gebhart/patrepeval huggingface dataset:
Nitric oxide and cGMP: mediators of pelvic nerve-stimulated erection in dogs (1993)

We sought to determine whether the L-arginine-nitric oxide-guanosine 3',5'-cyclic monophosphate (cGMP) pathway, known to mediate neurostimulation-induced smooth muscle relaxation in penile tissue of rabbits and humans in vitro, is operative also in vivo. Adult male dogs (n = 9) were subjected to direct electrical stimulation of the pelvic nerves to induce penile tumescence. Intracavernous injection of the nitric oxide-releasing substance S-nitroso-N-acetylpenicillamine resulted in similar tumescence. Intracavernous injection of a specific inhibitor of nitric oxide synthesis, NG-nitro-L-arginine, blocked pelvic nerve-stimulated tumescence, and this was partially reversed by intracavernous injection of the nitric oxide precursor L-arginine. Furthermore, neurostimulated tumescence was inhibited by methylene blue, an inhibitor of cytosolic guanylate cyclase and enhanced by M&B 22948, a cGMP phosphodiesterase inhibitor. These in vivo findings support the hypothesis that cavernous smooth muscle relaxation and penile tumescence are mediated by nitric oxide and cGMP.
Augmented Repair of Achilles Tendon Ruptures (1997)

We performed a series of repairs of Achilles tendon ruptures in athletes using suture augmented with a polyethylene terephthalate mesh synthetic graft. No postoperative immobilization was used. The 29 patients were aged 25 to 54 years and all practiced sports a minimum of 4 hours weekly. At the followup, ranging from 6 months to 5 years, ankle mobility was normal in all but one patient, who had lost 15 degrees of extension. All the patients were able to do a series of 10 single-limb heel raises without any impairment when compared with the uninjured side. Average ankle flexion strength was 96% that of the uninjured side (range, 87% to 110%). There were no reruptures, although in two instances problems with scarring occurred. All patients but one were able to resume their sports activities at the same level of intensity as they had before their injuries. These results testify to the advantage of not using postoperative immobilization and beginning functional rehabilitation immediately in patients with such lesions.
BMP2-mediated alteration in the developmental pathway of fetal mouse brain cells from neurogenesis to astrocytogenesis (2001)

We show that when telencephalic neural progenitors are briefly exposed to bone morphogenetic protein 2 (BMP2) in culture, their developmental fate is changed from neuronal cells to astrocytic cells. BMP2 significantly reduced the number of cells expressing microtubule-associated protein 2, a neuronal marker, and cells expressing nestin, a marker for undifferentiated neural precursors, but BMP2 increased the number of cells expressing S100-beta, an astrocytic marker. In telencephalic neuroepithelial cells, BMP2 up-regulated the expression of negative helix-loop-helix (HLH) factors Id1, Id3, and Hes-5 (where Hes is homologue of hairy and Enhancer of Split) that inhibited the transcriptional activity of neurogenic HLH transcription factors Mash1 and neurogenin. Ectopic expression of either Id1 or Id3 (where Id is inhibitor of differentiation) inhibited neurogenesis of neuroepithelial cells, suggesting an important role for these HLH proteins in the BMP2-mediated changes in the neurogenic fate of these cells. Because gliogenesis in the brain and spinal cord, derived from implanted neural stem cells or induced by injury, is responsible for much of the failure of neuronal regeneration, this work may lead to a therapeutic strategy to minimize this problem.
Bias caused by template annealing in the amplification of mixtures of 16S rRNA genes by PCR (1996)

The PCR is used widely for the study of rRNA genes amplified from mixed microbial populations. These studies resemble quantitative applications of PCR in that the templates are mixtures of homologs and the relative abundance of amplicons is thought to provide some measure of the gene ratios in the starting mixture. Although such studies have established the presence of novel rRNA genes in many natural ecosystems, inferences about gene abundance have been limited by uncertainties about the relative efficiency of gene amplification in the PCR. To address this question, three rRNA gene standards were prepared by PCR, mixed in known proportions, and amplified a second time by using primer pairs in which one primer was labeled with a fluorescent nucleotide derivative. The PCR products were digested with restriction endonucleases, and the frequencies of genes in the products were determined by electrophoresis on an Applied Biosystems 373A automated DNA sequencer in Genescan mode. Mixtures of two templates amplified with the 519F-1406R primer pair yielded products in the predicted proportions. A second primer pair (27F-338R) resulted in strong bias towards 1:1 mixtures of genes in final products, regardless of the initial proportions of the templates. This bias was strongly dependent on the number of cycles of replication. The results fit a kinetic model in which the reannealing of genes progressively inhibits the formation of template-primer hybrids.
Minimizing the Inhibitory Effect of Neutralizing Antibody for Efficient Gene Expression in the Liver With Adeno-associated Virus 8 Vectors (2012)

Neutralizing antibodies (NAbs) against adeno-associated viruses (AAVs) are known to interfere with AAV vector-mediated gene transfer by intravascular delivery. Evading the inhibitory effects of antibodies against AAV vectors is necessary for efficient transfer of therapeutic genes clinically. For this purpose, we tested the efficacy of saline flushing in order to avoid contact of vectors with NAbs present in blood. Direct injection of the AAV8 vector carrying the factor IX (FIX) gene into the portal vein of macaques using saline flushing achieved transgene-derived FIX expression (4.7 ± 2.10-10.1 ± 5.45% of normal human FIX concentration) in the presence of NAbs. Expression was as efficient as that (5.43 ± 2.59-12.68 ± 4.83%) in macaques lacking NAbs. We next tested the efficacy of saline flushing using less invasive balloon catheter-guided injection. This approach also resulted in efficient expression of transgene-derived FIX (2.5 ± 1.06-9.0 ± 2.37%) in the presence of NAbs (14-56× dilutions). NAbs at this range of titers reduced the efficiency of transduction in the macaque liver by 100-fold when the same vector was injected into mesenteric veins without balloon catheters. Our results suggest that portal vein-directed vector delivery strategies with flushing to remove blood are efficacious for minimizing the inhibitory effect of anti-AAV antibodies.
Four‐dimensional cone‐beam computed tomography and digital tomosynthesis reconstructions using respiratory signals extracted from transcutaneously inserted metal markers for liver SBRT (2011)

The authors have successfully demonstrated that motion tracking of fiducial markers and the subsequent 4D reconstruction of CBCT and DTS are possible. Due to the significant reduction in motion-induced image blur, it is anticipated that such technology will be useful in image-guided liver SBRT treatments.
Challenges and developing solutions for increasing the benefits of IL-2 treatment in tumor therapy (2014)

Interleukin-2 (IL-2) is a cytokine with pleiotropic effects on the immune system. Systemic IL-2 treatment has produced durable responses in melanoma and renal cancer patients, but unfortunately this is effective only in a fraction of patients. Moreover, IL-2 treatment also engenders serious side effects, which limit its clinical utility. It is now appreciated that IL-2 not only stimulates NK and effector T cells but also has a critical role in the generation and maintenance of regulatory T cells, which act to dampen immune responses. Thus, successful immunotherapy of cancers using IL-2 has to address two fundamentally important issues: (1) how to limit side effects yet be active where it is needed, and (2) how to preferentially activate effector T cells while limiting the stimulation of Tregs. Strategies are now being developed to address these critical obstacles that may lead to a renaissance of IL-2 therapy.
Shrinkable, stiffness-controllable soft manipulator based on a bio-inspired antagonistic actuation principle (2014)

This paper explores a new hybrid actuation principle combining pneumatic and tendon-driven actuators for a soft robotic manipulator. The fusion of these two actuation principles leads to an overall antagonistic actuation mechanism whereby pneumatic actuation opposes tendon actuation - a mechanism commonly found in animals where muscles can oppose each other to vary joint stiffness. We are taking especially inspiration from the octopus who belongs to the class of Cephalopoda; the octopus uses its longitudinal and transversal muscles in its arms to achieve varied motion patterns; activating both sets of muscles, the octopus can control the arm stiffness over a wide range. Our approach mimics this behavior and achieves comparable motion patterns, including bending, elongation and stiffening. The proposed method combines the advantages of tendon-driven and pneumatic actuated systems and goes beyond what current soft, flexible robots can achieve: because the new robot structure is effectively an inflatable, sleeve, it can be pumped up to its fully inflated volume and, also, completely deflated and shrunk. Since, in the deflated state, it comprises just its outer “skin” and tendons, the robot can be compressed to a very small size, many times smaller when compared to its fully-inflated state. In this paper, we describe the mechanical structure of the soft manipulator. Proof-of-concept experiments focus on the robot's ability to bend, to morph from completely shrunk to entirely inflated as well as to vary its stiffness.
Parsing floor plan images (2017)

This paper introduces a method for analyzing floor plan images using wall segmentation, object detection, and optical character recognition. We introduce a challenging new real-estate floor plan dataset, R-FP, evaluate different wall segmentation methods, and propose fully convolutional networks (FCN) for this task. We explore architectures with different pixel-stride values and more compact ones with skipped pooling layers. An FCN-2s with a 2-pixel stride layer achieves state-of-the-art performance, obtaining a mean Intersection-over-Union score of 89.9% on R-FP, and 94.4% on the public CVC-FP data set. Using OCR and object detection, we estimate room sizes. Finally, we show applications in automatic 3D model building and interactive furniture fitting.
Nivolumab in Previously Untreated Melanoma without BRAF Mutation (2014)

Nivolumab was associated with significant improvements in overall survival and progression-free survival, as compared with dacarbazine, among previously untreated patients who had metastatic melanoma without a BRAF mutation. (Funded by Bristol-Myers Squibb; CheckMate 066 ClinicalTrials.gov number, NCT01721772.).
Broadly Neutralizing Antibodies Targeted to the Membrane-Proximal External Region of Human Immunodeficiency Virus Type 1 Glycoprotein gp41 (2001)

The identification and epitope mapping of broadly neutralizing anti-human immunodeficiency virus type 1 (HIV-1) antibodies (Abs) is important for vaccine design, but, despite much effort, very few such Abs have been forthcoming. Only one broadly neutralizing anti-gp41 monoclonal Ab (MAb), 2F5, has been described. Here we report on two MAbs that recognize a region immediately C-terminal of the 2F5 epitope. Both MAbs were generated from HIV-1-seropositive donors, one (Z13) from an antibody phage display library, and one (4E10) as a hybridoma. Both MAbs recognize a predominantly linear and relatively conserved epitope, compete with each other for binding to synthetic peptide derived from gp41, and bind to HIV-1(MN) virions. By flow cytometry, these MAbs appear to bind relatively weakly to infected cells and this binding is not perturbed by pretreatment of the infected cells with soluble CD4. Despite the apparent linear nature of the epitopes of Z13 and 4E10, denaturation of recombinant envelope protein reduces the binding of these MAbs, suggesting some conformational requirements for full epitope expression. Most significantly, Z13 and 4E10 are able to neutralize selected primary isolates from diverse subtypes of HIV-1 (e.g., subtypes B, C, and E). The results suggest that a rather extensive region of gp41 close to the transmembrane domain is accessible to neutralizing Abs and could form a useful target for vaccine design.
“Orgies of Gesticulation”? Pedigree and Performance Codes in Sir Johnston Forbes-Robertson's and Ruggero Ruggeri's Silent Films ofHamlet (2006)

This paper examines two silent feature films of Hamlet—one English, one Italian. Hepworth and Plumb's film starring Sir Johnston Forbes-Robertson was made in 1913 for Gaumont. Rodolfi's film starring Ruggero Ruggeri was made in 1917 for Rodolfi-Film. Both actors had already been celebrated for their stage Hamlets and the films are inscribed in markedly different ways with the legacy of those earlier stage productions. As part of considering this legacy, I examine the relationship of each actor to the Shakespearean words necessarily excised from the filmic performance and of each to a set of inherited pantomimic performance codes. The English film is more widely known, exhibited, and discussed than the Italian film. In this paper I suggest that its network of extra-textual associations (theatrical, English socially prestigious) may have proved as beguiling as its particular filmic attributes. I use a comparison of the divergent critical fates of these films as the spur to discussing the marketing, profile, and trends of critical reception for material that equivocates tellingly about its intended market and medium allegiances.
Networking named content (2009)

Network use has evolved to be dominated by content distribution and retrieval, while networking technology still speaks only of connections between hosts. Accessing content and services requires mapping from the what that users care about to the network's where. We present Content-Centric Networking (CCN) which treats content as a primitive - decoupling location from identity, security and access, and retrieving content by name. Using new approaches to routing named content, derived heavily from IP, we can simultaneously achieve scalability, security and performance. We implemented our architecture's basic features and demonstrate resilience and performance with secure file downloads and VoIP calls.
Analysis of Campylobacter jejuni capsular loci reveals multiple mechanisms for the generation of structural diversity and the ability to form complex heptoses (2004)

We recently demonstrated that Campylobacter jejuni produces a capsular polysaccharide (CPS) that is the major antigenic component of the classical Penner serotyping system distinguishing Campylobacter into >60 groups. Although the wide variety of C. jejuni serotypes are suggestive of structural differences in CPS, the genetic mechanisms of such differences are unknown. In this study we sequenced biosynthetic cps regions, ranging in size from 15 to 34 kb, from selected C. jejuni strains of HS:1, HS:19, HS:23, HS:36, HS:23/36 and HS:41 serotypes. Comparison of the determined cps sequences of the HS:1, HS:19 and HS:41 strains with the sequenced strain, NCTC11168 (HS:2), provides evidence for multiple mechanisms of structural variation including exchange of capsular genes and entire clusters by horizontal transfer, gene duplication, deletion, fusion and contingency gene variation. In contrast, the HS:23, HS:36 and HS:23/36 cps sequences were highly conserved. We report the first detailed structural analysis of 81-176 (HS:23/36) and G1 (HS:1) and refine the previous structural interpretations of the HS:19, HS:23, HS:36 and HS:41 serostrains. For the first time, we demonstrate the commonality and function of a second heptose biosynthetic pathway for Campylobacter CPS independent of the pathway for lipooligosaccharide (LOS) biosynthesis and identify a novel heptosyltransferase utilized by this alternate pathway. Furthermore, we show the retention of two functional heptose isomerases in Campylobacter and the sharing of a phosphatase for both LOS and CPS heptose biosynthesis.
Statistical variation of aberration structure and image quality in a normal population of healthy eyes (2002)

A Shack-Hartmann aberrometer was used to measure the monochromatic aberration structure along the primary line of sight of 200 cyclopleged, normal, healthy eyes from 100 individuals. Sphero-cylindrical refractive errors were corrected with ophthalmic spectacle lenses based on the results of a subjective refraction performed immediately prior to experimentation. Zernike expansions of the experimental wave-front aberration functions were used to determine aberration coefficients for a series of pupil diameters. The residual Zernike coefficients for defocus were not zero but varied systematically with pupil diameter and with the Zernike coefficient for spherical aberration in a way that maximizes visual acuity. We infer from these results that subjective best focus occurs when the area of the central, aberration-free region of the pupil is maximized. We found that the population averages of Zernike coefficients were nearly zero for all of the higher-order modes except spherical aberration. This result indicates that a hypothetical average eye representing the central tendency of the population is nearly free of aberrations, suggesting the possible influence of an emmetropization process or evolutionary pressure. However, for any individual eye the aberration coefficients were rarely zero for any Zernike mode. To first approximation, wave-front error fell exponentially with Zernike order and increased linearly with pupil area. On average, the total wave-front variance produced by higher-order aberrations was less than the wave-front variance of residual defocus and astigmatism. For example, the average amount of higher-order aberrations present for a 7.5-mm pupil was equivalent to the wave-front error produced by less than 1/4 diopter (D) of defocus. The largest pupil for which an eye may be considered diffraction-limited was 1.22 mm on average. Correlation of aberrations from the left and right eyes indicated the presence of significant bilateral symmetry. No evidence was found of a universal anatomical feature responsible for third-order optical aberrations. Using the Marechal criterion, we conclude that correction of the 12 largest principal components, or 14 largest Zernike modes, would be required to achieve diffraction-limited performance on average for a 6-mm pupil. Different methods of computing population averages provided upper and lower limits to the mean optical transfer function and mean point-spread function for our population of eyes.
PARP Expression Is Increased in Astrocytes but Decreased in Motor Neurons in the Spinal Cord of Sporadic ALS Patients (2003)

The evidence for increased oxidative stress and DNA damage in amyotrophic lateral sclerosis (ALS) prompted studies to determine if the expression of poly(ADP-ribose) polymerase (PARP) is increased in ALS. Using Western analyses of postmortem tissue, we demonstrated that PARP-immunoreactivity (PARP-IR) was increased 3-fold in spinal cord tissues of sporadic ALS (sALS) patients compared with non-neurological disease controls. Despite the increased PARP-IR, PARP mRNA expression was not increased significantly. Immunohistochemical analyses revealed PARP-IR was increased in both white and gray matter of sALS spinal cord. While PARP-IR was predominantly seen in astrocytes, large motor neurons displayed reduced staining compared with controls. This result contrasts sharply to the staining of Alzheimer and MPTP-induced Parkinson diseased tissue, where poly(ADP-ribose) (PAR)-IR was seen mostly in neurons, with little astrocytic staining. PARP-IR was increased in the pellet fraction of sALS homogenates compared with control homogenates, representing potential PARP binding to chromatin or membranes and suggesting a possible mechanism of PARP stabilization. The present results demonstrate glial alterations in sALS spinal cord tissue and support the role of glial alterations in sALS pathogenesis. Additionally, these results demonstrate differences in sALS spinal motor neurons and astrocytes compared to brain neurons and astrocytes in Alzheimer disease and MPTP-induced Parkinson disease despite the presence of markers for oxidative stress in all 3 diseases.
Xom interacts with and stimulates transcriptional activity of LEF1/TCFs： implications for ventral cell fate determination during vertebrate embryogenesis (2007)

LEF1/TCFs 是高活动性组调停的包含盒子的 transcriptional 因素在早胚胎开始和 tumorigenesis.Beta-catenin 期间发信号的正规 Wnt/beta-catenin 在 dorsalization 期间与 LEF1/TCFs 和 transactivates LEF1/TCF-mediated 抄写形成建筑群。尽管调停 LEF 的抄写也在 ventralization 被含有，内在的分子的机制很好没被理解。用脊椎动物 Xenopus laevis 模型系统，我们发现那 Xom，它是有双角色 oftranscriptional 的 ventralizing homeobox 蛋白质激活和压抑，通过它的 N 终端 transactivation 领域(男孩) 通过它的 homeodomain andtransactivates LEF1/TCF-mediated 抄写与 LEF1/TCF 形成建筑群。我们的数据表演缺乏 N 终端男孩的那 Xom 自己没有通过腹的基因，如此的 asBMP4 和 Xom 到 transactivate，但是保留能力压制背面的基因倡导者的 transcriptional 激活例如 Goosecoid 倡导者，显示 transactivation 和压抑是 Xom 的可分离的函数。Xom 与 BMP4 形成一个积极援助环支持 ventralization 并且压制背面的基因表示，这被要求了。与 LEF1/TCFs 的 Xom transactivation 的一个必要角色一致在早胚胎开始期间，我们发现缺乏 TAD 的主导否定的 Xom 异种的那表情失败到援助 BMP4 和原因的腹的发信号灾难的效果在 gastrulation 期间。我们的数据建议 Xom 和 LEF1/TCF-factors 的功能的相互作用为腹的房间命运决心和那 LEF1/TCF 是必要的因素可以作为集中的一个点工作调停在早胚胎开始期间 Wnt/beta-catenin 和 BMP4/Xom 小径发信号联合。
Bcl-2 prevents apoptosis induced by perforin and granzyme B, but not that mediated by whole cytotoxic lymphocytes (1997)

Two pathways have been implicated in the induction of apoptosis by cytotoxic T cells: the granule exocytosis pathway and a pathway using CD95 (Fas/APO-1). To test whether apoptosis induced by either of these pathways could be blocked by Bcl-2, we exposed bcl-2-transfected cells to CTL derived from normal, perforin-deficient, or CD95 ligand mutant (gld) mice. Although the levels of Bcl-2 expression achieved were able to protect FDC-P1 and Yac-1 transfectants from a variety of apoptotic stimuli, the cells were not protected from cytolysis mediated by CTL from any of these sources, by NK cells, or granules isolated from CTL. However, Bcl-2 expression significantly inhibited apoptosis induced by purified granzyme B and perforin. These results suggest that while Bcl-2 is capable of inhibiting the apoptotic pathway utilized by perforin and granzyme B, other granule components can bypass this block. We conclude that CTL harbor potent killing mechanism(s) in addition to those provided by CD95 ligand or perforin and granzyme B that cannot be overcome by Bcl-2.