Miracle-dz/UniFAR-FTUs huggingface dataset:
Macropinocytosis Is the Entry Mechanism of Amphotropic Murine Leukemia Virus

ABSTRACT The entry mechanism of murine amphotropic retrovirus (A-MLV) has not been unambiguously determined. We show here that A-MLV is internalized not by caveolae or other pinocytic mechanisms but by macropinocytosis. Thus, A-MLV infection of mouse embryonic fibroblasts deficient for caveolin or dynamin, and NIH 3T3 cells knocked down for caveolin expression, was unaffected. Conversely, A-MLV infection of NIH 3T3 and HeLa cells was sensitive to amiloride analogues and actin-depolymerizing drugs that interfere with macropinocytosis. Further manipulation of the actin cytoskeleton through conditional expression of dominant positive or negative mutants of Rac1, PAK1, and RhoG, to increase or decrease macropinocytosis, similarly correlated with an augmented or inhibited infection with A-MLV, respectively. The same experimental perturbations affected the infection of viruses that use clathrin-coated-pit endocytosis or other pathways for entry only mildly or not at all. These data agree with immunofluorescence studies and cryo-immunogold labeling for electron microscopy, which demonstrate the presence of A-MLV in protrusion-rich areas of the cell surface and in cortical fluid phase (dextran)-filled macropinosomes, which also account for up to a half of the cellular uptake of the cell surface-binding lectin concanavalin A. We conclude that A-MLV use macropinocytosis as the predominant entry portal into cells. IMPORTANCE Binding and entry of virus particles into mammalian cells are the first steps of infection. Understanding how pathogens and toxins exploit or divert endocytosis pathways has advanced our understanding of membrane trafficking pathways, which benefits development of new therapeutic schemes and methods of drug delivery. We show here that amphotropic murine leukemia virus (A-MLV) pseudotyped with the amphotropic envelope protein (which expands the host range to many mammalian cells) gains entry into host cells by macropinocytosis. Macropinosomes form as large, fluid-filled vacuoles (up to 10 μm) following the collapse of cell surface protrusions and membrane scission. We used drugs or the introduction of mutant proteins that affect the actin cytoskeleton and cell surface dynamics to show that macropinocytosis and A-MLV infection are correlated, and we provide both light- and electron-microscopic evidence to show the localization of A-MLV in macropinosomes. Finally, we specifically exclude some other potential entry portals, including caveolae, previously suggested to internalize A-MLV.
Increasing Incidence of Mucormycosis in University Hospital, Belgium

To determine why incidence of mucormycosis infections was increasing in a large university hospital in Belgium, we examined case data from 2000–2009. We found the increase was not related to voriconazole use but most probably to an increase in high-risk patients, particularly those with underlying hematologic malignancies.
A Physics-Based Circuit Aging Model for Mixed-Mode Degradation in SiGe HBTs

A physics-based silicon-germanium (SiGe) heterojunction bipolar transistor (HBT) aging model for mixed-mode stress based on the lucky-electron model and reaction-diffusion theory is developed for integration with compact models. An effective aging parameter extraction method is described, and the aging model parameters are fit for a modern SiGe HBT platform. The aging model is implemented as a wrapper in the Cadence Spectre circuit simulator. Device-level aging simulations are shown to be well-matched to measured degradation data. The aging model is further used to explore the effects of aging on a simple current mirror circuit, showing a decrease in mirror ratio with degradation.
A hidden Markov model approach to speech synthesis

This paper describes a novel technique for producing smooth speech parametric representation evolution by means of an application of traditional hidden Markov modeling techniques. It is based on the consideration that HMM training is able to locate the main acoustic events which occur during the speech process; thus the obtained decomposition can be used to reproduce the linguistic units utilized for training. This is accomplished by interpolating the state-related features values with some weighting functions, as it is done for temporal decomposition technique [1] [15]. Results will be given for isolated word synthesis.
Physiologically Based Pharmacokinetic Model Qualification and Reporting Procedures for Regulatory Submissions: A Consortium Perspective

This work provides a perspective on the qualification and verification of physiologically based pharmacokinetic (PBPK) platforms/models intended for regulatory submission based on the collective experience of the Simcyp Consortium members. Examples of regulatory submission of PBPK analyses across various intended applications are presented and discussed. European Medicines Agency (EMA) and US Food and Drug Administration (FDA) recent draft guidelines regarding PBPK analyses and reporting are encouraging, and to advance the use and acceptability of PBPK analyses, more clarity and flexibility are warranted.
The Impact of Clostridum Difficile on Surgical Rate Among Ulcerative Colitis Patients: A Systemic Review and Meta-analysis

There is growing recognition of the impact of Clostridum difficile infection (CDI) on patients with inflammatory bowel disease. Clostridium difficile infection causes greater morbidity and mortality. This study aimed to evaluate the impact of C. difficile on surgical risk among ulcerative colitis (UC) patients. We searched the following databases: MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, ACP Journal Club, DARE, CMR, and HTA. Studies were included if fulfilled the following criteria: (1) Cohort or case–control studies, which involved a comparison group that lacked CDI, (2) Patients were given a primary diagnosis of UC, (3) Comorbidity of CDI was evaluated by enzyme immunoassay of stool for C. difficile toxin A and B or C. difficile stool culture, (4) Studies evaluated surgical rate, and (5) Studies reported an estimate of odds ratio, accompanied by a corresponding measure of uncertainty. Five studies with 2380 patients fulfilled the inclusion criteria. Overall, meta-analysis showed that UC with CDI patients had a significant higher surgical rate than patients with UC alone. (OR=1.76, 95% CI=1.36–2.28). C. difficile infection increased the surgical rate in UC patients. However, results should be interpreted with caution, given the limitations of this stud.
1,25‐Dihydroxyvitamin D3 Alters the Profile of Bone Marrow‐Derived Dendritic Cells of NOD Mice

Abstract: 1,25‐dihydroxyvitamin D3 [1,25(OH)2D3] prevents autoimmune diabetes in nonobese diabetic (NOD) mice. A major target for 1,25(OH)2D3 in the immune system is the dendritic cell (DC). Since important DC abnormalities have been described in NOD mice, we investigated the effects of 1,25(OH)2D3 on the yield and phenotype of DCs generated from bone marrow of NOD mice compared to control congenic nonobese diabetes‐resistant (NOR) mice. In both mouse strains, exposure of the bone marrow‐derived cells to 1,25(OH)2D3 increased the proportion of CD11c+ DCs after culture. Surface expression of MHC II, CD86, and CD54 on NOR‐derived DCs was decreased after 1,25(OH)2D3 treatment, while CD40 remained unchanged. On NOD‐derived DCs, 1,25(OH)2D3 only inhibited the expression of MHC II and CD86. 1,25(OH)2D3 inhibited IL‐12 and IL‐10 secretion after IFNγ and LPS stimulation. In vitro treatment with 1,25(OH)2D3 alters DC yield from bone marrow cultures and alters the phenotype of the cells in NOD as well as in NOR mice. NOD‐derived DCs were more resistant to the 1,25(OH)2D3 effects than were NOR‐derived DCs.
Addition of neuA, the Gene Encoding N-Acylneuraminate Cytidylyl Transferase, Increases the Discriminatory Ability of the Consensus Sequence-Based Scheme for Typing Legionella pneumophila Serogroup 1 Strains

ABSTRACT The standard sequence-based method for the typing of Legionella pneumophila serogroup 1 strains was extended by using the gspA and neuA alleles. The use of neuA as a seventh allele for typing significantly increased the index of discrimination calculated for a panel of unrelated strains (from 0.932 to 0.963) and subdivided some known large common complexes (e.g., 1,4,3,1,1,1). This modification to the standard method is proposed as the method of choice in the epidemiological investigation of L. pneumophila infections.
Methylophilus flavus sp. nov. and Methylophilus luteus sp. nov., aerobic, methylotrophic bacteria associated with plants.

Novel yellow, obligately methylotrophic and restricted facultatively methylotrophic bacteria, respectively designated strains Ship(T) and Mim(T), with the ribulose monophosphate pathway of C(1) assimilation are described. Cells were strictly aerobic, Gram-negative, asporogenous, non-motile rods that multiply by binary fission, were mesophilic and neutrophilic and synthesized indole-3-acetic acid and exopolysaccharide. The predominant cellular fatty acids were C(16 : 0) and C(16 : 1). The major ubiquinone was Q-8. The predominant phospholipids were phosphatidylethanolamine and phosphatidylglycerol; diphosphatidylglycerol was absent. The two strains lacked α-ketoglutarate dehydrogenase and glutamate dehydrogenase. They assimilated ammonium via the glutamate cycle enzymes glutamine synthetase and glutamate synthase. The DNA G+C contents of strains Ship(T) and Mim(T) were 50.7 and 54.5 mol% (T(m)), respectively. The level of 16S rRNA gene sequence similarity between these strains was very high (99.8 %) but they shared a low level of DNA-DNA relatedness (44 %). Based on 16S rRNA gene sequence analysis and low levels of DNA-DNA relatedness with the type strains of recognized species of the genus Methylophilus (31-36 %), strains Ship(T) and Mim(T) are considered to represent novel species of the genus Methylophilus, for which the names Methylophilus flavus sp. nov. (type strain Ship(T) =DSM 23073(T) =VKM B-2547(T) =CCUG 58411(T)) and Methylophilus luteus sp. nov. (type strain Mim(T) =DSM 22949(T) =VKM B-2548(T) =CCUG 58412(T)) are proposed.
Pre-1.94 to post-1.88 Ga sediment depositional environment and c. 1.94 Ga felsic magmatism in the Knaften area, northern Sweden

ABSTRACT The Knaften area is situated in the northern part of the Bothnian Basin in the central Svecofennian province of Sweden. Sedimentary rocks are here conformably intercalated with mafic to intermediate volcanic rocks. The depositional environment in the south-eastern part of the Knaften area was syn-orogenic deep water where tectonic activity caused volcanism and faulting. Mass flow processes transported material down slope and formed turbidites and debris flow deposits. Later, two phases of deformation affected the supracrustal rocks. Detrital zircons in a turbiditic sedimentary rock gave ages between 2.07 and 1.88 Ga, and between 2.93 and 2.62 Ga, indicating a substantial Archean component. The 1.88 Ga maximum depositional age is coeval with those of other supracrustal successions in the region, e.g., the mainly sedimentary Härnö and Vargfors groups, as well as the mainly volcanic Skellefte and Arvidsjaur groups. Zircons in the Knaften granite and the Knaften porphyry dyke have U-Pb ages of 1939 ± 3 Ma and 1939 ± 4 Ma, respectively. They confirm previously poorly constrained 1.95–1.94 Ga ages for these rocks. The intrusions cross-cut the mafic to intermediate volcanic rocks that, by consequence, must be older than 1.94 Ga. The new zircon data thus point to an age difference of about 50 to 60 million years between the felsic magmatism and the deposition of the dated turbiditic sediments. The oldest volcanic rocks (pre-1.94 Ga) in the Knaften area are evidence of at least one additional depositional stage in the Svecofennian tectonic evolution.
The Effectiveness of Academic Library Deans and Directors: A Literature Review

As with other organizations in higher education, academic libraries face increasing pressure to assess their work and be more accountable for returns on investment. Although most academic library deans are subject to some type of internal performance review, a broader examination of what makes library deans and directors effective could provide valuable guidance for current and future library leaders. This article reviews some of the core theories of leadership effectiveness in the mainstream management literature and examines recent publications related to effective library leadership. Because few such studies have been conducted, the review was expanded to include studies of academic deans outside of the library as well as studies suggesting interesting new directions for research into academic library leader effectiveness. Although the literature in the area of dean effectiveness is somewhat scattered, the findings of individual works are intriguing and suggest several topics for further research. This review also produced suggestions related to methodology. Future researchers should ground investigations of library leadership effectiveness within existing leadership theories. For empirical works, researchers should consider using previously developed, validated instruments in order to be able to compare results with the larger body of leadership effectiveness research.
A High Extinction Ratio Polarization Beam Splitter With MMI Couplers on InP Substrate

A high extinction ratio (ER) polarization beam splitter with three different multimode interference couplers on InP substrate was designed by a three-dimensional beam propagation method. Simulations show that the polarization ER (PER) is over 34 dB and internal loss is <;0.8 dB for both TE and TM polarizations. The PER imbalance between the two polarization states has been reduced to 22 dB. The total length of the device is <;950 μm. The effects of the width of the input port on the performance of the device are discussed in detail.
A low-offset dynamic comparator with area-efficient and low-power offset cancellation

A low-offset two-stage dynamic comparator has been proposed for parallel multi-channel processing. Low offset is achieved from two aspects: 1st-stage offset cancellation and 2nd-stage offset suppression. A fully dynamic offset cancellation scheme based on current auto-zeroing is adopted to effectively cancel out the 1st-stage offset. It features small area overhead and low energy consumption. For the 2nd-stage offset suppression, a high gain is designed for the 1st-stage dynamic amplifier by optimizing the overdrive voltage of input transistors. To maintain low offset performance across a wide range of input commonmode voltages, the overdrive voltage of the input pair is required to stay low. Therefore, a tail current source is employed for the 1st stage to ensure constant common-mode discharging current. As a result, the overdrive voltage can be stably kept low under various operation conditions. The proposed comparator has been designed in a standard CMOS 0.18 μm process. It operates under a supply voltage of 1.2 V at 10 MHz. Simulation results have verified the low-offset property of the comparator. The input-referred offset (1 σ) is reduced from 19.25 mV to 1.296 mV after cancellation and it remains constant with the input commonmode voltage changing from 0 V to 0.8 V. The offset is further reduced to 771 μV when the 2nd-stage input pair are enlarged by 4 times. At the same time, the energy consumption is increased from 147 fJ/Conv to 168 fJ/Conv.
Pawn or Potentates: Corporate Governance in Indian Central Public Sector Enterprises

The Department of Public Enterprises had made submissions of Self Evaluation Reports, for the purpose of corporate governance, mandatory for all central government owned enterprises. Despite this, an alarming 40% of the enterprises did not do so. This study examines the impact of external policy tools and internal firm specific factors on corporate governance of central public sector enterprises (CPSEs). We use a dataset of all manufacturing and non-financial services owned by the central government of India for the year 2010-11. Using probit, ordered logit and Heckman’s sample selection models, the study finds that the probability and quality of corporate governance is positively influenced by the CPSE getting into a Memorandum of Understanding (MoU) with the central government of India, and hence, enjoying more autonomy in terms of day to day operations. Besides these, internal factors, including bigger size and lower debt size contribute significantly to better corporate governance.
How and Why Some Issues Spread Fast In Social Media

This paper brings together current insights from various disciplines into the spreading of social media posts.By astructured literature review of peer-reviewed literature 39 recent articles on diffusion in social media were located. The search spanned 10 years, although all the papers found were published after 2009, indicating that the examination and observation of spread patterns in social media is still in an early stage. The analysisfocused on spread patterns and factors that may explain how rapidly issues spread in the online environment. Based on the findings, from an organizational perspective a model is constructed and directions for future research are suggested.The model focuses on characteristics of the issue, of the social media involved, actor resources and general factors. A better understanding of how social media posts spread helps organizations to be prepared for upcoming issues and crises, such as launching early rumour detection to prevent losses in organizational and brand image.
Endogenous electric current is associated with normal development of the vertebrate limb

A steady ionic current is driven out of both developing and regenerating amphibian limbs. In the developing limbs of anurans and urodeles, focal outwardly directed current (0.5–2 μA/cm2) predicts the location of mesenchyme accumulations producing the early bud. Here, we report measurements of a similar outwardly directed ionic current associated with the development of the limb bud in the mouse and chick embryo by using a noninvasive, self‐referencing electrode for the measurement of extracellular current. In both the mouse and chick embryo, flank currents were usually inwardly directed — the direction of Na+ uptake by ectoderm. Outward currents associated with the mouse limb bud ranged from 0.04–10.8 μA/cm2. Mouse limb bud and flank currents were similar to those measured in amphibian larvae, because they were reversibly collapsed and/or reversed by application of 30 μM amiloride, a Na+ channel blocker. Unlike the amphibian embryos, flank ectoderm adjacent to the mouse limb bud in the anterior/posterior axis was usually associated with outwardly directed ionic current. This raises the possibility of a different, or changing, gradient of extracellular voltage experienced by mesenchyme cells in this plane of development than that observed in other regions of the limb bud. In the chick flank caudal to the somites, a striking reversal of the inwardly directed flank currents to very large (∼100 μA/cm2) outwardly directed currents occurred three developmental stages before limb bud formation. We tested the relevance of this outwardly directed ionic current to limb formation in the chick embryo by reversing it by using an artificially applied “countercurrent” pulled through a microelectrode inserted just beneath the caudal ectoderm of the embryo. This application was performed for approximately 6 hr 2.5–3 developmental stages before hindlimb bud formation. This method resulted in abnormal limb formation by the tenth day of gestation in some embryos, whereas all control embryos developed normally. These data suggest an early physiological control of limb development. © 2001 Wiley‐Liss, Inc.
A Recursive Formulation for a Rank Sum Statistic Used to Detect Genomic Copy Number Variation

Copy number variation (CNV) results from duplications and deletions of genomic DNA. Since CNVs were found to correlate with a number of genetic diseases, detecting and characterizing CNV is a major goal of genetic research. Recently, a rank-based method has been developed to analyze raw CNV. This method involves a rank comparison of a sample DNA across multiple DNA sections, against multiple controls. The overall CNV of the sample is then determined by a statistical comparison of the sample’s Rank-Sum against the discrete null distribution. As such, the accuracy of this method depends, to a large degree, on an accurate representation of the null distribution. So far, the exact null distribution has only been approximated using the continuous Irwin-Hall distribution. This study includes the rigorous proof of several recursive formulations for the weights of the random Rank-Sum statistic. Unexpectedly, these recursive formulae give the generalized form of the binomial coefficients. The descriptive statistics of the exact null distribution are also derived. The approximated Irwin-Hall distribution is compared to the exact null distribution, from which it is shown to underestimate the standard deviation and overestimate the kurtosis. Using data simulations, the approximated Irwin-Hall distribution also increases the likelihood of type I error (false positive) and gives an overstatement of the test power. Hence, the use of these recursive formulae improves the ability of this rank-based method to detect CNV.
Middle school plunge: a mixed-methods study exploring 6th grade students' perceptions of their transition to middle school experiences and its influences on school achievement and performance for urban youth

v List of Figures xiii List of Tables xv Chapter I: Introduction 1 Statement of the Problem 4 Background of the Study 6 Impetus of the Study 8 Research Questions 10 Significance of the Study 10 Conclusion 11 Chapter II: Review of Related Literature 13 Introduction 13 Definition of Urban Schools 14 Suburban Versus Urban Student Achievement Disparity in New Jersey Schools 15 The Middle School Plunge 18 Pre and Post Educational Plunge Experiences 21 “Fourth Grade Slump” Phenomenon 21 “Eighth Grade Cliff” Phenomenon 24 “Economic Slump” Phenomenon 25 Middle School Transition Change Factors 26 Biological and Physiological Changes 26 Cognitive Learning Development 27
Histological analysis of loaded zirconia and titanium dental implants: an experimental study in the dog mandible.

OBJECTIVE To assess whether or not peri-implant soft tissue dimensions and hard tissue integration of loaded zirconia implants are similar to those of a titanium implant. MATERIALS AND METHODS In six dogs, two one-piece zirconia implants (VC, ZD), a two-piece zirconia implant (BPI) and a control one-piece titanium implant (STM) were randomly placed. CAD/CAM crowns were cemented at 6 months. Six months later, animals were killed and histomorphometric analyses were performed, including: the level of the mucosal margin, the extent of the peri-implant mucosa, the marginal bone loss and the bone-to-implant contact (BIC). Means of outcomes variables were calculated together with their corresponding 95% confidence intervals. RESULTS In general, the mucosal margin was located coronally to the implant shoulder. The buccal peri-implant mucosa ranged between 2.64 ± 0.70 mm (VC) and 3.03 ± 1.71 mm (ZD) (for all median comparisons p > 0.05). The relative marginal bone loss ranged between 0.65 ± 0.61 mm (BPI) and 1.73 ± 1.68 mm (ZD) (buccal side), and between 0.55 ± 0.37 mm (VC) and 1.69 ± 1.56 mm (ZD) (lingual side) (p > 0.05). The mean BIC ranged between 78.6% ± 17.3% (ZD) and 87.9% ± 13.6% (STM) without statistically significant differences between the groups (p > 0.05). CONCLUSIONS One- and two-piece zirconia rendered similar peri-implant soft tissue dimensions and osseointegration compared to titanium implants that were placed at 6 months of loading. Zirconia implants, however, exhibited a relatively high fracture rate.