Miracle-dz/UniFAR-FTUs huggingface dataset:
Phorbol ester induced trafficking‐independent regulation and enhanced phosphorylation of the dopamine transporter associated with membrane rafts and cholesterol

We examined the mechanisms involved in protein kinase C (PKC)‐dependent down‐regulation of dopamine transporter (DAT) activity and cell surface expression by treating heterologously expressing cells with the clathrin‐mediated endocytosis inhibitor concanavalin A (Con A) or the cholesterol depleter/membrane raft disrupter methyl‐β‐cyclodextrin (MβC) prior to treatment with the PKC activator phorbol 12‐myristate, 13‐acetate (PMA). Con A blocked PMA‐induced surface reductions of DAT but only partially inhibited down‐regulation, while MβC partially blocked down‐regulation but did not inhibit loss of cell surface DAT, demonstrating that PKC‐induced DAT down‐regulation occurs by a combination of trafficking and non‐trafficking processes. Using density‐gradient centrifugation, we found that DATs are distributed approximately equally between Triton‐insoluble, cholesterol‐rich membrane rafts and Triton‐soluble non‐raft membranes. DATs in both populations are present at the cell surface and are active for dopamine and cocaine binding. PMA‐induced loss of cell surface DAT occurred only from non‐raft populations, demonstrating that non‐raft DATs are regulated by trafficking events and indicating the likelihood that the cholesterol‐dependent non‐trafficking regulatory mechanism occurs in rafts. PMA did not affect the DAT raft‐non‐raft distribution but stimulated the phosphorylation of DAT to a substantially greater level in rafts than non‐rafts. These findings reveal a previously unknown role for cholesterol in DAT function and demonstrate the presence of distinct subcellular DAT populations that possess multiple regulatory differences that may impact dopaminergic neurotransmission.
Risk Factors for Developing Pneumonia in Patients with Diabetes Mellitus Following Acute Ischaemic Stroke

Objectives: To evaluate markers of infection and identify risk factors for the development of pneumonia following acute ischaemic stroke in patients with diabetes mellitus. Methods: Patients with diabetes mellitus (n = 106) who were hospitalized after acute ischaemic stroke with (n = 32) or without (n = 74) pneumonia at admission were included in the study. Levels of C-reactive protein (CRP) and interleukin-6 (IL-6), white blood cell (WBC) count, mean body temperature and severity of stroke on the National Institutes of Health Stroke Scale were measured at the time of admission. The degree of disability according to the modified Rankin Scale was assessed after 30 days. Results: Raised levels of IL-6 and CRP, older age, more severe stroke, longer duration of hospitalization and dysphagia were significantly associated with the development of pneumonia. Patients with pneumonia had significantly worse outcomes compared with nonpneumonia patients after 1 month. Raised WBC count and mean body temperature were not significant predictors of pneumonia. Conclusions: Markers of infection, more severe ischaemic stroke, dysphagia and older age may help in predicting the occurrence of pneumonia at stroke onset.
Iatrogenic bile duct injury: a population-based study of 152 776 cholecystectomies in the Swedish Inpatient Registry.

HYPOTHESIS Older age, male sex, and low yearly hospital volume of cholecystectomy may increase the risk of bile duct injury (BDI), whereas the use of intraoperative cholangiography may decrease the risk. The incidence of BDI at cholecystectomy may have increased after the introduction of laparoscopic cholecystectomy. DESIGN Nationwide population-based study of all cholecystectomies registered in the Swedish Inpatient Registry from 1987 through 2001. SETTING All hospitals performing inpatient cholecystectomies in Sweden. PATIENTS Cholecystectomies were identified using International Classification of Diseases, Ninth and 10th Revisions surgical procedure codes. After exclusion of patients with hepatobiliary and pancreatic malignancies, patients with codes indicating reconstructive bile duct operations within 1 year after cholecystectomy were considered BDI cases. Risk factors for BDI were analyzed using multivariate logistic regression. The incidence proportion of BDI was calculated by dividing the number of cases by the number of cholecystectomies. MAIN OUTCOME MEASURES Relative risks were estimated using odds ratios with 95% confidence intervals, and incidence proportion was used to describe incidence. RESULTS Among 152 776 cholecystectomies, 613 reconstructed BDIs (0.40%) were identified. Older age and male sex were positively associated with BDI, whereas intraoperative cholangiography was negatively associated with BDI. The incidence proportion of BDI was 0.40% from 1987 to 1990, decreased to 0.32% from 1991 to 1995, and increased to 0.47% from 1996 to 2001. The mean yearly hospital volume did not affect the risk of BDI. CONCLUSIONS Older age and male sex increased the risk of BDI, whereas intraoperative cholangiography was protective. There was a small to moderate long-term increase in the risk of BDI after the introduction of laparoscopic cholecystectomy compared with the pre-laparoscopic era.
Differences in the infrared bright pupil response of human eyes

In this paper, we describe experiments conducted to explain observed differences in the bright pupil response of human eyes. Many people observe the bright pupil response as the red-eye effect when taking flash photography. However, there is significant variation in the magnitude of the bright pupil response across the population. Since many commercial gaze-tracking systems use the infrared bright pupil response for eye detection, a clear understanding of the magnitude and cause of the bright pupil variation gives critical insight into the robustness of gaze tracking systems. This paper documents studies we have conducted to measure the bright pupil differences using infrared light and hypothesis factors that lead to these differences.
A Bioinformatician's Guide to Metagenomics

SUMMARY As random shotgun metagenomic projects proliferate and become the dominant source of publicly available sequence data, procedures for the best practices in their execution and analysis become increasingly important. Based on our experience at the Joint Genome Institute, we describe the chain of decisions accompanying a metagenomic project from the viewpoint of the bioinformatic analysis step by step. We guide the reader through a standard workflow for a metagenomic project beginning with presequencing considerations such as community composition and sequence data type that will greatly influence downstream analyses. We proceed with recommendations for sampling and data generation including sample and metadata collection, community profiling, construction of shotgun libraries, and sequencing strategies. We then discuss the application of generic sequence processing steps (read preprocessing, assembly, and gene prediction and annotation) to metagenomic data sets in contrast to genome projects. Different types of data analyses particular to metagenomes are then presented, including binning, dominant population analysis, and gene-centric analysis. Finally, data management issues are presented and discussed. We hope that this review will assist bioinformaticians and biologists in making better-informed decisions on their journey during a metagenomic project.
Book Review: The New Paradigm of Immunity to Tuberculosis

The treatment of tuberculosis presents an enormous challenge to global health. Tuberculosis is a leading cause of death from infectious diseases worldwide, second only to the human immunodeficiency virus (HIV). Although several therapeutics and vaccines are available to treat and prevent tuberculosis infections, more virulent varieties of tuberculosis and increased drug resistance in the form of multi, extreme, and total drug resistant disease are major emergent threats. Mycobacterium tuberculosis is an obligate human pathogen and has co-evolved with humans for millennia, thus it has influenced the immune system of individuals who live in tuberculosis endemic regions. It is essential that therapeutic and research strategies targeted at tuberculosis should reflect this co-evolution. Elucidating the basic biology and immunology of tuberculosis is relevant to increasing and consolidating our fundamental understanding of the disease; thus, facilitating the development of therapeutics that will eradicate the disease and enable the immune system to achieve protection from tuberculosis. The book, The New Paradigm of Immunity to Tuberculosis edited by Maziar Divangahi (1), seeks to address the need for a comprehensive understanding of the immunological processes underlying tuberculosis infection by combining immunological and research perspectives. There are several comprehensive reviews and textbooks about immunity to tuberculosis infection, particularly concentrating on genetic susceptibilities (2) and therapeutics (3). However, the unique contribution of this book is that it is the most contemporary resource, which draws on the expertise of 25 distinguished international specialists to provide a single authoritative book on the induction and maintenance of immunity against tuberculosis infection.
Witnessing peer rejection during early adolescence: Neural correlates of empathy for experiences of social exclusion

Neuroimaging studies with adults have begun to reveal the neural bases of empathy; however, this research has focused on empathy for physical pain, rather than empathy for negative social experiences. Moreover, this work has not examined adolescents who may frequently witness and empathize with others that experience negative social experiences such as peer rejection. Here, we examined neural activity among early adolescents observing social exclusion compared to observing inclusion, and how this activity related to both trait empathy and subsequent prosocial behavior. Participants were scanned while they observed an individual whom they believed was being socially excluded. At least one day prior to the scan they reported their trait empathy, and following the scan they wrote emails to the excluded victim that were rated for prosocial behavior (e.g., helping, comforting). Observing exclusion compared to inclusion activated regions involved in mentalizing (i.e., dorsomedial prefrontal cortex), particularly among highly empathic individuals. Additionally, individuals who displayed more activity in affective, pain-related regions during observed exclusion compared to inclusion subsequently wrote more prosocial emails to excluded victims. Overall findings suggest that when early adolescents witness social exclusion in their daily lives, some may actually ‘feel the pain’ of the victims and act more prosocially toward them as a result.
Regular expression matching for reconfigurable packet inspection

Recent intrusion detection systems (IDS) use regular expressions instead of static patterns as a more efficient way to represent hazardous packet payload contents. This paper focuses on regular expressions pattern matching engines implemented in reconfigurable hardware. A nondeterministic finite automata (NFA) based implementation was presented, which takes advantage of new basic building blocks to support more complex regular expressions than the previous approaches. The methodology is supported by a tool that automatically generates the circuitry for the given regular expressions, outputting VHDL representations ready for logic synthesis. Furthermore, techniques to reduce the area cost of our designs and maximize performance when targeting FPGAs were included. Experimental results show that our tool is able to generate a regular expression engine to match more than 500 IDS regular expressions (from the Snort ruleset) using only 25K logic cells and achieving 2 Gbps throughput on a Virtex2 and 2.9 on a Virtex4 device. Concerning the throughput per area required per matching non-meta character, our design is 3.4 and 10 times more efficient than previous ASIC and FPGA approaches, respectively
Degradation of rRNA in Salmonella strains: a novel mechanism to regulate the concentrations of rRNA and ribosomes

We have previously shown that the 23S rRNA of Salmonella strains is highly fragmented by specific enzyme cleavages. In this article, we report that 23S rRNA of Salmonella strains is rapidly degraded as the cells enter the stationary phase. More than 90% of the 23S rRNA is degraded when the cells reach the stationary phase. The rate of degradation of 23S rRNA correlated with its degree of fragmentation. This degradation is probably mediated by newly synthesized protein factor(s), since treatment with chloramphenicol or rifampin inhibits the rRNA degradation. We propose that degradation of 23S rRNA is a novel mechanism in the regulation of the bacterial 23S rRNA and ribosome concentration and that this additional regulatory mechanism provides some selective advantage to cells.
TCP in wireless environments: problems and solutions

The Internet provides a platform for rapid and timely information exchange among a disparate array of clients and servers. TCP and IP are separately designed and closely tied protocols that define the rules of communication between end hosts, and are the most commonly used protocol suite for data transfer in the Internet. The combination of TCP/IP dominates today's communication in various networks from the wired backbone to the heterogeneous network due to its remarkable simplicity and reliability, TCP has become the de facto standard used in most applications ranging from interactive sessions such as Telnet and HTTP, to bulk data transfer like FTP. TCP was originally designed primarily for wired networks. In a wired network, random bit error rate, a characteristic usually more pronounced in the wireless network, is negligible, and congestion is the main cause of packet loss. The emerging wireless applications, especially high-speed multimedia services and the advent of wireless IP communications carried by the Internet, call for calibration and sophisticated enhancement or modifications of this protocol suite for improved performance. Based on the assumption that packet losses are signals of network congestion, the additive increase multiplicative decrease congestion control of the standard TCP protocol reaches the steady state, which reflects the protocol's efficiency in terms of throughput and link utilization. However, this assumption does not hold when the end-to-end path also includes wireless links. Factors such as high BER, unstable channel characteristics, and user mobility may all contribute to packet losses. Many studies have shown that the unmodified standard TCP performs poorly in a wireless environment due to its inability to distinguish packet losses caused by network congestion from those attributed to transmission errors. In this article, following a brief introduction to TCP, we analyze the problems TCP exhibits in the wireless IP communication environment, and illustrate viable solutions by detailed examples.
Investigation of extended blinks and interblink intervals in subjects with and without dry eye

Background The purpose of this study was to investigate the occurrence and duration of extended blinks ≥ 70 msec and their associated interblink intervals in normal subjects and in subjects with mild to moderate dry eye. Methods This single-center, prospective, double-blind study included 11 subjects with dry eye and eight subjects with normal eyes. Extended blinks were defined as lid closure in at least two successive video frames (≥70 msec). Digital video imaging of each subject’s eyes was recorded while the subject viewed a 10-minute documentary. The subjects did not know that blink was the outcome being measured. Following capture, the videos were manually analyzed in a masked fashion for the occurrence of extended blinks. The length of the interblink interval (ie, time between blinks) before and after these extended blinks (the interblink interval ratio) was calculated, as well as differences in lid contact times. Results The dry eye group had a median extended blink duration which was 2.53 times longer than that of the normal group. For subjects with dry eye, interblink intervals post-extended blink were significantly longer than interblink intervals pre-extended blink (P < 0.001). Interblink intervals did not lengthen significantly in normal subjects. In both groups, the duration of the extended blink was significantly (P = 0.001) and positively correlated with interblink interval ratio (post-extended to pre-extended blink interblink interval), such that for each doubling of extended blink duration, the interblink interval ratio increased by 10%. Blinks longer than one second in duration occurred almost exclusively in subjects with dry eye. Conclusion This study reports three central findings: blink duration tended to be longer in subjects with dry eye; a lengthening of the interblink interval after an extended blink occurred in subjects with dry eye but not in those without dry eye; and a longer blink duration was associated with a significantly increased interblink interval ratio in all subjects.
Paying for Performance in Population Health: Lessons From Health Care Settings

The appeal of pay-for-performance in health care derives from the conceptual view that paying doctors and hospitals more to deliver better care will encourage them to deliver better care. What lessons can be learned from the successes and failures of pay-for-performance in health care settings that apply to pay-for-performance in population health? We argue that pay-for-performance requires conditions that are not easily met in population health settings. Pay-for-performance has focused on narrow clinical problems whose success depends on identifiable actors with the motivation and resources to change clinical processes or outcomes. In contrast, population health has broad goals, many antecedents, and no single, identifiable fiduciary (a person who holds assets in trust for a beneficiary). Nevertheless, with careful attention, conditions for successful pay-for-performance in population health might be met.
Outage Analysis for Optimal Beamforming MIMO Systems in Multikeyhole Channels

In this correspondence, we present statistical properties for the maximum eigenvalue of multikeyhole multiple-input multiple-output (MIMO) channels. Our results are general for arbitrary numbers of transmit and receive antennas, and arbitrary number of keyholes of differing powers. These results are applied to study the outage performance of optimal beamforming systems and the impact of keyholes' power distribution is characterized with the aid of a majorization theory result.
Inverse Multiple Instance Learning for Classifier Grids

Recently, classifier grids have shown to be a considerable alternative for object detection from static cameras. However, one drawback of such approaches is drifting if an object is not moving over a long period of time. Thus, the goal of this work is to increase the recall of such classifiers while preserving their accuracy and speed. In particular, this is realized by adapting ideas from Multiple Instance Learning within a boosting framework. Since the set of positive samples is well defined, we apply this concept to the negative samples extracted from the scene: Inverse Multiple Instance Learning. By introducing temporal bags, we can ensure that each bag contains at least one sample having a negative label, providing the required stability. The experimental results demonstrate that using the proposed approach state-of-the-art detection results can by obtained, however, showing superior classification results in presence of non-moving objects.
Wind‐Eroded Crater Floors and Intercrater Plains, Terra Sabaea, Mars

Ancient impact craters with wind‐eroded layering on their floors provide a record of resurfacing materials and processes on early Mars. In a 54 km Noachian crater in Terra Sabaea (20.2°S, 42.6°E), eolian deflation of a friable, dark‐toned layer up to tens of meters thick has exposed more resistant, underlying light‐toned material. These layers differ significantly from strata of similar tone described in other regions of Mars. The light‐toned material has no apparent internal stratification, and visible/near‐infrared spectral analysis suggests that it is rich in feldspar. Its origin is ambiguous, as we cannot confidently reject igneous, pyroclastic, or clastic alternatives. The overlying dark‐toned layer is probably a basaltic siltstone or sandstone that was emplaced mostly by wind, although its weak cementation and inverted fluvial paleochannels indicate some modification by water. Negative‐relief channels are not found on the crater floor, and fluvial erosion is otherwise weakly expressed in the study area. Small impacts onto this crater's floor have exposed deeper friable materials that appear to contain goethite. Bedrock outcrops on the crater walls are phyllosilicate bearing. The intercrater plains contain remnants of a post‐Noachian thin, widespread, likely eolian mantle with an indurated surface. Plains near Hellas‐concentric escarpments to the north are more consistent with volcanic resurfacing. A 48 km crater nearby contains similar dark‐over‐light outcrops but no paleochannels. Our findings indicate that dark‐over‐light stratigraphy has diverse origins across Mars and that some dark‐toned plains with mafic mineralogy are not of igneous origin.
Interleukin 10 reduces the release of tumor necrosis factor and prevents lethality in experimental endotoxemia

Because of its ability to efficiently inhibit in vitro cytokine production by activated macrophages, we hypothesized that interleukin (IL) 10 might be of particular interest in preventing endotoxin-induced toxicity. We therefore examined the effects of IL-10 administration before lipopolysaccharide (LPS) challenge in mice. A marked reduction in the amounts of LPS-induced tumor necrosis factor (TNF) release in the circulation was observed after IL-10 pretreatment at doses at low as 10 U. IL-10 also efficiently prevented the hypothermia generated by the injection of 100 micrograms LPS. Finally, pretreatment with a single injection of 1,000 U IL-10 completely prevented the mortality consecutive to the challenge with 500 micrograms LPS, a dose that was lethal in 50% of the control mice. We conclude that IL-10 inhibits in vivo TNF secretion and protects against the lethality of endotoxin in a murine model of septic shock.
On the explicit construction and statistics of Calabi-Yau flux vacua

We explicitly construct and study the statistics of flux vacua for type IIB string theory on an orientifold of the Calabi-Yau hypersurface P[1,1,2,2,6], parametrised by two relevant complex structure moduli. We solve for these moduli and the dilaton field in terms of the set of integers defining the 3-form fluxes and examine the distribution of vacua. We compare our numerical results with the predictions of the Ashok-Douglas density det(−R−ω), finding good overall agreement in different regions of moduli space. The number of vacua are found to scale with the distance in flux space. Vacua cluster in the region close to the conifold singularity. Large supersymmetry breaking is more generic but supersymmetric and hierarchical supersymmetry breaking vacua can also be obtained. In particular, the small superpotentials and large dilaton VEVs needed to obtain de Sitter space in a controllable approximation are possible but not generic. We argue that in a general flux compactification, the rank of the gauge group coming from D3 branes could be statistically preferred to be very small. e-mail: J.P.Conlon@damtp.cam. ac.uk e-mail: F.Quevedo@damtp.cam. ac.uk