gebhart/patrepeval huggingface dataset:
Cascade RPN: Delving into High-Quality Region Proposal Network with\n Adaptive Convolution (2019)

This paper considers an architecture referred to as Cascade Region Proposal\nNetwork (Cascade RPN) for improving the region-proposal quality and detection\nperformance by \\textit{systematically} addressing the limitation of the\nconventional RPN that \\textit{heuristically defines} the anchors and\n\\textit{aligns} the features to the anchors. First, instead of using multiple\nanchors with predefined scales and aspect ratios, Cascade RPN relies on a\n\\textit{single anchor} per location and performs multi-stage refinement. Each\nstage is progressively more stringent in defining positive samples by starting\nout with an anchor-free metric followed by anchor-based metrics in the ensuing\nstages. Second, to attain alignment between the features and the anchors\nthroughout the stages, \\textit{adaptive convolution} is proposed that takes the\nanchors in addition to the image features as its input and learns the sampled\nfeatures guided by the anchors. A simple implementation of a two-stage Cascade\nRPN achieves AR 13.4 points higher than that of the conventional RPN,\nsurpassing any existing region proposal methods. When adopting to Fast R-CNN\nand Faster R-CNN, Cascade RPN can improve the detection mAP by 3.1 and 3.5\npoints, respectively. The code is made publicly available at\n\\url{https://github.com/thangvubk/Cascade-RPN.git}.\n
Identification of a serpin-enzyme complex receptor on human hepatoma cells and human monocytes. (1990)

Formation of the covalently stabilized complex of alpha 1-antitrypsin (alpha 1-AT) with neutrophil elastase, the archetype of serine proteinase inhibitor serpin-enzyme complexes, is associated with structural rearrangement of the alpha 1-AT molecule and hydrolysis of a reactive-site peptide bond. An approximately 4-kDa carboxyl-terminal cleavage fragment is generated. alpha 1-AT-elastase complexes are biologically active, possessing chemotactic activity and mediating increases in expression of the alpha 1-AT gene in human monocytes and macrophages. This suggested that structural rearrangement of the alpha 1-AT molecule, during formation of a complex with elastase, exposes a domain that is recognized by a specific cell surface receptor or receptors. To test this hypothesis, the known three-dimensional structure of alpha 1-AT and comparisons of the primary structures of the serpins were used to select a potentially exteriorly exposed and highly conserved region in the complexed form of alpha 1-AT as a candidate ligand (carboxyl-terminal fragment, amino acids 359-374). We show here that synthetic peptides based on the sequence of this region bind specifically and saturably to human hepatoma cells and human monocytes (Kd = 4.0 X 10(-8) M, 4.5 X 10(5) plasma membrane receptors per cell) and mediate increases in synthesis of alpha 1-AT. Binding of peptide 105Y (Ser-Ile-Pro-Pro-Glu-Val-Lys-Phe-Asn-Lys-Pro-Phe-Val-Tyr-Leu-Ile) is blocked by alpha 1-AT-elastase complexes, antithrombin III (AT III)-thrombin complexes, alpha 1-antichymotrypsin (alpha 1-ACT)-cathepsin G complexes, and, to a lesser extent, complement component C1 inhibitor-C1s complexes, but not by the corresponding native proteins. Binding of peptide 105Y is also blocked by peptides with sequence corresponding to carboxy-terminal fragments of the serpins AT III and alpha 1-ACT, but not by peptides having the sequence of the extreme amino terminus of alpha 1-AT. The results also show that peptide 105Y inhibits binding of 125I-labeled alpha 1-AT-elastase complexes. Thus, these studies demonstrate an abundant, relatively high-affinity cell surface receptor which recognizes serpin-enzyme complexes (SEC receptor). This receptor is capable of modulating the production of at least one of the serpins, alpha 1-AT. Since the ligand specificity is similar to that previously described for in vivo clearance of serpin-enzyme complexes, the SEC receptor may also be involved in the clearance of certain serpin-enzyme complexes.
Induction of Protective Immunity against Lethal Anthrax Challenge with a Patch (2004)

Anthrax vaccine patches stimulated robust and functional immune responses that protected against lethal challenge. Demonstration of responses in the lung suggests that a mechanism exists for protection against challenge with aerosolized anthrax spores. A formulated, pressure-sensitive, dry adhesive patch, which is stable and can be manufactured in large scale, elicited comparable immunoglobulin G and TNA responses, suggesting that an anthrax vaccine patch is feasible and should advance into clinical evaluation.
Molecular-weight-dependent mobilities in regioregular poly(3-hexyl-thiophene) diodes (2005)

We have investigated the transport properties in the direction perpendicular to the substrate of regioregular poly(3-hexyl-thiophene) of different molecular weights (MW) in a diode geometry. In these devices, which exhibit space-charge-limited behavior, we find that the mobility values at room temperature increase from 1.33×10−5cm2∕Vsto3.30×10−4cm2∕Vs as the MW is increased from 2.9to31.1kg∕mol. The mobility is found to be field independent for high MW films, but field dependent for the low MW films. The current–voltage characteristics of the diodes are also studied as a function of temperature from 160Kto300K. The activation energy for carrier transport, extracted from the Arrhenius plot, is found to decrease gradually from 143meVto126meV as the MW is increased.
Flattened optical multicarrier generation of 12.5GHz spaced 256 channelsbased on sinusoidal amplitude and phase hybrid modulation (2001)

A novel flattened optical multicarrier generation scheme that is based on a sinusoidal amplitude-phase hybrid modulation technique is proposed. The performance of this proposed scheme is confirmed analytically and experimentally, and its support of up to 256 channels is demonstrated.
Architecture for Personal Text Entry Methods (2003)

Abstract: Text entry is special kind of human-computer interaction in one respect: it is a highly learned activity, and unlike some others it needs to be so. Writing is not an inborn or trivially acquired skill like pointing and reacting to simple stimuli. Because learning a writing method is expensive, users benefit from using the same method in different situations. We describe an architecture that supports text entry methods that follow the user from device to device. The architecture consists of a server and text entry method implementations that the server downloads from the Internet. Text entry method selection is based on user preference and input device compatibility. We use Java for implementing the text entry methods so that the same code can be run on different platforms. The server is not similarly platform independent. Currently we have implementations for
Sulfhydryl Oxidase from Egg White (1999)

Both metalloprotein and flavin-linked sulfhydryl oxidases catalyze the oxidation of thiols to disulfides with the reduction of oxygen to hydrogen peroxide. Despite earlier suggestions for a role in protein disulfide bond formation, these enzymes have received comparatively little general attention. Chicken egg white sulfhydryl oxidase utilizes an internal redox-active cystine bridge and a FAD moiety in the oxidation of a range of small molecular weight thiols such as glutathione, cysteine, and dithiothreitol. The oxidase is shown here to exhibit a high catalytic activity toward a range of reduced peptides and proteins including insulin A and B chains, lysozyme, ovalbumin, riboflavin-binding protein, and RNase. Catalytic efficiencies are up to 100-fold higher than for reduced glutathione, with typical K(m) values of about 110-330 microM/protein thiol, compared with 20 mM for glutathione. RNase activity is not significantly recovered when the cysteine residues are rapidly oxidized by sulfhydryl oxidase, but activity is efficiently restored when protein disulfide isomerase is also present. Sulfhydryl oxidase can also oxidize reduced protein disulfide isomerase directly. These data show that sulfhydryl oxidase and protein disulfide isomerase can cooperate in vitro in the generation and rearrangement of native disulfide pairings. A possible role for the oxidase in the protein secretory pathway in vivo is discussed.
Thrombopoietin Combined with Early‐Acting Growth Factors Effectively Expands Human Hematopoietic Progenitor Cells In Vitro (1999)

Thrombopoietin (TPO) is established as a powerful stimulant of megakaryocyte differentiation and platelet production both in vivo and in vitro. In preparation for future transplantation of ex vivo expanded CD34+ hematopoietic progenitor cells (HPCs), we have examined the in vitro effect of TPO on cultures of HPC when combined with other early-acting hematopoietic growth factors (GFs) in an attempt to decrease post-transplant thrombocytopenia and accelerate engraftment. By adding TPO to all possible combinations of GM-CSF, IL-3, and c-kit ligand (CKL) in a suspension culture system, we found a significant increase in both relative and absolute numbers of cells in cultures containing TPO of the megakaryocytic lineage and CD34+ cells after 14 days of culture. The most efficient GF combinations for expansion of cell populations of the megakaryocytic lineage and HPCs were TPO, GM-CSF, and CKL, which increased the number of cells of the megakaryocytic lineage 78 fold and the number of CD34+ cells 1.8 fold. The number of CD34+ cells decreased in the cultures containing GM-CSF and CKL with no TPO present, and the number of cells of the megakaryocytic lineage was increased merely 27 fold. Based on our findings, we suggest adding cells from HPCs expanded in cultures containing TPO, GM-CSF, and CKL to unexpanded stem cells for stem cell transplantation.
Selective nucleophilic replacement of the benzylsulfanyl group in 2,4‐disulfanyl‐substituted thieno[2,3‐d]pyrimidin‐6‐carboxylic acid derivatives by secondary amines (2005)

Abstract Thieno[2,3‐ d ]pyrimidines with benzylsulfanyl and allylsulfanyl group in the presence of other alkylsul‐fanyl substituents react selectively under mild conditions with secondary amines under replacement of the benzyl or allyl residue whereas the other substituents remain intact. This enables the synthesis of different basic substituted derivatives with potentially biologically activity.
Scaled‐up production of mammalian neural precursor cell aggregates in computer‐controlled suspension bioreactors (2006)

The clinical use of neural precursor cells (NPCs) for the treatment of neurological diseases, such as Parkinson's disease and Huntington's disease, requires overcoming the scarcity of these cells through controlled expansion. The main objective of the present study was to develop a large-scale computer-controlled bioprocess for the expansion of mammalian NPCs in suspension culture by scaling up existing reactor protocols. In order to support the oxygen demands of the maximum cell densities achieved, the volumetric mass transfer coefficient was kept above 1.10/h while scaling-up from small-scale 125 mL vessels to large-scale 500 mL bioreactors. In addition, the maximum shear stress at the impeller tip was maintained between 0.30 and 0.75 Pa to reduce damage to the cells. The resulting large-scale bioprocess achieved maximum viable cell densities of 1.2 x 10(6) cells/mL and a batch multiplication ratio of 9.1. Moreover, the process successfully maintained the NPC characteristics observed in small-scale studies.
Fast evaluation of union-intersection expressions (2007)

We show how to represent sets in a linear space data structure such that expressions involving unions and intersections of sets can be computed in a worst-case efficient way. This problem has applications in e.g. information retrieval and database systems. We mainly consider the RAM model of computation, and sets of machine words, but also state our results in the I/O model. On a RAM with word size $w$, a special case of our result is that the intersection of $m$ (preprocessed) sets, containing $n$ elements in total, can be computed in expected time $O(n (\log w)^2 / w + km)$, where $k$ is the number of elements in the intersection. If the first of the two terms dominates, this is a factor $w^{1-o(1)}$ faster than the standard solution of merging sorted lists. We show a cell probe lower bound of time $Ω(n/(w m \log m)+ (1-\tfrac{\log k}{w}) k)$, meaning that our upper bound is nearly optimal for small $m$. Our algorithm uses a novel combination of approximate set representations and word-level parallelism.
DISTRIBUTION AND ANTI‐INFLAMMATORY EFFECT OF MESALAZINE ON CARRAGEENAN‐INDUCED COLITIS IN THE RABBIT (1996)

1. A controlled-release preparation of mesalazine microgranules (PentasaR; Ferring AS, Vanlose, Denmark) releases the active ingredient over a wide area from the small intestine to the rectum and is consequently expected to bring about therapeutic benefits to patients with ulcerative colitis and Crohn's disease. 2. Mesalazine microgranules (50 or 150 mg/kg per day) were administered orally to each rabbit with carrageenan-induced colitis for six weeks. Its inhibitory effect on colonic mucosal damage was assessed in terms of the microscopic damage scores, leukotriene B4 concentrations and concentrations of mesalazine derivatives. 3. At the end of the experiment, the mesalazine 150 mg group had gained a significantly greater bodyweight than the control group. Microscopic damage was significantly lower in the 150 mg group than in the untreated control group. Tissue concentrations of 5-aminosalicylic acid and acetyl-5-amino-salicylic acid in the small and large intestine were higher in the 150 mg group than in the 50 mg group. Mucosal leukotriene B4 levels tended to be lower in rabbits receiving the larger dose of mesalazine. 4. The present study indicates that slow release 5-amino-salicylic acid at the larger dose reaches the large bowel in sufficiently high concentrations following oral administration and significantly reduces carrageenan-induced colitis in the rabbit.
Terminal-modified polylysine-based chelating polymers: highly efficient coupling to antibody with minimal loss in immunoreactivity (1991)

A method is suggested for the preparation of chelating polymers containing a single terminal reactive group capable of interaction with proteins. These polymers were synthesized from N-CBZ-polylysine and DTPA and contain a terminal SH or pyridyldisulfide group. A polymer molecule with MW 13,500 is able to carry up to 40 DTPA residues. Polymers easily and quantitatively bind with antibodies (Fab fragments of antimyosin antibodies R11D10) with minimal effect on antibody immunoreactivity as revealed in ELISA assay and in direct immunoanalysis. Conjugates prepared can chelate radioactive metal ions reaching very high specific radioactivity (greater than 1 mCi 111In/10 micrograms of protein). Perspectives for their application are discussed.
Anti–CTLA-4 therapy broadens the melanoma-reactive CD8 + T cell response (2014)

Anti-CTLA-4 treatment improves the survival of patients with advanced-stage melanoma. However, although the anti-CTLA-4 antibody ipilimumab is now an approved treatment for patients with metastatic disease, it remains unknown by which mechanism it boosts tumor-specific T cell activity. In particular, it is unclear whether treatment amplifies previously induced T cell responses or whether it induces new tumor-specific T cell reactivities. Using a combination ultraviolet (UV)-induced peptide exchange and peptide-major histocompatibility complex (pMHC) combinatorial coding, we monitored immune reactivity against a panel of 145 melanoma-associated epitopes in a cohort of patients receiving anti-CTLA-4 treatment. Comparison of pre- and posttreatment T cell reactivities in peripheral blood mononuclear cell samples of 40 melanoma patients demonstrated that anti-CTLA-4 treatment induces a significant increase in the number of detectable melanoma-specific CD8 T cell responses (P = 0.0009). In striking contrast, the magnitude of both virus-specific and melanoma-specific T cell responses that were already detected before start of therapy remained unaltered by treatment (P = 0.74). The observation that anti-CTLA-4 treatment induces a significant number of newly detected T cell responses-but only infrequently boosts preexisting immune responses-provides strong evidence for anti-CTLA-4 therapy-enhanced T cell priming as a component of the clinical mode of action.
Patch‐Clamp Analysis of Direct Steroidal Modulation of Glutamate Receptor‐Channels (1994)

Steroid hormones regulate the neuroendocrine and behavioral functions of the brain by using a number of diverse cellular mechanisms. Many steroids exert rapid electrophysiological effects on neurons, involving specific interactions with membrane components, such as neurotransmitter receptors. Previous studies suggest that the steroids, estrogen and pregnenolone sulfate (PS), might directly modulate glutamate receptors. The present experiments utilized patch-clamp recording of glutamate receptor-channels in excised membrane patches to test for direct modulation by these steroids. Characteristic single-channel activity from N-methyl-D-aspartate (NMDA) receptors could be elicited in both inside-out and outside-out patches excised from acutely dissociated hippocampal neurons. PS, but not 17 beta-estradiol, increased the open probability of NMDA channel activity in inside-out and outside-out patches. The PS-induced increase in open probability could be attributed to an increase in both frequency of opening and mean open time of the NMDA receptor, though the effect on frequency of opening was more prominent. The non-NMDA agonist, kainate, induced continuous shifts and increased noise in the baseline current of outside-out patches, but rarely activated clearly resolvable single-channel openings. 17 beta-estradiol and PS had no apparent effect on the kainate-induced currents. These findings suggest that some steroids can directly modulate glutamate receptors, but other steroids may utilize indirect mechanisms for regulating glutamatergic synaptic transmission.
Incidental magnetization transfer contrast in fast spin‐echo imaging of cartilage (1996)

In this article, the authors illustrate the contributions of incidental magnetization transfer contrast (MTC) to the signal characteristics of patellar cartilage on routine, multiplanar fast spin-echo (FSE) images. Incidental MTC diminishes the signal of patellar cartilage by 30% on routine FSE scans. Spectral fat saturation does not significantly increase incidental MTC on multislice FSE acquisitions. By increasing the contrast between synovial fluid and patellar cartilage, incidental MTC may account for greater conspicuousness of chondromalacia on FSE as compared to conventional spin-echo images. Incidental MTC may also alter or obscure the normal, laminar appearance of hyaline cartilage on short-TE, FSE images.
“10” (2003)

Journal of the American Academy of Orthopaedic Surgeons: January 2003 - Volume 11 - Issue 1 - p 5
Creation of Novel Cell-Penetrating Peptides for Intracellular Drug Delivery Using Systematic Phage Display Technology Originated from Tat Transduction Domain (2007)

Many biologically active proteins need to be delivered intracellularly to exert their therapeutic action inside the cytoplasm. Cell penetrating peptides (CPPs) have been developed to efficiently deliver a wide variety of cargo in a fully biological active form into a range of cell types for the treatment of multiple preclinical disease models. To further develop this methodology, we established a systematic approach to identify novel CPPs using phage display technology. Firstly, we screened a phage peptide library for peptides that bound to the cell membrane. Secondly, to assess functionality as intracellular carriers, we recombined cDNAs of binding peptides with protein synthesis inhibitory factor (PSIF) to create fusion proteins. Randomly chosen clones were cultured and expression of peptide-PSIF fusion proteins induced, followed by screening of protein synthesis activity in cells. Using this systematic approach, novel and effective CPPs were rapidly identified. We suggest that these novel cell-penetrating peptides can utilized as drug delivery tools for protein therapy or an analytical tool to study mechanisms of protein transduction into the cytoplasm.
A Universal and Facile Approach for the Formation of a Protein Hydrogel for 3D Cell Encapsulation (2015)

A universal and facile approach to modifying proteins so that they can rapidly form hydrogel upon mixing with crosslinkers is presented. The concept of it is to introduce maleimide, which is highly reactive with dithiol‐containing crosslinkers via thiol‐ene click chemistry, onto proteins. Bovine serum albumin (BSA) is used as a model protein due to its good stability and low cost. The results here show that a protein hydrogel can be readily formed by blending modified BSA and resilin‐related peptide crosslinker solutions at a proper ratio. The hydrogel exhibits good elasticity and tunable mechanical as well as biochemical properties. Moreover, it allows convenient 3D cell encapsulation and shows good biocompatibility. Muscle cells embedded in the hydrogel are promoted to spread by incorporating arginyl‐glycyl‐aspartic acid (RGD)‐containing peptide into the system, thus warranting a bright future of it in regenerative medicine.
Appendix to Chapter 16 (1991)

Probability theory is nowadays applied in a huge variety of fields including physics, engineering, biology, economics and the social sciences. This book is a modern, lively and rigorous account which has Doob's theory of martingales in discrete time as its main theme. It proves important results such as Kolmogorov's Strong Law of Large Numbers and the Three-Series Theorem by martingale techniques, and the Central Limit Theorem via the use of characteristic functions. A distinguishing feature is its determination to keep the probability flowing at a nice tempo. It achieves this by being selective rather than encyclopaedic, presenting only what is essential to understand the fundamentals; and it assumes certain key results from measure theory in the main text. These measure-theoretic results are proved in full in appendices, so that the book is completely self-contained. The book is written for students, not for researchers, and has evolved through several years of class testing. Exercises play a vital rôle. Interesting and challenging problems, some with hints, consolidate what has already been learnt, and provide motivation to discover more of the subject than can be covered in a single introduction.
A novel murine anti-human Fas mAb which mitigates lymphadenopathy without hepatotoxicity (2000)

Defects in Fas-mediated apoptosis are implicated in autoimmune diseases including rheumatoid arthritis (RA). Although induction of Fas-mediated apoptosis could have therapeutic effects on these diseases, it might cause deleterious effects in liver as Fas ligand or an agonistic anti-murine Fas antibody Jo2 causes severe hepatic injury in mice. We report here on the interesting characteristics of the newly obtained anti-Fas mAb, HFE7A, which cross-reacts with the Fas molecules of various species ranging from human to mouse and mitigates autoimmune symptoms without hepatotoxicity in mice. The administration of HFE7A to mice induced apoptosis in the thymocytes, although administration of HFE7A to mice or to marmosets did not induce any sign of hepatitis. The effect of HFE7A on liver is different from that of anti-murine Fas antibody Jo2, which causes acute and lethal hepatic injury to mice. Administration of HFE7A reduced lymphadenopathy and abnormal T cells in MRL-gld/gld mice. HFE7A induced apoptosis in synovial cells prepared from RA patients. Surprisingly, HFE7A protected mice from fulminant hepatitis induced by Jo2. Therefore, HFE7A is a potential therapeutic antibody not only for autoimmune diseases including RA but also for fulminant hepatitis.
Effect of Heart Transplantation on Survival in Ambulatory and Decompensated Heart Failure (2008)

HTx remains an effective treatment of advanced HF. Prioritization of patients with refractory HF is rational, because they are the first to benefit.