gebhart/patrepeval huggingface dataset:
Blockade of PDGF Receptors by Crenolanib Has Therapeutic Effect in Patient Fibroblasts and in Preclinical Models of Systemic Sclerosis (2017)

Systemic sclerosis (SSc) is a multi-organ fibrotic disease with few treatment options. Activated fibroblasts are the key effector cells in SSc responsible for the excessive production of collagen and the development of fibrosis. Platelet-derived growth factor (PDGF), a potent mitogen for cells of mesenchymal origin, has been implicated in the activation of SSc fibroblasts. Our aim was to examine the therapeutic potential of crenolanib, an inhibitor of PDGF receptor signaling, in cultured fibroblasts and in angiotensin II-induced skin and heart fibrosis. Crenolanib effectively inhibited proliferation and migration of SSc and healthy control fibroblasts and attenuated basal and transforming growth factor-β-induced expression of CCN2/CTGF and periostin. In contrast to healthy control fibroblasts, SSc fibroblasts proliferated in response to PDGFAA, whereas a combination of PDGFAA and CCN2 was required to elicit a similar response in healthy control fibroblasts. PDGF receptor α mRNA correlated with CCN2 and other fibrotic markers in the skin of SSc patients. In mice challenged with angiotensin II, PDGF receptor α-positive cells were increased in the skin and heart. These PDGF receptor α-positive cells co-localized with PDGF receptor β, procollagen, and periostin. Treatment with crenolanib attenuated the skin and heart fibrosis. Our data indicate that inhibition of PDGF signaling presents an attractive therapeutic approach for SSc.
Methods in laboratory investigation. Monoclonal antibodies to type IV collagen: probes for the study of structure and function of basement membranes. (1983)

Type IV collagen is one of the main constituents of basement membranes, yet it is unknown whether the structural framework at different sites is assembled from one unique type of molecule or whether different type IV collagen molecules exist. To study the composition, chemical identity, and organization of this protein in different organs we have prepared monoclonal antibodies to a type IV collagen preparation from human placenta. Swiss Webster mice were hyperimmunized, and splenic cells were fused with the three different myeloma cell lines SP2/0, NS1, and U1. Type IV collagen-specific hybrids were selected and cloned by limiting dilution and on hard agar. Monoclonal antibodies secreted by two clones were extensively characterized by ELISA-inhibition assay, immunoprecipitation, rotary shadowing, and immunofluorescence techniques. Unlike conventionally raised antibodies in rabbits, both monoclonal antibody reagents show species-specific binding exclusively to native type IV collagen from human placenta but not to a similar preparation from calf lung or to other types of collagen. After heat denaturation of the antigen binding was no longer observed. The M3F7 antibody-binding site is located within the triple helical domain of the type IV molecule, approximately 900 A removed from the amino terminal end as visualized by a metal shadow casting technique. The monoclonal antibody M3F7 precipitates material from pepsin-derived and radiolabeled type IV collagen, and analysis of the polypeptide chains in the immunoprecipitate by sodium dodecyl sulfate polyacrylamide gel electrophoresis suggests that two major fragments are contained in the precipitate, which yield polypeptides of about 100 and 50 kilodaltons. After rotary shadowing of antigen-antibody mixtures native collagen fragments of two different size classes that bind antibody are visualized. One fragment is approximately 1500 A in length, and the other measures about 2700 to 3000 A. The localization of the antigenic site on these fragments suggests that both are generated by pepsin cleavage at a site about 900 A removed from the amino terminal end. In immunofluorescence experiments the monoclonal antibodies stained all basement membranes in kidney, lung, placenta, or skin, suggesting that at least the type IV collagen molecule recognized by these monoclonal antibodies is shared by a variety of vascular and epithelial basement membranes.
Satellite Observations of the Tropical Terrestrial Carbon Balance and Interactions With the Water Cycle During the 21st Century (2021)

Abstract A constellation of satellites is now in orbit providing information about terrestrial carbon and water storage and fluxes. These combined observations show that the tropical biosphere has changed significantly in the last 2 decades from the combined effects of climate variability and land use. Large areas of forest have been cleared in both wet and dry forests, increasing the source of carbon to the atmosphere. Concomitantly, tropical fire emissions have declined, at least until 2016, from changes in land‐use practices and rainfall, increasing the net carbon sink. Measurements of carbon stocks and fluxes from disturbance and recovery and of vegetation photosynthesis show significant regional variability of net biosphere exchange and gross primary productivity across the tropics and are tied to seasonal and interannual changes in water fluxes and storage. Comparison of satellite based estimates of evapotranspiration, photosynthesis, and the deuterium content of water vapor with patterns of total water storage and rainfall demonstrate the presence of vegetation‐atmosphere interactions and feedback mechanisms across tropical forests. However, these observations of stocks, fluxes and inferred interactions between them do not point unambiguously to either positive or negative feedbacks in carbon and water exchanges. These ambiguities highlight the need for assimilation of these new measurements with Earth System models for a consistent assessment of process interactions, along with focused field campaigns that integrate ground, aircraft and satellite measurements, to quantify the controlling carbon and water processes and their feedback mechanisms.
Expression and location of Hsp70/Hsc-binding anti-apoptotic protein BAG-1 and its variants in normal tissues and tumor cell lines. (1998)

BAG-1 is a multifunctional protein that blocks apoptosis and interacts with several types of proteins, including Bcl-2 family proteins, the kinase Raf-1, certain tyrosine kinase growth factor receptors, and steroid hormone receptors, possibly by virtue of its ability to regulate the Hsp70/Hsc70 family of molecular chaperones. Two major forms of the human and mouse BAG-1 proteins were detected by immunoblotting. The longer human and mouse BAG-1 proteins (BAG-1L) appear to arise through translation initiation at noncanonical CTG codons located upstream of and in-frame with the usual ATG codon used for production of the originally described BAG-1 protein. Immunoblotting experiments using normal tissues revealed that BAG-1L is far more restricted in its expression and is present at lower levels than the more prevalent BAG-1 protein. Human but not mouse tissues also produce small amounts of an additional isoform of BAG-1 of intermediate size (BAG-1M) that probably arises through translation initiation at yet another site involving an ATG codon. All three isoforms of human BAG-1 (BAG-1, BAG-1M, and BAG-1L) retained the ability to bind Hsc70. Subcellular fractionation and immunofluorescence confocal microscopy studies indicated that BAG-1L often resides in the nucleus, consistent with the presence of a nuclear localization sequence in the NH2-terminal unique domain of this protein. In immunohistochemical assays, BAG-1 immunoreactivity was detected in a wide variety of types of cells in normal adult tissues and was localized to either cytosol, nucleus, or both, depending on the particular type of cell. In some cases, cytosolic BAG-1 immunostaining was clearly associated with organelles resembling mitochondria, consistent with the reported interaction of BAG-1 with Bcl-2 and related proteins. Furthermore, experiments using a green fluorescence protein (GFP)-BAG-1 fusion protein demonstrated that overexpression of Bcl-2 in cultured cells can cause intracellular redistribution of GFP-BAG-1, producing a membranous pattern typical of Bcl-2 family proteins. The BAG-1 protein was found at high levels in several types of human tumor cell lines among the 67 tested, particularly leukemias, breast, prostate, and colon cancers. In contrast to normal tissues, which only rarely expressed BAG-1L, tumor cell lines commonly contained BAG-1L protein, including most prostate, breast, and leukemia cell lines, suggesting that a change in BAG-1 mRNA translation frequently accompanies malignant transformation.
Single–machine scheduling with random machine breakdowns and randomly compressible processing times (2000)

This work presents a model of single–machine scheduling problem. The machine is failure–prone and subject to random breakdowns. The processing time is a deterministic sequence that is randomly compressible, which may be from the introduction of new technology or addition of new equipment. Taking into account the cost for the random breakdowns and the random compressible processing time, our objective is to find the optimal scheduling policy to minimize an objective function. Under simple conditions, it is shown that the optimal sequence possesses a V-shape property
LIND/ABIN-3 Is a Novel Lipopolysaccharide-inducible Inhibitor of NF-κB Activation (2006)

Recognition of lipopolysaccharide (LPS) by Toll-like receptor (TLR)4 initiates an intracellular signaling pathway leading to the activation of nuclear factor-kappaB (NF-kappaB). Although LPS-induced activation of NF-kappaB is critical to the induction of an efficient immune response, excessive or prolonged signaling from TLR4 can be harmful to the host. Therefore, the NF-kappaB signal transduction pathway demands tight regulation. In the present study, we describe the human protein Listeria INDuced (LIND) as a novel A20-binding inhibitor of NF-kappaB activation (ABIN) that is related to ABIN-1 and -2 and, therefore, is further referred to as ABIN-3. Similar to the other ABINs, ABIN-3 binds to A20 and inhibits NF-kappaB activation induced by tumor necrosis factor, interleukin-1, and 12-O-tetradecanoylphorbol-13-acetate. However, unlike the other ABINs, constitutive expression of ABIN-3 could not be detected in different human cells. Treatment of human monocytic cells with LPS strongly induced ABIN-3 mRNA and protein expression, suggesting a role for ABIN-3 in the LPS/TLR4 pathway. Indeed, ABIN-3 overexpression was found to inhibit NF-kappaB-dependent gene expression in response to LPS/TLR4 at a level downstream of TRAF6 and upstream of IKKbeta. NF-kappaB inhibition was mediated by the ABIN-homology domain 2 and was independent of A20 binding. Moreover, in vivo adenoviral gene transfer of ABIN-3 in mice reduced LPS-induced NF-kappaB activity in the liver, thereby partially protecting mice against LPS/D-(+)-galactosamine-induced mortality. Taken together, these results implicate ABIN-3 as a novel negative feedback regulator of LPS-induced NF-kappaB activation.
Bone Marrow Aspirate: Rationale and Aspiration Technique (2016)

Adult bone marrow is a rich source of stem cells that can be induced to undergo differentiation into a variety of adult tissues. This chapter presents a technique for obtaining such stem cells from bone marrow aspirate (BMA) for use in implant site development. The aspiration procedure is simple and has minimal post-operative morbidity. It eliminates the need for a second surgical site to harvest autogenous bone and the stem cells contained within the aspirate populate the graft site with osteoblasts. The biological rationale for use of bone marrow aspirate is also briefly discussed.
Symptom Provocation During Aerobic and Dynamic Supervised Exercise Challenges in Adolescents With Sport-Related Concussion (2021)

The ASEC alone may not detect symptom provocation in a significant proportion of concussion patients who otherwise would develop symptoms during a DSEC.
An Evaluation of Stratified Sampling of Microarchitecture Simulations (2004)

Recent research advocates applying sampling to accelerate microarchitecture simulation. Simple random sampling offers accurate performance estimates (with a high quantifiable confidence) by taking a large number (e.g., 10,000) of short performance measurements over the full length of a benchmark. Simple random sampling does not exploit the often repetitive behaviors of benchmarks, collecting many redundant measurements. By identifying repetitive behaviors, we can apply stratified random sampling to achieve the same confidence as simple random sampling with far fewer measurements. Our oracle limit study of optimal stratified sampling of SPEC CPU2000 benchmarks demonstrates an opportunity to reduce required measurement by 43x over simple random sampling. Using our oracle results as a basis for comparison, we evaluate two practical approaches for selecting strata, program phase detection and IPC profiling. Program phase detection is attractive because it is microarchitecture independent, while IPC profiling directly minimizes stratum variance, therefore minimizing sample size. Unfortunately, our results indicate that: (1) program phase stratification falls far short of optimal opportunity, (2) IPC profiling requires expensive microarchitecturespecific analysis, and (3) both methods require large sampling unit sizes to make strata selection feasible, offsetting their reductions of sample size. We conclude that, without better stratification approaches, stratified sampling does not provide a clear advantage over simple random sampling. 1.
Automatic Sequence Design of Major Histocompatibility Complex Class I Binding Peptides Impairing CD8+ T Cell Recognition (2003)

An automatic protein design procedure was used to compute amino acid sequences of peptides likely to bind the HLA-A2 major histocompatibility complex (MHC) class I allele. The only information used by the procedure are a structural template, a rotamer library, and a well established classical empirical force field. The calculations are performed on six different templates from x-ray structures of HLA-A0201-peptide complexes. Each template consists of the bound peptide backbone and the full atomic coordinates of the MHC protein. Sequences within 2 kcal/mol of the minimum energy sequence are computed for each template, and the sequences from all the templates are combined and ranked by their energies. The five lowest energy peptide sequences and five other low energy sequences re-ranked on the basis of their similarity to peptides known to bind the same MHC allele are chemically synthesized and tested for their ability to bind and form stable complexes with the HLA-A2 molecule. The most efficient binders are also tested for inhibition of the T cell receptor recognition of two known CD8(+) T effectors. Results show that all 10 peptides bind the expected MHC protein. The six strongest binders also form stable HLA-A2-peptide complexes, albeit to varying degrees, and three peptides display significant inhibition of CD8(+) T cell recognition. These results are rationalized in light of our knowledge of the three-dimensional structures of the HLA-A2-peptide and HLA-A2-peptide-T cell receptor complexes.
A comparison of polynomial approximations and artificial neural netsas response surfaces (1992)

Artificial neural nets and polynomial approximations were used to develop response surfaces for several test problems. Based on the number of functional evaluations required to build the approximations and the number of undetermined parameters associated with the approximations, the performance of the two types of approximations was found to be comparable. A rule of thumb is developed for determining the number of nodes to be used on a hidden layer of an artificial neural net, and the number of designs needed to train an approximation is discussed.
Tight Bounds for Adversarially Robust Streams and Sliding Windows via Difference Estimators (2020)

In the adversarially robust streaming model, a stream of elements is presented to an algorithm and is allowed to depend on the output of the algorithm at earlier times during the stream. In the classic insertion-only model of data streams, Ben-Eliezer et. al. (PODS 2020, best paper award) show how to convert a non-robust algorithm into a robust one with a roughly $1/\varepsilon$ factor overhead. This was subsequently improved to a $1/\sqrt{\varepsilon}$ factor overhead by Hassidim et. al. (NeurIPS 2020, oral presentation), suppressing logarithmic factors. For general functions the latter is known to be best-possible, by a result of Kaplan et. al. (CRYPTO 2021). We show how to bypass this impossibility result by developing data stream algorithms for a large class of streaming problems, with no overhead in the approximation factor. Our class of streaming problems includes the most well-studied problems such as the $L_2$-heavy hitters problem, $F_p$-moment estimation, as well as empirical entropy estimation. We substantially improve upon all prior work on these problems, giving the first optimal dependence on the approximation factor. As in previous work, we obtain a general transformation that applies to any non-robust streaming algorithm and depends on the so-called twist number. However, the key technical innovation is that we apply the transformation to what we call a difference estimator for the streaming problem, rather than an estimator for the streaming problem itself. We then develop the first difference estimators for a wide range of problems. Our difference estimator methodology is not only applicable to the adversarially robust model, but to other streaming models where temporal properties of the data play a central role. (Abstract shortened to meet arXiv limit.)
Safety and technical efficacy of over-the-wire balloons for the treatment of subarachnoid hemorrhage–induced cerebral vasospasm (2006)

Over-the-wire balloons involve a low risk for vessel rupture. The anterior cerebral artery remains difficult to access and successfully treat with current devices. Further improvements in balloon design, such as smaller inflated diameters and better tracking, are necessary. Finally, thromboembolic complications remain an important concern, and severe vasospasm may recur after balloon angioplasty.
Modeling energy of the clock generation and distribution circuitry (2002)

In this paper, we propose an analytical model that accurately accounts for all the load per independent unit that has to be driven by the clock distribution network, the power budget required by the clock generation circuitry and the energy required to distribute the clock all around the chip. Such a model is of extreme importance in completing a framework for architectural-level decisions on total power budget. The validation of the analytical model for the clock generation circuit energy using VLSI layouts shows an average error of 9% as compared to the actual values.
Prevention of spontaneous hepatocellular carcinoma in long-evans cinnamon rats with hereditary hepatitis by th administration of d-penicillamine (1993)

Acute hepatitis spontaneously develops in the Long-Evans Cinnamon rat at the age of 4 mo, and eventually hepatocellular carcinoma develops after the chronic hepatitis that persists for over a year. Previously, abnormal copper accumulation was found in the livers of Long-Evans Cinnamon rats from birth, and it was reported that short-term administration of D-penicillamine, a copper-chelating agent, prevented acute hepatitis in Long-Evans Cinnamon rats. In this study we investigated whether long-term administration of D-penicillamine could also prevent chronic hepatitis and subsequent hepatocellular carcinoma in Long-Evans Cinnamon rats. During long-term observation, which was continued from 11 to 70 wk after birth, no elevation of serum transaminase levels was observed in the Long-Evans Cinnamon rats treated with D-penicillamine. Moreover, no histological changes characteristic of the chronic hepatitis were observed in D-penicillamine-treated Long-Evans Cinnamon rats, which were killed at 70 wk of age. Furthermore, placental glutathione S-transferase-positive foci, described as a marker for preneoplastic lesions in the liver, were not detected, and thus hepatocarcinogenesis was completely prevented in D-penicillamine-treated Long-Evans Cinnamon rats. We also found that the amount of 8-hydroxy-deoxyguanosine, one of oxidative DNA damage products in the liver, was decreased in the Long-Evans Cinnamon rats treated with D-penicillamine. These findings suggest that a process of the prolonged liver-cell injury and regeneration was essential for spontaneous development of hepatocellular carcinoma in Long-Evans Cinnamon rats with abnormal copper metabolism.
ELECTIVE LAPAROSCOPIC CHOLECYSTECTOMY: IMPLICATIONS OF PROLONGED WAITING TIMES FOR SURGERY (2003)

Prolonged waiting times for elective LC are associated with morbidity in 14% of patients at the Launceston General Hospital. This, combined with frequent cancellation of elective surgery, may result in significant costs to the health-care sector.
Normal Glucagon Signaling and β-Cell Function After Near-Total α-Cell Ablation in Adult Mice (2011)

An extremely low amount of α-cells is sufficient to prevent a major counter-regulatory deregulation, both under physiologic and diabetic conditions. We previously reported that α-cells reprogram to insulin production after extreme β-cell loss and now conjecture that the low α-cell requirement could be exploited in future diabetic therapies aimed at regenerating β-cells by reprogramming adult α-cells.
Magnetic Nanoparticles: A Versatile Method for the Reductive, One‐Pot Synthesis of Bare, Hydrophilic and Hydrophobic Magnetite Nanoparticles (Adv. Funct. Mater. 8/2011) (2011)

Abstract A biocompatible, reliable, and particularly versatile synthesis of magnetic iron oxide nanoparticles (IONPs) is presented that uses iron(III) acetylacetonate Fe(acac) 3 as an iron precursor and sodium borohydride as a reducing agent. Both the reaction temperature and the concentration of the reducing agent have considerable effects on the IONP size. These dependencies can be used to prepare IONPs ranging in size from 5 to 8 nm, as determined by transmission electron microscopy (TEM). Synthesis at room temperature or with higher sodium borohydride concentrations always resulted in smaller particle sizes. Powder X‐ray diffraction patterns show the presence of an iron oxide phase with a cubic unit cell and allow for the determination of the lattice parameters and average crystallite sizes for all synthesized IONPs. Transmission Mössbauer spectroscopy shows that the as‐synthesized IONPs are pure magnetite (Fe 3 O 4 ) and is further used to elucidate the reaction pathway by analyzing iron intermediates formed prior to nanoparticle formation and precipitation. TEM and high‐resolution TEM reveal quasi‐spherical shapes and lattice fringes for most IONPs. With only minor modifications of the synthesis procedure, this versatile, one‐pot synthesis is proven to be suitable for the production of bare (uncoated) IONPs, IONPs with hydrophilic poly(ethylene glycol), L ‐arginine, and L ‐glutamic acid coatings, as well as IONPs with hydrophobic coatings such as oleic acid. All coated IONPs were characterized by FT‐IR spectroscopy. In addition, the bare IONPs could easily be modified post‐synthesis with a suitable capping agent using ultrasonication. To verify the biocompatibility of the IONPs, in vitro cytotoxicity studies were carried out on bare IONPs with intestinal (Caco2) and liver epithelial (HepG2) cell cultures using an 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay. Phase contrast microscopy after hematoxylin‐eosin staining showed the intact morphology of the Caco2 and HepG2 cells treated with IONPs.