Miracle-dz/UniFAR-FTUs huggingface dataset:
Towards developing HIV‐2 lentivirus‐based retroviral vectors for gene therapy: Dual gene expression in the context of HIV‐2 LTR and Tat

Because of the distinct ability of retroviruses to integrate into the target cell genome and thus achieve long‐term expression, retrovirus vectors hold great promise for stable gene transfer. Such vectors derived from human immunodeficiency retroviruses (HIVs) and other lentiviruses are envisioned to possess several advantages, especially for in vivo gene therapy of HIV infection and acquired immunodeficiency syndrome (AIDS) where targeting CD4+ T cells/macrophages and pluripotent non‐dividing stem cells would be required. Among these is the ability of HIVs to transduce nondividing cells in contrast to the murine retroviruses which require target cell mitosis. The advantages of the lentivirus vectors will be further enhanced by the development of multigenic vectors carrying more than one gene in a dependent or independent transcriptional unit. Separate from the issue of transduction efficiency, information is needed about the impact of the configuration of the genes in a multigenic vector on their expression. Towards this end, we investigated the expression of genes specifically directed by the HIV‐2 LTR and Tat in a prototypic minimal transfer vector. We found that the expression of a gene in a dual gene configuration depended upon its position in the transcriptional unit and that the insertion of an internal translational initiation mechanism improved the expression of the downstream gene. Apparently not sufficiently appreciated previously, these effects were promoter and cell‐type dependent. Our data also suggest that the commonly used cellular or viral promoters may be orders of magnitude less effective than HIV‐2 LTR in the presence of Tat, and thus may not be useful as internal promoters in the context of the HIV‐2 LTR:Tat regulatory loop. J. Med. Virol. 54:118–128, 1998. © 1998 Wiley‐Liss,Inc.
Resettable Zero Knowledge in the Bare Public-Key Model under Standard Assumption

In this paper we resolve an open problem regarding resettable zero knowledge in the bare public-key (BPK for short) model: Does there exist constant round resettable zero knowledge argument with concurrent soundness for $\mathcal{NP}$ in BPK model without assuming \emph{sub-exponential hardness}? We give a positive answer to this question by presenting such a protocol for any language in $\mathcal{NP}$ in the bare public-key model assuming only collision-resistant hash functions against \emph{polynomial-time} adversaries.
Interim Report IR-05-021 Assessing Changes in Age and Size at Maturation in Collapsing Populations of Atlantic Cod ( Gadus morhua )

2 Introduction . 3 Materials and Methods . 6 Northern (2J3KL) cod. 6 Southern Grand Bank (3NO) cod . 7 St. Pierre Bank (3Ps) cod. 8 Analyzed data . 8 Maturation reaction norms. 10 Survival and age at 50% maturity. 13 Results . 13 Survival, growth, and age at 50% maturity . 13 Maturation reaction norms. 14 Discussion. 16 Acknowledgments . 21 References . 23 Tables . 31 Figure captions . 34 Figures . 36
Modification of K+ channel–drug interactions by ancillary subunits

Reconciling ion channel α‐subunit expression with native ionic currents and their pharmacological sensitivity in target organs has proved difficult. In native tissue, many K+ channel α‐subunits co‐assemble with ancillary subunits, which can profoundly affect physiological parameters including gating kinetics and pharmacological interactions. In this review, we examine the link between voltage‐gated potassium ion channel pharmacology and the biophysics of ancillary subunits. We propose that ancillary subunits can modify the interaction between pore blockers and ion channels by three distinct mechanisms: changes in (1) binding site accessibility; (2) orientation of pore‐lining residues; (3) the ability of the channel to undergo post‐binding conformational changes. Each of these subunit‐induced changes has implications for gating, drug affinity and use dependence of their respective channel complexes. A single subunit may modulate its associated α‐subunit by more than one of these mechanisms. Voltage‐gated potassium channels are the site of action of many therapeutic drugs. In addition, potassium channels interact with drugs whose primary target is another channel, e.g. the calcium channel blocker nifedipine, the sodium channel blocker quinidine, etc. Even when K+ channel block is the intended mode of action, block of related channels in non‐target organs, e.g. the heart, can result in major and potentially lethal side‐effects. Understanding factors that determine specificity, use dependence and other properties of K+ channel drug binding are therefore of vital clinical importance. Ancillary subunits play a key role in determining these properties in native tissue, and so understanding channel–subunit interactions is vital to understanding clinical pharmacology.
Surface chemistry dependence of water adsorption on solid substrates in humid ambient and humidity effects on wear of copper and glass surfaces

Adsorbed water is present on nearly all surfaces exposed to the ambient and can greatly influence tribological properties such as adhesion, friction and wear. This paper reviews how the effects of the surface chemistry, such as oxidised or terminated by different functional groups, greatly influences the water adsorption isotherm thickness as well as the structure of adsorbed water. The thickness and activity of the adsorbed water greatly affect the wear between different material surfaces. Sufficient adsorbed water could induce a detrimental effect such as galvanic corrosion between dissimilar metals or a beneficial effect strengthening soda lime glass.
Effect of Gate Insulator Thickness on RF Power Gain Degradation of Vertically Scaled GaN MIS-HEMTs at 40 GHz

We present an initial study of the RF reliability of SiN x/InAlN/AlN/GaN MIS-HEMTs with a molecular-beam epitaxy deposited SiN x gate insulator thickness varying from 0 (Schottky gate) to 6 nm. T-gate devices with 120 nm gate length were stressed under continuous-wave 40-GHz large-signal RF operation, biased in class AB with VDS = 20 V. Degradation in large-signal output power gain was observed to various degrees for all devices. For structures with a 3- or 6-nm gate insulator thickness, output power degraded by approximately 1 dB or less after 250 h of operation. A rapid decrease in output power was observed for structures with a 1-nm gate insulator or a Schottky gate, with a 1-dB decrease in output power within the first 10 h of operation. Degradation in output power was associated with a reduction in drain current, likely caused by hot-electron-related trapping as the drain current was fully recoverable after exposing the devices to UV light. Simulations show that as the gate insulator thickness is reduced, the peak lateral electric field in the channel increases, which would be consistent with an increase in hot-electron-related degradation.
Natural inhibitor from Candida albicans blocks release of azurophil and specific granule contents by chemotactic peptide-stimulated human neutrophils

A product released by Candida albicans hyphae which was previously determined to block the neutrophil respiratory burst also inhibited the degranulation response elicited by the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP). When neutrophils were incubated with 100 micrograms of this Candida hyphal inhibitory product (CHIP) per ml and stimulated with 1,000 nM FMLP, release of the azurophil granule marker beta-glucuronidase and the specific granule marker lactoferrin was decreased to 31.2 +/- 5.7 and 35.7 +/- 5.3% of control, respectively. Inhibition was concentration dependent, with a half-maximal reduction of beta-glucuronidase and lactoferrin release being induced by 4 and 1 micrograms of CHIP per ml, respectively. In contrast to these striking alterations in response to FMLP, CHIP had no significant effect on lactoferrin release stimulated by phorbol myristate acetate. Moreover, actin polymerization, which has been suggested to be involved in regulation of degranulation, was unaffected by CHIP whether the neutrophils were stimulated by FMLP or phorbol myristate acetate. The selectivity of inhibition of neutrophil degranulation thus provides additional confirmation that CHIP is a useful agent for exploring human neutrophil activation pathways.
Use of the QOL-AD for measuring quality of life in people with severe dementia--the LASER-AD study.

BACKGROUND Health-related quality of life (HR-QOL) scales are particularly important in older people as global outcome measures for interventions. It is known that people with mild to moderate dementia can provide valid assessments of their own QOL, but it is unclear whether these instruments are useful in those with severe dementia. OBJECTIVE We examined the usefulness of the QOL scale in Alzheimer's disease (QOL-AD) in people with severe dementia by considering the ability of older people with a Mini-Mental State Examination (MMSE) score of <12 and their caregivers to complete this scale, as well as its construct validity and internal consistency. METHODS Data were collected from people with Alzheimer's disease and their caregivers using a range of instruments measuring cognition, mood, behaviour, QOL and functional ability. RESULTS Of 79 participants and their caregivers, 41 (52%) could complete the QOL-AD. Cognition and functional abilities were significantly higher in the completers than in the non-completers (P < 0.001). The QOL-AD showed internal consistency and construct validity as it correlated with ability to look after self, fewer limitations due to physical health, positive mood status and low levels of apathy. CONCLUSIONS There is evidence for the validity and reliability of the QOL-AD in people with MMSE scores of 3-11, as well as the practicality of administering the scale in this population. The scale is unlikely to generate useful information for people with MMSE scores of <3. QOL does not decrease as cognition worsens. This throws into question most people's assumption that decreasing cognition worsens QOL. We consider that it may be important to inform the public of this, as living wills are used increasingly in our culture.
Assessing the Biological Significance of Gene Expression Signatures and Co-Expression Modules by Studying Their Network Properties

Microarray experiments have been extensively used to define signatures, which are sets of genes that can be considered markers of experimental conditions (typically diseases). Paradoxically, in spite of the apparent functional role that might be attributed to such gene sets, signatures do not seem to be reproducible across experiments. Given the close relationship between function and protein interaction, network properties can be used to study to what extent signatures are composed of genes whose resulting proteins show a considerable level of interaction (and consequently a putative common functional role). We have analysed 618 signatures and 507 modules of co-expression in cancer looking for significant values of four main protein-protein interaction (PPI) network parameters: connection degree, cluster coefficient, betweenness and number of components. A total of 3904 gene ontology (GO) modules, 146 KEGG pathways, and 263 Biocarta pathways have been used as functional modules of reference. Co-expression modules found in microarray experiments display a high level of connectivity, similar to the one shown by conventional modules based on functional definitions (GO, KEGG and Biocarta). A general observation for all the classes studied is that the networks formed by the modules improve their topological parameters when an external protein is allowed to be introduced within the paths (up to the 70% of GO modules show network parameters beyond the random expectation). This fact suggests that functional definitions are incomplete and some genes might still be missing. Conversely, signatures are clearly not capturing the altered functions in the corresponding studies. This is probably because the way in which the genes have been selected in the signatures is too conservative. These results suggest that gene selection methods which take into account relationships among genes should be superior to methods that assume independence among genes outside their functional contexts.
On Neural Codes and Perception

Bill Newsome is a professor in the Department of Neurobiology at the Stanford University School of Medicine. He received his B.S. in physics from Stetson University in 1974 and his Ph.D. in biology from Caltech in 1980. Following postdoctoral work at MH, he served on the faculty at SUNY Stony Brook before joining the Stanford faculty in 1988. His research has focused on the neural mechanisms underlying visual perception and visually guided behavior. Bill was a corecipient of the Rank Prize in optoelectronics in 1992, and received the Minerva Foundation's Golden Brain Award in the same year. This fall he received the Spencer Award, granted yearly by the College of Physicians and Surgeons at Columbia University for highly original contributions to research in neurobiology. In addition, he won the Kaiser Award for excellence in preclinical teaching granted annually by the Stanford School of Medicine.
Immunohistochemical analysis of atypical ductular reaction in the human liver, with special emphasis on the presence of growth factors and their receptors.

AIMS/BACKGROUND The objective of this study was to characterize the expression of transforming growth factor-alpha/epidermal growth factor receptor, hepatocyte growth factor/c-met, transforming growth factor-beta/Type I-II transforming growth factor-beta receptors, stem cell factor, urokinase plasminogen activator, smooth muscle actin, CD34 and alpha-fetoprotein in human liver samples with (sub)massive necrosis of different etiology containing atypical ductular reaction. METHODS Their presence was studied by immunohistochemistry on paraffin-embedded tissue sections. RESULTS Transforming growth factor-alpha and -beta, hepatocyte growth factor and their receptors were demonstrated in the ductules; additionally stem cell factor and urokinase plasminogen activator were also expressed. The atypical ductules were surrounded by smooth muscle actin-positive activated stellate cells. CONCLUSION These phenotypic similarities confirm that the atypical ductules in the human liver may be equivalent of oval cells in the rat liver, which are regarded as the progeny of stem cells. That is, the atypical ductular proliferation may correspond to a stem cell-fed regenerative process.
Intermediate-Level Visual Representations and the Construction of Surface Perception

Visual processing has often been divided into three stagesearly, intermediate, and high level vision, which roughly correspond to the sensation, perception, and cognition of the visual world. In this paper, we present a network-based model of intermediate-level vision that focuses on how surfaces might be represented in visual cortex. We propose a mechanism for representing surfaces through the establishment of ownershipa selective binding of contours and regions. The representation of ownership provides a central locus for visual integration. Our simulations show the ability to segment real and illusory images in a manner consistent with human perception. In addition, through ownership, other processes such as depth, transparency, and surface completion can interact with one another to organize an image into a perceptual scene.
Enterobacterial infection modulates major histocompatibility complex class I expression on mononuclear cells

Major histocompatibility complex (MHC) class I expression is reduced in several viral infections, but it is not known whether the same happens during infections caused by intracellular enterobacteria. In this study, the expression of MHC class I antigens on peripheral blood mononuclear cells (PBMC) from 16 patients with Salmonella, Yersinia, or Klebsiella infection was investigated. During or after the acute infection, the expression of MHC class I antigens was markedly decreased in eight patients, all with genotype HLA‐B27, and six out of eight with reactive arthritis (ReA). A significant decrease of monomorphic MHC class I was found in three patients, of HLA‐B27 in eight (P<0·05) and of HLA‐A2 in two. However, patients negative for the HLA‐B27 genotype, or healthy HLA‐B27‐positive individuals, did not have a significant decrease of MHC class I antigens. During the decreased expression on the cell surface, intracellular retention of MHC class I antigens was observed, whereas HLA‐B27 mRNA levels did not vary significantly. This is the first evidence that enterobacterial infection may down‐regulate expression of MHC class I molecules in vivo and that down‐regulation is predominant in patients with the HLA‐B27 genotype.
The establishment of human-computer interaction based on Word2Vec

In this paper, a novel method was proposed a interactive chat robot base on Word2vec. This paper use Jieba to segment the sentence entered by the user and use Word2vec to find the word vector. And then by calculating the relevance of the words to match the thesaurus, and then make the system output the message that the user wants to know. So the users can not only limit the input of one or two words, but can be entered in accordance with the user's own meaning.
Wound Microbiology and Associated Approaches to Wound Management

SUMMARY The majority of dermal wounds are colonized with aerobic and anaerobic microorganisms that originate predominantly from mucosal surfaces such as those of the oral cavity and gut. The role and significance of microorganisms in wound healing has been debated for many years. While some experts consider the microbial density to be critical in predicting wound healing and infection, others consider the types of microorganisms to be of greater importance. However, these and other factors such as microbial synergy, the host immune response, and the quality of tissue must be considered collectively in assessing the probability of infection. Debate also exists regarding the value of wound sampling, the types of wounds that should be sampled, and the sampling technique required to generate the most meaningful data. In the laboratory, consideration must be given to the relevance of culturing polymicrobial specimens, the value in identifying one or more microorganisms, and the microorganisms that should be assayed for antibiotic susceptibility. Although appropriate systemic antibiotics are essential for the treatment of deteriorating, clinically infected wounds, debate exists regarding the relevance and use of antibiotics (systemic or topical) and antiseptics (topical) in the treatment of nonhealing wounds that have no clinical signs of infection. In providing a detailed analysis of wound microbiology, together with current opinion and controversies regarding wound assessment and treatment, this review has attempted to capture and address microbiological aspects that are critical to the successful management of microorganisms in wounds.
The ribosome-associated complex antagonizes prion formation in yeast

Abstract The number of known fungal proteins capable of switching between alternative stable conformations is steadily increasing, suggesting that a prion-like mechanism may be broadly utilized as a means to propagate altered cellular states. To gain insight into the mechanisms by which cells regulate prion formation and toxicity we examined the role of the yeast ribosome-associated complex (RAC) in modulating both the formation of the [PSI+] prion – an alternative conformer of Sup35 protein – and the toxicity of aggregation-prone polypeptides. The Hsp40 RAC chaperone Zuo1 anchors the RAC to ribosomes and stimulates the ATPase activity of the Hsp70 chaperone Ssb. We found that cells lacking Zuo1 are sensitive to over-expression of some aggregation-prone proteins, including the Sup35 prion domain, suggesting that co-translational protein misfolding increases in Δzuo1 strains. Consistent with this finding, Δzuo1 cells exhibit higher frequencies of spontaneous and induced prion formation. Cells expressing mutant forms of Zuo1 lacking either a C-terminal charged region required for ribosome association, or the J-domain responsible for Ssb ATPase stimulation, exhibit similarly high frequencies of prion formation. Our findings are consistent with a role for the RAC in chaperoning nascent Sup35 to regulate folding of the N-terminal prion domain as it emerges from the ribosome.
The Effects of Strength Training on Muscle Architecture in Humans

The present paper reviews previous studies on changes in muscle architecture in humans as a result of strength training. Muscle architecture here refers to 1) muscle size, 2) pennation angle, and 3) muscle fiber length. Training-induced changes are summarized respectively. A typical outcome of strength training is muscle hypertrophy, which is manifested as an increase in muscle size evaluated by cross-sectional area and muscle volume. However, changes also occur in pennation angles and, possibly, in muscle fiber lengths. Increased pennation angles after training have the detrimental effect of producing a reduced force transmission from muscle fibers to tendon, which might lead to a decrease in specific tension or muscle force per physiological cross-sectional area. Recent in vivo studies on human muscles have revealed that changes in pennation angles resulting from training and contraction are much greater than previously thought.
Mechanism of control of trophoblast invasion in situ

We have previously shown that first trimester human trophoblast cells share in vitro invasive properties with malignant cells. In this study we show that the in situ control of trophoblast invasion is provided by the uterine microenvironment. Trophoblast cells were labeled with 125l‐deoxyuridine and examined for their ability to invade an epithelium‐free human amniotic membrane in vitro under various conditions. The degree of invasion was determined as the percentage of the radioactivity retained within the membrane. Conditioned media from first trimester human decidual cells (DCM) suppressed invasion of trophoblast cells in the amnion invasion assay. This suppression was prevented by addition of neutralizing anti‐TGF β antibody or neutralizing antibody to tissue inhibitor of metalloproteinases (TIMP‐1) to the DCM, and mimicked by TGFβ,. These antibodies also augmented invasion beyond control levels, suggesting that trophoblast cells may also produce these factors. A bioassay for TGFβ activity, measured by antiproliferative effect on the mink lung epithelial cell line Mv 1 Lu, revealed that decidual cells produced this factor only in the latent form, whereas the active form was produced by the trophoblast. A decrease in collagenase type IV activity in the conditioned media of trophoblast cultures was observed when TGFβ was added to these cultures. Removal of endogenous TGFβ in trophoblast cultures by addition of anti‐TGFβ antibody resulted in down‐regulation of TIMP message as determined by Northern analysis. These results indicate that (a) decidua‐derived (and to a minor extent trophoblast‐derived) TGFβ is the prime mediator in the control of invasion by first trimester trophoblast, the latent form of TGFβlikely being activated by trophoblast‐derived proteinases; (b) induction of TIMPby TGFβ in both trophoblast and decidua is the final pathway in this control.