gebhart/patrepeval huggingface dataset:
Overcoming target epitope masking resistance that can occur on low-antigen-expresser AML blasts after IL-1RAP chimeric antigen receptor T cell therapy using the inducible caspase 9 suicide gene safety switch (2021)

Although chimeric antigen receptor CAR) T cell immunotherapies are an undeniable and unequivocal success, knowledge obtained from the monitoring of the first clinical trials targeting the CD19 antigen in B malignancies, either refractory/relapsed acute lymphoid leukemia (ALL) or lymphomas, contributed to the identification of tumor cell escape in about 30-50% of B-ALL. Resistance occurred due to loss of surface expression of the antigen (rCD19-) or to the early disappearance or inactivation of CAR T cells (rCD19+). In a recently reported clinical case, rCD19- relapse resulted from masking of the antigen by the CAR at the surface of B-ALL leukemia cells following the unexpected viral transduction of a leukemic cell present in the cytapheresis sample. The objective of this work was to reproduce this epitope-masking resistance model, in the context of acute myeloid leukemia (AML), based on our immunotherapeutic CAR T cell model targeting the accessory protein of the interleukin-1 receptor (IL-1RAP) expressed by leukemic stem cells. As AML primary blasts express different levels of IL-1RAP, we modeled transduction of different AML tumor cell lines screened for density of antigenic sites with our lentiviral vectors carrying a third-generation IL-1RAP CAR, an iCASP9 suicide gene, and a truncated CD19 surface gene. We demonstrated that primary AML blasts can be easily transduced (74.55 ± 21.29%, n = 4) and that CAR T cytotoxicity to IL-1RAP is inversely correlated with epitope masking in relation to the number of antigenic sites expressed on the surface of IL-1RAP+ lines. Importantly, we showed that, in vitro, a 24-h exposure of IL-1RAP+/CAR+ leukemia lines to Rimiducid eliminated >85% of the cells. We confirmed that the expression of IL-1RAP CAR by an IL-1RAP+ leukemic cell, by decreasing the membrane availability of the targeted antigen, can induce resistance while a high epitope density maintains sensitivity to CAR T cells. Moreover, the presence of the iCASP9/Rimiducid suicide system safety switch makes this immunotherapy approach safe for application in a future phase 1 clinical trial.
Global DNA methylation and hydroxymethylation differ in hepatocellular carcinoma and cholangiocarcinoma and relate to survival rate (2015)

A significant DNA hypomethylation distinguishes HCC from CC, while DNA hypo-hydroxymethylation characterizes both HCC and CC, and a PBMC DNA mCyt content ≥5.59% relates to a favorable outcome in primary liver cancers.
Solvent-free synthesis of thioglycosides by ball milling (2009)

Thioglycosides have been prepared in excellent yields by three different routes from a range of readily available glycosyl halides under solvent-free conditions employing a planetary ball mill.
Genome Sequence of the Bacteriocin-Producing Lactobacillus curvatus Strain CRL705 (2011)

Lactobacillus curvatus is one of the most prevalent lactic acid bacteria found in fermented meat products. Here, we present the draft genome sequence of Lactobacillus curvatus CRL705, a bacteriocin producer strain isolated from an Argentinean artisanal fermented sausage, which consists of 1,833,251 bp (GC content, 41.9%) and two circular plasmids of 12,342 bp (pRC12; GC, 43.9%) and 18,664 bp (pRC18; GC, 34.4%).
Leveraging Performance of Multiroot Data Center Networks by Reactive Reroute (2010)

Data center networks (DCNs) usually have a regular topology providing high bandwidth and low latency with multi-paths. In a data-intensive application on DCNs, it is important to be able to use all the available bandwidth. However, this is not easy to achieve because of the locality of congestion information. In this paper, we propose a reactive reroute strategy to incorporate with IEEE 802.1Qau standards on Ethernet-based DCNs so that we can exploit the multipath property of a network to reduce congestion, and hence improve performance. We show by simulation that the throughput is significantly higher and the number of out-of-order packets induced by rerouting is limited.
Continuous Assessment of Gait Velocity in Parkinson's Disease from Unobtrusive Measurements (2007)

The ability to assess the neurological state of patients with neurodegenerative diseases on a continuous basis is an important component of future care for these chronically ill patients. In this paper we describe a set of algorithms to infer gait velocity and its variability using data from an unobtrusive sensor network by incorporating a simple dynamic description of a patient's movements within his or her residence. The sensors include a combination of passive motion detectors and active radio frequency identification tags. The dynamic model is a simple 4 state hidden Markov model. We investigated the ability of this model to assess gait velocity and its variability using data from a six month pilot study of several patients with early stage Parkinson's disease
Fish oil reduces ethanol‐induced damage of the duodenal mucosa in humans (1991)

Eight healthy volunteers were studied before and after 3 weeks of dietary supplementation with fish oil (10.5 g day-1, 18% (1.9 g) eicosapentaenoic acid). Duodenal mucosal lesions were induced by instillation of 40 ml ethanol (40%). Mean endoscopic lesion score was lower after fish oil treatment (1.62 +/- 0.32; mean +/- SEM) than before (3.25 +/- 0.31; P less than 0.01). Histologic lesion score fell from 22.75 +/- 1.98 before treatment to 13.50 +/- 1.51 after fish oil (P less than 0.01). Basal and pentagastrin-stimulated gastric acid output remained unaffected. Release of prostaglandin E2, 6-keto-prostaglandin F1 alpha, and thromboxane B2 from biopsy specimens of the duodenal mucosa in vitro was not significantly altered after fish oil ingestion. In the same in vitro system calcium ionophore A23187-induced release of total leukotriene C (LTC) increased from 10.6 +/- 1.5 ng g-1 mucosa 20 min before treatment to 30.4 +/- 3.2 ng after fish oil. High pressure liquid chromatography analysis showed that this increase was partly due to formation of LTC5 as after fish oil 28% of total LTC were identified as LTC5 whereas 72% were LTC4. We conclude that in humans fish oil reduces ethanol-induced damage of the duodenal mucosa without inhibiting gastric acid secretion or stimulating prostaglandin formation. It remains to be clarified if the changes in leukotriene formation are relevant for the mucosaprotective fish oil effect.
CXCR6 Upregulation Contributes to a Proinflammatory Tumor Microenvironment That Drives Metastasis and Poor Patient Outcomes in Hepatocellular Carcinoma (2012)

CXC chemokines and their cognate receptors have been implicated widely in cancer pathogenesis. In this study, we report a critical causal relationship between CXCR6 expression and tumorigenesis in the setting of human hepatocellular carcinoma (HCC). Among the CXC chemokine receptors, only CXCR6 was detected in all the hepatoma cell lines studied. Moreover, in HCC tissue, CXCR6 expression was significantly higher than in noncancerous liver tissues. Reduction of CXCR6 or its ligand CXCL16 in cancer cells reduced cell invasion in vitro and tumor growth, angiogenesis, and metastases in vivo. Importantly, loss of CXCR6 led to reduced Gr-1+ neutrophil infiltration and decreased neoangiogenesis in hepatoma xenografts via inhibition of proinflammatory cytokine production. Clinically, high expression of CXCR6 was an independent predictor of increased recurrence and poor survival in HCCs. Human HCC samples expressing high levels of CXCR6 also contained an increased number of CD66b+ neutrophils and microvessels, and the combination of CXCR6 and neutrophils was a superior predictor of recurrence and survival than either marker used alone. Together, our findings suggest that elevated expression of CXCR6 promotes HCC invasiveness and a protumor inflammatory environment and is associated with poor patient outcome. These results support the concept that inhibition of the CXCR6-CXCL16 pathway may improve prognosis after HCC treatment.
A fully integrated GMSK modulator using BiCMOS Σ-Δ frequency synthesizer with automatic loop gain calibration (2005)

A 2.7 V 16 mA GMSK modulator using a /spl Sigma/-/spl Delta/ frequency synthesizer with automatic loop gain calibration is implemented on a 3.2 mm/sup 2/ die area using a 0.35 /spl mu/m BiCMOS process. It meets the GSM transmit spectral mask specification and achieves a close-in phase noise of -90 dBc/Hz and spurious noise level of -75 dBc/Hz without modulation.
A Conserved Functional Domain of <i>Drosophila</i> Coracle Is Required for Localization at the Septate Junction and Has Membrane-organizing Activity (1998)

The protein 4.1 superfamily is comprised of a diverse group of cytoplasmic proteins, many of which have been shown to associate with the plasma membrane via binding to specific transmembrane proteins. Coracle, a Drosophila protein 4.1 homologue, is required during embryogenesis and is localized to the cytoplasmic face of the septate junction in epithelial cells. Using in vitro mutagenesis, we demonstrate that the amino-terminal 383 amino acids of Coracle define a functional domain that is both necessary and sufficient for proper septate junction localization in transgenic embryos. Genetic mutations within this domain disrupt the subcellular localization of Coracle and severely affect its genetic function, indicating that correct subcellular localization is essential for Coracle function. Furthermore, the localization of Coracle and the transmembrane protein Neurexin to the septate junction display an interdependent relationship, suggesting that Coracle and Neurexin interact with one another at the cytoplasmic face of the septate junction. Consistent with this notion, immunoprecipitation and in vitro binding studies demonstrate that the amino-terminal 383 amino acids of Coracle and cytoplasmic domain of Neurexin interact directly. Together these results indicate that Coracle provides essential membrane-organizing functions at the septate junction, and that these functions are carried out by an amino-terminal domain that is conserved in all protein 4.1 superfamily members.
Extracellular Ca2+ Increases Cytosolic Free Ca2+ in Freshly Isolated Rat Odontoblasts (1999)

Recent evidence suggests that extracellular Ca2+ may modulate cell function in mineralized tissue. To determine whether dentinogenic cells, in particular, are sensitive to extracellular Ca2+, fura-2 microfluorometry was used to monitor intracellular calcium levels in odontoblasts freshly isolated from rat incisor. In response to applications of 0.5-4.0 mM extracellular calcium (CaCl2), most odontoblasts (84%; 107/128) showed an increase in intracellular calcium. For the majority of these cells (70%; 75/107), the typical response was biphasic; there was an initial, transient increase in intracellular calcium which reached peak levels within 30-50 s and decayed rapidly, followed by a slower (> 300 s) recovery toward basal levels. In general, the response of these cells to calcium was repeatable and the mean calcium concentration for the half-maximal response was approximately 1.3 mM. This effect could be partially blocked by either 200 microM lanthanum, a nonspecific blocker of Ca2+ channels, or 20 microM dantrolene, a potent inhibitor of Ca2+ release from internal stores. Used in combination, lanthanum, and dantrolene nearly abolished the calcium response completely. In addition, this response was sensitive to the dihydropyridine-sensitive calcium channel blocking agent nicardipine (60 microM), indicating a role for voltage-gated calcium channels during these events. These results show that odontoblasts respond to external calcium through mechanisms involving both influx of external calcium as well as release of calcium from internal stores and suggest a role for extracellular calcium in regulating the function of these cells.
Tyrosine-specific protein kinase activity is associated with the purified insulin receptor. (1983)

Highly purified human placental insulin receptors were obtained by sequential affinity chromatography on wheat germ agglutinin and insulin-agarose. The preparation had an insulin binding capacity of 4,700 pmol/mg of protein approaching theoretical purity. The purified receptor revealed three major bands of Mr 135,000, 95,000, and 52,000 in NaDodSO4/polyacrylamide gel electrophoresis after reduction by dithiothreitol. All three bands were immunoprecipitated by anti-insulin-receptor antibodies. When this preparation was incubated with [gamma-32P]ATP in the presence of MnCl2 (2 mM) and analyzed in NaDodSO4/acrylamide gel electrophoresis, only the Mr 95,000 band was labeled. Preincubation with several concentrations of insulin increased the 32P incorporation into this peptide in dose-dependent fashion, whereas insulin-like growth factors were approximately equal to 2% as potent and epidermal growth factor had little or no effect, consistent with their known affinities for the insulin receptor. Insulin stimulation of phosphorylation of the Mr 95,000 subunit of the receptor was observed also in immunoprecipitates of this highly purified insulin receptor by anti-insulin-receptor antibodies. Phosphoamino acid determination revealed only phosphotyrosine in both the basal and insulin-stimulated states. These data suggest that a tyrosine-specific protein kinase activity is closely associated with insulin receptor, and this may be important in the signal transmission required for insulin action.
<sup>18</sup>F-Labeled Tracers for Positron Emission Tomography Studies in the Neurosciences (1996)

Fluorine-18 is a positron emitting isotope of fluorine. It has the longest half-life (110 minute) and the lowest positron energy (0.635 Mev) of the four common positron emitters for positron emission tomography (PET). PET, in conjunction with appropriate radiotracers labeled with fluorine-18, has been used to assess functional activity, biochemical transformations and drug pharmacokinetics and pharmacodynamics in the human and animal body. The PET method, F-18 labeling of organic molecules, and some of the applications of F-18 labeled compounds in the neurosciences (brain and heart) are described. Positron Emission Tomography (PET) is an imaging method which uses short-lived positron emitting isotopes to track labeled compounds in the living human and animal body (see Table I for the commonly used positron emitters). In a PET study, a radiotracer labeled with a short-lived positron emitting isotope is administered either by intravenous injection or inhalation and the spatial and temporal distribution of the
Arden - Architecture Development Environment (2002)

This paper describes Arden, which is being developed to help architecture design. Arden includes a retargetable compiler and a back-end simulation tool that uses the concepts of object-oriented programming (OOP) to achieve model reusability. The code generator in the Arden compiler uses a tree pattern matching method for instruction selection. An experimental bottom-up matching algorithm that reduces the pattern matching to a numerical computation problem can reduce the space complexity and the search time. A useful instruction description language has been proposed to simplify the architecture specifications. We have implemented the DLX architecture with only 49 rules. Arden has been able to output DLX assembly code and has the same performance as GNU cc output.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">></ETX>
Compensation Design for DC Blocking Multilayer Ceramic Capacitor in High-Speed Applications (2011)

The shunt parasitic capacitance of a multilayer ceramic capacitor (MLCC) mounting structure seriously degrades the performance of the MLCC in high-speed applications. In this paper, we propose a new compensation design method with which the reference planes underneath the surface mount technology pads and MLCC are cleared to eliminate the excessive capacitance effect. An analytical model is derived to compute the optimal clear parameters using conformal mapping, and the result of the analytical model closely matches with that of Ansoft 2-D Extractor. It is convenient for the printed circuit board (PCB) designer to utilize this model to obtain the optimal compensation parameters without building the 2-D or 3-D models of the MLCC mounting structure. Simulation and measurement results show that the compensation design is effective in improving the signal integrity of dc blocking MLCCs mounted on high-speed PCBs.
CloudFlow: Cloud-wide Policy Enforcement Using Fast VM Introspection (2014)

Government and commercial enterprises are increasingly considering cloud adoption. Clouds improve overall efficiency by consolidating a number of different clients' software virtual machines onto a smaller set of hardware resources. Unfortunately, this shared hardware also creates inherent side-channel vulnerabilities, which an attacker can use to leak information from a victim VM. Side-channel vulnerabilities are especially concerning when different principals are constrained by regulations. A classic example of these regulations are Chinese Wall policies for financial companies, which aim to protect the financial system from illicit manipulation by separating portions of the business with conflicting interests. Although efficient prevention of side channels is difficult within a single node, there is a unique opportunity within a cloud. This paper proposes a low-overhead approach to cloud wide information flow policy enforcement: identifying side channels which could potentially be used to violate a security policy through run-time introspection, and reactively migrating virtual machines to eliminate node-level side-channels. In this paper we describe CloudFlow-an information flow control extension for OpenStack. CloudFlow includes a novel, virtual machine introspection mechanism that is orders of magnitude faster than previous approaches. CloudFlow efficiently and transparently enforces information flow policies cloud-wide, including information leaks through undesirable side-channels. Additionally, CloudFlow has potential uses for cloud management and resource-efficient virtual machine scheduling.
Passive Optics No-Moving-Parts Barcode Scanners (2004)

For the first time, to the best of our knowledge, passive optics no-moving-parts barcode or one-dimensional (1-D) data scanners are reported. The proposed scanners are based on high-speed wavelength selection coupled with a planar wavelength dispersive element (such as a diffraction grating) to produce 1-D spatially scanned beams. The electronically controlled wavelength-encoded beam positioning allows for high-speed barcode or 1-D data handling operations. The demonstrated no-moving-parts barcode scanner designed to operate in the 1550-nm band exhibits high (>25 dB) dynamic range, high angular as well as linear scan resolution, eye-safe operation, and attests to the simplicity and functionality of the proposed scanners for use in barcode reading.
Identification of a Common Subnuclear Localization Signal (2007)

Proteins share peptidic sequences, such as a nuclear localization signal (NLS), which guide them to particular membrane-bound compartments. Similarities have also been observed within different classes of signals that target proteins to membrane-less subnuclear compartments. Common localization signals affect spatial and temporal subcellular organization and are thought to allow the coordinated response of different molecular networks to a given signaling cue. Here we identify a higher-order and predictive code, {[RR(I/L)X(3)r]((n, n > or = 1))+[L(phi/N)(V/L)]((n,n>1))}, that establishes high-affinity interactions between a group of proteins and the nucleolus in response to a specific signal. This position-independent code is referred to as a nucleolar detention signal regulated by H(+) (NoDS(H+)) and the class of proteins includes the cIAP2 apoptotic regulator, VHL ubiquitylation factor, HSC70 heat shock protein and RNF8 transcription regulator. By identifying a common subnuclear targeting consensus sequence, our work reveals rules governing the dynamics of subnuclear organization and ascribes new modes of regulation to several proteins with diverse steady-state distributions and dynamic properties.
Socio-economic Contributions of Micro and Small Enterprises: The Case of Jimma City (2013)

This study examined micro and small enterprises economic of peoples in Jimma city. The study used inferential and descriptive design, and was carried out on 82 organized/cooperated MSEs in Jimma city. Samples were randomly selected through stratification in each activity of the sector. Results were analyzed and changed to tables, charts and bar-graphs, and some of them were tested using Chi techniques. The findings of the study has shown that there is a socio improvement through participating in employment creation, saving and income generation, developing entrepreneur's skills and knowledge, and gender empowering, changing many peoples' social issues and also ways of acquiring businesses and linking different levels of enterprises to facilitate its development. R responded that the overall socio-economic improvement of the peoples was good. Even though the MSEs have such great roles in changing peoples' living conditions, th activities of the sector was constrained by many factors like lack of financial capacity, lack of working and production places, rules and regulatory procedures, lack of capacity to compete larger enterprises, and insufficiency of business development se economic infrastructures. Though, there are strategies to combat problems in the city, these challenges also leads to importance to put some suggestions for the improvement of the enterprises activities. In this case enabling environment f is very crucial, especially, to encourage and promote the sector and there should be an integrated effort of government to lead the support, the need to participate private sectors and non-governmental organizations in the MSEs d
The Application of Solution and Laser Ablation Based ICP-MS and Solution Based AES for the Provenance Determination of Selected Food and Drink Produce (2010)

The provenance identification of selected types of food and drink was undertaken from data obtained using both solution and laser ablation based inductively coupled plasma mass spectrometry (ICP-MS) and solution based inductively coupled plasma atomic emission spectroscopy (ICP-AES) analysis of selected food and drink materials (pork, wine, tea, coffee and olive oil). Quantitative determination of up to 55 elements was undertaken using solution based ICP-MS and AES while counts per second data for 49 elements was used for samples analyzed using Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS). ICP-AES was used to determine the concentrations of Na, K, Ca, Mg and Fe where appropriate. A quantitative analytical methodology for LA-ICP-MS analysis of olive oil was also developed and preliminary trials undertaken. Additional information, to establish more detailed geographic resolution in provenance determination, especially for tea and coffee (plantation of origin), was provided by the incorporation of data for light stable isotope distribution patterns ( 2 H (D), 13 C and 15 N). LA-ICP-MS was used for the direct analysis of olive oil and coffee beans. The use of laser ablation for the analysis of olive oil has the potential to overcome problems associated with both acid dissolution and thermal oxidation of this material, which are the traditional methods of sample dissolution and which either introduce significant contamination or cause the loss of volatile organo-metallic compounds that may be indicative for provenance determination. Results from the overall study indicated that it was possible not only to establish country of origin of the study materials but also in some cases to improve resolution of provenance to state of origin (wine and pork), and even plantation of origin (tea and coffee).