Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization of wild-type and an active-site mutant in Escherichia coli of short-chain acyl-CoA dehydrogenase from Megasphaera elsdenii.

The objective of this work is to determine the molecular mechanism and regulation of short-chain acyl-CoA dehydrogenase (SCAD) from Megasphaera elsdenii. To achieve this, the gene coding for SCAD from M. elsdenii was cloned and sequenced. Site-directed mutagenesis was then used to identify an amino acid residue that is required for the proposed mechanism. To clone the gene, the amino acid sequence of the 50 N-terminal residues of SCAD from M. elsdenii was determined. This sequence information was utilized to synthesize two sets of mixed oligonucleotide primers which were then used to generate a 120-bp specific probe from M. elsdenii DNA by the polymerase chain reaction (PCR) method. The 120-bp probe was used to screen a M. elsdenii genomic DNA library cloned into Escherichia coli. The gene encoding M. elsdenii SCAD was identified from this library, sequenced, and expressed. The cloned SCAD gene contained an open reading frame which revealed a high degree of sequence identity with an open reading frame protein sequence of the human SCAD and the rat medium-chain acyl-CoA dehydrogenase (MCAD) (44% and 36% identical residues in paired comparisons for human SCAD and rat MCAD, respectively). Recombinant SCAD expressed from a pUC119 vector accounted for 35% of the cytosolic protein in the Escherichia coli crude extract. The expressed protein had similar activity, redox potential properties, and nearly identical amino acid composition to native M. elsdenii SCAD. In addition, a site-directed Glu367 Gln mutant of SCAD expressed from a pUC119 vector was shown to have minimal reductive and oxidative pathway activity with butyryl-CoA and crotonyl-CoA, respectively. (ABSTRACT TRUNCATED AT 250 WORDS)
Transshipment problem with penalty in crossdocking distribution networks

In this paper we study a new type of transshipment problem, the flows through the crossdock are constrained by fixed transportation schedules and any cargos delayed at the last moment of the time horizon of the problem will incur relative high inventory penalty cost. The problem is known to be NP-complete in the strong sense. We therefore focus on developing efficient heuristics. Based on the problem structure, we propose a Genetic Algorithm to solve the problem efficiently. Computational experiments under different scenarios show that GA outperforms CPLEX solver.
Attitudes about Genetics in Underserved, Culturally Diverse Populations

Objective: New medical discoveries regarding genetic susceptibility to common chronic diseases, and the decoding of the human genome have increased public attention to genetics. What information is understood and what attitudes exist towards genetics and genetic research have not been well examined in underserved, culturally diverse communities. Methods: To better understand attitudes and beliefs towards genetics and genetic testing in these groups, we conducted eight focus groups with 55 patients and health care workers in New York City and Westchester, N.Y. , in English, Spanish, and Chinese. Results: Focus group participants had limited understanding about genetics or genetic testing. Newborn screening was the least-known genetic issue, even among health care workers. Regardless of their cultural group, most participants expressed a desire for more information about genetics and genetic tests. Latinos and Chinese participants generally expressed positive attitudes towards genetic studies and genetic testing, with the possibility of preventing diseases cited as the main advantage. Black Americans and Non-Hispanic Whites reported mixed feelings about genetic research and genetic testing. Concerns expressed included: anxiety before receiving test results or waiting for a disease to develop, fear of genetic discrimination by health and life insurance companies and employers, not having the financial means to deal with genetic diseases in themselves or a sick child, concern that children and adults are having too many tests. Black Americans expressed the most concern for possibly harmful use of genetic information. Conclusions: Minority populations of diverse cultures have limited knowledge about genetics and genetic testing, would like to have more information, and are not well reached by the current educational approaches. Participants knew the least about newborn screening, a test that is mandatory in the New York State. While genetic knowledge by minority populations was perhaps not different from the level of knowledge of consumers in general, minority populations are at particular risk of being left behind because of historically poor access to information and services.
Localization of the lipopolysaccharide recognition complex in the human healthy and inflamed premature and adult gut

Background: Microbiota in the intestinal lumen provide an abundant source of potentially detrimental antigens, including lipopolysaccharide (LPS), a potent immunostimulatory product of Gram‐negative bacteria recognized by the host via TLR‐4 and MD‐2. An aberrant immune response to LPS or other bacterial antigens has been linked to inflammatory bowel disease (IBD) and necrotizing enterocolitis (NEC). Methods: We investigated which cells express MD‐2 in the normal and inflamed ileum from neonates and adults by immunohistochemistry. Moreover, MD‐2 and TLR4 mRNA expression in normal adult ileum was studied by reverse‐transcription polymerase chain reaction (RT‐PCR) on cells isolated by laser capture microdissection. Results: Premature infants did not show MD‐2 expression either in epithelial cells or in the lamina propria. Similarly, MD‐2 was absent in epithelial cells and lamina propria inflammatory cells in preterm infants with NEC. MD‐2 protein in the healthy term neonatal and adult ileum was predominantly expressed by Paneth cells and some resident inflammatory cells in the lamina propria. MD‐2 and TLR‐4 mRNA expression was restricted to crypt cells. Also in IBD, Paneth cells were still the sole MD‐2‐expressing epithelial cells, whereas inflammatory cells (mainly plasma cells) were responsible for the vast majority of the MD‐2 expression. Conclusions: The absence of MD‐2 in the immature neonatal gut suggests impaired LPS sensing, which could predispose neonates to NEC upon microbial colonization of the immature intestine. The apparent expression of MD‐2 by Paneth cells supports the critical concept that these cells respond to luminal bacterial products in order to maintain homeostasis with the intestinal microbiota in vivo. (Inflamm Bowel Dis 2010;)
An extremely high dose of losartan affords superior renoprotection in the remnant model.

BACKGROUND Rats subjected to 5/6 renal ablation (NX) exhibit large renal amounts of angiotensin II (Ang II) and of its main receptor, AT-1R. At previously used doses, AT-1R blockers (ARB) offer only partial renal protection. A possible explanation for this limited effect is that these doses are insufficient to block most of the abnormally expressed AT-1R. We investigated whether extremely high doses of the ARB, losartan (L), offer better protection than conventional doses in the NX model. METHODS Thirty days after NX, tail-cuff pressure (TCP), albuminuria (U(alb)V, mg/day), glomerulosclerosis index (GSI), fractional interstitial area (%INT), and macrophage infiltration (MO) were evaluated in a separate group (NX(pre)). The remaining rats were then subdivided among 4 groups: NX+V, receiving vehicle; NX+L50, treated with L, at the "conventional" dose of 50 mg/kg/day; NX+L500, receiving L, 500 mg/kg/day; and NX+HH, receiving hydrochlorothiazide and hydralazine to lower blood pressure to a similar extent as in group L500. RESULTS After a month of treatment, blood pressure and renal vascular resistance were lowest in group L500. Glomerular pressure was lowered by a similar extent by L50 and L500, while GFR was similar among groups. U(alb)V, TCP, and renal injury were only partially reduced by L50 120 days after renal ablation. By contrast, L500 arrested renal inflammation and glomerular/interstitial injury at pretreatment levels, and promoted regression of hypertension and U(alb)V, causing no apparent untoward effects. CONCLUSION The renal protection afforded by ARB in NX is dose dependent. Maximal protection may require doses several fold higher than those currently employed.
Insulinoma in Iran: a 20-year review

BACKGROUND The time between onset of symptoms of insulinoma to diagnosis ranges from 10 days to more than 20 years. To help physicians make an earlier diagnosis, we defined the clinical, imaging and paraclinical characteristics of insulinoma in cases from seven referral hospitals in Iran over two decades. METHODS The medical records of 68 cases with biochemical or histological evidences of insulinoma were reviewed. RESULTS More males were affected (53%). The mean age at diagnosis was 39±15.3 years. The mean duration of symptoms was 39.9±59.3 months. Eighty-four percent of patients had been initially misdiagnosed as cereberovascular accident (CVA), epilepsy, conversion disorder, and others). Neuroadrenergic symptoms were observed in 89.6% and and neuroglycopenic symptoms in 97% of patients. Mean diameter of tumours was 2.9 cm (range, 1 cm to 8.5 cm). Of 52 pathologically confirmed cases of insulinoma, 43 tumours (87.8%) were single and 49 (94.2%) were benign. Fifty-five patients had undergone surgery, with a successful outcome in 44 (80%). CONCLUSION The high incidence of neuroglycopenic symptoms suggest the clinical impression of insulinoma when patients present with a suggestive clinical syndrome. The clinical impression is essential to decrease the frequent delay in the diagnosis of insulinoma.
The effectiveness of brief alcohol interventions in primary care settings: a systematic review.

ISSUES Numerous studies have reported that brief interventions delivered in primary care are effective in reducing excessive drinking. However, much of this work has been criticised for being clinically unrepresentative. This review aimed to assess the effectiveness of brief interventions in primary care and determine if outcomes differ between efficacy and effectiveness trials. APPROACH A pre-specified search strategy was used to search all relevant electronic databases up to 2006. We also hand-searched the reference lists of key articles and reviews. We included randomised controlled trials (RCT) involving patients in primary care who were not seeking alcohol treatment and who received brief intervention. Two authors independently abstracted data and assessed trial quality. Random effects meta-analyses, subgroup and sensitivity analyses and meta-regression were conducted. KEY FINDINGS The primary meta-analysis included 22 RCT and evaluated outcomes in over 5800 patients. At 1 year follow up, patients receiving brief intervention had a significant reduction in alcohol consumption compared with controls [mean difference: -38 g week(-1), 95%CI (confidence interval): -54 to -23], although there was substantial heterogeneity between trials (I(2) = 57%). Subgroup analysis confirmed the benefit of brief intervention in men but not in women. Extended intervention was associated with a non-significantly increased reduction in alcohol consumption compared with brief intervention. There was no significant difference in effect sizes for efficacy and effectiveness trials. CONCLUSIONS Brief interventions can reduce alcohol consumption in men, with benefit at a year after intervention, but they are unproven in women for whom there is insufficient research data. Longer counselling has little additional effect over brief intervention. The lack of differences in outcomes between efficacy and effectiveness trials suggests that the current literature is relevant to routine primary care.
THe impact of recent regulatory reforms of the rating industry

This Thesis investigates the recent regulatory reforms applied to the credit ratings industry in Europe and the US. It analyses the impact on credit rating agencies (CRAs) and financial markets. The prior literature on CRA regulation is focused on the US markets and is limited to investigations of competition between CRAs. The impact of recently implemented regulations for CRAs in Europe has received very little academic attention and presents a highly topical research avenue. This Thesis makes several novel contributions to the literature, including (i) critical perspectives on the new regulation, especially in the EU; (ii) the impact of the solicitation status of sovereign ratings upon bank ratings; and (iii) whether European Securities Markets Authority (ESMA) rating identifiers affect the quality of ratings. Several methodologies are applied to enhance the robustness of the findings, including ordered probit analyses, fixed effects models, covariate matching (CVM) and propensity score matching (PSM). An extensive sample of rating actions by the largest CRAs (Fitch, Moody’s and S&P) during 2006 to 2014 is utilised. The critical review of the EU’s CRA regulation sheds light on several shortcomings and raises a need for reassessment. Some assumptions presented by the European Commission (EC) lack underlying evidence and are subjective in nature. Disclosures by CRAs have been inconsistent, which may reflect ambiguity in the regulations. Compliance with new regulation has affected the CRAs’ operating costs, which confirms earlier fears expressed by CRAs. Additional evidence is presented relating to CRAs’ business models. The second empirical chapter identifies that changes to the solicitation status of sovereigns induced by new disclosure rules have an adverse effect on banks domiciled in these countries. This has policy implications for regulators and banks since the ceiling effect identified in the study can lead to higher costs and harm the intermediaries. In the final empirical chapter, ESMA’s requirement for rating identifiers is questioned since it does not have any discernible impact on the quality of ratings reported by CRAs. This finding is of interest to policymakers, market participants and academics since the quality of ratings is linked to banking regulation and affects financial stability.
Impact of Dynamic 18F-FDG PET on the Early Prediction of Therapy Outcome in Patients with High-Risk Soft-Tissue Sarcomas After Neoadjuvant Chemotherapy: A Feasibility Study

Dynamic PET (dPET) studies with 18F-FDG were performed in patients with soft-tissue sarcomas who received neoadjuvant chemotherapy early in the course of therapy. The goal of the study was to evaluate the impact of early dPET studies and assess their value with regard to the therapy outcome using histopathologic data. Methods: The evaluation included 31 patients with nonmetastatic soft-tissue sarcomas, who were treated with neoadjuvant chemotherapy consisting of etoposide, ifosfamide, and doxorubicin. Patients were examined before the onset of therapy and after the completion of the second cycle. Histopathologic response served for reference and was available for 25 of 31 patients. Response was defined as less than 10% viable tumor tissue in the resected tumor tissue. The following parameters were retrieved from dPET studies: standardized uptake value (SUV); fractal dimension; 2-compartment model with computation of K1, k2, k3, and k4 (unit, 1/min); fractional blood volume; and influx according to Patlak. Results: The mean SUV was 4.6 before therapy and 2.8 after 2 cycles. The mean influx was 0.059 before therapy and 0.043 after 2 cycles. The mean SUV was 3.9 in the responders and 5.5 in the nonresponders before therapy. After therapy, responders revealed a mean SUV of 2.5, whereas nonresponders had a mean SUV of 3.5. We used linear discriminant analysis to categorize the patients into 2 groups: response (n = 12) and nonresponse (n = 13). The correct classification rate of the responders (positive predictive value) was generally higher (>67%) than that for the nonresponders. Finally, the combined use of the 2 predictor variables, namely SUV and influx, of each study led to the highest accuracy of 83%. This combination was particularly useful for the prediction of responders (positive predictive value, 92%). The use of the percentage change in maximum SUV led to an accuracy of 58%. Conclusion: On the basis of these results, only a multiparameter analysis based on kinetic 18F-FDG data of a baseline study and after 2 cycles is helpful for the early prediction of chemosensitivity in patients with soft-tissue sarcomas receiving neoadjuvant chemotherapy.
A non-linear ultrasonic scattering approach for micro bubble concentration quantification

Ultrasonic imaging of microbubble contrast agents and their concentration quantification is an ongoing problem, complicated by the lack of accurate attenuation compensation (TGC) algorithms and by the complex behaviour of microbubbles. Indeed the ultrasound contrast agents behave non linearly in the power range for medical imaging, while the biological tissues behave mainly linearly. Such quantification is required to allow the physicians to estimate the local blood perfusion in the biological tissues. But the different imaging methods developed to distinguish the agent from the surrounding tissues do not give an accurate representation of local agent concentration, which therefore has to be qualitatively estimated by the physicians. In this paper, we expand an existing automatic attenuation compensation algorithm by introducing a nonlinear relationship between insonating power and scattering when medium acoustic pressure is used (0.33 MI - 0.52 MI at 3 MHz), and model amplitude modulation (AM). An acquisition system is set up to allow acquisitions of radio frequency data from Sonovuereg suspension with a programmable ultrasound scanner and a sectorial probe. Results show that the behaviour of microbubble clouds with pressure and concentration follow the evolution expected from the assumptions formulated to be able to develop the model. In particular, the proposed equations for concentration estimation correctly predict the true concentration in the range [0-228] muL/L.
Molecular staging of colorectal cancer in African‐American and Caucasian patients using phenotypic expression of p53, Bcl‐2, MUC‐1 AND p27kip‐1

The gold standard for clinical outcome of most cancers has been the clinical and pathologic staging of the tumors after surgery. For colorectal cancer (CRC), nodal involvement at the time the primary tumor is resected has been the most reliable indicator of clinical outcome; however, recently, combinations of molecular markers have been reported to be equivalent to pathologic or clinical staging in predicting clinical outcome. In addition, molecular markers can be used in conjunction with clinical or pathologic staging to provide a stronger indicator of clinical outcome than staging alone. We propose that “molecular staging” be added to pathologic staging to aid in predicting clinical outcome and making therapeutic decisions for colorectal cancers, especially stage II and III CRCs. We have reported that the clinical usefulness of most molecular markers varies with the ethnic group of the patients and the anatomic location of CRCs; this complicates the evaluation of prognostic biomarkers and requires much larger numbers of cases to be evaluated. Nevertheless, nuclear accumulation of p53 (p53nac) and phenotypic expression of Bcl‐2, MUC‐1 and p27kip‐1 may be molecular markers approaching acceptance for use in molecular staging of specific subgroups of colorectal cancers. © 2001 Wiley‐Liss, Inc.
Radical-induced purine lesion formation is dependent on DNA helical topology

Abstract Herein we report the quantification of purine lesions arising from gamma-radiation sourced hydroxyl radicals (HO•) on tertiary dsDNA helical forms of supercoiled (SC), open circular (OC), and linear (L) conformation, along with single-stranded folded and non-folded sequences of guanine-rich DNA in selected G-quadruplex structures. We identify that DNA helical topology and folding plays major, and unexpected, roles in the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) and 8-oxo-7,8-dihydro-2'-deoxyadenosine (8-oxo-dA), along with tandem-type purine lesions 5′,8-cyclo-2′-deoxyguanosine (5′,8-cdG) and 5′,8-cyclo-2′-deoxyadenosine (5′,8-cdA). SC, OC, and L dsDNA conformers together with folded and non-folded G-quadruplexes d[TGGGGT]4 (TG4T), d[AGGG(TTAGGG)3] (Tel22), and the mutated tel24 d[TTGGG(TTAGGG)3A] (mutTel24) were exposed to HO• radicals and purine lesions were then quantified via stable isotope dilution LC-MS/MS analysis. Purine oxidation in dsDNA follows L > OC ≫ SC indicating greater damage towards the extended B-DNA topology. Conversely, G-quadruplex sequences were significantly more resistant toward purine oxidation in their unfolded states as compared with G-tetrad folded topologies; this effect is confirmed upon comparative analysis of Tel22 (∼50% solution folded) and mutTel24 (∼90% solution folded). In an effort to identify the accessibly of hydroxyl radicals to quadruplex purine nucleobases, G-quadruplex solvent cavities were then modeled at 1.33 Å with evidence suggesting that folded G-tetrads may act as potential oxidant traps to protect against chromosomal DNA damage.
Monocyte chemotactic protein-1 deficiency attenuates and high-fat diet exacerbates bone loss in mice with Lewis lung carcinoma

Bone loss occurs in obesity and cancer-associated complications including wasting. This study determined whether a high-fat diet and a deficiency in monocyte chemotactic protein-1 (MCP-1) altered bone structural defects in male C57BL/6 mice with Lewis lung carcinoma (LLC) metastases in lungs. Compared to non-tumor-bearing mice, LLC reduced bone volume fraction, connectivity density, trabecular number, trabecular thickness and bone mineral density and increased trabecular separation in femurs. Similar changes occurred in vertebrae. The high-fat diet compared to the AIN93G diet exacerbated LLC-induced detrimental structural changes; the exacerbation was greater in femurs than in vertebrae. Mice deficient in MCP-1 compared to wild-type mice exhibited increases in bone volume fraction, connectivity density, trabecular number and decreases in trabecular separation in both femurs and vertebrae, and increases in trabecular thickness and bone mineral density and a decrease in structure model index in vertebrae. Lewis lung carcinoma significantly decreased osteocalcin but increased tartrate-resistant acid phosphatase 5b (TRAP 5b) in plasma. In LLC-bearing mice, the high-fat diet increased and MCP-1 deficiency decreased plasma TRAP 5b; neither the high-fat diet nor MCP-1 deficiency resulted in significant changes in plasma concentration of osteocalcin. In conclusion, pulmonary metastasis of LLC is accompanied by detrimental bone structural changes; MCP-1 deficiency attenuates and high-fat diet exacerbates the metastasis-associated bone wasting.
Effect of interface charges on the efficiency of perovskite based solar cells

In spite of the excellent reported efficiencies, perovskite based solar cells are still plagued by concerns related to stability and hysteresis. While the major physical phenomena related to carrier generation and transport are fairly well understood through theoretical models and simulations, the crucial role of interfaces is not well explored in the community. In this manuscript we show, through detailed numerical simulations, that interface charges significantly affect the electrostatics of the device under illumination thus leading to sub-optimal performance, especially the fill factor. Indeed, this work highlights the need for proper interface passivation and provides a predictive framework towards exploring the effect of interface charges on the eventual device stability and performance degradation.