Heptamethine cyanine dyes are widely used for in vivo near-infrared (NIR) fluorescence imaging and NIR laser-induced cancer phototherapy due to their good optical properties. Since most of heptamethine cyanine dyes available commercially are highly hydrophobic, they can usually be used for in vivo applications after formation of complexes with blood plasma proteins, especially serum albumin, to increase aqueous solubility. The complex formation between cyanine dyes and albumin improves the chemical stability and optical property of the hydrophobic cyanine dyes, which is the bottom of their practical use. In this study, the complexes between three different heptamethine cyanine dyes, namely clinically available indocyanine green (ICG), commercially available IR-786 and zwitterionic ZW800-Cl, and bovine serum albumin (BSA), were prepared to explore the effect of cyanine dyes on their tumor uptake and retention. Among the three complexes, IR-786©BSA exhibited increased tumor accumulation with prolonged tumor retention, compared to other complexes. Moreover, IR-786 bound to BSA played an important role in tumor growth suppression due to its cytotoxicity. To achieve complete tumor ablation, the tumor targeted by IR-786©BSA was further exposed to 808 nm laser irradiation for effective photothermal cancer treatment.


Education is the most fundamental but an important enabler of knowledge economy. Knowledge economy is based on the production, dissemination and use of knowledge as the main driver of growth, wealth creation and employment. The purpose of this study is to examine the impact and contribution of the educational background of Sri Lankan business leaders and their second tier leaders towards the development of knowledge economy. By doing so, the paper aims to present an agenda for Sri Lankan Universities to bring into focus their attention on skills development systems in the perspective of knowledge economy. The research is based on a study of the educational background of 24 business leaders and 65 second tier leaders of 15 diversified public blue- chip companies in Sri Lanka. This is accomplished through the collection of each individual's data and grouping them to identify the educational patterns among the business leadership and the contribution of local universities to their education. The main findings is that the Sri Lankan University Degree holders among the senior leaders of these companies are so inadequate that they are analogous to/with the foreign university degree holders and the senior leaders who have professional qualifications in finance, economics and management domains are of the right caliber to draw an analogy between the senior leaders who have University degrees. This research is focused on diversified public blue-chip companies, and therefore the generalization of results to other companies must be cautious. Further, the research is based on publicly available data through company annual reports and there are instances of unavailability of relevant data. This is an attempt on one hand to identify whether the lack of local university education among the business leaders and second level leaders is a rationale for Sri Lanka to be still at an inferior level of development of knowledge economy and then on the other hand to see whether the configuration and course contents of Sri Lankan universities have been conducive to the development of knowledge economy.


In this chapter we will first evaluate the effectiveness of our approach in designing an energy-efficient architecture for hand-held multimedia computers. In particular we will compare the power dissipation of the test-bed of Mobile Digital Companion with a traditional architecture using a typical multimedia application. Then we give some suggestions for future research. We conclude with some general conclusions about the main issues discussed in this thesis. The connection-centric approach with application domain specific modules gives a number of advantages like (energy) efficient processing, high performance, elimination of useless data copies, relieve of the general-purpose processor, and the possibility of an adequate energy management. We already gave some practical and theoretical background on the amount of energy that can be saved using such an architecture. In this section we will show the effectiveness on the energy consumption of our architecture using a typical multimedia application. We will do this by comparing the power consumption of wirelessly receiving and playing MP3 music on a traditional architecture and on a Mobile Digital Companion. We will further compare the power dissipation of these architectures when idling, and waiting for an external event. Two considerations have to be made when interpreting the resulting power dissipation: • The architecture of a Mobile Digital Companion as described in this thesis encompasses various levels in the design cycle. The design approach is vertical oriented, which implies that all layers of the system are involved, and an optimal effect on the performance and efficiency is reached only when all layers cooperate. This thesis only covers the general system architecture, the interconnection architecture, and the wireless interface.


The present PET study investigates the role of prosodic clues (pitch, pause) in processing the oral speech syntactic structure. The stimuli used were syntactically simple sentences and sentences with different syntagmatic segmentation. They were presented binaurally to twelve right-handed, musically untrained native Russian speakers. One condition reflected automatic perceptual processing, the other understanding of meaning. Significantly increased brain responses occurred in the right inferior posterior frontal region (BA 44, 45,9) and in the right cerebellum (medio-inferior area) in the second condition. The results further support the notion that auditory speech comprehension is not restricted to the left hemisphere. The underlying mechanisms and the respective role of the right hemisphere and cerebellum structures during speech processing are discussed.


As attitude-researches point out, students tend to sustain an aversion to mathematics, while remaining largely ignorant of how deeply embedded it is in the world around them. Most students however are able to recognize patterns and numerous research and empirical evidence indicates that they become easily motivated when mathematical connections are presented in ways which relate to their experiences by triggering their natural curiosities. PISA and TIMSS results and recommendations are that students should find education enjoyable, develop self-belief and stamina to address challenging problems and situations. Experience-centered education of mathematics through arts and playful activities might be an effective way to grasp the complex relationship between mathematics attitudes and joy of learning and support the students in their study achievements. In this article we show that creating visual illusions, paradox structures and 'impossible' figures through playful and artistic procedures, holds an exciting pedagogical opportunity for raising students' interest towards mathematics and natural sciences and technical aspects of visual arts. There are certain digital games as well, which employ visual illusions as a part of their game mechanic. Most of these games were not designed as an educational game, but they may be used for educational purposes, to clarify mathematical concepts behind and related to visual illusions (symmetry, perspective, isometric projection etc.).


With the action-oriented approach first introduced by the CEFR (Common European Framework of Reference for Languages), the goal of language teaching witnessed a transition from transmission of information (exchange of information) in the classroom to acting together (social action) in and/or outside the classroom and hence from training successful communicators to training social actors. The implementation of the action-oriented approach in language textbooks in the form of mini-projects, however, is an issue not addressed commonly in the field. This study critically analyses the tasks named as 'projects' at the end of the first, sixth and eighth units of the English textbook "Ingilizce 7" used in the secondary schools in Turkey to show that they do not reflect the characteristics of mini-projects as a form of the application of the action-oriented approach in language textbooks. Secondly, how these tasks can be transformed into mini-projects is explained.


Abstract Martinez, AF, Lessi, GC, Carvalho, C, and Serrao, FV. Association of hip and trunk strength with three-dimensional trunk, hip, and knee kinematics during a single-leg drop vertical jump. J Strength Cond Res 32(7): 1902–1908, 2018—Kinematic changes have been correlated with different lower-limb injuries. Movement is influenced by multiple factors and strength is one of the contributors that can influence it. Thus, the aim of this study was to evaluate the correlation among trunk and hip isometric strength with trunk and lower-limb kinematics during a single-leg drop vertical jump. Twenty-three healthy recreational female athletes aged between 18 and 35 years underwent isometric evaluation of hip abductor, hip extensor, and lateral trunk muscle strength and 3-dimensional trunk and lower-limb kinematics during a single-leg drop vertical jump. Pearson's correlation coefficients (r) were calculated to establish the association among hip and trunk strength and trunk, hip, and knee kinematics. As result, no significant correlations were found between the peak and movement excursion values of kinematic and hip and trunk isometric strength data. The lack of correlation between isometric strength and kinematics in healthy female athletes indicates that intervention programs should not be focused solely on strength exercises to influence the movement pattern during single-landing activities.


Urinary bladder cancers represent a spectrum of diseases that can be grouped into three general categories: superficial, invasive and metastasis. Each differs in clinical behavior, prognosis and primary management. For superficial tumors, the aim is to prevent recurrences and progression to an incurable stage, recognizing that surgical removal of the bladder (over treatment for most tumors) is curative up to a point. For more invasive disease, the issue becomes how to determine which tumors can be cured with a single therapy such as surgery, and which, by virtue of a high metastatic potential, requires an integrated systemic approach to achieve cure. For metastatic disease, combination chemotherapy is the standard yet, despite responses in more than 50% of cases, overall cure rates remain low, and progression has been minimal over the past few years. We analyzed histopathological and immunohistochemical 70 patients with bladder carcinomas searching the stage, the grade and other associated lesions. The results showed that 70% were papillary transitional carcinomas infiltrated in lamina propria (T1), and almost 22.85% represent non-invasive papillary carcinomas (Ta); we found only five cases in Tis stage (7.15%). The immunohistochemistry investigated three antibodies: p53 oncoprotein, bcl-2 oncoprotein and retinoblastoma protein (pRb). We noticed the antibodies distribution related to stage: carcinoma in situ (Cis or Tis) high percent of p53 (69) and bcl-2 (37.5%). Concerning the superficial tumors we found low values of p53 in T1 (45%) versus invasive tumors (51%); oncoprotein bcl-2 is higher in T1 (35%) versus non-invasive one (6%).


This paper presents our experience using a domain-specific functional language, WaveScript, to build embedded sensing applications used in scientific research. We focus on a recent computervision application for detecting birds in their natural environment. The application was ported from a prototype in C++. In reimplementing the application, we gained a much cleaner factoring of its functionality (through higher-order functions and better interfaces to libraries) and a near-linear parallel speed-up with no additional effort. These benefits are offset by one substantial downside: the lack of familiarity with the language of the original vision researchers, who understandably tried to use the language in the familiar way they use C++ and thus ran into various problems.


Human mucin MUC3 and rodent Muc3 are widely assumed to represent secretory mucins expressed in columnar and goblet cells of the intestine. Using a 3'-oligonucleotide probe and in situ hybridization, we observed expression of rat Muc3 mostly in columnar cells. Two antibodies specific for COOH-terminal epitopes of Muc3 localized to apical membranes and cytoplasm of columnar cells. An antibody to the tandem repeat (TR) sequence (TTTPDV)3, however, localized to both columnar and goblet cells. On CsCl gradients, Muc3 appeared in both light- and heavy-density fractions. The lighter species was immunoreactive with all three antibodies, whereas the heavier species reacted only with anti-TR antibody. Thus Muc3 is expressed in two forms, a full-length membrane-associated form found in columnar cells (light density) and a carboxyl-truncated soluble form present in goblet cells (heavy density). In a mouse model of human cystic fibrosis, both soluble Muc3 and goblet cell Muc2 were increased in amount and hypersecreted. Thus Muc2 and Muc3 contribute to the excess intestinal luminal mucus of cystic fibrosis mice.


Abstract A visit to a Chinese city of any size – looking up at downtown billboards, riding public transport, shopping at a mall – is to be in the presence of a Chinese celebrity endorsing a product, lifestyle or other symbols of "the good life." Celebrity in China is big business, feeding off and nourishing the advertising-led business model that underpins the commercialized media system and internet. It is also a powerful instrument in the party-state's discursive and symbolic repertoire, used to promote regime goals and solidify new governmentalities through signalling accepted modes of behaviour for mass emulation. The multi-dimensional celebrity persona, and the public interest it stimulates in off-stage lives, requires an academic focus on the workings of celebrity separate to the products that celebrities create in their professional roles. The potential to connect with large numbers of ordinary people, and the emergence of an informal celebrity-making scene in cyberspace symptomatic of changing attitudes towards fame among Chinese people, marks the special status of celebrity within China's constrained socio-political ecology. The motivation for this article is to further scholarly understanding of how celebrity operates in China and to bring this expression of popular culture into the broader conversation about contemporary Chinese politics and society. 摘要 身处中国任何大中小城市, 无论是市中心广告牌、公共交通工具还是购物中心, 随处可见中国名人明星所代言的产品、生活方式及其他象征 "美好生活" 的事物。商业媒体体制和网络主要依赖于广告为中心的商业模式, 而中国名人明星作为一项巨型产业, 则与该模式相辅相成。同时, 名人产业也是党和国家话语及象征的强有力工具,通过名人发出可接受的行为信号, 鼓励大众效仿, 从而起到推动政体目标、巩固新治理术的目的。多方位的名人形象以及名人在舞台下的生活所激发的公众兴趣, 要求学术界对其运作方式做出分析, 并与名人在职业角色中塑造的作品分开。名人在互联网上与普罗大众进行互动的潜力, 以及新兴的互联网络名人现象, 都象征了民众对名望观念的蜕变, 同时也反映出名人在中国有限的社会政治生态中的特殊地位。本文旨在对中国的名人运作进行深入的学术探讨, 并在当代中国政治与社会的宏观背景下分析流行文化。


A seminal result of Håstad (2001) shows that it is NP-hard to find an assignment that satisfies 1/|G|+ε fraction of the constraints of a given k-LIN instance over an abelian group, even if there is an assignment that satisfies (1−ε) fraction of the constraints, for any constant ε>0. Engebretsen, Holmerin and Russell (2004) later showed that the same hardness result holds for k-LIN instances over any finite non-abelian group. Unlike the abelian case, where we can efficiently find a solution if the instance is satisfiable, in the non-abelian case, it is NP-complete to decide if a given system of linear equations is satisfiable or not, as shown by Goldmann and Russell (1999). Surprisingly, for certain non-abelian groups G, given a satisfiable k-LIN instance over G, one can in fact do better than just outputting a random assignment using a simple but clever algorithm. The approximation factor achieved by this algorithm varies with the underlying group. In this paper, we show that this algorithm is optimal by proving a tight hardness of approximation of satisfiable k-LIN instance over any non-abelian G, assuming P≠ NP. As a corollary, we also get 3-query probabilistically checkable proofs with perfect completeness over large alphabets with improved soundness. Our proof crucially uses the quasi-random properties of the non-abelian groups defined by Gowers (2008).


AIMS
Venous thromboembolism is an important cause of postoperative morbidity and mortality in bariatric surgery. Studies of direct oral anticoagulants (DOACs) are not available in this surgical field. The objective of this phase 1 clinical trial was to investigate pharmacokinetic and pharmacodynamic (PK/PD) parameters of rivaroxaban in bariatric patients.

METHODS
In this single-centre study, obese patients received single oral doses of rivaroxaban (10 mg) 1 day prior to and 3 days after bariatric surgery. PK and PD parameters were assessed at baseline and during 24 h after drug ingestion.

RESULTS
Six Roux-en-Y gastric bypass patients and six sleeve gastrectomy patients completed the study. Mean rivaroxaban area under plasma concentration-time curve, peak plasma concentration, time to peak plasma concentration and terminal half-life were 971.9 μg·h l-1 (coefficient of variation: 10.6), 135.3 μg l-1 (26.7), 1.5 h and 13.1 h (34.1) prior to and 1165.8 (21.9), 170.0 (15.9), 1.5 and 8.9 (44.6) postsurgery for SG patients and 933.7 μg·h l-1 (22.3), 136.5 μg l-1 (10.7), 1.5 h und 13.8 h (46.6) prior to and 1029.4 (7.4), 110.8 (31.8), 2.5 and 15 (60.0) postsurgery for Roux-en-Y gastric bypass patients, respectively. Prothrombin fragments (F1 + 2) decreased during the first 12 hours and increased thereafter in the pre- and the postbariatric setting. Thrombin-antithrombin complexes dropped within 1-3 h in the prebariatric setting and remained low after surgery until they increased at 24 h postdose. Rivaroxaban was well tolerated and no relevant safety issues were observed.

CONCLUSIONS
Bariatric surgery does not appear to alter PK of rivaroxaban in a clinically relevant way. Effective prophylactic postbariatric anticoagulation is supported by changes in PD.


BACKGROUND:Anesthesia and sedation are associated with paradoxical breathing. Respiratory inductance plethysmography (RIP) permits measurement of respiratory motion in clinical settings not conducive to spirometry, but correlation of RIP volume changes and spirometer flow in the time domain is degraded by the development of paradoxical breathing. The Hilbert-Huang transform (HHT) is a nonlinear signal analysis method that permits the instantaneous magnitude and phase of nonstationary signals to be estimated in the frequency domain. We hypothesized that these frequency domain estimates would provide higher correlation between RIP and spirometer signals than time domain signals during the transition between normal and paradoxical breathing. METHODS:From 51 patients undergoing sevoflurane anesthesia for minor procedures, a 5-minute epoch containing transitions between pressure support ventilation and spontaneous ventilation was selected for analysis. Pearson correlation for models based on HHT magnitude and phase was compared with models based on time domain signals. Bland-Altman analysis was performed to assess deviation from linearity in the models. RESULTS:For the 51 patients analyzed, the modulation of tidal volume over the epoch ranged from 30% to 215% of epoch mean. The coefficient of determination for time domain analysis was 0.62 ± 0.2 compared with 0.93 ± 0.07 for the HHT model incorporating phase. This improvement of 0.31 (99% confidence interval, 0.24–0.37) was significant (P < 0.0001). No trend was observed in prediction residuals. CONCLUSIONS:Under conditions of changing ventilation, HHT-derived magnitude and phase measures provide higher correlation with spirometry than those obtained with traditional time domain methods.


This paper presents a new perturbation technique for developing efficient iterated local search procedures for the asymmetric traveling salesman problem(ATSP). This perturbation technique uses global information on ATSP instances to speed-up computation and to improve the quality of the tours found by heuristic method. The main idea is to escape from a local optima by introducing perturbation on the out-of-kilter ares in the problem instance. For a local search heuristic, we use known which finds optimum or near-optimum solutions by applying the out-of-kilter algorithm to the ATSP. The performance of our algorithm has been tested and compared with known method perturbing on randomly chosen ares. A number of experiments has been executed both on the well-known TSPLIB instances for which the optimal tour length is known, and on randomly generated instances. For 27 TSPLIB instances, the presented algorithm has found optimal tours on all instances. And it has effectively found tours near AP lower bound on randomly generated instances.


The eruption of Boko Haram and its insurgency in 2009 caused the loss of life and property that is unprecedented in northern Nigeria's history since independence. Various tools and approaches have been used in analyzing a phenomenon with a view to offering solutions to it. People from various walks of life including professionals and experts have expressed their views and opinions about groups, their activities and ways to limit them. Since the group is rightly or wrongly associated and identified with Islam in its activities, experts especially the ulama analyze the group from an Islamic perspective using the Qur'an and Sunnah and the actions of the salaf as their basis for offering solutions. to group problems. With this background, this paper examines the role of Ulama in dealing with the imbroglio of Boko Haram by using the Ulama model of Al Azhar University in particular. The historical method was adopted with data mostly collected from printed materials and the internet. This paper recommends among other things that our scholars should follow some of the approaches used by Al'azhar scholars in eliminating the influence of extremist and rebel groups. .


Molybdenum disulfide (MoS2) is systematically studied using Raman spectroscopy with ultraviolet and visible laser lines. It is shown that only the Raman frequencies of $ E_{2{\rm g}}^1 $ and $ A_{{\rm 1g}}^{} $ peaks vary monotonously with the layer number of ultrathin MoS2 flakes, while intensities or widths of the peaks vary arbitrarily. The coupling between electronic transitions and phonons are found to become weaker when the layer number of MoS2 decreases, attributed to the increased electronic transition energies or elongated intralayer atomic bonds in ultrathin MoS2. The asymmetric Raman peak at 454 cm−1, which has been regarded as the overtone of longitudinal optical M phonons in bulk MoS2, is actually a combinational band involving a longitudinal acoustic mode (LA(M)) and an optical mode ($ A_{{\rm 2u}}^{} $). Our findings suggest a clear evolution of the coupling between electronic transition and phonon when MoS2 is scaled down from three‐ to two‐dimensional geometry.


Assuming that it is still valid to distinguish policy into phases (agenda, formulation, implementation and evaluation), this text presents the evolution of the academic reflection and highlights the relevance of studying implementation today. It also brings forth some research results as a contribution to the debate on methodological issues in the assessment of the implementation process, as a specific subarea of the research on policy assessment for the study of educational policies. Based on a reflection on the literature produced and on the methodology employed in research on education, it retrieves the changes and opportunities in the field of the implementation of educational policy as a field of practical research, which, these last twenty years, has become an arena of fierce conflicts and of interests, because of a large budget policy. It also approaches the multiple dimensions of welfare state.


Intestinal bacterial flora of febrile neutropenic patients had significantly diverse. However, there were scanty reports of microbiota alteration of adult patients with acute myeloid leukemia (AML). Stool samples of each treatment-naïve AML patient were collected at the day before induction chemotherapy initiation (pretreatment), first day of neutropenic fever and first day of bone marrow recovery. Bacterial DNA was extracted from stool and sequenced bacterial 16s ribosomal RNA genes by next-generation sequencing. Relative abundance, overall richness, Shannon's diversity index and Simpson's diversity index were calculated. Ten cases of AML patients (4 men and 6 women) were included with median age of 39 years (range: 19-49) and all of patients developed febrile neutropenia. Firmicutes were dominated over the period of neutropenic fever and subsequent declined after bone marrow recovery contrast to Bacteroidetes and Proteobacteria. Enterococcus was more abundant at febrile neutropenia period compared to pretreatment while Bacteroides and Escherichia was notably declined during the febrile neutropenia. At the operational taxonomic units (OTUs) level, there was significant higher level of overall richness of pretreatment period than febrile neutropenic episode. Both of the diversity indexes of Shannon and Simpson were considerably decreased at febrile neutropenic period. Adult AML patients with first episode of febrile neutropenia after initial intensive chemotherapy demonstrated the significant decrease of gut microbiota diversity and the level of diversity consistently remained constant despite of bone marrow recovery.


Many papers have been written about resource allocation problems in distributed systems. In solving these optimization problems there has always been a trade-off between the optimality of the solution, the expense in deriving a solution and the complexity of the problem being solved. For problems in Wide Area Networks, the complexity of the problem is immediately more complicated than those for Local Area Networks as the variable communication costs become another factor in the optimization function. In this paper, we show that in practice Wide Area Networks have more structure than usually assumed. Given this, a structured model is presented that can be used to approximate Wide Area Networks and allow "better" solutions to optimization problems due to its properties. A measure is also presented that can be used to determine how close the allocation is to an optimal solution.


BACKGROUND
Difficulty with the proximal lesion approach and durability of endoscopic ultrasonography (EUS) instruments usually limits its application for lower gaotrointestina (GI) lesions to locoregional staging of rectal cancer. This study investigated the value of colonoscopic miniprobe ultrasonography for differential diagnosis and treatment strategy in patients with colorectal subepithelial lesions (SEL).

METHODS
Miniprobe ultrasonography was Performed in 40 consecutive patients with suspected colorectal SEL or residual lesions after endoscopic resection at one medical center by the same endoscopist (C-J Lin). The EUS images and procedure records were reviewed. The final diagnosis of these lesions was confirmed by cross section imaging, histopathologic findings, or clinical follow-up.

RESULTS
Miniprobe EUS allowed high-resolution imaging and a successful approach to all colorectal SEL through the working channel of a sigmoidoscope or colonoscope without breakdown of the miniprobe. Thirteen patients, suspected of having rectal carcinoid tumors (mean size, 6.9 +/- 3.3 mm), were treated radically by endoscopic mucosal resection using a transparent cap (EMRC) after EUS confirmation of no muscular invasion. Three patients had no residual or recurrent carcinoid tumor on EUS examination after previous empiric polypectomy or biopsy. EUS detected submucosal lipomas (mean size, 18.5 mm; range, 8.6-25.6 mm) in ten patients however, only two patients underwent endoscopic resection. Five patients had suspected rectal myogenic stromal tumors on EUS; three were transferred for surgical resection due to uterine myoma compression (N = 2) or mucinous adenocarcinoma of the appendix with rectal metastasis (N = 1), and two had uterine myoma detected by gynecologic ultrasound or CT. One appendiceal stone with orifice obstruction mimicking cecal submucosal tumor was proved by surgical resection. One patient had hemorrhoids proved by hemorrhoidectomy. One patient was proved to have proctitis cystica profunda by EMRC. The other six patients had various benign lesions, which were diagnosed and followed-up by EUS without progression. In thirty-five of forty patients (88%) colorectal SEL were managed uneventfully according to EUS interpretation.

CONCLUSIONS
Miniprobe ultrasonography can be a useful supplement to routine colonoscopy and provide treatment guidance for suspected colorectal subepithelial lesions.


Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA

Melanoma is an aggressive skin cancer characterized by gene mutations, high metastatic potential and few clinically effective systemic therapies. BRAF, MEK1 kinase inhibitors and CTLA4 antagonist have improved patient survival, but only a subset of patients respond or derived long-lasting clinical benefit, illustrating the need for discovery of additional targets and pathways that may be inhibited with small molecules. Given the clinical impact of inhibitors of the ubiquitin-proteasome system in other cancers, we explored the potential for aberrant deubiquitinase (DUB) activity to play a role in the tumorigenic properties of melanoma. We also assessed whether specific DUBs play a role in apoptotic responsiveness and resistance to kinase inhibitors. Initially, we noted that the activity of several DUBs, including Usp9x and Usp5, was elevated in melanoma compared to normal melanocytes. Further, Usp9x and Usp5 expression and activity were up-regulated by expression of BRAFV600E in 293T cells and kinase inhibition partially suppressed both Usp9x and Usp5 activity in vemurafenib sensitive, but not resistant cells. Usp9x knockdown (KD) in BRAF mutant or wild-type melanoma did not affect 2-dimensional cell growth or survival but significantly amplified the apoptotic activity of BRAF or MEK1 inhibitors, respectively. Usp5 KD in melanoma suppressed cell growth by reinforced the S/G2-M checkpoint, enhanced extrinsic caspase activation through modulation of p53 and FAS levels and amplified the apoptotic activity of kinase inhibitors (and other chemotherapeutic agents) and overcame vemurafenib resistance in A375R cells. To further assess the clinical relevance of activated DUBs in melanoma, primary human melanoma explants characterized for their metastatic efficiency in patients and NSG mice demonstrated that Usp9x and Usp5 expression and activity were elevated in efficient metastasizers, but only a subset of inefficient metastasizers, suggesting a potential role for DUBs in the regulation of metastatic potential. To investigate that possibly, control and Usp9x KD cells were grown in Matrigel or suspension culture and colony growth and survival, as well as Usp9x activity were examined. Usp9x KD significantly suppressed melanoma colony growth and fully reduced survival of highly metastatic SK-Mel147 cells in 3D culture. Growth in 3D conditions resulted in activation of Usp9x, but also increased their sensitivity (IC50 <400 nM) to our partially selective Usp9x inhibitor, EOAI3402143 (G9). G9 inhibits both Usp9x and Usp5 activity and phenocopied the activities of both Usp9x and Usp5 KD cells. G9 was safely administered to NSG mice, with complete block of melanoma growth. We conclude that targeted inhibition of specific DUBs will suppress metastatic melanoma and amplify existing melanoma therapies.

Citation Format: Harish Potu, Anupama Pal, Hanshi Sun, Luke Peterson, Moshe Talpaz, Monique Verhaegen, Juxiang Cao, Ugur Eskiocak, Sean Morrison, Nicholas J. Donato. Deubiquitinases Usp9x and Usp5 control tumorigenicity and apoptotic responsiveness in malignant melanoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4435. doi:10.1158/1538-7445.AM2014-4435


The programme of action globally endorsed at the International Conference on Population and Development (ICPD) emphasised the need for equity in gender relations with a special focus on men's shared responsibility and active involvement to promote reproductive and sexual health. If men are brought into a wide range of reproductive health services in such a way that they are supported as equal partners and responsible parents, as well as clients in their own right, better outcomes are expected in reproductive health indicators such as contraception acceptance and continuation, safer sexual behaviours, use of reproductive health services, and reduction in reproductive morbidity and mortality. This paper focuses on these key questions. What does men's involvement mean and how should it be operationalised? What does shared responsibility mean for various reproductive health problems subsumed within the reproductive health framework? Programmes to involve men should be designed to address three major goals: (1) Improve sexual and reproductive health of men and women, (2) generate men's support for women's actions related to reproduction and respect for women's reproductive and sexual rights, and (3) promote responsible and healthy reproductive and sexual behaviour in young men and boys. Gender inequality is a major barrier that must be overcome if these goals are to be met. Improving the reproductive well-being of women and men requires freeing them both from restricted gender roles.


Abstract Given a variety K of lattice-ordered algebras, A ∈ K is catalytic if for all B ∈ K, K(A, B) is a lattice for the pointwise order. The catalytic objects are determined for various varieties of distributive-lattice-ordered algebras. The characterisations obtained do not show an overall unity and exhibit diverse behaviour. Duality is employed extensively. Its usefulness in this context depends on the existence of an order-isomorphism between K(A, B) and the corresponding dual horn-set. Criteria for the existence of such an order-isomorphism are investigated for dualities of the Davey-Werner type. The relationship between catalytic objects and colattices is also discussed.


ABSTRACT Cystic echinococcosis is a zoonotic infection caused by the larval stage of the cestode Echinococcus granulosus. Chemotherapy currently employs benzimidazoles; however, 40% of cases do not respond favorably. With regard to these difficulties, novel therapeutic tools are needed to optimize treatment in humans. The aim of this work was to explore the in vitro and in vivo effects of tamoxifen (TAM) against E. granulosus. In addition, possible mechanisms for the susceptibility of TAM are discussed in relation to calcium homeostasis, P-glycoprotein inhibition, and antagonist effects on a putative steroid receptor. After 24 h of treatment, TAM, at a low micromolar concentration range (10 to 50 μM), inhibited the survival of E. granulosus protoscoleces and metacestodes. Moreover, we demonstrated the chemotherapeutic and chemopreventive pharmacological effects of the drug. At a dose rate of 20 mg/kg of body weight, TAM induced protection against the infection in mice. In the clinical efficacy studies, a reduction in cyst weight was observed after the administration of 20 mg/kg in mice with cysts developed during 3 or 6 months, compared to that of those collected from control mice. Since the collateral effects of high TAM doses have been largely documented in clinical trials, the use of low doses of this drug as a short-term therapy may be a novel alternative approach for human cystic echinococcosis treatment.


The simultaneous use of willow as a vegetation filter and an energy crop can respond both to the increasing energy demand and to the problem of the soil and water contamination. Its characteristics guarantee that the resources are used economically. As a vegetation filter, willow uptakes organic and inorganic contaminants. As a fast growing energy crop it meets the requirements of rural areas without the exploitation of existing forestry. The aim of the research was to gather knowledge on the thermal behaviour of willow, uptaking contaminants and then used as an energy crop. For this reason pyrolysis experiments were performed in two different scales. In analytical scale metal-contaminated wood was investigated and bench scale pyrolysis experiments were performed with nitrogen-enriched willow, originated from a wastewater treatment plant. Results of the pyrolysis showed that 51-81 % of the wastewater derived nitrogen of willow was captured in the char product. Char had low surface area (1.4 to 5.4 m2/g), low bulk density (0.15–0.18 g/cm3), high pH values (7.8–9.4) and high water-holding capacity (1.8 to 4.3 cm3/g) while the bioavailability of char nutrients was low. Links were also established between the pyrolysis temperature and the product properties for maximising the biochar provided benefits for soil applications. Results also showed that the metal binding capacity of wood varied from one metal ion to another, char yield increased and levoglucosan yield decreased in their presence. While char yield was mainly affected by the concentration of the metal ions, levoglucosan yield was more dependent on the type of the ionic species. Combustion experiments were also carried out with metal-enriched char. The burnout temperatures, estimated ignition indices and the conversion indicate that the metal ions type and not the amount were the determining factors during the combustion. Results presented in the Thesis provide better understanding on the thermal behaviour of nitrogen-enriched and metal contaminated biomass which is crucial to design effective pyrolysis units and combustors. These findings are relevant for pyrolysis experiments, where the goal is to yield char for energetic or soil applications.


To inform debate on medical manpower planning and aspects of medical education, we gathered data on graduates of three Irish medical schools in 1978. Twenty six years later, four of the 236 graduates had died and seven were untraceable. All but one of the remainder were in clinical practice and in a wide range of disciplines. A third were overseas. The implications of these findings are briefly discussed.


This paper presents a detailed model for simulation of a Superconducting Magnetic Energy Storage (SMES) system. SMES technology has the potential to bring real power storage characteristic to the utility transmission and distribution systems. The principle of SMES system operation is reviewed in this paper. To understand transient and dynamic performance of a SMES system, a detailed SMES system benchmark model is given with extensive simulation results. This system is demonstrated using an electromagnetic transient program-PSCAD/EMTDC.


Purpose
This paper aims to explore the use of lived experience research in peer work.

Design/methodology/approach
A suite of user-friendly and engaging lived experience research resources was introduced to consumers by peer workers. In-depth interviews were conducted with 33 consumer participants and five peer workers about their experiences. The data were analysed using qualitative content analysis.

Findings
The role of the peer workers appeared critical in ensuring that participants, despite their varied needs, preferences and backgrounds, derived optimum benefit from each resource. Features in resource delivery that promoted a positive experience included presenting the resources in the context of an existing relationship, providing clear explanations, going through resources together, encouraging reflection, taking enough time; and flexible delivery. Peer workers viewed the resources as potentially useful in their everyday peer work and as a valuable addition to their peer work toolkit.

Practical implications
The benefit of lived experience research to consumers is likely to be optimised by supportive and thoughtful delivery of the resources. Peer workers have the skills and are in an ideal position to do this. Bringing lived experience research to consumers provides peer workers with a potentially unique and helpful approach for supporting and promoting recovery and is congruent with their overall practice.

Originality/value
Lived experience research has the potential to benefit consumers directly but is rarely brought to their attention. This paper is the first to examine the potential role of peer workers in introducing learnings from lived experience research to consumers.


The lateral mobility of dilute concentrations of fluorescently labeled lipids doped into supported membranes is found to change upon receptor ligand binding at the membrane surface, even when the lipid is not directly involved in the binding event. Experiments using membrane microarrays are performed that illustrate the use of lipid mobility measurements as an effectively label-free strategy of detecting binding on membrane surfaces.


Background: Medication management of inotropes and vasopressors are essential in critically ill patients, as it is considered as important life-saving medications. The present study was carried out to understand the effect of these drugs on unstable patient and identifying drug-related problems like significant interactions, adverse effects, incompatibility and its factors. Methods: A prospective observational study was carried out in the medical, surgical Intensive Care Unit for a period of 6 months. All the interventions and drug related problems were categorized based on the Pharmaceutical Care Network Europe. Results: Out of 150 study population male patients were more and the majority of patients were from the age group of 60-80 years (56.66%). Most of the admissions were due to septic shock (50%). Noradrenaline (64%) were mostly prescribed. This study illustrates that there is an increased effect of drugs on hemodynamic instability based on mean arterial pressure and heart rate. By comparing before and after administration there was a significant (P<0.0001) increased effect in unstable patients. Among 108 significant drug interactions, dobutamine (50.92%) shows high in frequency. Tachycardia (18.66%) is the most common adverse drug reactions. Among 11 incompatible combinations, Dobutamine+pantoprazole (30.18%) shows the highest and the factors affecting the incompatibility of drugs such as diluents used, rate and duration of infusion, pH of drug solution. Out of 126 recommendations given by clinical pharmacist, 70 problems were solved. Conclusion: Interventions made by a clinical pharmacist improves medication safety in critically ill patients by the safe and effective use of inotropes and vasopressors.


A rare case of mucinous nodules on the skin overlying rheumatoid synovitis in a 79‐year‐old man is described. The patient had a five year history of RA. The patient had complained of arthralgia in the left elbow joint, and X‐ray demonstrated narrowing of the joint space along with bone destruction. He underwent an intraarticular injection of dexamethazone and lidocaine. Three weeks later, he noticed two dome‐shaped nodules about 5 mm in size developing on the elbow. Histopathological examination demonstrated poorly defined mucinous nodules in the upper dermis. The mucinous material positively stained with alcian blue and colloid iron, and was metachromatic with toluidine blue. These positive stainings disappeared after hyaluronidase digestion. Five to six weeks after being resected, both nodules recurred. Lesional injections of triamcinolone were effective. The intraarticular injections preceding the appearance of the nodules might have created channels from the joint space to the skin. Leakage of activated synovial cells, which produced hyaluronic acid, through the channels might have caused the mucinous stroma of the nodules.


A Japanese version of the Sensation-Seeking Scale was developed based on Zuckerman's SSS Form IV. Items of Zuckerman's Form IV were translated into Japanese and were administered to Japanese undergraduates (458 males and 431 females). The results were factor-analysed to select items for the scales. Four factors were originally postulated, but the results were more easily interpretable when five factors were extracted, especially in the female sample. This fifth factor was regarding marihuana use and sexual behavior. In order to match the structure of the scales for both males and females, items highly loaded with this factor were eliminated and the results for the remaining items were again factor-analysed. Then the following four scales were constructed; Thrill and Adventure Seeking (TAS), Experience Seeking (ES), Disinhibition (Dis), and Boredom Susceptibility (BS). Items of TAS scale were highly consistent with Zuckerman's TAS items of Form V. But items of ES, Dis and BS scales were different from those of Zuckerman's and the scales turned out to be those uniquely constructed from Form IV. The test-retest reliabilities (test-retest interval was three months) of the total SSS were .87 and .73 in males and females, respectively. TAS, ES and Dis reliabilities were ranging from .74 to .86 for males, and .74 to .82 for females. However, males' and females' BS were less reliable (.54 and .48 respectively). Internal consistency reliabilities (KR-20) of the total SSS were .75 for males and .65 for females. TAS, ES and Dis reliabilities were ranging from .56 to .67 for males, and .47 to .61 for females. But the BS scale showed poor reliability (.29 for both males and females).


Background Pancreatic ductal adenocarcinoma (PDAC) remains an important cause of cancer death. Changes in apoptosis signaling in pancreatic cancer result in chemotherapy resistance and aggressive growth and metastasizing. The aim of this study was to characterize the apoptosis pathway in pancreatic cancer computationally by evaluation of experimental data from high-throughput technologies and public data bases. Therefore, gene expression analysis of microdissected pancreatic tumor tissue was implemented in a model of the apoptosis pathway obtained by computational protein interaction prediction. Methodology/Principal Findings Apoptosis pathway related genes were assembled from electronic databases. To assess expression of these genes we constructed a virtual subarray from a whole genome analysis from microdissected native tumor tissue. To obtain a model of the apoptosis pathway, interactions of members of the apoptosis pathway were analysed using public databases and computational prediction of protein interactions. Gene expression data were implemented in the apoptosis pathway model. 19 genes were found differentially expressed and 12 genes had an already known pathophysiological role in PDAC, such as Survivin/BIRC5, BNIP3 and TNF-R1. Furthermore we validated differential expression of IL1R2 and Livin/BIRC7 by RT-PCR and immunohistochemistry. Implementation of the gene expression data in the apoptosis pathway map suggested two higher level defects of the pathway at the level of cell death receptors and within the intrinsic signaling cascade consistent with references on apoptosis in PDAC. Protein interaction prediction further showed possible new interactions between the single pathway members, which demonstrate the complexity of the apoptosis pathway. Conclusions/Significance Our data shows that by computational evaluation of public accessible data an acceptable virtual image of the apoptosis pathway might be given. By this approach we could identify two higher level defects of the apoptosis pathway in PDAC. We could further for the first time identify IL1R2 as possible candidate gene in PDAC.


Various opinions have been presented on the merits and demerits that breastfeeding gives for the allergic onset of the babies. In this report, we focused on whether food proteins eaten by mother mice and secreted into breast milk as IgA-immune complexes contribute to the allergy prevention through oral tolerance in infants who ingest the milk. BALB/c mice were divided into two groups; E-group fed only egg white proteins and M-group fed only cow's milk proteins as a dietary protein source. After immunizing M-group infants fed their own mother's milk with ovalbumin/alum, diarrhea associated with experimental Th2 intestinal inflammation was induced by oral administration of ovalbumin. The diarrhea was dramatically suppressed in E-group infants. Concomitantly, low level of serum anti-ovalbumin- and ovomucoid-IgG1 and IgE, suppression of IL-4 synthesis by spleen cells, and low incidence of anaphylactic death after intravenous injection of ovalbumin were observed preferentially in E-infants. Immune complexes of respective dietary proteins and IgA were found in the breast milk obtained from each group of mother. Oral administration of pseudo immune complex chemically synthesized with ovalbumin and monoclonal mouse IgA in advance effectively suppressed anti-ovalbumin-IgG1 synthesis in adult mice after immunization with ovalbumin. The tolerance induced by the pseudo immune complex of ovalbumin diminished spontaneously while mice did not take egg white proteins. Thus, immune tolerance and then prevention of allergic disorder against dietary proteins were acquired via breastfeeding by mothers feeding the relevant proteins, probably through the immune complexes of dietary proteins and sIgAs secreted into breast milk.


In 3D topological insulators achieving a genuine bulk-insulating state is an important research topic. Recently, the material system (Bi,Sb)2(Te,Se)3 (BSTS) has been proposed as a topological insulator with high resistivity and a low carrier concentration (Ren et al 2011 Phys. Rev. B 84 165311). Here we present a study to further refine the bulk-insulating properties of BSTS. We have synthesized BSTS single crystals with compositions around x = 0.5 and y = 1.3. Resistance and Hall effect measurements show high resistivity and record low bulk carrier density for the composition Bi 1.46 ?> Sb 0.54 ?> Te 1.7 ?> Se 1.3 ?> . The analysis of the resistance measured for crystals with different thicknesses within a parallel resistor model shows that the surface contribution to the electrical transport amounts to 97% when the sample thickness is reduced to 1 μm. The magnetoconductance of exfoliated BSTS nanoflakes shows 2D weak antilocalization with &agr; ≃ − 1 ?> as expected for transport dominated by topological surface states.


Little is known about the long-term persistence of positive effects induced by a physical conditioning programme in cystic fibrosis. Therefore, this study determined the effects of a 6-month conditioning programme on peak oxygen uptake (primary outcome) and other markers of fitness, physical activity, anthropometry, lung function and quality of life (secondary outcomes), 18 and 24 months after the programme was initiated. Patients with cystic fibrosis aged 12–40 yrs were randomly assigned to an intervention (n = 23) and a control (n = 15) group. The intervention group consented to add 3 h of sports per week for ≥6 months to their previous activities. Controls were asked to maintain their level of activity for 12 months. Patients were seen at baseline and after 3, 6, 12, 18 and 24 months. There was no significant difference between groups at baseline. The intervention induced positive effects on peak oxygen uptake (difference in changes from baseline to the 18- and 24-month assessments between groups: 3.72±1.23 mL·min−1·kg−1; p<0.01), maximal workload (0.37±0.11 W·kg−1; p<0.01), vigorous physical activity (1.63±0.82 h·week−1; p<0.05), forced vital capacity (6.06±2.87% predicted; p<0.05) and perceived health (9.89±4.72; p<0.05). A home-based partially supervised physical conditioning programme can improve physical fitness, lung function and perceived health long after the intervention has ended.


IMPORTANCE
Between 1980 and 2000, the prevalence of obesity increased significantly among adult men and women in the United States; further significant increases were observed through 2003-2004 for men but not women. Subsequent comparisons of data from 2003-2004 with data through 2011-2012 showed no significant increases for men or women.

OBJECTIVE
To examine obesity prevalence for 2013-2014 and trends over the decade from 2005 through 2014 adjusting for sex, age, race/Hispanic origin, smoking status, and education.

DESIGN, SETTING, AND PARTICIPANTS
Analysis of data obtained from the National Health and Nutrition Examination Survey (NHANES), a cross-sectional, nationally representative health examination survey of the US civilian noninstitutionalized population that includes measured weight and height.

EXPOSURES
Survey period.

MAIN OUTCOMES AND MEASURES
Prevalence of obesity (body mass index ≥30) and class 3 obesity (body mass index ≥40).

RESULTS
This report is based on data from 2638 adult men (mean age, 46.8 years) and 2817 women (mean age, 48.4 years) from the most recent 2 years (2013-2014) of NHANES and data from 21,013 participants in previous NHANES surveys from 2005 through 2012. For the years 2013-2014, the overall age-adjusted prevalence of obesity was 37.7% (95% CI, 35.8%-39.7%); among men, it was 35.0% (95% CI, 32.8%-37.3%); and among women, it was 40.4% (95% CI, 37.6%-43.3%). The corresponding prevalence of class 3 obesity overall was 7.7% (95% CI, 6.2%-9.3%); among men, it was 5.5% (95% CI, 4.0%-7.2%); and among women, it was 9.9% (95% CI, 7.5%-12.3%). Analyses of changes over the decade from 2005 through 2014, adjusted for age, race/Hispanic origin, smoking status, and education, showed significant increasing linear trends among women for overall obesity (P = .004) and for class 3 obesity (P = .01) but not among men (P = .30 for overall obesity; P = .14 for class 3 obesity).

CONCLUSIONS AND RELEVANCE
In this nationally representative survey of adults in the United States, the age-adjusted prevalence of obesity in 2013-2014 was 35.0% among men and 40.4% among women. The corresponding values for class 3 obesity were 5.5% for men and 9.9% for women. For women, the prevalence of overall obesity and of class 3 obesity showed significant linear trends for increase between 2005 and 2014; there were no significant trends for men. Other studies are needed to determine the reasons for these trends.


Polymer based nanoparticle formulations attract attention as potentially highly tunable drug delivery systems. Interfacial deposition is a well-established technique, based on solvent displacement that is being used to form both polymer nanoparticles, as well as drug loaded polymer nanoparticles.
However currently, there is limited understanding of the underlying polymer - nanoparticle assembly mechanisms and this limits our ability to rationally design and optimise them. At the same time, conventional methods for the preparation of polymer-drug nanoparticles suffer from low encapsulation efficiencies and drug loadings, making them undesirable to the pharmaceutical industry.
In this thesis, a method used to polymer-coat the surface of iron oxide nanoparticles was translated to produce polymer-coated drug nanoparticles. In order to provide an holistic overview of the system and the underlying phenomena, both computational and experimental methods were used.
More particularly, all atom molecular dynamics simulations were employed to study the behaviour of the drug nanoparticles and the polymers during the interfacial deposition method. The system was built as a biphasic model, containing an aqueous-drug loaded-phase and an organic-polymer rich-phase. The model was a miniature in the atomistic level of the expected experimental set-up, keeping the ratios and concentrations as close as possible to pre-existing iron oxide nanoparticle work.
On a parallel path, experimental studies were performed. The polymers were synthesised and fully characterised. Then, the formation of drug-free polymer nanoparticles via the method was studied and the properties of these nanoparticles were analysed. Interestingly, when the drug was introduced into the method in the form of drug microparticles suspended in the aqueous region, polymer-coated drug nanoparticles were produced. These nanoparticles were stable, significantly different to the drug-free polymer nanoparticles and were characterised for their size and morphology. Further analysis of the polymer-coated drug nanoparticle suspensions revealed high encapsulation efficiencies and impressive drug loadings.
We conclude with some proposed future work on modelling polymer-based drug delivery systems, moving towards a "structure based formulation design" to complement the process of "structure based drug design" which is already very well established in the pharmaceutical industry.


`The beginning of the twenty-first century stands a good chance of being identified in history as the time when humankind first came to grips with the Universe ... The emergence of the standard cosmological model had left by the wayside many concepts which in the late 1990s had still had possible relevance for our Universe'. Do these confident assertions by the authors of this new cosmology textbook show that we have reached an `end of history' regarding the big questions of cosmic origins, or is this just more in the line of Landau's quip: `Cosmologists are often in error, but never in doubt'? Despite Landau's comment having some justice at the time, a lot can change in science in over 50 years, and there is indeed a fair case that our overall picture of the Universe has converged. The standard cosmology is dominated by vacuum energy, and contains clumped dark matter whose inhomogeneity was seeded by quantum fluctuations during a period of `inflation', when the vacuum energy was very much higher than it is today. All the theoretical elements of this picture were put in place during a remarkable period of about three years at the start of the 1980s—a revolution surely comparable with the dawn of quantum mechanics in the 1920s. Consistency of this theory with observations hardened progressively during the 1990s, and all serious resistance finally evaporated in 2003 with the first detailed sky maps of the microwave background from NASA's WMAP satellite. The philosophy of this textbook is therefore a good one: rather than dwelling on how we arrived at our current understanding, the aim is to give a clear and clean presentation of the theory, preparing the interpretative framework for the new datasets that are set to arrive in the near future. This represents a deliberate departure from the broader perspective of the book written by the same authors (in the opposite order) in 2000: Lyth and Liddle's view is that the past decade has added so many new observations that the field has changed beyond the point where a simple update is sufficient, and it is hard to disagree. The benefits of the new approach show themselves in the elegance with which the book sets up the formalism for describing metric fluctuations in an expanding Universe, and how such fluctuations are generated during an early phase when the Universe is assumed to be dominated by the energy density of one or more hypothetical scalar fields. The key observables that let us probe this era are the scale-dependence of the density fluctuation spectrum; the tensor fluctuations (primordial gravity waves); and the extent to which the fluctuations deviate from a random-phase Gaussian character. Lyth in particular is an acknowledged master of this material, and has been responsible for creating significant parts of the formalism being described in the book. The fine details of calculating the origin of structure in exotic models are all present, and are set in the context of a nice pedagogical exposition and revision of relevant background in general relativity and field theory. This is a complete guide that can take a graduate student from undergraduate knowledge to calculations at the forefront of research. This book will thus be an indispensable companion for those researchers working in the theory of structure in the early Universe, and those teaching it at the postgraduate level. I have already found it useful for sharpening arguments in lecture notes that I previously regarded as fairly mature. It is not the only book in this area, but it is really the best on the fundamental topics where it concentrates its efforts. On the issue of computing the observational consequences of inflationary fluctuations (i.e. galaxy clustering and anisotropies in the Cosmic Microwave Background), Dodelson's Modern Cosmology (Academic Press) will probably have more appeal to most readers, simply because it treats these matters at greater length and with more use of physical analogy. But readers with some previous exposure to these topics will enjoy the stripped-down clarity of Lyth and Liddle's presentation. Dodelson also has the advantage that he gives outline solutions to his exercises, whereas Lyth and Liddle do not. I do think this is a pity, since students learn nothing from defeat by a problem they cannot solve, but can benefit enormously from struggling and then consulting a hint that helps them see where the key difficulty lay; something for the second edition, perhaps? In all of this, though, we should not lose sight of something a little peculiar. This is a textbook that provides great detail on a mature theory, which has seen great efforts and huge refinements over the past 30 years. And yet we have almost no idea if inflation is the correct theory of the early Universe. Some semi-popular treatments, even quite sophisticated ones, claim that observations of the CMB have proved inflation to be true, and one encounters many students who believe this excessive claim. The enthusiasm of advocates is understandable, since inflation has seen some great successes. Before it was suggested, we knew empirically that the early Universe must have had a mechanism for almost perfectly eliminating spatial curvature in the initial conditions, and generating fluctuations in an acausal manner, so that the Universe is very nearly uniform on large spatial scales, but not quite. The triumph of inflation is that it was designed to solve the first problem, and subsequently realized to offer in addition a possible solution to the second. But we really would like more direct evidence that the energy density was once dominated by a scalar field, and Lyth and Liddle's book is devoted to calculating the three observational signatures: `tilt' of the fluctuation spectrum, relic gravity waves, and non-Gaussianity. The first of these has already been seen, and if the other two signatures can be verified, then we would have a set of interlocking tests that could provide consistent verification of the theory. But as the authors admit in a coda, there are many models where these additional features will never be observable. Inflation would then remain in its current state: provisional acceptance by virtue of lack of an alternative. For the health of cosmology, we have to hope that future observations will be richer than this; as the data come in, Lyth and Liddle will be an essential guide.


IP boxes or patent boxes can be introduced so as to promote research and development (R&D) activities or attract mobile IP assets, but they can also cause harmful tax competition. Action 5 of BEPS project has analysed this problem and proposes the application of a 'nexus approach' that aligns R&D expenditures with the conferment of tax benefits. If this nexus approach is adopted by EU member states, they will have to respect state aid rules and fundamental freedoms. This paper analyses the OECD's nexus approach, the Anglo-German joint statement proposing a 'modified nexus approach', and the Italian IP box. The compatibility with EU law of all three and their likeliness to prevent harmful tax competition is assessed.


The aetiology of focal, preganancy-like mammary changes in non-pregnant and non-lactating women is discussed on the basis of the literature and a material of 31 patients. Such changes were found in one or more glandular lobules in 3 per cent of the breast tissue specimens received in our departments. As a rule, this finding was made in women who had been pregnant and who had been or were on oestrogenic or on contraceptive medication. They occurred in fertile, menopausal, as well as in post-menopausal women. Often they were seen many years after the pregnancy and/or intake of hormones. They were observed also in women who had never been pregnant or on hormone medication, and even in men on oestrogen therapy. It is likely, therefore, that focal pregnancy-like changes in non-pregnant and non-lactating women indicate a selective susceptibility of the mammary glandular tissue to oestrogen. Accordingly, we interpret the change as a normal histological variant.


This essay identifies five paradigms that are basic to understanding the historical emergence and uses of the generic idea of "religion" in the Christian cultures of Europe and America. The spread of this concept has been sufficiently thorough in recent centuries as to make religion appear to be a "social fact," to use Durkheim's phrase, rather than so many cultural expressions and different social practices. The supremacy of Euro-American culture -and an academy still saturated with Christian ideas--has enjoined other cultures and forms of religiosity to conform to this idea of religion; for these cultures contentment with the status quo can vie with the anxieties of influence, including "modernization." The key paradigms discussed are the following: Christianity as the prototype; religion as the opposite of reason; the modem formulation of "world religions"; the cultural necessity of religion; and critical analysis of the Western "construction" of religion. These paradigms demonstrate the limits on theoretical variety in the field, the difficulty in making real changes in set ways of thinking, and productive foci for interdisciplinary methods of study.


Over the past decade, tissue engineering in the field of medicine has proven to provide alternative therapies for tissue or organ implants, especially providing a functional implantation and avoiding immune rejection of tissues and organs. [...].


Bimetallic nanoparticles (BNPs) are promising candidates for fundamental research and applications as their physico-chemical properties can in many cases be tuned continuously or enhanced with respect to the mono-metallic particles. Here we investigate the possibility of fabricating silver-indium and silver-aluminium BNPs in the range of 4-5 nm diameter and of varying stoichiometry by laser vaporization and gas condensation in the gas phase. We analyse their crystalline structure and segregation behaviour using transmission electron microscopy and probe their oxidation state in optical absorption measurements by tracking spectral changes of the localized surface plasmon resonance (LSPR). These complementary techniques show that, despite the small size and the high reactivity especially of aluminium, the BNPs form a silver-rich alloyed core surrounded by an oxide shell. Exposure to air leads to consecutive oxidation, whereas annealing the BNPs in a reducing atmosphere stabilizes the alloyed particle cores, as demonstrated by a narrow and blue-shifted LSPR. This is a first step towards the stabilization of non-oxidized bimetallic nanoparticles combining a noble and a trivalent metal.


Care provided by a primary care practice that embraces the medical home model is better organized, more accessible, and less stressful to coordinate—so say parents of children who have special health-care needs. Here is a look at how you and your practice benefit from providing family-centered care within the medical home model.


Due to the limited energy resources, energy efficient operation of sensor node is a key issue in wireless sensor networks. Clustering is an effective method to prolong the lifetime of energy constrained wireless sensor network. However, clustering in wireless sensor network faces several challenges such as selection of an optimal group of sensor nodes as cluster, optimum selection of cluster head, energy balanced optimal strategy for rotating the role of cluster head in a cluster, maintaining intra and inter cluster connectivity and optimal data routing in the network. In this paper, we propose a protocol supporting an energy efficient clustering, cluster head selection/rotation and data routing method to prolong the lifetime of sensor network. Simulation results demonstrate that the proposed protocol prolongs network lifetime due to the use of efficient clustering, cluster head selection/rotation and data routing. So this paper propose realistic routing technique base on clustering. Keywords-Wireless Sensor Networks, Clustering


UNLABELLED
Resistance to thyroid hormone (RTH) syndrome is caused by thyroid hormone beta receptor (TRbeta) mutations. Goiter, learning disabilities, psychological abnormalities, sinus tachycardia, hearing deficits, short stature, and growth delay are among the most common symptoms in patients with RTH. Alopecia areata (AA) is an autoimmune disease of the hair follicle, frequently associated with other autoimmune disorders. In some cases local alopecia of different genetic backgrounds could be misdiagnosed as AA. We describe here clinical, biochemical and genetic features of a family having RTH syndrome, caused by a novel TRbeta mutation, coexistent with alopecia. Mutational analyses of the TRbeta gene and the hairless gene (HR) in genomic DNA were performed. The index patient is a 9-4/12 year-old boy with RTH due to a novel heterozygous missense mutation of the TRbeta gene (I353V), and diffuse, patchy alopecia without autoimmune thyroid disease. This mutation was also detected in his father and elder brother, who also have local alopecia. One of his paternal aunts and paternal grandmother have local alopecia and they have previously been operated for goiter. Although they refused any genetic analysis, the pre-operative medical report of the paternal aunt was compatible with RTH. A second paternal aunt has alopecia totalis universalis but has no RTH mutation in genomic DNA. Genomic DNA sequence of the HR gene of the family (index patient, two brothers, father, mother and second paternal aunt) was normal as well.

CONCLUSION
We speculate that RTH due to a novel I353V TRbeta mutation could be causally related to different phenotypic expressions of alopecia in this family, either by a direct effect of unresponsiveness to T3 of the hair follicle or by the modulated action of the HR gene.


High spin states in 90Mo have been populated through the 59Co (35Cl,2p2n) 90Mo reaction at a beam energy of 116 MeV. Level lifetimes of the positive-parity decay sequence are measured by using the Doppler shift attenuation method. It is observed that the M1 transition strengths show a substantial enhancement at high spin. This behaviour may be related to occupation of high Ω orbitals by a pair of g9/2 protons. A deformed, oblate, shape is suggested above the 13+ state.


Establishing an optimal intercooled aero engine constitutes a coupled problem where the conceptual design of the intercooler and the engine has to be considered simultaneously. The heat transfer and pressure loss characteristics will depend on the choice of the intercooler architecture. Hence, to be able to optimize the performance of an intercooled aero engine, the performance characteristics of a given intercooler architecture has to be known in the parameter range anticipated for the aero engine optimization. In this thesis, several design concepts of a two-pass cross flow tubular intercooler for aero engine application have been analyzed by the use of computational fluid dynamics simulations and system level assessments. The work comprises 3D coupled CFD analysis of the internal flow (in-flow, cross-over and out-flow duct) using porous media modelling for the tube stacks. Several design iterations on the internal flow configuration has been performed applying two splitter vanes and a flow guide vane. A parametric study of the external heat transfer and pressure loss is included. Correlations for two configurations (straight tube and involute spiral tube) are provided for system level assessments of this intercooler concept. In addition to providing heat transfer and pressure loss characteristics, the correlations are set up to allow intercooler installation space constraints to be taken into account. The fuel burn benefits of the presented intercooled engine are attributed to the use of a variable geometry separate exhaust nozzle and to providing an adequate amount of intercooling. The amount of intercooling should be sufficient to enable the high OPR at take-off, and allow a compact engine design. In cruise, on the other hand, it is beneficial to reduce the intercooling to establish an optimum between intercooling and incurred pressure losses.


The adult tapeworm, Hymenolepis diminuta, living in the lumen of the intestine of its normal rat host was shown to sensitize the intestine. The growth of worms in a secondary infection, given 8, 23, or 41 days after the primary infection had been removed by anthelmintic treatment, was 0.5, 3, and 25%, respectively, of that in the control worms. Thus, there is a strong initial resistance to a challenge infection, but this resistance weakens fifty-fold between days 8 and 41 postinfection. Even primary infections of five worms, which would have survived indefinitely if not expelled by anthelmintics, depressed the growth by over 80% of secondary infections given 8 days later. Rats given a light primary infection manifested their sensitivity only by depressing the growth of challenge worms, but in strongly sensitized rats, worm growth was stunted severely (or the worms destrobilated), partial worm expulsion occurred, and the remaining worms migrated to a more anterior position in the intestine. We suggest that the rapid waning of memory indicates that the protective mechanism evoked in the intestine has as its primary biological function the limitation of the number of worms that can accumulate in the intestine in concurrent infections, not the prevention of reinfection after the loss of worms from previous infections.


Recent advances in both camera technology as well as supporting computing hardware have made it significantly easier to acquire, transmit, process and store large amounts of image data. As a consequence a number of image databases, specifically face databases, have been collected, often with the expressed goal of sharing the data with others. Due to concerns about the privacy of the individuals visible in the scene, data dissemination is particularly difficult for medical face databases depicting patients.

For most data usage scenarios however, knowledge of the identity of people in the image is not required. This makes the case for image de-identification, the removal of identifying information from images, prior to sharing of the data. The implicit goal of these methods is to protect privacy and preserve data utility, for example the ability to recognize gender or facial expressions from de-identified images. While privacy protection methods are well established for field-structured data, work on images is still limited.

The appearance of a face is influenced by a number of factors including (but not limited to) identity, pose, facial expression, illumination, and gender. Algorithms have been developed to factorize facial appearance into these underlying components using linear and bilinear as well as tensor models. In this paper we describe a novel framework for the de-identification of facial images. We use Active Appearance Models (AAMs) for initial parameterization, before we apply a multi-factor model which unifies linear, bilinear, and quadratic models to factorize the face parameters into identity and non-identity components. The resulting representation is then de-identified according to one of multiple privacy protection models.

We evaluate the proposed face de-identification system on a large-scale still image face database, the CMU Multi-PIE database. We measure face recognition performance on de-identified images as well as data utility (quantified as accuracy of facial expression recognition) using a support vector machine classifier trained on the original data. In comparison to naive blur de-identification as well as to the previously proposed formal k-Same algorithm our method preserves data utility much better while providing equivalent privacy protection. Our framework directly extends from single images to image sequences. We demonstrate this by de-identifying videos of subjects displaying pain expressions.


Sweet sorghum [Sorghum bicolor (L.) Moench] is recognized as a promising biomass energy crop for meeting the increasing
demand for bioenergy feedstocks. Field experiments were conducted at sites in northern and southern Louisiana for 2 yr to assess
planting date and harvest maturity effects on yield from primary plantings and ratoon crops. The cultivar M81-E was evaluated
using a split plot arrangement of treatments in randomized complete block designs. Planting date from mid-March to early July
was the primary plot treatment. Harvest maturity at the early heading (EH) or hard dough (HD) stage was assigned as the subplot
treatment. A range of planting dates from mid-March to early June produced substantial yields of biomass and fermentable sugar
with appropriate harvest maturity and could support sugar mill operation for up to three additional months. However, sweet
sorghum planted in early May and harvested at the HD stage produced 30 to 210% more fermentable sugar than other tested
planting dates and maturity combinations. Ratoon crop production was not dependable showing inconsistent tiller growth with
resultant low biomass yields. Correlation coefficients of sugar yield with biomass or other quantitative agronomic characteristics
were higher than 0.79, while that with brix was only 0.32 (P < 0.0001). Production management in Louisiana from long season
cultivars such as M81-E based on a single harvest 150 to 160 d from planting at the HD stage can provide more biomass and
fermentable sugar than can production management targeting a ratoon crop.


Theories of distributive justice have great difficulties in conceptualizing immigration as a political rather than a moral problem. Exploring the reasons for this reductive move, and explaining why it is self-defeating, this paper argues that immigration poses a thoroughly political problem because spatial boundaries are posited from the first-person plural perspective of a 'we.' Yet the politics of boundaries deployed in immigration policy are also necessarily problematic: while polities claim a right to include and exclude aliens because a territory is held to be the own place of their citizens, an act of inclusion and exclusion gives rise to a 'we.' This circularity disrupts—without effacing—the inside/outside and right/fact distinctions that underpin the right to closure polities claim for themselves. The stake of this disruption is temporal no less than spatial: as polities close themselves into a legal space through a mutual promise to which there is no direct access, distributive justice requires that authorities decide what promises had been made in the light of boundary crossings that determine what promises can be kept.


Companies have caught the changes in consumer perceptions and have developed corporate social responsibility (CSR) as long run survival strategy. The CSR signals that companies are overcoming the logic of the short term. The question is whether an evolution towards something similar that we call State social responsibility (SSR) is possible. State social responsibility is exerted when the State, in absence (or in case of ineffectiveness) of a formal supranational law, protects the rights of current and future generations of its citizens and citizens of other states and/or raises the current generations' awareness regarding the opportunities reduction generated in space and time by meta-externalities. States would signal the tendency to overcome their short-sighted logic if the meta-externalities became a crucial question in their agenda.


The slow pace of firm valuation and the rising occurrences of fraud have been attributed in part to corporate governance. This research aims to educate the companies and their management who are capable of reversing the current pace to a much better pace. This study also aims to ascertain the firm value response to internal and external corporate governance using evidence from the Nigerian stock market, which covers the period from 2012 to 2019. To determine the response of firm value to the internal and external corporate governance mechanisms, two indexes were determined using the Principal Component Analysis (PCA), and data was sourced from the annual reports of the sampled firms listed on the Nigerian stock market. The variables used were firm value proxied by Tobin's Q, and the internal corporate governance index composed of board independence, board meeting, board size, and board education; and then the external corporate governance index was represented by corporate disclosures, audit type, timeliness of reporting, and corporate governance code. The data was analyzed through a series of tests including the descriptive statistics, PCA, correlation matrix, and panel data static estimators, amongst others. The findings obtained from the analysis show that internal corporate governance has a positive and significant influence on firm valuation and that external corporate governance has a negative and insignificant influence on firm valuation.


Medical procedures such as seed implantation, biopsies, and treatment injections require inserting a needle tip to a specific target location inside the human body. This is difficult because (1) needle insertion causes soft tissues to displace and deform, and (2) it is often difficult or impossible to obtain precise imaging data during insertion. We are developing a sensorless planning system for needle insertion that incorporates numerical optimization with a soft tissue simulation based on a dynamic FEM formulation that models the effects of needle tip and frictional forces using a 2D mesh. In this paper we describe a sensorless planning algorithm for radioactive seed implantation that computes needle insertion offsets that compensate for tissue deformations. We apply the method to seed implantation during permanent seed prostate brachytherapy to minimize seed placement error in simulation without relying on real-time imaging.


Abstract During the 20th century, urbanization has increasing and represented a major demographic and environmental change in developed countries. This ever-changing urban environment has an impact on disease patterns and prevalence, namely on noncommunicable diseases, such as asthma and allergy, and poses many challenges to understand the relationship between the changing urban environment and the children health. The complex interaction between human beings and urbanization is dependent not only on individual determinants such as sex, age, social or economic resources, and lifestyles and behaviors, but also on environment, including air pollution, indoors and outdoors, land use, biodiversity, and handiness of green areas. Therefore, the assessment and identification of the impact of urban environment on children's health have become a priority and many recent studies have been conducted with the goal of better understanding the impacts related to urbanization, characterizing indoor air exposure, identifying types of neighborhoods, or characteristics of neighborhoods that promote health benefits. Thus, this review focuses on the role of urban environmental factors on pediatric asthma.


: Objective: To screen earthquake victims at risk of Posttraumatic Stress Disorder (PTSD), at 1 month after the event, and to anticipate the service needs at medical camps. Methodology: The design of study was descriptive cross-sectional, conducted at Pakistan Islamic Medical Association Medical Camp, held in Mian Muhammad Bukhsh Academy, Pulmanda, Mirpur, Azad Kashmir, on 20th October, 2019. Earthquake victims who presented at medical camp were selected randomly and screened through face-to-face clinical interviews by medical officers using Trauma Screening Questionnaire (TSQ) modified to relate to the earthquake, using cut-off value of 6. Considering the ethical issues, our study was intended to be kept as close to routine clinical practice as possible. Cross tabulations were used to analyze the variables with bivariate analysis of factors involved. Results: A total of 45 patients were screened, out of which 37 met the inclusion criteria. 6 (16.2%) were males and 31 (83.8%) were females, with the mean age of the sample being 38±16 years. Out of 37, 28 (75.7%) were found to be susceptible to developing Posttraumatic Stress Disorder (PTSD) out of which 3 were males and 25 were females. The mean Trauma Screening Questionnaire score of samples was 6.9±2.0. Conclusion: Evidence of high frequency of susceptibility to developing Posttraumatic Stress Disorder (PTSD) in earthquake victims demands for a system of screening of at-risk individuals at medical camps and their active monitoring and cognitive therapy as required.


Common sense—meaning a traditional attack on perceived problems—is repeatedly cited as the best way to improve a neighborhood. But after reviewing multiple attempts to address problems in middle neighborhoods, this author argues that common sense approaches are not working. This chapter offers alternate approaches that are being used by residents and city officials around the country to reinvigorate middle neighborhoods.


The aromatic ring substitution reaction of 3-methyl phenol with methyl α-eleostearate under acidic conditions was carried out. The product was analyzed to find out if 3-methyl phenol was subjected to the ring substitution reaction with methyl α-eleostearate at its conjugated double bonds. Up to two molecules of 3-methyl phenol were addition-reacted with the conjugated triene of the eleostearyl group of methyl α-eleostearate. The 4-position of 3-methyl phenol was preferentially subjected to the cresol's ring substitution. When 3-methyl phenol was reacted with a relatively large amount of methyl α-eleostearate, the substitution reaction occurred at the 6- as well as 4-position of 3-methyl phenol, to yield a methyl α-eleostearate dimer having 3-methyl phenol units in its molecule. The above results were confirmed by infrared (IR), nuclear magnetic resonance (NMR), and high-speed liquid chromatographic (HLC) analyses, and the results of a previous paper connected with reaction of 3-methyl phenol were supported by the results of this paper.


We consider the problem of episodic reinforcement learning where there are multiple stakeholders with different reward functions. Our goal is to output a policy that is socially fair with respect to different reward functions. Prior works have proposed different objectives that a fair policy must optimize including minimum welfare, and generalized Gini welfare. We first take an axiomatic view of the problem, and propose four axioms that any such fair objective must satisfy. We show that the Nash social welfare is the unique objective that uniquely satisfies all four objectives, whereas prior objectives fail to satisfy all four axioms. We then consider the learning version of the problem where the underlying model i.e. Markov decision process is unknown. We consider the problem of minimizing regret with respect to the fair policies maximizing three different fair objectives -- minimum welfare, generalized Gini welfare, and Nash social welfare. Based on optimistic planning, we propose a generic learning algorithm and derive its regret bound with respect to the three different policies. For the objective of Nash social welfare, we also derive a lower bound in regret that grows exponentially with $n$, the number of agents. Finally, we show that for the objective of minimum welfare, one can improve regret by a factor of $O(H)$ for a weaker notion of regret.


Time warping finds use in many fields of time series analysis, and it has been effectively implemented in many different application areas. Rather than focusing on a particular application area we approach the general problem definition, and employ principal curves, a powerful machine learning tool, to improve the noise robustness of existing time warping methods. The increasing noise level is the most important problem that leads to unnatural alignments. Therefore, we tested our approach in low signal-to-noise ratio (SNR) signals, and obtained satisfactory results. Moreover, for the signals denoised by principal curve projections we propose a differential equation-based time warping method, which has a comparable performance with lower computational complexity than the existing techniques.


BACKGROUND
The purpose of this study was to evaluate the predictability of implant placement at the time of maxillary molar extraction using a modified insertion technique and implant design.

METHODS
At the time of maxillary molar extraction, 83 tapered-end implants with an apical diameter of 4.1 mm and a neck diameter of 6.5 mm were placed in maxillary first or second molar sites, following manipulation of the remaining interradicular bone with osteotomes. Regenerative materials, consisting of demineralized freeze-dried bone allograft (DFDBA) and/or osseous coagulum, and bioabsorbable or non-resorbable membranes were placed, and passive soft-tissue primary closure was attained in all cases.

RESULTS
Soft-tissue closure was maintained until the time of clinical reentry 6 months after implant insertion in 81 of 83 sites. Loss of primary soft-tissue closure in the other two areas did not result in complete uncovering of the cover screw and implant top. All implants were clinically immobile at the time of implant uncovery 6 months after insertion and were restored with single crowns. All implants were functioning successfully for up to 18 months (mean: 12.4 months).

CONCLUSION
The combination of atraumatic removal of hopeless maxillary molars, controlled manipulation of the residual interradicular bone, insertion of implants of the aforementioned design, and use of appropriate regenerative materials at the time of implant insertion predictably afforded a stable implant for restoration with a single crown.


A diver uses typically a compass, a depth gauge and a timer for underwater navigation. Especially when it comes to advanced diving in caves or wrecks, navigation and knowledge about the current position is extremely important, otherwise the diver might not find his way back to the surface and drown as soon as the breathing gas supply is finished. Other approaches are based on ultrasound transmitters that allow simple navigation tasks, however they are useless for applications like cave, wreck or long distance diving. The current paper describes a navigation platform for divers which is based on a handset with a depth sensor and a display, an inertial measurement unit incorporation gyroscopes, accelerometers and magentometers and an interface to attach different kinds of flow sensors for velocity measurement. A first prototype was developed. Additionally a buoy with an integrated GSM/GPS transmitter and a reference system for laboratory measurements can be attached. The prototype was validated in a pool and tests with the GPS reference system were carried out in the open sea.


Objective: Some studies have shown that it is possible to evaluate tubal permeability through MRI. Our aim is to perform a prospective study and to perform a comprehensive review in the literature regarding HSG-MRI. Methods: We carried out a PUBMED search using the following keywords: hysterosalpingogram, hysterosalpingography, magnetic resonance imaging and MRI. As inclusion criteria, we included only papers published in English, and exams ran on humans. We also conducted a prospective inclusion of patients who had visited a human reproduction clinic between May/2017 and April/2019 for laboratory image diagnoses using HSG-MRI. Results: Following the inclusion and exclusion criteria, we included seven original papers. Review papers and those written in a language other than English, were excluded. Between the period of May/2017 and April/2019, we selected ten patients for our study. The average exam duration was 30 minutes. Cervical catheterization was possible in all cases. There were no major complications. We highlight that in 8/9 of patients, we could directly visualize uterine tubes with contrast (excluding one patient with bilateral tubal ligation). Conclusions: Our initial experience with HSG-MRI shows promise. We demonstrated an optimized protocol for conducting an HSG-MRI (with excellent image quality). HSG-MRI had some advantages, such as not using ionized radiation, less pain and being able to analyze pelvic anatomy. Patients referred for a pelvic MRI as part of a more detailed investigation into infertility can also benefit from undergoing a simultaneous HSG using MRI.


Abstract Chloroplast DNA (cpDNA) atpB-rbcL intergenic spacers of individuals of Alsophila podophylla, collected from eight relict populations distributed in Hainan and Guangdong Province, southern China, were sequenced. Sequence sizes were 726 or 727bp. Base composition had a high A+T content of 62.67–63.00%. Sequences were assessed as evolutionarily neutral (Tajima's criterion D = −0.80683, P > 0.10 and Fu and Li's test D* = 1.42648, P > 0.05; F* = 0.76638, P > 0.10). Eight haplotypes were identified based on a statistical parsimony algorithm. A high level of haplotype diversity (h = 0.618) and a low nucleotide diversity (Dij = 0.00208) were detected in A. podophylla. Populations from Hainan shared common haplotypes with those from Guangdong. A network and a NJ tree constructed from cpDNA haplotypes both suggested a close genetic relationship among populations distributed in Hainan and Guangdong. Observed FST (=0.10537), gene flow Nm (=2.12), AMOVA (Only 0.49% of variation was partitioned among regions, P = 0.09), and DNA divergence data consistently indicated that no geographical differentiation occured at the interregional level. Geographic isolation has not yet resulted in population differentiations within A. podophylla populations in Hainan and Guangdong. Phylogeographical patterns of atpB-rbcL haplotypes demonstrate a 'star-like' feature, which means that populations of A. podophylla have experienced population expansion, and, since then there has been insufficient time to form a more complicated population structure. The majority of haplotypes coalesced near the tip of the NJ tree, indicating recent coalescence events as well. Moreover, a demographic signature of population expansion was detected by mismatch distribution analysis of atpB-rbcL sequences of A. podophylla.


Targeting the two degradation systems, ubiquitin proteasome pathway and ubiquitin signal autophagy lysosome system, plays an important function in cancer prevention. Borneol is called an "upper guiding drug". Luteolin has demonstrated anticancer activity. The fact that borneol regulates luteolin can be sufficient to serve as an alternative strategy. Borneol activates luteolin to inhibit E1 and 20S activity (IC50 = 118.8 ± 15.7 μM) and perturb the 26S proteasome structure in vitro. Borneol regulates luteolin to inhibit 26S activity (IC50 = 157 ± 19 μM), induces apoptosis (LC50 = 134 ± 4 μM), and causes pre-G1 and G0/G1 arrest in HepG2 cells. Borneol regulates luteolin to induce ubiquitin signal autophagic degradation, resulting in induction of E1, reduction of USP47, and accumulation of p62 in HepG2 reporter cells. Interestingly, luteolin decreased Ub conjugates, while borneol increased the accumulation of Ub conjugates in HepG2 reporter cells. E1, p62, and ubiquitin levels were downregulated in borneol-treated HepG2 reporter cells at 24 h. These observations suggest a potential autophagic inhibitor of borneol that may guide luteolin in the ubiquitin proteasome pathway and the ubiquitin signal autophagic degradation.