gebhart/patrepeval huggingface dataset:
HyperDepth: Learning Depth from Structured Light without Matching (2016)

Structured light sensors are popular due to their robustness to untextured scenes and multipath. These systems triangulate depth by solving a correspondence problem between each camera and projector pixel. This is often framed as a local stereo matching task, correlating patches of pixels in the observed and reference image. However, this is computationally intensive, leading to reduced depth accuracy and framerate. We contribute an algorithm for solving this correspondence problem efficiently, without compromising depth accuracy. For the first time, this problem is cast as a classification-regression task, which we solve extremely efficiently using an ensemble of cascaded random forests. Our algorithm scales in number of disparities, and each pixel can be processed independently, and in parallel. No matching or even access to the corresponding reference pattern is required at runtime, and regressed labels are directly mapped to depth. Our GPU-based algorithm runs at a 1KHz for 1.3MP input/output images, with disparity error of 0.1 subpixels. We show a prototype high framerate depth camera running at 375Hz, useful for solving tracking-related problems. We demonstrate our algorithmic performance, creating high resolution real-time depth maps that surpass the quality of current state of the art depth technologies, highlighting quantization-free results with reduced holes, edge fattening and other stereo-based depth artifacts.
High-throughput mutation profiling of CTCL samples reveals KRAS and NRAS mutations sensitizing tumors toward inhibition of the RAS/RAF/MEK signaling cascade (2011)

Cutaneous T-cell lymphomas (CTCLs) are malignancies of skin-homing lymphoid cells, which have so far not been investigated thoroughly for common oncogenic mutations. We screened 90 biopsy specimens from CTCL patients (41 mycosis fungoides, 36 Sézary syndrome, and 13 non-mycosis fungoides/Sézary syndrome CTCL) for somatic mutations using OncoMap technology. We detected oncogenic mutations for the RAS pathway in 4 of 90 samples. One mycosis fungoides and one pleomorphic CTCL harbored a KRAS(G13D) mutation; one Sézary syndrome and one CD30(+) CTCL harbored a NRAS(Q61K) amino acid change. All mutations were found in stage IV patients (4 of 42) who showed significantly decreased overall survival compared with stage IV patients without mutations (P = .04). In addition, we detected a NRAS(Q61K) mutation in the CTCL cell line Hut78. Knockdown of NRAS by siRNA induced apoptosis in mutant Hut78 cells but not in CTCL cell lines lacking RAS mutations. The NRAS(Q61K) mutation sensitized Hut78 cells toward growth inhibition by the MEK inhibitors U0126, AZD6244, and PD0325901. Furthermore, we found that MEK inhibitors exclusively induce apoptosis in Hut78 cells. Taken together, we conclude that RAS mutations are rare events at a late stage of CTCL, and our preclinical results suggest that such late-stage patients profit from MEK inhibitors.
Correlates of independent HIV-1 replication in the CNS and of its control by antiretrovirals (2002)

Quantification of HIV RNA in CSF is clinically useful, particularly in patients with neurologic disorders. CSF penetration of antiretrovirals must be considered when choosing treatments, mainly in patients with higher CSF viral loads, advanced disease, and CNS disorders associated with significant macrophage activation.
The Heparin-Binding Exosite Is Critical to Allosteric Activation of Factor IXa in the Intrinsic Tenase Complex:  The Role of Arginine 165 and Factor X (2007)

Heparin inhibits the intrinsic tenase complex (factor IXa-factor VIIIa) via interaction with a factor IXa exosite. To define the role of this exosite, human factor IXa with alanine substituted for conserved surface residues (R126, N129, K132, R165, N178) was characterized. Chromogenic substrate hydrolysis by the mutant proteases was reduced 20-30% relative to factor IXa wild type. Coagulant activity was moderately (N129A, K132A, K126A) or dramatically (R165A) reduced relative to factor IXa wild type. Kinetic analysis demonstrated a marked reduction in apparent cofactor affinity (23-fold) for factor IXa R165, and an inability to stabilize cofactor activity. Factor IXa K126A, N129A, and K132A demonstrated modest reductions ( approximately 2-fold) in apparent cofactor affinity, and accelerated decay of intrinsic tenase activity. In the absence of factor VIIIa, factor IXa N178A and R165A demonstrated a defective Vmax(app) for factor X activation. In the presence of factor VIIIa, Vmax(app) varied in proportion to the predicted factor IXa-factor VIIIa concentration. However, factor IXa R165A had a 65% reduction in the kcat for factor X, suggesting an additional effect on catalysis. The ability of factor IXa to compete for physical assembly into the intrinsic tenase complex was enhanced by EGR-chloromethylketone bound to the factor IXa active site or addition of factor X, and reduced by selected mutations in the heparin-binding exosite (N178A, K126A, R165A). These results suggest that the factor IXa heparin-binding exosite participates in both cofactor binding and protease activation, and cofactor affinity is linked to active site conformation and factor X interaction during enzyme assembly.
Uniform Anchoring of Nematic Liquid Crystals on Self-Assembled Monolayers Formed from Alkanethiols on Obliquely Deposited Films of Gold (1996)

This paper demonstrates that self-assembled monolayers (SAMs) formed by chemisorption of alkanethiols on the surface of obliquely deposited, 10 nm-thick, films of gold are useful in studies of the anchoring of liquid crystals (LCs) on surfaces. Self-assembled monolayers supported on obliquely deposited gold permit uniform anchoring of nematic LCs over centimeter-scales. In contrast, SAMs prepared on films of gold deposited with no preferred direction cause nematic phases to form 10−100 μm scale domains with optical axes having random azimuthal orientations. Self-assembled monolayers prepared from either CH3(CH2)15SH or CH3(CH2)9SH on films of gold deposited obliquely induce near-planar and azimuthally uniform anchoring of nematic phases of 4-cyano-4'-pentylbiphenyl (5CB). Mixed SAMs formed by coadsorption of CH3(CH2)15SH and CH3(CH2)9SH cause homeotropic anchoring of nematic phases of 5CB on films of gold deposited without a preferred direction and produce a small tilt (3−5°) from the normal on gold deposited obliquely onto glass substrates. The contact angles (advancing and receding) of hexadecane are indistinguishable when measured on SAMs supported on gold with and without a preferred direction. Liquid crystals can be used to detect anisotropy in these surfaces that cannot be measured by the wetting of simple fluids such as hexadecane.
Regulation of human growth hormone gene expression by insulin-like growth factor I in transfected cells. (1987)

Insulin-like growth factor I (IGF-I), a target hormone for growth hormone (GH) action, has been shown to regulate rat GH gene transcription. We further investigated its direct action on the human GH gene transfected in human choriocarcinoma cells (JEG3) which possess abundant IGF-I receptors. The 2.6 kilobase (kb) hGH gene (EcoRI fragment) in pUC18 (phGH) was transfected into cells by calcium-phosphate-dimethyl sulfoxide shock. The cells were subsequently treated for 72 h, when GH gene expression was measured. 8-Bromo-cAMP (Br-cAMP, 2.5 mM) and hydrocortisone (100 nM), respectively, stimulated GH secretion in transfected cells by 50% over unstimulated control cells, while combined treatment with these two agents caused a 340% increase of GH secretion as measured by radioimmunoassay. IGF-I (6.5 nM) did not suppress the basal level of Gh secretion but did inhibit the stimulated GH secretion by over 50%. Immunoprecipitation analysis showed that 8-Br-cAMP + hydrocortisone markedly increased newly synthesized 22-kDa [35S]GH. This de novo GH synthesis was inhibited by IGF-I. Northern gel analysis of poly(A) RNA showed that 8-Br-cAMP + hydrocortisone induced a 1.0-kb mRNA species as detected with 32P-labeled hGH-cDNA. IGF-I suppressed the GH mRNA induced by cAMP + hydrocortisone as well as suppressing a larger 2.2-kb GH mRNA precursor. The results show that the transfected human GH gene was expressed and regulated in homologous cells. The 2.6-kb hGH fragment therefore contains non-tissue-specific cis-acting regulatory elements responsive to cAMP, hydrocortisone, and IGF-I. Specific IGF-I-responsive GH DNA sequences may therefore reside in the 0.5-kb 5'-flanking region, or in an intron, as described for hydrocortisone.
Evidence Suggesting That Galanin (GAL), Melanin-Concentrating Hormone (MCH), Neurotensin (NT), Proopiomelanocortin (POMC) and Neuropeptide Y (NPY) Are Targets of Leptin Signaling in the Hypothalamus (1998)

Leptin (OB protein) reduces food intake by acting at the hypothalamic level. The purpose of the present study was to identify potential targets of leptin signaling in the hypothalamus in ad-lib fed rats. Central administration of leptin (5 μg) for 3 days decreased food intake and body weight gain in association with a decrease in hypothalamic galanin (GAL), melanin-concentrating hormone (MCH), proopiomelanocortin (POMC) and neuropeptide Y (NPY) gene expression and with an increase in neurotensin (NT) gene expression. In pair-fed rats, NPY gene expression was increased and there was no change in either MCH, GAL, POMC or NT gene expression. This study identifies GAL, MCH, POMC and NT as non-NPY targets of leptin signaling and suggests that leptin’s action on food intake and body weight is most likely mediated by inhibiting excitatory (e.g. NPY, MCH, GAL, POMC) and stimulating inhibitory (e.g., NT) signals in the feeding circuitry.
Multi-modal sensing using photoactive thin films (2014)

The need for a reliable prognosis of the health of structural systems has promoted the development of sensing technologies capable of simultaneously detecting multiple types of damage. However, conventional sensors are designed to only measure a specific structural response (e.g., strain, displacement, or acceleration). This limitation forces one to use a wide variety of sensors densely instrumented on a given structure, which results in high overhead costs and requires extensive signal processing of raw sensor data. In this study, a photoactive thin film that has been engineered for multi-modal sensing to selectively detect strain and pH is proposed. In addition, the thin film is self-sensing in that it does not require external power to operate. Instead, light illumination causes the photoactive film to generate an electrical current, whose magnitude is directly related to applied strains (for deformations, impact or cracks) or pH (as a precursor of corrosion). First, the thin films were fabricated by spin-coating photoactive and conjugated polymers like poly(3-hexylthiophene) (P3HT). The thin film was also encoded with pH sensitivity by integrating polyaniline (PANI) as one component within the multilayered film architecture. Second, the optical response of the P3HT and PANI thin films subjected to applied strains or pH was characterized using absorption spectroscopy. Lastly, it was also verified that the thin films could selectively sense strain or pH depending on the wavelengths of light used for sensor interrogation.
Protein tyrosine kinases, with emphasis on the Src family. (1994)

Protein tyrosine phosphorylation is recognized to be an important regulatory event, particularly in those pathways that control cell growth and differentiation. Phosphorylation on tyrosine may either decrease or increase the enzymatic activity of substrate proteins. In addition, tyrosine phosphorylated sequences associate with Src homology 2 (SH2) domains, and thus tyrosine phosphorylation also serves to regulate protein/protein interactions. Many protein tyrosine kinases have been described to date: several are the receptors for peptide growth factors; others are expressed in the cytoplasm and nucleus. The main subject of this review will be the Src family of protein tyrosine kinases, a group of nine enzymes thought to play important roles in several signal transduction pathways.
A mutation at the universally conserved position 529 in Escherichia coli 16S rRNA creates a functional but highly error prone ribosome. (1995)

A base substitution of G to U was constructed at position 529 in Escherichia coli 16S rRNA. The U529 mutant ribosomes were functional and present on polysomes but were highly error prone and caused a progressive loss of cell viability. They displayed elevated levels of readthrough of stop codons and frameshifting, and an increase in thermal sensitivity of beta-galactosidase, suggestive of missense errors. These results demonstrate that the university conserved G529 is involved in tRNA selection at the A site during protein synthesis.
Beamforming via Large and Dense Antenna Arrays Above a Clutter (2013)

The paper sheds light on the beamforming (BF) performance of large (potentially unconstrained in size) as well as dense (but physically constrained in size) antenna arrays when equipped with arbitrarily many elements. Two operational modes are investigated: Single-layer BF and multi-layer BF. In the first mode, a realistic BF criterion namely the average BF gain is revisited and employed to understand the far-field and the near-field effects on the BF performance of large-scale antennas above a clutter. The diminishing throughput returns in a single-layer BF mode versus the number of antennas necessitate multi-layering. In the multi-layer BF mode, the RF coverage is divided into a number of directive non-overlapping sector-beams in a deterministic manner within a multi-user multi-input multi-output (MIMO) system. The optimal number of layers that maximizes the user's sum-rate given a constrained antenna array is found as a compromise between the multiplexing gain (associated with the number of sector-beams) and the inter-beam interference, represented by the side lobe level (SLL).
Binding Site Detection and Druggability Index from First Principles (2009)

In drug discovery, it is essential to identify binding sites on protein surfaces that drug-like molecules could exploit to exert a biological effect. Both X-ray crystallography and NMR experiments have demonstrated that organic solvents bind precisely at these locations. We show that this effect is reproduced using molecular dynamics with a binary solvent. Furthermore, analysis of the simulations give direct access to interaction free energies between the protein and small organic molecules, which can be used to detect binding sites and to predict the maximal affinity that a drug-like molecule could attain for them. On a set of pharmacologically relevant proteins, we obtain good predictions for druggable sites as well as for protein-protein and low affinity binding sites. This is the first druggability index not based on surface descriptors and, being independent of a training set, is particularly indicated to study unconventional targets such as protein-protein interactions or allosteric binding sites.
Organoapatites: Materials for artificial bone. III. Biological testing (1993)

This article reports on the in vivo testing of new artificial bone materials we have termed "organoapatites." These materials consist of mineral networks in which organic polymers are intimately dispersed by nucleation and growth of apatite crystals from a mother liquor containing the organic substances. Organoapatites were tested as implants in adult canine cortical bone for periods in the range from 12-35 weeks and fluorochromes were used in the model to investigate the kinetics of bone growth or repair. The analysis of histological samples was carried out using histomorphometric methods as well as fluorescence microscopy. Results showed excellent apposition of poly(amino acid) organoapatites with mineralized bone and fibrous encapsulation when a synthetic polyelectrolyte was the only organic component. This observation suggests that the molecularly dispersed organic dopant amounting to only 2-3% by weight of the microstructure can play a critical role in the tissue response to the implant. Relative to apatite controls, organoapatites were also found to have greater resistance to fragmentation in vivo and those containing amino acid units revealed interfacial bioerosion accompanied by regeneration of mineralized tissue. Design of organoapatite compositions and microstructures may therefore be useful in achieving the specific rate of biological response which is clinically desired.
Bone marrow fibrosis in myelofibrosis: pathogenesis, prognosis and targeted strategies (2016)

Bone marrow fibrosis is a central pathological feature and World Health Organization major diagnostic criterion of myelofibrosis. Although bone marrow fibrosis is seen in a variety of malignant and non-malignant disease states, the deposition of reticulin and collagen fibrosis in the bone marrow of patients with myelofibrosis is believed to be mediated by the myelofibrosis hematopoietic stem/progenitor cell, contributing to an impaired microenvironment favoring malignant over normal hematopoiesis. Increased expression of inflammatory cytokines, lysyl oxidase, transforming growth factor-β, impaired megakaryocyte function, and aberrant JAK-STAT signaling have all been implicated in the pathogenesis of bone marrow fibrosis. A number of studies indicate that bone marrow fibrosis is an adverse prognostic variable in myeloproliferative neoplasms. However, modern myelofibrosis prognostication systems utilized in risk-adapted treatment approaches do not include bone marrow fibrosis as a prognostic variable. The specific effect on bone marrow fibrosis of JAK2 inhibition, and other rationally based therapies currently being evaluated in myelofibrosis, has yet to be fully elucidated. Hematopoietic stem cell transplantation remains the only curative therapeutic approach that reliably results in resolution of bone marrow fibrosis in patients with myelofibrosis. Here we review the pathogenesis, biological consequences, and prognostic impact of bone marrow fibrosis. We discuss the rationale of various anti-fibrogenic treatment strategies targeting the clonal hematopoietic stem/progenitor cell, aberrant signaling pathways, fibrogenic cytokines, and the tumor microenvironment.
Myocardin is a master regulator of smooth muscle gene expression (2003)

Virtually all smooth muscle genes analyzed to date contain two or more essential binding sites for serum response factor (SRF) in their control regions. Because SRF is expressed in a wide range of cell types, it alone cannot account for smooth muscle-specific gene expression. We show that myocardin, a cardiac muscle- and smooth muscle-specific transcriptional coactivator of SRF, can activate smooth muscle gene expression in a variety of nonmuscle cell types via its association with SRF. Homodimerization of myocardin is required for maximal transcriptional activity and provides a mechanism for cooperative activation of smooth muscle genes by SRF-myocardin complexes bound to different SRF binding sites. These findings identify myocardin as a master regulator of smooth muscle gene expression and explain how SRF conveys smooth muscle specificity to its target genes.
Clinical pharmacology of buprenorphine: Ceiling effects at high doses (1994)

This study shows a plateau on buprenorphine effects, consistent with its partial agonist classification, and that single doses of buprenorphine up to 70 times the recommended analgesic dose are well tolerated by nondependent humans.
Modern reaction-based indicator systems (2009)

Traditional analyte-specific synthetic receptors or sensors have been developed on the basis of supramolecular interactions (e.g., hydrogen bonding, electrostatics, weak coordinative bonds). Unfortunately, this approach is often subject to limitations. As a result, increasing attention within the chemical sensor community is turning to the use of analyte-specific molecular indicators, wherein substrate-triggered reactions are used to signal the presence of a given analyte. This tutorial review highlights recent reaction-based indicator systems that have been used to detect selected anions, cations, reactive oxygen species, and neutral substrates.
Inhibition of histamine secretion by wortmannin through the blockade of phosphatidylinositol 3-kinase in RBL-2H3 cells. (1993)

The surface engagement of high affinity immunoglobulin E receptor (Fc epsilon RI) of rat basophilic leukemia 2H3 (RBL-2H3) cells induced histamine secretion and leukotriene release following activation of the tyrosine kinase Lyn together with phosphatidylinositol 3-kinase (PI3-kinase). Wortmannin inhibited the activity of partially purified PI3-kinase from calf thymus, as well as the PI3-kinase activity in anti-PI3-kinase p85 immunoprecipitates from RBL-2H3 cells, at a concentration as low as 1.0 nM and with IC50 values of 3.0 nM, but did not inhibit PI4-kinase activity. The inhibition of PI3-kinase by wortmannin was irreversible. Wortmannin inhibited both Fc epsilon RI-mediated histamine secretion and leukotriene release up to 80% with IC50 values of 2.0 and 3.0 nM, respectively. Wortmannin inhibited PI3-kinase activity in intact cells up to 80% with an IC50 value of 2.0 nM, which is almost equal to those for PI3-kinase in vitro and for histamine secretion and leukotriene release. With anti-wortmannin antibody, we have shown that wortmannin binds to the 110-kDa protein, but not to PI3-kinase 85-kDa regulatory subunit both in vitro and in whole cells. Furthermore, there was a positive correlation between the potencies of wortmannin derivatives as inhibitors of PI3-kinase and as inhibitors of histamine secretion. Wortmannin had no effect on the activation of the tyrosine kinase Lyn. These results suggest that PI3-kinase is involved in the signal transduction pathway responsible for histamine secretion following stimulation of Fc epsilon RI and that wortmannin blocks these responses through direct interaction with the catalytic subunit of this enzyme.
Mutational activation of CheA, the protein kinase in the chemotaxis system of Escherichia coli (1994)

In Escherichia coli and Salmonella typhimurium, appropriate changes of cell swimming patterns are mediated by CheA, an autophosphorylating histidine protein kinase whose activity is regulated by receptor/transducer proteins. The molecular mechanism underlying this regulation remains unelucidated but may involve CheA shifting between high-activity and low-activity conformations. We devised an in vivo screen to search for potential hyperkinase variants of CheA and used this screen to identify two cheA point mutations that cause the CheA protein to have elevated autokinase activity. Each point mutation resulted in alteration of proline 337. In vitro, CheA337PL and CheA337PS autophosphorylated significantly more rapidly than did wild-type CheA. This rate enhancement reflected the higher affinities of the mutant proteins for ATP and an increased rate constant for acquisition by CheA of the gamma-phosphoryl group of ATP within a kinetically defined CheA.ATP complex. In addition, the mutant proteins reacted with ADP more rapidly than did wild-type CheA. We considered the possibility that the mutations served to lock CheA into an activated signaling conformation; however, we found that both mutant proteins were regulated in a normal fashion by the transducer Tsr in the presence of CheW. We exploited the activated properties of one of these mutants to investigate whether the CheA subunits within a CheA dimer make equivalent contributions to the mechanism of trans phosphorylation. Our results indicate that CheA trans phosphorylation may involve active-site residues that are located both in cis and in trans to the autophosphorylation site and that the two protomers of a CheA dimer make nonequivalent contributions in determining the affinity of the ATP-binding site(s) of CheA.