gebhart/patrepeval huggingface dataset:
Subnanometer optical coherence tomographic vibrography (2012)

The ability to quantify and visualize submicrometer-scale oscillatory motions of objects in three dimensions has a wide range of application in acoustics, materials sciences, and medical imaging. Here we demonstrate that volumetric snapshots of rapid periodic motion can be captured using optical coherence tomography (OCT) with subnanometer-scale motion sensitivity and microsecond-scale temporal resolution. This technique, termed OCT vibrography, was applied to generate time-resolved volumetric vibrographs of a miniature drum driven acoustically at several kilohertz.
Double-Target Antisense U7 snRNAs Promote Efficient Skipping of an Aberrant Exon in Three Human -Thalassemic Mutations (1999)

We have used three beta-thalassemic mutations, IVS2-654, -705 and -745, that create aberrant 5' splice sites (5' ss) and activate a common cryptic 3' ss further upstream in intron 2 of the human beta-globin gene to optimize a generally applicable exon-skipping strategy using antisense derivatives of U7 small nuclear RNA (snRNA). Introducing a modified U7 snRNA gene carrying an antisense sequence against the cryptic 3' ss into cultured cells expressing the mutant beta-globin genes, restored correct beta-globin mRNA splicing for all three mutations, but the efficiency was much weaker for IVS2-654 than for the other mutations. The length of antisense sequence influenced the efficiency with an optimum of approximately 24 nucleotides. Combining two antisense sequences directed against different target sites in intron 2, either on separate antisense RNAs or, even better, on a single U7 snRNA, significantly enhanced the efficiency of splicing correction. One double-target U7 RNA was expressed on stable transformation resulting in permanent and efficient suppression of the IVS2-654 mutation and production of beta-globin. These results suggest that forcing the aberrant exon into a looped secondary structure may strongly promote its exclusion from the mRNA and that this approach may be used generally to induce exon skipping.
Identification of markers linked to disease-resistance genes by bulked segregant analysis: a rapid method to detect markers in specific genomic regions by using segregating populations. (1991)

We developed bulked segregant analysis as a method for rapidly identifying markers linked to any specific gene or genomic region. Two bulked DNA samples are generated from a segregating population from a single cross. Each pool, or bulk, contains individuals that are identical for a particular trait or genomic region but arbitrary at all unlinked regions. The two bulks are therefore genetically dissimilar in the selected region but seemingly heterozygous at all other regions. The two bulks can be made for any genomic region and from any segregating population. The bulks are screened for differences using restriction fragment length polymorphism probes or random amplified polymorphic DNA primers. We have used bulked segregant analysis to identify three random amplified polymorphic DNA markers in lettuce linked to a gene for resistance to downy mildew. We showed that markers can be reliably identified in a 25-centimorgan window on either side of the targeted locus. Bulked segregant analysis has several advantages over the use of near-isogenic lines to identify markers in specific regions of the genome. Genetic walking will be possible by multiple rounds of bulked segregation analysis; each new pair of bulks will differ at a locus identified in the previous round of analysis. This approach will have widespread application both in those species where selfing is possible and in those that are obligatorily outbreeding.
Mesenchymal stromal cells (2006)

Mesenchymal stromal cells are a biologically important cell population that are able to support hematopoiesis, can differentiate along mesenchymal and nonmesenchymal lineages in vitro, are capable of suppressing alloresponses and appear to be nonimmunogenic. These properties suggest emerging roles for mesenchymal stromal cells in cell therapy.
Metabolic Catastrophe in Mice Lacking Transferrin Receptor in Muscle (2015)

Transferrin receptor (Tfr1) is ubiquitously expressed, but its roles in non-hematopoietic cells are incompletely understood. We used a tissue-specific conditional knockout strategy to ask whether skeletal muscle required Tfr1 for iron uptake. We found that iron assimilation via Tfr1 was critical for skeletal muscle metabolism, and that iron deficiency in muscle led to dramatic changes, not only in muscle, but also in adipose tissue and liver. Inactivation of Tfr1 incapacitated normal energy production in muscle, leading to growth arrest and a muted attempt to switch to fatty acid β oxidation, using up fat stores. Starvation signals stimulated gluconeogenesis in the liver, but amino acid substrates became limiting and hypoglycemia ensued. Surprisingly, the liver was also iron deficient, and production of the iron regulatory hormone hepcidin was depressed. Our observations reveal a complex interaction between iron homeostasis and metabolism that has implications for metabolic and iron disorders.
Hardware Acceleration of Software Transactional Memory (2005)

Transactional memory (TM) systems seek to increase scalability, reduce programming complexity, and overcome the various semantic problems associated with locks. Software TM proposals run on stock processors and provide substantial flexibility in policy, but incur significant overhead for data versioning and validation in the face of conflicting transactions. Hardware TM proposals have the advantage of speed, but are typically highly ambitious, embed significant amounts of policy in silicon, and provide no clear migration path for software that must also run on legacy machines. We advocate an intermediate approach, in which hardware is used to accelerate a TM implementation controlled fundamentally by software. We present a system, RTM, that embodies this approach. It consists of a novel transactional MESI (TMESI) protocol and accompanying TM software. TMESI eliminates the key software overheads of data copying, garbage collection, and validation, without introducing any global consensus algorithm in the cache coherence protocol (a commit is allowed to perform using only a few cycles of completely local operation). The only change to the snooping interface is a “threatened” signal analogous to the existing “shared” signal. By leaving policy to software, RTM allows us to experiment with a wide variety of policies for contention management, deadlock and livelock avoidance, data granularity, nesting, and virtualization.
Abstract 11349: The Natriuretic Peptide Prohormones are Processed into Active Peptides in the Normal Human Circulation and the Processing is Preserved in Heart Failure (2012)

Introduction: We have reported that proBNP1-108 circulates in normal humans and is processed to mature BNP1-32 in human blood thus advancing the novel paradigm that proBNP1-108 is a circulating hormone. To date it remains unclear if proANP1-127 and proCNP1-103 also are processed in the circulation. We thought to determine if pre/proNP is processed in circulation and the processed forms can activate cGMP production, the second messenger of the natriuretic peptide receptors GC-A and GC-B. Since BNP1-32 is deficient and most abundant circulating BNP molecular form is proBNP1-108 in heart failure (HF), we hypothesize that each pro-or preproNPs is processed into active forms in normals but may not be in HF patients ex vivo . Methods: Fresh serum or EDTA plasma was obtained from normal volunteers (n=11) and patients with HF (n=12). Samples were incubated with or without exogenous pro- or preproNP tagged with 6 Histidines in the C-terminal end to facilitate isolation of mature processed forms. The processed peptides were isolated by immunoprecipitation and detected by Western Blot, and then sequenced. GC-A or GC-B expressing HEK293 cells were treated with or without the isolated peptides for 10 min and cGMP activity was measured. Results: All three precursor pre/pro NPs were processed in normal human serum. Specifically, proBNP1-108 was processed into BNP1-32*, preproANP1-151 was processed into ANP1-28* and preproCNP1-126 was processed into CNP1-53* in normal human serum (*confirmed by sequence analysis). Processed forms from each pre/proNPs were significantly increased at 5 min and persisted for 15 min, with no significant difference between normals and HF patients. Isolated processed peptides from preproANP and proBNP significantly stimulated cGMP production in GC-A cells, and those from preproCNP significantly stimulated cGMP production in GC-B cells in a pattern similar to mature ANP, BNP, and CNP. Conclusions: All three pre/proNPs are processed in both normal and HF circulation and all processed NPs are biologically active cGMP-activating molecular forms. There is no impaired processing of exogenous non-glycosylated pre/proNPs in HF, suggesting the emerging new concept about the processing of proNPs in the circulation of both normal and disease states.
All-silicon omnidirectional mirrors based on one-dimensional photonic crystals (2003)

We report on the fabrication of monolithic omnidirectional mirrors based on one-dimensional photonic crystals. The mirrors are comprised of chirped and unchirped multiple layers of microporous silicon. Porosities have been chosen to achieve an optimal low refractive index nL∼1.5 and a high refractive index nH∼2.55. Unchirped structures, centered in the near-infrared, exhibit an omnidirectional reflection band of 100 nm, in agreement with the calculated photonic band structure. Chirped structures exhibit an enlarged omnidirectional stop band (340 nm). Given the possibility of easily tailoring the optical thickness of porous silicon, this material is shown to be very practical for engineering omnidirectional mirrors.
Imbalance of Th1/Th2 transcription factors in patients with lupus nephritis (2006)

Patients with active lupus nephritis have increased T-bet and depressed GATA-3 expression in the urinary sediment and kidney tissue, indicating a predominant Th1 type of T-lymphocyte activation.
Polarimetry in turbid, birefringent, optically active media: A Monte Carlo study of Mueller matrix decomposition in the backscattering geometry (2009)

Determination of the intrinsic polarization properties of a complex turbid medium such as biological tissue in the backscattering geometry (a geometry that is convenient for in situ applications) is complicated due to the confounding influence of scattering, and due to simultaneous occurrence of several polarization effects. We have investigated the polar decomposition approach of Mueller matrices to delineate individual intrinsic polarization parameters (specifically linear retardance δ and optical rotation ψ) of a birefringent, chiral, turbid medium in the backscattering geometry, using Mueller matrices generated with polarization-sensitive Monte Carlo simulations. The results show that near the exact backscattering direction, the interplay of the scattering-induced linear retardance and diattenuation on the intrinsic values for δ and ψ is coupled in a complex interrelated way, due to contribution of the backscattered photons. In contrast, these effects were significantly reduced for detection positions at distances larger than a transport length away from the point of illumination. Simultaneous determination of the intrinsic values for δ and ψ of a birefringent, chiral, turbid medium in the backward detection geometry can thus be accomplished by decomposing the Mueller matrices recorded at distances larger than a transport length away from the point of illumination. Determination of the intrinsic values for these polarization parameters in backscattering geometry could be significant in, for example, for quantification of tissue structural anisotropy and for noninvasive blood glucose measurements of diabetic patients.
Comprehend Medical: A Named Entity Recognition and Relationship Extraction Web Service (2019)

Comprehend Medical is a stateless and Health Insurance Portability and Accountability Act (HIPAA) eligible Named Entity Recognition (NER) and Relationship Extraction (RE) service launched under Amazon Web Services (AWS) trained using state-of-the-art deep learning models. Contrary to many existing open source tools, Comprehend Medical is scalable and does not require steep learning curve, dependencies, pipeline configurations, or installations. Currently, Comprehend Medical performs NER in five medical categories: Anatomy, Medical Condition, Medications, Protected Health Information (PHI) and Treatment, Test and Procedure (TTP). Additionally, the service provides relationship extraction for the detected entities as well as contextual information such as negation and temporality in the form of traits. Comprehend Medical provides two Application Programming Interfaces (API): 1) the NERe API which returns all the extracted named entities, their traits and the relationships between them and 2) the PHId API which returns just the protected health information contained in the text. Furthermore, Comprehend Medical is accessible through AWS Console, Java and Python Software Development Kit (SDK), making it easier for non-developers and developers to use.
Saul Miller (2013)

Geoff lumbers in like a goods train.

He is grinding through the gears wheezily by the time he shunts into position, taking the chair like it is buffers. Still, the recoil holds him.

He looks me straight in the eye. ‘The gout’s better, at any rate. Since I gave up on your cheap pills.’

I expected something like this. ‘I make mistakes, yes,’ I mumble, quoting Nixon in my embarrassment. ‘But for personal gain, never!’

‘It is, indeed, hard for the strong to be just to the weak! ‘ counters Geoff with a dose of de Valera. ‘You still never should have given me that stuff.’

‘I warned you that you will have pain,’ …
The Immunoglobulin-like Module of gp130 Is Required for Signaling by Interleukin-6, but Not by Leukemia Inhibitory Factor (1998)

The transmembrane protein gp130 is a shared component of the receptor complexes for the interleukin-6 (IL-6)-type cytokines, which include IL-6, leukemia inhibitory factor (LIF) and oncostatin M (OSM). In addition to its role in the generation of high affinity receptors, gp130 is required for signal transduction by these cytokines. In the present study we have examined the role of the N-terminal located, extracellular immunoglobulin (Ig)-like module of gp130 in signal transduction by IL-6 and LIF. We have expressed wild-type human gp130 or three mutants in murine myeloid M1-UR21 cells that lack functional endogenous gp130 but express the IL-6 receptor (IL-6R) and the LIF receptor (LIFR). By measuring cellular responses, such as morphological changes upon differentiation, soft agar colony formation, and induction of tyrosine phosphorylation of the signal transducer and activator of transcription, STAT3, we show that signaling by IL-6, but not LIF, is significantly reduced by mutations in the Ig-like module of gp130. However, the binding of 125I-labeled IL-6 or LIF is not affected by these mutations. We also present evidence that the Ig-like module forms part of the epitope of an anti-gp130 monoclonal antibody that neutralizes the bioactivity of IL-6, but not of LIF or OSM. The data suggest that gp130-activation by IL-6 and LIF requires different regions of gp130, that the Ig-like module of gp130 may be required for IL-6-induced gp130 dimerization, and that the stoichiometry of the high affinity IL-6 receptor-complex differs from those of the receptor-complexes for LIF and OSM.
The Reactome pathway knowledgebase (2013)

Reactome (http://www.reactome.org) is a manually curated open-source open-data resource of human pathways and reactions. The current version 46 describes 7088 human proteins (34% of the predicted human proteome), participating in 6744 reactions based on data extracted from 15 107 research publications with PubMed links. The Reactome Web site and analysis tool set have been completely redesigned to increase speed, flexibility and user friendliness. The data model has been extended to support annotation of disease processes due to infectious agents and to mutation.
The Cell Surface Receptor DC-SIGN Discriminates betweenMycobacterium Species through Selective Recognition of the Mannose Caps on Lipoarabinomannan (2003)

Interactions between dendritic cells (DCs) and Mycobacterium tuberculosis, the etiological agent of tuberculosis, most likely play a key role in anti-mycobacterial immunity. We have recently shown that M. tuberculosis binds to and infects DCs through ligation of the DC-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) and that M. tuberculosis mannose-capped lipoarabinomannan (ManLAM) inhibits binding of the bacilli to the lectin, suggesting that ManLAM might be a key DC-SIGN ligand. In the present study, we investigated the molecular basis of DC-SIGN ligation by LAM. Contrary to what was found for slow growing mycobacteria, such as M. tuberculosis and the vaccine strain Mycobacterium bovis bacillus Calmette-Guérin, our data demonstrate that the fast growing saprophytic species Mycobacterium smegmatis hardly binds to DC-SIGN. Consistent with the former finding, we show that M. smegmatis-derived lipoarabinomannan, which is capped by phosphoinositide residues (PILAM), exhibits a limited ability to inhibit M. tuberculosis binding to DC-SIGN. Moreover, using enzymatically demannosylated and chemically deacylated ManLAM molecules, we demonstrate that both the acyl chains on the ManLAM mannosylphosphatidylinositol anchor and the mannooligosaccharide caps play a critical role in DC-SIGN-ManLAM interaction. Finally, we report that DC-SIGN binds poorly to the PILAM and uncapped AraLAM-containing species Mycobacterium fortuitum and Mycobacterium chelonae, respectively. Interestingly, smooth colony-forming Mycobacterium avium, in which ManLAM is capped with single mannose residues, was also poorly recognized by the lectin. Altogether, our results provide molecular insight into the mechanisms of mycobacteria-DC-SIGN interaction, and suggest that DC-SIGN may act as a pattern recognition receptor and discriminate between Mycobacterium species through selective recognition of the mannose caps on LAM molecules.
Stroke amplifier for deformable mirrors (2004)

We demonstrate a simple optical configuration that amplifies the usable stroke of a deformable mirror. By arranging for the wavefront to traverse the deformable mirror more than once, we correct it more than once. The experimental implementation of the idea demonstrates a doubling of 2.0 and 2.04 by two different means.
Waste Not, Want Not: Why Rarefying Microbiome Data Is Inadmissible (2014)

Current practice in the normalization of microbiome count data is inefficient in the statistical sense. For apparently historical reasons, the common approach is either to use simple proportions (which does not address heteroscedasticity) or to use rarefying of counts, even though both of these approaches are inappropriate for detection of differentially abundant species. Well-established statistical theory is available that simultaneously accounts for library size differences and biological variability using an appropriate mixture model. Moreover, specific implementations for DNA sequencing read count data (based on a Negative Binomial model for instance) are already available in RNA-Seq focused R packages such as edgeR and DESeq. Here we summarize the supporting statistical theory and use simulations and empirical data to demonstrate substantial improvements provided by a relevant mixture model framework over simple proportions or rarefying. We show how both proportions and rarefied counts result in a high rate of false positives in tests for species that are differentially abundant across sample classes. Regarding microbiome sample-wise clustering, we also show that the rarefying procedure often discards samples that can be accurately clustered by alternative methods. We further compare different Negative Binomial methods with a recently-described zero-inflated Gaussian mixture, implemented in a package called metagenomeSeq. We find that metagenomeSeq performs well when there is an adequate number of biological replicates, but it nevertheless tends toward a higher false positive rate. Based on these results and well-established statistical theory, we advocate that investigators avoid rarefying altogether. We have provided microbiome-specific extensions to these tools in the R package, phyloseq.
A recombinant adenovirus type 35 fiber knob protein sensitizes lymphoma cells to rituximab therapy (2009)

Many tumors, including lymphomas, up-regulate expression of CD46 to escape destruction by complement. Tumor cells are therefore relatively resistant to therapy by monoclonal antibodies, which act through complement-dependent cytotoxicity (CDC). From an Escherichia coli expression library of adenovirus type 35 fiber knob mutants, we selected a variant (Ad35K(++)) that had a higher affinity to CD46 than did the natural Ad35 fiber knob. We demonstrated that incubation of lymphoma cells with recombinant Ad35K(++) protein resulted in transient removal of CD46 from the cell surface. Preincubation of lymphoma cells with Ad35K(++) sensitized cells to CDC, triggered by the CD20-specific monoclonal antibody rituximab. In xenograft models with human lymphoma cells, preinjection of Ad35K(++) dramatically increased the therapeutic effect of rituximab. Blood cell counts and organ histology were normal after intravenous injection of Ad35K(++) into mice that express human CD46. The presence of polyclonal anti-Ad35K(++) antibodies did not affect the ability of Ad35K(++) to enhance rituximab-mediated CDC in in vitro assays. The Ad35K(++)-based approach has potential implications in monoclonal antibody therapy of malignancies beyond the combination with rituximab.
Circulatory effects of splanchnic nerve stimulation in developing swine (1985)

The relative maturity of immediate intestinal circulatory responses to efferent splanchnic nerve stimulation for 20 s was tested in 34 piglets (1 day-1 mo old) under pentobarbital anesthesia (15-30 mg/kg). Aortic pressure, heart rate, and superior mesenteric arterial flow (measured by electromagnetic flow transducers) were recorded simultaneously. Intestinal vascular resistance was calculated as mean aortic pressure/mean arterial flow. Resistance increased in most animals during experimental inhibition of the carotid sinus baroreceptor reflex. Transection of the splanchnic nerve decreased mesenteric resistance in all animals. Nerve stimulation at 2 Hz was not effective in all of the youngest animals; at 3 Hz, mesenteric resistance increased in all animals. The latency of this response was shorter at each increase in stimulation frequency. The aortic pressure rise associated with splanchnic nerve stimulation was greater with each increase in frequency. This rise was attenuated or absent after adrenalectomy and during postganglionic fiber stimulation. The vasoconstrictor effect of splanchnic nerve stimulation was attenuated after alpha-adrenergic receptor blockade with phentolamine in a dose (0.25-0.75 mg/kg) that blocked vasoconstrictor effects of norepinephrine (0.5 micrograms/kg). We conclude that alpha-adrenergic mechanisms are functional, although not mature, and that sympathetic vasoconstrictor tone is present in the intestinal circulation of swine at birth.