gebhart/patrepeval huggingface dataset:
Effect of the myb gene product on expression of the PCNA gene in fibroblasts. (1991)

Tk-ts13 cells are BHK-derived fibroblasts that have a G1-specific temperature sensitive (ts) mutation so that the cells arrest in the G1 phase of the cell cycle at the restrictive temperature of 39.6 degrees. We have introduced into these cells a plasmid carrying the human c-myb cDNA under the control of the early SV40 promoter. The resulting cell line, ts13 myb cells, express the c-myb RNA and protein and, when serum-stimulated, they undergo one round of DNA replication even at the restrictive temperature. Under the same conditions, the parent cell line (tk-ts13 cells) are blocked in G1 and fail to replicate DNA. We have investigated the expression of two late growth-regulated genes, PCNA and histone H3, in tk-ts13 and in ts 13 myb cells, both at permissive and restrictive temperature. At the permissive temperature of 34 degrees, the mRNA levels for PCNA and histone H3 increase markedly after serum stimulation in both cell lines, reaching a peak at the time of DNA synthesis. At the restrictive temperature of 39.6 degrees, the mRNA's for PCNA, and histone H3 are detectable in serum-stimulated ts13 myb cells while they are not detectable in the parent tk-ts13 cell line. Run-on transcription assays indicate that these 2 genes are transcribed in tk-ts13 cells equally well at permissive and nonpermissive temperatures, and that the presence of the myb product does not significantly increase their rates of transcription. The stability of the respective mRNA's is roughly the same at either temperature and in both types of cells. These results indicate: (1) a constitutively expressed c-myb gene product confers to fibroblasts the ability of temporarily by-passing a ts block in the G1 phase of the cell cycle and (2) the myb product, under these conditions, regulates the mRNA levels of PCNA and histone H3 either directly or indirectly by a post-transcriptional mechanism.
A Machine Learning‐Enabled Autonomous Flow Chemistry Platform for Process Optimization of Multiple Reaction Metrics (2020)

Abstract Self‐optimization of chemical reactions using machine learning multi‐objective algorithms has the potential to significantly shorten overall process development time, providing users with valuable information about economic and environmental factors. Using the Thompson Sampling Efficient Multi‐Objective (TS‐EMO) algorithm, the self‐optimization flow chemistry system in this report demonstrates the ability to identify optimum reaction conditions and trade‐offs (Pareto fronts) between conflicting optimization objectives, such as yield, cost, space‐time yield, and E‐factor, in a data efficient manner. Advantageously, the robust system consists of exclusively commercially available equipment and a user‐friendly MATLAB graphical user interface, and was shown to autonomously run 131 experiments over 69 hours uninterrupted.
Control of Combustor Instabilities Using an Artificial Neural Network (2000)

It is well-known that phase-shifting controllers used for active combustion control must be manually adjusted in order to maintain control over a broad range of operating combustor operating conditions. If one assumes that the thermoacoustic instabilities are linearly stabilizable, then what is needed is a method to determine, and ultimately predict, the frequency response of the plant for any range of operating conditions, so the controller design can be automatically updated to track the changing plant gain/phase relationships that are observed with changing heat release. A unique test-based, design process has been proposed to predict the gain/phase characteristics required of a proportional, phase-shifting controller that can stabilize the thermoacoustic instabilities. In this paper, that process is used to automate the design of a fixed-gain feedback controller that limits the amplitudes of any feedback induced instabilities (to some pre-specified level) while providing the best control of the targeted limit cycling pressure oscillations. The paper describes how a neural network was trained, using the suggested design process, to predict the frequency response of the thermoacoustics in a tube combustor at frequencies adjacent to the limit cycle frequency using certain operating conditions that included a sparsely-sampled temperature profile, total air/fuel flow rate, and equivalence ratio. The neural net training was performed using complex valued, open-loop frequency response function data as the desired signal with the previously mentioned operating conditions as the input signals. (The open loop data was collected for a narrow frequency range surrounding the limit cycle instability by performing a sine dwell at discrete frequencies). Once the neural network was trained, it was used to predict the approximate phase and gain margins as a function of temperature and flow conditions. The margins were then used to automatically update and design a fixed shape feedback controller having the proper phase and magnitude to ensure stability and control in the face of changing operating conditions. A companion paper describes the methodology that underlies the automated design of the feedback controller gain and phase delay.
Hypercoagulability in rats is increased by low doses of the direct thrombin inhibitor melagatran, but is reduced by the direct Factor Xa inhibitor rivaroxaban (2008)

85236 presented at the European Society of Cardiology (ESC) Congress 2008, Munich, Germany; 30 August–3 September 2008
Great Toe Transplantation (2022)

Despite being relatively uncommon in the general population, thumb amputations cause severe disability. More than 3,300 thumb amputations occurred in the United States. The thumb makes up around 40% of the function of the hand. Therefore, losing it would result in significant medical, hospital, and societal costs. Thumb reconstruction surgery's primary goal is to restore grip strength, including the range of motion, fine and tripod pinch, power grasp, strength, and sensibility, while secondary goals include restoring hand aesthetics. In cases of thumb replantation, like-for-like replacement is possible; however, when thumb replantation is not possible, great toe-to-hand transplantation is the best available reconstruction. When compared with other reconstructive options such as osteoplastic thumb reconstruction, pollicization, second toe transplantation, and the use of a thumb prosthesis, great toe transplantation provides superior function and aesthetics. For restoring pinch, sensitivity, strength, and aesthetics of the hand with well-tolerated donor site morbidity, toe to thumb transplantation is regarded as the gold standard.
Transcriptional Cartography Integrates Multiscale Biology of the Human Cortex (2022)

Abstract The cerebral cortex underlies many of our unique strengths and vulnerabilities - but efforts to understand human cortical organization are challenged by reliance on incompatible measurement methods at different spatial scales. Macroscale features such as cortical folding and functional activation are accessed through spatially dense neuroimaging maps, whereas microscale cellular and molecular features are typically measured with sparse postmortem sampling. Here, we integrate these distinct windows on brain organization by building upon existing postmortem data to impute, validate and analyze a library of spatially dense neuroimaging-like maps of human cortical gene expression. These maps allow spatially unbiased discovery of cortical zones with extreme transcriptional profiles or unusually rapid transcriptional change which index distinct microstructure and predict neuroimaging measures of cortical folding and functional activation. Modules of spatially coexpressed genes define a family of canonical expression maps that integrate diverse spatial scales and temporal epochs of human brain organization - ranging from protein-protein interactions to large-scale systems for cognitive processing. These module maps also parse neuropsychiatric risk genes into subsets which tag distinct cyto-laminar features and differentially predict the location of altered cortical anatomy and gene expression in patients. Taken together, the methods, resources and findings described here advance our understanding of human cortical organization and offer flexible bridges to connect scientific fields operating at different spatial scales of human brain research.
THE PREDICTIVE VALUE OF DONOR LIVER BIOPSIES FOR THE DEVELOPMENT OF PRIMARY NONFUNCTION AFTER ORTHOTOPIC LIVER TRANSPLANTATION (1991)

Methods of accurately assessing the suitability of donor livers prior to transplantation are required if the incidence of primary nonfunction (PNF) is to be reduced. This study evaluated the ability of donor liver biopsies to predict the development of primary nonfunction after transplantation. From June 1987 until May 1990, 170 liver transplants were performed in 147 patients. A total of 124 donor liver biopsies were obtained and divided into three groups. Group 1 biopsies (n = 77) were obtained after revascularization of the liver, group 2 biopsies (n = 19) were obtained prior to donor hepatectomy but examined only after implantation, and group 3 biopsies (n = 28) were obtained as in group 2, but were examined prior to implantation. Three of 89 (3.4%) livers interpreted as having normal histology developed primary nonfunction, while one of 26 (3.8%) biopsies interpreted as having a minimal or moderate amount of fatty infiltration developed primary nonfunction. PNF occurred in 7 of 8 livers with severe fatty infiltration (3), hydropic degeneration (3), and centrilobular necrosis (1). A fourth liver with hydropic degeneration and poor function ultimately failed requiring retransplantation 8 weeks later. Analysis of liver function revealed progressive elevation in aspartate-aminotransferase, alanine-aminotransferase, lactate dehydrogenase, and serum ammonia (NH3) with increasing degrees of fatty infiltration. Donor age and weight was also found to be significantly higher in livers with fatty infiltration. This study suggests that donor liver biopsies demonstrating normal histology or minimal-to-moderate fatty infiltration function adequately, but that donor livers with severe fatty infiltration or hydropic degeneration function poorly and should not be transplanted.
Immunohistochemical Detection of Somatostatin sst2a Receptors in the Lymphatic, Smooth Muscular, and Peripheral Nervous Systems of the Human Gastrointestinal Tract: Facts and Artifacts<sup>1</sup> (1999)

The cellular distribution of the somatostatin sst2A receptor protein was investigated in the lymphatic, smooth muscular, and nervous components of the human gastrointestinal tract using subtype-specific antibody R2-88 for immunohistochemical staining of cryostat and formalin-fixed, paraffin-embedded tissue sections. Germinal centers of intestinal lymphatic follicles were immunostained, exhibiting a predominantly plasma membrane localization of the receptor. Similarly, nerve fibers and cells in the submucosal and myenteric plexus were stained for sst2A. Antibody preabsorption with 100 nmol/L antigen peptide abolished staining in all of these tissues, and immunohistochemical staining correlated with the labeling observed after receptor autoradiography using the sst2-preferring radioligand 125I-[Tyr3]octreotide. Cytoplasmic immunostaining was detected in gastrointestinal smooth muscle cells and was inhibited by antibody pre-absorption with antigen peptide. However, 125I-[Tyr3]octreotide autoradiography was negative, and Western blots showed no band at the usual 70-90 kDa location for sst2A. Instead, a band was observed at 205 kDa. This band comigrated with the rabbit myosin standard, which was also stained with R2-88, although antibody sensitivity for myosin was less than 0.002% of that for the sst2A receptor. Rigorous computer-based sequence analysis demonstrated the peptide sequence chosen for antibody production was unique. Moreover, standard sequence alignment protocols were unable to identify the sequences in myosin responsible for the observed reactivity with the R2-88 antiserum. The observed cross-reactivity emphasizes the need for extensive controls to prove the specificity of immunostaining for such low abundance proteins as receptors even when the peptide sequence chosen for antibody production is unique. This study demonstrates for the first time the presence of specific sst2A receptor protein by immunohistochemistry in the human gastrointestinal lymphatic and nervous components, but not in gastrointestinal circular and longitudinal smooth muscle.
Complete primary structure of the human alpha 2 type V procollagen COOH-terminal propeptide. (1985)

Recently we presented the partial covalent structure of a type V collagen chain. Analysis of amino acids 796-1020 in the human alpha 2(V) Gly-X-Y region showed strong conservation of charged positions with the interstitial collagens but also revealed substitutions unique to type V. To gain more information about this procollagen and primarily to resolve the ambiguous nature of the 3' noncollagenous propeptide, we sequenced several cDNA clones coding for amino acids adjacent to the carboxyl end of the alpha chain. Here we report the complete primary structure of the alpha 2(V) COOH-terminal propeptide. In general, the latter sequence (270 residues) bears a greater degree of similarity to those of the interstitial rather than the basement membrane procollagens. Compared to the interstitial procollagens, however, more divergence has occurred in alpha 2(V) surrounding the conserved N-asparaginyl-linked carbohydrate attachment site at residues 171-173, and alpha 2(V) possesses an additional potential glycosylation site (Asn-Lys-Thr) located in a hypervariable region near the NH2 terminus. Although certainly premature to form any rigid hypothesis, a pattern emerges that may be characteristic of alpha 2 versus alpha 1 chains. Both the alpha 2(I) and alpha 2(V) telopeptides are devoid of a lysine, which in alpha 1 chains forms an interchain cross-link with residue 87 of the collagenous region. Also in contrast to the interstitial alpha 1 carboxyl propeptides is the absence in alpha 2(I) and alpha 2(V) of a cysteine that probably participates in an interchain disulfide bond. Therefore, one can speculate that those alpha 2 chains, represented only once in procollagen trimers, may not be under the same selective pressure as alpha 1 chains to maintain certain residues responsible for stabilizing the triple helical molecules.
A regression model with a hidden logistic process for feature extraction from time series (2013)

A new approach for feature extraction from time series is proposed in this paper. This approach consists of a specific regression model incorporating a discrete hidden logistic process. The model parameters are estimated by the maximum likelihood method performed by a dedicated Expectation Maximization (EM) algorithm. The parameters of the hidden logistic process, in the inner loop of the EM algorithm, are estimated using a multi-class Iterative Reweighted Least-Squares (IRLS) algorithm. A piecewise regression algorithm and its iterative variant have also been considered for comparisons. An experimental study using simulated and real data reveals good performances of the proposed approach.
The Validity of Retiming Sequential Circuits (1995)

Retiming has been proposed as an optimization step for sequential circuits represented at the net-list level. Retiming moves the latches across the logic gates and in doing so changes the number of latches and the longest path delay between the latches. In this paper we show by example that retiming a design may lead to differing simulation results when the retimed design replaces the original design. We also show, by example, that retiming may not preserve the testability of a sequential test sequence for a given stuck-at fault as measured by a simulator. We identify the cause of the problemas forward retiming moves across multiple-fanout points in the circuit. The primary contribution of this paper is to show that, while an accurate logic simulation may distinguish the retimed circuit fromthe original circuit, a conservative three-valued simulator cannot do so. Hence, retiming is a safe operation when used in a design methodology based on conservative three-valued simulation starting each latch with the unknown value.
Worst-case efficiency ratio in false-name-proof combinatorial auction mechanisms (2010)

This paper analyzes the worst-case efficiency ratio of false-name-proof combinatorial auction mechanisms. False-name-proofness generalizes strategy-proofness by assuming that a bidder can submit multiple bids under fictitious identifiers. Even the well-known Vickrey-Clarke-Groves mechanism is not false-name-proof. It has previously been shown that there is no false-name-proof mechanism that always achieves a Pareto efficient allocation. Consequently, if false-name bids are possible, we need to sacrifice efficiency to some extent. This leaves the natural question of how much surplus must be sacrificed. To answer this question, this paper focuses on worst-case analysis. Specifically, we consider the fraction of the Pareto efficient surplus that we obtain and try to maximize this fraction in the worst-case, under the constraint of false-name-proofness. As far as we are aware, this is the first attempt to examine the worst-case efficiency of false-name-proof mechanisms.We show that the worst-case efficiency ratio of any false-name-proof mechanism that satisfies some apparently minor assumptions is at most 2/(m + 1) for auctions with m different goods. We also observe that the worst-case efficiency ratio of existing false-name-proof mechanisms is generally 1/m or 0. Finally, we propose a novel mechanism, called the adaptive reserve price mechanism that is false-name-proof when all bidders are single-minded. The worst-case efficiency ratio is 2/(m + 1), i.e., optimal.
Administration of interleukin-6 stimulates multilineage hematopoiesis and accelerates recovery from radiation-induced hematopoietic depression (1991)

Hematopoietic depression and subsequent susceptibility to potentially lethal opportunistic infections are well-documented phenomena following radiotherapy. Methods to therapeutically mitigate radiation-induced myelosuppression could offer great clinical value. In vivo studies in our laboratory have demonstrated that interleukin-6 (IL-6) stimulates pluripotent hematopoietic stem cell (CFU-s), granulocyte-macrophage progenitor cell (GM-CFC), and erythroid progenitor cell (CFU-e) proliferation in normal mice. Based on these results, the ability of IL- 6 to stimulate hematopoietic regeneration following radiation-induced hematopoietic injury was also evaluated. C3H/HeN female mice were exposed to 6.5 Gy 60Co radiation and subcutaneously administered either saline or IL-6 (1,000 micrograms/kg) on days 1 through 3 or 1 through 6 postexposure. On days 7, 10, 14, 17, and 22, femoral and splenic CFU-s, GM-CFC, and CFU-e contents and peripheral blood white cell, red cell, and platelet counts were determined. Compared with saline treatment, both 3-day and 6-day IL-6 treatments accelerated hematopoietic recovery; 6-day treatment produced the greater effects. For example, compared with normal control values (N), femoral and splenic CFU-s numbers in IL-6-treated mice 17 days postirradiation were 27% N and 136% N versus 2% N and 10% N in saline-treated mice. At the same time, bone marrow and splenic GM-CFC values were 58% N and 473% N versus 6% N and 196% N in saline-treated mice; bone marrow and splenic CFU-e numbers were 91% N and 250% N versus 31% N and 130% N in saline-treated mice; and peripheral blood white cell, red cell, and platelet values were 210% N, 60% N, and 24% N versus 18% N, 39% N, and 7% N in saline- treated mice. These studies demonstrate that therapeutically administered IL-6 can effectively accelerate multilineage hematopoietic recovery following radiation-induced hematopoietic injury.
Multi-Tasking RGS Proteins in the Heart (2005)

Regulator of G-protein-signaling (RGS) proteins play a key role in the regulation of G-protein-coupled receptor (GPCR) signaling. The characteristic hallmark of RGS proteins is a conserved approximately 120-aa RGS region that confers on these proteins the ability to serve as GTPase-activating proteins (GAPs) for G(alpha) proteins. Most RGS proteins can serve as GAPs for multiple isoforms of G(alpha) and therefore have the potential to influence many cellular signaling pathways. However, RGS proteins can be highly regulated and can demonstrate extreme specificity for a particular signaling pathway. RGS proteins can be regulated by altering their GAP activity or subcellular localization; such regulation is achieved by phosphorylation, palmitoylation, and interaction with protein and lipid-binding partners. Many RGS proteins have GAP-independent functions that influence GPCR and non-GPCR-mediated signaling, such as effector regulation or action as an effector. Hence, RGS proteins should be considered multifunctional signaling regulators. GPCR-mediated signaling is critical for normal function in the cardiovascular system and is currently the primary target for the pharmacological treatment of disease. Alterations in RGS protein levels, in particular RGS2 and RGS4, produce cardiovascular phenotypes. Thus, because of the importance of GPCR-signaling pathways and the profound influence of RGS proteins on these pathways, RGS proteins are regulators of cardiovascular physiology and potentially novel drug targets as well.
Kwanzoquinones A—G and Other Constituents of Hemerocallis fulva “Kwanzo” Roots and Their Activity Against the Human Pathogenic Trematode Schistosoma mansoni. (2003)

Abstract For Abstract see ChemInform Abstract in Full Text.
A Gain-of-Function Mutation in <i>EPO</i> in Familial Erythrocytosis (2018)

Familial erythrocytosis with elevated erythropoietin levels is frequently caused by mutations in genes that regulate oxygen-dependent transcription of the gene encoding erythropoietin ( EPO). We identified a mutation in EPO that cosegregated with disease with a logarithm of the odds (LOD) score of 3.3 in a family with autosomal dominant erythrocytosis. This mutation, a single-nucleotide deletion (c.32delG), introduces a frameshift in exon 2 that interrupts translation of the main EPO messenger RNA (mRNA) transcript but initiates excess production of erythropoietin from what is normally a noncoding EPO mRNA transcribed from an alternative promoter located in intron 1. (Funded by the Gebert Rüf Foundation and others.).