To classify or not to classify, that is the question?

Allostery has come of age; the number, breadth and functional roles of documented protein allostery cases are rising quickly. Since all dynamic proteins are potentially allosteric and allostery plays crucial roles in all cellular pathways, sorting and classifying allosteric mechanisms in proteins should be extremely useful in understanding and predicting how the signals are regulated and transmitted through the dynamic multi-molecular cellular organizations. Classification organizes the complex information thereby unraveling relationships and patterns in molecular activation and repression. In signaling, current classification schemes consider classes of molecules according to their functions; for example, epinephrine and norepinephrine secreted by the central nervous system are classified as neurotransmitters. Other schemes would account for epinephrine when secreted by the adrenal medulla to be hormone-like. Yet, such classifications account for the global function of the molecule; not for the molecular mechanism of how the signal transmission initiates and how it is transmitted. Here we provide a unified view of allostery and the first classification framework. We expect that a classification scheme would assist in comprehension of allosteric mechanisms, in prediction of signaling on the molecular level, in better comprehension of pathways and regulation of the complex signals, in translating them to the cascading events, and in allosteric drug design. We further provide a range of examples illustrating mechanisms in protein allostery and their classification from the cellular functional standpoint.

At present, a big effort of the scientific community has been directed toward a more proper and standardized approach to the patients affected by degenerative scoliosis, and recent attention has turned toward the development of classification schemes. A literature analysis highlighted several classification schemes developed for degenerative scoliosis patients: the Simmons classification system, the Aebi system, the Faldini working classification system, the Schwab system, and the Scoliosis Research Society system. Aim of the current manuscript is to scrutinize the available literature in order to provide a comprehensive overview of these current classification schemes for adult scoliosis, by describing and commenting clinical development, limits and potential of their application together with their implications for surgical planning.

Twelve lung neuroendocrine tumors with morphologic features of carcinoid tumors but with mitotic count >10/2 mm are reported. There were 7 males and 5 females, with age ranging from 56 to 78 years. Four cases were from never-smokers. All tumors showed architectural and cytomorphologic features of carcinoid tumor, including organoid nesting, insular, trabecular, or acinar growth, and tumor cells with low nucleocytoplasmic ratio, abundant cytoplasm, ovoid to round nuclei, and salt and pepper chromatin. Angulated or confluent nesting, insular or lobular growth pattern was also seen. Nuclear irregularities and anisonucleosis were focally present. Mitotic count ranged from 11 to 61/2 mm. Punctate-type necrosis was present in 8 tumors. Anaplastic cytology, large infarct-type necrosis, desmoplasia, or marked inflammatory infiltrate was not found in any of the tumors. One tumor occurred in the background of diffuse idiopathic pulmonary neuroendocrine hyperplasia. All tumors were treated by resection, and all but 1 patient subsequently developed metastasis, and 7 died of the tumor. For metastatic tumors, 4 patients were treated by platinum-based chemotherapy with no apparent response, whereas 3 other patients were treated by combined capecitabine and temozolomide-novel chemotherapy for well-differentiated neuroendocrine tumor/carcinoid tumor-2 of them responded. This subset of tumor would be classified as large cell neuroendocrine carcinoma according to the current WHO classification scheme, but their clinical and pathologic features appear to have more in common with the carcinoid tumor group than large cell neuroendocrine carcinoma, therefore, identification of this subset may be relevant for further therapeutic management.

Diagnosis and classification of myelodysplastic syndromes

We present a new classification scheme for the currents Jμ(x) = Qμν(x)Cν(x) in terms of the solutions of the Killing equations for Cμ(x). The new scheme enables us to treat any coordinate transformations (e.g., special conformal transformations), and to discuss the mass spectra for the scalar particles in a conformally-invariant system. Moreover, with the aid of the generalized Goldstone theorem exploited in the previous article under the same title, we shall point out the nonexistence of the Goldstone boson with regard to the special conformal transformations.

Chemical characterization and serological properties of a unique O-polysaccharide of the Proteus mirabilis Sm 99 clinical strain – Identification of a new, O81, serotype

The clinical management of pediatric liver tumors involves stratification into risk groups. One previously defined, high-risk group of hepatoblastomas is the small cell undifferentiated variant. In light of molecular studies showing SMARCB1 deletion in these tumors, it is now recognized that most small cell, undifferentiated liver tumors represent an aggressive unrelated tumor—the malignant rhabdoid tumor (MRT). SMARCB1 is a member of the chromatin remodeling SWI/SNF complex and encodes the INI1 protein. The histologic diagnosis of MRT is currently based on INI1 negative immunoreactivity and the presence of rhabdoid morphology. INI1-negative small cell liver tumors lacking classic rhabdoid morphology are often misclassified as small cell undifferentiated hepatoblastomas (SCUD-HB), according to the current classification. Pediatric liver tumors diagnosed between 2003–2017 as SCUD-HB (four cases) or MRT (two cases) were identified from the Columbia University Pathology Department Archives. All tumors were associated with normal or low serum alpha fetoprotein levels, and showed an absence of immunohistochemical staining of hepatocellular markers (Hep-par1, Arginase) and loss of INI1 staining. Two cases were initially diagnosed as MRT, one with prominent rhabdoid morphology, the other with predominant small cell morphology. The remaining four cases with small cell morphology were classified as SCUD-HB. Ancillary molecular studies confirmed the loss of SMARCB1, supporting the diagnosis of MRT in all cases, proving morphology an unreliable criterion. It is critical to eliminate the term INI1-negative hepatoblastoma from the current classification scheme, and classify INI1-negative tumors as MRT, particularly since high-risk HB-chemotherapy regimens are not effective for treating MRT.

Recent years have seen major changes in the classification criteria and taxonomy of viruses. The current classification scheme, also called “megataxonomy of viruses”, recognizes six different viral realms, defined based on the presence of viral hallmark genes (VHGs). Within the realms, viruses are classified into hierarchical taxons, ideally defined by the phylogeny of their shared genes. To enable the detection of shared genes, viruses have first to be clustered, and there is currently a need for tools to assist with virus clustering and classification. Here, VirClust is presented. It is a novel, reference-free tool capable of performing: (i) protein clustering, based on BLASTp and Hidden Markov Models (HMMs) similarities; (ii) hierarchical clustering of viruses based on intergenomic distances calculated from their shared protein content; (iii) identification of core proteins and (iv) annotation of viral proteins. VirClust has flexible parameters both for protein clustering and for splitting the viral genome tree into smaller genome clusters, corresponding to different taxonomic levels. Benchmarking on a phage dataset showed that the genome trees produced by VirClust match the current ICTV classification at family, sub-family and genus levels. VirClust is freely available, as a web-service and stand-alone tool.

Identity-based attacks (IBAs) are one of the most serious threats to wireless networks. Recently, there is an increasing interest in using the received signal strength (RSS) to detect IBAs in wireless networks. However, current schemes tend to generate excessive false alarms in the mobile scenario. In this paper, we propose a stronger Reciprocal Channel Variation-based Identification and classification (RCVIC) scheme for the mobile wireless networks, which exploits the reciprocity of the wireless fading channel and RSS variations naturally incurred by mobility to improve the detection performance. Different from current schemes only detect IBAs, RCVIC scheme conducts a multi-stage detection processes. If the IBAs are detected, RCVIC scheme partitions the received frames into two classes. The frames in the same class should be sent from the same senders, which could benefit the further analysis, such as network forensics, attacker localizing and trajectory analysis, etc. The feasibility of RCVIC are numerically evaluated through theoretical analysis and simulations. It is further validated through experiments using off-the-shelf 802.11 devices under different attacking patterns in real indoor and outdoor mobile scenarios.

A Clue to Diagnosing Connective Tissue Disease-Associated Interstitial Lung Disease

With the rapid growth in mobile commerce (m-commerce) applications, the need for providing suitable infrastructure to support these applications has become critical. Secure multicast is a key element of this infrastructure, in particular, to support group m-commerce applications such as mobile auctions, product recommendation systems, and financial services. Despite considerable attention to m-commerce security, most existing security solutions focus on unicast communications. On the other hand, numerous solutions for secure multicast exist that are not specifically designed with m-commerce as a target environment. Clearly, to address secure multicast in m-commerce, we must start by forming a comprehensive picture of the different facets of the problem and its solutions. In this chapter, we identify system parameters and subsequent security requirements for secure multicast in m-commerce. Attacks on m-commerce environments may undermine satisfying these security requirements resulting, at most times, in major losses. We present a taxonomy of common attacks and identify core services needed to mitigate these attacks and provide efficient solutions for secure multicast in m-commerce. Among these services, authentication and key management play a major role. Given the varying requirements of m-commerce applications and the large number of current key management schemes, we provide a taxonomy and a set of performance metrics to aid m-commerce system designers in the evaluation and selection of key management schemes.

Cutaneous vasculitis encompasses a highly heterogeneous group of disorders of diverse etiology, pathogenesis, and clinical features. Recent reexamination of clinical pathologic features have yielded no insights assisting our understanding of current clinical classification schemes and strengthening our clinical approach. Erythema nodosum is a common cutaneous disorder for which new etiologies continue to be described. Pyoderma gangrenosum is an uncommon ulcerative cutaneous condition that remains a therapeutic problem.

In 1997, Soergel et al1 published the first set of normative values for ambulatory blood pressure monitoring (ABPM) in children. Since then, the clinical utility of ABPM has increased dramatically, and now, ABPM is accepted as the standard method to confirm the diagnosis of hypertension in children. Despite significant progress in the field of pediatric ABPM, many important questions remain unanswered. One of the most controversial issues is how to define ambulatory hypertension in children. The purpose of this review is to discuss the limitations of the current pediatric ABPM classification scheme and to provide the justification and rationale for a new classification.

The extratropical transition (ET) of tropical cyclones in the North Atlantic basin is explored using the framework of the Cyclone Phase Space (CPS). Analyses from the U.S. Navy Operational Global Atmospheric Prediction System (NOGAPS) and National Centers for Environmental Prediction Aviation Model (AVN) are used to diagnose CPS locations of 19 Atlantic tropical cyclones that underwent ET in the years 1998–2002. A nonhierarchical cluster analysis technique, the k-means method, is employed to determine physically meaningful clusters of cyclone structure in this CPS dataset. The cluster analysis successfully partitions observations into subsets representing distinct cyclone structures. It is also found that, while current operational cyclone classification schemes are successful at defining some storm structures, cluster analysis assists in defining a "gray area" of transitioning tropical cyclones, an area where operational schemes overlap. A mean path through the CPS of tropical cyclones undergoing ET is proposed. This CPS path is explored using a synoptic life cycle developed from NOGAPS-derived clusters. The resulting climatology highlights distinct stages of ET, beginning with a tropical cyclone isolated from midlatitude influences to its north and ending with an extratropical cyclone, deeply embedded in the midlatitude westerlies. Similar cluster solutions, derived using data from both the NOGAPS and AVN models, suggest that the clusters found in this analysis are not model specific and indicate natural stages of the ET process. However, there are differences between the model CPS solutions, suggesting the use of an observational approach to validating cyclone phase and thus to defining ET.

Personalized diagnosis of medulloblastoma subtypes across patients and model systems