AIDS Inhibitors of HIV-1 Protease, Krzysztof Appelt A Review of Structural Studies of HIV-1 Reverse Transcriptase and Implications for Drug Design, Jianping Ding, Kalyan Das, Prem N. S. Yadav, Yu Hsiou, Wanyi Zhang, Stephen H. Hughes, and Edward Arnold Retroviral Integrase: Structure as a Foundation for Drug Design, Alison B. Hickman and Fred Dyda Arthritis and Inflammation Bradykinin Receptor Antagonists, Donald J. Kyle Cancer Design of Purine Nucleoside Phosphorylase Inhibitors, Y. Sudhakara Babu, John A. Montgomery, Charles E. Bugg, W. Michael Carson, Sthanam V. L. Narayana, William J. Cook, Steven E. Ealick, Wayne C. Guida, Mark Erion, and John Secrist III Structural Implications in the Design of Matrix-Metalloproteinase Inhibitors, John C. Spurlino Structure - Function Relationships in Hydroxysteroid Dehydrogenases, Igor Tsigelny and Michael Baker Design of ATP Competitive Specific Inhibitors of Protein Kinases Using Template Modeling, Janusz M. Sowadski, Charles A. Ellis, Rolf Karlsson, and Madhusudan Diabetes Mellitis Structural Studies of Aldose Reductase Inhibition, David K. Wilson, J. Mark Petrash, and Florante A. Quiocho Heart Diseases Structure-Based Design of Thrombin Inhibitors, Patricia C. Weber and Michael Czarniecki Design of Antithrombotic Agents Directed at Factor Xa, William C. Ripka Polypeptide Modulators of Sodium Channel Function as a Basis for the Development of Novel Cardiac Stimulants, Raymond S. Norton Rational Design of Renin Inhibitors, V. Dhanaraj and J. B. Cooper Parkinson's Disease Structural Aspects in the Inhibitor Design of Catechol O-Methyltransferase, Jukka Vidgren and Martti Ovaska Sleeping Sickness Antitrypanosomiasis Drug Development Based on Structures of Glycolytic Enzymes, Christopher L. M. J. Verlinde, Hidong Kim, Bradley E. Bernstein, Shekhar C. Mande, and Wim G. J. Hol Immune Diseases and Cytokines Progress in the Design of Immunomodulators Based on the Structure of Interleukin-1, Glen Spraggon and Pandi Veerapandian Structure and Functional Studies of Interferon: A Solid Foundation for Rational Drug Design, Michael A. Jarpe, Carol H. Pontzer, Brian E. Szente, and Howard M. Johnson Antivirals The Design of Anti-Influenza Virus Drugs from the X-Ray Molecular Structure of Influenza Virus Neuraminidase, Joseph N. Varghese Rhinoviral Capsid-Binding Inhibitors: Structural Basis for Understanding Rhinoviral Biology and for Drug Design, Vincent L. Giranda and Guy D. Diana Novel Methodologies The Integration of Structure-Based Design and Directed Combinatorial Chemistry for New Pharmaceutical Discovery, Roger Bone and F. Raymond Salemme Structure-Based Combinatorial Ligand Design, Amedeo Caflisch and Claus Ehrhardt Peptidomimetic and Neopeptide Drug Discovery: Impact on Structure-Based Drug Design, Tomi K. Sawyer


Abstract It is pointed out that in many one-sided testing situations for a real-valued parameter θ, the monotonicity of the power function hinges on the stochastic order of the underlying family of distributions [Fθ] rather than on the stronger property of monotone likelihood ratio of the family. An elementary proof, accessible to students of introductory probability and statistics, is presented.


Ectopic decidua is defined as extrauterine deposits of decidual stromal cells. It occurs in 85-100% of pregnancies. Focal sites can be present in various locations, yet a peritoneal location is rare. A 24- year- old woman underwent a cesarean section in 39th week of her first pregnancy, during which adhesions of the omentum to the fundus, entire left side of the uterus, and a part of the right front abdominal wall were found. An operative specimen was taken for a pathohistological analysis under the assumption of being fibrous adhesive tissue. The analysis revealed ectopic decidual tissue composed of large, polygonal cells with eosinophilic cytoplasm, and large nuclei with conspicuous nucleoli infiltrated with mature fatty cells and lymphocytes. Strong staining for vimentin was observed in the decidual cell cytoplasm and for a progesterone- receptor in the cell nuclei, medium staining was detected for S-100, and negative staining for CK 5/ 6, HMB-45, desmin, smooth muscle actin, estrogen and androgen- receptors. We present this case in order to educate clinicians and pathologists about the phenomenon of ectopic deciduosis. Although it can exist as asymptomatic condition, we point out the importance of considering this condition since it can result in serious pathology, like intraperitoneal hemorrhage and labour obstruction, if remains unrecognized. Another pitfall is possible confusion of this entity with other conditions. A resemblance to adhesions of the omentum and malignant neoplastic lesions, like squamous cell and metastatic carcinoma, metastatic melanoma, malignant decidual mesothelioma, metastatic mucin -producing adenocarcinoma, can be deceiving. These obstacles may present a pitfall to clinicians and pathologists, with a negative impact on patient treatment and outcome.


Overcoming the end-replication problem is a major hurdle for cancer cells due to progressive telomere shortening that results from excessive cell division during tumorigenesis. While most cancers activate telomerase to maintain their telomere length, about five percent of cancers use a telomerase-independent telomere maintenance mechanism, termed alternative lengthening of telomeres (ALT). Despite its low overall frequency in cancer, ALT is enriched in several cancer subtypes, including pediatric high grade glioma (HGG). Previous work in our laboratory suggests that nearly half of pediatric HGG utilize the ALT mechanism. To date, therapeutic options are largely ineffective for children with HGG, reflected in the dismal five-year survival rate, which is less than 33 percent. Our goal is to better harness ALT as a clinical marker in pediatric HGG, specifically by identifying drugs that target ALT-positive cancers. In order to study ALT in this context, we obtained and characterized a panel of six pediatric HGG cell lines. Two of the six cell lines in this panel display hallmarks of the ALT pathway. To assess the potential of ALT as a therapeutic biomarker in pediatric HGG, we measured cell viability in the presence of inhibitors, stratifying our analysis by ALT status. ALT is predicted to occur via a homologous-recombination-based mechanism. As such, we focused our attention on inhibitors of the DNA damage response, as well as agents that induce DNA damage. Treatment with inhibitors of DNA-PK, RAD51, and MRE11 did not result in significant differences in cell viability when stratified by ALT status, nor did treatment with temozolomide or hydroxyurea. However, inhibitors of ATR (VE-821, VE-822/VX-970, and AZD-6738) and CHK1 (MK-8776) led to significantly greater reductions in cell viability in ALT-positive cells. In order to further our understanding of the mechanism through which ATR inhibition preferentially targets ALT-positive cell lines, we examined the effect of these inhibitors on ALT-specific properties, such as the presence of ultrabright telomeric foci and extrachromosomal telomeric DNA (c-circles). Preliminary results indicate that ATR inhibition does not diminish these ALT-associated properties and, therefore, the differential sensitivity to these agents is unlikely to be due to directly blocking the ALT telomere maintenance mechanism. Continued study of the effect of ATR/CHK1 inhibition on ALT-positive cells will yield further insight into the mechanism of ALT-specific toxicity. Overall, we have identified ATR/CHK1 as a promising pathway to target for ALT-positive pediatric HGG. Our goal is to better understand the relationship between ATR/CHK1 signaling and ALT in order to effectively translate this observation to the clinic, both for pediatric HGG and for other ALT-positive cancers. Citation Format: Jacqueline A. Brosnan-Cashman, Anthony J. Rizzo, Ezgi Goger, Kaylar M. Myers, Reza Zarinshenas, Christine Davis, Ming Yuan, Dinesh Rakheja, Eric H. Raabe, Charles G. Eberhart, Christopher M. Heaphy, Alan K. Meeker. ALT-positive pediatric high grade glioma cells display chemosensitivity to ATR pathway inhibition [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3466. doi:10.1158/1538-7445.AM2017-3466


Patients with the severe form of leukocyte adhesion deficiency syndrome do not express the CD11/CD18 adhesion complex on any of their leukocytes. Nevertheless, their lymphocytes, unlike their phagocytes, emigrate to extravascular sites of inflammation, demonstrating that surface proteins other than CD11/CD18 can mediate lymphocyte adherence to endothelium. Using a B-lymphoblastoid cell line (B-LCL) established from a CD11/CD18-deficient patient and cultured human umbilical vein endothelial cells (HEC), we investigated the CD11/CD18-independent mechanism(s) of lymphocyte adherence to endothelium. Monoclonal antibodies directed to the alpha 4 polypeptide (CD49d) and the beta 1 polypeptide (CD29) of the lymphocyte VLA-4 integrin receptor (CD49d/CD29), and to vascular cell adhesion molecule-1 (VCAM-1) on the endothelial cell significantly inhibited the adherence of the CD11/CD18-deficient B-LCL to untreated HEC and to HEC treated with recombinant human tumor necrosis factor-alpha. We suggest that the interaction of the lymphocyte receptor VLA-4 with the endothelial ligand VCAM-1 induced by cytokines at sites of inflammation or immune reaction represents a CD11/CD18-independent pathway of lymphocyte emigration.


Introduced alien species are recognised to be a major threat to native biodiversity. The American mink ( Mustela vison ) is a highly adaptable, naturalised predator in the UK, introduced as part of the fur trade in the 1920"s. The species became established in the wild in the 1950"s through purposeful releases and escapes and since establishing the mink has been held accountable for the decline of many native species, most notably the water vole ( Arvicola terrestris ). There are currently nine species of carnivore in the UK, and American mink presents competition for native predators, particularly those that have similar lifestyles. In recent years interspecific competition within carnivore communities has been recognised as an important factor in the structuring of an ecosystem, and evidence suggests that competition from recovering otter populations are leading to declines in mink. In this review the American mink is discussed in the context of its ecology and invasive success, and its impact on biodiversity both as a predator and a competitor.


This study was designed to assess if there are consistent treatment, stage, severity, effort and demographic effects which predict long-term changes across the multiple behaviors of smoking, diet and sun exposure. A secondary data analysis integrated data from four studies on smoking cessation (N = 3927), three studies on diet (N = 4824) and four studies on sun exposure (N = 6465). Across all three behaviors, behavior change at 24 months was related to treatment, stage of change, problem severity and effort effects measured at baseline. There were no consistent demographic effects. Across multiple behaviors, long-term behavior changes are consistently related to four effects that are dynamic and open to change. Behavior changes were not consistently related to static demographic variables. Future intervention research can target the four effects to determine if breakthroughs can be produced in changing single and multiple behaviors.


More than four million personal records of US government workers are thought to have been hacked and stolen, it has been. With US investigators blaming the Chinese government (although the Chinese deny involvement), this incident shows how data could be the new frontier for those in cyberspace with a political agenda. In April 2015, the US Office of Personnel Management (OPM) – the body that provides the human resources function for the federal government and is responsible for background checks for security clearances – realised its records had been hacked. Along with the direct personnel details, there are a whole range of references and contacts contained in the OPM records. The sensitive data could be used to identify people with security clearances, and could be used for the impersonation or blackmail of federal employees. Someone with security clearance could be exposed to identity fraud, where an intruder could gain access to sensitive information using the stolen identifies. The data could also be used to hack into other government sites. For example, intruders recently attempted to breach the Inland Revenue Service's systems (this time it was blamed on Russia) using personal information taken from tax returns stolen during other commercial breaches. Such attacks create a certain amount of national humiliation. The hacking of confidential data from Sony highlighted how embarrassing it can be for information to leak. The contents of its sensitive emails are now searchable on Wikileaks, and we have probably only seen the tip of the iceberg in terms of the data that was taken.


Humorous events often take place in pediatric emergency departments without being recorded. A written account of amusing situations occurring in an emergency department has been compiled over 20 years by personnel at a large urban children's hospital. Data from this reference were analyzed for humorous content and presented in the following categories: most interesting chief complaints, suspicious sounding chief complaints, favorite telephone inquiries, and illustrative cases. This study demonstrates that an emergency department may be a fertile source of medical humor. Recognition of these statements and events helps to relieve the stress of medical training and emergency department work.


Spirulina is a type of filamentous blue-green microalgae known to be rich in nutrients and to have pharmacological effects, but the effect of spirulina on the small intestine epithelium is not well understood. Therefore, this study aims to investigate the proliferative effects of spirulina crude protein (SPCP) on a rat intestinal epithelial cells IEC-6 to elucidate the mechanisms underlying its effect. First, the results of wound-healing and cell viability assays demonstrated that SPCP promoted migration and proliferation in a dose-dependent manner. Subsequently, when the mechanisms of migration and proliferation promotion by SPCP were confirmed, we found that the epidermal growth factor receptor (EGFR) and mitogen-activated protein (MAPK) signaling pathways were activated by phosphorylation. Cell cycle progression from G0/G1 to S phase was also promoted by SPCP through upregulation of the expression levels of cyclins and cyclin-dependent kinases (Cdks), which regulate cell cycle progression to the S phase. Meanwhile, the expression of cyclin-dependent kinase inhibitors (CKIs), such as p21 and p27, decreased with SPCP. In conclusion, our results indicate that activation of EGFR and its downstream signaling pathway by SPCP treatment regulates cell cycle progression. Therefore, these results contribute to the research on the molecular mechanism for SPCP promoting the migration and proliferation of rat intestinal epithelial cells.


We present a case of chronic liver disease with selective and exclusive hepatocyte endoplasmic reticulum storage of alpha 1-antichymotrypsin in the form of granules, detected by specific immunohistochemistry at the light microscopy level and corresponding to material found in dilated endoplasmic reticulum of hepatocytes by electron microscopy. The patient had intermediate deficiency of alpha 1-antichymotrypsin. Thus, the hepatocyte accumulation of alpha 1-antichymotrypsin may indicate the presence of an export block resembling that of a closely-related protein, namely PiZ alpha 1-antitrypsin. It is proposed that hepatocyte storage of alpha 1-antichymotrypsin may be an expression of an inborn error of metabolism bearing the characteristics of endoplasmic reticulum storage diseases such as PiZ alpha 1-antitrypsin deficiency and hereditary hypofibrinogenaemia.


The purpose of this study was to investigate the effects of Chungkookjang viscous biopolymer supplementation on blood glucose and serum lipid-lowering in Streptozotocin (STZ)-induced diabetic rats. The rats were divided into three experimental groups; a normal group (N), diabetic control group (D), and a diabetic group with the supplementation of Chungkookjang viscous biopolymer (DCB). The groups were given experimental diets for four weeks. The normal group (C) was fed a casein-based diet, and the Chungkookjang viscous bio-polymer group (DCB) received 3% biopolymer added to the casein-based diet. In the diabetic group (D), food intake increased significantly, but weight gain decreased significantly. The food efficiency ratio was significantly lower in the diabetic group. Liver weight increased significantly in the D group as compared to the N group. However, the DCB group showed a significant decrease in liver weight when compared to the D group. Blood glucose decreased significantly in the DCB group after receiving the experimental diet for four weeks, as compared to the diabetic control (p<0.05). Serum triglyceride levels were significantly lower in the DCB group than in the D group, whereas HDL-cholesterol levels were significantly higher (p<0.05). Total cholesterol was decreased in DCB group, but there were no significant differences. Also, LDL-cholesterol level was not significantly different among the experimental groups. Hepatic triglyceride and cholesterol were lower in the DCB group with no significant differences among groups. These results indicate that dietary supplementation of Chungkookjang viscous biopolymer improved glucose lowering and lipid metabolism in diabetic rats.


An invaluable guide to the art and mind of Virginia Woolf, "A Writer's Diary" was drawn by her husband from the personal record she kept over a period of twenty-seven years. Included are entries that refer to her own writing and those that are clearly writing exercises, accounts of people and scenes relevant to the raw material of her work, and finally, comments on books she was reading. The first entry is dated 1918 and the last, three weeks before her death in 1941. Between these points of time unfolds the private world - the anguish, the triumph, the creative vision - of one of the great writers of our century.


Guided depth map super-resolution (GDSR), as a hot topic in multi-modal image processing, aims to upsample low-resolution (LR) depth maps with additional information involved in high-resolution (HR) RGB images from the same scene. The critical step of this task is to effectively extract domain-shared and domain-private RGB/depth features. In addition, three detailed issues, namely blurry edges, noisy surfaces, and over-transferred RGB texture, need to be addressed. In this paper, we propose the Spherical Space feature Decomposition Network (SSDNet) to solve the above issues. To better model cross-modality features, Restormer block-based RGB/depth encoders are employed for extracting local-global features. Then, the extracted features are mapped to the spherical space to complete the separation of private features and the alignment of shared features. Shared features of RGB are fused with the depth features to complete the GDSR task. Subsequently, a spherical contrast refinement (SCR) module is proposed to further address the detail issues. Patches that are classified according to imperfect categories are input into the SCR module, where the patch features are pulled closer to the ground truth and pushed away from the corresponding imperfect samples in the spherical feature space via contrastive learning. Extensive experiments demonstrate that our method can achieve state-of-the-art results on four test datasets, as well as successfully generalize to real-world scenes. The code is available at \url{https://github.com/Zhaozixiang1228/GDSR-SSDNet}.


Coagulation and fibrinolysis are processes that form and dissolve fibrin, respectively. These processes are exquisitely regulated and protect the organism from excessive blood loss or excessive fibrin deposition. Regulation of these cascades is accomplished by a variety of mechanisms involving cellular responses, flow, and protein-protein interactions. With respect to regulation mediated by protein-protein interaction, the coagulation cascade appears to be more complex than the fibrinolytic cascade because it has more components. Yet each cascade is regulated by initiators, cofactors, feedback reactions, and inhibitors. Coagulation is also controlled by an anticoagulant pathway composed of (minimally) thrombin, thrombomodulin, and protein C. 1 Protein C is converted by the thrombin/thrombomodulin complex to activated protein C (APC), which catalyzes the proteolytic inactivation of the essential cofactors required for thrombin formation, factors Va and VIIIa. An analogous antifibrinolytic pathway has been identified recently. This pathway provides an apparent symmetry between coagulation and fibrinolysis and is also composed of thrombin, thrombomodulin, and a zymogen that is activated to an enzyme. The enzyme proteolytically inactivates a cofactor to attenuate fibrinolysis. However, unlike APC, which is a serine protease, the antifibrinolytic enzyme is a metalloprotease that exhibits carboxypeptidase B–like activity. Within a few years of each other, 5 groups independently described a molecule that accounts for this antifibrinolytic activity. We refer to this molecule as thrombin activatable fibrinolysis inhibitor (TAFI), a name that is based on functional properties by which it was identified, assayed, and purified. (Because of the preferences of some journals "activatable" is occasionally referred to as "activable.") This review will encompass a historical account of efforts to isolate TAFI and characterize it with respect to its activation, activity, regulation, and potential function in vivo.


Objectives: Tendon recovery after a surgical operation or traumatic injury is still one of the challenges of rehabilitation. Many recently formulated treatments have been designed to improve these procedures. This study aimed to evaluate the effects of recombinant basic fibroblast growth factor (bFGF) and cold atmospheric plasma (CAP) on calcaneus tendon healing and regeneration in rabbit models. Material and Methods: This study subdivided 40 mature male New Zealand white rabbits into four groups (n=10 in each). The defect was made under general conditions, and the wound was closed without treatment. The experimental groups included sham (without treatment), bFGF (operated bFGF in the injured area), CAP (used CAP in the injured area), and bFGF/CAP (used both CAP and bFGF) in the injured area. This study used trichrome and reticulin stains to evaluate collagen production and other tissue factors. Also, hydroxyproline levels were measured for better observation of collagen synthesis. Pathological evaluation of the defective tendon was performed on days 60 and 120 after surgery. Results: The improvement of new and parallel tendon formation was the best in the bFGF/CAP group at both times, especially 120 days after surgery. An increase in hydroxyproline levels was also seen on the sampling days. Conclusions: The experiment showed that bFGF/CAP combination significantly improved tendon remodeling in the injured areas.


The purpose of this paper is to explore barriers to the change management in the public sector of educational institutions such as public schools of the Ministry of Education in the GCC countries. The exploration of the research is based on the ADKAR change management model that consists of five key elements, which are awareness, desire, knowledge, ability and reinforcement. The ADKAR model was used for many reasons, among these reasons is that it allows management to separate the change process into parts, pinpointing where change is failing and addressing that impact point.,Five public schools and employees from the educational directorate were taken as samples in this study. The unit of analysis was the employees, and data on these change drivers were collected from questionnaires and interviews.,The study findings were articulated through strengths and weaknesses. The strengths were the desire to change and networking. The weaknesses were the knowledge element such as the absence of predetermining guideline for the implementation of the system; another observed weakness was in the leader's authority, where leaders do not have clear definition of authority and responsibility to take a decision; and finally the deficiency in performance appraisal for not being taken on regular basis and the rewarding system for not being linked to performance appraisal.,The information and feedback collected from the questionnaire may not represent all of the facts of the questionnaire subject; therefore, the researchers may have to use an unstructured interview to enhance the quality of information obtained. Due to the long bureaucratic procedures for issuance of permission from the higher research authorities (Scientific Research Directorate) to apply the questionnaire in the Ministry of Education, this took nearly three weeks, which was long considering the time available to end the research and resulted in a significant change in the project schedule.,This study provides an empirical evidence that gives a deep insight about the elements that act as barriers to change in the public sector of educational institutions, as there are certain elements that are tied to the nature and characteristics of the public sector itself that act as barriers to change.,Knowledge development is an essential part of the public sector development scheme. Effective training programs are the most important means to develop knowledge, considering that it has to be properly designed and delivered. Training programs should also be structured in a way that fills the knowledge gaps that exist between the present state and the future state. One useful technique for filling and assessing the gaps between the current state and future state requirements is by writing new job descriptions for employees, which should include details of knowledge and skills needed to perform that role during and after the transition.


DOOR Online began as a collaborative effort between a number of agencies and people from the disabled community in Colorado. The shared goal was to develop an accessible, searchable resource listing for people with disabilities, their families, and community supports. DOOR Online, the result of this effort, is a database of local, state, and national resources that can be accessed directly through the Internet or the statewide library network.


In our research, we study mechanisms of knowledge dissemination based on the structural and social networks surrounding the edition history of a single text: the Tractatus de sphaera by Johannes de Sacrobosco. By applying methods from network analysis, we investigate how specific commentaries on the text circulated, which actors were responsible for them and what factors supported or hindered the spread of specific kinds of knowledge. The basis of this investigation is represented by CorpusTracer, a database that stores the required data in a suitable format and with the required level of expressivity. In this article, we present the design of our database and our data model based on CIDOC-CRM and FRBRoo. We discuss the implementation and suitability of the conceptual and technical realization for our research question. We conclude that FRBRoo fits well to the task at hand. We found that the comparatively complex data structure it requires can be sufficiently abstracted through current implementation methods. As the research continues, our data model will have to grow and we expect that the presented methods will be sufficient to accommodate our future requirements. .................................................................................................................................................................................


OBJECTIVE
To investigate the effect of dexmedetomidine pretreatment on hypoxia/reoxygenation-induced injury in human umbilical vein endothelial cells and the possible mechanism.

METHODS
Cultured human umbilical vein endothelial cell-12 (HUVEC-12) were randomly divided into four groups(n = 24): group control (C), group dexmedetomidine (D), group hypoxia/reoxygenation (H/R), group hypoxia/reoxygenation plus dexmedetomidine (H/R+D). In groups D and H/R+D, Dexmedetomidine 50 µmol/L was added to the culture medium and the cells were incubated for 2 h. Then groups C and D were exposed to regular incubator and incubated for 12 h, groups H/R and H/R+D were incubated in an anaerobic chamber for 6 h and then returned to a regular incubator and incubated for 6 h. Cell growth conditions were observed under inverted microscope, the cell viability and apoptosis were measured by methyl thiazolyl tetrazolium (MTT) assay and flow cytometry respectively. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to detect the expression of CHOP mRNA. Western blotting was used to detect the expression of CHOP and cleaved caspase-3 protein.

RESULTS
Compared with group C, the cell survival rate was significantly decreased, the expression of CHOP mRNA and CHOP protein, cleaved caspase-3 protein were up-regulated, the apoptotic rate was significantly increased in group H/R and group H/R+D (P < 0.05),No significant difference was found in group D (P > 0.05);compared with group H/R, the cell survival rate was significantly increased, the expression of CHOP mRNA and CHOP protein, cleaved caspase-3 protein were down-regulated, the apoptotic rate was decreased significantly in the group H/R+D (P < 0.05).

CONCLUSIONS
Dexmedetomidine pretreatment can effectively attenuate hypoxia/reoxygenation-induced apoptosis to human umbilical vein endothelial cell-12. The mechanism maybe related with down-regulating the expression of CHOP.


Moir\'e quantum matter has emerged as a novel materials platform where correlated and topological phases can be explored with unprecedented control. Among them, magic-angle systems constructed from two or three layers of graphene have shown robust superconducting phases with unconventional characteristics. However, direct evidence for unconventional pairing remains to be experimentally demonstrated. Here, we show that magic-angle twisted trilayer graphene (MATTG) exhibits superconductivity up to in-plane magnetic fields in excess of 10 T, which represents a large ($2\sim3$ times) violation of the Pauli limit for conventional spin-singlet superconductors. This observation is surprising for a system which is not expected to have strong spin-orbit coupling. Furthermore, the Pauli limit violation is observed over the entire superconducting phase, indicating that it is not related to a possible pseudogap phase with large superconducting amplitude pairing. More strikingly, we observe reentrant superconductivity at large magnetic fields, which is present in a narrower range of carrier density and displacement field. These findings suggest that the superconductivity in MATTG is likely driven by a mechanism resulting in non-spin-singlet Cooper pairs, where the external magnetic field can cause transitions between phases with potentially different order parameters. Our results showcase the richness of moir\'e superconductivity and may pave a new route towards designing next-generation exotic quantum matter.


Properly identify the relationship between export and innovation is key to designing efficient policy instruments. However, there is still no consensus on how has to be the direct causal relationship between innovation and export. In this paper the authors develop an empirical analysis for the Chilean manufacturing sector which seeks to unravel this relationship. Specifically, an econometric model for various industrial sub-sectors of the Chilean economy for the period 1995-2010, controlling for the level of productivity of each signature, among other variables is presented. Unlike other studies, we consider the total expenditure on innovation rather than just R&D, which can cover a wider range of activities that seek productive within the firm improvements spectrum, while increasing the number of companies that are studied. The results show that in most subsectors, the export propensity or put another way: participation in global market cause, in Granger terms, an increased effort in innovation. Specifically, for the subsectors of minerals and base metals, and metal-mechanical, mutual Granger causality is presented. Finally, for the subsectors wood and paper no statistical significance was evident of Granger causality between innovation and export in any sense. With these results, some policy conclusions for Chile are discussed in relation to instruments of export promotion and innovation.


ABSTRACT Little research has been undertaken into how children with complex communication needs living in residential care are encouraged to express their views, be involved in decision-making, and importantly, make it known when they are unhappy. This group are often placed a long distance from home and can be some of the most vulnerable children in the care system. Ensuring they have access to a communication method, people who understand their communication and support to empower them to grow their capacity is not only a right and a safeguarding mechanism, it is also important in preparation for adulthood and for leaving care. This unique paper reports on the English arm of a European project, which aimed to devise the first international monitoring system to prevent abuse of disabled children in residential settings. Trained professionals examined how disabled children were heard, and encouraged to be involved in decision-making within 10 case-study residential settings. To aid international development of good practice, this paper focuses on positive aspects of practice. Examples are used to illustrate how all forms of communication can be encouraged and used positively to both protect and empower disabled children in residential care. Implications for practice are presented to support practitioners to create positive communication environments.


Eye functioning in locomotive operators remains at high level for a long time, in spite of exposure to complex of occupational hazards, but without correction of early visual disorders some diseases might involve accomodation, refraction and neurosensory divisions of eye, with subsequently more difficult operator's work at railway and the railway traffic safety hazard.


Background: Progress in evaluation research depends on the continuous generation of scholarly knowledge and its dissemination in the community. One way of disseminating findings is to publish in scientific journals and researchers, institutions, and even whole countries are assessed by their output in these journals. Particularly with regard to countries, there is an uneven distribution of research productivity in evaluation journals. A viable model for predicting countries' research output in international evaluation journals, however, has not yet been developed. Purpose: The purpose of this study was to develop and test a model for the prediction of countries' research output in international evaluation journals by predictors from the research, economic, and social/political system. Setting: NA Intervention: NA Research Design: A cross-sectional design was used for predicting research output in evaluation journals across countries. Data Collection and Analysis: Our sample consists of 65 countries that made contributions to ten international peer-reviewed evaluation journals. We collected data for the period from 2009 to 2013 and predicted the number of authorships across countries by using boosted regression trees, a machine learning procedure. Findings: Our model provided accurate predictions of countries' research output. Research productivity in the social sciences had the strongest effect, followed by economic prosperity, control of corruption, and age of evaluation society. The model was generalizable to another period of time with only marginal loss in predictive accuracy.


Results from a long-term clinical trial conducted by cancer researchers at Houston Methodist Hospital show that combining radiation treatment with "suicide gene therapy," a technique in which prostate cancer cells are genetically modified so they signal a patient's immune system to attack them, provides a safe and effective one-two punch against the disease. The researchers compared two arms of patients and report high five-year overall survival rates of 97 percent and 94 percent, respectively. That's a


The system of good governance is able to realize the governance of the country clean and free from Collusion and Nepotism Corruption (UU 28 year1998). One of the steps of the Banjarbaru City Inspectorates to realize Good Corporate Governance is through the transparency of performance accountability of government agencies  in managing regional finances, most of which are funded by public funds. Performance accountability of government agencies presents budget allocations and realization for implementing key tasks in achieving performance indicators. The achievement of this performance indicator can be accounted for and realized through a performance-based budget. However, in its implementation, supervision, control, responsibility and assessment of  performance accountability of government agencies  is needed. This is where the role of the Internal Control System  is in charge of carrying out oversight of the running of the government and the management of financial areas that are clean and responsible. The purpose of this study was to find out whether the Performance Based Budget  and Internal Control System  had an effect on the Performance Accountability of Government Agencies  at Banjarbaru City Inspectorates. The sample used amounted to 39 respondents. The sampling technique is prurposive sampling. The analytical method used in this study is multiple regression analysis. The results of the study indicate that the implementation of the budget, budget reporting, control activities and monitoring (supervision) has an influence on Performance Accountability of Government Agencies . Budget planning, performance evaluation, control environment, risk assessment, information and communication have no effect on Performance Accountability of Government Agencies.


Using a dynamical z-pinch discharge, intense radiation of hydrogen-like carbon was produced. Operating the discharge with a maximum current of 105 kA and a period of 274 ns, the Balmer transition at 18.23 nm appeared as a short (< 8 ns FWHM) and bright (230 kW in ) peak emitted from a cylindrical volume with a radius of at the centre of the vessel. The results are compared with predictions of models for a z-pinch discharge. Optical gain for the Balmer transition was determined to be less than in agreement with the prediction of the model.


In this paper, we present a baseband algorithm for estimation and compensation of transmitter and receiver IQ imbalance for OFDM in a frequency-selective fading channel. We show by simulations that the negative effect of IQ imbalance on system performance can be almost completely removed by the proposed algorithm. The algorithm is an iterative loop, consisting of consecutively channel estimation, Rx IQ imbalance estimation, Tx IQ imbalance estimation and data estimation


This study, for any unknown physical process y=f(x1,...,xn), is concerned with the: 1) fuzzy partition of n-dimensional input space X=X1timesmiddotmiddotmiddottimesXn into K different clusters, 2) estimating the process behavior ycirc=f(xcirc) for a given input xcirc=(xcirc1,middotmiddotmiddot,xcircn )isinX, and 3) fuzzy approximation of the process, with uncertain input-output identification data {(x(k)plusmndeltaxk ),(y(k)plusmnvk)}k=1,..., using a Sugeno type fuzzy inference system. A unified min-max approach (that attempts to minimize the worst-case effect of data uncertainties and modeling errors on estimation performance), is suggested to provide robustness against data uncertainties and modeling errors. The proposed method of min-max fuzzy parameters estimation does not make any assumption and does not require a priori knowledge of upper bounds, statistics, and distribution of data uncertainties and modeling errors. To show the feasibility of the approach, simulation studies and a real-world application of physical fitness classification based on the fuzzy interpretation of physiological parameters, have been provided


This presentation provides an overview of our innovative and comprehensive process for embedding student digital and professional capabilities and assuring the learning of these capabilities for our Business School's accreditation and quality assurance purposes.  To avoid surface level compliance and ensure all academics were engaged in the change process, we remapped our Program Learning Outcomes to key Competency Goals that met the strategic direction of our Business School, and the University more broadly.
Five Competency Goals were developed: Global Citizenship; Ethical Reasoning; Analysis and Problem Solving; Job Ready; Digitally Adept. These were divided into 12 Objectives and underpinned by a suite of carefully designed rubrics to be workshopped and formalised as Assurance of Learning (AoL) Rubrics (Calma, 2021). We included our Business School's commitment to the Principles of Responsible Management Education (PRME) and ensured the United Nations, Sustainable Development Goals (SDGs) were met in our core competency areas and learning objectives.  Because the process followed the strategic direction of our business school, this process gave us a vehicle to showcase our priority areas, which included the innovative approaches taken by academics to enhance the Digitally Adept competency goal in student learning and assessment. An important aspect of the formalised process was the development of a digital Data Extraction Tool (rDET), developed by Ishpal Sandhu and Gillian Vesty, which allowed us to extract components of a rubric that matched each of the 5 competency goals and 12 learning objectives, not only for our AoL sample, but for all students in a course, regardless of course numbers.  This automated data collection tool has made it possible to easily capture a wide range of data to reveal distinct areas for improvement in terms of curriculum alignment, assessment design and/or changes that can be made to enhance student experience while getting them ready for life and work.
In a multi-dimensional constructive alignment process (Sridharan et al., 2015), the team validated the Competency Goals and Objectives, ensuring they were captured in assessments across all programs, and in all delivery locations. The suite of formal rubrics developed to measure the competency goals became the centrepiece of conversation among the program management teams. To ensure AoL sampling was a true representation of the practices across the Business School, all academics were asked to include the rubrics in their assessments.
Importantly, the alignment process undertaken was embedded in formal governance mechanisms and reporting through the hierarchy of committees. The rubrics and template developed was the mechanism to expose current practice gaps and/or achievements of each of the digitally adept learning objectives and competency goals. Recommendations for change in process and/or curriculum were made, and appropriate resourcing provided on agreement. It was important that successful achievement of the digitally adept learning objectives showcased the move away from exams to exemplary authentic learning assessment designs.


GAMING simulations (games) have been closely relatedwith systems, and particularly with systems characterised as being complex. There is a long history on the evolution of systems from simply technical and social, to socio-technical (STS) and all the way to complex (adaptive) systems (CAS). Within this ever-increasing complexity, an important question that can be raised is: What is the role of games? Or in other words, what do games have to offer, that other tools do not, that can help us understand and further explore these complex systems?


The observations were performed at the T193 telescope of the Haute-Provence Observatory, with the SOPHIE spectrograph. SOPHIE is dedicated to the search of extrasolar planets, and, thanks to its high resolution (R~75000), it enables accurate stellar RVs to be measured for SB2 components. The RVs of the components are derived using the TwO-Dimensional CORrelation algorithm TODCOR (Zucker & Mazeh 1994ApJ...420..806Z; Zucker et al. 2004, Cat. J/A+A/426/695). (3 data files).


We present the case of a suprahepatic tumor related to mature cystic teratoma, extragonadal germ cell tumors are rare and represent from 1.6 to 5% of all germ cell tumors, the most common site and the extragonadal presentation is the mediastinum (50-70%), retroperitoneum (30-40%), other rare locations pineal gland, sacrococcal region, prostate and bladder; however, the supra-hepatic location is not so common and is not documented in the literature.


Background The frequency of synonymous codon usage varies widely between organisms. Suboptimal codon content limits expression of viral, experimental or therapeutic heterologous proteins due to limiting cognate tRNAs. Codon content is therefore often adjusted to match codon bias of the host organism. Codon content also varies between genes within individual mammalian species. However, little attention has been paid to the consequences of codon content upon translation of host proteins. Methodology/Principal Findings In comparing the splicing repressor activities of transfected human PTB and its two tissue-restricted paralogs–nPTB and ROD1–we found that the three proteins were expressed at widely varying levels. nPTB was expressed at 1–3% the level of PTB despite similar levels of mRNA expression and 74% amino acid identity. The low nPTB expression was due to the high proportion of codons with A or U at the third codon position, which are suboptimal in human mRNAs. Optimization of the nPTB codon content, akin to the "humanization" of foreign ORFs, allowed efficient translation in vivo and in vitro to levels comparable with PTB. We were then able to demonstrate that all three proteins act as splicing repressors. Conclusions/Significance Our results provide a striking illustration of the importance of mRNA codon content in determining levels of protein expression, even within cells of the natural host species.


Aims

Most crops are supplemented with selenium (Se) through the exogenous addition of inorganic selenium fertilizer. There is a lack of in-depth research on organic selenium fertilizers. Meanwhile, the dosage range between human selenium deficiency and selenium toxicity is narrow, so the selenium content of agricultural products needs to be controlled within a reasonable interval.
Methods W

e analyzed and compared the Se accumulation and speciation in rice during three different growth stages (late tillering stage, initiate heading stage, and full heading stage) using three selenium fertilizers, selenite, fermented Se, and potassium Selenocyanoacetate (Se-AAF) via the foliar application.
Results

The selenium content in rice sprayed with organic selenium fertilizer was controlled in the relatively safe range and met the human selenium supplement requirement compared to the sprayed sodium selenite, which was too high of a dose. The percentage of organic Se and protein Se in brown rice was found to be similar in all three Se fertilizers. The highest organic selenium content of 91.57% was found in the grain of rice at the full heading stage by spraying Se-AAF. The main Se species in the grain was selenomethionine (SeMet), which reached 80% of the total selenium. Se-methyl selenocysteine(SeMeCys) was found only in Se-AAF. The grain quality showed that all three Se fertilizers increased the consistency of gelatinization.
Conclusions

Appropriately delaying the spraying time and selecting organic Se fertilizer as the Se source can help to produce green and safe selenium-rich rice.


What constitutes a high-rise building? A high-rise is, in fact, any building with more than 9 storeys and not just those striking skyscrapers which shape modern city skylines. In the past architects who designed such structures used to be the exception but in the last 10 years more and more architectural offices have begun to focus on this type of building. However, the sheer complexity of designing and planning the construction of a high-rise as opposed to other building types requires a wealth of specialized experience and expertise. The High-Rise Manual is the first comprehensive reference work on this subject. All relevant aspects of such an undertaking are examined in detail by some 24 specialist authors. Each step is extensively documented including the initial project planning, the building organisation, the laying of the foundations, the supporting structure, the building technology, the office design, and the Facility Management.


The global health crisis in non-communicable diseases (NCDs) reveals a deep global health inequity that lies at the heart of global justice concerns. Mirroring the HIV/AIDS epidemic, NCDs bring into stark relief once more the human consequences of trade policies that reinforce global inequities in treatment access. Recognising distributive justice issues in access to medicines for their populations, World Trade Organisation (WTO) members confirmed the primacy of access to medicines for all in trade and public health in the landmark Doha Declaration on the TRIPS Agreement and Public Health of 2001.


The existence of alpha 1-adrenoceptors with low affinity for prazosin (alpha 1L group: alpha 1L and alpha 1N subtypes) has been proposed in addition to alpha 1-adrenoceptor subtypes with high affinity for prazosin (alpha 1H group: alpha 1A, alpha 1B and alpha 1D subtypes). A newly synthesized alpha 1-adrenoceptor antagonist, JTH-601 (N-(3-hydroxy-6-methoxy-2,4,5-trimethylbenzyl)-N-methyl-2-(4-hydro xy-2-isopropyl-5-methyl-phenoxy) ethylamine hemifumarate) showed approximately a 10 times higher affinity for the alpha 1L group, a similar affinity for the alpha 1A subtype, but a more than 10 times lower affinity for the alpha 1B and alpha 1D subtypes when compared with prazosin. These results provide a further pharmacological evidence that alpha 1-adrenoceptors with low affinity for prazosin exist in addition to those with high affinity for prazosin, suggesting that JTH-601 may be useful for characterising the alpha 1-adrenoceptor subtypes.


To compare the process of protein folding in the cell with refolding following denaturation in vitro, we have investigated and compared the kinetics of renaturation of a full-length protein upon dilution from concentrated urea with the rate of folding in the course of biosynthesis. Formation of enzymatically active bacterial luciferase, an alpha beta heterodimer, occurred 2 min after completion of beta-subunit synthesis in an Escherichia coli cell-free system. Renaturation of urea-denatured beta subunit, either in the presence of the cell-free protein synthesis system or in buffer solutions, proceeded more slowly. Cellular components present in the cell-free protein synthesis system slightly accelerated the rate of refolding of urea-unfolded beta subunit. The results indicate that the luciferase beta subunit begins the folding process cotranslationally and that cotranslational folding contributes to the rapid formation of the native structure in the cell.


Removing power line noise and other frequency-specific artifacts from electrophysiological data without affecting neural signals remains a challenging task. Recently, an approach was introduced that combines spectral and spatial filtering to effectively remove line noise: Zapline (de Cheveigné, 2020). This algorithm, however, requires manual selection of the noise frequency and the number of spatial components to remove during spatial filtering. Moreover, it assumes that noise frequency and spatial topography are stable over time, which is often not warranted. To overcome these issues, we introduce Zapline-plus, which allows adaptive and automatic removal of frequency-specific noise artifacts from M/EEG and LFP data. To achieve this, our extension first segments the data into periods (chunks) in which the noise is spatially stable. Then, for each chunk, it searches for peaks in the power spectrum, and finally applies Zapline. The exact noise frequency around the found target frequency is also determined separately for every chunk to allow fluctuations of the peak noise frequency over time. The number of to-be-removed components by Zapline is automatically determined using an outlier detection algorithm. Finally, the frequency spectrum after cleaning is analyzed for suboptimal cleaning and parameters are adapted accordingly if necessary before re-running the process. The software creates a detailed plot for monitoring the cleaning. We showcase the efficacy of the different features of our algorithm by applying it to four openly available data sets, two EEG sets containing both stationary and mobile task conditions, and two MEG sets containing strong line noise.


An investigation in rice was undertaken to study the nature and magnitude of heterosis for yield and yield component traits involving ten high yielding lines and three superior grain quality testers and thirty hybrids were developed through line x tester mating design. Observations were recorded for days to 50% flowering, plant height, number of productive tillers per plant, panicle length, number of filled grains per panicle, hundred grain weight and single plant yield. Significant heterosis for grain yield and yield component traits were observed in most of the hybrids. Nine hybrids exhibited positive and significant heterosis over standard check but six crosses over better parent for single plant yield plant. Standard heterosis and heterobeltiosis for grain yield ranged from -15.64 to 20.04% and -23.75 to 15.50%, respectively. A total of four hybrids viz., ADT 39 x I.W.Ponni, ADT 43 x I.W.Ponni, ADT 49 x I.W.Ponni and CO (R) 50 x I.W.Ponni were recorded higher grain yield over both better parent and standard check and were identified as best hybrids for exploiting hybrid vigor. Most of the heterotic crosses for grain yield per plant were accompanied by heterosis for two or more component traits.


Abstract This study has as its main objective to evaluate the effectiveness of the welding process by electrical resistance in a composite poly (ether-imide) matrix reinforced with continuous fibres of carbon, from the study of the thermal and mechanical properties of the welded joint. To evaluate the thermal properties of the welded material, samples were subjected to analysis by thermogravimetry and by thermomechanical analysis. With the intention to study the resulting weld interface, studies were made from the shear tests ILSS and Iosipescu, as well as end-notched flexure (ENF). The results of the thermal analysis in laminated non-welded PEI/carbon fibre show that the beginning of degradation for these composites is 460 °C, and it is also evident that the glass transition temperature of welded samples is about 15% higher than the results from samples not welded. The mechanical tests show that there was an increase of 32 and 20%, respectively, in interlaminar shear results for the ILSS- and Iosipescu-welded samples when they are compared to samples not welded. The ENF test results show satisfactory values of interlaminar fracture toughness in the composite welded from the values found in the literature.


Skeletal muscle contractile function is impaired during acute ischemia such as that experienced by peripheral vascular disease patients. We therefore, examined the effects of dichloroacetate, which can alter resting metabolism, on canine gracilis muscle contractile function during constant flow ischemia. Pretreatment with dichloroacetate increased resting pyruvate dehydrogenase complex activity and resting acetylcarnitine concentration by approximately 4- and approximately 10-fold, respectively. After 20-min contraction the control group had demonstrated an approximately 40% reduction in isomeric tension whereas the dichloroacetate group had fatigued by approximately 25% (P < 0.05). Dichloroacetate resulted in less lactate accumulation (10.3 +/- 3.0 vs 58.9 +/- 10.5 mmol.kg-1 dry muscle [dm], P < 0.05) and phosphocreatine hydrolysis (15.6 +/- 6.3 vs 33.8 +/- 9.0 mmol.kg-1 dm, P < 0.05) during contraction. Acetylcarnitine concentration fell during contraction by 5.4 +/- 1.8 mmol.kg-1 dm in the dichloroacetate group but increased by 10.0 +/- 1.9 mmol.kg-1 dm in the control group. In conclusion, dichloroacetate enhanced contractile function during ischemia, independently of blood flow, such that it appears oxidative ATP regeneration is limited by pyruvate dehydrogenase complex activity and acetyl group availability.


Extracellular vesicles isolation from urine was severely interfered by polymeric Tamm-Harsefall protein due to its ability to entrap exosome. Studies had been reported to optimize the extraction of urine extracellular vesicles by using reducing agents, surfactants, salt precipitation or ultrafiltration, but rarely based on highly specific purification methods. We optimized the density gradient centrifugation method for the isolation of urinary small extracellular vesicles (sEV) and compared seven differential centrifugation protocols to obtain the high-yield and high-purity sEV isolation procedures. Our study showed Tris sucrose gradient centrifugation at 25°C had more concentrated distribution of exosomal marker in the gradient compared to Tris sucrose gradient centrifugation at 4°C and PBS sucrose gradient centrifugation. Dissolving the 16000 g pellet using Tris, Nonidet™ P 40 or Dithiothreitol then pooling the supernatants did not increase the exosomal markers and number of nanoparticles in sEV preparation compared to the control and PBS groups. Differential centrifugation at room temperature without ultrafiltration recovered more exosome-like vesicles, exosomal markers and nanoparticles than that at 4°C or combining ultrafiltration. Differential centrifugation at RT without ultrafiltration and salt precipitation recovered the highest number of nanoparticles than other protocols. However, differential centrifugation at RT combining 100 kd ultrafiltration obtained the highest purity of sEV calculated by Nanoparticle number/Total protein. In conclusion, we had established two urinary sEV isolation procedures that can recovered higher yield of sEV and more pure preparation of sEV. It is not recommended to treating 16000 g pellet with reducing agents or surfactants to increase the yield of sEV.


Micro-Electron Diffraction (MicroED) has recently emerged as a powerful method for the analysis of biological structures at atomic resolution. This technique has been largely limited to protein nanocrystals which grow either as needles or plates measuring only a few hundred nanometres in thickness. Furthermore, traditional microED data processing uses established X-ray crystallography software that is not optimised for handling compound effects that are unique to electron diffraction data. Here, we present an integrated workflow for microED, from sample preparation by cryo-focused ion beam milling, through data collection with a standard Ceta-D detector, to data processing using the DIALS software suite, thus enabling routine atomic structure determination of protein crystals of any size and shape using microED. We demonstrate the effectiveness of the workflow by determining the structure of proteinase K to 2.0 Å resolution and show the advantage of using protein crystal lamellae over nanocrystals.


The amount of data in our society has been exploding in the era of big data today. In this paper, we address several open challenges of big data stream classification, including high volume, high velocity, high dimensionality, and high sparsity. Many existing studies in data mining literature solve data stream classification tasks in a batch learning setting, which suffers from poor efficiency and scalability when dealing with big data. To overcome the limitations, this paper investigates an online learning framework for big data stream classification tasks. Unlike some existing online data stream classification techniques that are often based on first-order online learning, we propose a framework of Sparse Online Classification (SOC) for data stream classification, which includes some state-of-the-art first-order sparse online learning algorithms as special cases and allows us to derive a new effective second-order online learning algorithm for data stream classification. We conduct an extensive set of experiments, in which encouraging results validate the efficacy of the proposed algorithms in comparison to a family of state-of-the-art techniques on a variety of data stream classification tasks.


As accounting programs increase their online offerings, understanding the challenges of maintaining academic integrity online is crucial. This study documents an emerging method of online academic dishonesty—on-demand services from academic resource sites (ARS) such as Chegg.com. ARS are web-based repositories of textbook problems, homework solutions, etc., and many of them employ subject-matter experts to answer questions in real time, potentially during active exams. In periods of fewer online exam safeguards, 13–25 percent of intermediate accounting students are identified as using Chegg during exams. Corroborating evidence shows an anomalous improvement in student performance in online exams with minimal safeguards, which is attenuated by an increase in mitigation policies. Survey responses confirm that students are familiar with and use ARS, including 10 percent who acknowledge use during quizzes or exams. These findings help formulate suggestions about practices educators can employ to decrease pervasive use of ARS in online learning.
 JEL Classifications: M49.


Background Subjective and objective sleep disturbances have been reported in premanifest Huntington's disease (pre-HD). These disturbances have the potential to induce structural and functional changes to the brain, including cognitive deficits, and may facilitate, or even contribute to, disease onset and progression. Treatment of sleep disturbances could therefore improve function in affected individuals. Here, we investigated the effects of a non-pharmaceutical, short duration multidisciplinary therapy intervention on subjective and objective sleep in pre-HD participants. Aims To evaluate the effects of multidisciplinary therapy on sleep patterns and subjective sleep quality in pre-HD participants. Methods Eleven pre-HD participants aged 40 ± 11 years (5 male) underwent a twelve week multidisciplinary therapy intervention consisting of three, two hour sessions per week encompassing supervised group exercise and cognitive training. Objective (actigraphy) and subjective (Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, Consensus Sleep Diary) measures of sleep were obtained at baseline, six weeks and twelve weeks. Stress, depression and anxiety were measured at each time-point using the Perceived Stress Scale and the Hospital Anxiety and Depression Scale (as potential confounders of sleep abnormalities). Results All participants completed the required number of therapy sessions (30 sessions in total) for the study. Decreases, relative to baseline, in sleep onset latency (d > 0.5) and number and duration of awakenings (d > 0.2) were observed following the 12 week intervention. Subjective sleep quality also improved following 12 weeks of physical and cognitive training (d > 0.5). Conclusion This study provides evidence that multidisciplinary therapy has the potential to improve subjective and objective sleep quality in pre-HD. It is possible that a longer intervention duration may further improve sleep quality outcomes in this population.


Bicyclo[2.2.1]heptane-2-exo, 3-exo, 5-exo-tricarboxyl-5-endo-acetic dianhydride (4a, BSDA) and its 5-endo-carboxyl-5-exo-acetic isomer (4b) with an alicyclic and spiro structure were prepared from a Diels-Alder adduct of itaconic anhydride with cyclopentadiene via three steps. Fully alicyclic polyimides were synthesized by polycondensations of an alicyclic diamine, 2, 5(6)-bis(aminomethyl)bicyclo[2.2.1]heptane (BBH) with four kinds of cycloaliphatic dianhydrides including BSDA in HMPA. Although inherent viscosities of the poly(amic acid) were somewhat low, the polymer solutions gave the free-standing polyimide films after curing. The films were soluble in organic polar solvents such as DMAc and NMP.


We present a physically-based approach to grasping and manipulation of virtual objects that produces visually realistic results, addresses the problem of visual interpenetration of hand and object models, and performs force rendering for force-feedback gloves in a single framework. Our approach couples tracked hand configuration to a simulation-controlled articulated hand model using a system of linear and torsional spring-dampers. We discuss an implementation of our approach that uses a widely-available simulation tool for collision detection and response. We illustrate the resulting behavior of the virtual hand model and of grasped objects, and we show that the simulation rate is sufficient for control of current force-feedback glove designs. We also present a prototype of a system we are developing to support natural whole-hand interactions in a desktop-sized workspace.


Farming has been described as one of the most hazardous activities by many authors. The study was conducted to analyse occupational and environmental hazards associated with cassava processing and analysed the knowledge level of the processors on the hazards associated with cassava processing. A multistage sampling procedure was adopted in selecting the respondents for the study. One hundred and eighty respondents were sampled for the study using interview schedule but only one hundred and seventy-one questionaires were suitable for analysis. The data collected were described using frequency count, percent, mean, standard deviation and pie charts while perason' correlation was employed to make deductions. Results show that majority (79.9 %) of the respondents were female with about 68.4 percent married. Majority (62.6%) of the respondents were rated as having moderate knowledge of hazards associated with cassava processing. Age (r=0.5271), years of schooling (r=0.7251) and level of travelling (r=0.4139) were found to be significantly correlated with knowledge of hazards at 0.01 level of significance while household size (r=0.3815) had positive and significant relationship with hazards at 0.05 level of significance. The study therefore established that education could be used to educate cassava processors on the various hazards associated with cassava processing in the study area.


The optimal topological structure of the piezoelectric materials involved in road traffic harvesters is covered with the linearized models obtained using practical measurements. The behavior of that harvesters is analyzed in order to obtain practical results that guarantees the optimal tracked maximum power point of operation. Our specifically designed (patent pending) test bench generates regular traffic that emulates the real road traffic. In order to compare the measured response from the simulation test bench, data were collected from a real traffic sensing installation, build in an inner road of our University Campus. Experimental results are presented for piezoelectric cable, although the results obtained from a commercial piezoelectric are presented to explore the effect of mechanical amplification in order to improve the previous results.


Abstract In this article, we first present some integral inequalities for Gauss-Jacobi type quadrature formula involving generalized relative semi-(r; m; h)-preinvex mappings. And then, a new identity concerning twice differentiable mappings defined on m-invex set is derived. By using the notion of generalized relative semi-(r; m; h)-preinvexity and the obtained identity as an auxiliary result, some new estimates with respect to Hermite-Hadamard, Ostrowski and Simpson type inequalities via fractional integrals are established. It is pointed out that some new special cases can be deduced from main results of the article.


This paper investigates the capacity problem for some multiple-access scenarios with cooperative transmitters. First, a general Multiple-Access Channel (MAC) with common information, i.e., a scenario where p transmitters send private messages and also a common message to q receivers and each receiver decodes all of the messages, is considered. The capacity region of the discrete memoryless channel is characterized. Then, the general Gaussian fading MAC with common information wherein partial Channel State Information (CSI) is available at the transmitters (CSIT) and perfect CSI is available at the receivers (CSIR) is investigated. A coding theorem is proved for this model that yields an exact characterization of the throughput capacity region. Finally, a two-transmitter/one-receiver Gaussian fading MAC with conferencing encoders with partial CSIT and perfect CSIR is studied and its capacity region is determined. For the Gaussian fading models with CSIR only (transmitters have no access to CSIT), some numerical examples and simulation results are provided for Rayleigh fading.


[1] A three-dimensional primitive equation numerical model was applied to Lake Erie on a 2 km grid to study its summer circulation and thermal structure. Model results were compared to long-term observations of currents and temperature made in 2005 at several locations, mostly in its central basin. In the shallow and mostly unstratified western basin circulation is driven by Detroit River inflow (modified to some extent by wind) and is from west to east. In the central basin (which is of intermediate depth and has a relatively flat bottom), the modeled circulation is anticyclonic (clockwise), driven by anticyclonic vorticity in the surface wind, and the thermocline is bowl-shaped, in line with observations. In the deep part of the eastern basin, the thermocline is dome-shaped and circulation is cyclonic (counterclockwise), due to density gradients (a configuration typical for other large deep lakes), while shallower areas are occupied by anticyclonic circulation driven by anticyclonic wind vorticity. In the central basin, modeled temperature and circulation patterns are quite sensitive to the specification of the wind field. Anticyclonic wind vorticity leads to thinning of the hypolimnion in the central basin and earlier destratification in the fall.


Choriocarcinoma, a malignant tumor deriving from the trophoblastic tissue, is mostly associated with adverse pregnancy. Early metastasis is very common in patient with choriocarcinoma, but the cases of intestinal metastasis are definitely rare. Herein, we reported a case of jejunal choriocarcinoma revealed by endoscopy. Segmental resection of the jejunum as well as biopsy of liver nodules were performed. The patient was classified as super high-risk choriocarcinoma and received chemotherapy and surgical treatment. Unfortunately, the patient ultimately died of liver rupture.


One of golf's preeminent commentators with more than fifty years of experience, Ben Wright relates the wealth of experiences he's gained from writing and broadcasting about the world's greatest golfers and courses, and his take on the infamous interview that cost him his twenty-three-year career as a golf announcer with CBS Sports. In Good Bounces and Bad Lies, Wright brings the reader into the world of professional golf--and professional golf broadcasting--depicting in equal measure the game's grace and tradition as well as its often raucous behind-the-scenes character. Wright tells of the ups and downs of his expansive career, relating dozens of funny and outrageous anecdotes along the way. Having known such greats as Ben Hogan, Arnold Palmer, Jack Nicklaus, Seve Ballesteros, Tom Watson, and many other prominent figures in the world of golf, Wright gives the true insider's perspective. Although controversial, Wright is an entertaining and engaging figure who personifies the elegance and audacity of the game of golf. This Bison Books edition features a new afterword by the author.


It is not easy to study socially marginalized groups such as gays, ethnic minorities, and others. This is, however, an extremely relevant topic in the consumer behavior area since the status of members of a modern consumer society is largely denied to stigmatized social groups (Barbosa, 2006). The objective of this work is to shed light on how gay men in Rio de Janeiro use the discourse associated with their possessions to build and maintain the symbolic and hierarchical boundaries between the gay and heterosexual worlds, as well as to investigate the role consumption plays in this boundary setting. An ethnographic observation of a group of gay men in Rio de Janeiro was conducted, along with 20 semi-structured interviews with openly gay men between 2005 and 2008. The results suggest that: (a) the world culturally built by gays seems to be divided into a gay world and a heterosexual world, where the division between these two worlds not only happens in their minds, but also in their possessions and purchasing decisions; (b) the meaning of gay mens' places of consumption range from profane to sacred along their lives; and (c) in the gay world, the body is seen both as a cultural construction and as an asset.


Manatee can be transported by air, out of water for 22 hours. But its skin should be kept moist,at a temperature of 21 and above.
It has been found that the pair of manatees in our captivity can live on common waterhyacinth (Eichhornia crassipes) as the main substitute for food.They not only grow well but also produce young calf.
The gestation for the two baby manatees takes 387 and 370 days respectively. The average period of 378.5 days fundamentally agrees with what has been recorded in some available material of estimation. For instance, Jennison has estimated the period to be 365 days (Crandall, 1964)
In his report, Estanislau Kostka Pinto Da Silveira (1975) said that manatees probably have sexual intercourse in a bellyto-belly position. Our observation confirms that manatees really copulate in that way.
No report has ever been made on the process of manatee's parturition. From our observation we have collected the following data: In her secoond birth the pregnant manatee has shown more obvious signs of impending parturition.The body position during parturition remains the same as usual. Some time after the foetal membr ane appears at the vaginal orifice,amniotic fluid begins to flow and lasts for about l1/2 hours until the foetus comes out. Placenta is discharged 91/2 hours later.
According to our observation, the baby manatee spurts out of the water instinctively on its own and takes the first breath.This is contrary to the description in some writings which ccnclvee that it is the mother rranatee
which supports the baby out of the water.
The gesture of nursing shows that both mother and taby are submerged
in the water, their bodies parallel with the water level, while the mother extends one of its fore flippers diagonally, the baby sucks the nipple in the mother's armpit.Thus the two bodies form an acute angle.


Dravet syndrome (DS) is caused by dominant mutations of the SCN1A gene, encoding the NaV1.1 sodium channel α subunit. Gene targeted mouse models of DS mutations replicate patients' phenotype and show reduced γ‐aminobutyric acid (GABA)ergic inhibition. However, little is known on the properties of network hyperexcitability and on properties of seizure generation in these models. In fact, seizures have been studied thus far with surface electroencephalography (EEG), which did not show if specific brain regions are particularly involved. We have investigated hyperexcitability and epileptiform activities generated in neuronal networks of a mouse model of DS.


Khageri Khola sub-watershed of the Chitwan district is stressed by climate change and is facing changes in its water source. The main objective of this study was to assess the status of water sources, their importance, water source issues, and distribution of water sources as well as to suggest appropriate conservation and management measures. Various participatory tools such as household interviews, focus group discussions and stakeholder's consultations were used. In total, 56 water sources were identified in eight micro-watersheds in Khageri Khola sub-watershed. The overall water sources were found decreasing with moderate (43%) to insufficient (32%) amount of water available for drinking. People meet their current water demand through tap water (43%) and tube wells/wells (38%). Conservation and management measures such as tree plantation, solar planning (solar power for water pumping system) for wildlife, construction of water tanks and bamboo plantation have been adopted. Hence, upstream soil erosion should be reduced to save downstream sources from flash floods by emphasizing land use planning. Regular observation, capital funding for water sources and catchment conservation and awareness programs are further required to minimize the possible risks on water


A 3.7-kilobase (kb) genomic clone of the human beta-globin gene, including 1.5-kb upstream and approximately 0.5-kb downstream, was utilized in chromosomal in situ hybridization for precise mapping of the beta-globin locus on peripheral blood lymphocyte-derived metaphases from a normal male, and for further evaluation of a clonal t(7;11) (q22;p15) translocation on bone marrow-derived metaphases from a 46-year-old male with erythroleukemia. Analyses of 205 midmetaphases from a normal male hybridized with the tritium-labeled beta-globin probe and stained with quinacrine mustard dihydrochloride revealed approximately 12% of spreads to have silver-grain deposition over the p15 band of chromosome 11. Of the 365 silver grains observed to be located on or beside chromosomes, 25 (approximately 7%) grains were localized in band p15. Karyotype analysis of a bone marrow specimen from the patient with erythroleukemia revealed hypodiploidy with various unidentified marker chromosomes as well as a presumably balanced translocation between 7q and 11p . Chromosomal in situ hybridization showed localization of silver grains at the junction between chromosomes 7 and 11 as well as to the normal chromosome 11, indicating that the beta-globin locus had not been translocated in the chromosomal rearrangement. This case demonstrates the value of chromosomal in situ hybridization in the definition of chromosome rearrangements and provides further evidence for the localization of the beta-globin gene to 11p15 .


In recent years Dutch aid projects have focused more on institutional strengthening. The overall impact of this type of aid has been limited. This paper explores possible reasons for this. In Egypt, it appeared to be difficult to make significant changes in the institutional setting. Main constraints were the low salaries, recruitment and personnel policies and the organisational culture within the government. Another factor that may have played a role is inadequate recognition of cultural backgrounds of the international consultants advising in Egypt. This is explored using Hofstede?s and Trompenaar?s typologies of culture and their effects on management. Maslow?s Hierarchy of Needs, as applied to the environment of institutional strengthening, is also considered. Adjusting an organisational culture to improve efficiency and sustainability of the organisation is a long and difficult process and should not be seen as an extension of tradition technical assistance aid projects, but rather it should be implemented as a dedicated long-term project. A major finding is that short-term consultancies may only be effective for idea generation, and not as instruments for implementing change management. Managerial capacity building should be a long-term activity with gradual change, particularly in government settings. Recognition of organisation culture in light of trans-national cultural typologies by Hofstede and Trompenaars, as well as, acceptance of the most pressing needs of the target group as the responsibility of one and the same financing agency are found lacking in traditional Development Aid.


Background High prevalence of ocular surface disorders includes eye dryness and corneal ulcer among intensive care unit patients remains an issue. This study aimed to compare the effectiveness of Lubratex ointment and vitamin A eye ointment in preventing ocular surface disorders in intensive care unit patients. Methods A single-center randomized clinical trial was conducted in critically ill patients of vitamin A eye ointment and Lubratex ointment in preventing ocular surface disorders. Forty-one eligible patients were randomly assigned to administered vitamin A eye ointment in one eye and Lubratex ointment in the other eye. After five days, using fluorescein and Schirmer's tests, an ophthalmologist examined patients and specified those with ocular surface disorders. Results The results showed a significant decrease in the incidence of dry eye (p ≤ 0.001) and corneal ulcer (p = 0.002) with the use of Lubratex ointment. Conclusions Although Lubratex ointment was more effective than vitamin A ointment in preventing ocular surface disorders, further research is needed to confirm the findings of the present study.


The rat submandibular gland contains several members of the kallikrein family. In the present study we purified and raised an antiserum against one of these enzymes, i.e., esterase B, which was first described by Khullar et al. in 1986. N-terminal amino acid analysis revealed complete homology between esterase B and the kallikrein family gene RSKG-7. For characterization of the antiserum, flat-bed isoelectrofocusing with immunoblotting was superior to immunoelectrophoresis and double immunodiffusion in detecting and identifying crossreacting proteins. This was due to the fact that kallikrein-like enzymes were readily separated by isoelectrofocusing, and immunoreactivity was easily detected by the sensitive peroxidase-anti-peroxidase staining after blotting onto nitrocellulose membrane. Immunohistochemical controls were carried out accordingly, including homologous as well as crossreacting antigens. In the submandibular gland, esterase B was detected exclusively in all granular convoluted tubular cells, co-localized with tissue kallikrein and tonin. Some staining was also observed in striated duct cells; however, this staining reaction was induced by cross-reactivity with kallikrein, since staining was abolished by addition of kallikrein as well as esterase B to the primary antiserum. It was therefore concluded that like tonin and antigen gamma, but unlike kallikrein, esterase B was not detected in the striated ducts of the submandibular, parotid, or sublingual glands. This separation in anatomic distribution between esterase B and kallikrein may indicate that prokallikrein activation is not the only biological function of esterase B.


Probability forecasts for binary events play a central role in many applications. Their quality is commonly assessed with proper scoring rules, which assign forecasts a numerical score such that a correct forecast achieves a minimal expected score. In this paper, we construct e-values for testing the statistical significance of score differences of competing forecasts in sequential settings. E-values have been proposed as an alternative to p-values for hypothesis testing, and they can easily be transformed into conservative p-values by taking the multiplicative inverse. The e-values proposed in this article are valid in finite samples without any assumptions on the data generating processes. They also allow optional stopping, so a forecast user may decide to interrupt evaluation taking into account the available data at any time and still draw statistically valid inference, which is generally not true for classical p-value based tests. In a case study on postprocessing of precipitation forecasts, state-of-the-art forecasts dominance tests and e-values lead to the same conclusions.


Transfusion-associated bacterial sepsis is the most common microbiological risk of transfusion and is caused mostly by platelet concentrates (PCs). The most frequently identified bacterial contaminants of PCs are coagulase-negative staphylococci (CNS). In order to learn more about the distribution, source and risk of the CNS that are involved in bacterial contamination of PCs, CNS strains isolated during platelet screening were collected and characterized to the species level with three different methods: 16S rRNA and sodA gene sequencing, matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and amplified fragment length polymorphism (AFLP) analysis. AFLP analysis was also used for the typing of the CNS strains. A total of 83 CNS strains were analysed by sequencing and 8 different CNS species were identified, with Staphylococcus epidermidis being the predominant species. MALDI-TOF MS and AFLP analysis confirmed these results to a large extent. However, MALDI_TOF MS could not identify all strains to the species level and AFLP analysis revealed an additional, likely novel, CNS species. The species identified are mainly recognized as being part of the normal skin flora. Typing of the CNS strains by AFLP analysis showed that there was not a unique strain which is significantly more often present during bacterial contamination of PCs.


BACKGROUND
Ehlers-Danlos syndrome (EDS) is a heterogeneous group of rare inherited diseases involving connective tissue. Vascular EDS (vEDS) is associated with abnormal type III collagen, which is an essential component of skin, hollow organs and arterial walls, and causes potentially fatal visceral and arterial complications. The surgical management of these patients is challenging and should be limited to life-saving procedures.

CASE DESCRIPTION
We report a case of a 42-year-old male who presented a hemorrhagic shock due to spontaneous rupture of an ascending branch of the left colic artery. The coexisting presence of multiple abdominal vascular abnormalities suggested the diagnosis of vEDS, later confirmed by the discovery of a new missense mutation in the COL3A1 gene with pathogenic significance. The post-operative course was marked by a mechanical ileus caused by an ischemic stenosis of the descending colon. Failure of conservative management and the well-known risk of colonic perforation in these patients led to the decision to perform a diverting ileostomy.

CONCLUSION
The management of these patients is difficult, and risk-benefit assessments must be made on a case-by-case basis. Less invasive procedures should be considered whenever possible.


ABSTRACT Attenuated poxvirus vectors expressing human immunodeficiency virus type 1 (HIV-1) antigens are considered promising HIV/AIDS vaccine candidates. Here, we describe the nature of T cell immune responses induced in healthy volunteers participating in a phase I clinical trial in Spain after intramuscular administration of three doses of the recombinant MVA-B-expressing monomeric gp120 and the fused Gag-Pol-Nef (GPN) polyprotein of clade B. The majority (92.3%) of the volunteers immunized had a positive specific T cell response at any time postvaccination as detected by gamma interferon (IFN-γ) intracellular cytokine staining (ICS) assay. The CD4+ T cell responses were predominantly Env directed, whereas the CD8+ T cell responses were similarly distributed against Env, Gag, and GPN. The proportion of responders after two doses of MVA-B was similar to that obtained after the third dose of MVA-B vaccination, and the responses were sustained (84.6% at week 48). Vaccine-induced CD8+ T cells to HIV-1 antigens after 1 year were polyfunctional and distributed mainly within the effector memory (TEM) and terminally differentiated effector memory (TEMRA) T cell populations. Antivector T cell responses were mostly induced by CD8+ T cells, highly polyfunctional, and of TEMRA phenotype. These findings demonstrate that the poxvirus MVA-B vaccine candidate given alone is highly immunogenic, inducing broad, polyfunctional, and long-lasting CD4 and CD8 T cell responses to HIV-1 antigens, with preference for TEM. Thus, on the basis of the immune profile of MVA-B in humans, this immunogen can be considered a promising HIV/AIDS vaccine candidate.


Leaf nitrogen (N) and phosphorus (P) have been used widely in the ecological stoichiometry to understand nutrient limitation in plant. However,few studies have focused on the relationship between root nutrients and environmental factors. The main objective of this study was to clarify the pattern of root and leaf N and P concentrations and the relationships between plant nitrogen (N) and phosphorus (P) concentrations with climatic factors under low temperature conditions in the northern Tibetan Plateau of China. We conducted a systematic census of N and P concentrations, and the N∶P ratio in leaf and root for 139 plant samples, from 14 species and 7 families in a dry Stipa purpurea alpine steppe on the northern Tibetan Plateau of China. The results showed that the mean root N and P concentrations and the N∶P ratios across all species were 13.05 mg g−1, 0.60 mg g−1 and 23.40, respectively. The mean leaf N and P concentrations and the N∶P ratio were 23.20 mg g−1, 1.38 mg g−1, and 17.87, respectively. Compared to global plant nutrients concentrations, plants distributing in high altitude area have higher N concentrations and N∶P, but lower P concentrations, which could be used to explain normally-observed low growth rate of plant in the cold region. Plant N concentrations were unrelated to the mean annual temperature (MAT). The root and leaf P concentrations were negatively correlated with the MAT, but the N∶P ratios were positively correlated with the MAT. It is highly possible this region is not N limited, it is P limited, thus the temperature-biogeochemical hypothesis (TBH) can not be used to explain the relationship between plant N concentrations and MAT in alpine steppe. The results were valuable to understand the bio-geographic patterns of root and leaf nutrients traits and modeling ecosystem nutrient cycling in cold and dry environments.


This paper describes hydrodynamic focusing inside a micromachined flow cytometer. Flow cytometry is a process whereby cells are analyzed and sorted based on hydrodynamic focusing phenomenon and specific cellular characteristics. In this study, the hydrodynamic focusing phenomenon is first modeled by employing potential flow theory. Then the flow field inside the flow cytometer is numerically simulated. The effect of the device geometry and relative sheath and sample flow rate on the focusing of the center flow is explored systematically. At last, a micromachine-based flow chamber is designed and fabricated on plastic substrates as a micro flow cytometer. Hydrodynamic focusing is verified with the use of microscopic visualization of water sheath flows and dyecontaining sample flow. Experimental data indicate that the size of focused sample stream can be reduced to about 3mm, which is applicable to cell sorting and counting. @DOI: 10.1115/1.1385514#


A patient presented with sudden headache and isolated bilateral third nerve palsy. Neuroradiologic examination disclosed a giant aneurysm of the right internal carotid artery. At postmortem examination, the aneurysm compressed and stretched both oculomotor nerves.


Abstract Vegetation changes in the Indus River basin within the past 10.8 million years were investigated based on the analysis of n-fatty acids and their carbon isotopes in sediments from IODP Site U1457 in the Laxmi Basin of the Arabian Sea. The δ13C of long-chain n-C32 fatty acid shifted from −34 to −22 ‰ from 10 to 6.3 Ma, while the δ13C of mid-chain n-C24 fatty acid was nearly constant at around −23 to −22 ‰ over the same period. This large difference in the δ13C values suggests that the mid-chain fatty acids reflect the contribution of aquatic vascular C3 plants. Before 6.3 Ma, the average chain length of n-fatty acids and the δ13C values of long-chain fatty acids were negatively correlated, suggesting that the δ13C values reflected the relative abundance of terrestrial C3 versus aquatic C3 plants in the Indus River basin and western India. After 5.8 Ma, the average chain length was variable, but the δ13C values remained nearly the same, suggesting that the δ13C values reflected heavier δ13C values of both aquatic C3 and C4 plants. A three-end-member model calculation suggests that terrestrial C3 plants were replaced by C4 plants in the Indus River basin and western India from 9.7 or 8.2 to 6.3 Ma. Aridification in those areas during the late Miocene period may have driven the replacement of terrestrial C3 plants by C4 plants. An episodic increase in the abundance of terrestrial plants around 8 Ma is attributed to elevated precipitation by regionally enhanced moisture transport.


Studying the hysteretic relationships embedded in high‐frequency suspended‐sediment concentration and river discharge data over 600+ storm events provides insight into the drivers and sources of riverine sediment during storm events. However, the literature to date remains limited to a simple visual classification system (linear, clockwise, counter‐clockwise, and figure‐eight patterns) or the collapse of hysteresis patterns to an index. This study leverages 3 years of suspended‐sediment and discharge data to show proof‐of‐concept for automating the classification and assessment of event sediment dynamics using machine learning. Across all catchment sites, 600+ storm events were captured and classified into 14 hysteresis patterns. Event classification was automated using a restricted Boltzmann machine (RBM), a type of artificial neural network, trained on 2‐D images of the suspended‐sediment discharge (hysteresis) plots. Expansion of the hysteresis patterns to 14 classes allowed for new insight into drivers of the sediment‐discharge event dynamics including spatial scale, antecedent conditions, hydrology, and rainfall. The probabilistic RBM correctly classified hysteresis patterns (to the exact class or next most similar class) 70% of the time. With increased availability of high‐frequency sensor data, this approach can be used to inform watershed management efforts to identify sediment sources and reduce fine sediment export.


ABSTRACT Migrant labour has increasingly become key to the functioning of many economies including in Asia. While existing studies have generated rich understandings of precarity, there remains a paucity of studies that shed new light on how migration infrastructures shape the production of multidimensional forms of precarity in the global South. Drawing on a case study of Nepali migrant workers engaged in the manufacturing and service sectors in Malaysia, this article examines migrant workers' precarious experiences and the role of regulatory, commercial, workplace and socio-economic infrastructures in shaping migrant experiences. It unpacks multidimensional categories of migrant precarity transcending oft-discussed economic forms of precarity, which provide a heuristic tool for researchers to reveal the underlying precarity-generating specific political, social, and economic processes. The article argues that migrant precarity results from the complex interplay between workplace and regulatory infrastructures in receiving country, which is worsened by the workings of commercial and socio-economic infrastructures in sending country. The article has demonstrated how migration infrastructures established by the regulatory and commercial actors purportedly for facilitating migration and benefiting migrant workers have instead produced and exacerbated migrant precarity.


Cellular binding and entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are mediated by its spike glycoprotein (S protein), which binds with not only the human angiotensin-converting enzyme 2 (ACE2) receptor but also glycosaminoglycans such as heparin. Cell membrane-coated nanoparticles ("cellular nanosponges") mimic the host cells to attract and neutralize SARS-CoV-2 through natural cellular receptors, leading to a broad-spectrum antiviral strategy. Herein, we show that increasing surface heparin density on the cellular nanosponges can promote their inhibition against SARS-CoV-2. Specifically, cellular nanosponges are made with azido-expressing host cell membranes followed by conjugating heparin to the nanosponge surfaces. Cellular nanosponges with a higher heparin density have a larger binding capacity with viral S proteins and a significantly higher inhibition efficacy against SARS-CoV-2 infectivity. Overall, surface glycan engineering of host-mimicking cellular nanosponges is a facile method to enhance SARS-CoV-2 inhibition. This approach can be readily generalized to promote the inhibition of other glycan-dependent viruses.