Miracle-dz/UniFAR-FTUs huggingface dataset:
Combined glyco- and protein-Fc engineering simultaneously enhance cytotoxicity and half-life of a therapeutic antibody

While glyco-engineered monoclonal antibodies (mAbs) with improved antibody-dependent cell-mediated cytotoxicity (ADCC) are reaching the market, extensive efforts have also been made to improve their pharmacokinetic properties to generate biologically superior molecules. Most therapeutic mAbs are human or humanized IgG molecules whose half-life is dependent on the neonatal Fc receptor FcRn. FcRn reduces IgG catabolism by binding to the Fc domain of endocytosed IgG in acidic lysosomal compartments, allowing them to be recycled into the blood. Fc-engineered mAbs with increased FcRn affinity resulted in longer in vivo half-life in animal models, but also in healthy humans. These Fc-engineered mAbs were obtained by alanine scanning, directed mutagenesis or in silico approach of the FcRn binding site. In our approach, we applied a random mutagenesis technology (MutaGenTM) to generate mutations evenly distributed over the whole Fc sequence of human IgG1. IgG variants with improved FcRn-binding were then isolated from these Fc-libraries using a pH-dependent phage display selection process. Two successive rounds of mutagenesis and selection were performed to identify several mutations that dramatically improve FcRn binding. Notably, many of these mutations were unpredictable by rational design as they were located distantly from the FcRn binding site, validating our random molecular approach. When produced on the EMABling® platform allowing effector function increase, our IgG variants retained both higher ADCC and higher FcRn binding. Moreover, these IgG variants exhibited longer half-life in human FcRn transgenic mice. These results clearly demonstrate that glyco-engineering to improve cytotoxicity and protein-engineering to increase half-life can be combined to further optimize therapeutic mAbs.
The impact of physical training on endothelial function in myocardial infarction survivors: pilot study.

BACKGROUND Endothelial dysfunction (ED) may indirectly influence the outcome of patients with coronary artery disease. AIM To assess the influence of cardiac rehabilitation (CR) on endothelial function in patients after ST-segment elevation myocardial infarction (STEMI). METHODS Twenty-nine patients scheduled for CR were included in the study. CR began at least four weeks after STEMI and consisted of 12 or 24 training sessions. Endothelial function assessment was performed before and after CR, using reactive hyperaemia peripheral arterial tonometry. RESULTS Before the CR, ED was diagnosed in 16 of 29 (55.2%) patients. A total of 25 patients had two assessments of endothelial function: before and after CR. In univariate analysis the factors of negative response of endothelial function to CR were: higher baseline hyperaemia index (lnRHI) (odds ratio [OR] for positive response to CR 0.01; 95% confidence interval [CI] 0.00-0.33; p = 0.01) and higher peak serum troponin I level during index hospitalisation (OR 0.97; 95% CI 0.94-1.00; p = 0.04). The independent, negative predictor of response to CR was lnRHI (OR 0.01; 95% CI 0.01-0.16; p = 0.03). Patients training for 24 sessions (n = 16) had similar lnRHI changes to those of patients training for 12 sessions (n = 9); [0.16 (-0.06)-0.30 vs. 0.10 (0.05-0.15); p = 0.44, respectively]. CONCLUSIONS ED is a frequent abnormality in STEMI survivors. Despite the lack of statistically significant improvement of endothelial function after CR in the analysed group of patients, some factors can influence the efficacy of this type of physical activity. The best effect of CR on endothelial function was observed in patients with baseline ED.
Calibration of PRISM and AVNIR-2 Onboard ALOS “Daichi”

The Advanced Land Observing Satellite [(ALOS); nicknamed ldquoDaichirdquo] was successfully launched on January 24, 2006, and it continues to work very well. This paper describes the calibrations of two optical instruments onboard ALOS, which are the Panchromatic Remote-sensing Instrument for Stereo Mapping (PRISM) and Advanced Visible and Near-Infrared Radiometer type 2 (AVNIR-2). PRISM consists of three panchromatic radiometers and is used to derive a digital surface model (DSM) with high spatial resolution, which is an objective of the ALOS mission. AVNIR-2 has four radiometric bands from blue to near infrared, which are used for investigating regional environment issues such as land-use and land-cover classifications, and disaster monitoring. In this paper, we introduce the calibration and validation plan, methodologies, accuracy assessments of the standard products, image quality evaluations for PRISM and AVNIR-2, and their results. Geometric calibration is important in generating a precise DSM by a stereo pair image of PRISM. The relative geometric calibrations of both PRISM and AVNIR-2 are conducted by evaluating accuracies within one scene and evaluating sensor alignments as absolute calibration. For absolute geometric accuracies, we achieved 8.1 m for nadir-looking images and 9.3 m for forward- and backward-looking images of PRISM; we also achieved 114.2 m for AVNIR-2. PRISM is also radiometrically calibrated both relatively and absolutely. PRISM relative radiometric calibration is accomplished by using acquired images over homogeneous targets, such as oceans, deserts, ice, and snow areas, as well as nighttime observation. Simultaneously observed images with calibrated AVNIR-2 are used for absolute radiometric calibration by cross-calibration. The absolute radiometric accuracy of the PRISM nadir-looking radiometer is similar to that of AVNIR-2.
Adapting pediatric psychology interventions: lessons learned in treating families from the Middle East.

OBJECTIVE Pediatric psychologists are increasingly called upon to treat children from non-Western countries, whose cultures may contrast with a Western medical setting. Research on cultural adaptations of evidence-based treatments (EBTs), particularly for individuals from the Middle East, is sparse. To address this need, we discuss clinical issues encountered when working with patients from the Middle East. METHODS Synthesis of the literature regarding culturally adapted EBTs and common themes in Middle Eastern culture. Case vignettes illustrate possible EBT adaptations. RESULTS Integrating cultural values in treatment is an opportunity to join with patients and families to optimize care. Expectations for medical and psychological treatment vary, and collaborations with cultural liaisons are beneficial. CONCLUSIONS Critical next steps include systematic development, testing, and training in culturally adapting EBTs in pediatric medical settings. Increased dialogue between clinicians, researchers, and cultural liaisons is needed to share knowledge and experiences to enhance patient care.
Novel folded single split ring resonator and its application to eliminate scan blindness in infinite phased array

In this letter, a simple electric metamaterial is proposed based on grounded folded single split ring resonator (SRR). The grounded SRR results in a compacter size. The proposed metamaterial exhibits a negative effective permittivity ∊e and positive effective permeability μe under electric excitation, and its electric resonant frequency is easily changeable from 4.5GHz to 5.7GHz by adjusting the length of the folded arms. It is used to suppress the mutual coupling between elements in microstrip array by blocking the propagation of the excited surface waves in microstrip substrate, and eliminate the scan blindness in the infinite microstrip phased array. The results indicate its excellent application potential to improve the scanning performance of microstrip array. More interestingly, compared with the reported techniques, such as electromagnetic band-gap (EBG) structures and defected ground structures (DGSs), the new metamaterial almost has nearly zero thickness as an isolation wall, which means that it is very suitable for constructing the high-density array.
Caspase 8 gene variants in healthy North Indian population and comparison with worldwide ethnic group variations

BACKGROUND: Many strategies are being used for the quest for the disease causing genes. Inter-individual variations in several genes exist. Thus, even if they share the same disease-associated allele, the genomic backgrounds – and hence potential interacting alleles at other loci – of people with different regional ancestries may differ, with a consequent variation in the severity of their disease. MATERIALS AND METHOD: The present study was conducted to determine the distribution of Caspase 8 IVS12-19G/A, Caspase 8D302H, Caspase 8 -652del and Caspase 8 -678del polymorphisms (as frequency distribution of caspases in Indians generally is not yet known), which was then compared with different populations globally. Polymerase chain reaction (PCR)-based analysis was conducted in 205 normal healthy individuals of similar ethnicity. RESULTS: The variant allele frequencies were 17.6% (A) in Caspase 8 IVS12-19G/A, 13.2% (H) in Caspase 8D302H, 23.2% (Del) in Caspase 8 -652del and 24.6% (Del) in Caspase 8 -678del. Further, comparison of frequency distribution of these genes was done with various published studies of different ethnic groups globally. CONCLUSION: It is anticipated from our results that the frequency of these caspase genes exhibits distinctive patterns in India, which could perhaps be attributed to ethnic variation. This study is important as it can form a baseline for screening individuals who are at high risk due to exposure to environmental carcinogens and cancer predisposition, and therefore, might help in investigating linked polymorphisms in a way that will not obscure potential associations between genotype and phenotype.
Accumulation of γ‐globin mRNA in human erythroid cells treated with angelicin

The aim of the present study was to determine whether angelicin is able to increase the expression of γ‐globin genes in human erythroid cells. Angelicin is structurally related to psoralens, a well‐known chemical class of photosensitizers used for their antiproliferative activity in treatment of different skin diseases (i.e., psoriasis and vitiligo). To verify the activity of angelicin, we employed two experimental cell systems, the human leukemic K562 cell line and the two‐phase liquid culture of human erythroid progenitors isolated from normal donors. The results of our investigation suggest that angelicin, compared with cytosine arabinoside, mithramycin and cisplatin, is a powerful inducer of erythroid differentiation and γ‐globin mRNA accumulation of human leukemia K562 cells. In addition, when normal human erythroid precursors were cultured in the presence of angelicin, increases of γ‐globin mRNA accumulation and fetal hemoglobin (HbF) production, even higher than those obtained using hydroxyurea, were detected. These results could have practical relevance, as pharmacologically‐mediated regulation of the expression of human γ‐globin genes, leading to HbF induction, is considered a potential therapeutic approach in hematological disorders, including β‐thalassemia and sickle cell anemia.
A scalable approach of co-association cluster ensemble using representative points

Cluster ensembles are approaches to combine different clustering results to obtain a robust consensus partitioning. However, many cluster ensemble methods suffer from the problem of scalability since the extensive cost of calculating co-association matrix, which makes it hard to perform cluster ensemble on large scale datasets. In this paper, we proposed a scalable co-association cluster ensemble framework using a compressed version of co-association matrix formed by selecting representative points of origin instances. Experiments show that our method could get a comparable performance on medium size datasets to existing co-association ensemble method like CSPA or spectral clustering, and is able to handle large scale datasets.
Epigenetic defects of GNAS in patients with pseudohypoparathyroidism and mild features of Albright's hereditary osteodystrophy.

CONTEXT Several endocrine disorders that share resistance to PTH are grouped under the term pseudohypoparathyroidism (PHP). PHP type I, associated with blunted PTH-induced nephrogenous cAMP formation and phosphate excretion, is subdivided according to the presence or absence of additional endocrine abnormalities, Albright's hereditary osteodystrophy (AHO), and reduced Gsalpha activity caused by GNAS mutations. OBJECTIVE We sought to identify the molecular defect in four unrelated patients who were thought to have PHP-Ia because of PTH and TSH resistance and mild AHO features. METHODS Gsalpha activity and mutation analysis, and assessment of GNAS haplotype, methylation, and gene expression were performed for probands and family members. RESULTS Two patients showed modest decreases in erythrocyte Gsalpha activity. Instead of Gsalpha point mutations, however, all four patients showed methylation defects of the GNAS locus, a feature previously described only for PHP-Ib. Furthermore, one patient with an isolated loss of GNAS exon A/B methylation had the 3-kb STX16 deletion frequently identified in PHP-Ib patients. In all but one of the remaining patients, haplotype analysis excluded large deletions or uniparental disomy as the cause of the observed methylation changes. CONCLUSIONS Our investigations indicate that an overlap may exist between molecular and clinical features of PHP-Ia and PHP-Ib. No current mechanisms can explain the AHO-like features of our patients, some of which may not be linked to GNAS. Therefore, patients with hormone resistance and AHO-like features in whom coding Gsalpha mutations have been excluded should be evaluated for epigenetic alterations within GNAS.
Effect of atmosphere and duration of incubation on primary isolation of group A streptococci from throat cultures

The optimal incubation conditions for isolation of group A streptococci from throat cultures are controversial. Therefore, we compared the effects of aerobic and anaerobic incubations after 24 and 48 h on the recovery of group A streptococci. Throat swabs submitted to the clinical laboratory were inoculated onto duplicate 5% sheep blood agar plates, incubated aerobically or anaerobically (GasPak jar) at 35 degrees C, and examined semiquantitatively after 24 and 48 h. Group A streptococci were identified by the fluorescent-antibody technique. Of 1,040 specimens, 506 (48.6%) grew beta-hemolytic streptococci, including 200 (19.2%) group A streptococci. Group A streptococci were recovered significantly more often with anaerobic incubation than with aerobic incubation after 24 h (182 versus 138; P less than 0.001) and after 48 h (193 versus 174; P less than 0.05). Non-group A beta-hemolytic streptococci also were recovered significantly more often with anaerobic incubation after 24 and 48 h (P less than 0.001). Colony counts were not affected by the incubation atmosphere. We conclude that incubation of throat cultures in an anaerobic atmosphere is superior to incubation in air for detection of group A streptococci. The greater sensitivity of anaerobic incubation, however, may not justify the extra laboratory effort and cost required to differentiate group A streptococci from the non-group A streptococci detected as a result of anaerobic incubation. Throat cultures should be examined after 24 and 48 h, especially if plates are incubated aerobically.
Unsupervised learning of non-Gaussian mixtures with temporal dependencies

Classification methods typically make use only of labeled data, in what is known as supervised learning. In some applications, however, labeled data is either scarce or costly to obtain. For these applications, unsupervised or semisupervised learning are adequate, since they will be able to use unlabeled data. This work proposes a new method for unsupervised and semisupervised learning of non-Gaussian data mixtures with temporal dependencies represented by sequential independent component analysis mixture models (SICAMM). The proposed method was applied on simulated and real data, and its classification performance was compared with that of supervised learning SICAMM and ICAMM, and two semisupervised learning Bayesian networks. The real data application consisted of the detection of microarousals in sleep electroencephalographic (EEG) recordings for the purposes of sleep disorder diagnosis. Results show that the proposed method obtained better performance that the other considered methods.
cRGD-conjugated magnetic-fluorescent liposomes for targeted dual-modality imaging of bone metastasis from prostate cancer

Abstract We reported the development of multifunctional liposomes as a dual-modality probe to facilitate targeted magnetic resonance and fluorescent imaging of bone metastasis from advanced cancer. Multifunctional liposomes consisted of liposomes as a carrier, hydrophobic CdSe QDs in phospholipid bilayer, hydrophilic iron oxide nanoparticles in interior vesicle, lipid-PEG derivative on the surface and cRGDyk peptide conjugated to distal ends of lipid-PEG derivative. Excellent stability, effective detection signal, low toxicity, high resistance to phagocytosis by macrophages and good specificity to tumor of multifunctional liposomes were confirmed by in vitro characterization. The in vivo results demonstrated that multifunctional liposomes accumulated mainly in tumor and liver, indicating that targeted dual-modality imaging was achieved, and the results from two kinds of modalities were consistent and complementary. These findings provide a helpful strategy for detection of bone metastases in a more effective manner for initiation of appropriate therapy.
A two‐tier approach to mutation detection in the COL4A5 gene for Alport syndrome

About 85% of Alport syndrome is an X‐linked semi‐dominant condition caused by mutations in the collagen gene, COL4A5. The large size and high GC content of this gene have presented diagnostic laboratories with problems in identifying mutations with greater than about a 50% success rate since the gene was first cloned 16 years ago. An RNA based approach is adopted here for a first pass mutation scanning coupled with more traditional exon‐by‐exon screening to increase the rate of mutation identification. Twenty‐one mutations were identified in twenty‐five patients with clear Alport syndrome including four gross deletions, two deep intronic mutations, three frameshifts, three splice site mutations, eight missense mutations and one inframe deletion. © 2006 Wiley‐Liss, Inc.
QoS improvement in IEEE802.11e with The smart set MAC layer parameters

This paper is on the improvement of Quality of Service (QoS) of IEEE802.11e by intelligently setting the MAC layer parameters. During the EDCA period, the backoff time is the main component of IEEE802.11e standard to access the channel which includes various parameters such as CW and AIFS. Assigning constant priority to access the channel regardless of the queue length of traffic type raises many problems such as degrading the QoS of non-realtime traffic in presence of high realtime traffic. The proposed scheme, named Smart EDCA (S-EDCA) addresses those problems by intelligently assigning the CW of different types of traffic such as voice and video. It is done by setting these parameters using a neural network in an AP that sets the parameters according to the queue length of different traffics and their priorities. The simulation results show QoS improvement of the proposed scheme compared to the IEEE802.11e standard.
Upolu virus and Aransas Bay virus, Two Presumptive Bunyaviruses, Are Novel Members of the Family Orthomyxoviridae

ABSTRACT Emerging and zoonotic pathogens pose continuing threats to human health and ongoing challenges to diagnostics. As nucleic acid tests are playing increasingly prominent roles in diagnostics, the genetic characterization of molecularly uncharacterized agents is expected to significantly enhance detection and surveillance capabilities. We report the identification of two previously unrecognized members of the family Orthomyxoviridae, which includes the influenza viruses and the tick-transmitted Thogoto and Dhori viruses. We provide morphological, serologic, and genetic evidence that Upolu virus (UPOV) from Australia and Aransas Bay virus (ABV) from North America, both previously considered potential bunyaviruses based on electron microscopy and physicochemical features, are orthomyxoviruses instead. Their genomes show up to 68% nucleotide sequence identity to Thogoto virus (segment 2; ∼74% at the amino acid level) and a more distant relationship to Dhori virus, the two prototype viruses of the recognized species of the genus Thogotovirus. Despite sequence similarity, the coding potentials of UPOV and ABV differed from that of Thogoto virus, instead being like that of Dhori virus. Our findings suggest that the tick-transmitted viruses UPOV and ABV represent geographically distinct viruses in the genus Thogotovirus of the family Orthomyxoviridae that do not fit in the two currently recognized species of this genus. IMPORTANCE Upolu virus (UPOV) and Aransas Bay virus (ABV) are shown to be orthomyxoviruses instead of bunyaviruses, as previously thought. Genetic characterization and adequate classification of agents are paramount in this molecular age to devise appropriate surveillance and diagnostics. Although more closely related to Thogoto virus by sequence, UPOV and ABV differ in their coding potentials by lacking a proposed pathogenicity factor. In this respect, they are similar to Dhori virus, which, despite the lack of a pathogenicity factor, can cause disease. These findings enable further studies into the evolution and pathogenicity of orthomyxoviruses.
The Shape of The Oprah Supply Curve

The Oprah Supply Curve shows the relationship between the quantity of Oprah Winfrey supplied and her income. Although even a Nobel laureate has speculated on the shape of that curve, its shape has not been estimated. We estimate its shape by using variation in the number of new episodes per season of Oprah's television show, The Oprah Winfrey Show. The curve appears to be backward bending. Thus, while Oprah may not be an obvious target for taxation, a higher tax rate might expand the quantity of services she supplies while also increasing tax revenues.
Multiple access channel with full-duplex amplify-and-forward transmitter cooperations

In this paper, a full-duplex (FD) amplify-and-forward (AF) transmitter cooperative communication scheme is proposed for multiple access channel (MAC). In particular, two FD transmitters simultaneously transmit information to a common receiver and help each other's transmissions with the AF relaying scheme. By considering the accumulation of the residual self-interference and additive noise (RIAN) at each transmitter, the asymptotic channel's input-output relationship is derived, as the number of transmission blocks goes to infinity. Then, two decoding schemes, i.e., forward and backward decoding, are proposed, and their corresponding achievable rate regions are obtained by solving some optimization problems. Finally, numerical results validate the analysis.
Trellis codes for the optical direct-detection channel

It is observed that the reduced complexity minimum distance search method of Zehavi and Wolf (1987) can be extended from codes designed using the squared Euclidean distance measure to any measure which is additive over the code branches. C.N. Georghiades (1989) has derived such a metric for codes for the direct-detection optical channel. The search method is applied to find codes for four- and eight-point overlapping pulse position modulation (OPPM), with large minimum distance and a small number of codewords at that distance. >