gebhart/patrepeval huggingface dataset:
Label‐Free Tracking of Single Organelle Transportation in Cells with Nanometer Precision Using a Plasmonic Imaging Technique (2015)

Imaging and tracking of nano- and micrometer-sized organelles in cells with nanometer precision is crucial for understanding cellular behaviors at the molecular scale. Because of the fast intracellular dynamic processes, the imaging and tracking method must also be fast. In addition, to ensure that the observed dynamics is relevant to the native functions, it is critical to keep the cells under their native states. Here, a plasmonics-based imaging technique is demonstrated for studying the dynamics of organelles in 3D with high localization precision (5 nm) and temporal (10 ms) resolution. The technique is label-free and can track subcellular structures in the native state of the cells. Using the technique, nanometer steps of organelle (e.g., mitochondria) transportation are observed along neurite microtubules in primary neurons, and the 3D structure of neurite microtubule bundles is reconstructed at the nanometer scale from the tracks of the moving organelles.
Origins of HIV and the AIDS Pandemic (2011)

Acquired immunodeficiency syndrome (AIDS) of humans is caused by two lentiviruses, human immunodeficiency viruses types 1 and 2 (HIV-1 and HIV-2). Here, we describe the origins and evolution of these viruses, and the circumstances that led to the AIDS pandemic. Both HIVs are the result of multiple cross-species transmissions of simian immunodeficiency viruses (SIVs) naturally infecting African primates. Most of these transfers resulted in viruses that spread in humans to only a limited extent. However, one transmission event, involving SIVcpz from chimpanzees in southeastern Cameroon, gave rise to HIV-1 group M-the principal cause of the AIDS pandemic. We discuss how host restriction factors have shaped the emergence of new SIV zoonoses by imposing adaptive hurdles to cross-species transmission and/or secondary spread. We also show that AIDS has likely afflicted chimpanzees long before the emergence of HIV. Tracing the genetic changes that occurred as SIVs crossed from monkeys to apes and from apes to humans provides a new framework to examine the requirements of successful host switches and to gauge future zoonotic risk.
Spatial computation (2004)

This paper describes a computer architecture, Spatial Computation (SC), which is based on the translation of high-level language programs directly into hardware structures. SC program implementations are completely distributed, with no centralized control. SC circuits are optimized for wires at the expense of computation units.In this paper we investigate a particular implementation of SC: ASH (Application-Specific Hardware). Under the assumption that computation is cheaper than communication, ASH replicates computation units to simplify interconnect, building a system which uses very simple, completely dedicated communication channels. As a consequence, communication on the datapath never requires arbitration; the only arbitration required is for accessing memory. ASH relies on very simple hardware primitives, using no associative structures, no multiported register files, no scheduling logic, no broadcast, and no clocks. As a consequence, ASH hardware is fast and extremely power efficient.In this work we demonstrate three features of ASH: (1) that such architectures can be built by automatic compilation of C programs; (2) that distributed computation is in some respects fundamentally different from monolithic superscalar processors; and (3) that ASIC implementations of ASH use three orders of magnitude less energy compared to high-end superscalar processors, while being on average only 33% slower in performance (3.5x worst-case).
Breadth of Neutralizing Antibodies Elicited by Stable, Homogeneous Clade A and Clade C HIV-1 gp140 Envelope Trimers in Guinea Pigs (2010)

The native envelope (Env) spike on the surface of human immunodeficiency virus type 1 (HIV-1) is trimeric, and thus trimeric Env vaccine immunogens are currently being explored in preclinical immunogenicity studies. Key challenges have included the production and purification of biochemically homogeneous and stable trimers and the evaluation of these immunogens utilizing standardized virus panels for neutralization assays. Here we report the binding and neutralizing antibody (NAb) responses elicited by clade A (92UG037.8) and clade C (CZA97.012) Env gp140 trimer immunogens in guinea pigs. These trimers have been selected and engineered for optimal biochemical stability and have defined antigenic properties. Purified gp140 trimers with Ribi adjuvant elicited potent, cross-clade NAb responses against tier 1 viruses as well as detectable but low-titer NAb responses against select tier 2 viruses from clades A, B, and C. In particular, the clade C trimer elicited NAbs that neutralized 27%, 20%, and 47% of tier 2 viruses from clades A, B, and C, respectively. Heterologous DNA prime, protein boost as well as DNA prime, recombinant adenovirus boost regimens expressing these antigens, however, did not result in an increased magnitude or breadth of NAb responses in this system. These data demonstrate the immunogenicity of stable, homogeneous clade A and clade C gp140 trimers and exemplify the utility of standardized tier 1 and tier 2 virus panels for assessing the NAb responses of candidate HIV-1 Env immunogens.
Targeting of the non-mutated tumor antigen HER2/neu to mature dendritic cells induces an integrated immune response that protects against breast cancer in mice (2012)

Immunization of mice with HER2 protein vaccine targeting DEC+ DCs in vivo induced high levels of T- and B-cell immunity. Non-targeted HER2 protein was poorly immunogenic for CD4+ and CD8+ T cells. This vaccination approach provided long-term survival benefit for mice challenged with neu-expressing tumor following as little as 2.7 μg of HER2 protein incorporated in the vaccine. Vaccine-induced CD4+ and CD8+ T cells were both essential for tumor protection. This immunization strategy demonstrates great potential towards the development of vaccines for breast cancer patients.
Remote measurement of breathing rate in real time using a high precision, single-point infrared temperature sensor (2012)

This paper presents a novel approach for remotely monitoring a user's breathing rate in real-time using a high precision, single-point infrared sensor. Remote breathing detection is especially useful for rehabilitative robotic applications such as post-stroke and post-operative cardiac therapies, where continuous monitoring of a patient's physical stress level can be used to adjust the level and duration of physical exertion throughout the course of therapy. Additionally, socially assistive robots which discreetly collect breathing information from their users, can customize interactions based on the perceived physiological state of the patient. The proposed approach is an important potential improvement for therapies where user mobility is an inherent part of the therapy and when users have a general aversion to being fitted with sensors. Further, due to its relatively small size and modular design, existing rehabilitative robot systems can be retrofitted with the proposed breathing detection system to enhance and extend their functionality. This research delivers a new technique for capturing changes in the sub-nasal skin surface temperature to monitor breathing events. Temperatures are obtained by tracking the sub-nasal region of the face, continuously targeting and sampling the infrared sensor. The breathing rate is automatically extracted using a sinusoidal curve-fitting function which provides an estimated rate in breaths per minute. Results from preliminary tests show this system effectively captures breathing rates within an error rate of under 2 breaths per minute in excess of 70% of typical test cases.
The Serine Repeat Antigen (SERA) Gene Family Phylogeny in Plasmodium: The Impact of GC Content and Reconciliation of Gene and Species Trees (2004)

Plasmodium falciparum is the parasite responsible for the most acute form of malaria in humans. Recently, the serine repeat antigen (SERA) in P. falciparum has attracted attention as a potential vaccine and drug target, and it has been shown to be a member of a large gene family. To clarify the relationships among the numerous P. falciparum SERAs and to identify orthologs to SERA5 and SERA6 in Plasmodium species affecting rodents, gene trees were inferred from nucleotide and amino acid sequence data for 33 putative SERA homologs in seven different species. (A distance method for nucleotide sequences that is specifically designed to accommodate differing GC content yielded results that were largely compatible with the amino acid tree. Standard-distance and maximum-likelihood methods for nucleotide sequences, on the other hand, yielded gene trees that differed in important respects.) To infer the pattern of duplication, speciation, and gene loss events in the SERA gene family history, the resulting gene trees were then "reconciled" with two competing Plasmodium species tree topologies that have been identified by previous phylogenetic studies. Parsimony of reconciliation was used as a criterion for selecting a gene tree/species tree pair and provided (1) support for one of the two species trees and for the core topology of the amino acid-derived gene tree, (2) a basis for critiquing fine detail in a poorly resolved region of the gene tree, (3) a set of predicted "missing genes" in some species, (4) clarification of the relationship among the P. falciparum SERA, and (5) some information about SERA5 and SERA6 orthologs in the rodent malaria parasites. Parsimony of reconciliation and a second criterion--implied mutational pattern at two key active sites in the SERA proteins-were also seen to be useful supplements to standard "bootstrap" analysis for inferred topologies.
Myofilament Ca2+ sensitivity in intact versus skinned rat ventricular muscle. (1994)

The Ca2+ sensitivity of myofilaments was compared before and after skinning in the same rat trabeculae at a diastolic sarcomere length of 2.2 to 2.3 microns. Trabeculae from rat right ventricle were loaded with fura-2 salt by iontophoretic microinjection, and [Ca2+]i was determined from the epifluorescence at 510 nm when excited at 340 and 380 nm. Steady-state activation was achieved by stimulating the muscle at 10 Hz after 10 to 20 minutes of application of ryanodine (5 mumol/L). The muscles were then skinned with Triton X-100 (1%) for 15 to 25 minutes and subsequently activated with solutions containing varied [Ca2+]. The intact force-[Ca2+] relation was highly cooperative (Hill coefficient, 4.87 +/- 0.35; n = 10), with a low [Ca2+]i required for half-maximal activation (K1/2) (0.62 +/- 0.03 mumol/L). After skinning, the Hill coefficient fell to 2.72 and the K 1/2 shifted rightward to 2.2 mumol/L in the presence of 1.2 mmol/L free Mg2+. Because of uncertainty regarding the appropriate [Mg2+], we measured [Mg2+]i at 0.72 +/- 0.06 mmol/L (n = 11) with Mg-fura-2 salt. When activating solutions were modified to contain [Mg2+] = 0.5 mmol/L, the force-[Ca2+] relation was shifted to the left (K 1/2 = 0.93 +/- 0.1, n = 10) with a Hill coefficient of 3.75 +/- 0.37, but the changes were not sufficient to superimpose with the intact force-[Ca2+] relation (P < .05 versus intact). These results suggest that, despite the significant effect of Mg2+ on the force-[Ca2+] relation in skinned muscles, the Ca2+ responsiveness of the myofilaments is still altered by skinning.(ABSTRACT TRUNCATED AT 250 WORDS)
Faster cyclic loess: normalizing RNA arrays via linear models (2004)

The Splus/R function for fastlo normalization is available from the authors.
Enantioselective synthesis of levomilnacipran (2012)

A novel approach for the asymmetric synthesis of the active (1S,2R)-enantiomer of the antidepressant milnacipran is reported. The two stereogenic centers borne by the cyclopropane ring were sequentially installed starting from phenylacetic acid.
Secretion of α1‐antitrypsin by alveolar epithelial cells (1994)

We have investigated the ability of alveolar epithelial cells (human A549 cell line and rat type-II pneumocytes) to produce alpha 1-antitrypsin (AAT). Northern blot analysis demonstrated the presence of an AAT-specific mRNA transcript in A549 cells. Unstimulated A549 cells secreted immunoreactive AAT at a rate of 0.51 +/- 0.04 ng/10(6) cells/h, with a modified glycosylation compared to serum AAT. AAT formed a complex with neutrophil elastase. Rat type-II pneumocytes secreted immunoreactive AAT. Our results suggest that alveolar epithelial cells could participate in antiprotease defense within the lung through local AAT production.
Linear Fuzzy PID Control (2007)

This chapter contains sections titled: Fuzzy P Controller Fuzzy PD Controller Fuzzy PD+I Controller Fuzzy Incremental Controller Tuning Scaling Simulation Study: Higher-Order Process Practical Considerations* Summary Notes and References
A new static memory cell based on reverse base current (RBC) effect of bipolar transistor (2003)

A novel SRAM (static random access memory) cell, which consists of a bipolar transistor and an MOS transistor, is proposed. The device, which is based on the reverse base current (RBC) effect, has been fabricated by conventional BiCMOS technology, using double poly-Si. A cell size of 8.58 mu m/sup 2/ has been realized in a 1.0- mu m ground rule. The results indicate that the RBC cell can be applied to very-high-density SRAMs, as large as 16 Mb or beyond.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A cyclophilin from the polycentric anaerobic rumen fungus Orpinomyces sp. strain PC-2 is highly homologous to vertebrate cyclophilin B. (1995)

A cyclophilin (CyP) purified to homogeneity from the polycentric anaerobic rumen fungus Orpinomyces sp. strain PC-2 had a molecular mass of 20.5 kDa and a pI of 8.1. The protein catalyzed the isomerization of the prolyl peptide bond of N-succinyl-Ala-Ala-(cis,trans)-Pro-Phe p-nitroanilide with a kcat/Km value of 9.3 x 10(6) M-1.s-1 at 10 degrees C and pH 7.8. Cyclosporin A strongly inhibited this peptidylprolyl cis-trans isomerase activity with an IC50 of 19.6 nM. The sequence of the first 30 N-terminal amino acids of this CyP had high homology with the N-terminal sequences of other eukaryotic CyPs. By use of a DNA hybridization probe amplified by PCR with degenerate oligonucleotide primers designed based on the amino acid sequences of the N terminus of this CyP and highly conserved internal regions of other CyPs, a full-length cDNA clone was isolated. It possessed an open reading frame encoding a polypeptide of 203 amino acids with a calculated molecular weight of 21,969, containing a putative hydrophobic signal peptide sequence of 22 amino acids preceding the N terminus of the mature enzyme and a C-terminal sequence, Lys-Ala-Glu-Leu, characteristic of an endoplasmic reticulum retention signal. The Orpinomyces PC-2 CyP is a typical type B CyP. The amino acid sequence of the Orpinomyces CyP exhibits striking degrees of identity with the corresponding human (70%), bovine (69%), mouse (68%), chicken (66%), maize (61%), and yeast (54%) proteins. Phylogenetic analysis based on the CyP sequences indicated that the evolutionary origin of the Orpinomyces CyP was closely related with CyPs of animals.
Hemostats, sealants, and adhesives: components of the surgical toolbox (2008)

The surgical toolbox is expanding, and newer products are being developed to improve results. Reducing blood loss so that bloodless surgery can be performed may help minimize morbidity and length of stay. As patients, hospital administrators, and government regulators desire less invasive procedures, the surgical technical challenge is increasing. More operations are being performed through minimally invasive incisions with laparoscopic, endoscopic, and robotic approaches. In this setting, tools that can reduce bleeding by causing blood to clot, sealing vessels, or gluing tissues are gaining an increasing importance. Thus, hemostats, sealants, and adhesives are becoming a more important element of surgical practice. This review is designed to facilitate the reader's basic knowledge of these tools so that informed choices are made for controlling bleeding in specific clinical situations. Such information is useful for all members of the operative team. The team includes surgeons, anesthesiologists, residents, and nurses as well as hematologists and other medical specialists who may be involved in the perioperative care of surgical patients. An understanding of these therapeutic options may also be helpful to the transfusion service. In some cases, these materials may be stored in the blood bank, and their appropriate use may reduce demand for other transfusion components. The product classification used in this review includes hemostats as represented by product categories that include mechanical agents, active agents, flowables, and fibrin sealants; sealants as represented by fibrin sealants and polyethylene glycol hydrogels; and adhesives as represented by cyanoacrylates and albumin cross-linked with glutaraldehyde. Only those agents approved by the Food and Drug Administration (FDA) and presently available (February 2008) for sale in the United States are discussed in this review.
The local repressor AcrR plays a modulating role in the regulation of acrAB genes of Escherichia coli by global stress signals (1996)

Genes acrAB encode a multidrug efflux pump in Escherichia coli. We have previously reported that transcription of acrAB is increased under general stress conditions (i.e. 4% ethanol, 0.5 M NaCl, and the stationary phase in Luria-Bertani medium). In this study, lacZ transcriptional fusions and an in vitro gel mobility shift assay have been utilized to study the mechanisms governing the regulation of acrAB. We found that a closely linked gene, acrR, encoded a repressor of acrAB. Nevertheless, the general stress conditions increased transcription of acrAB in the absence of functional AcrR, and such conditions surprisingly increased the transcription of acrR even more strongly than that of acrAB. These results suggest that the general-stress-induced transcription of acrAB is primarily mediated by global regulatory pathway(s), and that one major role of AcrR is to function as a specific secondary modulator to fine tune the level of acrAB transcription and to prevent the unwanted overexpression of acrAB. To our knowledge, this represents a novel mechanism of regulating gene expression in E. coli. Evidence also suggests that the up-regulation of acrAB expression under general stress conditions is not likely to be mediated by the known global regulators, such as MarA or SoxS, although elevated levels of these proteins were shown to increase the transcription of acrAB.
Anatomical Connectivity of the Subgenual Cingulate Region Targeted with Deep Brain Stimulation for Treatment-Resistant Depression (2007)

Chronic deep brain stimulation (DBS) of subgenual cingulate white matter results in dramatic remission of symptoms in some previously treatment-resistant depression patients. The effects of stimulation may be mediated locally or via corticocortical or corticosubcortical connections. We use tractography to define the likely connectivity of cingulate regions stimulated in DBS-responsive patients using diffusion imaging data acquired in healthy control subjects. We defined 2 distinct regions within anterior cingulate cortex based on anatomical connectivity: a pregenual region strongly connected to medial prefrontal and anterior midcingulate cortex and a subgenual region with strongest connections to nucleus accumbens, amygdala, hypothalamus, and orbitofrontal cortex. The location of electrode contact points from 9 patients successfully treated with DBS lies within this subgenual region. The anatomical connectivity of the subgenual cingulate region targeted with DBS for depression supports the hypothesis that treatment efficacy is mediated via effects on a distributed network of frontal, limbic, and visceromotor brain regions. At present, targeting of DBS for depression is based on landmarks visible in conventional magnetic resonance imaging. Preoperatively acquired diffusion imaging for connectivity-based cortical mapping could improve neurosurgical targeting. We hypothesize that the subgenual region with greatest connectivity across the distributed network described here may prove most effective.
Selective Solubilization of Hemagglutinin and Neuraminidase from Influenza Viruses (1975)

A novel approach is described for the isolation of hemagglutinin and neuraminidase from influenza viruses. In contrast to published procedures, the two glycoproteins are selectively solubilized, leaving an intact viral subparticle which contains lipid, RNA and non-glycoproteins. The pronounced differences in size allow a simple separation of the solubilized proteins from the virus ‘core’.
Biosynthesis of heparin. Use of Escherichia coli K5 capsular polysaccharide as a model substrate in enzymic polymer-modification reactions (1991)

A capsular polysaccharide from Escherichia coli K5 was previously found to have the same structure, [-(4)beta GlcA(1)----(4)alpha GlcNAc(1)-]n, as that of the non-sulphated precursor polysaccharide in heparin biosynthesis [Vann, Schmidt, Jann & Jann (1981) Eur. J. Biochem. 116, 359-364]. The K5 polysaccharide was N-deacetylated (by hydrazinolysis) and N-sulphated, and was then incubated with detergent-solubilized enzymes from a heparin-producing mouse mastocytoma, in the presence of adenosine 3'-phosphate 5'-phospho[35S] sulphate ([35S]PAPS). Structural analysis of the resulting 35S-labelled polysaccharide revealed the formation of all the major disaccharide units found in heparin. The identification of 2-O-[35S]sulphated IdoA (L-iduronic acid) as well as 6-O-[35S]sulphated GlcNSO3 units demonstrated that the modified K5 polysaccharide served as a substrate in the hexuronosyl C-5-epimerase and the major O-sulphotransferase reactions involved in the biosynthesis of heparin. The GlcA units of the native (N-acetylated) E. coli polysaccharide were attacked by the epimerase only when PAPS was present in the incubations, whereas those of the chemically N-sulphated polysaccharide were epimerized also in the absence of PAPS, in accord with the notion that N-sulphate groups are required for epimerization. With increasing concentrations of PAPS, the mono-O-sulphated disaccharide unit-IdoA(2-OSO3)-GlcNSO3- was progressively converted into the di-O-sulphated species -IdoA(2-OSO3)-GlcNSO3(6-OSO3)-. A small proportion of the 35S-labelled polysaccharide was found to bind with high affinity to the proteinase inhibitor antithrombin. This proportion increased with increasing concentration of PAPS up to a level corresponding to approximately 1-2% of the total incorporated 35S. The solubilized enzymes thus catalysed all the reactions required for the generation of functional antithrombin-binding sites.