gebhart/patrepeval huggingface dataset:
Posttranscriptional regulation of chimeric human transferrin genes by iron (1993)

Transferrin, the transferrin receptor, and ferritin are integral to the body's management of iron, an element required for life but highly toxic when present in excess. The transferrin receptor and ferritin are regulated posttranscriptionally by iron: the transferrin receptor by mRNA stability and ferritin by mRNA translation. Results described here indicate that transferrin, like ferritin, is regulated by iron at the level of translation. Chimeric genes introduced into the mouse genome were composed of the human transferrin 5' regulatory region fused to the chloramphenicol acetyl transferase (CAT) reporter gene. Iron administration to transgenic mice resulted in a significant decrease of transferrin-directed CAT enzyme activity and CAT protein in liver, but no significant decrease in human transferrin-CAT mRNA levels. Binding of specific RNA iron regulatory elements by proteins in cytoplasmic extracts have been shown to regulate ferritin and transferrin receptor synthesis. Similar results have been obtained with transferrin mRNA. A decreased binding of human transferrin 5'-untranslated region RNA by factors in cytoplasmic extracts of livers from mice receiving iron was found when compared to extracts from control mice. A human transferrin RNA-protein complex migrated electrophoretically with the same mobility as a ferritin iron responsive element RNA-iron responsive element binding protein complex. The ferritin iron responsive element RNA also competed with the human transferrin 5'-untranslated region RNA-protein complexes formed and vice versa. Therefore, iron modulation of human transferrin may share a factor common or similar to that observed in ferritin and transferrin receptor iron modulation.
Terahertz two-dimensional high-Q photonic crystal waveguide cavities (2008)

Numerical simulations were used to design a variety of high-Q resonant cavities for integration into a terahertz 2D photonic crystal waveguide. After fabrication, the transmission characteristics of each integrated cavity were explored. These photonic waveguide-coupled cavities demonstrate resonances with linewidths approaching 10 GHz. The results compare favorably to previous observations of rectangular waveguide cavities. Good agreement between the experimental results and the numerical simulations was obtained.
Combining Multiple Biomarker Models in Logistic Regression (2008)

In medical research, there is great interest in developing methods for combining biomarkers. We argue that selection of markers should also be considered in the process. Traditional model/variable selection procedures ignore the underlying uncertainty after model selection. In this work, we propose a novel model-combining algorithm for classification in biomarker studies. It works by considering weighted combinations of various logistic regression models; five different weighting schemes are considered in the article. The weights and algorithm are justified using decision theory and risk-bound results. Simulation studies are performed to assess the finite-sample properties of the proposed model-combining method. It is illustrated with an application to data from an immunohistochemical study in prostate cancer.
Widespread Muscle Expression of an AAV9 Human Mini-dystrophin Vector After Intravenous Injection in Neonatal Dystrophin-deficient Dogs (2010)

Duchenne (DMD) and golden retriever (GRMD) muscular dystrophy are caused by genetic mutations in the dystrophin gene and afflict striated muscles. We investigated systemic gene delivery in 4-day-old GRMD dogs given a single intravenous injection of an AAV9 vector (1.5 x 10(14) vector genomes/kg) carrying a human codon-optimized human mini-dystrophin gene under control of the cytomegalovirus (CMV) promoter. One of the three treated dogs was euthanized 9 days later due to pre-existing conditions. Scattered mini-dystrophin-positive myofibers were seen by immunofluorescent (IF) staining in numerous muscles. At the end of the 16-week study, the other two dogs showed generalized muscle expression of mini-dystrophin in ~15% to nearly 100% of myofibers. Western blot and vector DNA quantitative PCR results agreed with the IF data. Delayed growth and pelvic limb muscle atrophy and contractures were seen several weeks after vector delivery. T-2 weighted magnetic resonance imaging (MRI) at 8 weeks showed increased signal intensity compatible with inflammation in several pelvic limb muscles. This marked early inflammatory response raised concerns regarding methodology. Use of the ubiquitous CMV promoter, extra-high vector dose, and marked expression of a human protein in canine muscles may have contributed to the pathologic changes seen in the pelvic limbs.
Numerical analysis of alpha-particle-induced soft errors in floating channel type surrounding gate transistor (FC-SGT) DRAM Cell (2003)

This paper clarifies alpha-particle-induced soft error mechanisms in floating channel type surrounding gate transistor (FC-SGT) DRAM cells. One FC-SGT DRAM cell consists of an FC-SGT and a three-dimensional (3-D) storage capacitor. The cell itself arranges bit line (BL), storage node and body region in a silicon pillar vertically and achieves cell area of 4F/sup 2/ (F: feature size) per bit. In FC-SGT DRAM cells, the parasitic bipolar current is a major factor to cause soft errors. When an alpha particle penetrates the silicon pillar, generated electrons are collected to the storage node or BL due to the tunneling and diffusion mechanisms. On the other hand, holes are swept into the body region and accumulated. Consequently, the current flows not only in the surface but also in the entire body region due to the floating body effect. This parasitic bipolar current becomes the largest when an alpha particle penetrates the silicon pillar along the vertical axis. However, in case of FC-SGT DRAM cells, the surrounding gate structure can suppress the floating body effect compared with floating channel type SOI DRAM cells. As a result, the loss of the stored charge in the storage capacitor can be drastically decreased by using FC-SGT DRAM cell. Therefore, FC-SGT DRAM is a promising candidate for future high-density DRAMs having high soft-error immunity.
High-Speed Servo Technology For Optical Disk Drive (1988)

This paper describes servo technology for the improvement of data transfer rate and access time in a high-speed optical disk drive. First, read-write characteristics of the continuous composite servo format and the sampled servo format are discussed in terms of the recording power conditions needed to achieve a stable data read-out. Next, An optical head with the laser diode and optics separated from the positioner carriage is presented. The separated optical head&apos;s tracking servo stability and spot collimating performance are discussed. Finally, a new two-dimensional rotary lens actuator with a high resonant frequency is proposed.
The Significance of Tetramerization in Promoter Recruitment by Stat5 (1999)

Stat5a and Stat5b are rapidly activated by a wide range of cytokines and growth factors, including interleukin-2 (IL-2). We have previously shown that these signal transducers and activators of transcription (STAT proteins) are key regulatory proteins that bind to two tandem gamma interferon-activated site (GAS) motifs within an IL-2 response element (positive regulatory region III [PRRIII]) in the human IL-2Ralpha promoter. In this study, we demonstrate cooperative binding of Stat5 to PRRIII and explore the molecular basis underlying this cooperativity. We demonstrate that formation of a tetrameric Stat5 complex is essential for the IL-2-inducible activation of PRRIII. Stable tetramer formation of Stat5 is mediated through protein-protein interactions involving a tryptophan residue conserved in all STATs and a lysine residue in the Stat5 N-terminal domain (N domain). The functional importance of tetramer formation is shown by the decreased levels of transcriptional activation associated with mutations in these residues. Moreover, the requirement for STAT protein-protein interactions for gene activation from a promoter with tandemly linked GAS motifs can be relieved by strengthening the avidity of protein-DNA interactions for the individual binding sites. Taken together, these studies demonstrate that a dimeric but tetramerization-deficient Stat5 protein can activate only a subset of target sites. For functional activity on a wider range of potential recognition sites, N-domain-mediated oligomerization is essential.
Glucagon-induced autophagy and proteolysis in rat liver: mediation by selective deprivation of intracellular amino acids. (1979)

Amino acid deprivation and glucagon are both potent inducers of autography and proteolysis in liver. Because glucagon enhanced the metabolic utilization of some amino acids, the catabolic response to both of these stimuli could be achieved by a lowering of intracellular amino acid pools. Alternatively, glucagon could act independently of amino acids. To clarify the mode of hormonal action and also the relationship between the two cellular responses, livers from fed rats were perfused, with and without glucagon, with plasma amino acids over a concentration range of 0 to 10 times normal. Individual amino acids constancy at each level was ensured by perfusion in the single-pass mode. Amino acids alone strongly regulated autophagy and proteolysis in a coordinated fashion; maximal suppression was achieved at twice normal concentration; both effects increased rapidly to maximum at less than normal concentration. Corresponding effects of glucagon, however, could be elicited only at intermediate amino acid levels. None was noted at 4 and 10 times normal; at 0, hormonal stimulation was minimal. The amino acid inhibition was selective because it did not block cyclic AMP production or glycogenolysis. Intracellular pool measurements and systematic alteration of perfusate amino acid composition indicated that the autophagic and proteolytic effects of glucagon are mediated by a hormonally induced depletion of glycine, alanine, glutamate, and glutamine; of these, glutamine alone is the most effective. We conclude that the stimulation of intracellular protein degradation in liver is a manifestation of deprivation-induced autophagy which results from a decrease in certain intracellular glucogenic amino acids, notably glutamine.
Solving the Weighted Region Least Cost Path Problem Using Transputers (1989)

The weighted region least cost path problem involves finding the minimal cost path between a source point and a goal point through a plane that has been subdivided into weighted regions. In this thesis, we investigate a new parallel approach which seeks to take advantage of the distributed, asynchronous computing environment provided by the INMOS Transputer. The algorithm consists of a family of local, asynchronous, iterative and parallel procedures. The program is implemented on a network of transputers using a parallel version of the C programming language and tested on various maps of triangulated weighted regions. Results were favorable in terms of producing a near optimum path and reduced processing time.
Transforming Growth Factor-&#946;: A Molecular Target for the Future Therapy of Glioblastoma (2005)

The median survival of patients with glioblastoma treated by surgery, radiotherapy and chemotherapy is in the range of 12 months. These limits in the efficacy of current treatment modalities call for the development of novel therapeutic approaches targeting the specific biological features of this type of cancer. Glioblastomas are a rich source of immunosuppressive molecules which may interfere with immune recognition and rejection as well as clinical strategies of active immunotherapy. The most prominent glioblastoma-associated immunosuppressant is the cytokine, transforming growth factor (TGF)-beta, a multifunctional cytokine which not only interferes with multiple steps of afferent and efferent immune responses, but also stimulates migration, invasion and angiogenesis. The complex regulation of TGF-beta bioavailability includes its synthesis as a proprotein, proteolytic processing by furin-like proteases, assembly in a latent complex, and finally liberation from latency by multiple effector mechanisms, a process collectively referred to as activation. Several in vitro paradigms and rodent glioma models have been used to demonstrate that the antagonism of TGF-beta holds promise for the treatment of glioblastoma, employing antisense strategies, inhibition of pro-TGF-beta processing, scavenging TGF-beta by decorin, or blocking TGF-beta activity by specific TGF-beta receptor (TGF-betaR) I kinase antagonists. Moreover, the local application of TGF-beta(2) antisense oligonucleotides is currently evaluated in a randomized clinical trial for recurrent malignant glioma. In summary, we propose that TGF-beta-antagonistic treatment strategies are among the most promising of the current innovative approaches for glioblastoma, particularly in conjunction with novel approaches of cellular immunotherapy and vaccination.
Nonpeptide αvβ3 Antagonists. Part 11:  Discovery and Preclinical Evaluation of Potent αvβ3 Antagonists for the Prevention and Treatment of Osteoporosis (2004)

3-(S)-Pyrimidin-5-yl-9-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-nonanoic acid (5e) and 3-(S)-(methylpyrimidin-5-yl)-9-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-nonanoic acid (5f) were identified as potent and selective antagonists of the alpha(v)beta(3) receptor. These compounds have excellent in vitro profiles (IC(50) = 0.07 and 0.08 nM, respectively), significant unbound fractions in human plasma (6 and 4%), and good pharmacokinetics in rat, dog, and rhesus monkey. On the basis of the efficacy shown in an in vivo model of bone turnover following once-daily oral administration, these two compounds were selected for clinical development for the treatment of osteoporosis.
Measuring Research on County Agricultural Technological Innovation Ability Index (2011)

Taking the mechanism of technological construction guidance theory and mode which consists of “objective-construction-evaluation-construction-objective” as a starting point, on the basis of county agricultural technological innovation ability and its index definition, this paper researches the constructing system of county agricultural technological innovation ability. Firstly, on the basis of defining county agricultural technological innovation ability and the definition of index, according to the principle of purposefulness, scientificity , systematicness, integration of dynamic state and static state, integration of quantitativeness and qualitativeness and so on, we construct the multi-level measuring system of county agricultural technological innovation ability, including 4 first-level indices, namely technological innovation environment, technological innovation basis, technological innovation ability, and technological innovation efficiency; 15 second-level indices, such as technological policy, technological system mechanism, technological institution construction, ability of innovation subject, ability of industrial expansion, scale merit, technological contribution rate. Moreover, this system has 45 third-level indices. Then, by using unascertained mathematics method and AHM method, we establish the multi-level unascertained composite measuring model of county agricultural technological innovation ability index. Finally, by using the survey data of one county in Hebei Province, and the established county agricultural technological innovation ability index model, we get the county agricultural technological innovation ability index of 0.711 by calculation, that is, the innovation ability is at the intermediate level, namely the modern agricultural sub-stage. The empirical research proves the correctness and applicability of this model.
Blood Lactate Accumulation: Hemodynamics and Acid Base Status (2002)

The authors evaluated the relationship between blood lactate accumulation and hemodynamics in a prospective controlled animal study. Seven healthy pigs were anesthetized and mechanically ventilated with a 0.6 fraction of inspired oxygen to achieve a normal PaCO 2 . Catheters for blood sampling, lactate infusion, and hemodynamic assessment were inserted into the femoral vein and femoral artery. Bolus infusions (466 µmol • kg — 1 over 1 minute) of a neutral solution of sodium lactate were given at 0, 30, 60, and 90 minutes. Each bolus was followed by continuous infusion of the same lactate solution (31.7 µmol • kg — 1 • min —1 after the first, with the rate doubled after each subsequent bolus). Arterial blood samples were drawn at baseline and at 30, 60, 90, and 120 minutes, with simultaneous hemodynamic assessment. Significant increases were seen in blood lactate (from 1.6 ± 0.4 mmol/L at baseline to 4.4 ± 0.8 at 30 minutes, 8.0 ± 1.0 at 60 minutes, and 14.4 ± 2.1 at 90 minutes), pH (from 7.40 ± 0.03 to 7.44 ± 0.05 at 30 minutes, 7.50 ± 0.05 at 60 minutes, and 7.56 ± 0.04 at 90 minutes), and HCO 3 — (from 28 ± 1.4 mmol/L to 30 ± 0.7 at 30 minutes, 34 ± 0.9 at 60 minutes, and 37 ± 1.2 at 90 minutes). PaCO 2 decreased significantly from 44 ± 3 torr at baseline to 40 ± 4.7 torr at 90 minutes. Blood pressure decreased after each lactate bolus, recovering within 2 minutes initially but not after later injections. Cardiac output, heart rate, and glucose increased significantly, mean arterial pressure and systemic vascular resistance decreased, and stroke volume did not change. Thus, the accumulation of blood lactate due to exogenous administration of a neutral solution of sodium lactate was associated with significant systemic vasodilation, increased cardiac output, increased heart rate, and metabolic alkalosis.
What Is a B-Cell Epitope? (2009)

The antigenicity of proteins resides in different types of antigenic determinants known as continuous and discontinuous epitopes, cryptotopes, neotopes, and mimotopes. All epitopes have fuzzy boundaries and can be identified only by their ability to bind to certain antibodies. Antigenic cross-reactivity is a common phenomenon because antibodies are always able to recognize a considerable number of related epitopes. This places severe limits to the specificity of antibodies. Antigenicity, which is the ability of an epitope to react with an antibody, must be distinguished from its immunogenicity or ability to induce antibodies in a competent vertebrate host. Failure to make this distinction partly explains why no successful peptide-based vaccines have yet been developed. Methods for predicting the epitopes of proteins are discussed and the reasons for the low success rate of epitope prediction are analyzed.
Potential role of nonstatin cholesterol lowering agents (2011)

Although statins, 3β-hydroxy-3β-methylglutaryl coenzyme A reductase (HMGR) inhibitors, have revolutionized the management of cardiovascular diseases by lowering serum low density lipoproteins, many patients suffer from their side effects. Whether the statin side effects are related to their intrinsic toxicity or to the decrease of HMGR main isoprenoid end products, which are essential compounds for cell viability, is still debated. In addition to HMGR, the key and rate limiting step of cholesterol synthesis, many enzymes are involved in this multi-step pathway whose inhibition could be taken into account for a "nonstatin approach" in the management of hypercholesterolemia. In particular, due to their unique position downstream from HMGR, the inhibition of squalene synthase, farnesyl diphosphate farnesyltransferase (FDFT1), squalene epoxidase (SQLE), and oxidosqualene cyclase:lanosterol synthase (OSC) should decrease plasma levels of cholesterol without affecting ubiquinone, dolichol, and isoprenoid metabolism. Thus, although FDFT1, SQLE and OSC are little studied, they should be considered as perspective targets for the development of novel drugs against hypercholesterolemia. Here, structure-function relationships of FDFT1, SQLE, and OSC are reviewed highlighting the advantages that the downstream inhibition of HMGR could provide when compared to the statin-based therapy.
Cytokine regulation of humoral immunity : basic and clinical aspects (1996)

Partial table of contents: GENERAL CONCEPTS. B-Cell Subpopulations and Microenvironments (T. Waldschmidt). Immunoglobulin Class Switching (M. Lorenz & A. Radbruch). CYTOKINES. Interleukin-2 (M. McIlraith & P. Lipsky). Interleukin-5 (K. Takatsu). Interferon-Gamma (C. Snapper). Neuropeptides (H. Kimata). PATHOPHYSIOLOGY. IgE Regulation in Allergy and Helminth Parasite Infections (R. Coffman). Regulation of Mucosal Immunity (K. Beagley, et al.). Index.
Serum LH, FSH, Prolactin and Progesterone from Birth to Puberty in Female and Male Rats (1974)

Serum LH, FSH, prolactin and progesterone were determined in male and female prepuberal rats. Neonates of both sexes had high LH and FSH levels, the values in the females being higher than those in the males. Serum prolactin and progesterone were low in neonatal rats. A curious LH secretion pattern occurred in female rats between days 10 and 20; high LH levels were observed in 10–15‰ of the rats during this time, whereas the male rats showed only minor fluctuations. At the same time serum FSH was elevated in both sexes. Again, the values in the females were higher than in the males. Serum prolactin was still low, whereas progesterone rose slightly in both sexes. Serum LH and FSH remained low between days 21 and the immediate peripuberal period (i.e., days 37–45) in males and females, and serum prolactin rose steadily during this period. Progesterone also increased following the prolactin pattern. All hormones (LH, FSH, prolactin and progesterone) were increased during the peripuberal period with cyclic fluctuations in the females. The close relation of prolactin and progesterone secretion in the immature rat is discussed.(Endocrinology94: 1003, 1974)
Role of serum amyloid P component in bacterial infection: Protection of the host or protection of the pathogen (2000)

Serum amyloid P component (SAP) binds to Streptococcus pyogenes, and we show here that it also binds to Neisseria meningitidis, including a lipopolysaccharide (LPS)-negative mutant, and to rough variants of Escherichia coli. Surprisingly, this binding had a powerful antiopsonic effect both in vitro and in vivo, reducing phagocytosis and killing of bacteria. Furthermore, SAP knockout mice survived lethal infection with S. pyogenes and rough E. coli J5, organisms to which SAP binds. The susceptibility of SAP(-/-) mice was fully restored by injection of isolated human SAP. However, SAP(-/-) mice were more susceptible than wild-type animals to lethal infection with E. coli O111:B4, a smooth strain to which SAP does not bind, suggesting that SAP also has some host defense function. Although SAP binds to LPS in vitro, SAP(-/-) mice were only marginally more susceptible to lethal LPS challenge, and injection of large amounts of human SAP into wild-type mice did not affect sensitivity to LPS, indicating that SAP is not a significant modulator of LPS toxicity in vivo. In contrast, the binding of SAP to pathogenic bacteria enabled them to evade neutrophil phagocytosis and display enhanced virulence. Abrogation of this molecular camouflage is thus potentially a novel therapeutic approach, and we show here that administration to wild-type mice of (R)-1-[6-(R)-2-carboxy-pyrrolidin-1-yl]-6-oxo-hexanoyl]pyrrolidine -2- carboxylic acid, a drug that inhibits SAP binding, significantly prolonged survival during lethal infection with E. coli J5.
Obesity-induced inflammatory changes in adipose tissue (2003)

Obesity is associated with a state of chronic, low-grade inflammation. Two manuscripts in this issue of the JCI (see the related articles beginning on pages 1796 and 1821) now report that obese adipose tissue is characterized by macrophage infiltration and that these macrophages are an important source of inflammation in this tissue. These studies prompt consideration of new models to include a major role for macrophages in the molecular changes that occur in adipose tissue in obesity.