297 research outputs found
An Automated System to Mitigate Loss of Life at Unmanned Level Crossings
AbstractEvery life is precious and is worth saving. This paper proposes the design and implementation of a system to mitigate the loss of life at unmanned railway level crossings. This system uses the advancements in Communication, Embedded Systems and Internet of Things to develop a real-time, early warning system for unmanned level crossings across India. The outcome of this work is to provide an audio-visual indication to the commuter warning about an approaching train. The need for such systems and its design implementation and feasibility is discussed in this paper
Allosteric serine hydroxymethyltransferase from monkey liver: Temperature induced conformational transitions
The homogeneous serine hydroxymethyltransferase from monkey liver was optimally activate at 60° C and the Arrhenius plot for the enzyme was nonlinear with a break at 15° C. The monkey liver enzyme showed high thermal stability of 62°C, as monitored by circular dichroism at 222 nm, absorbance at 280 nm and enzyme activity. The enzyme exhibited a sharp co-operative thermal transition in the range of 50°-70° (Tm= 65°C), as monitored by circular dichroism. L-Serine protected the enzyme against both thermal inactivation and thermal disruption of the secondary structure. The homotropic interactions of tetrahydrofolate with the enzyme was abolished at high temperatures (at 70°C, the Hill coefficient value was 1.0). A plot of h values vs. assay temperature of tetrahydrofolate saturation experiments, showed the presence of an intermediate conformer with an h value of 1.7 in the temperature range of 45°-60°C. Inclusion of a heat denaturation step in the scheme employed for the purification of serine hydroxymethyltransferase resulted in the loss of cooperative interactions with tetrahydrofolate. The temperature effects on the serine hydroxylmethyltransferase, reported for the first time, lead to a better understanding of the heat induced alterations in conformation and activity for this oligomeric protein
Comparison of the conformation and stability of the native dimeric, monomeric, tetrameric and the desensitized forms of the nucleotide pyrophosphatase from Mung bean (Phaseolus aureus) seedlings
A homogenous and crystalline form of nucleotide pyrophosphatase (EC 3.6.1.9) from Phaseolus aureus (mung bean) seedlings was used for the study of the regulation of enzyme activity by adenine nucleotides. The native dimeric form of the enzyme had a helical content of about 65% which was reduced to almost zero values by the addition of AMP. In addition to this change in the helical content, AMP converted the native dimer to a tetramer. Desensitization of AMP regulation, without an alteration of the molecular weight, was achieved either by reversible denaturation with 6 M urea or by passage through a column of Blue Sepharose but additionof phydroxymercuribenzoate desensitized the enzyme by dissociating the native dimer to a monomer. The changes in the quaternary structure and conformation of the enzyme consequent to AMP interaction or desensitization were monitored by measuring the helical content, EDTA inactivation and Zn2+ reactivation, stability towards heat denaturation, profiles of urea denaturation and susceptibility towards proteolytic digestion. Based on these results and our earlier work on this enzyme, we propose a model for the regulation of the mung bean nucleotide pyrophosphatase by association-dissociation and conformational changes. The model emphasizes that multiple mechanisms are operative in the desensitization of regulatory proteins
Dynamics in Fip1 regulate eukaryotic mRNA 3<sup>′</sup> end processing
Cleavage and polyadenylation factor (CPF/CPSF) is a multiprotein complex essential for mRNA 3′ end processing in eukaryotes. It contains an endonuclease that cleaves pre-mRNAs, and a polymerase that adds a poly(A) tail onto the cleaved 3′ end. Several CPF subunits, including Fip1, contain intrinsically disordered regions (IDRs). IDRs within multiprotein complexes can be flexible, or can become ordered upon interaction with binding partners. Here, we show that yeast Fip1 anchors the poly(A) polymerase Pap1 onto CPF via an interaction with zinc finger 4 of another CPF subunit, Yth1. We also reconstitute a fully recombinant 850-kDa CPF. By incorporating selectively labeled Fip1 into recombinant CPF, we could study the dynamics of Fip1 within the megadalton complex using nuclear magnetic resonance (NMR) spectroscopy. This reveals that a Fip1 IDR that connects the Yth1- and Pap1-binding sites remains highly dynamic within CPF. Together, our data suggest that Fip1 dynamics within the 3′ end processing machinery are required to coordinate cleavage and polyadenylation.</p
Dynamics in Fip1 regulate eukaryotic mRNA 3<sup>′</sup> end processing
Cleavage and polyadenylation factor (CPF/CPSF) is a multiprotein complex essential for mRNA 3′ end processing in eukaryotes. It contains an endonuclease that cleaves pre-mRNAs, and a polymerase that adds a poly(A) tail onto the cleaved 3′ end. Several CPF subunits, including Fip1, contain intrinsically disordered regions (IDRs). IDRs within multiprotein complexes can be flexible, or can become ordered upon interaction with binding partners. Here, we show that yeast Fip1 anchors the poly(A) polymerase Pap1 onto CPF via an interaction with zinc finger 4 of another CPF subunit, Yth1. We also reconstitute a fully recombinant 850-kDa CPF. By incorporating selectively labeled Fip1 into recombinant CPF, we could study the dynamics of Fip1 within the megadalton complex using nuclear magnetic resonance (NMR) spectroscopy. This reveals that a Fip1 IDR that connects the Yth1- and Pap1-binding sites remains highly dynamic within CPF. Together, our data suggest that Fip1 dynamics within the 3′ end processing machinery are required to coordinate cleavage and polyadenylation.</p
Network algorithmics and the emergence of the cortical synaptic-weight distribution
When a neuron fires and the resulting action potential travels down its axon
toward other neurons' dendrites, the effect on each of those neurons is
mediated by the weight of the synapse that separates it from the firing neuron.
This weight, in turn, is affected by the postsynaptic neuron's response through
a mechanism that is thought to underlie important processes such as learning
and memory. Although of difficult quantification, cortical synaptic weights
have been found to obey a long-tailed unimodal distribution peaking near the
lowest values, thus confirming some of the predictive models built previously.
These models are all causally local, in the sense that they refer to the
situation in which a number of neurons all fire directly at the same
postsynaptic neuron. Consequently, they necessarily embody assumptions
regarding the generation of action potentials by the presynaptic neurons that
have little biological interpretability. In this letter we introduce a network
model of large groups of interconnected neurons and demonstrate, making none of
the assumptions that characterize the causally local models, that its long-term
behavior gives rise to a distribution of synaptic weights with the same
properties that were experimentally observed. In our model the action
potentials that create a neuron's input are, ultimately, the product of
network-wide causal chains relating what happens at a neuron to the firings of
others. Our model is then of a causally global nature and predicates the
emergence of the synaptic-weight distribution on network structure and
function. As such, it has the potential to become instrumental also in the
study of other emergent cortical phenomena
SKP2 drives the sensitivity to neddylation inhibitors and cisplatin in malignant pleural mesothelioma
Relationship of cognitive function in patients with schizophrenia in remission to disability: a cross-sectional study in an Indian sample
Background: Cognitive deficits in various domains have been consistently replicated in patients with schizophrenia. Most studies looking at the relationship between cognitive dysfunction and functional disability are from developed countries. Studies from developing countries are few. The purpose of the present study was to compare the neurocognitive function in patients with schizophrenia who were in remission with that of normal controls and to determine if there is a relationship between measures of cognition and functional disability.
<p/>Methods: This study was conducted in the Psychiatric Unit of a General Hospital in Mumbai, India. Cognitive function in 25 patients with schizophrenia in remission was compared to 25 normal controls. Remission was confirmed using the brief psychiatric rating scale (BPRS) and scale for the assessment of negative symptoms (SANS). Subjects were administered a battery of cognitive tests covering aspects of memory, executive function and attention. The results obtained were compared between the groups. Correlation analysis was used to look for relationship between illness factors, cognitive function and disability measured using the Indian disability evaluation and assessment scale.
<p/>Results: Patients with schizophrenia showed significant deficits on tests of attention, concentration, verbal and visual memory and tests of frontal lobe/executive function. They fared worse on almost all the tests administered compared to normal controls. No relationship was found between age, duration of illness, number of years of education and cognitive function. In addition, we did not find a statistically significant relationship between cognitive function and scores on the disability scale.
<p/>Conclusion: The data suggests that persistent cognitive deficits are seen in patients with schizophrenia under remission. The cognitive deficits were not associated with symptomatology and functional disability. It is possible that various factors such as employment and family support reduce disability due to schizophrenia in developing countries like India. Further studies from developing countries are required to explore the relationship between cognitive deficits, functional outcome and the role of socio-cultural variables as protective factors
Potential diagnostic and prognostic role of micro-environment in malignant pleural mesothelioma
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