Miracle-dz/UniFAR-FTUs huggingface dataset:
Watching proteins function with time-resolved x-ray crystallography

Macromolecular crystallography was immensely successful in the last two decades. To a large degree this success resulted from use of powerful third generation synchrotron x-ray sources. An expansive database of more than 100 000 protein structures, of which many were determined at resolution better than 2 Å, is available today. With this achievement, the spotlight in structural biology is shifting from determination of static structures to elucidating dynamic aspects of protein function. A powerful tool for addressing these aspects is time-resolved crystallography, where a genuine biological function is triggered in the crystal with a goal of capturing molecules in action and determining protein kinetics and structures of intermediates (Schmidt et al 2005a Methods Mol. Biol. 305 115–54, Schmidt 2008 Ultrashort Laser Pulses in Biology and Medicine (Berlin: Springer) pp 201–41, Neutze and Moffat 2012 Curr. Opin. Struct. Biol. 22 651–9, Šrajer 2014 The Future of Dynamic Structural Science (Berlin: Springer) pp 237–51). In this approach, short and intense x-ray pulses are used to probe intermediates in real time and at room temperature, in an ongoing reaction that is initiated synchronously and rapidly in the crystal. Time-resolved macromolecular crystallography with 100 ps time resolution at synchrotron x-ray sources is in its mature phase today, particularly for studies of reversible, light-initiated reactions. The advent of the new free electron lasers for hard x-rays (XFELs; 5–20 keV), which provide exceptionally intense, femtosecond x-ray pulses, marks a new frontier for time-resolved crystallography. The exploration of ultra-fast events becomes possible in high-resolution structural detail, on sub-picosecond time scales (Tenboer et al 2014 Science 346 1242–6, Barends et al 2015 Science 350 445–50, Pande et al 2016 Science 352 725–9). We review here state-of-the-art time-resolved crystallographic experiments both at synchrotrons and XFELs. We also outline challenges and further developments necessary to broaden the application of these methods to many important proteins and enzymes of biomedical relevance.
Herpes Simplex Virus Type 1 Portal Protein UL6 Interacts with the Putative Terminase Subunits UL15 and UL28

ABSTRACT The herpes simplex virus type 1 (HSV-1) UL6, UL15, and UL28 proteins are essential for cleavage of replicated concatemeric viral DNA into unit length genomes and their packaging into a preformed icosahedral capsid known as the procapsid. The capsid-associated UL6 DNA-packaging protein is located at a single vertex and is thought to form the portal through which the genome enters the procapsid. The UL15 protein interacts with the UL28 protein, and both are strong candidates for subunits of the viral terminase, a key component of the molecular motor that drives the DNA into the capsid. To investigate the association of the UL6 protein with the UL15 and UL28 proteins, the three proteins were produced in large amounts in insect cells with the baculovirus expression system. Interactions between UL6 and UL28 and between UL6 and UL15 were identified by an immunoprecipitation assay. These results were confirmed by transiently expressing wild-type and mutant proteins in mammalian cells and monitoring their distribution by immunofluorescence. In cells expressing the single proteins, UL6 and UL15 were concentrated in the nuclei whereas UL28 was found in the cytoplasm. When the UL6 and UL28 proteins were coexpressed, UL28 was redistributed to the nuclei, where it colocalized with UL6. In cells producing either of two cytoplasmic UL6 mutant proteins and a functional epitope-tagged form of UL15, the UL15 protein was concentrated with the mutant UL6 protein in the cytoplasm. These observed interactions of UL6 with UL15 and UL28 are likely to be of major importance in establishing a functional DNA-packaging complex at the portal vertex of the HSV-1 capsid.
Venturing Beyond the Rule of Thumb in the Valuation of Small Accounting Practices: An Exploration in the Italian Market

The study explores the prediction accuracy of a P/Sales multiple – derived from the regression of transaction values on value drivers identified consistently with prior studies – in the highly standardized and homogenous context of the transfer of Small Accounting Practices. We find that the regressed P/Sales multiple significantly outperforms other multiples – often adopted as rule of thumb valuation metrics in the industry – such as simple industry harmonic-averaged P/Sales or P/EBITDA. The median absolute error is 4.70% for the regressed multiple vs 11.30% for the best alternative metric (P/Sales harmonic mean). Moreover, we observe that non-financial information specific to the context of Small Accounting Practices, namely the location in big cities, is value relevant and complements financial and deal characteristics information.
A Study of Factor XHIa and MAC 387 Immunolabeling in Normal and Pathological Skin

Immunolabeling with two new antibodies, Factor XIII a and MAC 387, has been studied in routinely processed biopsy specimens of normal skin, subcutaneous tissues, lymph nodes, and a variety of pathological conditions. These presumptive cell markers of the monocyte-macrophage lineage appear to label totally different and possibly mutually exclusive subsets of cells. In normal skin, Factor XIII a labeled fixed dermal connective tissue cells, emphasizing their dendritic morphological appearance. Factor XIII a expression in fibroproliferative conditions and spindle cell tumors varied: in particular, scars, keloids, and dermatofibrosarcomas do not label, whereas histiocytomas, fibrous papule of the nose, and atypical fibroxanthomas were well labeled. In inflammatory conditions, increased numbers of Factor XIII a cells were found, but most macrophages and epithelioid and multinucleate cells did not label. In contrast, normal dermal connective tissue cells did not label with MAC 387, nor did the constituent cells of various fibroproliferative disorders. In inflammatory conditions, variable numbers of MAC 387-positive cells were observed, corresponding to histiocytes and macrophages, but labeling of epithelioid cells and multinucleate foreign body giant cells was variable. Histiocytosis X cells do not express either label. The theoretical and practical implications of these results are explored
Ml-KNN Algorithm Based on Frequent Item Sets

In order to solve the problem of ignoring the correlation between class labels, this paper describes a new method for multi-label classification based on the frequent item sets to classify an unseen instance on the basis of its k nearest neighbors ( MLFI-KNN). For each unseen instance, MLFI-KNN takes its k-nearest neighbors in the training set and counts the number of occurrences of each label in this neighborhood, and then utilizes the FP-growth algorithm to obtain the frequent item sets between the labels that these neighboring instances include, in order to determine the predicted label set. Experiments on benchmark dataset demonstrate the effectiveness of the proposed approach as compared to some existing well-known methods.
MMSpace: Kinetically-augmented telepresence for small group-to-group conversations

A novel research prototype, called MMSpace, was developed for realistic social telepresence in small group-to-group conversations. MMSpace consists of kinetic display avatars, which can change pose and position by automatically mirroring the remote user's head motions. To fully explore its potential beyond previous alternatives, MMSpace has the following novel features. First, it targets symmetric group-to-group telepresence. Second, the kinetic avatars of MMSpace can produce highly accurate, low latency, and silent physical motions, by using 4-Degree-of-Freedom (DoF) direct-drive actuators, and they can express a wide range of natural human behaviors like head gestures and changing attitudes, as well as indicating the focus of attention. Third, MMSpace supports eye contact between every pair of participants, by integrating i) directional visual attention cues indicated by avatar's kinetic pose change, ii) line-of-sight alignment among the positions of persons, avatars and cameras, and iii) attention-based camera switching, which allows an avatar to always show its owner's face looking directly toward the person that the avatar's owner is looking at. The prototype targets the 2 × 2 setting, and subjective evaluations based on group discussions indicate that the kinetic display avatar is superior to static displays in various aspects including gaze-awareness, eye-contact, perception of other nonverbal behaviors, mutual understanding, and sense of telepresence.
Non-life insurance expenditure in developed and developing economies

This dissertation examines the determinants of non-life insurance expenditure using a panel dataset in the short term, long term and at product level. By undertaking a comprehensive empirical analysis, this dissertation fills existing gaps in literature and uncovers some important yet unexplored linkages between social-economic-cultural factors and non-life insurance expenditure.
Epidemiologic Usefulness of Spoligotyping for Secondary Typing ofMycobacterium tuberculosis Isolates with Low Copy Numbers of IS6110

ABSTRACT Restriction fragment length polymorphism (RFLP) analysis of IS6110 is commonly used to DNA fingerprintMycobacterium tuberculosis. However, low-copy (≤5) IS6110 M. tuberculosis strains are poorly differentiated, requiring secondary typing. When spoligotyping was used as the secondary method, only 13% of Maryland culture-positive tuberculosis (TB) patients with low-copy IS6110-spoligotyped clustered strains had epidemiologic linkages to another patient, compared to 48% of those with high-copy strains clustered by IS6110 alone (P < 0.01). Spoligotyping did not improve a population-based molecular epidemiologic study of recent TB transmission.
A Simple Fragment of Cyclic Acyldepsipeptides Is Necessary and Sufficient for ClpP Activation and Antibacterial Activity

The development of new antibacterial agents, particularly those with unique biological targets, is essential to keep pace with the inevitable emergence of drug resistance in pathogenic bacteria. We identified the minimal structural component of the cyclic acyldepsipeptide (ADEP) antibiotics that exhibits antibacterial activity. We found that N‐acyldifluorophenylalanine fragments function via the same mechanism of action as ADEPs, as evidenced by the requirement of ClpP for the fragments' antibacterial activity, the ability of fragments to activate Bacillus subtilis ClpP in vitro, and the capacity of an N‐acyldifluorophenylalanine affinity matrix to capture ClpP from B. subtilis cell lysates. N‐acyldifluorophenylalanine fragments are much simpler in structure than the full ADEPs and are also highly amenable to structural diversification. Thus, the stage has been set for the development of non‐peptide activators of ClpP that can be used as antibacterial agents.
Innovation, sustainability and democracy: an analysis of grassroots contributions

In this paper we introduce an area of activity that has flourished for decades in all corners of the globe, namely grassroots innovation for sustainable development. We also argue why innovation in general is a matter for democracy. Combining these two points, we explore how grassroots innovation can contribute to what we call innovation democracy, and help guide innovation so that it supports rather than hinders social justice and environmental resilience. Drawing upon qual- itative case studies from empirical domains including energy, food, and manufacture, we suggest it does so in four related ways: 1. Processes of grassroots innovation can help in their own right to cultivate the more democratic practice of innovation more generally. 2. Grassroots innovations that result from these processes can support citi- zens and activities in ways that can contribute to practice of democracy. 3. Grassroots innovations can create particular empowering sociotechnical configurations that might otherwise be suppressed by interests around more mainstream innovation systems. 4. Grassroots innovations can help nurture general levels of social diversity that are important for the health of democracy in its widest political senses. The paper finishes with a few suggestions for how societies committed to innovation democracy can better support and benefit from grassroots activity, by working at changes in culture, infrastructure, training, investment, and openness.
Validation and Utility of the Patient Health Questionnaire in Diagnosing Mental Disorders in 1003 General Hospital Spanish Inpatients

Objective To determine whether the Spanish version of the patient health questionnaire (PHQ) has validity and utility for diagnosing mental disorders in general hospital inpatients. Methods Participants in the study were 1003 general hospital inpatients, randomly selected from all admissions over an 18-month period. All of them completed the PHQ, the Beck Depression Inventory (BDI), and measures of functional status, disability days, and health care use, including length of hospital stay. They also had a structured interview with a mental health professional. Results A total of 416 (42%) of the 1003 general hospital inpatients had a PHQ diagnosis. There was good agreement between PHQ diagnoses and those of an independent mental health professional (for the diagnosis of any PHQ disorder, &kgr; = 0.74; overall accuracy, 88%; sensitivity, 87%; specificity, 88%), similar to the original English version of the PHQ in primary care patients. Patients with PHQ diagnoses had more functional impairment, disability days, and health care use than did patients without PHQ diagnoses (group main effects for functional status measures and disability days, p < .001; group main effects for health care use, p < .01). The group main effect for hospital length of stay was not significant. An index of depression symptom severity calculated from the PHQ correlated significantly both with the number of depressive symptoms detected at interview and the total BDI score. PHQ administration was well accepted by patients. Conclusions The Spanish version of the PHQ has diagnostic validity in general hospital inpatients comparable to the original English version in primary care.
Building dynamic capabilities for high margin product development: a corporate control style perspective

Abstract This article contributes to the dynamic capabilities (DCs) literature by exploring the link between sensing, seizing and reconfiguring and firm performance defined as commercially successful high margin products development (HMPD). Our qualitative findings are based on semi-structured interviews conducted within a multinational telecommunication corporation. Our qualitative findings show that the sensing, seizing and reconfiguring aspects of DCs positively influence firm performance. Moreover, the level of positive influence of DCs on performance depends on the corporate control style (CCS) of the firm, since CCS directly affects the seizing and reconfiguring activities of DCs. CCS also regulates the link between sensing and seizing DCs activities and firm performance. We find evidence that there is no specific order in which the sensing, seizing, and reconfiguring activities occur. We also find that the identification of ’Surge’ and ‘Lurch‘events is a key channel for managers to enhance DCs in their firms.
A Battery Energy Storage interface for wind power systems with the use of grid side inverter

This paper presents a novel concept of Energy Storage System (ESS) interfacing with the grid side inverter in wind energy conversion systems. The inverter system used here is formed by cascading a 2-level inverter and a three level inverter through a coupling transformer. The constituent inverters are named as the “main inverter” and the “auxiliary inverter” respectively. The main inverter is connected with the rectified output of the wind generator while the auxiliary inverter is attached to a Battery Energy Storage System (BESS). The BESS ensures constant power dispatch to the grid irrespective of change in wind condition. Furthermore, this unique combination of BESS and inverter eliminates the need of additional dc-dc converters. Novel modulation and control techniques are proposed to address the problem of non-integer, dynamically-changing dc-link voltage ratio, which is due to random wind changes. Strategies used to handle auxiliary inverter dc-link voltage imbalances and controllers used to charge batteries at different rates are explained in detail. Simulation results are presented to verify the efficacy of the proposed modulation and control techniques in suppressing random wind power fluctuations.
MCL-1 Is a Key Antiapoptotic Protein in Human and Rodent Pancreatic β-Cells

Induction of endoplasmic reticulum stress and activation of the intrinsic apoptotic pathway is widely believed to contribute to β-cell death in type 1 diabetes (T1D). MCL-1 is an antiapoptotic member of the BCL-2 protein family, whose depletion causes apoptosis in rodent β-cells in vitro. Importantly, decreased MCL-1 expression was observed in islets from patients with T1D. We report here that MCL-1 downregulation is associated with cytokine-mediated killing of human β-cells, a process partially prevented by MCL-1 overexpression. By generating a β-cell–specific Mcl-1 knockout mouse strain (βMcl-1KO), we observed that, surprisingly, MCL-1 ablation does not affect islet development and function. β-Cells from βMcl-1KO mice were, however, more susceptible to cytokine-induced apoptosis. Moreover, βMcl-1KO mice displayed higher hyperglycemia and lower pancreatic insulin content after multiple low-dose streptozotocin treatment. We found that the kinase GSK3β, the E3 ligases MULE and βTrCP, and the deubiquitinase USP9x regulate cytokine-mediated MCL-1 protein turnover in rodent β-cells. Our results identify MCL-1 as a critical prosurvival protein for preventing β-cell death and clarify the mechanisms behind its downregulation by proinflammatory cytokines. Development of strategies to prevent MCL-1 loss in the early stages of T1D may enhance β-cell survival and thereby delay or prevent disease progression.
Overexpression of Hexokinase II in Transgenic Mice

Hexokinase II (HKII) is the predominant isozyme expressed in peripheral insulin-responsive tissues. To explore the role of HKII in muscle glucose metabolism, two lines of transgenic mice were generated where overexpression was restricted to striated muscle; HKII protein levels and activity were increased by 3–8-fold. Oral glucose tolerance, intravenous insulin tolerance, and insulin and lactate levels were unaffected in transgenic mice. There was a trend toward increased levels of muscle glycogen; however, glucose-6-phosphate levels were increased by 43% in transgenic skeletal muscle following in vivo glucose and insulin administration. Using 2-[3H]deoxyglucose as a tracer, in vitro basal and insulin-stimulated glucose uptake were determined in extensor digitorum longus, soleus, and epitrochlearis muscles. Maximal insulin-stimulated glucose uptake was increased by 17% (extensor digitorum longus), 34% (soleus), and 90% (epitrochlearis) in transgenic muscles; basal and submaximal glucose uptake was also modestly increased in soleus and epitrochlearis. These data suggest that increased muscle HKII (corresponding to the upper end of the physiologic range) may not be sufficient to augment net in vivo glucose homeostasis. However, glucose phosphorylation can represent a rate-limiting step for skeletal muscle glucose utilization since muscle glucose-6-phosphate levels are increased during in vivo hyperinsulinemia and hyperglycemia; furthermore, basal and insulin-mediated muscle glucose uptake can be increased by a selective increase in HKII expression.
Learning Commission Report: Connecting schools with communities

Pursuing Equity Through Rich Accountabilities (PETRA) is an Australian Research Council funded Linkage project being conducted through a partnership between researchers at The University of Queensland, Victoria University, and the Queensland Department of Education, Training and Employment (DETE). The PETRA project has been conducted with a group of eight schools in the Wide Bay Burnett region of Queensland at the behest of DETE. This region is among the lowest SES areas in Queensland, where education is more regionalised than elsewhere in Australia.
Application of artificial neural networks in lithofacies interpretation used for 3D geological modelling

This paper represents a study using Artificial Neural Networks (ANN) to perform automatic interpretation of lithofacies in a reservoir scale. This technique having been used successfully to interpret lithofacies automatically in the Sha20 Block, Shanian oilfield. Description and interpretation from a cored section in the key well was used to train the Supervised neural network. Having trained the network, it was then used to recognise and interpret the units vertically and laterally in the studied reservoir. The unsupervised neural network was run to classify the cored interval into 2and 6 classes respectively and the results were then compared with the supervised network output. The results were observed to be over 87% accurate. Then a 3D geological model was built using the sequential indicator simulation method, the excellent results obtained from the developed model shows that the method is quite effective and gets satisfying prediction precision for the lithofacies in reservoir modeling.
A Method of Recognizing Finger Motion Using Wavelet Transform of Surface EMG Signal

In this paper, an identification method of finger motions using the wavelet transform of multi-channel electromyography (EMG) signal is presented. The first step of this method is to analyze surface EMG signal detected from the subject's upper arm using the multi-resolution of wavelet transform, and extract features using the variance, maximum and mean absolute value of the wavelet coefficients. In this way, a new feature space is established by wavelet coefficients. The second step is to import the feature values into an artificial neural network (ANN) to identify the finger motion. Based on the results of experiments, it is concluded that this method is effective in identification of finger motion. Thus, it provides an alternative approach to use the surface EMG in controlling the finger motion of a multi-fingered prosthetic hand