gebhart/patrepeval huggingface dataset:
Distributions of melanoma growth stimulatory activity of growth-regulated gene and the interleukin-8 receptor B in human wound repair. (1995)

The alpha-chemokines have been implicated as regulators of proliferation and differentiation of normal keratinocytes and as mediators of keratinocyte maturation and migration in inflammatory processes that involve the skin. Using the cutaneous wound repair model, we examined the sites and temporal sequence of the appearance of melanoma growth stimulatory activity or growth-regulated gene (MGSA/GRO;ligand) and the type B interleukin (IL)-8 receptor (IL-8RB) to which MGSA/GRO binds. Human burn tissues (n = 44) representing days 2 to 12 after injury were obtained during surgical debridement, fixed in 4% paraformaldehyde, and embedded in paraffin. Immunolocalizations were performed with polyclonal antisera for both ligand and receptor, as well as a monoclonal antibody for the IL-8 RB. Western blot analysis confirmed the presence of the IL-8 RB in immunoprecipitates of epidermal keratinocyte lysates. In normal skin, MGSA/GRO protein was restricted to sites populated by differentiated keratinocytes (suprabasal compartments, inner root sheath cells, and dermal sweat ducts). MGSA/GRO protein was barely detectable within epithelial margins and islands of burn wounds where the migrating/proliferating keratinocyte populations reside, but staining intensities increased as cells matured into the outer layers. Weak diffuse staining was detected in areas of neutrophilic infiltration (granulation tissue and overlying exudates). By contrast, in normal skin the IL-8 RB was detected in specific locations within epidermal and dermal compartments of healing wounds. In the dermis, polyvalent antibodies detected receptor immunoreactivity most prominently in dermal sweat ducts and endothelium of capillaries, whereas this immunoreactivity was inconspicuous in sections stained with the monoclonal antibody. Receptor immunostaining was noted in migrating/proliferating keratinocytes in epithelial margins and islands but was in the outer layers or in hypertrophic epidermis adjacent to wounds. This same pattern was observed in epidermal appendages such as hair follicles and eccrine sweat ducts. In granulation tissues, IL-8 RB was noted in numerous fibroblasts and in subpopulations of macrophages and smooth muscle. The presence of both MGSA/GRO and its receptor in human burn wounds implicate this cytokine as an autocrine or paracrine mediator of epidermal regeneration in both the inflammatory and proliferative phases of cutaneous wound repair.
Genetic immunization: a new era in vaccines and immune therapeutics (1997)

DNA inoculation represents a novel approach to vaccine and immune therapeutic development. The direct injection of gene expression cassettes into a living host transforms a number of cells into factories for production of the introduced gene products. Expression of these delivered genes has important immunological consequences and may result in the specific immune activation of the host against the novel expressed antigens. The recent demonstration by laboratories that these immune responses are protective in some infectious disease experimental models as well as cancers is viewed with cautious optimism. Further, the relatively short development times, ease of large-scale production, low development, manufacturing, and distribution costs all combine with immunological effectiveness to suggest that this technology will dramatically influence the production of a new generation of experimental vaccines and immune therapies. It is hoped that DNA inoculation will ultimately lead to new vaccines that are immunologically effective and economically accessible to all nations.
Insulin-dependent diabetes induced by pancreatic beta cell expression of IL-15 and IL-15Rα (2013)

Increased serum levels of IL-15 are reported in type 1 diabetes (T1D). Here we report elevated serum soluble IL-15Rα levels in human T1D. To investigate the role of IL-15/IL-15Rα in the pathogenesis of T1D, we generated double transgenic mice with pancreatic β-cell expression of IL-15 and IL-15Rα. The mice developed hyperglycemia, marked mononuclear cell infiltration, β-cell destruction, and anti-insulin autoantibodies that mimic early human T1D. The diabetes in this model was reversed by inhibiting IL-15 signaling with anti-IL2/IL15Rβ (anti-CD122), which blocks IL-15 transpresentation. Furthermore, the diabetes could be reversed by administration of the Janus kinase 2/3 inhibitor tofacitinib, which blocks IL-15 signaling. In an alternative diabetes model, nonobese diabetic mice, IL15/IL-15Rα expression was increased in islet cells in the prediabetic stage, and inhibition of IL-15 signaling with anti-CD122 at the prediabetic stage delayed diabetes development. In support of the view that these observations reflect the conditions in humans, we demonstrated pancreatic islet expression of both IL-15 and IL-15Rα in human T1D. Taken together our data suggest that disordered IL-15 and IL-15Rα may be involved in T1D pathogenesis and the IL-15/IL15Rα system and its signaling pathway may be rational therapeutic targets for early T1D.
Real-time RT-PCR in COVID-19 detection: issues affecting the results (2020)

Due to the rapid spread and increasing number of coronavirus disease 19 (COVID-19) cases caused by a new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), rapid and accurat...
A Viterbi algorithm with soft-decision outputs and its applications (2003)

The Viterbi algorithm (VA) is modified to deliver the most likely path sequence in a finite-state Markov chain, as well as either the a posteriori probability for each bit or a reliability value. With this reliability indicator the modified VA produces soft decisions to be used in the decoding of outer codes. The inner software output Viterbi algorithm (SOVA) accepts and delivers soft sample values and can be regraded as a device for improving the signal-to-noise ratio, similar to an FM demodulator. Several applications are investigated to show the gain over the conventional hard-deciding VA, including concatenated convolutional codes, concatenation of trellis-coded modulation with convolutional FEC (forward error correcting) codes, and coded Viterbi equalization. For these applications additional gains of 1-4 dB as compared to the classical hard-deciding algorithms were found. For comparison, the more complex symbol-to-symbol MAP, whose optimal a posteriori probabilities can be transformed into soft outputs, was investigated.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
New technique for producing highly uniform droplet streams over an extended range of disturbance wavenumbers (1987)

A recent discovery about a well-studied phenomenon leads to the formation of ultracoherent streams of liquid drops. A remarkably straightforward, although previously unreported, method of drop generation from capillary streams, which involves the imposition of an amplitude modulated sinusoidal carrier disturbance, is discussed. The amplitude-modulated disturbance results in the production of highly stable droplet streams over a previously unattainable range of wavenumbers. A decrease in the speed variation of the drops within the stream, which is a result of the amplitude modulation, is demonstrated over a range of nondimensional wavenumbers from 0.4 to 0.04. The nondimensional wavenumber is the ratio of stream circumference to disturbance wavelength. It is suggested that amplitude modulating the capillary stream’s disturbance may also decrease the diameter variation of the drops.
Visualization of specific DNA sequences in living mouse embryonic stem cells with a programmable fluorescent CRISPR/Cas system (2014)

Labeling and tracing of specific sequences in living cells has been a major challenge in studying the spatiotemporal dynamics of native chromatin. Here we repurposed the prokaryotic CRISPR/Cas adaptive immunity system to specifically detect endogenous genomic loci in mouse embryonic stem cells. We constructed a catalytically inactive version of the Cas9 endonuclease, fused it with eGFP (dCas9-eGFP) and co-expressed small guide RNAs (gRNAs) to target pericentric, centric, and telomeric repeats, which are enriched in distinct nuclear structures. With major satellite specific gRNAs we obtained a characteristic chromocenter (CC) pattern, while gRNAs targeting minor satellites and telomeres highlighted smaller foci coinciding with centromere protein B (CENP-B) and telomeric repeat-binding factor 2 (TRF2), respectively. DNA sequence specific labeling by gRNA/dCas9-eGFP complexes was directly shown with 3D-fluorescent in situ hybridization (3D-FISH). Structured illumination microscopy (3D-SIM) of gRNA/dCas9-eGFP expressing cells revealed chromatin ultrastructures and demonstrated the potential of this approach for chromatin conformation studies by super resolution microscopy. This programmable dCas9 labeling system opens new perspectives to study functional nuclear architecture.
Label-free photoacoustic imaging of human palmar vessels: a structural morphological analysis (2018)

We analysed the vascular morphology of the palm using a photoacoustic tomography (PAT) instrument with a hemispherical detector array. The three-dimensional (3D) morphology of blood vessels was determined noninvasively. Overall, 12 females and 11 males were recruited as healthy volunteers. Their ages were distributed almost evenly from 22 to 59 years. In all cases, many vascular networks were observed just beneath the skin and were determined to be veins anatomically. To analyse the major arteries, the layer containing the subcutaneous venous network was removed from the image. The analysis focused on the common and proper palmar digital arteries. We used the curvature of these arteries as a parameter to analyse their morphologies. There was no significant difference in the curvature between genders when comparing the subjects as a whole. The blood vessel curvature increased with age. Good agreement was found between the 3D numerical analysis results and the subjective evaluation of the two-dimensional (2D) projection image. The PAT system enabled visualization of the 3D features of blood vessels in the palm and noninvasive analysis of arterial tortuousness.
NETL Extreme Drilling Laboratory Studies High Pressure High Temperature Drilling Phenomena (2008)

The U.S. Department of Energy’s National Energy Technology Laboratory (NETL) established the Extreme Drilling Laboratory to engineer effective and efficient drilling technologies viable at depths greater than 20,000 ft. This paper details the challenges of ultradeep drilling, documents reports of decreased drilling rates as a result of increasing fluid pressure and temperature, and describes NETL’s research and development activities. NETL is invested in laboratory-scale physical simulation. Its physical simulator will have capability of circulating drilling fluids at 30,000 psi and 480°F around a single drill cutter. This simulator is not yet operational; therefore, the results will be limited to the identification of leading hypotheses of drilling phenomena and NETL’s test plans to validate or refute such theories. Of particular interest to the Extreme Drilling Laboratory’s studies are the combinatorial effects of drilling fluid pressure, drilling fluid properties, rock properties, pore pressure, and drilling parameters, such as cutter rotational speed, weight on bit, and hydraulics associated with drilling fluid introduction to the rock-cutter interface. A detailed discussion of how each variable is controlled in a laboratory setting will be part of the conference paper and presentation.
Kynostatin (KNI-227 and -272, highly potent anti-HIV agents: conformationally constrained tripeptide inhibitors of HIV protease containing allophenylnorstatine. (1992)

Selective and potent HIV protease inhibitors containing allophenylnorstatine [Apns; (2S, 3S)-3-amino-2-hydroxy-4-phenylbutyric acid] as a transition-state mimic were designed and synthesized. Among them, conformationally constrained tripeptide derivatives, kynostatin (KNI)-227 and -272 (Fig. 1), exhibited highly potent antiviral activities against a wide spectrum of HIV isolates. Ready availability due to the simple synthetic procedure and the excellent antiviral properties indicate that KNI-227 and KNI-272 are promising candidates as selective anti-AIDS drugs.
High endogenous nitrogenase activity in isolated heterocysts of Anabaena sp. strain CA after nitrogen starvation (1983)

Metabolically active heterocysts were isolated from a mutant of Anabaena sp. strain CA with fragile vegetative cells. Heterocysts isolated from cultures grown in 1% CO2 in air reduced C2H2 at 57 and 10 nmol of C2H2 per mg (dry weight) per min under H2 and Ar, respectively. However, if whole filaments were sparged with 1% CO2 in 99% Ar for 12 h before heterocyst isolation, these heterocysts showed C2H2 reduction rates of 83 nmol of C2H4 per mg (dry weight) per min under either H2 or Ar, or 40% the activity of whole filaments grown in 1% CO2 in air. Heterocysts isolated from cultures sparged with 100% Ar or 1% CO2 in 99% N2 had the same C2H2 reduction pattern as heterocysts from cultures grown in 1% CO2 in air, i.e., low activity under Ar and high activity under H2. Labeling of whole filaments incubated with NaH14CO3 for 12 h under 1% CO2 in air or 1% CO2 in 99% Ar resulted in a twofold higher accumulation of 14C-labeled compounds in vegetative cells and heterocysts of Ar-incubated cells. Our results suggest that during incubation under 1% CO2 in 99% Ar, presumably a nitrogen starvation condition, continuing photosynthetic fixation of CO2 leads to accumulation of material(s) in the heterocysts that supports a high, persistent endogenous rate of C2H2 reduction. This material appears to be, in part, glycogen.
ChemInform Abstract: INFRARED IDENTIFICATION OF THE PT(N2) AND PT(N2)2 COMPLEXES IN LOW TEMPERATURE MATRICES (1973)

Abstract Binäre Pt‐N2‐Komplexe werden in Edelgas‐ und N 2 ‐Matrizen bei 14°Kbeobachtet.
Erythropoietin stimulates the tyrosine phosphorylation of Shc and its association with Grb2 and a 145-Kd tyrosine phosphorylated protein (1993)

Although the erythropoietin receptor (EpR) lacks a tyrosine kinase consensus sequence within its proline-rich intracellular domain, addition of its ligand to Ep-responsive cells stimulates the rapid and transient tyrosine phosphorylation of a number of cellular proteins. The characterization of these phosphorylatable substrates, which include 5 major phosphoproteins with molecular masses of approximately 145, 130, 97, 72, and 56 Kd is an essential step in understanding the signal transduction pathways used by Ep. Recently, we and others have shown that the major 72-Kd tyrosine phosphorylated protein is the EpR itself. We now report, using both murine DA-3 and human MO7E cell lines engineered to express high levels of biologically responsive EpRs (and designated DA-ER and MO7-ER, respectively), that the major 56-Kd tyrosine phosphorylated protein is the recently identified SH2- containing protein, p52shc. Interestingly, in Ep-stimulated cells, anti- Shc antibodies coprecipitate the major 145-Kd tyrosine phosphorylated protein in both DA-ER and MO7-ER cells. Tyrosine phosphorylation of both proteins is detectable within 30 seconds of incubation with Ep at 37 degrees C, reaches a maximum between 2 and 5 minutes, and declines by 30 minutes. In addition, tyrosine phosphorylated Shc appears capable of associating with the activated EpR, but this could only be shown in MO7-ER cells. Lastly, as has been shown previously with the tyrosine kinase containing receptors for epidermal growth factor, platelet derived growth factor, and insulin, activation of the EpR leads to the association of p52shc with the 25-Kd polypeptide, Grb2. Taken together, our data suggest that the previously reported increases in rasGTP observed with Ep result, in part, from the tyrosine phosphorylation of Shc and its association with Grb2 and/or a tyrosine phosphorylated 145- Kd protein.
Nephron adaptation to renal injury or ablation (1985)

In early stages of permanent renal injury or extensive ablation, structural and functional adaptations associated with hypertrophy partially compensate for nephron losses. Glomerulotubular balance is maintained in these conditioned nephrons by intrinsic tubule and peritubular capillary adaptations that parallel single nephron glomerular filtration rate (SNGFR). Studies of Na+-H+ exchange in renal cortical brush border membrane vesicles indicate that tubule functional adaptation is not tied to loss of renal mass per se but rather to factors such as dietary protein content that set the level of SNGFR. Likewise, the structural heterogeneity that follows chronic renal injury or extreme ablation of renal mass is less a consequence of nephron injury than of adaptation linked to dietary protein intake. Indeed, since dietary protein restriction blunts the need for compensatory glomerular hyperfiltration, there is neither a stimulus for nephron hypertrophy nor for enhanced tubule ion and fluid transport. In rats with remnant kidneys, experimentally induced diabetes mellitus, or severe hypertension, increases in glomerular pressures and flows precede proteinuria, glomerular sclerosis, and azotemia. Protein restriction prevents these hemodynamic adaptations as well as the late complications. Similar conclusions appear to be applicable to a wide spectrum of clinical circumstances characterized by reduced nephron number.
Hidden positivity and a new approach to numerical computation of Hausdorff dimension: higher order methods (2021)

In 2018, the authors developed a new approach to the computation of the Hausdorff dimension of the invariant set of an iterated function system or IFS. In this paper, we extend this approach to incorporate high order approximation methods. We again rely on the fact that we can associate to the IFS a parametrized family of positive, linear, Perron–Frobenius operators L_s , an idea known in varying degrees of generality for many years. Although L_s is not compact in the setting we consider, it possesses a strictly positive C^m eigenfunction v_s with eigenvalue R(L_s) for arbitrary m and all other points z in the spectrum of L_s satisfy |z| \le b for some constant b &lt; R(L_s) . Under appropriate assumptions on the IFS, the Hausdorff dimension of the invariant set of the IFS is the value s=s_* for which R(L_s) =1 . This eigenvalue problem is then approximated by a collocation method at the extended Chebyshev points of each subinterval using continuous piecewise polynomials of arbitrary degree r . Using an extension of the Perron theory of positive matrices to matrices that map a cone K to its interior and explicit a priori bounds on the derivatives of the strictly positive eigenfunction v_s , we give rigorous upper and lower bounds for the Hausdorff dimension s_* , and these bounds converge rapidly to s_* as the mesh size decreases and/or the polynomial degree increases.
Neurologic and Developmental Disability after Extremely Preterm Birth (2000)

Severe disability is common among children born as extremely preterm infants.
Stromal cell–derived factor 1 regulates primitive hematopoiesis by suppressing apoptosis and by promoting G0/G1 transition in CD34+ cells: evidence for an autocrine/paracrine mechanism (2002)

The stromal cell-derived factor 1 (SDF-1) chemokine has various effects on hematopoietic cell functions. Its role in migration and homing of hematopoietic progenitors is currently well established. Previously it was shown that SDF-1 stimulates myeloid progenitor proliferation in synergy with cytokines. Results of this study indicate that SDF-1 alone promotes survival of purified CD34(+) cells from human unmobilized peripheral blood (PB) by counteracting apoptosis as demonstrated by its capacity to reduce DNA fragmentation, annexin-V(+) cell number, and APO2.7 detection and to modulate bcl-2 homolog protein expression. The study demonstrates that SDF-1, produced by sorted CD34(+)CD38(+) cells and over-released in response to cell damage, exerts an antiapoptotic effect on CD34(+) cells through an autocrine/paracrine regulatory loop. SDF-1 participates in the autonomous survival of circulating CD34(+) cells and its effect required activation of the phosphotidyl inositol 3 kinase (PI3-K)/Akt axis. Cell sorting based on Hoechst/pyroninY fluorescences shows that SDF-1 production is restricted to cycling CD34(+) cells. SDF-1 triggers G(0) quiescent cells in G(1) phase and, in synergy with thrombopoietin or Steel factor, makes CD34(+) cells progress through S+G(2)/M phases of cell cycle. By assessing sorted CD34(+)CD38(-) and CD34(+)CD38(+) in semisolid culture, the study demonstrates that SDF-1 promotes survival of clonogenic progenitors. In conclusion, the results are the first to indicate a role for endogenous SDF-1 in primitive hematopoiesis regulation as a survival and cell cycle priming factor for circulating CD34(+) cells. The proposal is made that SDF-1 may contribute to hematopoiesis homeostasis by participating in the autonomous survival and cycling of progenitors under physiologic conditions and by protecting them from cell aggression in stress situations.
Production of α-1,3-galactosyltransferase null pigs by means of nuclear transfer with fibroblasts bearing loss of heterozygosity mutations (2004)

Hyperacute rejection of porcine organs by old world primate recipients is mediated through preformed antibodies against galactosyl-alpha-1,3-galactose (Galalpha-1,3-Gal) epitopes expressed on the pig cell surface. Previously, we generated inbred miniature swine with a null allele of the alpha-1,3-galactosyltransferase locus (GGTA1) by nuclear transfer (NT) with gene-targeted fibroblasts. To expedite the generation of GGTA1 null pigs, we selected spontaneous null mutant cells from fibroblast cultures of heterozygous animals for use in another round of NT. An unexpectedly high rate of spontaneous loss of GGTA1 function was observed, with the vast majority of null cells resulting from loss of the WT allele. Healthy piglets, hemizygous and homozygous for the gene-targeted allele, were produced by NT by using fibroblasts that had undergone deletional and crossover/gene conversion events, respectively. Aside from loss of Galalpha-1,3-Gal epitopes, there were no obvious phenotypic differences between these null piglets and WT piglets from the same inbred lines. In fact, congenital abnormalities observed in the heterozygous NT animals did not reappear in the serially produced null animals.