Miracle-dz/UniFAR-FTUs huggingface dataset:
Orthotopic liver transplantation for type I Crigler‐Najjar syndrome

A neurologically normal 3‐year‐old girl with Type I Crigler‐Najjar syndrome was successfully treated with orthotopic liver transplantation. Preoperative serum bilirubin concentrations as high as 31 mg per dl were not diminished with phenobarbital or phototherapy. Bilirubin fractionation of duodenal bile prior to transplantation revealed 87.1% unconjugated bilirubin and 12.9% monoconjugates as determined by alkaline methanolysis‐high‐performance liquid chromatography. Postoperatively, the serum bilirubin concentration quickly fell to normal. Uridine diphosphate glucuronyl transferase activity in the recipient liver was not detectable. The gallbladder bile bilirubin concentration of 23.9 mg per dl was less than 15% of previously reported normal values. Since devastating kernicteric brain injury is the invariable outcome of Type I Crigler‐Najjar syndrome, liver transplantation should be performed when phototherapy cannot maintain the serum bilirubin concentration at an unequivocally safe level.
Directed Evolution of Biosynthetic Pathways to Carotenoids with Unnatural Carbon Backbones

Over the course of evolution, nature continually discovers new small molecules through the alteration of biosynthetic enzymes and pathways by mutation and gene transfer. Hundreds of these natural products have proven indispensable to medicine, culture, and technology, greatly contributing to increases in the length and quality of human lives. Chemists have found that the “chemical space” surrounding natural products is especially rich in functional molecules, and synthesis of natural product analogs has uncovered many with new or improved properties. Inspired by nature’s search algorithm, we and others have conducted our own evolution of carotenoid biosynthetic pathways in the laboratory. Chapter 1 comprehensively reviews the motivations, accomplishments, and challenges of this research area as of early 2005, and describes in detail how biosynthetic routes to dozens of new carotenoids have been established. To expand the number of carotenoid backbones beyond the C30 and C40 carbon scaffolds that give rise to the ~700 known natural carotenoids, we subjected a carotenoid synthase, the enzyme responsible for carotenoid backbone synthesis, to directed evolution. Chapter 2 describes the evolution of the C30 carotenoid synthase CrtM from Staphylococcus aureus for the ability to synthesize C40 carotenoids. This work also resulted in novel carotenoids with C35 backbones. We later found that some of the CrtM mutants generated in this laboratory evolution experiment, as well as several secondgeneration variants, are also capable of synthesizing unnatural C45 and C50 carotenoid backbones when supplied with appropriate prenyl diphosphate precursors. ix Chapter 3 describes the creation of full-fledged pathways to carotenoid pigments based on the C45 and C50 scaffolds. Coexpression of the carotenoid desaturase CrtI from Erwinia uredovora resulted in the biosynthesis of at least 10 new C45 and C50 carotenoids with different systems of conjugated double bonds. We also present evidence of an unnatural asymmetric C40 carotenoid pathway beginning with the condensation of farnesyl diphosphate (FPP, C15PP) and farnesylgeranyl diphosphate (FGPP, C25PP). In addition to clarifying how CrtM and CrtI achieve their product specificities, this work also sheds light on the molecular mechanisms used by evolution to access new chemical diversity and the selective pressures that have shaped natural product biosynthesis.
The ontogeny of nasal shape: An analysis of sexual dimorphism in a longitudinal sample.

OBJECTIVES Potential integration between the nasal region and noncranial components of the respiratory system has significant implications for understanding determinants of craniofacial variation. There is increasing evidence that sexual dimorphism in body size and associated male-female differences in energetically relevant variables influence the development of the nasal region. To better understand this relationship, we examined the ontogeny of sexual dimorphism in nasal shape using a longitudinal series of lateral cephalograms. METHODS We collected a series of two dimensional coordinate landmark data from n = 20 males and n = 18 females from 3.0 to 20.0+ years of age totaling n = 290 observations across nine age groups. First, we tested whether there are sex differences in the nasal shape related to ontogenetic increases in body size (i.e., sitting height). Additionally, we examined whether there are male-female differences in patterns of nonallometric variation in nasal shape. Next, we tested whether there are sex differences in the strength of integration between the nasal region and other aspects of the facial skeleton. RESULTS Our results indicate that there are a number of similarities in patterns of morphological variation in the nasal region between males and females. However, as sitting height increases males exhibit a disproportionate increase in nasal region height that is not present in the female sample. Moreover, the male nasal region is less integrated with the surrounding facial skeleton when compared to the female sample. CONCLUSIONS These results are consistent with the hypothesis that sex differences in nasal development are associated with male-female differences in energetically relevant variables.
Larvicidal and mosquito repellent activities of Pine (Pinus longifolia, family: Pinaceae) oil.

BACKGROUND AND OBJECTIVES Various plant-based products are safe and biodegradable alternatives to synthetic chemicals for use against mosquitoes. Oil of Pinus longifolia is traditionally used for protection against mosquitoes in some rural areas but there is no documented report of its use against mosquitoes. The present study was undertaken to scientifically evaluate the activity of Pine oil against mosquitoes. METHODS The oil was procured from the market and its contents were chemically analysed. Larvicidal activity of oil was tested in laboratory bioassays, while repellent action was studied during whole night bait collections in field by direct application on the skin and after its impregnation on mats. RESULTS Results showed varying degree of larvicidal activity of Pine oil against mosquitoes with LC50 values ranging between 82 and 112 ppm. The Pine oil had strong repellent action against mosquitoes as it provided 100% protection against Anopheles culicifacies for 11 h and 97% protection against Culex quinquefasciatus for nine hours respectively. Electrically heated mats prepared from Pine oil provided, 94 and 88% protection against An. culicifacies and Cx. quinquefasciatus for 10 and seven hours respectively. INTERPRETAION AND CONCLUSION: Pine oil is effective against mosquito larvae at very higher doses which are not of any practical utility. However, Pine oil showed strong repellent action against An. culicifacies (malaria vector) and Cx. quinquefasciatus (pest mosquito). Thus its use could be popularised as mosquito repellent.
Impact of metformin on anti‐Müllerian hormone in women with polycystic ovary syndrome: a secondary analysis of a randomized controlled trial

Conclusions on the effect of metformin on circulating anti‐Müllerian hormone (AMH) levels in women with polycystic ovary syndrome (PCOS) are ambiguous. We performed a secondary analysis of a randomized, double‐blind, placebo‐controlled cross‐over trial. Fifty‐six women with hyperandrogenemic PCOS were included. Each woman served as her own control receiving a daily dose of either 1700 mg metformin or placebo for 6 months. After a 3‐month wash‐out period they received the opposite treatment. The decrease in AMH from a median of 49.5 to 46.9 pmol/L after 6 months on metformin was overall not significant (p = 0.81), nor were changes in obese women (from 49.5 to 38.2 pmol/L; p = 0.53). Comparing individual metformin/placebo AMH values, a small absolute decrease of 9.3 pmol/L (p = 0.03) was observed in obese women after 6 months relative to baseline, suggesting a trend towards decreasing values after metformin treatment, mainly in obese women.
Inorganic nitrogen retention by watersheds at Fernow Experimental Forest and Coweeta Hydrologic Laboratory

Because elevated N loading can impair both terrestrial and aquatic ecosystems, understanding the abiotic and biotic controls over retention and export of dissolved inorganic N (DIN) is crucial. Long-term research has been conducted on experimental watersheds at two U.S. Forest Service experimental forests in the Appalachian region: Fernow Experimental Forest (FEF) in West Virginia and Coweeta Hydrologic Laboratory (CHL) in North Carolina. While similar in vegetation and research history, FEF and CHL differ in climate, historic DIN deposition, and soils. We evaluated long-term patterns of DIN inputs and exports from three watersheds at each location with similar treatments including clear-cut harvest, conversion to conifer plantation (Norway spruce [Picea abies (L.) H. Karst. ] at FEF and white pine [Pinus strobus L. ] at CHL), as well as reference watersheds. We examined DIN export and retention in these watersheds, comparing treated and reference watersheds within each experimental forest and comparing similarly treated watersheds between the experimental forests. Despite current similar levels of N deposition, stream water DIN concentrations and exports were generally greater at FEF by almost an order of magnitude. We found differences between FEF and CHL in stream DIN concentrations, watershed export, and retention of DIN inputs not only in the untreated reference watersheds but also in the watersheds with similar disturbance treatment. We hypothesize that these differences are the result of site and vegetation differences as well as site history including long-term patterns of DIN deposition. We document the switch from biogeochemical to hydrologic controls that occurred when N availability exceeded N immobilization, due to either N deposition or biological N inputs.
Eficiência reprodutiva de vacas leiteiras mestiças

O objetivo foi avaliar o desempenho reprodutivo de vacas leiteiras mesticas. O projeto utilizou 83 vacas (Holandes/ Gir) com producao media de 18,5 kg de leite/dia/vaca da Fazenda Experimental do Gloria da Universidade Federal de Uberlândia. As visitas foram realizadas a cada 21 dias para coleta dos dados de partos e inseminacoes ocorridas de janeiro de 2013 a marco de 2014. Os animais aptos a reproducao foram submetidos ao protocolo de inseminacao artificial em tempo fixo, e aquelas com mais de 28 dias de inseminadas foram submetidas ao diagnostico de gestacao via ultrassonografia equipado com transdutor retal linear de 5-MHz e em caso de prenhes o exame foi repetido aos 45 dias para confirmacao. As vacas negativas ao exame foram re – sincronizadas. O intervalo parto concepcao e intervalo parto previsto foram analisados por analise de variância no programa MINITAB, incluindo-se o efeito da estacao do parto (outono/inverno x primavera/verao). O intervalo parto/concepcao medio das vacas foi de 118,14 dias. Observou-se tendencia (P = 0,065) do efeito da estacao do parto sobre o IPC, ou seja, as vacas (n=46) que pariram no outono/inverno tiveram menor IPC (101,80) em relacao as vacas (n=37) que pariram na primavera/verao (142,90). O intervalo parto previsto medio foi de 403,14 dias, e tambem foi observado tendencia (P= 0,065) do efeito da estacao do parto sobre o IPP , sendo este menor no outono/inverno (386,80) quando comparado a primavera/verao (427,90). Portanto, vacas que parem no outono/inverno tendem a ter menor IPC e menor IPP. Os dias medio em lactacao (DEL) do rebanho foi de 145 dias, por isso nao e um bom indice para avaliacao reprodutiva de rebanhos mesticos, devido a baixa persistencia de lactacao. Para o monitoramento das femeas bovinas foi implantado o controle reprodutivo em roda ou quadro das vacas, dividido em dez fases, respectivamente, periodo voluntario de espera, liberadas, inseminadas primeira vez, inseminadas segunda vez, inseminadas terceira vez, monta natural, terco inicial da gestacao, terco medio da gestacao, terco final da gestacao e periodo seco, e ainda esta em fase de experimentacao.
1 alpha,25-Dihydroxyvitamin D3 receptors in human thymic and tonsillar lymphocytes.

In vitro activated human peripheral blood lymphocytes possess the receptor protein for 1 alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3). In the present study we have examined whether activated lymphocytes that occur in vivo in human thymuses and tonsils also possess receptors for 1,25(OH)2D3. Freshly isolated lymphocyte preparations, from five separate surgical specimens of thymus and tonsil, were depleted of monocytes and examined, before and after fractionation on a density gradient of Percoll, for [3H] 1,25(OH)2D3 binding by means of sucrose density gradient sedimentation, by saturation analysis of the binding, and by DNA-cellulose chromatography. The state of activation of the lymphocyte preparations was determined using [3H] thymidine incorporation, DNA and RNA quantitation (using acridine orange), and by determining the presence or absence of markers of activation (interleukin-2 receptor, transferrin receptor, and HLA-DR molecules). In both the thymic and the tonsillar lymphocyte preparations we detected a 1,25(OH)2D3-binding molecule possessing sedimentation coefficient of 3.3 S and dissociation constant of 10(-10) M as well as DNA binding capability. In thymic lymphocytes, the 1,25(OH)2D3 receptor concentration correlated positively with the number of lymphocytes expressing the transferrin receptor (r = 0.84; p less than 0.05). In addition, in both thymic and tonsillar lymphocytes the concentration of 1,25(OH)2D3 receptors correlated positively with the number of cells in the G1a phase of the cell cycle (r = 0.79, p less than 0.01, and r = 0.88, p less than 0.001 for thymic and tonsillar lymphocytes, respectively). In contrast, the 1,25(OH)2D3 receptor concentration in these preparations did not correlate with the rate of cell proliferation. (ABSTRACT TRUNCATED AT 250 WORDS)
DNA-induced Secondary Structure of the Carboxyl-terminal Domain of Histone H1*

We have studied the secondary structure of the carboxyl-terminal domains of linker histone H1 subtypes H10 (C-H10) and H1t (C-H1t), free in solution and bound to DNA, by IR spectroscopy. The carboxyl-terminal domain has little structure in aqueous solution but becomes extensively folded upon interaction with DNA. The secondary structure elements present in the bound carboxyl-terminal domain include the α-helix, β-structure, turns, and open loops. The structure of the bound domain shows a significant dependence on salt concentration. In low salt (10 mm NaCl), there is a residual amount of random coil, 7% in C-H10 and 12% in C-H1t. In physiological salt concentrations (140 mm NaCl), the carboxyl termini become fully structured. Under these conditions, C-H10 contained 24% α-helix, 25% β-structure, 17% open loops, and 33% turns. The latter component could include a substantial proportion of the 310 helix. Despite their low sequence identity (∼30%), the representation of the different structural motifs in C-H1t was similar to that in C-H10. Examination of the changes in the amide I components in the 20–80 °C temperature interval showed that the secondary structure of the DNA-bound C-H1t is for the most part extremely stable. The H1 carboxyl-terminal domain appears to belong to the so-called disordered proteins, undergoing coupled binding and folding.
The role of positive vs. negative evidence in learning a novel dialect pattern: American English speakers’ grammatical intuitions on a-prefixing in Appalachian English

This paper focuses on the controversies surrounding the effect of linguistic input in language acquisition and investigates how learning of a dialectal pattern, a-prefixing in Appalachian English, can be modulated by positive vs. negative evidence in adult learners whose grammar does not contain this grammatical phenomenon. In an online acceptability judgment study, we measured gradient grammatical intuitions of 41 Appalachian English and 36 native speakers of American English on their perceived acceptability of carefully-matched grammatical and ungrammatical sentences with a-prefixing. We used 16 sentences (50% ungrammatical) for each of the 5 previously established constraints on a-prefixing, divided equally into a pre- and post-test session. The non-dialect speakers were further divided into 3 input groups depending on the type of input they received between the two tests: the positive-evidence group with only grammatical instances of a-prefixing, the negative-evidence group with explicit instruction concerning only ungrammaticality, and the control group with no input. Results indicated that, just like the baseline Appalachian English group, the non-dialect participants were able to distinguish grammatical sentences from ungrammatical ones, crucially in all of the 5 different constraints, prior to the treatment, although they significantly differed from the Appalachian English group in the strength of their judgments. The post-test results revealed a clear benefit of negative evidence on the learning of a novel grammatical phenomenon, albeit only concerning the responses to ungrammatical sentences, while accept-ability judgments for grammatical as well as ungrammatical sentences did not benefit from positive evidence alone. We suggest that the target-like intuitions of our non-dialect participants at the onset result from a deduction of tacitly known principles of English and linguistic universals. Concerning the differential effect of input categories on learning, we argue that exposure to only positive exemplars of the target phenomenon results in overly general hypotheses about its patterning in the language, which may push the learner to perceive new ungrammatical sentences better than their initial acceptability value. Negative exemplars, however, place a pressure on learners to notice the linguistic contexts in which the target phenomenon is not allowed to surface, thereby raising their awareness of the presence of rules.
Pharmacological Evaluation of Humanized Anti-Epidermal Growth Factor Receptor, Monoclonal Antibody h-R3, in Patients With Advanced Epithelial-Derived Cancer

Epidermal growth factor receptor (EGFR) overexpression has been detected in many tumors of epithelial origin, and it is often associated with tumor growth advantages and poor prognosis. h-R3 is a genetically engineered humanized antibody (mAb) that recognizes an epitope located in the extracellular domain of human EGFR. The antibody exhibited potent in vitro and in vivo antitumor effect on EGFR overexpressing cell lines. To study safety, pharmacokinetics, and biodistribution, 12 patients with advanced epithelial-derived tumors received single intravenous infusion of h-R3 at four dose levels. Safety evaluation was made according to World Health Organization toxicity criteria. For biodistribution, 3 mg of the total dose were labeled with 99m-Technetium and then pooled with the rest of the dose. Anterior and posterior whole-body images were acquired using a gamma camera. Blood samples were taken for pharmacokinetics, antiidiotypic response, and for soluble EGFR detection. After hR3 administration, no evidence of severe toxicity was observed. Secondary reactions were mild and moderate and mainly consisted of tremors, fever, and vomiting. No anaphylactic or skin reactions were detected. Qualitative analysis of whole-body images showed that the liver had the highest mAb uptake. Pharmacokinetic analysis revealed that elimination half-lives and the AUC increased linearly with dose, while total body clearance decreased when increasing doses of h-R3. No relation between shed EGFR and mAb clearance was found. No antiidiotypic response against h-R3 was detected. Several phase II trials are now underway to evaluate the efficacy of h-R3 in the treatment of advanced cancer patients.
Nutritional Status and Associated Risk Factors Among Adolescents Girls in Agarfa High School, Bale Zone, Oromia Region, South East Ethiopia

Adolescent have typically been considered as low risk for poor health and often receive few health care resource and attention. However, their approach ignores the fact that many health problems later in life can be improved by adopting health life style habits in adolescents. There is a shortage of studies about nutritional status and associated factors among adolescent girls. The objective of this study was to asses nutritional status of adolescent girls and associated factors in Agarfa high school, Bale zone, Oromia Region, south Eastern Ethiopia. Institutional based cross sectional study was conducted to assess nutritional status of and associated factors in adolescent. The sample size was calculated based on the single proportion formula using the prevalence of malnutrition in adolescents 27%, α=5% and degree of margin of error 5%. The final sample size was 212 adolescent girls. The study employed systematic sampling technique to select adolescents and the data were collected by using structured questionnaire. Descriptive statistics was used for reporting the different characteristics while chi square test will be employed to determine factors associated with nutritional status. In this study it can be concluded that the prevalence of underweight and overweight is high. This indicates the double burden of malnutrition among adolescent girls in this area. Dietary factors such as meal frequency, meal skipping and dietary diversity were the associated factor for nutritional status of adolescent girls. Appropriate nutrition education intervention should designed to improve the nutritional status of adolescents girls.
Consensus and synchronization of complex networks via proportional-integral coupling

In this paper we investigate the use of distributed PI actions to achieve consensus and synchronization in complex networks. We show that by extending the classical linear diffusive coupling with an integral action it is possible to achieve better performance and steady-state behavior than with more traditional strategies. After briefly summarizing the theoretical results, we investigate the viability of the proposed strategy via numerical simulations including a representative example inspired from power system models recently presented in the literature.
DAHREVA – Assessment of the validity of the dairy health recording systems in the Nordic countries

The Nordic disease databases have been in operation for several decades, but only limited efforts has been made to validate them. In 2007 a joint Nordic project was initiated with the aim to validate each national database and to compare the data validity between countries. Validation was made by “patient chart reviews” and by using a second source of data collected on-farm. The intention to treat sick cows also affects the completeness of the records, and this was evaluated by investigating attitudes of farmers and veterinarians. The results showed that the correctness of the data was high, but that completeness was less than 100% and it varied by disease complex and country. Standardization of disease registrations is necessary for valid between-country assessments, but adjustments for incompleteness can meanwhile be used. There were also differences between countries in the attitudes to treat sick cows, which also influences the comparability of disease records between countries.