gebhart/patrepeval huggingface dataset:
A novel protein tyrosine phosphatase expressed in lin(lo)CD34(hi)Sca(hi) hematopoietic progenitor cells (1996)

Stem cells are capable of extensive self-renewal in the absence of differentiation. The maintenance of this undifferentiated state occurs despite the fact that this cell is exposed to a milieu that is rich in a variety of growth and differentiation factors. A unifying feature of such hematopoietic factors is that they mediate their effects through the phosphorylation of tyrosine residues by various cellular kinases. Therefore, one mechanism that might inhibit such differentiation signals in the self-renewing stem cell is the dephosphorylation of tyrosine residues by protein tyrosine phosphatases (PTPs). We have thus investigated the types of tyrosine phosphatases expressed by murine embryonic lin(lo)CD34hiSca(hi) hematopoietic progenitor cells by using a consensus polymerase chain reaction (PCR) approach. Although many known tyrosine phosphatases were detected using this method, a novel PTP related to the previously described PTP PEST type enzymes, murine PTP PEP and murine/human PTP PEST, was also observed. Cloning of the full-length cDNA encoding this enzyme showed that it was indeed a novel new member of this family, with an amino terminal tyrosine phosphatase domain followed by a region rich in serine, threonine, and proline. The carboxy terminus of this novel PTP contained a short sequence that was homologous to a region of the murine PTP PEP that was involved with nuclear localization. Bacterial expression of the phosphatase domain showed that this enzyme could efficiently dephosphorylate tyrosines in vitro. Analysis of the expression of the novel nuclear PTP by quantitative PCR showed that the transcript disappeared as the lin(lo)CD34hiSca(hi) cells differentiated in the presence of interleukin-1, interleukin-3, erythropoietin, and granulocyte-macrophage colony-stimulating factor. In agreement with its potential role in the hematopoietic progenitor cell, this novel PTP was expressed at a barely detectable level in a very limited subset of adult tissues. However, analysis of several murine hematopoietic progenitor cell lines, but not of a differentiated T-cell line, showed a high level of expression of the novel PTP. These data suggest that this novel phosphatase may play a critical role in the maintenance of the undifferentiated state of the hematopoietic stem cell.
Environmental radioactivity in southern Serbia at locations where depleted uranium was used (2014)

In the 1999 bombing of the Federal Republic of Yugoslavia, NATO forces used ammunition containing depleted uranium. The cleaning of depleted uranium that followed was performed in southern Serbia by the Vinča Institute of Nuclear Sciences between 2002 and 2007 at the locations of Pljačkovica, Borovac, Bratoselce, and Reljan. This paper presents detailed results of radioactivity monitoring four years after cleaning (2011), which included the determination of gamma emitters in soil, water, and plant samples, as well as gross alpha and beta activities in water samples. The gamma spectrometry results showed the presence of natural radionuclides 226Ra, 232Th, 40K, 235U, 238U, and the produced radionuclide 137Cs (from the Chernobyl accident). In order to evaluate the radiological hazard from soil, the radium equivalent activity, the gamma dose rate, the external hazard index, and the annual effective dose were calculated. Considering that a significant number of people inhabit the studied locations, the periodical monitoring of radionuclide content is vital.
Endocrinology: The effect of antiprogestin (RU 486) and prostaglandin biosynthesis inhibitor (naproxen) on uterine fluid prostaglandin F2α concentrations (1994)

In the present study the effect of the antiprogestin RU 486 and the prostaglandin biosynthesis inhibitor, naproxen, on uterine fluid concentration of prostaglandin F2 alpha (PGF2 alpha) was investigated. RU 486, 200 mg, was administered two days after the luteinizing hormone (LH) surge and naproxen, 500 mg, was given every 12th hour five times starting 4 days after the LH surge. Uterine fluid was collected in the proliferative phase at ovulation and in the mid-luteal phase in a control and treatment cycle. The amount of PGF2 alpha was measured by gas chromatography-mass spectrometry. In the control cycle, the highest concentration of PGF2 alpha was found in the mid-luteal phase, and the lowest at the time of ovulation. Both RU 486 and naproxen reduced the PGF2 alpha concentration in uterine fluid considerably, or to 22-25% of that in the control cycle at the time of implantation. PGF2 alpha produced by the endometrium is believed to be of importance for the implantation of the blastocyst. Postovulatory treatment with RU 486 effectively prevents implantation, probably mainly by inhibiting the maturation of the endometrium during the secretory phase of the cycle. It is suggested that the inhibition of PGF2 alpha release through the uterine fluid caused by RU 486 may also be of importance.
Identification of S100A8 and S100A9 as Serological Markers for Colorectal Cancer (2009)

In search of novel serological protein biomarkers for human colorectal cancer (CRC), we analyzed CRC tissues using two-dimensional difference in-gel electrophoresis (2D-DIGE) on a narrow range IPG strip (pH 5.5-6.7). By comparing tumor tissues with matched normal tissues in a pairwise manner (n = 6), we identified 34 up-regulated and 17 down-regulated spots with intensity changes greater than 2-fold (Student's t-test, p < 0.05). Expression of both mRNA and protein levels of four proteins, adenosylhomocysteinase, Nm23-H1, S100A8 and S100A9, in CRC tissues was further evaluated by semiquantitative RT-PCR and Western blot analysis. The results revealed that all four proteins were elevated in the tumor tissues. We also confirmed, by immunohistochemistry, that adenosylhomocysteinase and Nm23-H1 were overexpressed in tumor cell cytoplasm and that S100A8 and S100A9 proteins were strongly expressed in tumor infiltrating immune cells. Western blot analysis with fractionated plasma samples showed that S100A8 and S100A9 were significantly increased in the plasma of CRC patients (n = 77) and colorectal adenoma patients (n = 11), compared to healthy controls (n = 21). The area under a receiver operating characteristic (ROC) curve was 0.91 for S100A8 and 0.89 for S100A9, which was superior to the established tumor marker carcinoembryonic antigen with 0.78 for the area under the ROC curve. Some patients with inflammatory diseases such as pancreatitis also showed elevated levels of the proteins. Importantly, in comparison to the control group, both proteins showed a remarkable change at the early stage of cancer. Therefore, we suggest S100A8 and S100A9 as candidates for serological biomarkers in combination with other serum markers that aid CRC diagnosis.
Role of Shc in T‐cell development and function (2003)

Shc is a prototype adapter protein that is expressed from the earliest stages of T-cell development. Shc becomes rapidly tyrosine phosphorylated after T-cell receptor (TCR) engagement. Expression of dominant negative forms of Shc in T-cell lines had also suggested a role for this adapter downstream of the TCR. However, until recently, the relative significance of Shc compared to several other adapters in T cells was unclear. Mice lacking Shc expression specifically in the T-cell lineage together with inducible expression of dominant negative Shc in transgenic mice have revealed an essential and nonredundant role for Shc in thymic T-cell development. Functional defects in a Jurkat T-cell line lacking Shc expression also suggest a role for Shc in mature T-cell functions. While the requirement of Shc in T-cell signaling is now established, precisely what signaling pathways downstream of Shc make this adapter unique are less clear. Although the Shc-mediated activation of the extracellular signal regulated kinase (Erk)/mitogen-activated protein kinase (MAPK) pathway could be one component, Shc likely signals to other pathways in T cells that are not yet discovered. A better molecular understanding of Shc function in the future could provide insights into how multiple adapters coordinate the various outcomes downstream of the TCR.
HIV-1 Replication and Potential Targets for Intervention (1992)

Intense research into fundamental processes of human immunodeficiency syndrome type 1 (HIV-1) replication has yielded knowledge that in many aspects equals or exceeds that of the oncogenic retroviruses. The availability of sensitive virus detection methods has allowed a more thorough characterization of the biology of virus persistence and latency in vivo and removed the dependence on in vitro models. As a clearer picture of the pattern of HIV-1 replication in vivo evolves, it becomes apparent that HIV-1 biology is distinct from that of the prototypic oncogenic retroviruses in several key aspects, particularly with regard to host cell range and determinants of viral permissiveness. In this respect it may be appropriate to examine the lentivirus, rather than the oncovirus model system to better understand the biology and pathogenesis of HIV-1 infection. This synopsis of recent and ongoing research developments in HIV-1 replication and pathogenesis emphasizes the determinants of host cell permissiveness, early events in virus replication, and underlying features in HIV-1 cytopathogenesis. In addition, basic viral replication processes which can be exploited for therapeutic intervention are discussed.
Immunosuppressive acidic protein in patients with ovarian cancer (1983)

Serum immunosuppressive acidic protein (IAP) was determined in 63 patients with ovarian tumors (33 benign and 30 malignant) and 79 healthy female controls, and was examined as a marker for ovarian cancer in comparison with carcinoembryonic antigen (CEA). The mean value of serum IAP in patients with ovarian cancer (1085 +/- 474 micrograms/ml) was statistically higher than those of both benign tumors (394 +/- 93 micrograms/ml) and controls (298 +/- 92 micrograms/ml). Elevated levels of IAP and CEA were found in 93.3% and 30.0% of patients with ovarian cancer, respectively. There were three false-positive cases with IAP and two with CEA. Elevation of IAP was recognized in all cancer patients in Stage I, whereas 33.3% of these patients showed elevated CEA. The occurrence of elevated serum IAP was not affected by tumor histologic features. Serial IAP determination appeared to provide a useful follow-up marker in patients in whom CEA was low in value. The measurement of serum IAP is highly recommended as an addition to the conventional diagnostic methods.
Accurate Quadrifocal Tracking for Robust 3D Visual Odometry (2007)

This paper describes a new image-based approach to tracking the 6DOF trajectory of a stereo camera pair using a corresponding reference image pairs instead of explicit 3D feature reconstruction of the scene. A dense minimisation approach is employed which directly uses all grey-scale information available within the stereo pair (or stereo region) leading to very robust and precise results. Metric 3D structure constraints are imposed by consistently warping corresponding stereo images to generate novel viewpoints at each stereo acquisition. An iterative non-linear trajectory estimation approach is formulated based on a quadrifocal relationship between the image intensities within adjacent views of the stereo pair. A robust M-estimation technique is used to reject outliers corresponding to moving objects within the scene or other outliers such as occlusions and illumination changes. The technique is applied to recovering the trajectory of a moving vehicle in long and difficult sequences of images.
Parametric Excitation (1951)

This paper outlines a theory of excitation of oscillations under the rather slow variations of a parameter on which a system depends. The basic equation is a Mathieu equation. The basic method consists in reducing the system to polar coordinates and applying perturbations.
Dysregulated bcl-2 expression inhibits apoptosis but not differentiation of retinoic acid-induced HL-60 granulocytes (1994)

The bcl-2-proto-oncogene appears to contribute to the development of certain malignancies by inhibiting programmed cell death (apoptosis). Mature granulocytes show a markedly limited life span and rapidly undergo apoptosis. To further define the relationship between apoptosis and granulocyte differentiation, we used retroviral vector-mediated gene transduction to introduce the normal bcl-2 gene into the HL-60 myeloid leukemia cell line and determined the response of these bcl-2-transduced HL-60 cells to the induction of granulocyte differentiation by retinoic acid (RA). Although the bcl-2-transduced HL-60 cells showed the same differentiative response to RA as did the parental HL-60 cells, the life span of the RA-induced, bcl-2-transduced HL-60 granulocytes was markedly prolonged compared with that of the RA-induced parental HL-60 granulocytes. DNA fragmentation studies indicate that this prolonged life span resulted from diminished apoptosis in the bcl-2-transduced cells. These studies indicate that bcl-2 is involved in regulating apoptosis in maturing granulocytes. Because bcl-2 over-expression did not interfere with RA-induced granulocyte differentiation, it appears that granulocyte differentiation and apoptosis are under distinct and separate regulatory controls.
The flip side of immune surveillance: immune dependency (2008)

The growths of many and perhaps all tumors may be stimulated rather than inhibited by a quantitatively low level of immunity. The reason tumors have antigens may be that tumors do not develop in vivo in the absence of at least a minimal immune reaction; in this sense, cancer may be considered an autoimmune disease. This review, based largely on the work of our own laboratory, outlines the data showing that the titration of anti-tumor immunity exhibits the phenomenon of hormesis, i.e. the dose-response curve is non-linear such that low levels of immunity are generally stimulatory but larger quantities of the same immune reactants may inhibit tumor growth. Evidence is also reviewed that suggests that the immune response may vary qualitatively and quantitatively during progression, such that there seems to be, during oncogenesis, a very low level of immune reaction that aids initial tumor growth, followed by a larger reaction that may cause remission of early neoplasms, followed, if the neoplasm survives, by a relative immunologic tolerance to the tumor that may be dependent, at least in part, on suppressor cells. This knowledge may help to explain some clinical observations concerning the relationships among tumor types and the organ distribution of metastases.
Electret Film-Enhanced Triboelectric Nanogenerator Matrix for Self-Powered Instantaneous Tactile Imaging (2014)

We report the first self-powered electronic skin that consists of light-emitting diode (LED) and triboelectric nanogenerator (TENG) arrays that can be utilized for spatially mapping applied instantaneous-touch events and tracking the movement location of the target object by recording the electroluminescent signals of the LEDs without external power sources. The electret film-based TENG can deliver an open-circuit voltage of about -1070 V, a short-circuit current density of 10 mA/m(2), and a power density of 288 mW/m(2) on an external load of 100 MΩ. The LEDs can be turned on locally when the back surface of the active matrix is touched, and the intensity of the emitted light depends on the magnitude of the applied local pressure on the device. A constructed active matrix of the LED-TENG array (8 × 7 pixels) can achieve self-powered, visual, and high-resolution tactile sensing by recording the electroluminescent signals from all of the pixels, where the active size of each pixel can be decreased to 10 mm(2). This work is a significant step forward in self-powered tactile-mapping visualization technology, with a wide range of potential applications in touchpad technology, personal signatures, smart wallpapers, robotics, and safety-monitoring devices.
Surface treatment of denim fabric for selective fading (2016)

A growing customer demand currently exists for denim apparel with a used, worn, faded appearance or even holes in the fabric. In this work, we examined the effect of treating denim with an aqueous solution of an oxidant prior to UV-C irradiation for localized fading of the fabric in order to obtain the faded, worn apperance sought by some jeans users. We propose a new technology using ultraviolet light in combination with an oxidant to modulate the degree of fading of denim fabric
Extrachromosomal and Chromosomal Gene Conversion in Mammalian Cells (1986)

We constructed substrates to study gene conversion in mammalian cells specifically without the complication of reciprocal recombination events. These substrates contain both an insertion mutation of the neomycin resistance gene (neoX) and an internal, homologous fragment of the neo gene (neo-526), such that gene conversion from neo-526 to neoX restores a functional neo gene. Although two reciprocal recombination events can also produce an intact neo gene, these double recombination events occur much less frequently that gene conversion in mammalian cells, We used our substrates to characterize extrachromosomal gene conversion in recombination-deficient bacteria and in monkey COS cells. Chromosomal recombination was also studied after stable integration of these substrates into the genome of mouse 3T6 cells. All extrachromosomal and chromosomal recombination events analyzed in mammalian cells resulted from gene conversion. Chromosomal gene conversion events occurred at frequencies of about 10(-6) per cell generation and restored a functional neo gene without overall effects on sequence organization.
Multiplex protein assays based on real-time magnetic nanotag sensing (2008)

Magnetic nanotags (MNTs) are a promising alternative to fluorescent labels in biomolecular detection assays, because minute quantities of MNTs can be detected with inexpensive giant magnetoresistive (GMR) sensors, such as spin valve (SV) sensors. However, translating this promise into easy to use and multilplexed protein assays, which are highly sought after in molecular diagnostics such as cancer diagnosis and treatment monitoring, has been challenging. Here, we demonstrate multiplex protein detection of potential cancer markers at subpicomolar concentration levels and with a dynamic range of more than four decades. With the addition of nanotag amplification, the analytic sensitivity extends into the low fM concentration range. The multianalyte ability, sensitivity, scalability, and ease of use of the MNT-based protein assay technology make it a strong contender for versatile and portable molecular diagnostics in both research and clinical settings.
Early clinical activity and pharmacodynamic effects of duvelisib, a PI3K-δ,γ inhibitor, in patients with treatment-naïve CLL. (2015)

7074 Background: Signaling via PI3K-δ and PI3K-γ has distinct and complementary effects on malignant B-cells and nonmalignant immune cells in chronic lymphocytic leukemia (CLL). Duvelisib, an oral PI3K-δ,γ inhibitor, has shown clinical activity in a phase 1 study, IPI-145-02. The activity of duvelisib monotherapy in pts with treatment-naïve (TN) CLL from this study are reported here. Methods: Following dose escalation, an expansion cohort of TN CLL pts was enrolled (n = 18). Response was based on iwCLL (2008) criteria. Safety included AEs and laboratory assessments. Pharmacodynamic assessments included peripheral blood (PB) flow cytometry for phospho-S473 AKT (pAKT) and Ki67, and measurement of serum chemokines and cytokines. Numbers of PB T-cell subsets were also monitored. Results: As of Oct 2014, 18 TN CLL pts received duvelisib 25 mg BID. The best ORR per iwCLL was 82% (PRs in 14/17 evaluable pts) with a median time on treatment of 53 weeks (range 8-69). Ten pts remain on treatment, while 8 discontinued, including 6 pts due to AEs. AEs overall were mostly Gr. 1 or 2. The most common ≥ Gr. 3 AEs were neutropenia (7/18) and ALT/AST increase (3/18). Inhibition of pAKT in CLL cells was rapid following a single dose and sustained through Cycle 2 Day 1 (C2D1). A reduction in the Ki67 proliferative fraction in both CLL and T-cells was also observed. The overall number of T-cells and T-cell subsets (CD4, CD8, memory cells) did not decrease through C3D1. Duvelisib also resulted in reductions in the median serum levels of CCL3, CCL4, CCL17, CCL22, CXCL10, CXCL13, IL-10, IL-12p40, MMP-9, IL-16, and TNFα to ≤ 50% of baseline at C1D8 and/or C2D1 (p < 0.01). Conclusions: Duvelisib 25 mg BID shows clinical activity in TN CLL pts.The inhibition of pAKT and Ki67 in CLL cells suggests duvelisib inhibits the PI3K pathway and suppresses malignant cell proliferation in TN CLL pts. In addition, the effect of duvelisib on serum chemokines, cytokines, and T-cell proliferation suggests that modulation of the tumor microenvironment may contribute to the observed early clinical activity of duvelisib in pts with TN CLL. These data support the further development of duvelisib in TN CLL, including combinations with other targeted therapies. Clinical trial information: NCT01476657.
Carotid Magnetic Resonance Imaging (2009)

Despite recent advances in the understanding and etiology of cardiovascular disease, it remains the leading cause of morbidity and mortality worldwide. A great deal of research has been dedicated to investigating and identifying plaque instability: the so-called "vulnerable plaque". A reliable, in vivo, imaging method capable of identifying plaque characteristics associated with high-risk plaque will be immensely useful for evaluating plaque status and predicting future events. With excellent soft-tissue contrast and resolution, magnetic resonance imaging (MRI) has the ability to visualize features of vulnerable plaques, as well as perform longitudinal studies on the etiology, progression, and regression of atherosclerotic plaque. This review will cover the current state-of-the-art and new developments in carotid MRI to characterize atherosclerosis and its use in clinical diagnoses and longitudinal studies to understand mechanisms of lesion progression and regression.
Reaktionen von 3-Dimethylamino-2,2-dimethyl-2H-azirin mit aromatischen Carbonsäurehydraziden (1978)

Reaction of 3-dimethylamino-2,2-dimethyl-2H-azirine (1) with salicylic acid hydrazide (2c) in acetonitrile at room temperature gives the amidrazone 3c as a primary product in 78% yield. Cyclization of 3c in methanol leads to the 1,2,5,6-tetrahydro-1,2,4-triazin-6-one 4, whereas the cyclization in DMSO gives a mixture of 4 and the 5-dimethylamino-2,4-dihydro-1,2,4-tri-azine 5. Benzoic acid hydrazides of type 6 react with 1 in acetonitril at 80°C to give the 1,3,4-oxadiazoles of type 7 in good yield.
Recursive Sample Classification and Gene Selection based on SVM: Method and Software Description # (2001)

Under the global pandemic of COVID-19, the use of artificial intelligence to analyze chest X-ray (CXR) image for COVID-19 diagnosis and patient triage is becoming important. Unfortunately, due to the emergent nature of the COVID-19 pandemic, a systematic collection of CXR data set for deep neural network training is difficult. To address this problem, here we propose a patch-based convolutional neural network approach with a relatively small number of trainable parameters for COVID-19 diagnosis. The proposed method is inspired by our statistical analysis of the potential imaging biomarkers of the CXR radiographs. Experimental results show that our method achieves state-of-the-art performance and provides clinically interpretable saliency maps, which are useful for COVID-19 diagnosis and patient triage.