Miracle-dz/UniFAR-FTUs huggingface dataset:
Dual flaA1 flaB1 mutant of Serpulina hyodysenteriae expressing periplasmic flagella is severely attenuated in a murine model of swine dysentery

The motility imparted by the periplasmic flagella (PF) of Serpulina hyodysenteriae is thought to play a pivotal role in the enteropathogenicity of this spirochete. The complex PF are composed of multiple class A and class B polypeptides. Isogenic strains containing specifically disrupted flaAl or flaB1 alleles remain capable of expressing PF, although such mutants display aberrant motility in vitro. To further examine the role that these proteins play in the maintenance of periplasmic flagellar structural integrity, motility, and fitness for intestinal colonization, we constructed a novel strain of S. hyodysenteriae which is deficient in both FlaA1 and FlaB1. To facilitate construction of this strain, a chloramphenicol gene cassette, with general application as a selectable marker in prokaryotes, was developed. The cloned flaAl and flaB1 genes were disrupted by replacement of internal fragments with chloramphenicol and kanamycin gene cassettes, respectively. The inactivated flagellar genes were introduced into S. hyodysenteriae, and allelic exchange at the targeted chromosomal flaA1 and flaB1 loci was verified by PCR analysis. Immunoblots or cell lysates with antiserum raised against purified FlaA or FlaB confirmed the absence of the corresponding sheath and core proteins in this dual flagellar mutant. These mutations selectively abolished the expression of the targeted genes without affecting the synthesis of other immunologically related FlaB proteins. The resulting flaA1 flaB1 mutant exhibited altered motility in vitro. Surprisingly, it was capable of assembling periplasmic flagella that were morphologically normal as evidenced by electron microscopy. The virulence of this strain was assessed in a murine model of swine dysentery by determining the incidence of cecal lesions and the persistence of S. hyodysenteriae in the gut. Mice challenged with the wild-type strain or a passage control strain showed a dose-related response to the challenge organism. The dual flagellar mutant was severely attenuated in murine challenge experiments, suggesting that the FlaA1 and FlaB1 proteins are dispensable for flagellar assembly but critical for normal flagellar function and colonization of mucosal surfaces of the gastrointestinal tract. This strain represents the first spirochete engineered to contain specifically defined mutations in more than one genetic locus.
An improved model of Rayleigh fading channel with Gaussian's PSD for aeronautical En-Route scenario

This paper proposes a novel model to describe Rayleigh flat fading channels with Gaussian power spectrum density featuring the aeronautical En-Route scenario. The presented method improves the Method of Exact Doppler Spread (MEDS)[1], which is one effective Sum-of-Sinusoids simulation modeling, by employing random processes to update the Doppler Frequency and Doppler Initial Phase for all individual sinusoids. It is shown the improved model can get a good convergence to the theory second-order statistics of real wireless communication channels, even if the number of the sinusoids employed is relatively small(i.e., N equals 8). The modified method helps to integrate a compact and area-efficient channel simulator on FPGA platform for the aeronautical En-Route scenario, which requires small number of sinusoids for simple and rapid implementation due to its high maximum Doppler Frequency and Gaussian power spectrum.
Defining a risk-based approach to the design and technology usage of systems to attain IT availability and recoverability requirements

This paper explains the rationale and overall concept for defining a risk-based approach to the design and technology usage of systems to achieve a set of differentiated business availability and recoverability classes. It provides an overview of the various dimensions being taken into consideration and also elaborates on the aspects that drive the differentiation of best practices or technical capabilities used to achieve the different classes. The paper elaborates on the generic process aspect of assessment of existing systems. It explains how we would utilize this foundation to establish guidelines for applications, the underlying technology and infrastructure, as well as the operational set-up. The principal motivations for the availability and recoverability classification are i) to improve the ability to fulfill the required levels of availability and recoverability and ii) to optimize the investment and operational cost. Businesses will classify their availability according to the distinctions defined here which will limit the extent of high cost critical applications. Additionally, applications will architect their designs for lower cost methods of achieving the desired level of availability. There is no cookie-cutter formula to accomplish these goals. Only if all pieces and building blocks of the architecture are designed from the beginning to fit to each other, will the entire system achieve optimized service availability levels.
Impact of STI stress on 40-nm dogbone layout N-MOSFETs

Based on the test structures and silicon measurement data done at 40nm technology, we analyze the impact of varying length between the contacted active-area and gate (S) on the performance of NMOS dogbone devices, such as saturation drain current (Idsat), threshold voltage (Vth), and leakage current (Ioff). The experiments show that as the length between the contacted active area and gate (S) is increased from 0.07um to 5.02um, both Idsat and Ioff reach the maximum at 0.62um and then gradually decrease, while Vth has a 19.7% monotonic decrease.
Taking steps: an African ageing agenda

Twenty years ago it would have been an impossible task to assemble African scientists and social welfare practitioners to discuss the subject of ageing. Very little researched information existed then and many African governments were likely to assert that ageing was no problem in their country. Even in the 1980s a great deal of scepticism existed in Africa about the need for African gerontology research. Today, and taking a cue from the deliberations of the first AGES workshop, there is no country in our region that is not confronted with the negative impacts of development and urbanization as their country charts its route towards modernization. Even though an ageing agenda still has a low profile on the economic desks of many African governments, the realisation that there are indeed difficulties to be overcome regarding the care of elderly people in Africa is widespread.
BRAF in Melanoma: Current Strategies and Future Directions

Selective BRAF inhibitors have now been established as a standard of care option for patients diagnosed with metastatic melanoma whose tumors carry a BRAF mutation. Their successful development represents a milestone in the treatment of this disease, and has the potential to impact therapy for other malignancies as well. The use of these agents, however, has introduced a number of critical questions about the optimal use and selection of patients for BRAF inhibitor therapy. This review discusses the current status of BRAF inhibitor clinical development, the clinicopathologic features of BRAF-mutated melanoma, as well as strategies for overcoming resistance. Clin Cancer Res; 19(16); 4326–34. ©2013 AACR.
Clinical and biological importance of cytogenetic abnormalities in childhood and adult acute lymphoblastic leukemia

Among the approximately 7,000 cytogenetically abnormal childhood and adult B- and T-lineage acute lymphoblastic leukemias (ALL) published to date, numerous recurring chromosomal aberrations and abnormality patterns have been identified, and it has been clearly shown that the cytogenetic features often correlate closely with specific morphologic, immunophenotypic, and clinical parameters. Thus, karyotypic investigations are now routinely performed for diagnostic and prognostic purposes in ALL, with the chromosomal abnormalities/cytogenetic patterns playing a major role for proper risk assessment and choice of treatment. At the same time, the cytogenetic analyses have resulted in the identification of more than 70 different genes, located at the breakpoints of ALL-associated structural chromosomal abnormalities, that are causally implicated in the leukemogenic process. Hence, the genetic studies have also improved our understanding of the mechanisms of leukemogenesis. However, the almost staggering amount of cytogenetic information presently available has made it increasingly difficult to obtain a general overview of the clinical and biological importance of karyotypic patterns in ALL. Here, we summarize and review the cytogenetic features of childhood and adult ALL, with emphasis on their molecular genetic consequences and their clinical impact.
Associations between obesity, adverse behavioral patterns and cardiovascular risk factors among adolescent inhabitants of a Greek island

Abstract Background: Excess weight, unhealthy lifestyle habits and their sequelae have become a well-recognized public health problem in most countries. The objective of the study was to examine the relationship of adolescent overweight/obesity with behavioral habits and their association with blood pressure (BP) and lipid profile. Methods: Anthropometric parameters, lifestyle, BP and lipid profile of 736 adolescents were evaluated cross-sectionally. The classifications of normal weight, overweight and obese were based on BMI z-scores. Results: About 42.1% of adolescents were overweight/obese, 11.3% were smokers, 33.2% consumed alcohol and 34% reported low activity. Males began smoking earlier, consumed alcohol more often, exercised less and spent more screen time than females. Alcohol consumption was more prevalent among smokers and was associated with higher BP and dyslipidemia. Smokers exercised less intensely and had lower high density lipoprotein-cholesterol (HDL-C) than non-smokers. Obesity was a risk factor for higher BP and dyslipidemia. Longer screen time was associated with higher triglycerides, while intense physical activity with lower systolic BP. Conclusions: Obesity is related to an adverse lipid and BP profile during adolescence. Clustering of hazardous habits was observed, which is known to aggravate the cardiovascular risk.
Ge MOSFETs performance: Impact of Ge interface passivation

We have systematically investigated Ge interface passivation methods, and the highest electron (1920 cm2/Vs) and hole mobility (725 cm2/Vs) have been demonstrated by dramatic reduction of Dit through the collaboration of self-passivation and valency passivation. In Si passivation, it is found that Si contributes to the upper half (worse) and lower one (better) in the bandgap differently. This study strongly suggests us that high performance Ge CMOS is really feasible.
Induction of vascular cell adhesion molecule‐1 expression by IL‐4 in human aortic smooth muscle cells is not associated with increased nuclear NF‐κB levels

Vascular cell adhesion molecule‐1 (VCAM‐1) and intercellular adhesion molecule‐1 (ICAM‐1) are upregulated in vascular endothelial and smooth muscle cells by cytokines produced at sites of inflammation. The cytokine profile for induction of VCAM‐1, however, is different for the two cell types. Tumor necrosis factor‐α (TNF‐α) induced both VCAM‐1 and ICAM‐1 expression in human umbilical vein endothelial cells (HUVECs; ED50 ∼ 300 and 30 U/ml, respectively). TNF‐α and interleukin‐1β (IL‐1β) stimulated cell surface ICAM‐1 expression, but not VCAM‐1 expression, in human aortic smooth muscle cells (HASMCs). Conversely, IL‐4 was a potent VCAM‐1 inducer in HASMCs (ED50 ∼ 100 pg/ml) but did not induce ICAM‐1 expression. Nuclear extracts from IL‐4‐treated cells were compared with untreated cells for relative nuclear factor‐kappa B (NF‐κB) levels by using an electrophoretic mobility shift assay and surface plasmon resonance techniques. No significant increase in nuclear NF‐κB DNA binding activity was detected in IL‐4‐treated HASMCs by either method of analysis. IL‐1β and TNF‐α stimulated nuclear NF‐κB levels by about fourfold and fivefold, respectively, in HASMCs. The antioxidant pyrrolidine dithiocarbamate (PDTC) similarly inhibited VCAM‐1 upregulation in HASMCs incubated with IL‐4 and in HUVECs incubated with TNF‐α (IC50s of 25 and 40 μM, respectively). These data suggest that a significant increase in nuclear NF‐κB levels is not necessary or sufficient for VCAM‐1 upregulation in HASMCs and does not determine the relative sensitivity to inhibition of gene expression by PDTC. J. Cell. Physiol. 180:381–389, 1999. © 1999 Wiley‐Liss, Inc.
Cadmium, Lung and Prostate Cancer: A Systematic Review of Recent Epidemiological Data

Cadmium (Cd) and its compounds were classified as "carcinogenic to humans (Group 1)" by IARC in 1993. The observation of an increased number of lung cancers in a U.S. cohort of cadmium-exposed workers and the finding of tumors in animals exposed to various cadmium compounds apparently played an important role in this assessment. Since this evaluation, several cohorts of cadmium exposed workers have been updated and some additional data regarding environmental exposure to cadmium and cancer risk have been published. The main purpose of this systematic review was to examine whether inclusion of the studies that were not available for the 1993 evaluation might change the overall assessment of the carcinogenic potential of cadmium compounds. A second objective was to examine whether the recent studies are qualitatively better than the older ones and whether they should receive more weight in this assessment. A third issue was to investigate whether a competing effect between nonmalignant respiratory disease (NMRD) and lung cancer may have affected the results for lung cancer in occupationally exposed cohorts. Overall, considering the results of the most recent studies does not suggest that the effect of cadmium on lung cancer increases with improvement of the study design but points to a lower relative risk in the groups exposed to cadmium in the absence of arsenic and nickel. No evidence was found to support the hypothesis that NMRD represents a competing cause of death reducing the mortality from lung cancer. The association between cadmium exposure and prostate cancer was not confirmed in the latest available updates. Studies in environmentally exposed populations do not indicate an increased relative risk of cancer.
Cytoplasmic Tail-Dependent Localization of CD1b Antigen-Presenting Molecules to MIICs

CD1 proteins have been implicated as antigen-presenting molecules for T cell-mediated immune responses, but their intracellular localization and trafficking remain uncharacterized. CD1b, a member of this family that presents microbial lipid antigens of exogenous origin, was found to localize to endocytic compartments that included the same specialized subset of endosomes in which major histocompatibility complex (MHC) class II molecules are proposed to bind endocytosed antigens. Unlike MHC class II molecules, which traffic to antigen-loading endosomal compartments [MHC class II compartments (MIICs)] primarily as a consequence of their association with the invariant chain, localization of CD1b to these compartments was dependent on a tyrosine-based motif in its own cytoplasmic tail.
A Synchronous Reference Frame Robust Predictive Current Control for Three-Phase Grid-Connected Inverters

This paper presents a new predictive current control for three-phase grid-connected inverters in the synchronous reference frame. The control combines a deadbeat control law with a diagonal Luenberger observer to estimate the future value of the grid currents. It provides a decoupled control of the active and reactive power and offers robustness against the computational delay inherent in the digital implementation and against filter and grid-impedance uncertainties. This control exhibits a very fast current response while widely improving the gain and phase margins of the traditional predictive controllers.
A clinical and histologic evaluation of implant integration in the posterior maxilla after sinus floor augmentation with autogenous bone, bovine hydroxyapatite, or a 20:80 mixture.

PURPOSE This study was designed to clinically and histologically evaluate the integration of titanium implants in different grafting materials used for maxillary sinus augmentation procedures. MATERIALS AND METHODS A total of 21 patients and 36 maxillary sinuses were augmented with (1) autogenous particulated bone from the mandibular ramus, (2) bovine hydroxyapatite (BH) with membrane coverage, or (3) an 80/20 mixture of BH and autogenous bone. The grafts were allowed to heal for 6 to 9 months prior to placement of microimplants for histology and standard implants for prosthetic rehabilitation. After another 6 months of healing, when abutments were connected, the microimplants were retrieved for histologic and morphometric analyses. The outcome of the standard implants was clinically evaluated after 1 year of loading. RESULTS The mean bone-implant contact was 34.6 +/- 9.5%, 54.3 +/- 33.1%, and 31.6 +/- 19.1% for autogenous bone, mixture of 20% autogenous bone/80% BH, and 100% BH, respectively. The corresponding values for the bone area parameter were 37.7 +/- 31.3%, 39.9 +/- 8%, and 41.7 +/- 26.6%. The BH area was found to be 12.3 +/- 8.5% and 11.8 +/- 3.6% for 20% autogenous bone/80% BH and 100% BH, respectively. There were no statistically significant differences for any parameter between any of the groups. After 1 year of loading, 6 of the 33 implants placed in autogenous bone grafts, 2 of the 35 implants placed in the BH/autogenous bone mixture, and 2 of 43 implants placed in BH were lost. There were no statistically significant differences between any of the groups. DISCUSSION The histomorphometric analysis showed no differences between the 3 groups, indicating that autogenous bone graft can be substituted with bovine hydroxyapatite to 80% or 100% when used for maxillary sinus floor augmentation. The effect of adding autogenous bone remains unclear but may allow for a reduction of the healing time. CONCLUSION The results from this clinical and histologic study indicate that similar short-term results can be expected when using autogenous bone, BH, or a mixture of them for maxillary sinus floor augmentation and delayed placement of dental implants.
Assessment of coagulopathy, endothelial injury, and inflammation after traumatic brain injury and hemorrhage in a porcine model

BACKGROUND Traumatic brain injury (TBI) and hemorrhagic shock (HS) can be associated with coagulopathy and inflammation, but the mechanisms are poorly understood. We hypothesized that a combination of TBI and HS would disturb coagulation, damage the endothelium, and activate inflammatory and complement systems. METHODS A total of 33 swine were allocated to either TBI + HS (n = 27, TBI and volume-controlled 40% blood loss) or controls (n = 6, anesthesia and instrumentation). TBI + HS animals were left hypotensive (mean arterial pressure, 30–35 mm Hg) for 2 hours. Blood samples were drawn at baseline, 3 minutes and 15 minutes after injury, as well as following 2 hours of hypotension. Markers of coagulation, anticoagulation, endothelial activation/glycocalyx shedding, inflammation, complement, and sympathoadrenal function were measured. RESULTS The TBI + HS group demonstrated an immediate (3 minutes after injury) activation of coagulation (prothrombin fragment 1 + 2, 289 ng/mL vs. 232 ng/mL, p = 0.03) and complement (C5a, 2.83 ng/mL vs. 2.05 ng/mL, p = 0.05). Shedding of the endothelial glycocalyx (syndecan 1) was evident 15 minutes after injury (851.0 ng/ml vs. 715.5 ng/ml, p = 0.03) while inflammation (tumor necrosis factor &agr; [TNF-&agr;], 81.1 pg/mL vs. 50.8 pg/mL, p = 0.03) and activation of the protein C system (activated protein C, 56.7 ng/mL vs. 26.1 ng/mL, p = 0.01) were evident following the 2-hour hypotension phase. CONCLUSION The combination of TBI and shock results in an immediate activation of coagulation and complement systems with subsequent endothelial shedding, protein C activation, and inflammation.
Subclinical ketosis in post-partum dairy cows fed a predominantly pasture-based diet: defining cut-points for diagnosis using concentrations of beta-hydroxybutyrate in blood and determining prevalence

AIMS: Firstly, to define, in dairy cows in the first 5 weeks post-calving fed a predominantly pasture-based diet, cut-points of concentrations of beta-hydroxybutyrate (BHBA) in blood, above which there were associations with purulent vaginal discharge (PVD), reduced pregnancy rates (PR) and decreased milk production, in order to better define subclinical ketosis (SCK) in such cattle; and secondly, to determine the prevalence, incidence and risk factors for SCK. METHODS: An observational field study was conducted in 565 cows from 15 spring-calving and predominantly pasture-fed dairy herds in two regions of New Zealand during the 2010– 2011 dairy season. Within each herd, a cohort of randomly selected cows (approximately 40 per herd) was blood sampled to determine concentrations of BHBA on six occasions at weekly intervals starting within 5 days of calving. The key outcome variables were the presence/absence of PVD at 5 weeks post-calving, PR after 6 weeks (6-week PR) and after the completion of the breeding season (final PR), and mean daily milk solids production. RESULTS: Two cut-points for defining SCK were identified: firstly concentration of BHBA in blood ≥1.2 mmol/L within 5 days post-calving, which was associated with an increased diagnosis of PVD (24 vs. 8%); and secondly concentration of BHBA in blood ≥1.2 mmol/L at any stage within 5 weeks post-calving, which was associated with decreased 6-week PR (78 vs. 85%). The mean herd-level incidence of SCK within 5 weeks post-calving was 68 (min 12; max 100)% and large variations existed between herds in peak prevalence of SCK and the interval post-calving at which such peaks occurred. Cows >8 years of age and cows losing body condition were at increased risk of SCK within 5 weeks of calving. CONCLUSIONS: Cows with concentration of BHBA in blood ≥1.2 mmol/L in early lactation had a higher risk of PVD and lower 6-week PR. Cow and herd-level prevalence of SCK varied widely in early lactation. CLINICAL RELEVANCE: Subclinical ketosis is common and is significantly associated with reproductive performance in mainly pasture-fed New Zealand dairy cattle. Controlling SCK may therefore result in improvements in herd reproductive performance. However considerable variation exists among herds in the incidence of SCK and in the timing of peak prevalence which means that herd-specific monitoring programmes are required to define herd SCK status accurately.
Effects of intravitreal erythropoietin therapy for patients with chronic and progressive diabetic macular edema.

BACKGROUND AND OBJECTIVE To determine the effects of intravitreal injections of erythropoietin in eyes with severe, chronic diabetic macular edema, 5 eyes of 5 patients underwent injections of rHuEPO alpha (EPO). PATIENTS AND METHODS All eyes had progressive vision loss and persistent or worsening edema with prior multi-modal treatment. EPO (5U/50 microL) was injected intravitreally every 6 weeks for three doses and followed for an additional 6 weeks with complete ocular examinations, fluorescein angiography, optical coherence tomography (OCT), and central field acuity perimetry. RESULTS Visual acuity of all patients was subjectively improved by 3 or more lines in 3 eyes and 1 line in 2 eyes. Visual acuity improved to a larger extent than anatomic improvement by OCT. Clearing of hard exudates but only minor improvement in leakage on fluorescein angiography was observed. Improvement in vision occurred within 1 week after the first injection and was maintained until the end point of the current case series (at 18 weeks after the first injection). CONCLUSION This case series seems to show a short-term positive response to EPO for a specific group of patients with chronic diabetic macular edema who were unresponsive to currently available therapies.