Miracle-dz/UniFAR-FTUs huggingface dataset:
Substitution of an Internal Disulfide Bridge with a Diselenide Enhances both Foldability and Stability of Human Insulin.

Insulin analogues, mainstays in the modern treatment of diabetes mellitus, exemplify the utility of protein engineering in molecular pharmacology. Whereas chemical syntheses of the individual A and B chains were accomplished in the early 1960s, their combination to form native insulin remains inefficient because of competing disulfide pairing and aggregation. To overcome these limitations, we envisioned an alternative approach: pairwise substitution of cysteine residues with selenocysteine (Sec, U). To this end, CysA6 and CysA11 (which form the internal intrachain A6-A11 disulfide bridge) were each replaced with Sec. The A chain[C6U, C11U] variant was prepared by solid-phase peptide synthesis; while sulfitolysis of biosynthetic human insulin provided wild-type B chain-di-S-sulfonate. The presence of selenium atoms at these sites markedly enhanced the rate and fidelity of chain combination, thus solving a long-standing challenge in chemical insulin synthesis. The affinity of the Se-insulin analogue for the lectin-purified insulin receptor was indistinguishable from that of WT-insulin. Remarkably, the thermodynamic stability of the analogue at 25 °C, as inferred from guanidine denaturation studies, was augmented (ΔΔGu ≈0.8 kcal mol-1 ). In accordance with such enhanced stability, reductive unfolding of the Se-insulin analogue and resistance to enzymatic cleavage by Glu-C protease occurred four times more slowly than that of WT-insulin. 2D-NMR and X-ray crystallographic studies demonstrated a native-like three-dimensional structure in which the diselenide bridge was accommodated in the hydrophobic core without steric clash.
Target detection and recognition with polarimetric SAR

Target detection and recognition using polarimetric SAR data has been studied by using PHARUS and RAMSES data collected during the MIMEX campaign. Additionally very high-resolution ISAR data was used. A basic detection and recognition scheme has been developed, which includes polarimetric speckle- filtering, CFAR detection and the extraction of geometrical, intensity and polarimetric features. From the SAR images we conclude that polarimetric features can be useful to discriminate targets from clutter. At resolutions of 1 meter or better, shape and orientation recognition can be obtained with these features. To classify the targets, other features or other techniques have to be used. Examples are polarimetric decomposition techniques, of which two have been explored using the ISAR data.
Chimeric antigen receptor T cells for acute lymphoblastic leukemia

Chimeric antigen receptor (CAR) modified T cells targeted to CD19 have resulted in unprecedented remission rates for adult and pediatric patients with relapsed and refractory B cell acute lymphoblastic leukemia (ALL). With regulatory approval for tisagenlecleucel and many other agents under active investigation, the use of CAR T cells for ALL continues to expand. While some remissions from anti‐CD19 CAR T cells are durable without a consolidative allogeneic stem cell transplantation, CD19 positive and negative relapses remain a significant concern fueling investigations into the biology of CAR T cell persistence and the development of CARTs that target more than 1 antigen. The treatment related toxicities of cytokine release syndrome and neurologic events are potentially life threatening but recent advances have improved understanding and management strategies. This review summarizes outcomes for patients with ALL treated with CD19‐CAR T cells while exploring the field's challenges and future directions.
Sun-induced Chl fluorescence and its importance for biophysical modeling of photosynthesis based on light reactions.

Recent progress in observing sun-induced Chl fluorescence (SIF) provides an unprecedented opportunity to advance photosynthesis research in natural environments. However, we still lack an analytical framework to guide SIF studies and integration with the well-developed active fluorescence approaches. Here, we derive a set of coupled fundamental equations to describe the dynamics of SIF and its relationship with C3 and C4 photosynthesis. These equations show that, although SIF is dynamically as complex as photosynthesis, the measured SIF simplifies photosynthetic modeling from the perspective of light reactions by integrating over the dynamic complexities of photosynthesis. Specifically, the measured SIF contains direct information about the actual electron transport from photosystem II to photosystem I, giving a quantifiable link between light and dark reactions. With much-reduced requirements on inputs and parameters, the light-reactions-centric, SIF-based biophysical model complements the traditional, dark-reactions-centric biochemical model of photosynthesis. The SIF-photosynthesis relationship, however, is nonlinear. This is because photosynthesis saturates at high light whereas SIF has a stronger tendency to keep increasing, as fluorescence quantum yield has a relatively muted sensitivity to light levels. Successful applications of the SIF-based model of photosynthesis will depend on a predictive understanding of several previously underexplored physiological and biophysical processes. Advances can be facilitated by coordinated efforts in plant physiology, remote sensing, and eddy covariance flux observations.
Inhibition of phosphodiesterase‐4 attenuates murine ulcerative colitis through interference with mucosal immunity

Ulcerative colitis (UC) is an aetiologically refractory inflammatory disease, accompanied by dysfunction of the epithelial barrier and intestinal inflammation. Phosphodiesterase‐4 (PDE4) serves as an intracellular proinflammatory enzyme, hydrolyzing and inactivating cAMP. Though PDE4 inhibitors have been approved for pulmonary and dermatological diseases, the role of PDE4 inhibition in modulating mucosal immunity in the intestine remains ill‐defined. This study was designed to explore whether PDE4 inhibition by apremilast exerts protective effects in dextran sulfate sodium‐induced murine UC.
Meta-neural networks that learn by learning

A novel method for training neural networks is introduced. The method uses an additional observing neural network called a meta-neural network (MNN) to direct the training of the basic neural network. The MNN provides the basic neural network with a step size and a direction vector which is optimal based on successful training strategies learned from problems solved previously. The combination of the MNN with the basic neural network is shown to improve learning rates for several problems when the MNN is trained on a similar problem. The MNN is shown to help solve the problem of sensitivity to initial weight vectors. In addition, computer simulations demonstrate the improvement in the learning rate of the enhanced neural network on a 4-b parity problem, when it has been trained on a different nonlinear Boolean function. <<ETX>>
You want me to check your grammar again? The usefulness of an online grammar checker as perceived by students

Feedback on students. writing is considered an instrumental part of the academic advising process. However, due to the time constraints of the student-adviser interaction, Academic Language and Learning (ALL) advisers may find it difficult to provide comprehensive feedback to students regarding their grammatical mistakes. One solution is to utilise online grammar checking tools as a complement to feedback from an adviser. These tools can save advisers. time and resources while at the same time promote greater self-directed learning and foster students. self-efficacy. In spite of this, many Australian higher education institutions have overlooked this intersection between grammar support and online automated technology. This paper presents an overview of Grammarly, a popular online grammar checking website. In addition, this paper provides preliminary results of an evaluation of Grammarly by students at two Navitas colleges, the Australian College of Applied Psychology (ACAP) and Navitas College of Public Safety (NCPS). The students. survey responses are analysed against Davis. (1989) Technology Acceptance Model (TAM), which offers a conceptual framework for predicting the acceptability and use of a technology. The results reveal that students perceive Grammarly as useful and easy to use, and students reported that Grammarly improved their writing and understanding of grammar rules.
THE FREQUENCY AND COLLOCATION OF MODAL VERBS IN ENGLISH AS A SECOND LANGUAGE TEXTBOOKS AS COMPARED TO STANDARD

The main objective of this study is to know whether the English as a second language (ESL) textbooks approved by the Ministère de l'Éducation, du Loisir et du Sport of Québec in 2007 and meant to be used by secondary school cycle two students in Québec as from 2008 prime the learner to use both modal verbs and modal verb patterns by means of frequencies similar to those in spoken English or in written English. To this end a corpus containing the above-mentioned textbooks was bui Il, and the frequencies of modal verbs and of modal verb patterns in this corpus, in the written corpus and in the spoken corpus of the British National Corpus were compared by carrying out statistical analyses. As regards modal verb frequencies, the only significant difference between the three corpora (the textbook corpus, the corpus of spoken English and the corpus ofwritten English) is the frequency ofcontracted modal verb forms. While they are numerous in spoken English, their frequencies in the textbook corpus and in the written English corpus are very close. Indeed, the targeted ESL textbooks rarely prime the learner to use the contracted forms 'Il and 'do The study also shows that can and will are the two most frequent modal verbs in the textbook corpus, which coincides with the finding that ESL speakers overuse these two modal verbs (Montero, Watts and Garcia-Carbonell (2007) and Debbie (2009)). ln contrast, the frequencies of modal verb patterns in the textbook corpus are similar to those in spoken English. The ESL textbooks selected for analysis tend to prime the leamer to use modal verbs by means of frequencies similar to those in written English but in simpler structures.
Dynamic Phenomena on Complex Networks

The work presented in this thesis concerns different aspects of dynamical processes on networks. We start providing an introduction to the science of complex networks. The first subject considered in this thesis is the theoretical characterization of exploration processes of complex networks, such as the ``traceroute'' process used to map the physical Internet. We introduce a theoretic model of traceroute exploration, that allows a mean-field analyses providing a better understanding of the relation between the topological properties of the original and sampled networks. This study shows that dynamical processes can be exploited to characterize unknown topological properties of real networks. A second part of the thesis is devoted to the study of weighted networks and their relations with the functional properties of networks. We will investigate the role played by the weights in determining the functional robustness of the system. In particular, we will consider the case study of the airports network. Other results can be extended to the case of weighted networks, such as some results on the percolation properties of networks. The last part of the thesis concerns the study the Naming Game, a model used to study the emergence of a communication system in a population of individuals. We show that the dynamical phenomena generated by the model depend strongly on the topology of the interactions.
K-distribution for multi-look processed polarimetric SAR imagery

A K-distribution has been developed to characterize the statistical properties of multi-look processed polarimetric SAR data. The probability density function (PDF) was derived as the product of a gamma distributed random variable and the polarimetric covariance matrix. The latter characterizes the speckle and the former depicts the inhomogeneity (texture). For multi-look data incoherently averaged from correlated one-look samples, the authors found that, for better modeling, the number of looks has to assume a non-integer value. A procedure was developed to estimate the equivalent number of looks and the parameter of the K-distribution. Experimental results using NASA/JPL 4-look and 16-1ook polarimetric SAR data substantiated this multi-look K-distribution. The authors also found that the multi-look process reduced the inhomogeneity and made the K-distribution less significant. <<ETX>>
Wavelet packet based audio coding using temporal masking

Conventional audio coding algorithms do not exploit knowledge of the temporal masking properties of the human auditory system, relying solely on simultaneous masking models. This paper presents wavelet packet based audio coding incorporating both temporal and simultaneous masking models. By applying a novel temporal masking model, following simultaneous masking, combined masking thresholds were calculated more accurately resulting in a bit rate reduction of approximately 25 kbps while preserving perceptual quality. This result was confirmed by semi-formal subjective test on audio signals.
Transaction Polymorphism in Java

Concurrent implementations of abstract types usually rely on lock-free primitives or locks and are highly tuned to support a finite set of e cient operations. However, it is very hard to extend such types for specific needs by adding new operations. The synchronization based on memory transactions, which is generally less e cient than based on lock-free primitives or locks, has been proposed in part to address this issue by ensuring that any set of transactional operations can run concurrently. This paper introduces transaction polymorphism, a synchronization technique that consists of providing more control to the programmer than traditional (monomorphic) transactions to achieve comparable performance to generic lock-based and lock-free solutions. We show in this paper that, maybe unsurprisingly, monomorphic transactions cannot reach the level of concurrency obtained with locks. As a drawback of sharing the same semantics that needs to be strong enough for various operations, monomorphic transactions seriously underutilize the concurrency potential of such operations. We describe a Java polymorphic transactional memory that includes three distinct transaction types, which we compare against four existing (monomorphic) STMs, as well as against existing lock-based and lock-free synchronization on a collection micro-benchmark and on the STMBench7 macrobenchmark. Our results show that polymorphism can be at least 2.4 times faster than any of these alternatives on 64 threads.
An Eastern Hepatobiliary Surgery Hospital/Portal Vein Tumor Thrombus Scoring System as an Aid to Decision Making on Hepatectomy for Hepatocellular Carcinoma Patients With Portal Vein Tumor Thrombus: A Multicenter Study

Portal vein tumor thrombus (PVTT) is a significant poor prognostic factor for hepatocellular carcinoma (HCC). Patients with PVTT limited to a first‐order branch of the main portal vein (MPV) or above could benefit from negative margin (R0) liver resection (LR). An Eastern Hepatobiliary Surgery Hospital (EHBH)/PVTT scoring system was established to predict the prognosis of HCC patients with PVTT after R0 LR and guide selection of subgroups of patients that could benefit from LR. HCC patients with PVTT limited to a first‐order branch of the MPV or above who underwent R0 LR as an initial therapy were included. The EHBH‐PVTT score was developed from a retrospective cohort in the training cohort using a Cox regression model and validated in a prospective internal validation cohort and three external validation cohorts. There were 432 patients in the training cohort, 285 in the prospective internal validation cohort, and 286, 189, and 135 in three external validation cohorts, respectively. The score was calculated using total bilirubin, α‐fetoprotein (AFP), tumor diameter, and satellite lesions. The EHBH‐PVTT score differentiated two groups of patients (≤/>3 points) with distinct long‐term prognoses (median overall survival [OS], 17.0 vs. 7.9 months; P < 0.001). Predictive accuracy, as determined by the area under the time‐dependent receiver operating characteristic curves (AUCs; 0.680‐0.721), was greater than that of the other commonly used staging systems for HCC and PVTT. Conclusion: The EHBH‐PVTT scoring system was more accurate in predicting the prognosis of HCC patients with PVTT than other staging systems after LR. It selected appropriate HCC patients with PVTT limited to a first‐order branch of the MPV or above for LR. It can be used to supplement the other HCC staging systems.
Carfilzomib or bortezomib with melphalan-prednisone for transplant-ineligible patients with newly diagnosed multiple myeloma.

The phase 3 CLARION study compared carfilzomib-melphalan-prednisone (KMP) with bortezomib-melphalan-prednisone (VMP) in transplant-ineligible newly diagnosed multiple myeloma (NDMM) patients. Patients were randomized 1:1 to KMP or VMP for nine 42-day cycles (C). Patients received carfilzomib on days (D) 1, 2, 8, 9, 22, 23, 29, 30 (20 mg/m2: C1D1, C1D2; 36 mg/m2 thereafter) or bortezomib on D1, 4, 8, 11, 22, 25, 29, 32 (1.3 mg/m2; D4, 11, 25, 32 omitted for C5-9). Melphalan (9 mg/m2) and prednisone (60 mg/m2) were administered on D1-4. The primary endpoint was progression-free survival (PFS). Nine hundred fifty-five patients were randomized (intention-to-treat population: KMP, n = 478; VMP, n = 477). Median PFS was 22.3 months with KMP vs 22.1 months with VMP (hazard ratio [HR], 0.906; 95% confidence interval [CI], 0.746-1.101; P = .159). Median overall survival was similar and not reached in either group (HR, 1.08; 95% CI, 0.82-1.43). Overall response rate was 84.3% for KMP and 78.8% for VMP. Complete response rate was 25.9% for KMP and 23.1% for VMP. Minimal residual disease-negative rates were 15.7% (KMP) and 15.5% (VMP). Adverse events (AEs) of interest (any grade) occurring with a ≥5% higher patient incidence in the KMP arm were acute renal failure (13.9% [KMP] vs 6.2% [VMP]) and cardiac failure (10.8% vs 4.3%). Grade ≥3 AE rates were 74.7% (KMP) and 76.2% (VMP). Grade ≥2 peripheral neuropathy was lower for KMP vs VMP (2.5% vs 35.1%). Treatment with KMP in CLARION did not yield a statistically significant difference in PFS vs VMP. This trial was registered at www.clinicaltrials. gov as #NCT01818752.
TypeLoader2: Automated submission of novel HLA and killer‐cell immunoglobulin‐like receptor alleles in full length

The Immuno Polymorphism Database (IPD) databases provide global, curated repositories for information regarding polymorphisms of genes of the immune system, thereby generating immense value for the research and clinical communities. The advent of high‐throughput genotyping in immunogenetics has led to dramatically growing numbers of heretofore unknown HLA and lately also killer‐cell immunoglobulin‐like receptor (KIR) alleles, which are to be curated and deposited in the IPD‐IMGT/HLA and IPD‐KIR databases, respectively. It is highly desirable that these novel alleles are characterised and submitted in full length, and that known alleles are extended to cover the complete gene sequence.
Recovery of Fungal Cells from Air Samples: a Tale of Loss and Gain

This work shed light on a significant issue regarding the loss of fungal spores when recovered from air samples using liquid medium and centrifugation to concentrate air particles before DNA extraction. We provide proof that the loss affects the overall fungal diversity of aerosols and that some taxa are differentially more affected than others. Furthermore, a laboratory experiment confirmed the environmental results obtained during field sampling. The filtration protocol described in this work offers a better description of the fungal diversity of aerosols and should be used in fungal aerosol studies. ABSTRACT There are limitations in establishing a direct link between fungal exposure and health effects due to the methodology used, among other reasons. Culture methods ignore the nonviable/uncultivable fraction of airborne fungi. Molecular methods allow for a better understanding of the environmental health impacts of microbial communities. However, there are challenges when applying these techniques to bioaerosols, particularly to fungal cells. This study reveals that there is a loss of fungal cells when samples are recovered from air using wet samplers and aimed to create and test an improved protocol for concentrating mold spores via filtration prior to DNA extraction. Results obtained using the new technique showed that up to 3 orders of magnitude more fungal DNA was retrieved from the samples using quantitative PCR. A sequencing approach with MiSeq revealed a different diversity profile depending on the methodology used. Specifically, 8 fungal families out of 19 families tested were highlighted to be differentially abundant in centrifuged and filtered samples. An experiment using laboratory settings showed the same spore loss during centrifugation for Aspergillus niger and Penicillium roquefortii strains. We believe that this work helped identify and address fungal cell loss during processing of air samples, including centrifugation steps, and propose an alternative method for a more accurate evaluation of fungal exposure and diversity. IMPORTANCE This work shed light on a significant issue regarding the loss of fungal spores when recovered from air samples using liquid medium and centrifugation to concentrate air particles before DNA extraction. We provide proof that the loss affects the overall fungal diversity of aerosols and that some taxa are differentially more affected than others. Furthermore, a laboratory experiment confirmed the environmental results obtained during field sampling. The filtration protocol described in this work offers a better description of the fungal diversity of aerosols and should be used in fungal aerosol studies.
Understanding Generation Y

Our research shows the biggest divide facing our society is not a gender divide, racial divide, income or technology divide but it is the generational divide. For those of us involved in engaging young people it must be remembered that the gap between us and them is constantly growing: school students are always aged 5-18 but we are getting older, so we must work harder to understand them and so remain relevant.
Performance of a CDMA radio communications system with feed-back power control and multipath dispersion

An investigation is made of the performance of a CDMA (code-division multiple access) radio system with feedback power control. Feedback power control delay, power delay profile and channel fading rate are used as parameters to characterize the channel performance. Tradeoffs between the use of single and multiple correlators per antenna for the multipath dispersive channel are shown. It is found that in some delay-spread environments, it may be better to turn off one of the correlators or lock all the correlators onto the strongest path. <<ETX>>