Miracle-dz/UniFAR-FTUs huggingface dataset:
Active targeting of chemotherapy to disseminated tumors using nanoparticle-carrying T cells

Nanoparticle-functionalized T cells actively transport a cytotoxic drug to systemic sites of lymphoma dissemination, enhancing the efficacy of antitumor chemotherapy. T cell backpacks carry chemo to tumors Getting drugs into tumors is no small feat, especially when they are disseminated throughout the body or harbored in the lymph nodes—often considered a “sanctuary” for cancer cells. Huang et al. devised a clever drug delivery system for such tumors that capitalizes on the natural movement of immune cells throughout the body. The authors first expanded T cells ex vivo under conditions that would make them home to lymphoid tissues. Then, nanocapsules loaded with a common chemotherapeutic were attached to the lymphocytes. The modified cells were infused into a mouse model of Burkitt’s lymphoma, where they carried their toxic backpacks to multiple lymphoid organs. The animals experienced not only reduced tumor burden but also prolonged survival compared with systemic therapy with the same drug. Because T cells are easily obtained from blood and are already being used in the clinic for cancer therapy, this “pharmacyte” strategy could be tailored to home to different organs, carrying unique cargos, in an effort to eradicate hard-to-reach tumors. Tumor cells disseminate into compartments that are poorly accessible from circulation, which necessitates high doses of systemic chemotherapy. However, the effectiveness of many drugs, such as the potent topoisomerase I poison SN-38, is hampered by poor pharmacokinetics. To deliver SN-38 to lymphoma tumors in vivo, we took advantage of the fact that healthy lymphocytes can be programmed to phenocopy the biodistribution of the tumor cells. In a murine model of disseminated lymphoma, we expanded autologous polyclonal T cells ex vivo under conditions that retained homing receptors mirroring lymphoma cells, and functionalized these T cells to carry SN-38–loaded nanocapsules on their surfaces. Nanocapsule-functionalized T cells were resistant to SN-38 but mediated efficient killing of lymphoma cells in vitro. Upon adoptive transfer into tumor-bearing mice, these T cells served as active vectors to deliver the chemotherapeutic into tumor-bearing lymphoid organs. Cell-mediated delivery concentrated SN-38 in lymph nodes at levels 90-fold greater than free drug systemically administered at 10-fold higher doses. The live T cell delivery approach reduced tumor burden significantly after 2 weeks of treatment and enhanced survival under conditions where free SN-38 and SN-38–loaded nanocapsules alone were ineffective. These results suggest that tissue-homing lymphocytes can serve as specific targeting agents to deliver nanoparticles into sites difficult to access from the circulation, and thus improve the therapeutic index of chemotherapeutic drugs with unfavorable pharmacokinetics.
DISTURBANCES OF THE VERTICAL MOTOR MUSCLES OF THE EYES

I. PHYSIOLOGIC ACTION OF THE VERTICAL MOTOR MUSCLES The disturbances occurring in the sphere of action of the vertical motor muscles of the eyes present such numerous and manifold problems to the ophthalmologist and so often give rise to unexpected and unpleasant therapeutic failures that many ophthalmologists dislike to meddle with such conditions and refer the patients to other specialists from the very beginning. There are two reasons for this. While the function of the lateral muscles of the eyes is easily comprehensible under normal and abnormal conditions and the rules for diagnosis and appropriate treatment of their disturbances may be expressed in a few sentences, the correct understanding of even the normal function of the vertical motor muscles presupposes an accurate knowledge of their anatomic and especially of their physiologic characteristics, which can be appreciated only by some one who is thoroughly familiar with the fundamental laws
Baltic Sea ice SAR segmentation and classification using modified pulse-coupled neural networks

A method for segmentation and classification of Baltic Sea ice synthetic aperture radar (SAR) images, based on pulse-coupled neural networks (PCNNs), is presented. Also, automated training, which is based on decomposing the total pixel value distribution into a mixture of class distributions, is presented and discussed. The algorithms have been trained and tested using logarithmic scale Radarsat-1 ScanSAR Wide mode images over the Baltic Sea ice. Before the decomposition into mixture of class distributions, an incidence angle correction, specifically designed for these Baltic Sea ice SAR images, is applied. Because the data distributions in the uniform areas of these images are very close to Gaussian distributions, the data are decomposed into a mixture of Gaussian distributions, using the Expectation-Maximazation algorithm. Only uniform image areas are used in the decomposition phase. The mixture of distributions is compared to the distributions of the Baltic Sea ice classes, based on earlier scatterometer measurements and visual video interpretations of the sea ice classes. The parameter values for the PCNN segmentation are defined based on this mixture of distributions. The PCNN segmentation results are also compared to the operational sea ice information of digitized ice charts and to visual interpretation of the sea ice class.
On the use of permanent symmetric scatterers for ship characterization

The symmetric scattering characterization method (SSCM) has been recently introduced for high-resolution characterization of certain targets under coherent conditions. SSCM is based on the Poincare/spl acute/ sphere representation, which supports a high-resolution decomposition of symmetric target scattering, as well as assessment and validation of the backscatter coherence. In this paper, the SSCM is investigated for ship characterization using Convair-580 polarimetric synthetic aperture radar (SAR) data. It is shown that the target Poincare/spl acute/ parameters permit identification of dominant scatterers with a significant symmetric scattering component. The polarization orientation angle of these quasi-symmetric scatterers is used to derive an estimate of the ship's pitch angle, under certain conditions. The effect of SAR system focus setting errors and Doppler centroid mistracking on the SSCM performance is investigated. It is shown that the SSCM is sensitive to the system focus setting and Doppler centroid shift. The first-order effects of these errors can be removed prior to the application of the SSCM method.
An Iterative Semidefinite and Geometric Programming Technique for the SINR Balancing in Two-Way Relay Network

In this paper, we consider a two-way amplify-and-forward relaying scheme, which consists of multiple transceivers and r relay nodes. Assuming that both the transceivers and the relays are equipped with single antennas, we deploy a signal-to-interference and noise-ratio (SINR) balancing technique, where the smallest of the transceivers SINRs is maximized under a total transmit power constraint. We solve this problem through an iterative procedure that uses semidefinite and geometric programming along with bisection search methods. We evaluate the performance of the proposed scheme in terms of the mean SINR for various relays and power at the relays.
A targeted real-time early warning score (TREWScore) for septic shock

TREWScore, a targeted early warning score for septic shock, identifies patients who develop septic shock before the onset of sepsis-related organ failure. Evening the score against sepsis Sepsis is a major cause of death, which remains difficult to treat despite modern antibiotics. Early aggressive treatment of this disease improves patient mortality, but the tools currently available in the clinic do not predict who will develop sepsis and its late manifestation, septic shock, until the patients are already in advanced stages of the disease. Henry et al. used readily available data from patient monitors and medical records to develop TREWScore, a targeted real-time early warning score that predicts in advance which patients are at risk for septic shock. With a median lead time of over 24 hours, this scoring algorithm may allow clinicians enough time to intervene before the patients suffer the most damaging effects of sepsis. Sepsis is a leading cause of death in the United States, with mortality highest among patients who develop septic shock. Early aggressive treatment decreases morbidity and mortality. Although automated screening tools can detect patients currently experiencing severe sepsis and septic shock, none predict those at greatest risk of developing shock. We analyzed routinely available physiological and laboratory data from intensive care unit patients and developed “TREWScore,” a targeted real-time early warning score that predicts which patients will develop septic shock. TREWScore identified patients before the onset of septic shock with an area under the ROC (receiver operating characteristic) curve (AUC) of 0.83 [95% confidence interval (CI), 0.81 to 0.85]. At a specificity of 0.67, TREWScore achieved a sensitivity of 0.85 and identified patients a median of 28.2 [interquartile range (IQR), 10.6 to 94.2] hours before onset. Of those identified, two-thirds were identified before any sepsis-related organ dysfunction. In comparison, the Modified Early Warning Score, which has been used clinically for septic shock prediction, achieved a lower AUC of 0.73 (95% CI, 0.71 to 0.76). A routine screening protocol based on the presence of two of the systemic inflammatory response syndrome criteria, suspicion of infection, and either hypotension or hyperlactatemia achieved a lower sensitivity of 0.74 at a comparable specificity of 0.64. Continuous sampling of data from the electronic health records and calculation of TREWScore may allow clinicians to identify patients at risk for septic shock and provide earlier interventions that would prevent or mitigate the associated morbidity and mortality.
Prefusion F–specific antibodies determine the magnitude of RSV neutralizing activity in human sera

Antibodies to the prefusion conformation of the RSV F glycoprotein neutralize natural infection. Neutralizing RSV Respiratory syncytial virus (RSV) infection causes cold-like symptoms in healthy adults but may be deadly in infants and other high-risk populations. However, no vaccine is currently available for RSV. Ngwuta et al. report that antibodies against an antigen site found in the RSV fusion glycoprotein (F) constitute most of the neutralizing antibody response in infected individuals. This site is found in the prefusion but not the postfusion form of the glycoprotein, suggesting that vaccines should be targeted to the prefusion version of this protein. Respiratory syncytial virus (RSV) is estimated to claim more lives among infants <1 year old than any other single pathogen, except malaria, and poses a substantial global health burden. Viral entry is mediated by a type I fusion glycoprotein (F) that transitions from a metastable prefusion (pre-F) to a stable postfusion (post-F) trimer. A highly neutralization-sensitive epitope, antigenic site Ø, is found only on pre-F. We determined what fraction of neutralizing (NT) activity in human sera is dependent on antibodies specific for antigenic site Ø or other antigenic sites on F in healthy subjects from ages 7 to 93 years. Adsorption of individual sera with stabilized pre-F protein removed >90% of NT activity and depleted binding antibodies to both F conformations. In contrast, adsorption with post-F removed ~30% of NT activity, and binding antibodies to pre-F were retained. These findings were consistent across all age groups. Protein competition neutralization assays with pre-F mutants in which sites Ø or II were altered to knock out binding of antibodies to the corresponding sites showed that these sites accounted for ~35 and <10% of NT activity, respectively. Binding competition assays with monoclonal antibodies (mAbs) indicated that the amount of site Ø–specific antibodies correlated with NT activity, whereas the magnitude of binding competed by site II mAbs did not correlate with neutralization. Our results indicate that RSV NT activity in human sera is primarily derived from pre-F–specific antibodies, and therefore, inducing or boosting NT activity by vaccination will be facilitated by using pre-F antigens that preserve site Ø.
A Compact 183-GHz Radiometer for Water Vapor and Liquid Water Sensing

ProSensing Inc. has developed a G-band (183 GHz) water vapor radiometer (GVR) for long-term unattended measurements of low concentrations of atmospheric water vapor and liquid water. Precipitable water vapor (PWV) and liquid water path (LWP) are estimated from zenith brightness temperatures measured using four double-sideband receiver channels, which are centered at 183.31 1, 183.31 3, 183.31 7, and 183.31 14 GHz. A prototype ground-based version of the instrument was deployed at the Department of Energy Atmospheric Radiation Measurement program's North Slope of Alaska site near Barrow, AK, in April 2005, where it collected data continuously for one year. This paper presents design details, laboratory test results, and examples of retrieved PWV and LWP from measured brightness temperature data.
Reduction in Brain Heparan Sulfate with Systemic Administration of an IgG Trojan Horse-Sulfamidase Fusion Protein in the Mucopolysaccharidosis Type IIIA Mouse.

Mucopolysaccharidosis Type IIIA (MPSIIIA), also known as Sanfilippo A syndrome, is an inherited neurodegenerative disease caused by mutations in the lysosomal enzyme, N-sulfoglucosamine sulfohydrolase (SGSH), also known as sulfamidase. Mutations in the SGSH enzyme, the only mammalian heparan N-sulfatase, cause accumulation of lysosomal inclusion bodies in brain cells comprising heparan sulfate (HS) glycosaminoglycans (GAGs). Treatment of MPSIIIA with intravenous recombinant SGSH is not possible because this large molecule does not cross the blood-brain barrier (BBB). BBB penetration by SGSH was enabled in the present study by re-engineering this enzyme as an IgG-SGSH fusion protein, where the IgG domain is a chimeric monoclonal antibody (mAb) against the mouse transferrin receptor (TfR), designated the cTfRMAb. The IgG domain of the fusion protein acts as a molecular Trojan horse to deliver the enzyme into brain via transport on the endogenous BBB TfR. The cTfRMAb-SGSH fusion protein bound to the mouse TfR with high affinity, ED50 = 0.74 ± 0.07 nM, and retained high SGSH enzyme activity, 10 043 ± 1003 units/mg protein, which is comparable to recombinant human SGSH. Male and female MPSIIIA mice, null for the SGSH enzyme, were treated for 6 weeks with thrice-weekly intraperitoneal injections of vehicle, 5 mg/kg of the cTfRMAb alone, or 5 mg/kg of the cTfRMAb-SGSH fusion protein, starting at the age of 2 weeks, and were euthanized 1 week after the last injection. Brain and liver HS, as determined by liquid chromatography-mass spectrometry, were elevated 30-fold and 36-fold, respectively, in the MPSIIIA mouse. Treatment of the mice with the cTfRMAb-SGSH fusion protein caused a 70% and 85% reduction in brain and liver HS, respectively. The reduction in brain HS was associated with a 28% increase in latency on the rotarod test of motor activity in male mice. The mice exhibited no injection related reactions, and only a low titer end of study antidrug antibody response was observed. In conclusion, substantial reductions in brain pathologic GAGs in a murine model of MPSIIIA are produced by chronic systemic administration of an IgG-SGSH fusion protein engineered to penetrate the BBB via receptor-mediated transport.
Effective Solution of 3-D Scattering Problems via Series Expansions: Applicability and a New Hybrid Scheme

Accurate and reliable evaluation of the electromagnetic field scattered by dielectric objects is a canonical problem in the electromagnetic community. In the framework of integral equation formulations, iterative techniques, and in particular conjugate gradient (CG) schemes, are widely used. However, when the number of parameters grows, CG techniques may become too demanding from a computational point of view. In this paper, we show that many forward scattering problems can be conveniently solved by means of very simple series expansions, which allow a lower computational complexity and memory storage with respect to other iterative schemes. In particular, we consider three different series expansions, namely: 1) the traditional Born series; 2) the contrast source-extended Born series, which is recently introduced by rewriting the traditional source-type integral equations; and 3) a new series, which is a hybridization of the previous ones. Theoretical conditions for the applicability of the series expansions are discussed, and practical tools to foresee that a problem can be solved by means of these simple iterative schemes are provided. Numerical examples are reported for the sake of comparison and to assess performance
Macroscopic Foam-Spray Models for Ocean Microwave Radiometry

We develop composition microwave electromagnetic models to calculate the emissivity of sea foam and spray. To describe foam nonuniformities, we suggest incorporating vertical profiles of an effective complex dielectric constant associated with two-phase (air-water) stratifications. We consider a certain structural hierarchy: Wet foam is modeled by mono- and polydispersed systems of bubbles; dry foam is represented by a statistical two-phase mixture containing thin water films and air; and spray is modeled by a discrete system of spherical water droplets. The impact of effective profiles on the spectral and polarization dependencies of the emissivity (signatures) is analyzed numerically using a multilayer computer-simulation technique. This technique allows us to provide a comprehensive model for variable configurations of complex effective profiles and different incidence angles. New results are generated for three basic compositions: ldquowater+foam+spray,rdquo ldquowater+spray,rdquo and ldquofoam+spray.rdquo We intend this modeling for use in advanced ocean remote sensing studies, including monitoring of gales, detection of two-phase wakes, estimations of air-sea fluxes and evaporation, and for retrieval purposes.
Observations, Modeling, and Applications of ERS-ENVISAT Coherence Over Land Surfaces

European Remote Sensing satellite (ERS) ENVISAT coherence is a new repeat-pass interferometric synthetic aperture radar product characterized by a very short repeat-pass interval between acquisitions (28min). In this paper, we investigate the properties of two 28-mins coherence images acquired over the regions of Paris, France, and Prague, Czech Republic, as well as a 35-day coherence image from Prague. Bare soils showed higher coherence compared to forests and urban areas. The range of coherence was larger for 28-min pairs, perpendicular baseline closer to 2km, and stable weather conditions between acquisitions. Coherence modeling shows that because of the long baseline: 1) significant surface decorrelation occurs when slopes are not accounted for in the common-band filtering and for variation of topography in the resolution cell and 2) volume decorrelation is significant. Temporal decorrelation seems to be relevant for vegetation even at the 28-min interval time scale. Observations and modeled coherence were found to be in good agreement. Land cover classification using coherence and backscatter has been tested for the Paris scene for mapping the four major classes. The classification accuracy was 86% when an edge-eroded version of the reference land cover map was used. It decreases to 68% when the full land cover map was used as reference because of local mismatches between the coherence image and the land cover map, and the reduced common band in range. The high coherence difference between forests and bare fields suggests the possibility to use the ERS-ENVISAT coherence for forest/nonforest mapping and estimation of biophysical properties of short vegetation. Coherence, decorrelation, ENVISAT Advanced Synthetic Aperture Radar (ASAR), European Remote Sensing satellite (ERS), land cover, synthetic aperture radar interferometry (InSAR).
AAV gene transfer delays disease onset in a TPP1-deficient canine model of the late infantile form of Batten disease

AAV-mediated gene transfer to ependymal cells in a dog model of Batten disease provides sustained enzyme replacement and delays disease onset. Gene therapy for Batten disease Repeated enzyme replacement therapy via infusion of the enzyme into blood vessels is an established treatment modality for many lysosomal storage diseases but not for those with significant brain involvement. In new work, Katz and colleagues test gene delivery of the missing enzyme to cells that line the fluid-filled spaces of the brain and measure secretion of the enzyme into the cerebrospinal fluid. Using a dog model of a lysosomal storage disease, they show that this strategy delayed disease onset, extended life span, and protected dogs from early cognitive decline, suggesting that this approach could improve the lives of children suffering from the same or similar diseases. The most common form of the childhood neurodegenerative disease late infantile neuronal ceroid lipofuscinosis (also called Batten disease) is caused by deficiency of the soluble lysosomal enzyme tripeptidyl peptidase 1 (TPP1) resulting from mutations in the TPP1 gene. We tested whether TPP1 gene transfer to the ependyma, the epithelial lining of the brain ventricular system, in TPP1-deficient dogs would be therapeutically beneficial. A one-time administration of recombinant adeno-associated virus (rAAV) expressing canine TPP1 (rAAV.caTPP1) resulted in high expression of TPP1 predominantly in ependymal cells and secretion of the enzyme into the cerebrospinal fluid leading to clinical benefit. Diseased dogs treated with rAAV.caTPP1 showed delays in onset of clinical signs and disease progression, protection from cognitive decline, and extension of life span. By immunostaining and enzyme assay, recombinant protein was evident throughout the brain and spinal cord, with correction of the neuropathology characteristic of the disease. This study in a naturally occurring canine model of TPP1 deficiency highlights the utility of AAV transduction of ventricular lining cells to accomplish stable secretion of recombinant protein for broad distribution in the central nervous system and therapeutic benefit.
FH535 Potentiation of Cigarette Smoke Condensate Cytotoxicity is Associated With Changes in β-Catenin and EGR-1 Signaling

Cigarette smoke condensate (CSC) has been reported to elicit morphological and transcriptional changes that suggest epithelial-to-mesenchymal transition (EMT) in cultured bronchial epithelial cells. The transdifferentiation potential of acute and prolonged CSC exposure alone or in combination with the β-catenin inhibitor, FH535, was investigated in the bronchial epithelial cell line, BEAS-2B, through assessment of cell morphology, transcript expression, protein expression, and protein localization. Changes in morphology, β-catenin translocation, E-cadherin expression, metalloproteinase expression, and fibronectin could be demonstrated independent of molecular or physiological evidence of EMT. FH535 was shown to increase CSC-induced cytotoxicity and depress β-catenin expression. However, FH535 effects were not limited to the β-catenin pathway as it also blocked the expression of early growth responsive protein 1 (EGR-1) target genes, fibronectin and phosphatase and tensin homologue, without affecting EGR-1 nuclear accumulation.