Miracle-dz/UniFAR-FTUs huggingface dataset:
Enzymatic synthesis of deoxyribonucleic acid. VIII. Frequencies of nearest neighbor base sequences in deoxyribonucleic acid.

Determination of deoxyribonucleotide sequence in a deoxyribonucleic acid molecule is important from both the chemical and genetic points of view. It is also essential for answering the question of whether DNA synthesized in vitro by polymerase (1, 2) is a faithful copy of the nucleotidel sequence of the primer DNA. Although enzymatically synthesized DNA has the same over-all nucleotide composition as the particular primer DNA (3), it could not be inferred that this synthesis is a replication of the nucleotide sequences of the primer. Because of the limitations of present methods, complete sequence studies have never been made. Sinsheimer (4) has been able to identify 16 of the 25 possible dinucleotide pairs resulting from enzymatic digestion of calf thymus DNA. From recent analyses of various DNA’s by Shapiro and Chargaff (5) and by Burton and Peterson (6), there is now information on the frequency of occurrence of a pyrimidine nucleotide flanked on both sides by purine nucleotides and on the frequencies of short runs of pyrimidine nucleotides in the polynucleotide chains. These workers were able to deduce that there is a nonrandom arrangement of pyrimidine nucleotides in all of the DNA’s examined. In the studies to be reported here, we have derived the frequencies of the 16 possible nearest neighbor pairs in a variety of DNA’s by the technique of enzymatic incorporation of 5’-Pazlabeled nucleotides into DNA and then degradation of the DNA into 3’-nucleotides. Briefly, we have found that: (a) each DNA directs the synthesis of a product which has a unique and nonrandom pattern of the 16 nearest neighbor frequencies; (b) the DNA synthesized has the same nearest neighbor frequencies whether the primer is native DNA or enzymatically prepared DNA containing only traces of the original native DNA; and (c) the pattern of nearest neighbor frequencies in every case involves both base-pairing of adenine to thymine and of guanine to cytosine between sister strands of DNA, and opposite “polarity” of the two strands as proposed in the Watson and Crick model (7).
Immune protection mediated by the probiotic Lactobacillus rhamnosus HN001 (DR20) against Escherichia coli O157:H7 infection in mice.

This study investigated the protective effects of feeding the immunoenhancing probiotic Lactobacillus rhamnosus HN001 against Escherichia coli O157:H7 infection in murine (BALB/c and C57BL/6 mice) challenge infection models. Mice were fed milk-based diets supplemented with L. rhamnosus HN001 (3 x 10(8) cfu g(-1)) for 7 days prior to and following oral challenge with E. coli O157:H7. Morbidity and feed intake were measured for 1 week following challenge; pathogen translocation to spleen, liver and blood, and humoral and cellular immunological responses (specific antibody and phagocytosis) were measured in a sub-sample of ostensibly healthy animals 1 week post-challenge. Results showed that, after challenge, L. rhamnosus HN001-fed mice exhibited lower cumulative morbidity and bacterial translocation rates, compared to non-probiotic-fed control mice. Significantly higher intestinal anti-E. coli IgA responses and blood leucocyte phagocytic activity were recorded among probiotic-fed mice compared to controls. These results demonstrate that feeding the probiotic L. rhamnosus HN001 to mice can reduce the severity of E. coli O157:H7 infection, and suggest that this reduction may be associated with enhanced humoral and cellular immune responses.
Ear Recognition With Score-Level Fusion Based On CMC In Long-Wave Infrared Spectrum

Only a few studies have been reported regarding human ear recognition in long wave infrared band. Thus, we have created ear database based on long wave infrared band. We have called that the database is long wave infrared band MIDAS consisting of 2430 records of 81 subjects. Thermal band provides seamless operation both night and day, robust against spoofing with understanding live ear and invariant to illumination conditions for human ear recognition. We have proposed to use different algorithms to reveal the distinctive features. Then, we have reduced the number of dimensions using subspace methods. Finally, the dimension of data is reduced in accordance with the classifier methods. After this, the decision is determined by the best sores or combining some of the best scores with matching fusion. The results have showed that the fusion technique was successful. We have reached 97.71% for rank-1 with 567 test probes. Furthermore, we have defined the perfect rank which is rank number when recognition rate reaches 100% in cumulative matching curve. This evaluation is important for especially forensics, for example corpse identification, criminal investigation etc.
Use of gene therapy in central nervous system repair

Recent advances have increased our molecular understanding of the central nervous system (CNS), in both health and disease. In order to realize the clinical benefits of these findings, new molecular‐based therapies need to be developed, such as CNS gene therapy. Although the field has suffered setbacks, it remains an attractive technology for providing new therapies in the post‐genomic world. The development of new vectors, and their extensive application in animal models of CNS disease, provides evidence suggesting that gene therapy will eventually become an accepted clinical option. In fact, the first gene therapy clinical trial for Parkinson's disease has recently begun. This review discusses how gene therapy has been applied in animal models, and how it may be used to repair the damage caused by CNS diseases and trauma in human beings. Furthermore, it explores how such treatments may be combined with, and augment, more conventional therapeutic approaches.
Fotemustine compared with dacarbazine in patients with disseminated malignant melanoma: a phase III study.

PURPOSE To compare fotemustine and dacarbazine (DTIC) in terms of overall response rate (ORR) as primary end-point and overall survival, duration of responses, time to progression, time to occurrence of brain metastases (BM), and to assess safety and quality of life in patients with disseminated cutaneous melanoma. PATIENTS AND METHODS Patients received either intravenous fotemustine 100 mg/m2 weekly for 3 weeks or DTIC 250 mg/m2/d for 5 consecutive days every 4 weeks (two cycles). Nonprogressive patients received a maintenance treatment every 4 weeks (fotemustine 100 mg/m2 or DTIC 250 mg/m2 for 5 days). RESULTS Two hundred twenty-nine patients were randomly assigned to fotemustine or DTIC arms. The best ORR was higher in the fotemustine arm than in the DTIC arm in the intent-to-treat population (n=229; 15.2% v 6.8%; P=.043) and in full analysis set (n=221) (15.5% v 7.2%; P=.053). Similar median durations of responses (5.8 months with fotemustine v 6.9 months with DTIC) and time to progression (1.8 v 1.9 months, respectively) were observed. In patients without BM at inclusion, the median time to BM was 22.7 months with fotemustine versus 7.2 months with DTIC (P=.059). Median survival was 7.3 months with fotemustine versus 5.6 months with DTIC (P=.067). The main toxicity was grade 3 to 4 neutropenia (51% with fotemustine v 5% with DTIC) and thrombocytopenia (43% v 6%, respectively). No significant difference was noted for quality of life between arms. CONCLUSION ORR was higher in the fotemustine arm compared to the DTIC arm in first-line treatment of disseminated melanoma. A trend in favor of fotemustine in terms of overall survival and time to BM was evidenced.
The Role of Generic Health‐Related Quality of Life Measures in Establishing Audiological Rehabilitation Outcomes

Objective: To review the status of generic functional health measures used with hearing‐impaired adults and to summarize the findings of studies that have utilized these outcome measures to assess the benefit of amplification. Design: Four basic generic quality of life measures used with the hearing‐impaired population for determining hearing aid benefit are reviewed and discussed. The measures include the Sickness Impact Profile, the Self Evaluation of Life Function, the Medical Outcomes Study, and the Dartmouth COOP Functional Health Assessment Charts. Results: The review of studies concerned with quality of life measures revealed that present day functional health status tools lack the necessary sensitivity to detect clinically meaningful improvements in patients with hearing impairment. Conclusions: Although we have good reason to believe that hearing aids improve quality of life, available functional health status measures lack the appropriate sensitivity to be used for assessing the benefit of amplification in individuals with hearing impairment. There is an urgent need for additional research to address this important area.
Evaluation of serum sIgE / total IgE ratio in predicting clinical response to allergen-specific immunotherapy

Background: To date, no predictive tests for the clinical response to allergen-specific immunotherapy (ASI) are available. Therefore an in vivo or in vitro test would be of great value. Objective: We sought to evaluate pretreatment parameters used in diagnosing allergic rhinitis and determining serum specific IgE (s-IgE) levels, serum total IgE (t-IgE) levels, and blood eosinophil counts and to identify whether can be used to predict clinical improvement in monosensitized patients with allergic rhinitis with or without asthma treated with immunotherapy. Methods: We analyzed 279 patients who had undergone 4 years of ASI administered either by means of the subcutaneous immunotherapy (76 patients) or sublingual immunotherapy (203 patients) routes. Serum t-IgE and s-IgE levels, blood eosinophil counts, and serum s-IgE/t-IgE ratios were calculated and tested for correlation with clinical response to ASI. Receiver operating characteristic curves were determined. Predicted probabilities and predictive areas under the curve were calculated. Results: The clinical response to ASI was effective in 145 (52.0%) of 279 total patients, 42 (55.2%) of 76 patients treated with subcutaneous immunotherapy, and 103 (50.7%) of 203 patients treated with sublingual immunotherapy. A significant correlation was found between the serum s-IgE/t-IgE ratio and the clinical response to ASI, with high ratios (>16.2) associated with an effective response. The sensitivity and specificity of the area under the curve of the ratio were higher than those of serum s-IgE and t-IgE alone. Conclusion: The calculation of the serum s-IgE/t-IgE ratio for predicting the clinical response to ASI offers an advantage over measuring t-IgE and s-IgE levels in monosensitized patients for the following allergens: grass, Parietaria judaica,
Local production of the alternative pathway component factor B is sufficient to promote laser-induced choroidal neovascularization.

PURPOSE Complement factor B (CFB) is a required component of the alternative pathway (AP) of complement, and CFB polymorphisms are associated with age-related macular degeneration (AMD) risk. Complement factor B is made in the liver, but expression has also been detected in retina and retinal pigment epithelium (RPE)-choroid. We investigated whether production of CFB by the RPE can promote AP activation in mouse choroidal neovascularization (CNV). METHODS Transgenic mice expressing CFB under the RPE65 promoter were generated and crossed onto factor B-deficient (CFB-KO) mice. Biological activity was determined in vitro using RPE monolayers and in vivo using laser-induced CNV. Contribution of systemic CFB was investigated using CFB-KO reconstituted with CFB-sufficient serum. RESULTS Transgenic mice (CFB-tg) expressed CFB in RPE-choroid; no CFB was detected in serum. Cultured CFB-tg RPE monolayers secreted CFB apically and basally upon exposure to oxidative stress that was biologically active. Choroidal neovascularization sizes were comparable between wild-type and CFB-tg mice, but significantly increased when compared to lesions in CFB-KO mice. Injections of CFB-sufficient serum into CFB-KO mice resulted in partial reconstitution of systemic AP activity and significantly increased CNV size. CONCLUSIONS Mouse RPE cells express and secrete CFB sufficient to promote RPE damage and CNV. This further supports that local complement production may regulate disease processes; however, the reconstitution experiments suggest that additional components may be sequestered from the bloodstream. Understanding the process of ocular complement production and regulation will further our understanding of the AMD disease process and the requirements of a complement-based therapeutic.
The many facets of PPAR : novel insights for the skeleton

Kawai M, Sousa KM, MacDougald OA, Rosen CJ. The many facets of PPAR : novel insights for the skeleton. Am J Physiol Endocrinol Metab 299: E3–E9, 2010. First published April 20, 2010; doi:10.1152/ajpendo.00157. 2010. —Peroxisome proliferator-activated receptor(PPAR ) is a nuclear receptor that functions as a master transcriptional regulator of adipocyte conversion. During PPAR transactivation, multiple signaling pathways interact with one another, leading to the differentiation of both white and brown adipose tissue. Ligand activation of the PPAR -RXR heterodimer complex also enhances insulin sensitivity, and this property has been heavily exploited to develop effective pharmacotherapies for the treatment of type 2 diabetes mellitus. PPAR is also expressed in stem cells and plays a critical role in mesenchymal stromal cell differentiation and lineage determination events. The many facets of PPAR activity within the bone marrow niche where adipocytes, osteoblasts, and hematopoietic cells reside make this molecule an attractive target for pharmacological investigation. Additional findings that osteoblasts can alter energy metabolism by influencing adiposity and insulin sensitivity, and observations of decreased bone turnover in diabetic subjects, underscore the contribution of the skeleton to systemic energy requirements. Studies into the role of PPAR in skeletal acquisition and maintenance may lead to a better understanding of the molecular mechanisms governing stromal cell differentiation in the mesenchyme compartment and whether PPAR activity can be manipulated to benefit skeletal remodeling events and energy metabolism.
The long-term effects of maternal obesity during pregnancy on the health of the offspring A systematic review

Objective: To evaluate whether there is an effect of maternal obesity during pregnancy on the long-term health of the child. Methods: The database PubMed was searched in January 2014 to identify relevant studies in English. Studies that focused on maternal obesity and the impact on the health of the offspring were included. Results: Six studies were included in this review. Two studies reported a higher risk of developing asthma, one a higher risk of developing metabolic syndrome and one a higher risk of developing attention deficit hyperactivity disorder (ADHD). The two remaining studies found higher inflammation markers and a higher risk of all-cause mortality and hospital admission after a cardiovascular event. Conclusions: These data show that offspring have a greater risk in developing asthma, metabolic syndrome, ADHD and higher levels of hs-CRP later in life. Also, the all-cause mortality is higher in the offspring when the mother was obese during pregnancy. Maternal obesity therefore does appear to have an effect on the health of the offspring. Hence, it is of great importance to prevent exposure of offspring to preconceptional maternal obesity and from the early embryonic period onwards. For this reason, lifestyle modification is of great importance for obese women with a wish to conceive.
Mucoid impaction of the bronchi in cystic fibrosis.

Mucoid impaction of the bronchi (MIB) is an unusual complication of adult asthma. In a review of 675 serial chest radiographs of 68 children and 2 adults with cystic fibrosis (CF), opacifications consistent with the diagnosis of MIB have been noted in 22 children and 1 adult, an overall incidence of 33%. The lesion of MIB in CF is a bronchusrelated complex of branched finger-like or nodular densities due to progressive distention of bronchi with tenacious mucopus. It is most commonly observed in the right upper lobe. Although it may spontaneously disappear, it tends to recur. Persistence of MIB for periods longer than 1 month can be related to subsequent bronchiectasis in the same segment. Clinical diagnosis is totally dependent on radiographic recognition, since symptoms and signs are characteristically lacking or non-specific. Atelectasis does not occur, probably because of collateral ventilation from adjacent uninvolved lung. Certain apparent differences have been noted between the adult (asthma) and childhood (CF) forms of MIB. Planigraphic and bronchographic studies in selected patients confirm the intrabronchial location of this process. Bronchial lavage is effective in washing out some impactions that have not responded to more conventional mucolytic and physical therapy. Recognition of MIB in a roentgenogram of a child should be considered presumptive evidence of CF, since similar opacifications are very rarely seen in children with other diseases. We believe that (1) progressive MIB at a subsegmental level is the major cause of bronchiectasis in CF and (2) secondary collateral ventilation may be the major cause of obstructive overinflation of the lungs in CF.
Exenatide therapy in insulin-treated type 2 diabetes and obesity.

BACKGROUND Exenatide, a GLP-1 analogue, is used in combination with oral anti-diabetic agents in type 2 diabetes and obesity, and promotes weight loss. Exenatide use in combination with insulin in insulin-treated type 2 diabetes and obesity is unlicensed in the UK and outcomes are unclear. AIMS To assess the effectiveness of exenatide in insulin-treated type 2 diabetes with obesity. DESIGN AND METHODS This prospective study included 174 consecutive patients with insulin-treated type 2 diabetes and obesity initiated on exenatide in our out-patient, between October 2007 and November 2008. Weight, BMI, HbA1c, serum fructosamine, total cholesterol, HDL-cholesterol and insulin doses were recorded at baseline, 3, 6 and 12 months. Side effect profiles were recorded. RESULTS Fourteen patients discontinued exenatide before 3 months of initiation, because of side effects, and were excluded. Data were analysed on remaining 160 people all of whom completed 6 months and 57 completed 12 months treatment. Mean weight loss was 10.7 +/- 5.7 kg and 12.8 +/- 7.5 kg (P < 0.001) at 6 and 12 months. Insulin doses dropped significantly (mean 144 +/- 90 U/day at baseline to 51 +/- 55 U/day and 55 +/- 53 U/day at 6 and 12 months). At 3 months, 25% came off insulin. There was little change in HbA1c. CONCLUSION Exenatide therapy in insulin-treated type 2 diabetes and obesity was associated with very significant reductions in weight and insulin doses. Exenatide should be considered in people with type 2 diabetes on insulin and have obesity, weight gain and poor glycaemic control.
[miR-141-3p regulates the expression of androgen receptor by targeting its 3'UTR in prostate cancer LNCaP cells].

OBJECTIVE To detect the target degradation of miR-141-3p on androgen receptor (AR) gene in LNCaP cells and demonstrate whether AR gene is a target of miR-141-3p. METHODS After prostate cancer cell line LNCaP was transfected with miR-141-3p mimics, expression levels of AR mRNA and protein in the LNCaP cells were detected by reverse transcription PCR and Western blotting, respectively. The 3'untranslated regions (3'UTR) of AR mRNA containing the binding site of miR-141-3p was amplified by PCR and inserted into pmiR-report vector (a 3'downstream luciferase reporter gene). The product was termed pmiR-AR-3'UTR. Double luciferase reporter system was employed to verify the potential target effect of miR-141-3p on pmiR-AR-3'UTR. RESULTS Transfection of miR-141-3p mimics decreased both mRNA and protein expression levels of AR in LNCaP cells. Compared with control group, miR-141-3p transfection significantly inhibited the activity of luciferase of pmiR-AR-3'UTR. CONCLUSION AR is a direct target gene of miR-141-3p.
Review of a personal experience in the management of carcinomatosis and sarcomatosis.

BACKGROUND Peritoneal surface malignancy can result from seeding of gastrointestinal cancer or abdomino-pelvic sarcoma; it can also occur as a primary disease, such as peritoneal mesothelioma. In the past, this clinical situation was treated only with palliative intent. METHODS An aggressive approach to peritoneal surface malignancy involves peritonectomy procedures, perioperative intraperitoneal chemotherapy and knowledgeable patient selection. The clinical assessments necessary for valid clinical judgements include the cancer histopathology (invasive vs expansive progression), the preoperative abdominal and pelvic CT, the peritoneal cancer index and the completeness of cytoreduction score. Proper patient selection is mandatory for optimizing the results of treatment. RESULTS In a series of phase II studies, appendiceal tumors with peritoneal seeding became the paradigm for success with an 85% long-term survival in selected patients. Carcinomatosis from colon cancer had an overall 5-year survival of 50% with selected patients. Also, sarcomatosis patients overall had a 40% 5-year survival in selected patients. Peritoneal mesothelioma showed a 36% 5-year survival. In all malignancies, early aggressive treatment of minimal peritoneal surface dissemination showed the greatest benefit. CONCLUSIONS Oncologists must accept responsibility for knowledgeable management of peritoneal surface dissemination of cancer because a curative approach has been demonstrated in large phase II studies and all historical controls show 0% long-term survival. Adjuvant phase III studies with perioperative intraperitoneal chemotherapy in diseases where peritoneal surface spread occurs are indicated.
Rediscovering Red Blood Cells: Revealing Their Dynamic Antigens Store and Its Role in Health and Disease

© 2012 Rafea and Souchelnytskyi, licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Rediscovering Red Blood Cells: Revealing Their Dynamic Antigens Store and Its Role in Health and Disease
Midline and laterality defects: Left and right meet in the middle †

The aim of this review is to summarize some of the recent advances in molecular embryology that help to explain the pathogenesis of holoprosencephaly (HPE), or its related malformation in model organisms, cyclopia, and laterality defects in humans, derived from detailed analysis of similar malformations in animal models. Recently, defects in several developmental pathways including those operated by the Sonic hedgehog and Nodal signaling factors have been implicated as causes of HPE or laterality defects in humans. Here we summarize the findings in animal models that indicate that both defects can be explained by mechanisms that relate to the proper development of the axial midline in vertebrates. BioEssays 23:888–900, 2001. Published 2001 John Wiley & Sons, Inc.