Miracle-dz/UniFAR-FTUs huggingface dataset:
Renal expression of SIBLING proteins and their partner matrix metalloproteinases (MMPs).

BACKGROUND Three members of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family of proteins have recently been shown to bind and activate specific promatrix metalloproteinases (MMPs) and to overcome the inhibition of tissue inhibitors of MMPs (TIMPs). Although usually associated with mineralized tissues, we have shown that the SIBLINGs and their MMP partners, when known, are coexpressed in salivary gland ductal cells. The present study examined the expression patterns of both the SIBLINGs and their MMP partners in adult kidney. METHODS The expression patterns of all five SIBLINGs known to date, and their MMP partners were determined in monkey kidney using immunohistochemistry and in situ hybridization techniques. RESULTS Bone sialoprotein (BSP) and its partner, MMP-2, were coexpressed in both the proximal and distal tubules. Osteopontin, as previously shown, was expressed in the distal tubules while its partner MMP-3 was expressed in both the proximal tubule and distal tubles. Dentin matrix protein-1 (DMP1) and MMP-9 were coexpressed throughout the nephron, including both parietal cells of Bowman's capsule and the thin limb of the loop of Henle. Dentin sialophosphoprotein (DSPP) and matrix extracellular phosphoglycoprotein (MEPE) were expressed in the proximal tubule and distal tubule, and proximal tubule, respectively. CONCLUSION In contrast to salivary gland in which all SIBLINGs and their MMP partners were coexpressed throughout the length of the ducts, these proteins were differentially expressed within the normal adult nephron. We hypothesize that the cells use the SIBLING/MMP pairs in the normal turnover of cell surface proteins and/or pericellular matrix proteins such as those in basement membranes.
Screening of mRNA Chemical Modification to Maximize Protein Expression with Reduced Immunogenicity

Chemical modification of nucleosides in mRNA is an important technology to regulate the immunogenicity of mRNA. In this study, various previously reported mRNA formulations were evaluated by analyzing in vitro protein expression and immunogenicity in multiple cell lines. For the macrophage-derived cell line, RAW 264.7, modified mRNA tended to have reduced immunogenicity and increased protein expression compared to the unmodified mRNA. In contrast, in some cell types, such as hepatocellular carcinoma cells (HuH-7) and mouse embryonic fibroblasts (MEFs), protein expression was decreased by mRNA modification. Further analyses revealed that mRNA modifications decreased translation efficiency but increased nuclease stability. Thus, mRNA modification is likely to exert both positive and negative effects on the efficiency of protein expression in transfected cells and optimal mRNA formulation should be determined based on target cell types and transfection purposes.
Variable Methylation of the Epstein-Barr Virus Wp EBNA Gene Promoter in B-Lymphoblastoid Cell Lines

ABSTRACT During the initial stages of Epstein-Barr virus (EBV) infection of peripheral resting B cells, transcription of the six genes encoding the EBV latency-associated nuclear antigens (EBNAs) is driven from Wp, a promoter that is present in multiple copies within the EBV major internal repeat. As infection progresses, transcription from Wp is downregulated following upregulation of EBNA gene transcription driven from a promoter, Cp, located ca. 3 kb upstream of the first copy of Wp. Recently published data have provided evidence that, concomitant with the switch in EBNA gene promoter usage, Wp becomes heavily methylated (R. J. Tierney et al., J. Virol. 74:10468-10479, 2000). Based on this observation, it has been argued that methylation of Wp plays a pivotal role in suppressing Wp activity in EBV-immortalized B-lymphoblastoid cell lines (LCLs). Here we present data compiled from analyses of Wp methylation in eight randomly selected low-passage-number B-LCLs. These data demonstrate that there is considerable variability in Wp methylation, both between different cell lines and within clonal LCLs. Overall, less methylation of Wp was noted in established, low-passage-number LCLs than was previously observed in bulk cultures of infected B cells at days 18 and 21 postinfection. Importantly, the majority of LCLs examined harbored both unmethylated and methylated copies of Wp. In addition, all low-passage-number LCLs examined contained both Cp- and Wp-initiated EBNA transcripts, arguing for the presence of some transcriptionally active copies of Wp. Taken together, these data argue that other factors, perhaps in conjunction with Wp methylation, play a role in suppressing Wp activity in LCLs.
Philosophy of Neuroscience and Options of Systems Science

Molecular biology as a research approach in psychiatry has gathered a huge amount of data that can hardly be used for explanation of mental disorders by cellular dysfunctions. In a philosophical sense "explanation" means the application of general laws on specific cases. This is more than description. Most findings of molecular biology only help to describe these processes more in detail. On contrary, systems biology aims to create a computer-based model of the cell. For this project mathematics plays a crucial role. In that respect systems biology also provides tools for data analysis.
Designing marine reserve networks for both conservation and fisheries management

Marine protected areas (MPAs) that exclude fishing have been shown repeatedly to enhance the abundance, size, and diversity of species. These benefits, however, mean little to most marine species, because individual protected areas typically are small. To meet the larger-scale conservation challenges facing ocean ecosystems, several nations are expanding the benefits of individual protected areas by building networks of protected areas. Doing so successfully requires a detailed understanding of the ecological and physical characteristics of ocean ecosystems and the responses of humans to spatial closures. There has been enormous scientific interest in these topics, and frameworks for the design of MPA networks for meeting conservation and fishery management goals are emerging. Persistent in the literature is the perception of an inherent tradeoff between achieving conservation and fishery goals. Through a synthetic analysis across these conservation and bioeconomic studies, we construct guidelines for MPA network design that reduce or eliminate this tradeoff. We present size, spacing, location, and configuration guidelines for designing networks that simultaneously can enhance biological conservation and reduce fishery costs or even increase fishery yields and profits. Indeed, in some settings, a well-designed MPA network is critical to the optimal harvest strategy. When reserves benefit fisheries, the optimal area in reserves is moderately large (mode ≈30%). Assessing network design principals is limited currently by the absence of empirical data from large-scale networks. Emerging networks will soon rectify this constraint.
Impaired auditory frequency discrimination in dyslexia detected with mismatch evoked potentials

Deficits in phonological skills appear to be at the heart of reading disability; however, the nature of this impairment is not yet known. The hypothesis that dyslexic subjects are impaired in auditory frequency discrimination was tested by using an attention‐independent auditory brain potential, termed mismatch negativity (MMN) while subjects performed a visual distractor task. In separate blocks, MMN responses to graded changes in tone frequency or tone duration were recorded in 10 dyslexic and matched control subjects. MMN potentials to changes in tone frequency but not to changes in tone duration were abnormal in dyslexic subjects. This physiological deficit was corroborated by a similarly specific impairment in discriminating tone frequency, but not tone duration, which was assessed separately. Furthermore, the pitch discrimination and MMN deficit was correlated with the degree of impairment in phonological skills, as reflected in reading errors of regular words and nonwords. It is possible that in dyslexia a persistent sensory deficit in monitoring the frequency of incoming sound may impair the feedback control necessary for the normal development of phonological skills. Ann Neurol 1999;45:495–503
Emotion is for influence

Functional approaches to emotion are rapidly gaining in popularity. Thus far the functions of emotions have been conceptualised and studied mainly at the intrapersonal level of analysis, the key question being how individuals are influenced by the emotions they experience. Relatively little is known about the interpersonal effects of emotions; that is, how one person's emotions influence other people's cognitions, attitudes, and behaviours. We propose that a primary function of emotion at this interpersonal level of analysis is to engender social influence. Our analysis is informed by emotion as social information theory (EASI; Van Kleef, 2009). This theory posits that emotional expressions produce interpersonal effects by triggering affective reactions and/or inferential processes in targets, depending on the target's information processing and the perceived appropriateness of the emotional expression. We review supportive evidence from various domains of social influence, including negotiation, leadership, attitude change, compliance, and conformity in groups. We consider the viability of emotional expressions as tools of social influence, discuss the functional equivalence of various forms of emotional expression, and address implications for theorising about emotion regulation and the functionality and evolution of emotion.
The centromeric nucleosome-like CENP–T–W–S–X complex induces positive supercoils into DNA

The centromere is a specific genomic region upon which the kinetochore is formed to attach to spindle microtubules for faithful chromosome segregation. To distinguish this chromosomal region from other genomic loci, the centromere contains a specific chromatin structure including specialized nucleosomes containing the histone H3 variant CENP–A. In addition to CENP–A nucleosomes, we have found that centromeres contain a nucleosome-like structure comprised of the histone-fold CENP–T–W–S–X complex. However, it is unclear how the CENP–T–W–S–X complex associates with centromere chromatin. Here, we demonstrate that the CENP–T–W–S–X complex binds preferentially to ∼100 bp of linker DNA rather than nucleosome-bound DNA. In addition, we find that the CENP–T–W–S–X complex primarily binds to DNA as a (CENP–T–W–S–X)2 structure. Interestingly, in contrast to canonical nucleosomes that negatively supercoil DNA, the CENP–T–W–S–X complex induces positive DNA supercoils. We found that the DNA-binding regions in CENP–T or CENP–W, but not CENP–S or CENP–X, are required for this positive supercoiling activity and the kinetochore targeting of the CENP–T–W–S–X complex. In summary, our work reveals the structural features and properties of the CENP–T–W–S–X complex for its localization to centromeres.
Essential role of the inositol 1,4,5-trisphosphate receptor/Ca2+ release channel in Ca2+ waves and Ca2+ oscillations at fertilization of mammalian eggs.

At fertilization mammalian eggs exhibit repetitive rises in the cytoplasmic Ca2+ concentration (Ca2+ oscillations), associated with propagating Ca2+ waves in the initial responses. The Ca2+ oscillation causes cortical granule exocytosis and resumption of second meiosis and affects later embryonic development. Recent studies using a function-blocking monoclonal antibody to the inositol 1,4,5-trisphosphate (InsP3) receptor/Ca2+ release channel demonstrated direct evidence that InsP3-induced Ca2+ release (IICR) from intracellular stores operates at fertilization of the hamster egg and that IICR is essential in the initiation, propagation, and oscillation of the sperm-induced Ca2+ rises. Ca(2+)-induced Ca2+ release (CICR) has also been suggested, but a sensitizing action of Ca2+ on the InsP3 receptor, i.e., Ca(2+)-sensitized IICR, can serve as a regenerative process of Ca2+ release and could be the basis for Ca2+ waves and Ca2+ oscillations. It is now apparent that signal transduction at fertilization is dependent on sperm-stimulated activation of phospholipase C which causes hydrolysis of phosphatidylinositol bisphosphate and production of InsP3, leading to IICR. On the other hand, Ca2+ signaling at fertilization of the sea urchin egg may also involve ryanodine receptor-mediated CICR.
High Prevalence of Abdominal, Intra-Abdominal and Subcutaneous Adiposity and Clustering of Risk Factors among Urban Asian Indians in North India

Objective To assess the prevalence of abdominal obesity including intra-abdominal and subcutaneous adiposity along with other cardiometabolic risk factors in urban Asian Indians living in New Delhi. Methods We conducted a cross-sectional epidemiological descriptive study with 459 subjects (217 males and 242 females), representing all socio-economic strata in New Delhi. The anthropometric profile [body mass index (BMI), waist circumference (WC) and skinfold thickness], fasting blood glucose (FBG) and lipid profile were recorded. Percent body fat (%BF), total abdominal fat (TAF), intra-abdominal adipose tissue (IAAT) and subcutaneous abdominal adipose tissue (SCAT) were quantified using predictive equations for Asian Indians. Results The overall prevalence of obesity was high [by BMI (>25 kg/m2), 50.1%]. The prevalence of abdominal obesity (as assessed by WC) was 68.9%, while that assessed by TAF was 70.8%. Increased IAAT was significantly higher in females (80.6%) as compared to males (56.7%) (p = 0.00) with overall prevalence being 69.3%. The overall prevalence of high SCAT was 67.8%, more in males (69.1%) vs. females (66.5%, p = 0.5). The prevalence of type 2 diabetes, the metabolic syndrome and hypertension was 8.5%, 45.3% and 29.2%, respectively. Hypertriglyceridemia, hypercholesterolemia and low levels of HDL-c were prevalent in 42.7%, 26.6% and 37% of the subjects, respectively. The prevalence of hypertriglyceridemia was significantly higher in males (p = 0.007); however, low levels of HDL-c were more prevalent in females as compared to males (p = 0.00). Conclusion High prevalence of generalized obesity, abdominal obesity (by measurement of WC, TAF, IAAT and SCAT) and dysmetabolic state in urban Asian Indians in north India need immediate public health intervention.
Replication schemes for peer-to-peer content in wireless mesh networks with infrastructure support

Many mobile devices e.g., smart phones, PDAs, portable computers and wireless routers e.g., WiFi access points nowadays are equipped with ad hoc transmission mode. In a dense environment such as a college/office campus, this creates the possibility of forming a wireless mesh network WMN in which mobile users communicate with each other through multiple wireless hops. This allows mobile users to exchange share files over the free access WMN rather than a carrier frequency such as 3G and WiMax. We consider a peer-to-peer P2P content sharing setting in a WMN, wherein the mesh network operator over-provision a number of mesh routers in the network with additional storage capacity and P2P-aware devices that are programmed to cache and store P2P content. Those mesh routers act as caches and participants in P2P content sharing. The aim of this setting is to both reduce the cost of communications between peers within the WMN i.e., reduce bandwidth and energy that P2P traffic consumes in the network, and enhance the performance of P2P content sharing i.e., reduce the average P2P content download delay. Our main contribution in this paper is an optimum P2P content replication strategy at the participating mesh routers. In particular, we determine the optimum number of replicas for every P2P file such that the average access cost of all files in the network is minimized. We propose a centralized algorithm that enables the participating mesh routers to implement the optimal strategy. We further propose a distributed low cost algorithm for P2P content replication at the participating mesh routers, and show that the distributed algorithm mimics the optimal strategy very well. The analytical and simulation results show that our replication strategy significantly reduces the average overall cost of accessing P2P files in the WMN as compared with other commonly used replication strategies. Copyright © 2013 John Wiley & Sons, Ltd.
Detection of staphylococcal enterotoxins by enzyme-linked immunosorbent assays and radioimmunoassays: comparison of monoclonal and polyclonal antibody systems

Murine monoclonal antibodies reactive with at least one of the serological types of staphylococcal enterotoxin were examined for use in assay systems for the detection of enterotoxin at the level of 1.0 ng of enterotoxin per ml. An antibody sandwich enzyme-linked immunosorbent assay was devised for each toxin type by identifying an effective antibody pair. One antibody (the coating antibody) was coated onto a polystyrene plate and removed the enterotoxin from the test solution; the second antibody (the probing antibody) was conjugated to horseradish peroxidase and detected the captured toxin. Enterotoxins A and E could be detected in the same system by the use of cross-reacting monoclonal antibodies. All subtypes of enterotoxin C could be detected in one assay system. Two effective systems were described for each of types B and D. Each of these systems, when compared with the homologous enterotoxin-specific polyclonal rabbit antibody systems, was found to compare favorably. The monoclonal enzyme-linked immunosorbent assay systems for the detection of enterotoxins A and C2 were examined for a variety of food extracts; no abnormal interference could be detected from these extracts. The monoclonal antibody systems were also compared with the homologous enterotoxin-specific polyclonal serum for the detection of enterotoxin by the competitive radioimmunoassay (RIA). Single monoclonal antibodies generally did not perform as well in the RIA as did the homologous toxin-specific polyclonal serum. However, pools of monoclonal antibodies were prepared that approached the sensitivity and precision of the polyclonal system for the detection of each toxin by the RIA.
Realizing strong PUF from weak PUF via neural computing

Physically Unclonable Functions (PUFs) are hardware-based security primitives that promise to provide an advantage in terms of area and power compared to hardware implementations of standard cryptography algorithms. PUFs harness manufacturing process variations to realize binary keys (Weak PUFs) or binary functions (SStrong PUFs). An ideal Strong PUF realizes a binary function that maps an m-bit input challenge to a random n-bit output response and offers an exponential number of such unique challenge-response pairs (CRPs). Hence, it is attractive for authentication applications. Unfortunately, most Strong PUF implementations are non-ideal, where an adversary can build a machine-learning model by observing a relatively few CRPs, making it possible to predict the output response of a PUF to a future challenge. Existence of such a model, or clone, constitutes a breach of security. In this paper, we make two contributions: first, we demonstrate that by leveraging a Weightless Neural Network (WNN), we can realize a CMOS Strong PUF from a Weak PUF. Next, we demonstrate that WNN based Strong PUFs offer robust resistance to machine-learning, while also delivering on uniqueness and reliability metrics — bringing it closer to an ideal Strong PUF. Neural network hardware is gaining importance for pattern matching and classification. This work demonstrates how such a design may be re-purposed for security. In the rest of the paper, we present architecture, practical implementation and analysis of Neural Network based PUFs.
Clustering of Web Users Based on Access

The clustering of the Web users based on their access patterns is studied. Access patterns of the Web users are extracted from Web servers' log les, and then organized into sessions which represent episodes of interaction between Web users and the Web server. Using attributed-oriented induction, the sessions are then generalized according to the page hierarchy which organizes pages according to their generalities. The generalized sessions are nally clustered using a hierarchical clustering method. Our experiments on a large real data set show that the method is eecient and practical for Web mining applications.
Designing continuous professional development programmes for teachers: A literature review

Abstract Continuous professional development is essential for upgrading and updating teachers because the rate of social and educational change makes pre-service training an inadequate basis for long term professional competence. The design of these continuous professional development programmes must be informed by an effective needs analysis that culminates from the teachers’ knowledge bases of curricula, instructional, content and pedagogical knowledge. The knowledge bases are conceptual frameworks upon which professional development should be based. Research shows that teachers perform better in professional development programmes whose design they are part of. This article is a literature review of professional development programmes for teachers in relation to teacher knowledge bases in South Africa. It articulates how high quality professional development programmes can be designed, implemented and evaluated, as well as the causes of failure and dissatisfaction associated with these programmes. It highlights strategies that teachers, subject specialists and curriculum developers can use to design professional development programmes that they can conduct in schools or externally to enhance high learning outcomes.
Noise or additional information? Leveraging crowdsource annotation item agreement for natural language tasks.

In order to reduce noise in training data, most natural language crowdsourcing annotation tasks gather redundant labels and aggregate them into an integrated label, which is provided to the classifier. However, aggregation discards potentially useful information from linguistically ambiguous instances. For five natural language tasks, we pass item agreement on to the task classifier via soft labeling and low-agreement filtering of the training dataset. We find a statistically significant benefit from low item agreement training filtering in four of our five tasks, and no systematic benefit from soft labeling.
The BCL2L1 and PGAM5 axis defines hypoxia-induced receptor-mediated mitophagy

Receptor-mediated mitophagy is one of the major mechanisms of mitochondrial quality control essential for cell survival. We previously have identified FUNDC1 as a mitophagy receptor for selectively removing damaged mitochondria in mammalian systems. A critical unanswered question is how receptor-mediated mitophagy is regulated in response to cellular and environmental cues. Here, we report the striking finding that BCL2L1/Bcl-xL, but not BCL2, suppresses mitophagy mediated by FUNDC1 through its BH3 domain. Mechanistically, we demonstrate that BCL2L1, but not BCL2, interacts with and inhibits PGAM5, a mitochondrially localized phosphatase, to prevent the dephosphorylation of FUNDC1 at serine 13 (Ser13), which activates hypoxia-induced mitophagy. Our results showed that the BCL2L1-PGAM5-FUNDC1 axis is critical for receptor-mediated mitophagy in response to hypoxia and that BCL2L1 possesses unique functions distinct from BCL2.