexible pH sensor based on miniature iridium oxide (IrO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">x</sub> ) and silver chloride (AgCl) sensing electrodes integrated on a deformable substrate, and batteryless wireless communication circuitry. The sensor tag and reader system is designed to achieve convenient, long-term, and on-demand wireless in situ monitoring of food quality, especially for large-quantity applications and continuous monitoring from place of production to retail stores. Low-cost IrO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">x</sub> sol-gel fabrication process was applied on polymeric substrates to form the flexible sensing films, and a sensitivity of -49.7 mV/pH was achieved. Inducting coupling provides electromagnetic energy from the reader to drive the transponder circuits that retransmit the sensor-data modulated signals back to the reader. The electrochemical potential created by the IrO <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">x</sub> /AgCl sensing electrodes is converted to a modulated frequency and the system achieves a sensitivity of 633 Hz/pH. The wireless pH sensing system was tested for in situ monitoring of the spoilage processes in fish meats continuously for over 18 h. The feasibility of wirelessly monitoring pH values in fish meats that could be used to identify spoilage remotely has been demonstrated.
DNA-centered approaches to characterize regulatory protein–DNA interaction complexes (2009)

Gene regulation is mediated by site-specific DNA-binding proteins or transcription factors (TFs), which form protein complexes at regulatory loci either to activate or repress the expression of a target gene. The study of the dynamic properties of these regulatory DNA-binding complexes has so far been dominated by protein-centered methodologies, aiming to characterize the DNA-binding behavior of one specific protein at a time. With the emerging evidence for a role of DNA in allosterically influencing DNA-binding protein complex formation, there is renewed interest in DNA-centered approaches to capture protein complexes on defined regulatory loci and to correlate changes in their composition with alterations in target gene expression. In this review, we present the current state-of-the-art in such DNA-centered approaches and evaluate recent technological improvements in the purification as well as in the identification of regulatory DNA-binding protein complexes within or outside their biological context. Finally, we suggest possible areas of improvement and assess the putative impact of DNA-centered methodologies on the gene regulation field for the forthcoming years.
Nutrient Supply and Intervertebral Disc Metabolism (2006)

The metabolic environment of disc cells is governed by the avascular nature of the tissue. Because cellular energy metabolism occurs mainly through glycolysis, the disc cells require glucose for survival and produce lactic acid at high rates. Oxygen is also necessary for cellular activity, although not for survival; its pathway of utilization is unclear. Because the tissues are avascular, disc cells depend on the blood supply at the margins of the discs for their nutrients. The nucleus and inner anulus of the disc are supplied by capillaries that arise in the vertebral bodies, penetrate the subchondral bone, and terminate at the bone-disc junction. Small molecules such as glucose and oxygen then reach the cells by diffusion under gradients established by the balance between the rate of transport through the tissue to the cells and the rate of cellular demand. Metabolites such as lactic acid are removed by the reverse pathway. The concentrations of nutrients farthest from the source of supply can thus be low; oxygen concentrations as low as 1% have been measured in the discs of healthy animals. Although gradients cannot be measured easily in humans, they can be calculated. Measured concentrations in surgical patients are in agreement with calculated values.
Modeling and fabrication of self-assembling micron-scale rollup structures (2004)

Self-assembling micron-scale structures based on standard photolithographic and thin film deposition techniques are investigated. Differences in residual stress between suc-cessive thin film layers causes the structures to roll up when an underlying sacrificial layer is removed. The primary structure of interest was a swiss-roll structure com-prised of alternating layers of metal and insulator so that the self-assembled system forms an RCL electrical circuit with a well-defined resonant frequency. So-called nanoscroll structures, comprised of two swiss-rolls attached at a common end, were the most commonly observed fabrication result and are expected to have electrical properties very similar to swiss rolls. It has been predicted that such electrical prop-erties lead to a negative effective magnetic permeability for a narrow frequency band, potentially in the far infrared region. These structures thus can contribute a vital component (peff &amp;lt; 0) necessary for developing a LHM (left-handed material). Many successful materials combinations have been demonstrated. The layers in the recom-mended system are (from the bottom up) silicon dioxide, chrome, gold, and chrome.
Duodenal—Jejunal Bypass Sleeve: A Totally Endoscopic Device for the Treatment of Morbid Obesity (2007)

Morbid obesity affects over 15 million people in the United States. Nonsurgical management produces sustained weight loss in less than 5% of patients. Despite associated comorbidities, less than 1% of obese patients seek surgical intervention. Less invasive procedures have been developed with varying success. The Endobarrier( trade mark) (GI Dynamics(trade mark), Watertown, MA) duodenal-jejunal bypass sleeve is a totally endoscopically delivered device designed to produce weight loss in the morbidly obese. We describe the first placement of a duodenal-jejunal bypass sleeve in a patient in the United States. A blinded, randomized, prospective clinical trial was approved by the Food and Drug Administration to evaluate safety and efficacy of a novel device for weight loss in the obese. The first patient enrolled was a 36-year-old woman with body mass index of 45.2. After informed consent, endoscopic placement of the device under general anesthesia was performed using fluoroscopy to confirm positioning. The device was placed without complications. At conclusion of the 3-month study period, the device was removed endoscopically. Total weight lost by the patient was 9.09 kg. Described herein is the first deployment of the duodenal-jejunal bypass sleeve in North America. The device is delivered in a totally endoscopic manner in morbidly obese patients. In our patient, total weight loss at 3 months was 9.09 kg. Continued follow-up and enrollment is ongoing to demonstrate patient safety and efficacy. Additional studies are being performed to elucidate mechanism of weight loss and future clinical applications of this device.
Spoken language recognition and understanding (1992)

The goal of this research is to demonstrate spoken language systems in support of interactive problem solving. The system accepts continuous speech input and handles multiple speakers without explicit speaker enrollment. The MIT spoken language system combines SUMMIT, a segment-based speech recognition system, and TINA, a probabilistic natural language system, to achieve speech understanding. The system engages in interactive dialogue with the user, providing output in the form of tabular displays, as well as spoken and written output. The system has been demonstrated on several applications, including travel planning and direction assistance.
On-chip microextraction for proteomic sample preparation of in-gel digests (2002)

Despite the high sensitivity and relatively high tolerance for contaminants of matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) there is often a need to purify and concentrate the sample solution, especially after in-gel digestion of proteins separated by two-dimensional gel electrophoresis (2-DE). A silicon microextraction chip (SMEC) for sample clean-up and trace enrichment of peptides was manufactured and investigated. The microchip structure was used to trap reversed-phase chromatography media (POROS R2 beads) that facilitates sample purification/enrichment of contaminated and dilute samples prior to the MALDI-TOF MS analysis. The validity of the SMEC sample preparation technique was successfully investigated by performing analysis on a 10 nM peptide mixture containing 2 m urea in 0.1 m phosphate-buffered saline with MALDI-TOF MS. It is demonstrated that the microchip sample clean-up and enrichment of peptides can facilitate identification of proteins from 2-DE separations. The microchip structure was also used to trap beads immobilized with trypsin, thereby effectively becoming a microreactor for enzymatic digestion of proteins. This microreactor was used to generate a peptide map from a 100 nM bovine serum albumin sample.
Miniaturizing Ultrasonic System for Portable Health Care and Fitness (2016)

We present a miniaturized portable ultrasonic imager that uses a custom ASIC and a piezoelectric transducer array to transmit and capture 2-D sonographs. The ASIC, fabricated in 0.18 μm 32 V CMOS process, contains 7 identical channels, each with high-voltage level-shifters, high-voltage DC-DC converters, digital TX beamformer, and RX front-end. The chip is powered by a single 1.8 V supply and generates 5 V and 32 V internally using on-chip charge pumps with an efficiency of 33% to provide 32 V pulses for driving a bulk piezoelectric transducer array. The assembled prototype can operate up to 40 MHz, with beamformer delay resolution of 5 ns, and has a measured sensitivity of 225 nV/Pa , minimum detectable signal of 622 Pa assuming 12 dB SNR ( 4σ larger than the noise level), and data acquisition time of 21.3 ms. The system can image human tissue as deep as 5 cm while consuming less than 16.5 μJ per pulse-echo measurement. The high energy efficiency of the imager can enable a number of consumer applications.
Nanoparticle tracking analysis monitors microvesicle and exosome secretion from immune cells (2012)

Nanoparticle tracking analysis permits the determination of both the size distribution and relative concentration of microvesicles, including exosomes, in the supernatants of cultured cells and biological fluids. We have studied the release of microvesicles from the human lymphoblastoid T-cell lines Jurkat and CEM. Unstimulated, both cell lines release microvesicles in the size range 70-90 nm, which can be depleted from the supernatant by ultracentrifugation at 100 000 g, and by anti-CD45 magnetic beads, and which by immunoblotting also contain the exosome-associated proteins Alix and Tsg101. Incubation with known potentiators of exosome release, the ionophores monensin and A23187, resulted in a significant increase in microvesicle release that was both time and concentration dependent. Mass spectrometric analysis of proteins isolated from ultracentrifuged supernatants of A23187-treated cells revealed the presence of exosome-associated proteins including heat-shock protein 90, tubulin, elongation factor α1, actin and glyceraldehyde 3-phosphate dehydrogenase. Additionally, treatment of peripheral blood monocyte-derived dendritic cells with bacterial lipopolysaccharide displayed an increase in secreted microvesicles. Consequently, nanoparticle tracking analysis can be effectively applied to monitor microvesicle release from cells of the immune system.
Base-stacking and base-pairing contributions to helix stability: thermodynamics of double-helix formation with CCGG, CCGGp, CCGGAp, ACCGGp, CCGGUp, and ACCGGUp (1983)

The thermodynamics of double-helix formation in 1 M NaCl have been measured spectrophotometrically for CCGG, CCGGp, CCGGAp, ACCGGp, CCGGUp, and ACCGGUp. The results indicate additional double-helical stability is conferred by the terminal unpaired bases. The 3' A stabilizes the double helix more than the 5' A or the 3' U. The increased stability is due to a more favorable enthalpy change for double-helix formation. Comparison of the thermodynamics for CCGG, ACCGGp, CCGGUp, and ACCGGUp indicates stacking interactions are somewhat more important than pairing interactions in determining the stability of the terminal AU base pairs in ACCGGUp.