gebhart/patrepeval huggingface dataset:
Labelling and imaging of single endogenous messenger RNA particlesin vivo (2015)

RNA molecules carry out widely diverse functions in numerous different physiological processes in living cells. The RNA life cycle from transcription, through the processing of nascent RNA, to the regulatory function of non-coding RNA and cytoplasmic translation of messenger RNA has been studied extensively using biochemical and molecular biology techniques. In this Commentary, we highlight how single molecule imaging and particle tracking can yield further insight into the dynamics of RNA particles in living cells. In the past few years, a variety of bright and photo-stable labelling techniques have been developed to generate sufficient contrast for imaging of single endogenous RNAs in vivo. New imaging modalities allow determination of not only lateral but also axial positions with high precision within the cellular context, and across a wide range of specimen from yeast and bacteria to cultured cells, and even multicellular organisms or live animals. A whole range of methods to locate and track single particles, and to analyze trajectory data are available to yield detailed information about the kinetics of all parts of the RNA life cycle. Although the concepts presented are applicable to all types of RNA, we showcase here the wealth of information gained from in vivo imaging of single particles by discussing studies investigating dynamics of intranuclear trafficking, nuclear pore transport and cytoplasmic transport of endogenous messenger RNA.
BingeOn Under the Microscope (2016)

The popularity of mobile devices for ubiquitous Internet access has led to exploding demand for relatively scarce cellular bandwidth. As a result, cellular operators increasingly turn to creative ways to manage their customers’ demand on capacity, using traffic shaping and transcoding and zero-rating. With zero-rating, Internet Service Providers (ISPs) do not charge users for traffic sent to/from certain services, often because those services agree to use limited bandwidth resources. Perhaps the most well-publicized of case in the U.S. is T-Mobile’s “BingeOn ” service, which zero-rates video streams from a large number of partner sites. In this paper, we address this issue by conducting a case study of T-Mobile’s zero-rating policy to understand its implications for users and content providers in terms of data quota, performance, and QoE. We focus on T-Mobile and BingeOn due to their recent controversy, but we believe that lessons learned from this exercise will readily apply to other carriers using similar technologies to implement their policies.
Glucose Transporter Expression in Brain: Relationship to Cerebral Glucose Utilization (1998)

Glucose is the principle energy source for mammalian brain. Delivery of glucose from the blood to the brain requires its transport across the endothelial cells of the blood-brain barrier and across the plasma membranes of neurons and glia, which is mediated by the facilitative glucose transporter proteins. The two primary glucose transporter isoforms which function in cerebral glucose metabolism are GLUT1 and GLUT3. GLUT1 is the primary transporter in the blood-brain barrier, choroid plexus, ependyma, and glia; GLUT3 is the neuronal glucose transporter. The levels of expression of both transporters are regulated in concert with metabolic demand and regional rates of cerebral glucose utilization. We present several experimental paradigms in which alterations in energetic demand and/or substrate supply affect glucose transporter expression. These include normal cerebral development in the rat, Alzheimer's disease, neuronal differentiation in vitro, and dehydration in the rat.
Leaderless polypeptides efficiently extracted from whole cells by osmotic shock (1997)

Three molecular foldases, DsbA, DsbC, and rotamase (ppiA), exhibited the unusual property of accumulating in an osmotically sensitive cellular compartment of Escherichia coli when their signal sequences were precisely removed by mutation. A mammalian protein, interleukin-1 (IL-1) receptor antagonist, behaved in a similar fashion in E. coli when its native signal sequence was deleted. These leaderless mutants (but not two control proteins overexpressed in the same system) were quantitatively extractable from whole cells by a variety of methods generally employed in the recovery of periplasmic proteins. A series of biochemical and genetic experiments showed that (i) leaderless DsbA (but not the wild type) was retained in a nonperiplasmic location; (ii) beta-galactosidase fusions to leaderless DsbA (but not to the wild type) exhibited efficient alpha complementation; (iii) none of the leaderless mutant proteins were substantially associated with cell membranes, even when they were overexpressed in cells; and (iv) leaderless DsbA was not transported to an osmotically sensitive compartment via a secA- or ftsZ-dependent mechanism. The observation that these proteins transit to some privileged cellular location by a previously undescribed mechanism(s)--absent their normal mode of (signal sequence-dependent) translocation--was unexpected. DsbA, rotamase, and IL-1, whose tertiary structures are known, appear to be structurally unrelated proteins. Despite a lack of obvious homologies, these proteins apparently have a common mechanism for intracellular localization. As this (putative) bacterial mechanism efficiently recognizes proteins of mammalian origin, it must be well conserved across evolutionary boundaries.
Newly developed primary culture of rat visceral adipocytes and their in vitro characteristics (2006)

We have recently developed a primary culture system for visceral adipocytes (VAs) using stomal-vascular cells (SVCs) isolated from the mesenteric fat tissue of male Sprague-Dawley rats of 3-5 weeks of age. Modified Dulbecco's modified Eagle medium (DMEM)/F12 containing 17 microM pantothenic acid, 33 microM biotin, 100 microM ascorbic acid, 1 microM octanoic acid, 50 nM triiodothyronine, 10 microg/ml insulin, 10% newborn calf serum (NCS), 100 units/ml penicillin and 100 microg/ml streptomycin was used as a basal culture medium, which did not contain any synthetic compounds usually used to promote adipogenesis, such as indomethacin, dexamethasone, or peroxisome proliferator-activated receptor (PPAR)-gamma agonists. The SVCs differentiated and proliferated efficiently, and formed a confluent monolayer in 3 days. The VAs accumulated lipids droplets in their cytoplasm at approximately 7 days. The differentiation rate from applied SVCs to mature adipocytes was >80% per culture. Adiponectin concentration in the medium increased from Day 5 to Day 7. Application of lipid emulsion stimulated maturation of the SVCs into VAs, as well as subsequent lipid accumulation. Norepinephrine (2 x 10(-5) mM) reduced the size of lipid particles and decreased triglyceride (TG) content in the matured adipocytes at 30 min. These results indicate that the new culture system is sufficient to maintain the physiological activity of visceral adipose tissue similar to that in vivo, making it an appropriate and useful tool for basic and applied research on obesity.
Algorithm 755: ADOL-C (1996)

The C++ package ADOL-C described here facilitates the evaluation of first and higher derivatives of vector functions that are defined by computer programs written in C or C++. The resulting derivative evaluation routines may be called from C/C++, Fortran, or any other language that can be linked with C. The numerical values of derivative vectors are obtained free of truncation errors at a small multiple of the run-time and randomly accessed memory of the given function evaluation program. Derivative matrices are obtained by columns or rows. For solution curves defined by ordinary differential equations, special routines are provided that evaluate the Taylor coefficient vectors and their Jacobians with respect to the current state vector. The derivative calculations involve a possibly substantial (but always predictable) amount of data that are accessed strictly sequentially and are therefore automatically paged out to external files.
Rapid Anastomosis of Endothelial Progenitor Cell–Derived Vessels with Host Vasculature Is Promoted by a High Density of Cotransplanted Fibroblasts (2009)

To ensure survival of engineered implantable tissues thicker than approximately 2-3 mm, convection of nutrients and waste products to enhance the rate of transport will be required. Creating a network of vessels in vitro, before implantation (prevascularization), is one potential strategy to achieve this aim. In this study, we developed three-dimensional engineered vessel networks in vitro by coculture of endothelial cells (ECs) and fibroblasts in a fibrin gel for 7 days. Vessels formed by cord blood endothelial progenitor cell-derived ECs (EPC-ECs) in the presence of a high density of fibroblasts created an interconnected tubular network within 4 days, compared with 5-7 days in the presence of a low density of fibroblasts. Vessels derived from human umbilical vein ECs (HUVECs) in vitro showed similar kinetics. Implantation of the prevascularized tissues into immune-compromised mice, however, revealed a dramatic difference in the ability of EPC-ECs and HUVECs to form anastomoses with the host vasculature. Vascular beds derived from EPC-ECs were perfused within 1 day of implantation, whereas no HUVEC vessels were perfused at day 1. Further, while almost 90% of EPC-EC-derived vascular beds were perfused at day 3, only one-third of HUVEC-derived vascular beds were perfused. In both cases, a high density of fibroblasts accelerated anastomosis by 2-3 days. We conclude that both EPC-ECs and a high density of fibroblasts significantly accelerate the rate of functional anastomosis, and that prevascularizing an engineered tissue may be an effective strategy to enhance convective transport of nutrients in vivo.
In Vitro Human T Cell Development Directed by Notch–Ligand Interactions (2008)

Traditionally, the study of human T cell development has relied on the availability of human and mouse thymic tissue. In this chapter, we outline a simple in vitro protocol for generating large numbers of human T-lineage cells from umbilical cord blood (CB)- derived hematopoietic stem cells (HSCs) using a bone marrow stromal cell line. This protocol is broken into three major steps: (1) the maintenance of a working stock of OP9 bone marrow stromal cells expressing the Notch receptor ligand Delta-like 1 (OP9- DL1), (2) the purification of human HSCs from umbilical CB, and (3) the initiation and maintenance/expansion of OP9-DL1 cocultures over time (see Fig. 1). The use of this system opens avenues for basic research as it equips us with a simple in vitro method for studying human T cell development.
Rising to the health challenge (2010)

The 2005-10 parliament will probably be remembered most for the scandal surrounding politicians’ expenses and the collapse of the banking system. But it is also likely to be remembered as a time when the UK had more nurse MPs than at any time.
Aspiration of Biological Viscoelastic Drops (2010)

Spherical cellular aggregates are in vitro systems to study the physical and biophysical properties of tissues. We present a novel approach to characterize the mechanical properties of cellular aggregates using a micropipette aspiration technique. We observe an aspiration in two distinct regimes: a fast elastic deformation followed by a viscous flow. We develop a model based on this viscoelastic behavior to deduce the surface tension, viscosity, and elastic modulus. A major result is the increase of the surface tension with the applied force, interpreted as an effect of cellular mechanosensing.
Trellis-coded modulation and transmit diversity: design criteria and performance evaluation (2002)

This paper presents the selection criteria for trellis codes used with the simple transmit diversity scheme proposed in Alamouti (1998) and reviewed in this paper. The optimum metrics for soft decision Viterbi decoding are derived and the asymptotic coding gains are calculated. The design method achieves both coding gain and a diversity order of 2 using 2 transmit antennas and 1 receive antenna. It is also demonstrated that trellis codes optimized for AWGN are also optimal for use in conjunction with the transmit diversity scheme in Rayleigh fading.
BRAIN COOLING IN THE PREVENTION OF BRAIN DAMAGE DURING PERIODS OF CIRCULATORY OCCLUSION IN DOGS (1954)

Harrison Department of Surgical Research, Schools of Medicine, University of Pennsylvania, Philadelphia, PA.
The Major Resistance Gene Cluster in Lettuce Is Highly Duplicated and Spans Several Megabases (1998)

At least 10 Dm genes conferring resistance to the oomycete downy mildew fungus Bremia lactucae map to the major resistance cluster in lettuce. We investigated the structure of this cluster in the lettuce cultivar Diana, which contains Dm3. A deletion breakpoint map of the chromosomal region flanking Dm3 was saturated with a variety of molecular markers. Several of these markers are components of a family of resistance gene candidates (RGC2) that encode a nucleotide binding site and a leucine-rich repeat region. These motifs are characteristic of plant disease resistance genes. Bacterial artificial chromosome clones were identified by using duplicated restriction fragment length polymorphism markers from the region, including the nucleotide binding site-encoding region of RGC2. Twenty-two distinct members of the RGC2 family were characterized from the bacterial artificial chromosomes; at least two additional family members exist. The RGC2 family is highly divergent; the nucleotide identity was as low as 53% between the most distantly related copies. These RGC2 genes span at least 3.5 Mb. Eighteen members were mapped on the deletion breakpoint map. A comparison between the phylogenetic and physical relationships of these sequences demonstrated that closely related copies are physically separated from one another and indicated that complex rearrangements have shaped this region. Analysis of low-copy genomic sequences detected no genes, including RGC2, in the Dm3 region, other than sequences related to retrotransposons and transposable elements. The related but divergent family of RGC2 genes may act as a resource for the generation of new resistance phenotypes through infrequent recombination or unequal crossing over.
Genomic structure and possible retroviral origin of the chicken CR1 repetitive DNA sequence family. (1984)

We have analyzed the sequence and structure of three CR1 family repetitive elements found in the region adjoining the 3' end of a chicken calmodulin gene. Members of this family are approximately equal to 300 base pairs long and are dispersed throughout the chicken genome. The present data, when taken together with that from four CR1s sequenced previously, reveal that the CR1 family has an overall structure possessing several features associated with the long terminal repeats of avian retroviruses. This finding implies that a retroviral mechanism may be responsible for the dispersion of CR1 sequences throughout the chicken genome. The seven different CR1 repeats that have been analyzed exist at defined locations in the chicken genome relative to nearby structural genes. A directional polarity has been assigned to the CR1 family based upon limited sequence homology to mammalian Alu-type sequences. Interestingly, whether present in 5' - or 3'-flanking DNA, the CR1 sequences have an inverse orientation such that they all "point toward" the nearby structural genes. This is consistent with the previously proposed concept that chicken CR1 sequences may be involved in defining the boundaries of active chromosomal domains of gene expression.
RANTES and MIP-1α Activate Stats in T Cells (1998)

The chemokines RANTES (regulated on activation, normal T cell expressed and secreted) and MIP (macrophage inflammatory protein)-1alpha have been implicated in regulating T cell functions. RANTES-induced T cell activation is apparently mediated via two distinct signal transduction cascades: one linked to recruitment of pertussis toxin-sensitive G proteins and the other linked to protein-tyrosine kinase activation. In this report, we identified that the transcription factors Stat1 and Stat3 (for signal transducers and activators of transcription) are rapidly activated in T cells in response to RANTES and MIP-1alpha. Nuclear extracts from MOLT-4 and Jurkat T cells treated with RANTES or MIP-1alpha contain tyrosine-phosphorylated Stat1:1 and Stat1:3 dimers that exhibit DNA-binding activity. We demonstrated that RANTES and MIP-1alpha treatment of Jurkat cells resulted in transcriptional activation of a Stat-inducible gene, c-fos, with kinetics consistent with Stat activation by these chemokines. RANTES and MIP-1alpha mediate their effects via shared chemokine receptors (CCRs): CCR1, CCR4, and CCR5. Our data revealed a concordance between chemokine-induced Stat activation and c-fos induction and CCR4 and CCR5 expression. These findings indicate that chemokine-mediated activation of G-protein-coupled receptors leads to signal transduction that invokes intracellular phosphorylation intermediates used by other cytokine receptors.
Purification of diacylglycerol:acyltransferase from rat liver to near homogeneity. (1994)

A method to isolate a protein related to the diacylglycerol:acyltransferase (DGAT) activity in rat liver microsomes has been developed. The microsomes were treated with sodium deoxycholate (DOC; 0.1 mg/mg protein) at a concentration of 1 mM, i.e., below the critical micellar concentration (CMC), to remove luminal and loosely bound proteins. Three percent of the DGAT activity and all of the acylCoA hydrolyse activity were present in the supernatant, i.e., among the extracted loosely bound proteins. The insoluble material, recovered as a pellet, was suspended in DOC (1.6 mg/ml and mg protein in the original microsomes), and subjected to multiple, short (1-2 sec) sonications. CHAPS (3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate; 5 mg/ml) was then added, and the sonication was repeated. The detergent-treated microsomal membranes were filtered through a 0.22-micron filter and chromatographed on a Superose 6 column from which the DGAT activity was recovered in a high molecular mass fraction. A monoclonal antibody that reacted with this fraction was raised and used in immunoaffinity experiments. This antibody removed 93 +/- 6% (mean +/- SD, n = 4) of the DGAT activity present in solution and 44 +/- 6% (mean +/- SD, n = 5) of the applied activity could be recovered after desorption. The antibody recognized a 60 kDa protein upon Western blot of rat liver microsomal proteins as well as of the DGAT-containing fraction from the Superose 6 column. A 60 kDa protein was highly enriched in the DGAT-containing retained fraction from the immunoaffinity chromatography. This 60 kDa protein reacted with the monoclonal antibody on Western blot. In addition to the 60 kDa protein, the retained fraction from the immunoadsorber contained a 77 kDa protein. This protein did not react with the monoclonal antibody on Western blots. Neither the 60 nor the 77 kDa protein reacted with antibodies to mouse immunoglobulins or showed any unspecific reaction with immunoglobulins.
Costimulatory blockade in patients with rheumatoid arthritis: A pilot, dose‐finding, double‐blind, placebo‐controlled clinical trial evaluating CTLA‐4Ig and LEA29Y eighty‐five days after the first infusion (2002)

Both of the costimulatory blocking molecules studied were generally safe and well tolerated. As compared with placebo, both CTLA-4Ig and LEA29Y demonstrated efficacy in the treatment of RA.
Chemically Active Substitutional Nitrogen Impurity in Carbon Nanotubes (2003)

We investigate the nitrogen substitutional impurity in semiconducting zigzag and metallic armchair single-wall carbon nanotubes using ab initio density functional theory. At low concentrations (less than 1 at. %), the defect state in a semiconducting tube becomes spatially localized and develops a flat energy level in the band gap. Such a localized state makes the impurity site chemically and electronically active. We find that if two neighboring tubes have their impurities facing one another, an intertube covalent bond forms. This finding opens an intriguing possibility for tunnel junctions, as well as the functionalization of suitably doped carbon nanotubes by selectively forming chemical bonds with ligands at the impurity site. If the intertube bond density is high enough, a highly packed bundle of interlinked single-wall nanotubes can form.
Challenges of thalidomide distribution in a hospital setting (1999)

The various physician, patient, and pharmacy requirements for participation in the System for Thalidomide Education and Prescribing Safety (S.T.E.P.S.) program and procedures that institutions may implement in order to comply with these requirements are described. In 1998, FDA approved the marketing of thalidomide (Thalomid, Celgene). Because of the drug's known teratogenic effects, FDA tightly controls the distribution of thalidomide in the United States. To comply with FDA requirements, Celgene developed the S.T.E.P.S. oversight program, which includes registration of thalidomide prescribers and pharmacies that dispense thalidomide, extensive patient education about the risks associated with thalidomide, and a registry of all patients receiving thalidomide. The S.T.E.P.S. program is considered part of the product label. The pharmacy requirements of the program were developed with a focus on a retail pharmacy practice model, which does not adequately reflect current hospital practice. The pharmacy department of the National Institutes of Health Clinical Center developed a model that adapts the S.T.E.P.S. program requirements to inpatient and outpatient institutional pharmacy practice. Procedures for registering patients and prescribers and dispensing thalidomide in the hospital setting were developed; the procedures were designed to meet the needs of both the inpatient and outpatient pharmacies and to comply with the requirements of the S.T.E.P.S. program.
Effect of Anticonvulsant Felbamate on GABAA Receptor System (1991)

Felbamate (FBM, 2-phenyl-1,3-propanediol dicarbamate), a potential antiepileptic drug (AED), has an unknown mechanism of action. We examined possible interaction of FBM with GABAA ergic transmission. FBM did not alter specific binding of ligands to GABA. benzodiazepine, and picrotoxin sites of the oligomeric GABAA receptor complex to rat brain membranes, nor did it enhance the effect of GABA on 36Cl-influx in well-characterized cultured spinal cord neurons. These results suggest that the anticonvulsant effect of FBM does not involve GABAA ergic transmission.
Deep learning spectroscopic stimulated Raman scattering microscopy (2019)

Spectroscopic stimulated Raman scattering (SRS) is a label-free chemical imaging modality enabling visualization of molecules in living systems with high specificity. Among various spectroscopic SRS imaging methods, a convenient way is through linearly chirping two femtosecond lasers and tuning their temporal delay, which in turn corresponds to different Raman shifts. Currently, the acquisition speed using a resonant mirror is 3 seconds (80 microseconds per spectrum), which is insufficient for imaging samples with high motility. In this work, we aim to push the imaging speed using a 50-kHz polygon scanner as a delay line tuner, achieving a speed of 20 microseconds per spectrum. At such high speeds, to overcome the signal level decrease due to reduced signal integration time, we apply a U-Net deep learning framework, which first takes pairs of spectroscopic SRS images at different speeds as training samples, with high-speed, low-signal images as input and low speed, high-signal ones as output. After training, the network is capable of rapidly transforming a low-signal spectroscopic image to a high-signal version. Consequently, our design can generate ultrafast spectroscopic SRS image while maintaining the signal level comparable to the output with longer signal integration time.