Miracle-dz/UniFAR-FTUs huggingface dataset:
A novel RNA binding protein that interacts with NMDA R1 mRNA: regulation by ethanol

Excitatory NMDA receptors are an important target of ethanol. Chronic ethanol exposure, in vivo and in vitro, increases polypeptide levels of NR1 subunit, the key subunit of functional NMDA receptors. In vitro, chronic ethanol treatment increases the half‐life of NR1 mRNA and this observation is dependent on new protein synthesis. The present study was undertaken to locate cis‐acting region(s) within the NR1 3′‐untranslated region (UTR) and identify NR1 3′‐UTR binding trans‐acting proteins expressed in mouse fetal cortical neurons. Utilizing RNA gel shift assays we identified a 156‐nt cis‐acting region that binds to polysomal trans‐acting proteins. This binding was highly specific as inclusion of cyclophilin RNA or tRNA did not interfere with cis–trans interactions. Importantly, the 3′‐UTR binding activity was significantly up‐regulated in the presence of ethanol. UV cross‐link analysis detected three NR1 3′‐UTR binding proteins and their molecular mass calculated by Northwestern analysis was ∼88, 60 and 47 kDa, respectively. Northwestern analysis showed a significant up‐regulation of the 88‐kDa protein after chronic ethanol treatment. The 88‐kDa protein was purified and identified by tandem mass spectrometry as the beta subunit of alpha glucosidase II (GIIβ). That GIIβ is indeed a trans‐acting protein and binds specifically to 3′‐UTR of NR1 mRNA was confirmed by RNA gel mobility supershift assays and immuno RT‐PCR. Western blotting data established a significant increase of GIIβ polypeptide in chronic ethanol‐exposed fetal cortical neurons. We hypothesize that the identified cis‐acting region and the associated RNA‐binding proteins are important regulators of NR1 subunit gene expression.
Incidence of Salmonella spp., Clostridium botulinum, and Vibrio parahaemolyticus in an estuary

A study of the incidence of Salmonella spp. , Vibrio parahaemolyticus-like organisms, and clostridium botulinum in samples collected at five stations located in the Upper Chesapeake Bay, a major estuary on the Atlantic Coast of the United States, was conducted in December 1973 through December 1974. C. botulinum types B and E were detected in 12.3% of the total sediment samples examined. V. parahaemolyticus was recovered from 10.4% of a total of 86 water, sediment, and suspended sediment samples. Of 131 samples examined for the presence of Salmonella spp. , approximately 3% were found to be positive for serologically confirmed Salmonella isolates. Shellfish examined during the investigation were also found to be free of enteric pathogens. The low frequency of occurrence of V. parahaemolyticus was attributed to the low salinities encountered at the sites included in the study. A low incidence of Salmonella spp. in the Upper Chesapeake Bay samples was found, whereas the distribution of C. botulinum appeared to be both random and autochthonous. A strong relationship between presence of potential pathogens and other generally accepted microbiological indicators of pollution was not observed.
Habitual use of the primate forelimb is reflected in the material properties of subchondral bone in the distal radius

Bone mineral density is directly proportional to compressive strength, which affords an opportunity to estimate in vivo joint load history from the subchondral cortical plate of articular surfaces in isolated skeletal elements. Subchondral bone experiencing greater compressive loads should be of relatively greater density than subchondral bone experiencing less compressive loading. Distribution of the densest areas, either concentrated or diffuse, also may be influenced by the extent of habitual compressive loading. We evaluated subchondral bone in the distal radius of several primates whose locomotion could be characterized in one of three general ways (quadrupedal, suspensory or bipedal), each exemplifying a different manner of habitual forelimb loading (i.e. compression, tension or non‐weight‐bearing, respectively). We employed computed tomography osteoabsorptiometry (CT‐OAM) to acquire optical densities from which false‐colour maps were constructed. The false‐colour maps were used to evaluate patterns in subchondral density (i.e. apparent density). Suspensory apes and bipedal humans had both smaller percentage areas and less well‐defined concentrations of regions of high apparent density relative to quadrupedal primates. Quadrupedal primates exhibited a positive allometric effect of articular surface size on high‐density area, whereas suspensory primates exhibited an isometric effect and bipedal humans exhibited no significant relationship between the two. A significant difference between groups characterized by predominantly compressive forelimb loading regimes vs. tensile or non‐weight‐bearing regimes indicates that subchondral apparent density in the distal radial articular surface distinguishes modes of habitually supporting of body mass.
Echo-enhanced transcranial color-coded duplex sonography in the diagnosis of cerebrovascular events: a validation study.

BACKGROUND AND PURPOSE Transcranial color-coded duplex sonography (TCCD) is a diagnostic technique for evaluation of intracranial arteries in patients with acute stroke. Echo-enhancing contrast agents (EEAs) are necessary to visualize intracranial vessels in up to 30% of patients because of limited acoustic bone windows. In this study, we assessed the diagnostic efficacy of echo-enhanced TCCD (eTCCD) in correlation with the gold standard, digital subtraction angiography (DSA). METHODS We prospectively evaluated all patients with eTCCD who subsequently underwent DSA for evaluation of cerebrovascular symptoms over a 24-month period. We administered Levovist as an EEA. Two blinded reviewers analyzed all eTCCD findings and correlated them with DSA. RESULTS We included 132 consecutive patients (40 women, 92 men; mean age, 58 +/- 14 years) with 164 datasets: 24/164 had normal findings, 98/164 had abnormalities of extracranial carotid arteries, 32/164 had abnormalities of intracranial arteries, and 21/164 had abnormalities in vertebrobasilar circulation as determined by DSA. For eTCCD, we found a sensitivity of 82% (95% confidence interval [CI]: 75%-90%), a specificity of 98% (95% CI: 90%-100%), a positive predictive value of 99% (95% CI: 94%-100%), and a negative predictive value of 75% (95% CI: 64%-85%); 7/164 (4%) examinations were inconclusive because of insufficient bone windows. The interobserver agreement was almost perfect (kappa value, 0.92; 95% CI: 0.87-0.97). CONCLUSION eTCCD provides high diagnostic validity for the status of the major intracranial arteries. In particular, a normal vessel status reliably assessed by an experienced sonographer could supersede further imaging procedures. In patients with acute ischemic stroke not eligible for established angiographic techniques, eTCCD may be useful as an alternative imaging technique.
Gestational diabetes mellitus--Indian guidelines.

Pregnancy induces progressive changes in maternal carbohydrate metabolism. As pregnancy advances insulin resistance and diabetogenic stress due to placental hormones necessitate compensatory increase in insulin secretion. When this compensation is inadequate gestational diabetes develops. ‘Gestational Diabetes Mellitus’ [GDM] is defined as carbohydrate intolerance with onset or recognition during pregnancy. Women diagnosed to have GDM are at increased risk of future diabetes predominantly type 2 DM as are their children [1]. Thus GDM offers an important opportunity for the development, testing and implementation of clinical strategies for diabetes prevention [2]. Timely action taken now in screening all pregnant women for glucose intolerance, achieving euglycemia in them and ensuring adequate nutrition may prevent in all probability, the vicious cycle of transmitting glucose intolerance from one generation to another [3].
Characterization of neurons responsive to noxious colorectal distension in the T13-L2 spinal cord of the rat.

1. One-hundred thirty-two neurons responsive to colorectal distension in the dorsal horn of the T13-L2 spinal segments of 35 spinalized and 7 intact, deeply pentobarbital-sodium-anesthetized rats were characterized for convergent cutaneous receptive fields, long ascending projections and responses to the intra-arterial administration of the algesic peptide bradykinin. All but 9 neurons had an identifiable excitatory cutaneous receptive field; all receptive fields were located on the lower abdomen, flank, and dorsal body surface. Electrical stimulation in the cutaneous fields of 28 neurons demonstrated that neurons responsive to colorectal distension receive afferent information carried by A- and C-fibers. Stimulus-response functions (SRFs) of 52 neurons excited by graded colorectal distension (20-100 mmHg, 20 s) were monotonic and accelerating, allowing extrapolation of threshold distending pressures to neuronal response. Neurons were subdivided into four classes based upon their response to an 80-mmHg, 20-s colorectal distension search stimulus. 2. Short-latency abrupt [SL-A] neurons (spinalized, n = 46; intact, n = 9) were excited at short latency; activity abruptly returned to base line on termination of distension. Six of 9 neurons in intact rats had long ascending projections as demonstrated by antidromic invasion from the contralateral, ventrolateral caudal medulla. Responses of SL-A neurons to colorectal distension were significantly greater in spinalized than in intact rats. Fifty-three of 55 SL-A neurons had convergent excitatory cutaneous receptive fields and most were responsive to both noxious and nonnoxious stimuli. Ten of 13 neurons tested were excited by intra-arterial bradykinin. The threshold distending pressure, determined from the SRFs of 29 neurons in both the spinalized and intact states, extrapolated to near 0 mmHg. 3. Short-latency sustained (SL-S) neurons (spinalized, n = 31; intact, n = 11) were also excited at short latency in response to colorectal distension, but responses were sustained for 4-50 s following termination of the distending stimulus. Nine of 11 SL-S neurons in intact rats had long ascending projections. All 42 SL-S neurons were spontaneously active and 41 of 42 had convergent excitatory cutaneous receptive fields, excited exclusively by noxious stimuli (n = 29) or excited by both noxious and nonnoxious stimuli (n = 12). Responses to colorectal distension and spontaneous activity were significantly greater in spinalized rats. Twelve of 12 neurons tested were excited by intra-arterial bradykinin. (ABSTRACT TRUNCATED AT 400 WORDS)
The Relationship between Pretend Play and False-Belief in 18-Month-Old Children

This experimental study examined the relationship between pretend play and false-belief. Eighteen-month-old children engaged in pretend play with an experimenter using various controlled behaviors and performed a false-belief task. The results showed that the children who understood pretend play performed better on the false-belief task. This suggests that pretended play and false-belief are related at the age of 18 months. Keywords—18-month-old, pretend play, false-belief task.
Project CARE: a randomized controlled trial of a behavioral intervention group for Alzheimer's disease caregivers.

PURPOSE The neuropsychiatric symptoms associated with Alzheimer's disease are a major contributor to caregiver distress and burden. Despite recent efforts to teach caregivers skills to manage neuropsychiatric symptoms and reduce burden, there continues to be limited evidence that these strategies have helped caregivers of individuals with Alzheimer's disease to effectively manage neuropsychiatric symptoms. We report here on Project CARE, a randomized controlled trial designed to test the effectiveness of a caregiver-based multicomponent behavioral intervention aimed to reduce caregiver distress related to neuropsychiatric symptoms, as well as general caregiver burden, and to decrease neuropsychiatric symptom severity among individuals with Alzheimer's disease. DESIGN AND METHODS The behavioral intervention involved five weekly sessions designed to teach caregivers specific techniques for managing patient neuropsychiatric symptoms in the home environment. Through the use of a randomized control trial, 80 caregivers were assigned to either the behavioral intervention group or a psychoeducational control group and were assessed both before and after the intervention. RESULTS Compared with caregivers in the control group, caregivers in the behavioral intervention group displayed significantly greater reductions in caregiver distress related to neuropsychiatric symptoms (p=.005). Global caregiver burden, however, did not decrease significantly for caregivers in either group (p>.05). Although it was not statistically significant, there was a trend toward greater reductions in care recipients' neuropsychiatric symptom severity in the intervention group (p=.10). IMPLICATIONS The current findings suggest that targeted, group-based behavioral interventions are effective for reducing distress related to neuropsychiatric symptoms among caregivers of individuals with Alzheimer's disease and for reducing care recipients' neuropsychiatric symptoms.
Ameliorating effect of S-2(ω-aminoalkylamino) alkylaryl sulfide (DRDE-07) on sulfur mustard analogue, 2-chloroethyl ethyl sulfide-induced oxidative stress and inflammation

Abstract Sulfur mustard (SM; 2,2′-dichloro diethyl sulfide), an alkylating chemical warfare agent, poses a major threat in both military conflict and chemical terrorism situations. 2-chloroethyl ethyl sulfide (CEES) is a monofunctional analogue of SM, frequently used in laboratory settings, therefore increasing chances of its exposure. S-2(ω-aminoalkylamino) alkylaryl sulfide (DRDE-07) is an analogue of amifostine reported to have protective effects against SM but its effect on CEES is largely unexplored. Therefore, this study was planned to explore the effects of DRDE-07 against CEES-induced toxicity. 0.75 LD50 (1068 mg/kg) of CEES was exposed percutaneously in the presence or absence of DRDE-07 (249 mg/kg p.o.) which is given prophylactically (before 30 minute) to male mice. Animals were sacrificed on 24 h, 7th day and 14th day of CEES exposure, and tissues were collected to study oxidative stress and inflammatory markers. CEES exposure depleted intracellular GSH level and activities of GSH-linked enzymes (GR, GPx and GST) which play a major role in GSH metabolism. CEES exposure augmented lipid peroxidation indicating severe oxidative stress. It also initiated inflammation causing an increase in proinflammatory (IL1-α, IL1-β, IL-6, TNF-α and IFN-ϒ) and corresponding decrease in anti-inflammatory cytokines (IL-4 and IL-10). This was also accompanied by neutrophils infiltration indicated by higher than normal myeloperoxidase (MPO) levels. DRDE-07 efficiently reduced the oxidative stress and also facilitated to resolve inflammatory alterations. This study thus evaluated the beneficial role of DRDE-07 in ameliorating the deleterious effects of CEES and can be potentially used against SM/CEES poisoning.
U.S High School Graduation Rates: Patterns and Explanations

I survey the evidence on patterns in U.S. high school graduation rates over the period 1970-2010 and report the results of new research conducted to fill in holes in the evidence. I begin by pointing out the strengths and limitations of existing data sources. I then describe six striking patterns in graduation rates. They include stagnation over the last three decades of the twentieth century, significant race-, income-, and gender-based gaps, and significant increases in graduation rates over the first decade of the twenty-first century, especially among blacks and Hispanics. I then describe the models economists use to explain the decisions of individuals to invest in schooling, and examine the extent to which the parameters of the models explain recent patterns in graduation rates. I find that increases in the nonmonetary costs of completing high school and the increasing availability of the GED credential help to explain stagnation in the face of substantial gaps between the wages of high school graduates and school dropouts. I point out that there are several hypotheses, but to date, very little evidence to explain the increases in high school graduation rates over the first decade of the twenty-first century. I conclude by reviewing the evidence on effective strategies to increase high school graduation rates, and explaining why the causal evidence is quite modest.
Poor Recovery and Short Survival of Infused Factor X in a Case of Acquired Factor X Deficiency and Amyloidosis

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A Role for RNAi in the Selective Correction of DNA Methylation Defects

DNA methylation is essential for silencing transposable elements and some genes in higher eukaryotes, which suggests that this modification must be tightly controlled. However, accidental changes in DNA methylation can be transmitted through mitosis (as in cancer) or meiosis, leading to epiallelic variation. We demonstrated the existence of an efficient mechanism that protects against transgenerational loss of DNA methylation in Arabidopsis. Remethylation is specific to the subset of heavily methylated repeats that are targeted by the RNA interference (RNAi) machinery. This process does not spread into flanking regions, is usually progressive over several generations, and faithfully restores wild-type methylation over target sequences in an RNAi-dependent manner. Our findings suggest an important role for RNAi in protecting genomes against long-term epigenetic defects.
Immune complexes and the complement factors C4 and C3 in cerebrospinal fluid and serum from patients with chronic progressive multiple sclerosis

ABSTRACT— Immune complexes (IC) have been found in both serum and cerebrospinal fluid (CSF) in multiple sclerosis (MS). The complement system is known to play a major role as a mediator of inflammation in immune complex disease. Therefore, we have investigated paired samples of serum and CSF from 32 patients with progressive MS for IC, the levels of the complement factors C4 and C3, and presence of their activation products (AP). IC was found in serum from 17 of the 32 MS patients (53%) and in CSF from 9 of 31 MS patients (29%). No correlation was found between the occurrence of IC in serum and in CSF. The levels of C3 in serum and CSF from the MS patients did not differ from the levels in a control group, whereas the levels of C4 in MS‐serum were elevated and the C4 levels in MS‐CSF reduced. A low level of CSF‐C4 correlated significantly to the occurrence of CSF‐IC. AP of C4 and C3 in serum were seen in 11 of the 32 patients (34%), appearing significantly more frequently among patients with circulating IC. No C4‐or C3AP could be identified in CSF.
Finite Size Effects in Highly Scaled Ruthenium Interconnects

Ru has been considered a candidate to replace Cu-based interconnects in VLSI circuits. Here, a methodology is proposed to predict the resistivity of (Ru) interconnects. First, the dependence of the Ru thin film resistivity on the film thickness is modeled by the semiclassical Mayadas-Shatzkes (MS) approach. The fitting parameters thus obtained are then used as input in a modified MS model for nanowires to calculate wire resistivities. Predicted experimental resistivities agreed within about 10%. The results further indicate that grain boundary scattering was the dominant scattering mechanism in scaled Ru interconnects.
Ustekinumab use in Crohn’s disease: a Canadian tertiary care centre experience

Abstract Objectives: Real world data regarding clinical response to ustekinumab in Crohn’s disease is lacking. We report our experience of ustekinumab use using a novel subcutaneous (SC) induction strategy and aim to identify predictors of response. Materials and Methods: A retrospective, observational study of compassionate ustekinumab use in Crohn’s disease was conducted with the use of a standard or high dose SC induction protocol. Symptomatic response was assessed after 3 months (short-term), and if remaining on therapy, within 3–12 months (medium-term) and at least 12 months (long-term). Endoscopic or radiologic response was assessed when available. Survival analysis of time to failure (cessation of ustekinumab) and multivariate logistic regression to identify predictors of response were performed. Results: Seventy-nine patients commenced ustekinumab, with six patients lost to follow-up and five asymptomatic at baseline. Symptomatic response was assessed in 68 patients; 56% (38) of patients had a short-term symptomatic response. Type of preceding anti-TNF response was the only significant predictor of short-term response, with primary non-response being a strong predictor. In the medium-term, symptomatic response occurred in 72% (30/42) of patients and endoscopic or radiologic response was achieved in 72% (26/36) of patients assessed. The median time to failure was 22 months. Maintenance dose escalation to 90 mg every 4 weeks was successful in three of 16 patients. Conclusions: Fifty-six percent of patients had short-term symptomatic response, with a history of primary non-response to prior anti-TNF therapy being a predictor of response. Dose escalation had only modest benefit.