Miracle-dz/UniFAR-FTUs huggingface dataset:
Activity-Dependent Phosphorylation by CaMKIIδ Alters the Ca2+ Affinity of the Multi-C2-Domain Protein Otoferlin

Otoferlin is essential for fast Ca2+-triggered transmitter release from auditory inner hair cells (IHCs), playing key roles in synaptic vesicle release, replenishment and retrieval. Dysfunction of otoferlin results in profound prelingual deafness. Despite its crucial role in cochlear synaptic processes, mechanisms regulating otoferlin activity have not been studied to date. Here, we identified Ca2+/calmodulin-dependent serine/threonine kinase II delta (CaMKIIδ) as an otoferlin binding partner by pull-downs from chicken utricles and reassured interaction by a co-immunoprecipitation with heterologously expressed proteins in HEK cells. We confirmed the expression of CaMKIIδ in rodent IHCs by immunohistochemistry and real-time PCR. A proximity ligation assay indicates close proximity of the two proteins in rat IHCs, suggesting that otoferlin and CaMKIIδ also interact in mammalian IHCs. In vitro phosphorylation of otoferlin by CaMKIIδ revealed ten phosphorylation sites, five of which are located within C2-domains. Exchange of serines/threonines at phosphorylated sites into phosphomimetic aspartates reduces the Ca2+ affinity of the recombinant C2F domain 10-fold, and increases the Ca2+ affinity of the C2C domain. Concordantly, we show that phosphorylation of otoferlin and/or its interaction partners are enhanced upon hair cell depolarization and blocked by pharmacological CaMKII inhibition. We therefore propose that otoferlin activity is regulated by CaMKIIδ in IHCs.
Genitourinary injuries in pelvic fracture morbidity and mortality using the National Trauma Data Bank.

BACKGROUND Pelvic fractures from blunt force trauma place the bladder and urethra at risk for injury, often resulting in significant complications. We sought to compare morbidity, mortality, and health care resource utilization in patients with and without genitourinary injuries (GUI) associated with pelvic fractures. METHODS In this retrospective study of patients with blunt force pelvic fractures, the incidence of GUI, initial emergency department data, mechanism of injury, morbidity, health care resource utilization, associated injuries, discharge disposition, and mortality were investigated using chi tests for categorical variables and Student's t test for continuous variables comparing pelvic fractures with and without GUI. Multiple logistic regression analysis was used to detect significant predictors of mortality. RESULTS Of the 31,380 patients with pelvic fractures, 1,444 had GUI. Men more commonly sustained pelvic fractures with GUI than women (66.14% vs. 33.86%). The incidence of urogenital, bladder, and urethral injuries for men and women was 5.34%, 3.41%, 1.54%, and 3.62%, 3.37%, 0.15%, respectively. Patients with GUI remained hospitalized longer (median 10 vs. 6 d, p < 0.001), had more intensive care unit stay days (median 3 vs. 1 d, p < 0.001), were less often discharged home (31.02% vs. 42.82%), and had an increased mortality rate (13.99% vs. 8.08%, p < 0.001) when compared with patients without GUI. Motor vehicle collisions were the most common mechanism of injury for all pelvic fractures. Spleen and liver were the most commonly injured abdominal organs associated with pelvic fractures as a whole. Pelvic fractures with GUI were more likely to result in associated injuries of the bowel, and reproductive organs. Although GUI was not found to be an independent predictor of mortality, age >or=65 years, initial systolic blood pressure in the emergency department 0 mm Hg to 90 mm Hg, Injury Severity Score >or=25, Glasgow coma score of <or=8, and female gender were independent predictors of mortality. CONCLUSION Patients sustaining a pelvic fracture with GUI have an increase in morbidity. Although GUI was not an independent predictor of mortality, patients who sustained a pelvic fracture with GUI had a greater number of concomitant injuries resulting in an increase in overall mortality compared with those without an associated GUI.
Host of Troubles: Multiple Host Ambiguities in HTTP Implementations

The Host header is a security-critical component in an HTTP request, as it is used as the basis for enforcing security and caching policies. While the current specification is generally clear on how host-related protocol fields should be parsed and interpreted, we find that the implementations are problematic. We tested a variety of widely deployed HTTP implementations and discover a wide range of non-compliant and inconsistent host processing behaviours. The particular problem is that when facing a carefully crafted HTTP request with ambiguous host fields (e.g., with multiple Host headers), two different HTTP implementations often accept and understand it differently when operating on the same request in sequence. We show a number of techniques to induce inconsistent interpretations of host between HTTP implementations and how the inconsistency leads to severe attacks such as HTTP cache poisoning and security policy bypass. The prevalence of the problem highlights the potential negative impact of gaps between the specifications and implementations of Internet protocols.
Treatment results of methotrexate and folinic acid as primary chemotherapy for nonmetastatic gestational trophoblastic neoplasia.

OBJECTIVE To evaluate the efficacy and toxicity of methotrexate and folinic acid (MTX-FA) chemotherapy in patients with nonmetastatic gestational trophoblastic neoplasia (NMGTN). MATERIAL AND METHOD Between 1997 and 2003, a total of 67 patients with NMGTN received treatment at the Chiang Mai University Hospital. Of the 67 patients, 55 were initially treated with methotrexate 1.0 mg/kg intramuscularly (IM) on day 1, 3,5, and 7 and folinic acid 0.1 mg/kg IM on day 2, 4, 6 and 8. Treatment courses were repeated every 14 days. Clinical characteristics and outcomes were analyzed RESULTS All 55 patients with NMGTN were cured. Of the 55 patients initially treated with MTX-FA, 49 (89%) achieved complete remission. Six (11%) patients developed methotrexate resistance, 3 were cured with actinomycin D, 1 were cured with 5-fluorouracil followed by etoposide, 2 required hystertectomy to attain remission. No serious toxicity was noted CONCLUSION Methotrexate and folinic acid chemotherapy is highly effective and well-tolerated in treating patients with nonmetastatic gestational trophoblastic neoplasia.
Scalable Network-Layer Defense Against Internet Bandwidth-Flooding Attacks

In a bandwidth-flooding attack, compromised sources send high-volume traffic to the target with the purpose of causing congestion in its tail circuit and disrupting its legitimate communications. In this paper, we present active Internet traffic filtering (AITF), a network-layer defense mechanism against such attacks. AITF enables a receiver to contact misbehaving sources and ask them to stop sending it traffic; each source that has been asked to stop is policed by its own Internet service provider (ISP), which ensures its compliance. An ISP that hosts misbehaving sources either supports AITF (and accepts to police its misbehaving clients), or risks losing all access to the complaining receiver-this is a strong incentive to cooperate, especially when the receiver is a popular public-access site. We show that AITF preserves a significant fraction of a receiver's bandwidth in the face of bandwidth flooding, and does so at a per-client cost that is already affordable for today's ISPs; this per-client cost is not expected to increase, as long as botnet-size growth does not outpace Moore's law. We also show that even the first two networks that deploy AITF can maintain their connectivity to each other in the face of bandwidth flooding. We conclude that the network-layer of the Internet can provide an effective, scalable, and incrementally deployable solution against bandwidth-flooding attacks.
To see an interphase chromosome or: How a disease can be associated with specific nuclear genome organization

The last hierarchical level of cellular genome organization is the spatial arrangement of chromosomes within the nuclear space. Despite of high regulatory potential and functional implications, issues concerning nuclear organization at chromosomal level are rarely addressed because of limitations in visualizing interphase chromosomes. The problem is especially seen when an attempt to associate specific patterns of nuclear genome organization with a pathological condition is made. Fortunately, advances in molecular cytogenetics have provided for a solution to visualize chromosomes in interphase nuclei at molecular resolution. A study in this issue of BioDiscovery shows the way of how to identify interphase chromosome architecture at molecular resolutions and demonstrates the involvement of specific nuclear genome organization in generating a cancercausing chromosomal aberration (translocation between chromosomes 8 and 21 in acute myelogenous leukemia). Authors’ findings suggest interphase molecular cytogenetic techniques (i.e. interphase chromosome-specific multicolor banding or ICS-MCB) to be required to perform studies regarding nuclear genome organization at chromosomal level and its role in disease pathogenesis.
A Framework for Predicting Query Response Time

In a typical OLTP environment, emphasis has been given on promising Service level Agreements (SLAs) for perceived query elapsed response time; the SQL queries are tested on the small size of database which may be a fraction of the production database. As time progresses the database grows and the earlier optimized queries may not hold SLA anymore. Once the application is deployed, it becomes difficult to modify the application or alter the production system. In this paper, we have discussed a framework for predicting the SQL query response time with growth of the database while being transparent to the production hardware, storage subsystem and DB Server. We have discussed various factors which can impact query response time and are also affected by the increase in the data size. We have presented a theoretical model for predicting the elapsed response time of SQL queries and also discussed a case study of Oracle lOg for implementing the proposed framework.
Fabrication and optical properties of noble metal nanostructures

Experimental and theoretical results are presented in Chapters 2, 3, and 4 on the effects of dielectric medium, particle size, and interparticle distance, respectively, on plasmon coupling in two-dimensional arrays of silver nanoparticles. The arrays were fabricated via the self-assembly of single crystal particles from c.a. 46 nm to 287 nm on PVP-modified glass substrates. Spin-coated poly(methylmethacrylate) layers were used to immobilize the particles and prevent their surface aggregation. Varying the thickness of the PMMA layer made it possible to change the average dielectric medium between the particles. UV-Visible spectra of different arrays were compared to the corresponding electron microscope images. It was found that increasing the dielectric function of the medium surrounding the particles promoted the coherent plasmon coupling of the particles. It was also observed that increasing the size of the particles in arrays resulted in red shifting and broadening of the coupled plasmon peak. The peak position against the particle size exhibited a linear trend, providing the possibility to adjust a lambda maximum by selecting an appropriate particle size. Decreasing the interparticle distance resulted in spectral shifting and broadening of the plasmon peak and affected the intensity and sharpness of the peaks. Smaller particles shifted to the red spectral range, where as larger particles shifted in the opposite direction upon decreasing the interparticle distance. The phenomenon known as Surface Enhanced Raman Spectroscopy (SERS) is presented in Chapter 5. An analysis of spectra from 20 different molecules adsorbed on SERS substrates revealed competitive Raman enhancement from different types of
Giant cavernous hemangioma coexistent with diffuse hepatic hemangiomatosis presenting as portal vein thrombosis and hepatic lobar atrophy

A combination of giant hepatic hemangioma and diffuse hemangiomatosis is extremely rare in adults. Even when they are large, hemangiomas are soft and rarely compress adjacent structures. A 78-year-old man presented with abdominal pain and distension. Ultrasonography, computed tomography, and magnetic resonance imaging demonstrated a large expansile mass replacing the medial segment and caudate lobe with diffusely scattered nodules in the entire liver. The large hilar mass contained a central nonenhancing area and had a mass effect, leading to left portal vein occlusion. The image findings also revealed two unprecedented findings: left lateral segmental atrophy of the liver and recent portomesenteric vein thrombosis. The hepatic lesions were confirmed with hemangiomas by ultrasonography-guided biopsy. We diagnosed intrahepatic portal vein obstruction caused by a mass effect of giant hepatic hemangioma coexistent with diffuse hemangiomatosis, resulting in hepatic segmental atrophy and extrahepatic portal vein thrombosis.
The application of Safe Scrum to IEC 61508 certifiable software

In order to develop a better understanding of the application of Scrum to IEC61508 certifiable software, we assessed the standard to see how Scrum could conform. Each section of part 3 of the standard was assigned one of the categories: (1) “OK” – no modification needed to Scrum or IEC61508, (2) “? ” – need to be discussed, (3) “Not OK” – need adaptation of Scrum Based on our assessment we proposed the Safe Scrum where the main idea is separation of concerns. Everything that is not part of the software development process is kept outside Scrum and will thus not be influenced by our choice of paradigm. In Safe Scrum, all requirements are split into safety critical requirements and other requirements and inserted into separate product backlogs. We then did a new assessment where we took the Safe Scrum into consideration. We found 15 issues where we need changes in order to make the process acceptable to Scrum and the safety assessors: how to structure development, plan for validating safety, create, review, select, design and ensure safety, write requirements for module testing, and test and evaluate the outputs from the safety lifecycle The first part of our model consists of the IEC61508 steps of developing the environment description and the SSRS phases 1-4. These initial steps result in the initial requirements of the system that is to be developed and is the key input to the second part of the model – the Safe Scrum process. Using an iterative and incremental approach means that the project can be continuously re-planned based on recent product experience. Between the iterations, experience can be used to re-prioritize the product backlogs. This makes the process flexible. When the sprints are completed, a final RAMS validation will be done. Since most of the system has been incrementally validated during the sprints, we expect the final RAMS validation to be less extensive than when using other development paradigms. This will also help us to reduce the time and cost needed for certification.
Fish Lateral Line Neurophysiological and Neurobehavioral Responses as a Sensitive Water Quality Monitoring System

Cadmium is a heavy metal ion that can cause deleterious effects on aquatic animals. This study uses both electrophysiological recordings from lateral line nerves and videotaping of schooling behavior to investigate the effects of cadmium exposure on fish. The fathead minnows were exposed to cadmium at a concentration of 450 μg/1 over a 24-hr period. Extracellular recording with a silver hook electrode was used to record compound action potentials from the lateral lines of control and experimental fish. After a short time exposure (24 hr) to cadmium ions, all of the electrophysiological activities of the lateral line nerves were suppressed. However, after a I 0-day recovery in clean water, the function of the lateral line nerves was regained. Schooling behavior observed under lighted conditions showed no significant difference (in terms of percentage of time forming a school) between control and experimental fish. Schooling behavior, however, was completely lost for experimental fish when observed under complete darkness but it was regained after a 10-day recovery in clean water. The current study shows that both electrophysiological recording from the lateral line nerve and observation of schooling behavior can be used as effective assay methods for cadmium toxicity studies. Focus Categories: MET, TS, WQL Kevwords: Biomonitoring, Heavy Metals, Lateral Line, Schooling Behavior, Mining, Pollutants, Toxic Substances
Confronting the Environmental Kuznets Curve

The environmental Kuznets curve posits an inverted-U relationship between pollution and economic development. Pessimistic critics of empirically estimated curves have argued that their declining portions are illusory, either because they are cross-sectional snapshots that mask a long-run "race to the bottom" in environmental standards, or because industrial societies will continually produce new pollutants as the old ones are controlled. However, recent evidence has fostered an optimistic view by suggesting that the curve is actually flattening and shifting to the left. The driving forces appear to be economic liberalization, clean technology diffusion, and new approaches to pollution regulation in developing countries.
40-Gb/s all-optical packet synchronization and address comparison for OTDM networks

We demonstrate a novel optical time division multiplexing packet-level system-synchronization and address-comparison technique, which relies on cascaded semiconductor-based optical logic gates operating at 50-Gb/s line rates. Synchronous global clock distribution is used to achieve fixed length packet-synchronization that is resistant to channel-induced timing delays, and straightforward to achieve using a single optical logic gate. Four-bit address processing is achieved using a pulse-position modulated header input to a single optical logic gate, which provides Boolean XOR functionality, low latency, and stability over >1 h time periods with low switching energy <100 fJ.
A Semantic Formalization of UML-RT Models with csp+t Processes Applicable to Real-time Systems Verification

When a semi-formal language (like UML-RT) and a formal specification language (like CSP+T) are combined to obtain a Real-Time System (RTS) software specification, it is important to ensure the possibility of verifying the derived system design. A formal semantics of CSP+T temporal operators in terms of CSP trace semantics is presented here, and also a compositional refinement of CSP+T process terms to perform the system's software verification. The semantics of the system requirements is preserved from their initial specification to the final system implementation. The inclusion relationship between the traces of increasingly refined process terms assures semantics preservation.
Discovering Latent Patterns with Hierarchical Bayesian Mixed-Membership Models

There has been an explosive growth of data-mining models involving latent structure for clustering and classification. While having related objectives these models use different parameterizations and often very different specifications and constraints. Model choice is thus a major methodological issue and a crucial practical one for applications. In this paper, we work from a general formulation of hierarchical Bayesian mixed-membership models in Erosheva [15] and Erosheva, Fienberg, and Lafferty [19] and present several model specifications and variations, both parametric and nonparametric, in the context of the learning the number of latent groups and associated patterns for clustering units. Model choice is an issue within specifications, and becomes a component of the larger issue of model comparison. We elucidate strategies for comparing models and specifications by producing novel analyses of two data sets: (1) a corpus of scientific publications from the Proceedings of the National Academy of Sciences (PNAS) examined earlier by Erosheva, Fienberg, and Lafferty [19] and Griffiths and Steyvers [22]; (2) data on functionally disabled American seniors from the National Long Term Care Survey (NLTCS) examined earlier by Erosheva [15, 16, 17], Erosheva and Fienberg [18]. Our specifications generalize those used in earlier studies. For example, we make use of both text and references to narrow the choice of the number of latent topics in our publications data, in both parametric and nonparametric settings. We then compare our analyses with the earlier ones, for both data sets, and we use them to illustrate some of the dangers associated with the practice of fixing the hyper-parameters in complex hierarchical Bayesian mixed-membership models to cut down the computational burden. Our findings also bring new insights regarding latent topics for the PNAS text corpus and disability profiles for the NLTCS data.
Abnormal kinetics of erythrocyte sodium lithium countertransport in patients with diabetic nephropathy in Thailand.

BACKGROUND In essential hypertension and diabetic nephropathy, sodium-lithium counter transport (Na/Li CT) is an inherited marker for metabolic influences of cardiovascular risk. The kinetics of Na/Li CT are modified by two types of thiol group in the membrane. In choline medium, the type 1 thiol reacts with N-ethtyl maleimide (NEM) to cause a decrease in Km and increase Vmax/Km ratio. However in the presence of external Na or Li both the type 1 or type 2 thiols react so that both Km and Vmax are reduced. Low Km of Na/Li CT has been previously reported to be a major abnormality in diabetic nephropathy (DN) and can be used to identify diabetic patients who are at high risk for DN. A recent study showed that the type 1 thiol protein controlling the Km of Na/Li CT was a 33-kD protein and the gene for this protein is going to be cloned. OBJECTIVE The authors sought to identify Na/Li CT kinetic abnormalities in Type 2 diabetes in Thai patients. MATERIAL AND METHOD Erythrocyte Na/Li CT kinetics and their modulation by thiol proteins were measured in erythrocytes from 22 patients with Type 2 diabetes and 42 normal control subjects. RESULTS The kinetics of Na/Li CT in untreated erythrocytes were similar Thiol protein alkylation with NEM generally caused both Vmax and Km to fall, but caused Km to rise in erythrocytes of diabetic patients, whose native Km was low. Thus, abnormalities in the regulation of Na/Li CT by key thiol proteins were found in about one-third of subjects with Type 2 diabetes in Thailand. CONCLUSION Membrane abnormalities may indicate a common pathway of pathological mechanism found in essential hypertension and diabetic nephropathy and may be used as a phenotype for further genetic studies of this transporter.
A metrics suite for concurrent logic programs

A large body of research in the measurement of software complexity has focused on imperative programs, but little effort has been made for logic programs. In this paper, complexity metrics for concurrent logic programs are proposed, which are specifically designed to quantify the information flow of concurrent logic programs. These metrics are defined based on the argument dependence net (ADN) of a concurrent logic program which is an arc-classified digraph to explicitly represent various program dependences between arguments in the program. The proposed metrics can be used to measure the complexity of a concurrent logic program from various different viewpoints.