Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of anesthetics on reflex micturition in the chronic cannula‐implanted rat

It is well known that urethane is a suitable anesthetic for acute studies and has been extensively recommended for investigations related to micturition physiology. This is mainly because of the capability of urethane anesthesia to spare reflex micturition as well as its easily established long‐lasting and stable anesthetic level. However, urethane anesthesia is usually restricted to acute experiments due to its potential toxicity. This study searched for an alternative to urethane that would be suitable for studies in which recovery from anesthesia was needed. The list of administered drugs was as follows: pentobarbital, thiobutabarbital, ketamine‐acepromazine, ketamine‐diazepam, tiletamine‐zolazepam, fentanyl‐droperidol, alphaxalone‐alphadolone, propofol, isoflurane, methoxyflurane, azaperone, tribromoethanol, and buprenorphine. Among these drugs, only tiletamine‐zolazepam spared the reflex micturition contractions. However, the duration of this anesthesia was too short (approximately 30 minutes) to complete the necessary testing and additional dosing of the anesthetic generally obliterated the micturition reflex. On the other hand, rats given i.v. urethane infusion (10% solution in 0.9% saline, 3.2–4.0 mg/kg/min, total dose 0.56–1.03 g/kg) maintained a stable anesthesia that permitted both reflex micturition and stereotaxic procedures. Rats moved spontaneously 3–16 hours after cessation of i.v. urethane anesthesia and completely recovered in 2 days without significant after‐effects. Bladder function was normal. No pathological changes were seen 1 week later. The present results suggest that urethane is the most suitable anesthetic for acute and chronic physiological experiments that require demonstration of reflex micturition. Neurourol. Urodynam. 19:87–99, 2000. © 2000 Wiley‐Liss, Inc.
Cognitive processes in spatial mapping: Evidence from a developmental spatial deficit

ABSTRACT We report a case study of an adolescent girl (N.K.Y.) with a developmental deficit affecting spatial processing. In a simple spatial mapping task, N.K. Y. shows a striking dissociation: She succeeds in one variant of the experiment in which the stimuli are objects, but struggles in a structurally identical task with people as stimuli. We present evidence that this dissociation stems from a tendency to automatically adopt the spatial perspective of other people, but not objects—a phenomenon also observed in neurotypical individuals. When adopting another person’s perspective, N.K. Y. imagines herself in the other’s position, representing the other’s left and right as if it were her own. N.K. Y. ’s deficit in relating left–right information to her own body then disrupts her performance. Our results shed light on the nature of N.K. Y. ’s deficit as well as the cognitive operations involved in spatial perspective taking.
Analysis of the Steroid Receptor Coactivator 1 (SRC1)-CREB Binding Protein Interaction Interface and Its Importance for the Function of SRC1

ABSTRACT The transcriptional activity of nuclear receptors is mediated by coactivator proteins, including steroid receptor coactivator 1 (SRC1) and its homologues and the general coactivators CREB binding protein (CBP) and p300. SRC1 contains an activation domain (AD1) which functions via recruitment of CBP and and p300. In this study, we have used yeast two-hybrid and in vitro interaction-peptide inhibition experiments to map the AD1 domain of SRC1 to a 35-residue sequence potentially containing two α-helices. We also define a 72-amino-acid sequence in CBP necessary for SRC1 binding, designated the SRC1 interaction domain (SID). We show that in contrast to SRC1, direct binding of CBP to the estrogen receptor is weak, suggesting that SRC1 functions primarily as an adaptor to recruit CBP and p300. In support of this, we show that the ability of SRC1 to enhance ligand-dependent nuclear receptor activity in transiently transfected cells is dependent upon the integrity of the AD1 region. In contrast, the putative histone acetyltransferase domain, the Per-Arnt-Sim basic helix-loop-helix domain, the glutamine-rich domain, and AD2 can each be removed without loss of ligand-induced activity. Remarkably, a construct corresponding to residues 631 to 970, which contains only the LXXLL motifs and the AD1 region of SRC1, retained strong coactivator activity in our assays.
Multiple Input Support in a Model-Based Interaction Framework

Developing for tabletops puts special requirements on interface programming frameworks: managing parallel input, device discovery, device equivalence, and describing combined interactions. We analyse these issues and describe the solutions that were used in IntuiKit, a model- based framework aimed at making the design and development of post-WIMP user interfaces more accessible. Some solutions are simple consequences of the support of multi- modality, while others are more specific to multiple touch. We illustrate these features through examples developed in several tabletop projects, including one application aimed at improving collaboration between air traffic controllers.
Toxicity of sulfuric acid mist to guinea pigs.

Young (1 to 2 mo) and old (1 to 5 yr) guinea pigs were exposed to from 0 to 90 mg/m/sup 3/ sulfuric acid mist. LD/sub 50/ for old animals was 50 mg/m/sup 3/ for 8 hr; for young animals it was 18 mg/m/sup 3/. Zero mortality threshold was at 20 mg/m/sup 3/ for old and 8 mg/m/sup 3/ for young. Difference with age was significant. Pathology included gross and microscopic hemorrhage, edema, congestion of tract and vessels, and leukocytes and RBC in alveolar spaces. Animals that survived had spotty congestion and hemorrhage, thickening of alveolar walls, subsiding inflammation. Young guinea pigs were exposed for up to 72 hr. Dose--time mortality curves show very little change with time for concentrations of 8, 12, or 16 mg/m/sup 3/. Higher concentrations show rapid change with time. There was the same type of damage; repair was slow. Respiratory difficulty was dependent mainly on concentration, whereas deep-seated, slowly-recoverable changes depend on both concentration, and time of exposure. Spasm reaction makes guinea pigs so sensitive; mortality response was not affected by total exposure as it kills quickly. However, lung damage increases with time--dose exposure. Toxicity cannot be based on mortality alone.
Improved methods for semiempirical solvation models

We present improved algorithms for the SMx (x = 1, 1a, 2, 3) solvation models presented previously [see the overview in C. J. Cramer and D. G. Truhlar, J. Comp.‐Aided Mol. Design, 6, 629 (1992)]. These models estimate the free energy of solvation by augmenting a semiempirical Hartree‐Fock calculation on the solute with the generalized Born (GB) model for electric polarization of the solvent and a surface tension term based on solvent‐accessible surface area. This article presents three improvements in the algorithms used to carry out such calculations, namely (1) an analytical accessible surface area algorithm, (2) a more efficient radial integration scheme for the dielectric screening computation in the GB model, and (3) a damping algorithm for updating the GB contribution to the Fock update during the iterations to achieve a self‐consistent field. Improvements (1) and (2) decrease the computer time, and improvement (3) leads to more stable convergence. Improvement (2) removes a small systematic numerical error that was explicitly absorbed into the parameterization in the SMx models. Therefore, we have adjusted the parameters for one of the previous models to yield essentially identical performance as was obtained originally while simultaneously taking advantage of improvement (2). The resulting model is called SM2.1. The fact that we obtain similar results after removing the systematic quadrature bias attests to the robustness of the original parameterization. © 1995 by John Wiley & Sons, Inc.
Protective anti‐mycobacterial T cell responses through exquisite in vivo activation of vaccine‐targeted dendritic cells

Vaccine efficacy largely depends upon DC targeting and activation. The most potent TLR soluble ligands induce diffuse DC activation, which may be associated with marked pro‐inflammatory responses and possibly adverse effects. This raises the concern that effective vaccine adjuvants may similarly rely on widespread DC activation. Using a promising candidate vaccine against tuberculosis (fusion protein of Ag85B and 6‐kDa early secretory antigenic target (ESAT‐6)) formulated in the potent IC31® adjuvant, DC targeting and activation was studied in vivo, following the fate of antigen and adjuvant in the draining lymph nodes, to define the magnitude of DC targeting/activation required in vivo to induce protective vaccine responses. Unexpectedly, protective IFN‐γ‐mediated Ag85B‐ESAT‐6/IC31® responses were associated to the activation of a minute population (less than 0.3%) of CD11c+ lymph node DC, without detectable systemic pro‐inflammatory responses. This activated peripheral tissue‐derived DC population, characterized by enhanced CD80, CD86, CD40 and IL‐12p40 expression, was only identified when focusing on adjuvant‐ or antigen‐labeled CD11c+ DC, which were found to support T cell proliferation. Immunization with aluminum hydroxide adjuvant (Alum) resulted in a similar proportion of antigen‐associated DC but without detectable enhancement of CD80, CD86, CD40 or IL‐12p40 expression. Thus, potent protective IFN‐γ‐producing responses may be elicited by the exquisite activation of a minute number of in vivo targeted DC.
CADASIL with cord involvement associated with a novel and atypical NOTCH3 mutation

Background Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is a hereditary cause of cerebral small-vessel disease associated with one of many recognised mutations of the NOTCH3 gene. Spinal cord involvement is not a recognised feature. The authors describe a unique CADASIL pedigree that manifested a stereotypical pattern of cord lesions, in association with a novel and atypical NOTCH3 mutation. Methods Clinical, radiological, laboratory and genetic characterisation of three affected family members. The associated NOTCH3 mutation was further evaluated by site-directed mutagenesis, immunohistochemistry, CBF1-transcription reporter assay, and screened for in 100 unrelated pathologically confirmed multiple sclerosis (MS) patients. Results Three members of a family presented with CADASIL caused by a novel NOTCH3 missense mutation, C212Y. Two daughters of the proband also manifested a distinctive pattern of cord lesions confined to the posterocentral zone, cerebral lesions showing both a demyelinating and a typical CADASIL topography, positive antinuclear antibodies and intrathecally derived oligoclonal bands. The mutation occurred in exon 4—that is, outside the Notch3 ligand-binding domain—yet unusually for this location impaired Notch function as assessed by Jagged1 signal transduction. The C212Y mutation did not occur in 100 separate MS cases. Conclusions This is the first description of an inherited pattern of cord lesions in association with CADASIL. The fact that certain features of dysregulated immunity also occurred, in association with a novel and atypical loss-of-function NOTCH3 mutation, supports evidence for functional interactions of Notch3 with the immune system, in addition to its vascular support role.
Pleiotropic Effects of Biguanides on Mitochondrial Reactive Oxygen Species Production

Metformin is widely prescribed as a first-choice antihyperglycemic drug for treatment of type 2 diabetes mellitus, and recent epidemiological studies showed its utility also in cancer therapy. Although it is in use since the 1970s, its molecular target, either for antihyperglycemic or antineoplastic action, remains elusive. However, the body of the research on metformin effect oscillates around mitochondrial metabolism, including the function of oxidative phosphorylation (OXPHOS) apparatus. In this study, we focused on direct inhibitory mechanism of biguanides (metformin and phenformin) on OXPHOS complexes and its functional impact, using the model of isolated brown adipose tissue mitochondria. We demonstrate that biguanides nonspecifically target the activities of all respiratory chain dehydrogenases (mitochondrial NADH, succinate, and glycerophosphate dehydrogenases), but only at very high concentrations (10−2–10−1 M) that highly exceed cellular concentrations observed during the treatment. In addition, these concentrations of biguanides also trigger burst of reactive oxygen species production which, in combination with pleiotropic OXPHOS inhibition, can be toxic for the organism. We conclude that the beneficial effect of biguanides should probably be associated with subtler mechanism, different from the generalized inhibition of the respiratory chain.
Scalpel Versus Electrocautery Dissections: The Effect on Wound Complications and Pro-Inflammatory Cytokine Levels in Wound Fluid

Aim: Electrocautery has been postulated as a risk factor for wound complications. This study was conducted to evaluate the effects of electrocautery and scalpel dissections on wound complications and local cytokine levels. Materials and Methods: Patients undergoing modified radical mastectomy were assigned to flap dissection with either electrocautery (n = 18) or scalpel (n = 20). Blood loss, drain volume and duration, seroma formation and wound complications were recorded. Tumor necrosis factor-alpha (TNF-a) and interleukin (IL)-6 levels were measured in drain fluids at postoperative 24 hours. Results: The electrocautery group had significantly reduced blood loss and total drain volume, but increased seroma formation rate. Significantly elevated levels of TNF-aa were measured in drain fluids of patients with electrocautery dissection. Conclusions: The use of electrocautery causes less bleeding and total drain output with an increased rate of seroma formation. Electrocautery dissection increases pro-inflammatory cytokine response in wound fluid, which may reflect an aggravated inflammation and increased potential for tissue damage.
Return of Functional Ability After Childbirth

Recovery of functional ability after childbirth was examined in a sample of 30 women who had vaginal deliveries and 40 who had cesarean births. Recovery of functional ability after childbirth was defined as the resumption of household, social and community, and occupational activities and assumption of infant care responsibilities. Only 51% of the women reported they had regained their usual level of energy by the end of the 6-week postpartum period; 72% of the vaginally delivered women reported regaining their physical energy within this period, but only 34% of the cesarean delivered women had done so. Differences were also noted between cesarean- and vaginally delivered women in the interval until assumption of infant care responsibilities and resumption of certain household tasks, socializing with friends, and participation in religious organizations. Recovery of functional ability was also found to be affected by maternal and neonatal complications, and their presence was associated with postponed return to employment. Findings suggest that the traditional 6-week recovery period from childbirth needs to be reconsidered, particularly for women experiencing cesarean deliveries or maternal or neonatal postdelivery complications.
Cost-effective and accurate nodes localization in heterogeneous wireless sensor networks

In this paper, we propose a novel low-cost localization algorithm tailored for multi-hop heterogeneous wireless sensor networks (HWSNs) where nodes' transmission capabilities are different. This characteristic, if not taken into account when designing the localization algorithm, may severely hinder its accuracy. Assuming different nodes' transmission capabilities, we develop a novel approach to derive the expected hop progress (EHP). Exploiting the latter, we propose a localization algorithm that is able to accurately locate the sensor nodes owing to a new low-cost implementation. Furthermore, we develop a correction mechanism which complies with the heterogeneous nature of WSNs to further improve localization accuracy without incurring any additional costs. Simulations results show that the proposed algorithm, whether applied with or without correction, outper-forms in accuracy the most representative WSN localization algorithms.
Underwater Object Tracking Using Sonar and USBL Measurements

In the scenario where an underwater vehicle tracks an underwater target, reliable estimation of the target position is required. While USBL measurements provide target position measurements at low but regular update rate, multibeam sonar imagery gives high precision measurements but in a limited field of view. This paper describes the development of the tracking filter that fuses USBL and processed sonar image measurements for tracking underwater targets for the purpose of obtaining reliable tracking estimates at steady rate, even in cases when either sonar or USBL measurements are not available or are faulty. The proposed algorithms significantly increase safety in scenarios where underwater vehicle has to maneuver in close vicinity to human diver who emits air bubbles that can deteriorate tracking performance. In addition to the tracking filter development, special attention is devoted to adaptation of the region of interest within the sonar image by using tracking filter covariance transformation for the purpose of improving detection and avoiding false sonar measurements. Developed algorithms are tested on real experimental data obtained in field conditions. Statistical analysis shows superior performance of the proposed filter compared to conventional tracking using pure USBL or sonar measurements.
Tubastatin A prevents hemorrhage-induced endothelial barrier dysfunction

Background Microvascular hyperpermeability resulting from endothelial barrier dysfunction (EBD) is associated with worse clinical outcomes in trauma-induced hemorrhagic shock. We have previously shown that treatment with Tubastatin A (TubA), a histone deacetylase 6 inhibitor, improves outcomes in animal models of shock. In this study, we investigate whether TubA treatment may prevent trauma-related EBD. Methods Wistar-Kyoto rats subjected to 40% hemorrhage were treated with TubA or vehicle control. Acute lung injury (ALI) was assessed histologically from tissues harvested 6 hours posthemorrhage. In vitro, human umbilical vein endothelial cells (HUVECs) were cultured in EGM BulletKit medium. Medium was exchanged for glucose-free Dulbecco’s Modified Eagle Medium (0.5% fetal bovine serum) with or without TubA, and cells were placed in an anoxic chamber (5% CO2, 95% N2, 20–48 hours). Expression of acetylated tubulin and hypoxia-inducible factor 1&agr; was measured by Western blot. Soluble Intercellular Adhesion Molecule-1 concentration within the medium, a marker of endothelial integrity, was determined using enzyme-linked immunosorbent assay. Monolayers were assessed for permeability via transwell assays using fluorescein isothiocyanate-labeled albumin. Results Rats treated with TubA had significantly reduced ALI relative to vehicle control. In vitro, TubA significantly attenuated anoxia-induced hyperpermeability, hypoxia-inducible factor 1&agr; expression, and glycocalyx shedding. Conclusions Our findings demonstrate that TubA prevents hemorrhage-induced ALI in rats. Additionally, we have shown that TubA prevents anoxia-induced EBD in vitro. Taken together, these results suggest that TubA could attenuate microvascular hyperpermeability related to hemorrhagic shock.
Identification of "Streptococcus milleri" group isolates to the species level with a commercially available rapid test system

Clinical isolates of the "Streptococcus milleri" species group were examined by conventional methods and a rapid, commercially available method for the identification of these strains to the species level. The levels of agreement between the identifications obtained with the commercially available system (Fluo-Card Milleri; KEY Scientific, Round Rock, Tex.) and conventional methods were 98% for 50 Streptococcus anginosus strains, 97% for 31 Streptococcus constellatus strains, and 88% for 17 isolates identified as Streptococcus intermedius. Patient records were also studied in order to gain information on the frequency and sites of isolation of each of the three "S. milleri" group species.
Breast reconstruction in pregnancy: a case report of multidisciplinary team approach in immediate autologous flap reconstruction for pregnancy‐associated breast cancer

This report presents the results of immediate breast reconstruction with autologous flap in Pregnancy‐associated breast cancer (PABC). There was no obstetrics and surgical complications in our report. Immediate breast reconstruction can be performed in PABC after a careful selection. Multidisciplinary team approach is the key in managing these groups of patients.
Targeting miR-21 to Treat Psoriasis

Targeting miR-21 may be a new way to treat psoriasis. A miR-21 Target in Psoriasis Psoriasis is a common inflammatory skin disease with no cure to date. Several targeted therapies are being tested in different clinical trials. Previous reports have shown that the microRNA miR-21 is expressed in psoriasis tissue, but whether miR-21 is causally involved in the disease is unclear. In new work, Guinea-Viniegra and colleagues target miR-21 using LNA-modified anti–miR-21 compounds. The authors show that antagonizing miR-21 in a psoriasis-like mouse model and in a mouse xenotransplantation model using patient-derived psoriasis tissue reduced psoriasis pathology. Thus, miR-21 may be a useful target in the treatment of psoriasis. Psoriasis is a common inflammatory skin disease with limited treatment options that is characterized by a complex interplay between keratinocytes, immune cells, and inflammatory mediators. MicroRNAs (miRNAs) are regulators of gene expression and play critical roles in many human diseases. A number of miRNAs have been described to be up-regulated in psoriasis, but their causal contribution to disease development has not been demonstrated. We confirm that miR-21 expression is increased in epidermal lesions of patients with psoriasis and that this leads to reduced epidermal TIMP-3 (tissue inhibitor of matrix metalloproteinase 3) expression and activation of TACE (tumor necrosis factor–α–converting enzyme)/ADAM17 (a disintegrin and metalloproteinase 17). Using patient-derived skin samples and mouse models of psoriasis, we demonstrate that increased miR-21 may be a consequence of impaired transcriptional activity of Jun/activating protein 1 (AP-1), leading to activation of the interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (Stat3) pathway. Inhibition of miR-21 by locked nucleic acid (LNA)–modified anti–miR-21 compounds ameliorated disease pathology in patient-derived psoriatic skin xenotransplants in mice and in a psoriasis-like mouse model. Targeting miR-21 may represent a potential therapeutic option for the treatment of psoriasis.