Miracle-dz/UniFAR-FTUs huggingface dataset:
Human Papillomavirus Type 5 E6 Oncoprotein Represses the Transforming Growth Factor β Signaling Pathway by Binding to SMAD3

ABSTRACT Mechanisms of cellular transformation associated with human papillomavirus type 5 (HPV5), which is responsible for skin carcinomas in epidermodysplasia verruciformis (EV) patients, are poorly understood. Using a yeast two-hybrid screening and molecular and cellular biology experiments, we found that HPV5 oncoprotein E6 interacts with SMAD3, a key component in the transforming growth factor β1 (TGF-β1) signaling pathway. HPV5 E6 inhibits SMAD3 transactivation by destabilizing the SMAD3/SMAD4 complex and inducing the degradation of both proteins. Interestingly, the E6 protein of nononcogenic EV HPV9 failed to interact with SMAD3, suggesting that downregulation of the TGF-β1 signaling pathway could be a determinant in HPV5 skin carcinogenesis.
Isolation and characterization of recombinant lambda gt11 bacteriophages expressing four different Mycobacterium intracellulare antigens

Four bacteriophages expressing different immunoreactive recombinant Mycobacterium intracellulare antigens were isolated from a lambda gt11 library with monoclonal antibodies to M. intracellulare. These four antibodies reacted with native M. intracellulare proteins of 54, 43, 40/38, and 22 kilodaltons. Southern blot hybridizations with DNA probes prepared from insert fragments of these bacteriophages confirmed the M. intracellulare derivation of the inserts. The physical maps of the immunoreactive phages were deduced by restriction enzyme digestions. The molecular weights of the expressed recombinant antigens were determined by Western (immuno-) blotting.
Radiochromic leuco dye micelle hydrogels: I. Initial investigation

This investigation reports the use of surfactants and colorless leuco triarylmethane dyes to form a new class of radiochromic micelle hydrogels for three-dimensional (3D) water-equivalent dosimetry. Gelatin gel samples with several surfactants and leuco dyes were prepared and evaluated for optical transparency, dose sensitivity and diffusion rates. The addition of Triton X-100, a non-ionic surfactant, at levels exceeding the critical micelle concentration provides a transparent hydrogel in which the water insoluble leuco Malachite Green (LMG) can dissolve. During irradiation, the LMG dye precursor converts to Malachite Green (MG+). The most sensitive reported LMG gel formulation contains 0.3 mM LMG leuco dye, 16 mM trichloroacetic acid, 7 mM Triton X-100 and 4% w/w gelatin. A diffusion coefficient of 0.14 mm2 h−1 was determined for MG+ in this gel by fitting the time-dependent degradation of the transmission profile after irradiating half of the sample. The diffusion rate was three times lower than the standard radiochromic ferrous xylenol-orange (FX) gel. The primary feature of this 3D hydrogel is that it introduces transparent, radiochromic, micelle hydrogels. The radiochromic response to dose is instantaneous and images are stable for several hours. A dosimetric characterization revealed that the dose response is reproducible to within 10% over five separate batches and independent of both energy and dose rate. Uniform pre-irradiation of samples to 5 Gy provided a subsequent near linear response to greater than 110 Gy. LMG gels when read with a fast optical CT scanner can provide full 3D dose distributions in less than 30 min post-irradiation. LMG micelle gels scanned with a 633 nm light source are a promising system for quantitative water- or tissue-equivalent 3D dose verification in the 5–100 Gy dose range. These gels are useful for the scanning of larger volume dosimeters (i.e. >15 cm diameter) since they are easily prepared with inexpensive ingredients, are transparent and have a low initial optical absorbance prior to irradiation. In this gel, only one colored molecular species is produced. This results in a linear relation between the concentration of the colored dye product and optical absorption independent of the sampled wavelength.
A Protease Pathway for the Repair of Topoisomerase II-DNA Covalent Complexes*

Despite rapid advances in the field of DNA repair, little is known about the repair of protein-DNA adducts. Previous studies have demonstrated that topoisomerase II (TopII)-DNA adducts (TopII-DNA covalent complexes) are rapidly degraded by the proteasome. It has been hypothesized that proteasomal degradation of TopII-DNA covalent adducts exposes TopII-concealed DNA double-strand breaks (DSBs) for repair. To test this hypothesis, the anticancer drug, VP-16 (etoposide), was employed to induce TopII-DNA covalent complexes in mammalian cells, and the involvement of proteasome in processing TopII-DNA covalent complexes into DSBs was investigated. Consistent with the hypothesis, VP-16-induced DSBs as monitored by neutral comet assay, as well as DNA damage signals (e.g. γ-H2AX) were significantly reduced in the presence of the proteasome inhibitor, MG132. Using both top2β knock-out mouse embryonic fibroblasts and Top2β small interfering RNA knockdown PC12 cells, as well as postmitotic neurons in which TopIIα was absent, we showed that VP-16-induced DNA damage signals were attenuated upon proteasome inhibition, suggesting the involvement of proteasome in the repair/processing of both TopIIα-DNA and TopIIβ-DNA adducts. By contrast, hydrogen peroxide-induced γ-H2AX was unaffected upon proteasome inhibition, suggesting a specific requirement of the proteasome pathway in the processing of TopII-DNA covalent complexes into DNA damage.
Enzyme-linked immunosorbent assay for detection of antibody in volunteers experimentally infected with human coronavirus strain 229 E

An enzyme-linked immunosorbent assay was developed for detecting antibody rises to human coronavirus strain 229E and related strains in paired sera from infected volunteers. There was a close correlation between development of colds infected volunteers. There was a close correlation between development of colds and significant antibody rises detected by the enzyme-linked immunosorbent assay. Furthermore, the assay was more sensitive than a neutralization assay. This enzyme-linked immunosorbent assay is an easy, accurate, and sensitive assay for measuring significant antibody rises to human coronavirus strain 229E group viruses, and it could be useful in the clinical diagnosis of these infections.
SYMMETRY AND VARIABILITY OF VERTICAL GROUND REACTION FORCE AND

Gait is a basic requirement for daily activity and is known as one of the most universal and complex of all human activities (Sadeghi et al, 2000). The aim of gait is to support the body against gravity while generating movements to propel the body forward. For producing the smooth rhythmical motion of the able-bodied gait, it requires precise coordination between the tasks of propulsion and balance (Winter & Crago, 2000).
Improving TCP performance for vertical handover in heterogeneous wireless networks

The incorporation of wireless local area networks (WLANs) into existing cellular networks as supplementary access technologies has become an issue of great interest. However, vertical handover (VHO), which allows users to roam between a WLAN and a cellular network, causes an abrupt change in certain link characteristics such as the round trip time and data rate. Owing to such changes, reordering problem and premature timeout occur and trigger unnecessarily fast retransmission during VHO, causing throughput degradation. Thus, we propose a new transmission control protocol (TCP) mechanism, which resolves the reordering problem by suppressing unnecessary retransmission caused by spurious duplicate acknowledgments (dupacks) incurred because of the reordering problem, and prevents premature timeout by employing an adaptive retransmission timer. We analytically investigate the throughput of our proposed TCP scheme. The numerical and simulation results show that our proposed TCP performs better in terms of throughput than other schemes appearing in the literature. Copyright © 2009 John Wiley & Sons, Ltd.
Broadly distributed T cell reactivity, with no immunodominant loci, to the pre‐erythrocytic antigen thrombospondin‐related adhesive protein of Plasmodium falciparum in West Africans

Protective immunity to malaria has been achieved in human volunteers utilizing the pre‐erythrocytic Plasmodium falciparum antigen, the circumsporozoite protein (CS). However, T cell reactivity to CS is focused on several highly polymorphic T cell epitope regions, potentially limiting the efficacy of any vaccine to specific malaria strains. Another important pre‐erythrocytic malaria antigen, the thrombospondin‐related adhesive protein (TRAP), can induce protection in animal models of malaria, but knowledge of human T cell responses is limited to the identification of CD8 T cell epitopes, with no CD4 epitopes identified to date. This comprehensive study assessed reactivity to overlapping peptides spanning almost the whole of P. falciparum TRAP (PfTRAP), as well as peptides selected on the basis of HLA class II‐binding motifs. A total of 50 naturally exposed Gambian adults were assessed to define 26 T cell epitopes in PfTRAP capable of inducing rapid IFN‐γ or IL‐4 production, as assessed by enzyme‐linked immunospot assays. In contrast to the CS protein, this reactivity was broadly distributed along the length of TRAP. Moreover, of the 26 epitopes identified, 10 were found to be conserved in West Africa.
The role of Smad3 in mediating mouse hepatic stellate cell activation

Transforming growth factor β (TGF‐β) is the most potent profibrogenic mediator in liver fibrosis. Although Smad proteins have been identified as intracellular mediators in the TGF‐β signaling pathway, the function of individual Smad proteins remains poorly understood. The aim of this study was to explore the contribution of Smad3 in mediating TGF‐β responses in a model of acute liver injury in vivo and in culture‐activated hepatic stellate cells (HSCs). Wild‐type, Smad3 heterozygous or Smad3 homozygous knockout mice were treated with a single intragastric administration of CCl4. After 72 hours, the induction of hepatic collagen α1(I) and α2(I) messenger RNA (mRNA) levels in Smad3 knockout mice was only 42% and 64%, respectively, of the levels induced in wild‐type mice. However, smooth muscle α‐actin (α‐SMA) was expressed at a slightly higher level in livers from knockout mice compared with wild‐type mice. In culture‐activated HSCs from Smad3 knockout mice, collagen α1(I) mRNA was 73% of wild‐type HSCs, but α‐SMA expression was the same. HSCs from knockout mice showed a higher proliferation rate than wild‐type HSCs. Smad3‐deficient HSCs did not form TGF‐β1–induced Smad‐containing DNA‐binding complexes. In conclusion, (1) maximal expression of collagen type I in activated HSCs requires Smad3 in vivo and in culture; (2) Smad3 is not necessary for HSC activation as assessed by α‐SMA expression; (3) Smad3 is necessary for inhibition of proliferation of HSCs, which might be TGF‐β–dependent; and (4) Smad3 is required for TGF‐β1–mediated Smad‐containing DNA‐binding complex formation in cultured HSCs.
Essential Role of Dopamine D2 Receptor in the Maintenance of Wakefulness, But Not in Homeostatic Regulation of Sleep, in Mice

Dopamine (DA) and its D2 receptor (R) are involved in cognition, reward processing, and drug addiction. However, their roles in sleep–wake regulation remain unclear. Herein we investigated the role of D2R in sleep–wake regulation by using D2R knock-out (KO) mice and pharmacological manipulation. Compared with WT mice, D2R KO mice exhibited a significant decrease in wakefulness, with a concomitant increase in non-rapid eye movement (non-REM, NREM) and REM sleep and a drastic decrease in the low-frequency (0.75–2 Hz) electroencephalogram delta power of NREM sleep, especially during the first 4 h after lights off. The KO mice had decreased mean episode duration and increased episode numbers of wake and NREM sleep, many stage transitions between wakefulness and NREM sleep during the dark period, suggesting the instability of the wake stage in these D2R KO mice. When the KO mice were subjected to a cage change or an intraperitoneal saline injection, the latency to sleep in the KO mice decreased to half of the level for WT mice. The D2R antagonist raclopride mimicked these effects in WT mice. When GBR12909, a dopamine transport inhibitor, was administered intraperitoneally, it induced wakefulness in WT mice in a dose-dependent manner, but its arousal effect was attenuated to one-third in the D2R KO mice. However, these 2 genotypes showed an identical response in terms of sleep rebound after 2, 4, and 6 h of sleep deprivation. These results indicate that D2R plays an essential role in the maintenance of wakefulness, but not in homeostatic regulation of NREM sleep.
WEST VIRGINIA: A 10-YEAR RETROSPECTIVE REVIEW

Accepted, November 17, 2003. OBJECTIVE: The purpose of this study was to profile all-terrain vehicle crash victims with neurological injuries who were treated at a Level I trauma center. METHODS: We retrospectively reviewed trauma registry data for 238 patients who were admitted to the Jon Michael Moore Trauma Center at the West Virginia University School of Medicine after all-terrain vehicle crashes, between January 1991 and December 2000. Age, helmet status, alcohol and drug use, head injuries, length of stay, disposition, and hospital costs were studied. Death rates, head injuries, age, helmet use, and safety legislation in all 50 states were compared. RESULTS: Eighty percent of victims were male, with an average age of 27.3 years. Only 22% of all patients were wearing helmets. Alcohol and/or drugs were involved in almost one-half of all incidents. Fifty-five of 238 patients sustained spinal axis injuries; only 5 were wearing helmets. One-third of victims (75 of 238 victims) were in the pediatric population, and only 21% were wearing helmets. Only 15% of victims less than 16 years of age were wearing helmets. There were a total of eight deaths; only one patient was wearing a helmet. CONCLUSION: In the United States, all-terrain vehicles caused an estimated 240 deaths/yr between 1990 and 1994, which increased to 357 deaths/yr between 1995 and 2000. Brain and spine injuries occurred in 80% of fatal crashes. West Virginia has a fatality rate approximately eight times the national rate. Helmets reduce the risk of head injury by 64%, but only 21 states have helmet laws. Juvenile passengers on adult-driven vehicles are infrequently helmeted ( 20%) and frequently injured ( 65%). We conclude that safety legislation would save lives.
Human cytomegalovirus UL36-38 and US3 immediate-early genes: temporally regulated expression of nuclear, cytoplasmic, and polysome-associated transcripts during infection

During permissive in vitro infection, the human cytomegalovirus (HCMV) UL36-38 and US3 immediate-early (IE) regions give rise to multiple distinct species of RNA in a temporally regulated manner. We have compared the temporally regulated expression of the UL36-38 and US3 regions with that of the well-characterized major IE (MIE) region. Northern (RNA) blot hybridizations with antisense RNA probes were used to examine RNA isolated from infected cells at IE, early, and late times after infection and from cells infected in the presence of anisomycin (used to block de novo viral protein synthesis) or in the presence of phosphonoformate (used to block HCMV DNA synthesis). Different US3 region transcripts were expressed in the cytoplasm during the IE and late phases of infection, with kinetics similar to those of the MIE region. In contrast, various cytoplasmic transcripts from the UL36-38 region were expressed during each of the IE, early, and late phases of infection, including some expressed from IE through late times. The levels of steady-state RNA from the US3 and MIE regions were increased dramatically by infection in the presence of anisomycin, predominantly because of an increase in multiply spliced transcripts. Two of the three UL36-38 IE transcripts were largely unaffected by anisomycin and were expressed abundantly throughout infection, but a third, multiply spliced UL36-38 IE transcript was abundant only during infection in the presence of anisomycin. Nuclear, cytoplasmic, and polysome-associated transcripts from the three IE regions were not significantly different qualitatively or quantitatively. These results suggest that posttranscriptional controls at the levels of nuclear retention or polysome exclusion of transcripts are not operative for the IE region genes. Overall, these results indicate common features of expression of US3, MIE, and UL36-38, in addition to distinctive expression of the UL36-38 region during all temporal phases of expression.
Novel Tactile-SIFT Descriptor for Object Shape Recognition

Using a tactile array sensor to recognize an object often requires multiple touches at different positions. This process is prone to move or rotate the object, which inevitably increases difficulty in object recognition. To cope with the unknown object movement, this paper proposes a new tactile-SIFT descriptor to extract features in view of gradients in the tactile image to represent objects, to allow the features being invariant to object translation and rotation. The tactile-SIFT segments a tactile image into overlapping subpatches, each of which is represented using a dn-dimensional gradient vector, similar to the classic SIFT descriptor. Tactile-SIFT descriptors obtained from multiple touches form a dictionary of k words, and the bag-of-words method is then used to identify objects. The proposed method has been validated by classifying 18 real objects with data from an off-the-shelf tactile sensor. The parameters of the tactile-SIFT descriptor, including the dimension size dn and the number of subpatches sp, are studied. It is found that the optimal performance is obtained using an 8-D descriptor with three subpatches, taking both the classification accuracy and time efficiency into consideration. By employing tactile-SIFT, a recognition rate of 91.33% has been achieved with a dictionary size of 50 clusters using only 15 touches.
Metastasis to organs in carcinoma of the uterine cervix: Influence of treatment on incidence and distribution

Two hundred seventy‐eight autopsied cases of various stages of cervical cancer treated at Roswell Park Memorial Institute, Buffalo, New York, were evaluated to determine the effect of treatment on the spread of the disease. Patients were categorized, according to the primary treatment, into four groups: radiation, 183 cases; surgery, 44 cases; combined radiation and surgery, 34 cases; and other methods, 17 cases. The main clinical parameters of prognostic value were equally present except for earlier clinical stages in the “surgery” and “combined” groups. Clinically, the patterns of recurrence varied with the treatment: increased central pelvic recurrences after surgery, lateral deep pelvic recurrences after combined treatment and distant metastases after radiation. The mean survival in all cases was higher than previously reported, and still higher after radiation. Renal failure and sepsis were the leading causes of death. In the autopsy findings patients having radiation showed an increased risk of extrapelvic metastases whereas the surgical group revealed an increased risk of general pelvic and extrapelvic metastases. This may be explained by the longer survival in both groups, with more frequent local control after radiation. Distant metastases were widespread and the distribution was unaffected by the kind of treatment given for the primary disease.
Conservative Treatment of Plantar Fasciitis and Posterior Heel Pain: A Review

This review focuses on the various techniques of conservative treatment of plantar fasciitis and posterior heel pain. Being the optimal therapy controversial, the intent is to drive surgeons and rehabilitation specialists in the choice of the strategies. The Data sources were MEDLINE, PubMed, CINAHL, EMBASE, and Psych INFO databases using the selected key words. Studies have been selected for review using as criteria English, adults, clinical population and intervention. Among several published studies about rehabilitation and fasciitis, only a few showed bases on scientific evidence. Moreover, many studies were heterogeneous and included different outcomes and evaluations. There is consensus that a specific rehabilitation program is necessary to avoid chronicity. However, the real efficacy of every specific treatment (orthoses, stretching, radiotherapy, botulin toxin, shock waves, corticosteroid therapy, and platelet rich plasma) is still questionable, and often related to the experience of the authors. In conclusion, patients undergoing physiotherapy obtain a better and faster outcome achievement than non-treated patients; however, evidence-based treatments, protocols and clinical trials are recommended.
Mutational analysis of neurotensin in familial restless legs syndrome

A susceptibility locus for restless legs syndrome (RLS) has been identified recently on chromosome 12q. This region contains several transcribed genes including neurotensin (NTS), which, as an important modulator of the dopaminergic transmission, represents a strong functional and positional candidate in the context of RLS. In this study, NTS was evaluated for mutational analysis. A panel of 19 individuals from 4 families supporting linkage to 12q was investigated using a combined denaturing high‐performance liquid chromatography (dHPLC) and direct sequencing method. Analysis of the NTS genomic sequence revealed 2 intronic polymorphisms and 1 variant located in the 5′ untranslated region (UTR). None of the observed variants co‐segregated with RLS and no disease‐associated polymorphisms were detected in any of the analyzed families. Based on these results, it is unlikely that NTS is the gene responsible for RLS in chromosome 12‐linked families. © 2003 Movement Disorder Society
Examination of HER3 targeting in cancer using monoclonal antibodies

Significance The human EGF receptor (EGFR/HER) family plays critical roles in tumor progression. Therefore, several therapies intercepting these receptors were developed and clinically approved. Importantly, patients treated with such therapeutics often develop resistance, and in some cases this resistance has been associated with activation of HER3. Potentially, HER3 blockade might overcome patient resistance. Hence, antibodies to HER3 have been developed by us and other researchers. However, it has remained unclear which antibody attributes are required for effective tumor inhibition. To address this issue, we generated several monoclonal antibodies, which were tested in vitro and in tumor-bearing animals. Our results suggest that anti-HER3 antibodies able to intercept stroma–tumor interactions, as well as accelerate HER3 degradation, might inhibit tumor growth better than other antibodies. The human EGF receptor (HER/EGFR) family of receptor tyrosine kinases serves as a key target for cancer therapy. Specifically, EGFR and HER2 have been repeatedly targeted because of their genetic aberrations in tumors. The therapeutic potential of targeting HER3 has long been underestimated, due to relatively low expression in tumors and impaired kinase activity. Nevertheless, in addition to serving as a dimerization partner of EGFR and HER2, HER3 acts as a key player in tumor cells’ ability to acquire resistance to cancer drugs. In this study, we generated several monoclonal antibodies to HER3. Comparisons of their ability to degrade HER3, decrease downstream signaling, and inhibit growth of cultured cells, as well as recruit immune effector cells, selected an antibody that later emerged as the most potent inhibitor of pancreatic cancer cells grown as tumors in animals. Our data predict that anti-HER3 antibodies able to intercept autocrine and stroma–tumor interactions might strongly inhibit tumor growth, in analogy to the mechanism of action of anti-EGFR antibodies routinely used now to treat colorectal cancer patients.