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Plant microRNA (miRNA) target MIMICs (MIMs) are non-coding RNA transcripts that can inhibit endogenous miRNAs, as they contain a miRNA binding site that forms a three nucleotide (nt) mismatch loop opposite the miRNA cleavage site upon miRNA binding. This loop renders the MIMs non-cleavable, presumably leading to sequestration of the miRNA and thus enabling the endogenous targets to be deregulated. Arabidopsis miR319 and miR159 are two closely related but distinct miRNA families, as they are functionally specific for two different sets of targets, TCP and MYB genes, respectively. Being offset by one nt, MIM319 and MIM159 should have specificity to their respective miRNA families. However, MIM319 and MIM159 plants appear indistinguishable, having highly similar developmental defects reminiscent of a loss-of-function mir159 mutant. In both MIM319 and MIM159 plants, miR159 and miR319 levels are reduced, and correspondingly, both MYB and TCP mRNA levels are elevated, implying that these MIMs are inhibiting both miR159 and miR319. These data demonstrate that MIMs are able to inhibit closely related miRNAs, including those with cleavage sites not opposite the three nt loop. This highlights that MIMs can have unintended off-target effects and that their use should include corresponding molecular analysis to investigate their impact on closely related miRNAs., (Copyright © 2015 Elsevier GmbH. All rights reserved.)

Purpose: Retinoblastoma (RB), a primary pediatric intraocular tumor, arises from primitive retinal layers. Several novel molecular strategies are being developed for the clinical management of RB. miRNAs are known to regulate cancer-relevant biological processes. Here, the role of selected miRNAs, namely, miR-532-5p and miR-486-3p, has been analyzed for potential therapeutic targeting in RB., Methods: A comprehensive bioinformatic analysis was performed to predict the posttranscriptional regulators (miRNAs) of the select panel of genes [Group 1: oncogenes (HMGA2, MYCN, SYK, FASN); Group 2: cancer stem cell markers (TACSTD, ABCG2, CD133, CD44, CD24) and Group 3: cell cycle regulatory proteins (p53, MDM2)] using Microcosm, DIANALAB, miRBase v 18, and REFSEQ database, and RNA hybrid. The expressions of five miRNAs, namely, miR-146b-5p, miR-532-5p, miR-142-5p, miR-328, and miR-486-3p, were analyzed by qRT-PCR on primary RB tumor samples (n = 30; including 17 invasive RB tumors and 13 noninvasive RB tumors). Detailed complementary alignment between 5' seed sequence of differentially expressed miRNAs and the sequence of target genes was determined. Based on minimum energy level and piCTAR scores, the gene targets were selected. Functional roles of these miRNA clusters were studied by using mimics in cultured RB (Y79, Weri Rb-1) cells in vitro. The gene targets (SYK and FASN) of the studied miRNAs were confirmed by qRT-PCR and western blot analysis. Cell proliferation and apoptotic studies were performed., Results: Nearly 1948 miRNAs were identified in the in silico analysis, From this list, only 9 upregulated miRNAs (miR-146b-5p, miR-305, miR-663b, miR-299, miR-532-5p, miR-892b, miR-501, miR-142-5p, and miR-513b) and 10 downregulated miRNAs (miR-1254, miR-328, miR-133a, miR-1287, miR-1299, miR-375, miR-486-3p, miR-720, miR-98, and miR-122*) were found to be common with the RB serum miRNA profile. Downregulation of five miRNAs (miR-146b-5p, miR-532-5p, miR-142-5p, miR-328, and miR-486-3p) was confirmed experimentally. Predicted common oncogene targets (SYK and FASN) of miR-486-3p and miR-532-5p were evaluated for their mRNA and protein expression in these miRNA mimic-treated RB cells. Experimental overexpression of these miRNAs mediated apoptotic cell death without significantly altering the cell cycle in RB cells., Conclusion: Key miRNAs in RB pathogenesis were identified by an in silico approach. Downregulation of miR-486-3p and miR-532-5p in primary retinoblastoma tissues implicates their role in tumorigenesis. Prognostic and therapeutic potential of these miRNA was established by the miRNA mimic strategy.

It has now been more than a quarter of a century since the U.S. Department of Defense (DoD) began its microwave and millimeter-wave monolithic integrated circuits (MIMIC) program. During that time, the Cold War ended and, as a result, there was a dramatic consolidation of defense companies. Many engineers, scientists, and others who participated in the program have changed companies, changed jobs, retired and, in some cases, died. The legacy of the program, however, remains: the establishment of the capabilities, infrastructure, and knowledge necessary to design and produce GaAs MMICs for nearly any application with high yield, at low cost, and possessing the specific performance and reliability characteristics required for their use in a huge number of system applications, both military and commercial [1][3]. This, in turn, has resulted in the United States' becoming the world leader in GaAs MMIC technology, a position that it still holds. The program played a major role in disproving the once popular statement that “GaAs is the material of the future and always will be.” This article describes the beginnings of the program and the strategy it used to achieve its goals. It also summarizes what has been accomplished and offers some advice based on the experience gained over the course of the program. [ABSTRACT FROM PUBLISHER]

Most common network protocols transmit variable size packets, whereas contemporary switches still operate with fixed- size cells, which are easier to transmit and buffer. This necessitates packet segmentation and reassembly modules, resulting in significant computation and communication overhead that might be too costly as switches become faster and bigger. It is, therefore, imperative to investigate an alternative mode of scheduling in which packets are scheduled contiguously over the switch fabric. This paper investigates the cost of packet-mode scheduling for the combined input-output-queued (CIOQ) switch architecture. We devise frame-based schedulers that allow a packet-mode CIOQ switch with small speedup to mimic an ideal output-queued switch, with bounded relative queuing delay. The schedulers are pipelined and based on matrix decomposition. Our schedulers demonstrate a trade-off between the switch speedup and the relative queuing delay incurred while mimicking an output-queued switch. When the switch is allowed to incur high relative queuing delay, a speedup arbitrarily close to two suffices to mimic an ideal output-queued switch. This implies that packet-mode scheduling does not require higher speedup than a cell-based scheduler. The relative queuing delay can be significantly reduced with just a doubling of the speedup. We further show that it is impossible to achieve zero relative queuing delay (that is, a perfect emulation), regardless of the switch speedup. In addition, simpler algorithms can mimic an output-queued switch with a bounded buffer size, using speedup arbitrarily close to one. Simulations confirm that packet-mode emulation with reasonable relative queuing delay can be achieved with moderate speedup. Furthermore, a simple and practical heuristic is shown by simulations to also provide effective packet-mode emulation. [ABSTRACT FROM PUBLISHER]

The diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is usually straightforward, but atypical presentations can represent a significant diagnostic challenge. This review highlights the clinical and electrophysiological 'red flags' that should make one consider an alternative diagnosis., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Introduction: The purpose of this study was to observe and evaluate 3-dimensional pulp cavity changes during orthodontic treatment., Methods: Eighty-seven patients formed the study sample and were divided into an experimental group (48 patients) and a control group (39 patients). Cone-beam computed tomographic (CBCT) records were obtained before the start of the treatment (T0) and after space closure for the experimental group, whereas for the control group CBCT images were obtained approximately 17-18 months (T1) after obtaining the first image (T0). CBCT data were reconstructed with surface and volume rendering software (Mimics; Materialise, Leuven, Belgium), and the volumetric images were modified to display the teeth from various orientations. Six anterior teeth were segmented and their pulps isolated. Paired t test was used to check for statistical significance., Results: The difference in the pulp volume was statistically significant at P < .05 for all the anterior teeth in the experimental group and at P < .05 for the right canine, P < .05 for the right and left lateral incisors, and P < .05 for the left central in the control group., Conclusions: Orthodontic treatment in the experimental group produced a significant decrease in the size of the pulp, which was statistically significant., (Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

As small volumes of prostate cancer are being detected with ever-increasing frequency, the pathologist is challenged to make more diagnostically out of less. This photoessay explores ten diagnostic problems that are noted with regularity by a provider of second opinions in prostate biopsy interpretation. These include: suboptimal submission of prostate cores, atypia with small size of the focus of concern, cytologic ambiguity of the focus of concern, issues with ordering and interpreting immunostains, atypia arising with high-grade prostatic intraepithelial neoplasia, benign mimics of cancer, omitting mention of extraprostatic tumor extension or of Gleason pattern 5, not recognizing intraductal carcinoma, and the differential diagnosis of cancer of urothelial versus prostatic origin., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The hip joint is one of the most frequent sites of osteoarthritis. Advances in diagnosis and clinical treatment have progressed dramatically in the last few decades; however, there are limitations associated with the lack of reliable measures for quantifying hip joint morphology. Current diagnostic measures of the hip are performed with pre-determined measures, typically lengths and angles, on 2D radiographic planes. The current measurement techniques do not utilize the inherent 3D nature of CT and MR imaging and do not necessarily quantify the relevant clinical pathologies. A valid and reliable measurement modality that measures the surface geometry of the femoral head is necessary for early diagnosis and treatment of hip disease. The purpose of this study was to establish a method to quantify femoral head morphology using a three-dimensional model. A novel measurement approach was applied to 45 cadaveric femurs (23 right; 22 left; nine female, 17 male) and their digitally reconstructed 3D CT models. The mean difference between the cadaveric and digital measures was -2.04 mm with 95% confidence limits (CI) of 13.67 mm and -17.75 mm, respectively. The digital measurement approach was found to have excellent intraobserver reliability (ICC = 0.99, CI 0.98-0.99) and interobserver reliability (ICC = 0.98, CI 0.93-0.99). This valid and reliable novel digital measurement approach enables quantification of the 3D surface geometry of the femoral head and is able to measure individual variations and potentially detect abnormalities. This method may be used to assist future studies to establish valid diagnostic measurements for femoral head and head-neck junction pathologies., (© 2014 Anatomical Society.)

Background: Previous literatures have shown a transient ischemic attack (TIA) mimic rate of 9-31%. We aimed to ascertain the proportion of stroke mimics amongst suspected TIA patients., Methods: A prospective observational study was performed in Ghaem Hospital, Mashhad, Iran during 2012-2013. Consecutive TIA patients were identified in a stroke center. The initial diagnosis of TIA was made by the resident of neurology and final diagnosis of true TIA versus TIA mimics was made after 3 months follow-up by stroke subspecialist., Results: A total of 310 patients were assessed during a 3-month period of which 182 (58.7%) subjects were male and 128 (41.3%) were female. Ten percent of the patients was categorized as a TIA mimic. The presence of hypertension, aphasia, duration of symptoms, and increased age was the strongest predictor of a true TIA. Migraine was the most common etiology of stroke mimic in our study., Conclusion: It seems that many signs and symptoms have low diagnostic usefulness for discrimination of true TIA from non-cerebrovascular events and predictive usefulness of any sign or symptom should be interpreted by a stroke neurologist.

This review summarizes a variety of clinical and histologic mimics of idiopathic inflammatory bowel disease. All the entities that are included demonstrate one or more histologic features typical of idiopathic inflammatory bowel disease that may lead to potential diagnostic confusion and misinterpretation by the pathologist. The elements of the clinical history, laboratory test results, and endoscopic findings that are helpful to the surgical pathologist in considering a diagnosis other than idiopathic inflammatory bowel disease are emphasized. On occasion, a poor response to standard treatment for idiopathic inflammatory bowel disease is the clue that prompts reconsideration of the initial diagnosis. Subtle histologic features, special stains, or other diagnostic methodologies that can aid in proper diagnosis are also discussed., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Many neurodegenerative diseases, like Parkinson's, Alzheimer's, or Huntington's disease, occur as a result of amyloid protein fibril formation and cell death induced by this process. Cyclic peptides (CPs) and their derivatives form a new class of powerful inhibitors that prevent amyloid fibrillation and decrease the cytotoxicity of aggregates. The strategies for designing CPs are described, with respect to their amino acid sequence and/or conformational similarity to amyloid fibrils. The implications of CPs for the study and possible treatment of amyloid-related diseases are discussed., (Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Gaucher disease is an autosomal recessive disorder caused by deficiency of the enzyme glucocerebrosidase. Although it is a monogenic disease, there is vast phenotypic heterogeneity, even among patients with the same genotype. MicroRNAs (miRNAs) are small non-coding RNAs involved in many biological processes and diseases. To determine whether miRNAs can affect glucocerebrosidase activity, we performed a screen of 875 different miRNA mimics. The screen was performed using Gaucher fibroblasts, and glucocerebrosidase activity was used as the initial outcome parameter. We found several miRNAs that either up- or down-regulated glucocerebrosidase activity. In follow-up assays, we confirmed that one specific miRNA (miR-127-5p) down-regulated both glucocerebrosidase activity and protein levels by down-regulation of LIMP-2, the receptor involved in proper trafficking of glucocerebrosidase from the endoplasmic reticulum to the lysosome. A conditioned media assay demonstrated that cells treated with this miRNA secreted glucocerebrosidase into the extracellular environment, supporting impaired LIMP-2 function. Two other miRNAs, miR-16-5p and miR-195-5p, were found to up-regulate glucocerebrosidase activity by greater than 40% and to enhance expression and protein levels of the enzyme. In conclusion, we show that miRNAs can alter glucocerebrosidase activity in patient cells, indicating that miRNAs can potentially act as modifiers in Gaucher disease.

Changes in cell surface glycosylation are a hallmark of the transition from normal to inflamed and neoplastic tissue. Tumor-associated carbohydrate antigens (TACAs) challenge our understanding of immune tolerance, while functioning as immune targets that bridge innate immune surveillance and adaptive antitumor immunity in clinical applications. T-cells, being a part of the adaptive immune response, are the most popular component of the immune system considered for targeting tumor cells. However, for TACAs, T-cells take a back seat to antibodies and natural killer cells as first-line innate defense mechanisms. Here, we briefly highlight the rationale associated with the relative importance of the immune surveillance machinery that might be applicable for developing therapeutics.

Cytology is increasingly being used in the evaluation of lung lesions. There are several potential pitfalls and mimics encountered in the evaluation of respiratory cytology specimens, making interpretation of respiratory cytology challenging. Familiarity with the mimics and the pitfalls is essential in avoiding a misdiagnosis because a false positive or false negative diagnosis may have significant management implications. This article focuses on the main classification of primary lung carcinoma - small cell carcinoma, adenocarcinoma and squamous cell carcinoma - with potential mimics discussed under each tumor category. We have attempted to separate pitfalls from common potential mimics and have suggested general rules when such pitfalls are encountered.