gebhart/patrepeval huggingface dataset:
A Longitudinal Study of Estrous Cyclicity in Aging C57BL/6J Mice: I. Cycle Frequency, Length and Vaginal Cytology1 (1982)

Cycle frequency, length, and vaginal cytology were measured longitudinally in three cohorts of singly housed virgin mice staggered across a 3-year interval. The age profiles of these parameters were qualitatively similar, but quantitatively different, among cohorts. Cycle frequency was initially low (Phase I), due to prolonged cycles and late-starting cycles, and did not peak (Phase II) until mice were 3-5 months old. Phase II lasted for 7-10 months, depending on the cohort. Thereafter cycle frequency declined steadily (Phase III). The average age of cessation of cyclicity varied among cohorts, occurring between 13 and 16 months of age. Age changes in cycle length paralleled those of cycle frequency. During Phase II, median cycle length was less than 5 days and variance was lowest. During Phases I and III, variance was about twofold greater and median cycle length was greater than 5 days. Although median cycle length remained stable for several months during Phase II, the peak period of 4-day cycles was much shorter. In all cohorts, 4-day cycles did not peak until 7-8 months of age and began to decline by 9 months. The decrease in 4-day cycles was associated with a progressive lengthening of cycles-first from 4 to 5 days, then to longer cycles. The fraction of cycles with extended cornification (greater than 2 days) increased with advancing age from less than 0.35 during the initial period of cycle lengthening to a maximum of 0.60. The observation that the initial phase o cycle prolongation was not usually associated with extended cornification is consistent with earlier evidence that this period is characterized by a delayed, rather than prolonged, preovulatory rise of estradiol. However, the increased fraction of prolonged cycles with extended cornification at later ages suggests that the preovulatory elevation of estradiol may ultimately be prolonged.
Transcending the Qualitative-Quantitative Debate: The Analytic and Systemic Approaches to Educational Research (1991)

There is a distinction to be made that transcends the one between the quantitative and qualitative research paradigms. It is a distinction between that kind of research that suits best the study of causal relations among selected variables and the study of complex learning environments undergoing change. Two studies illustrating the differences lead to the formulation of two approaches–the analytic and the systemic–which differ from each other in terms of the epistemological assumptions that underlie them. These differences are not accounted for by other contrasts such as "'basic-applied" or "quantitative-qualitative." The analytic approach mainly assumes that discrete elements of complex educational phenomena can be isolated for study, leaving all else unchanged. The systemic approach mainly assumes that elements are interdependent, inseparable, and even define each other in a transactional manner so that a change in one changes everything else and thus requires the study of patterns, not of single variables. It is, however, further argued that the validity of each approach is limited by the combination of assumptions made, phenomena chosen for study, questions asked, and research methodologies employed. Thus, the two approaches, by epistemological necessity, have to be employed complementarily.
Potassium-Induced Loop Conformational Transition of a Potent Anti-HIV Oligonucleotide (1997)

Abstract Spectroscopic, thermal denaturation and kinetic studies have revealed that DNA oligonucleotides 5′-d(GGGTGGGTGGGTGGGT) (T30695) and 5′-d(GTGGTGGGTGGGTGGGT) (T30177) form extremely stable intramolecular G-tetrads via a two-step process that involves the binding of one K+ ion to a central pair of G-quartets and two additional K+ ions, presumably, to the loops (Jing et al., (1997) Biochemistry in press). In that these oligonucleotides are potent HIV-1 inhibitors and among the most active HIV-1 integrase inhibitors yet identified, we have sought to further characterize the K+-induced folding process for the purpose of rational chemical modification of these anti-HIV agents. Our NMR investigation demonstrates that in the presence of Li+ ions, T30695 forms an unimolecular tetrad fold, stabilized by a pair of syn-anti-syn-anti G-quartets comprising a central core. The NMR spectrum of T30695 as a function of K+ titration reveals a well-defined transition that saturates upon addition of three K+ ions per oligomer. During this process, the initial Li+-dependent G-quartet structure converts into a highly symmetrical, stable form (the NMR detected melting transition temperature is increased by ∼ 20°C). The conformation of the G-quartet core remains unchanged, while the loosely structured loop residues become organized in a fashion which is stabilized by K+ ion binding and by interactions with the core. To explain these data, we propose a model wherein K+ binding to the loops induces structural rearrangement, to yield a planar array of loop bases in proximity to the underlying G-quartets. By reference to closely related homologues, which lack activity as an HIV-1 or integrase inhibitor, the possibility is discussed that this ion-coordinated loop structure is crucial to the biological activity of T30695.
The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14 (1993)

lin-4 is essential for the normal temporal control of diverse postembryonic developmental events in C. elegans. lin-4 acts by negatively regulating the level of LIN-14 protein, creating a temporal decrease in LIN-14 protein starting in the first larval stage (L1). We have cloned the C. elegans lin-4 locus by chromosomal walking and transformation rescue. We used the C. elegans clone to isolate the gene from three other Caenorhabditis species; all four Caenorhabditis clones functionally rescue the lin-4 null allele of C. elegans. Comparison of the lin-4 genomic sequence from these four species and site-directed mutagenesis of potential open reading frames indicated that lin-4 does not encode a protein. Two small lin-4 transcripts of approximately 22 and 61 nt were identified in C. elegans and found to contain sequences complementary to a repeated sequence element in the 3' untranslated region (UTR) of lin-14 mRNA, suggesting that lin-4 regulates lin-14 translation via an antisense RNA-RNA interaction.
Modeling and Simulation in Systems Engineering (2001)

Simulation and modeling are major assets in the engineering of systems of all types. This two-part series addresses the much expanded role for M&amp;S that is due to the prospect that evolutionary and adaptive engineering efforts are the wave of the future. The Department of Defense's Simulation BasedAcquisition initiative is a case in point, but some critical issues need to be addressed to bring it to fruition. In this first part, we set the background in systems engineering, information technology and the new role of complex adaptive system models that are changing our view of organizations as machines to organizations as organisms.
Stimulation of angiogenesis by adenosine on the chick chorioallantoic membrane. (1986)

The effect of adenosine on the vascular density of the chick chorioallantoic membrane was studied. Elvax polymer pellets containing 0.2-3.0 mg of adenosine were placed on the chorioallantoic membrane of 10-day embryos. Control pellets containing mannitol were placed at least 1 cm away. After 4 days the membrane was formalin-fixed and removed. A thin plastic coverslip, inscribed with concentric circles (4-8 mm in diameter), was placed over the pellet. A vascular density index was estimated at 20 X by counting the number of intercepts between vessels and the inscribed circles. Adenosine stimulated a dose-dependent increase (p less than 0.01) in the vascular density index with the 3-mg pellets inducing a 15% increase. Inosine, a major metabolite of adenosine, did not cause a change in the number of intercepts counted. The adenosine-stimulated increase in vascularity was blocked with 110 micrograms of methyl-isobutyl-xanthine injected daily into the albumin. Partial inhibition was observed with 55 micrograms/day. Methyl-isobutyl-xanthine by itself did not affect the vascular density index. Dipyridamole enhanced adenosine's stimulation of vascular growth an additional 52%. Given alone, however, it had no effect on the membrane's vascularity. These data support an angiogenic role for adenosine. The modest, but consistent, increase in the vascular density index stimulated by adenosine, and the fact that it may be released during tissue hypoxia, is consistent with an hypothesis that this nucleoside plays a modulatory role in vessel proliferation accompanying conditions of long-term hypoxia.
A Controlled Trial of Early versus Late Treatment with Zidovudine in Symptomatic Human Immunodeficiency Virus Infection (1992)

In symptomatic patients with HIV infection, early treatment with zidovudine delays progression to AIDS, but in this controlled study it did not improve survival, and it was associated with more side effects.
The Relation of Oxidative Stress and Hyperexcitation to Neurological Disease (1995)

The expression of a considerable range of neurological diseases is thought to involve two pathological states, namely, the production of excessive amounts of reactive oxygen species and neuronal hyperactivity. These events may represent an outcome of general vulnerable features of nervous tissue. Since they are associated with many unrelated diseases, the phenomena may be considered the final common pathways of a range of metabolic defects. Superimposed on these general signs of cellular impairment are the more specific features of each disorder. This review describes some of the evidence for the presence of hyperactivity and oxidative stress in various neurological disorders. Mechanisms whereby the states may interact and modulate each other are discussed. The manner in which such understanding has implications for the development of novel therapeutic approaches is also described.
B- to Z-DNA transition probed by oligonucleotides containing methylphosphonates. (1986)

The simulation of the B--Z-DNA transition by using space-filling models of the dimer d(C-G) shows the possibility of hydrogen-bond formation between the N-2 amino group of the partially rotated guanine and one of the 5'-phosphate oxygens of deoxyguanylic acid. To probe the importance of this postulated interaction, analogs of the hexamer d(C-G)3 were synthesized. These analogs contained a methylphosphonate linkage, of distinct stereochemistry, which replaced the first 5'-phosphate linkage of deoxyguanosine. The CD spectra in high salt concentration showed that the hexamer containing a methylphosphonate linkage with the RP stereochemistry formed Z-DNA to the same extent as d(C-G)3, whereas the hexamer containing a methylphosphonate linkage with the SP stereochemistry did not form Z-DNA. These results are consistent with a mechanism in which an interaction between the N-2 amino group of guanine and the prochiral SP oxygen of deoxyguanosine 5'-phosphate kinetically controls the formation of Z-DNA. A water bridge between the N-2 amino group of guanine and the 3'-phosphate oxygen of deoxyguanylic acid has been implicated in the stabilization of Z-DNA. To probe the importance of this water bridge, two additional analogs of the hexamer d(C-G)3 were synthesized. These analogs contained a methylphosphonate linkage, of distinct stereochemistry, that replaced the first deoxyguanosine 3'-phosphate. The CD spectra showed that the hexamer containing a methylphosphonate linkage of the RP stereochemistry underwent the transition to Z-DNA to the same extent as d(C-G)3, whereas the hexamer containing a methylphosphonate linkage of the SP stereochemistry underwent the transition to Z-DNA to a 35% lesser extent. Thus the water bridge involving the prochiral SP oxygen provides modest stabilization energy for Z-DNA. These studies, therefore, suggest that the B--Z-DNA transition is regulated both thermodynamically and kinetically through hydrogen-bond interactions involving phosphate oxygens and the N-2 amino group of guanine.
Direct gene transfer into rat liver cells by in vivo electroporation (1998)

In vivo electro-transfection efficiency and manner of transferred gene expression were investigated by fluorescence microscopic image analysis. Green fluorescent protein (GFP) gene was used as the genetic marker. Electroporation was carried out on the liver of live rats by use of disk electrodes mounted in the tips of tweezers, which were directly pressed onto the surface of a liver lobe in situ. Electroporation with eight electric pulses of 50 ms in duration at 50 V gave a good efficiency of transfection as judged by the induced GFP expression. Bright fluorescence of GFP appeared as dots, which were scattered around the area damaged by electroporation. The transfection efficiency increased as the amount of injected DNA was increased. The results indicate that the amount of induced gene expression can be controlled. Estimation of the efficiency of electro-gene transfer using the fluorescence of GFP and digital analysis of microscopic images was useful to determine the optimum conditions for local gene therapy in tissues and organs.
A platform incorporating trimeric antigens into self-assembling nanoparticles reveals SARS-CoV-2-spike nanoparticles to elicit substantially higher neutralizing responses than spike alone (2020)

Antigens displayed on self-assembling nanoparticles can stimulate strong immune responses and have been playing an increasingly prominent role in structure-based vaccines. However, the development of such immunogens is often complicated by inefficiencies in their production. To alleviate this issue, we developed a plug-and-play platform using the spontaneous isopeptide-bond formation of the SpyTag:SpyCatcher system to display trimeric antigens on self-assembling nanoparticles, including the 60-subunit Aquifex aeolicus lumazine synthase (LuS) and the 24-subunit Helicobacter pylori ferritin. LuS and ferritin coupled to SpyTag expressed well in a mammalian expression system when an N-linked glycan was added to the nanoparticle surface. The respiratory syncytial virus fusion (F) glycoprotein trimer-stabilized in the prefusion conformation and fused with SpyCatcher-could be efficiently conjugated to LuS-SpyTag or ferritin-SpyTag, enabling multivalent display of F trimers with prefusion antigenicity. Similarly, F-glycoprotein trimers from human parainfluenza virus-type 3 and spike-glycoprotein trimers from SARS-CoV-2 could be displayed on LuS nanoparticles with decent yield and antigenicity. Notably, murine vaccination with 0.08 µg of SARS-CoV-2 spike-LuS nanoparticle elicited similar neutralizing responses as 2.0 µg of spike, which was ~ 25-fold higher on a weight-per-weight basis. The versatile platform described here thus allows for multivalent plug-and-play presentation on self-assembling nanoparticles of trimeric viral antigens, with SARS-CoV-2 spike-LuS nanoparticles inducing particularly potent neutralizing responses.
Reciprocal Isomerization of Butyrate and Isobutyrate by the Strictly Anaerobic Bacterium Strain WoG13 and Methanogenic Isobutyrate Degradation by a Defined Triculture (1992)

Isomerization of butyrate and isobutyrate was investigated with the recently isolated strictly anaerobic bacterium strain WoG13 which ferments glutarate to butyrate, isobutyrate, CO(2), and small amounts of acetate. Dense cell suspensions converted butyrate to isobutyrate and isobutyrate to butyrate. C-nuclear magnetic resonance experiments proved that this isomerization was accomplished by migration of the carboxyl group to the adjacent carbon atom. In cell extracts, both butyrate and isobutyrate were activated to their coenzyme A (CoA) esters by acyl-CoA:acetate CoA-transferases. The reciprocal rearrangement of butyryl-CoA and isobutyryl-CoA was catalyzed by a butyryl-CoA:isobutyryl-CoA mutase which depended strictly on the presence of coenzyme B(12). Isobutyrate was completely degraded via butyrate to acetate and methane by a defined triculture of strain WoG13, Syntrophomonas wolfei, and Methanospirillum hungatei.
Measurement of mRNA of trophoblast-specific genes in cellular and plasma components of maternal blood (2006)

The present findings indicate that the concentration of hPL and beta hCG mRNA is significantly higher in the cellular component of maternal blood samples than in the plasma component. Cellular mRNA in maternal blood is useful for non-invasive evaluation of placental function.
Stereoscopic Video Synthesis from a Monocular Video (2007)

This paper presents an automatic and robust approach to synthesize stereoscopic videos from ordinary monocular videos acquired by commodity video cameras. Instead of recovering the depth map, the proposed method synthesizes the binocular parallax in stereoscopic video directly from the motion parallax in monocular video. The synthesis is formulated as an optimization problem via introducing a cost function of the stereoscopic effects, the similarity, and the smoothness constraints. The optimization selects the most suitable frames in the input video for generating the stereoscopic video frames. With the optimized selection, convincing and smooth stereoscopic video can be synthesized even by simple constant-depth warping. No user interaction is required. We demonstrate the visually plausible results obtained given the input clips acquired by ordinary handheld video camera.
Syk: A Novel Target for Treatment of Inflammation in Lung Disease (2009)

Spleen Tyrosine Kinase (Syk) is widely expressed in the immune system and functions in the transmission of inflammatory signals via ITAM-bearing cell surface receptors. The broad expression pattern and importance of Syk in regulating innate immunity and the inflammatory response have led to significant interest from the pharmaceutical industry to developing anti-Syk therapeutics for the treatment of inflammatory disorders such as allergic rhinitis and rheumatoid arthritis. While the function and regulation of Syk has been well-described in leukocytes, where its primary role is an early transducer of signaling following immunoreceptor engagement, Syk has recently been described in non-immune cells, such as the airway epithelium, that also play an important role in mediating the inflammatory response. This manuscript will focus on the expression and function of Syk in the context of inflammatory lung diseases, and review recent data that have demonstrated novel roles for Syk in airway epithelial cells, particularly its role in mediating the human rhinovirus (HRV) induced inflammatory response and viral cell entry. In addition, data describing the efficacy of novel Syk inhibitors in the management of inflammatory diseases in animal models and early clinical trials are also reviewed.
Are Xenopus oocytes unique in displaying functional IsK channel heterologous expression? (1993)

IsK is a novel membrane protein that induces a slow voltage-gated K+ current when expressed in Xenopus oocytes. Attempts were made to express this channel in several eukaryotic cells including the skeletal muscle cell line C2C12, the fibroblastic cell line CHO and the T lymphocyte cell line Jurkat. In spite of the clear demonstration of successful transfection, no IsK current could be recorded from these cells. Overexpression was also obtained using the vaccinia/T7 and baculovirus systems, again without any success in demonstrating the presence of the K+ current in the plasma membrane of infected cells. Bilayer reconstitution experiments using membranes highly enriched in IsK protein ruled out the possibility that the IsK protein could induce a K+ channel located in intracellular organelles. Collectively, these data suggest the possibility that IsK protein is part of a K+ channel complex but is only active in association with another protein endogenous to the Xenopus oocyte. Other hypotheses are also discussed.
Insulin down-regulates the inducible nitric oxide synthase pathway: nitric oxide as cause and effect of diabetes? (1997)

Evidence in this paper indicates that insulin can down-regulate the inducible nitric oxide synthase (iNOS) pathway in vivo. The iNOS pathway is up-regulated in diabetes-prone rats and mice and is associated with an autoimmune process. However, the results presented here indicate that macrophage nitric oxide (NO) production and iNOS mRNA expression are also elevated in rats or mice made diabetic by streptozotocin injection in which there is no primary autoimmune component. Insulin administration reduces NO production in autoimmune-prone and streptozotocin-induced diabetic rodents. Finally, insulin decreases macrophage NO production in normal hosts. These results indicate that the autoimmune paradigm is inadequate to explain increased NO in diabetes. As a potential mechanism to explain insulin-mediated regulation of NO production, TGF-1 may be involved because 1) macrophages from diabetic mice produce less TGF-beta1 than macrophages from normal hosts; 2) the circulating TGF-beta1 level is lower in diabetic mice; and 3) insulin administration increases circulating TGF-beta1 in normal mice. Together, these results provide evidence that increased NO in diabetes is not only a cause but also an effect of beta-cell destruction and results in part from a heretofore unrecognized immunomodulatory activity of insulin.
Micromachined endovascularly-implantable wireless aneurysm pressure sensors: from concept to clinic (2005)

Passive wireless pressure sensors, originally developed for use in harsh environments, have been adapted for use in the human body. The application of these sensors is as monitors of endovascularly repaired abdominal aortic aneurysms. For this application, the devices must be permanently implanted deep within the body and be functional for the remainder of the patient's life. Microelectromechanical systems (MEMS) manufacturing technologies have been utilized to fabricate sensors with sizes and form factors suitable for endovascular delivery and permanent implantation. The sensors are interrogated with an external measurement antenna and a real-time waveform of the pressure environment is extracted. This paper reports the development and clinical demonstration of these sensors.
High-transconductance p -type SiGe modulation-dopedfield-effect transistor (1995)

High-transconductance 1.5 µm-gate-length p-type modulation-doped field-effect transistors (MODFETs) have been fabricated using standard optical lithography on a high hole-mobility SiGe heterostructure grown by ultrahigh vacuum chemical vapour deposition (UHV-CVD). A maximum DC extrinsic (intrinsic) transconductance of 95 mS/mm (138 mS/mm) at room temperature has been achieved, which to our knowledge is the highest for p-type field-effect transistors at this gate length. A unity current-gain frequency ft of 2.1 GHz has been measured. The gate leakage current was quite low and was of the order of a few µA/mm. These enhancement-mode devices exhibit reasonable pinch-off characteristics.