Miracle-dz/UniFAR-FTUs huggingface dataset:
Mapping of the Antibody and T Cell Recognition Profiles of the HN Domain (Residues 449–859) of the Heavy Chain of Botulinum Neurotoxin A in Two High-Responder Mouse Strains

Using a set of synthetic overlapping peptides, encompassing the entire N-terminal domain (HN,) of the heavy (H) chain of botulinum neurotoxin serotype A (BoNT/A), we have mapped on HN, the regions recognized by Abs (B cells) and by T cells in two inbred mouse strains. After one BoNT/A toxoid injection, BALB/c T cells mounted a weak in vitro response to a region within overlap 687–705/701–719. The remaining peptides stimulated no detectable responses. After 3 injections, BALB/c T cells gave stronger responses to an expanded region within the overlap 687–705/701–719/715–733, peaking at 701–719. BoNT/A-primed BALB/c T cells showed substantial cross-reaction with BoNT/B but did not respond to TeNT. Unlike BALB/c T cells, BoNT/A-primed T cells of SJL cross-reacted well with both BoNT/B and with TeNT. They also recognized a lager epitope profile than the corresponding BALB/c T cells. After one injection with BoNT/A toxoid, SJL T cells responded in vitro to a number of the HN peptides. Regionswithin peptides 617–635 and 561–579 stimulated strong in vitro responses. Several peptides (463–481, 589–607, 659–677, 729–747, 827–845, and 841–859 revoked weak-to-medium proliferative activities. Four other peptides stimulated very low but reproducible responses (SI between 2.0 and 3.0). After 3 BoNT/A injections, SJL T cells responded in vitro strongly to peptides 463–481, 561–579, 617–635, 743–761, and 841–859. There were medium or weak responses to at least 10 other peptides. The cells also responded well to the l-chain peptide 218–231. Antisera of BALB/c and SJL, obtained after 3 injections with BoNT/A toxoid, protected at very high dilutions recipient mice against LD105 of BoNT/A. BALB/c Abs showed medium-to-high binding to peptides 533–551/547–565, 785–803, and 813–831/827–845. Four other peptides showed very low binding. The corresponding SJL Abs had high binding to the overlap 533–551/547–565/561–579, and peptides 743–761, 785–803, and 813–831. Three other peptides bound low amounts of Abs. The results indicate that the responses to each Ab or T cell epitope is under separate genetic control and that, in a given strain, the Ab and T cell recognition regions may coincide but, in addition, HN contains regions that are recognized only by Abs or only by T cells.
The influence of buprenorphine or bupivacaine on the post-operative effects of laparotomy and bile-duct ligation in rats

The post-operative effects of laparotomy and common bile-duct ligation were investigated in rats. Bile-duct ligation caused a significant reduction in food and water consumption, body weight and locomotor activity in the immediate post-operative period. Animals which underwent laparotomy in which bile-duct ligation was not carried out (sham operated groups) had significantly less depression of food and water consumption and body weight than groups which underwent bile-duct ligation. The detrimental effects on food and water consumption and body weight could be significantly reduced by the administration of buprenorphine (0·05 mg/kg, s/c), but not by infiltration of the surgical wound with the long-acting local anaesthetic agent, bupivacaine. The reduction of the depressant effects of surgery on food and water consumption by the opioid analgesic buprenorphine suggests that some of these changes may be related to the presence of post-operative pain.
Choosing wisely(®) in critical care: maximizing value in the intensive care unit.

Overuse of medical tests and treatments wastes health care resources and leads to unnecessary complications, while underuse results in delayed or missed diagnoses and treatment opportunities. Such problems are well recognized and there have been multiple attempts to correct inappropriate diagnostic testing and treatment over the past several decades. However, sustainable solutions have proven to be elusive. Several years ago, medical ethicist Howard Brody suggested that physicians take leadership in declaring what tests and interventions should be used less commonly. He recommended that professional societies develop a specialty’s top 5 list of “diagnostic tests or treatments that are very commonly ordered, that are among the most expensive services provided, and that have been shown by the currently available evidence not to provide any meaningful benefit to at least some major categories of patients. ” Dr Brody’s vision gave rise to the Choosing Wisely® Campaign, an effort designed to empower providers and patients by charging professional societies to develop lists of 5 common medical services “that patients and physicians should question. ” The top 5 list for critical care medicine was developed by the Critical Care Societies Collaborative (CCSC), a consortium representing the 4 professional societies most involved with providing care to critically ill patients—the American Association of CriticalCare Nurses, American College of Chest Physicians, American Thoracic Society, and Society of Critical Care Medicine. The critical care list is the only Choosing Wisely® list developed in partnership with a nursing professional society, which is important and noteworthy because it reflects the multiprofessional nature of critical care. The CCSC represents 150000 members; therefore, a list developed by the CCSC reflects the thinking of a wide range of stakeholders. It is hoped that such broad input will improve both the value and the acceptance of the list. The Choosing Wisely® list of the top 5 critical care services that patients and providers should question are: (1) ordering diagnostic tests at regular intervals (such as every day) rather than to answer specific clinical questions; (2) transfusing red blood cells in hemodynamically stable, nonbleeding ICU patients with a hemoglobin concentration of 7 g/dL or greater; (3) using parenteral nutrition in adequately nourished critically ill patients within the first 7 days of an ICU stay; (4) deeply sedating mechanically ventilated patients without a specific indication and without daily attempts to lighten sedation; and (5) continuing life support for patients at high risk for death or severely impaired functional recovery without offering patients and their families the alternative of care focused entirely on comfort (Table). The process and rationale for selecting each item on the critical care list are described in detail ©2014 American Association of Critical-Care Nurses doi: http://dx.doi. org/10.4037/ajcc2014481
Sex Differences in Human Thermoregulatory Response to Heat and Cold Stress

The current literature on male-female differences in response to thermal stress has been reviewed. Morphologically, women average 20% smaller body mass, 14% more body fat, 33% less lean body mass, but only 18% less surface area than men. Women have greater body insulation when vasoconstricted (except hands and feet) and a larger peripheral heat sink, but at the cost of (1) greater body fat burden, (2) less muscle mass and strength, and (3) smaller circulating blood volumes which requires greater physiological strain to balance heat production and loss. Under heat stress, women generally show (1) relatively more peripheral blood pooling, (2) greater heart rate increases, (3) more frequent circulatory embarassment, (4) lower maximal sweat rates, (5) higher skin temperatures with greater body heat storage, and (6) poorer maintenance of circulating blood volume with more impact from dehydration. Proportionately fewer women than men can be successfully heat acclimated. In the cold, women generally have (1) less capability for maximum heat production by either exercise or shivering, (2) a more extensively vasoconstricted periphery, (3) lower foot, hand, and mean skin temperatures, (4) greater surface heat losses, especially from the geometrically thinner extremities, (5) increased rates of extremity, but not core, cooling, and (6) relatively greater risk of cold injury.
Lyme disease or a complication of delusional parasitosis?

Australian & New Zealand Journal of Psychiatry, 48(1) severe depression with delusional thoughts about inappropriate digestive tract function, aversion to eating and further weight loss continued. We also observed further life-threatening weight loss despite a high-calorie diet. Apart from hyperthyroidism other diseases were excluded. The patient maintained compliance of all prescribed drugs (sertraline 100 mg/ day, risperidone 5 mg/day, mirtazapine 45 mg/day and methimazole 40 mg/day). Repeat blood tests showed TSH 46.8039 uIU/ml, fT4 1.47 ng/dl and fT3 1.60 pg/ml. On the basis of these results the endocrinologist diagnosed hypothyroidism. Treatment with 25 μg/day of levothyroxinum up to a dose of 150 μg/day was started and after a few weeks euthyroid (normal thyroid function) was obtained. Despite this the patient still had suicidal thoughts, nihilistic delusions and hypochondriacal delusions related to the necrobiosis of his digestive tract. As a result, ECT was commenced. The patient received a course of 12 procedures of ECT under anaesthesia every second day. Simultaneously, the patient received venlafaxine 225 mg/day and olanzapine 10 mg/day. ECT together with pharmacotherapy was effective. The patient’s mood, appetite and psychomotor drive increased and delusions with suicidal thoughts disappeared. This case report distinctly shows that the coexistence of a somatic disease (thyroid hormone imbalance) might cause a significant delay in the onset of starting ECT in patients with drugresistant depression. Therefore, it is crucial to obtain euthyroid as soon as possible, otherwise the inability to use ECT and antidepressant drugs can be fatal.
In Rat Hepatocytes Glucagon Increases Mammalian Target of Rapamycin Phosphorylation on Serine 2448 but Antagonizes the Phosphorylation of Its Downstream Targets Induced by Insulin and Amino Acids*

The major function of mammalian target of rapamycin (mTOR) is the control of cell growth. Insulin and amino acids regulate the mTOR pathway, and both are needed to promote its maximal activation. To further understand mTOR regulation by insulin and amino acids, we have studied the enzyme in primary cultures of hepatocytes. We show that insulin increases mTOR phosphorylation on Ser2448, a consensus phosphorylation site for protein kinase B (PKB). Ser2448 phosphorylation is also increased by amino acids, although they do not activate PKB. Furthermore, insulin and amino acids have an additive effect, indicating that they act through distinct pathways. We also show that phosphorylation of Ser2448 does not seem to modulate in vitro phosphorylation of eukaryotic initiation factor 4E-binding protein 1 by mTOR. However, stimulation of hepatocytes with insulin and amino acids leads to an increase in mTOR kinase activity. Rapamycin has no effect on insulin-, glucagon-, and 8-(4-chlorophenylthio)adenosine-cAMP-induced amino acid transport. Surprisingly, glucagon and 8-(4-chlorophenylthio)adenosine-cAMP, which do not activate PKB, stimulate the phosphorylation on Ser2448 of mTOR. However, glucagon inhibits amino acid- and insulin-induced activation of ribosomal S6 protein kinase 1 and phosphorylation of the translational repressor eukaryotic initiation factor 4E-binding protein 1. Our results demonstrate that glucagon, which is not able to activate but rather inhibits the mTOR pathways, stimulates the phosphorylation of mTOR on Ser2448. This finding suggests that phosphorylation of this site might not be sufficient for mTOR kinase activity but is likely to be involved in other functions.
Design considerations for high-voltage high-power full-bridge zero-voltage-switched PWM converter

A steady-state analysis is presented with complete characterization of the converter operation. A small-signal model of the converter is established. The design procedures based on the analysis are presented and the various losses in the circuit assessed. Critical design considerations for a high-power, high-voltage application are analyzed. The results of the analysis are verified using a high-voltage. 2 kW prototype. <<ETX>>
Fluid resuscitation with human albumin or hydroxyethyl starch—are there differences in the healing of experimental intestinal anastomoses?

Abstract Objectives. Restoration of the macro- and microcirculation is important for the healing of gastrointestinal anastomoses. Colloids and crystalloids are widely used for blood volume therapy. We evaluated the effects of human albumin, hydroxyethyl starch (HES) 130/0.4 and saline on the microcirculation and on wound healing in colon anastomoses in rats. Material and methods. Male Wistar rats received a colonic end-to-end anastomosis. The animals were randomized into three groups and a single 3-ml dose of either 20% human albumin, 6% HES 130/0.4 or 0.9% saline was applied intravenously. Six, 24, 48, 96 h and 2 weeks after the procedure, 10 animals per group were reanesthetized. Measurements of capillary blood flow, vessel permeability and anastomosis bursting pressure were performed. The amounts of vascular endothelial growth factor (VEGF) and IL-6 in the plasma were determined by enzyme-linked immunosorbent assays, and the mRNA levels of VEGF and collagen types I and III were measured by real-time polymerase chain reaction. Results. No significant differences were found between albumin, HES 130/0.4 and saline in capillary blood flow, vessel permeability and anastomotic bursting pressure in this rat model. Concentrations of collagen I and III mRNA were significantly elevated after 96 h in animals that had received HES 130/0.4 or albumin. RNA and protein levels of VEGF and interleukin-6 were unaffected by therapy. Conclusions. Human albumin, which is still widely used in the clinical setting, had no advantage over HES 130/0.4 and saline with regard to anastomotic healing in this animal model. Nevertheless, we prefer HES 130/0.4 because it is more effective for volume therapy than saline and has a better availability and is less expensive than human albumin.
The biology of the bile canaliculus, 1993

The bile canaliculus contains about 10% of the plasma membrane of the mammalian hepatocyte and comprises approximately 5 p,l/gm of liver in mammals. Despite application of many technologies, its contents have never been sampled in r~zuo or in cultured hepatocytes. Consequently, measurements of biliary components have been primarily performed with common duct bile that has traversed the entire biliary tract. In recent years, transport of fluorescence-labeled organic molecules has been studied with cultured hepatocyte doublets, microscopy and image analysis. Although valuable, this system is limited by artifactual closure of the bile canaliculus forming a sealed sphere, whereas the canaliculus in uiuo is a tubular structure uniting with bile ducts. For these reasons, studies have been performed with membrane vesicles, which are selectively enriched in the canalicular membrane vesicle (CMV) or sinusoidal (basolateral)
Configurations of Relationships in Different Media: FtF, Email, Instant Messenger, Mobile Phone, and SMS

This study analyzes the configurations of communication relationships in Korea through face-to-face, email, instant messaging, mobile phone, and short message service media. Through a web survey, we asked respondents to identify (1) for each of the five media (2) up to five of their most frequent communication partners, (3) the partner’s social role (including colleagues, family, friends), and (4) their own employment category. Individual-level and network-level analyses were used to compare variations in communication relationships and configurations of relationships among social roles overall, within each medium, and for different employment categories, and to identify configurations of relationships across media. IM, SMS, and mobile phone are distinctive media for students, mobile phone for homeworkers, and email for organizational workers. Moreover, mobile phones tend to be used in reinforcing strong social ties, and text-based CMC media tend to be used in expanding relationships with weak ties. Finally, face-to-face (FtF) seems to be a universal medium without significant differences across respondents’ employment categories.
Un análisis taxonómico de las políticas para PYME en Europa: Objetivos, instrumentos y empresas beneficiarias

Este trabajo trata de abordar desde una perspectiva analitica, el estudio de las politicas de apoyo a las PYME en Europa en sus tres dimensiones principales: los objetivos planteados, los instrumentos utilizados para alcanzar esos objetivos y los principales beneficiarios de las politicas. Los resultados apuntan la existencia de unos objetivos concretos vinculados a instrumentos que poseen una cierta coherencia a nivel europeo. Igualmente se obtiene un perfil bastante claro de la relevancia de las politicas orientadas al apoyo de las actividades internacionales de las empresas y a la formacion de los trabajadores. El estudio se apoya en tecnicas estadisticas de analisis multivariante
Lactobacillus rhamnosus GG and Streptococcus thermophilus induce suppressor of cytokine signalling 3 (SOCS3) gene expression directly and indirectly via interleukin‐10 in human primary macrophages

In the present study we have characterized T helper type 2 (Th2) [interleukin (IL)‐10]/Th1 (IL‐12) cytokine expression balance in human primary macrophages stimulated with multiple non‐pathogenic Gram‐positive bacteria used in the food industry and as probiotic substances. Bacteria representing Lactobacillus, Bifidobacterium, Lactococcus, Leuconostoc, Propionibacterium and Streptococcus species induced anti‐inflammatory IL‐10 production, although quantitative differences between the bacteria were observed. S. thermophilus was able to induce IL‐12 production, while the production of IL‐12 induced by other bacteria remained at a low level. The highest anti‐inflammatory potential was seen with bifidobacteria, as evidenced by high IL‐10/IL‐12 induction ratios. All studied non‐pathogenic bacteria were able to stimulate the expression of suppressor of cytokine signalling (SOCS) 3 that controls the expression of proinflammatory cytokine genes. Lactobacillus and Streptococcus species induced SOCS3 mRNA expression directly in the absence of protein synthesis and indirectly via bacteria‐induced IL‐10 production, as demonstrated by experiments with cycloheximide (CHX) and anti‐IL‐10 antibodies, respectively. The mitogen‐activated protein kinase (MAPK) p38 signalling pathway played a key role in bacteria‐induced SOCS3 gene expression. Enhanced IL‐10 production and SOCS3 gene expression induced by live non‐pathogenic Lactobacillus and Streptococcus is also likely to contribute to their immunoregulatory effects in vivo.
Improved Axillary Evaluation Following Neoadjuvant Therapy for Patients With Node-Positive Breast Cancer Using Selective Evaluation of Clipped Nodes: Implementation of Targeted Axillary Dissection.

PURPOSE Placing clips in nodes with biopsy-confirmed metastasis before initiating neoadjuvant therapy allows for evaluation of response in breast cancer. Our goal was to determine if pathologic changes in clipped nodes reflect the status of the nodal basin and if targeted axillary dissection (TAD), which includes sentinel lymph node dissection (SLND) and selective localization and removal of clipped nodes, improves the false-negative rate (FNR) compared with SLND alone. METHODS A prospective study of patients with biopsy-confirmed nodal metastases with a clip placed in the sampled node was performed. After neoadjuvant therapy, patients underwent axillary surgery and the pathology of the clipped node was compared with other nodes. Patients undergoing TAD had SLND and selective removal of the clipped node using iodine-125 seed localization. The FNR was determined in patients undergoing complete axillary lymphadenectomy (ALND). RESULTS Of 208 patients enrolled in this study, 191 underwent ALND, with residual disease identified in 120 (63%). The clipped node revealed metastases in 115 patients, resulting in an FNR of 4.2% (95% CI, 1.4 to 9.5) for the clipped node. In patients undergoing SLND and ALND (n = 118), the FNR was 10.1% (95% CI, 4.2 to 19.8), which included seven false-negative events in 69 patients with residual disease. Adding evaluation of the clipped node reduced the FNR to 1.4% (95% CI, 0.03 to 7.3; P = .03). The clipped node was not retrieved as an SLN in 23% (31 of 134) of patients, including six with negative SLNs but metastasis in the clipped node. TAD followed by ALND was performed in 85 patients, with an FNR of 2.0% (1 of 50; 95% CI, 0.05 to 10.7). CONCLUSION Marking nodes with biopsy-confirmed metastatic disease allows for selective removal and improves pathologic evaluation for residual nodal disease after chemotherapy.
An implementation of three-level BTB NPC voltage source converter based-PMSG wind energy conversion system

This paper presents an implementation of the three-level back-to-back neutral-point-clamp voltage source converter based PMSG wind energy conversion system (WECS). The generator-side converter performs the maximum power point then tracks, integrates and optimizes control with the d-axis stator current control (ZDSC), while the grid-side converter regulates the dc-link voltage and reactive power to the gird via voltage oriented control (VOC). An even simple modified unipolar CB-PWM strategy for the three-level BTB NPC VSC is implemented to simplify the modulation algorithm. The simulation results are demonstrated to provide the performance and stability of the three-level BTB NPC VSC based-PMSG WECS in both the stand-alone and grid-connected conditions.
A study of the rat neuropeptide B/neuropeptide W system using in situ techniques

In the rat, the neuropeptide B/neuropeptide W (NPB/NPW) system is composed of two ligands, neuropeptide B (NPB) and neuropeptide W (NPW), and one receptor, GPR7. Although preliminary analyses show roles in feeding, hormone secretion, and analgesia, the lack of a detailed anatomical map impairs our understanding of the NPB/NPW system. We demonstrate in this report the expression patterns of GPR7, NPB, and NPW precursor messenger ribonucleic acid (mRNA) in the rat brain by using in situ hybridization and in situ binding experiments. The amygdala expresses the highest levels of GPR7 mRNA and binding signals. Other nuclei with high levels of expression and binding are the suprachiasmatic and the ventral tuberomamillary nuclei. Moderate levels are seen in the dorsal endopiriform, dorsal tenia tecta, bed nucleus, and the red nucleus. Low levels are in the olfactory bulb, parastrial nucleus, hypothalamus, laterodorsal tegmentum, superior colliculus, locus coeruleus, and the nucleus of the solitary tract. Although the NPB precursor is mostly expressed at low levels in the brain, moderate expression is seen in anterior olfactory nucleus, piriform cortex, median preoptic nucleus, basolateral amygdala, hippocampus, medial tuberal nucleus, substantia nigra, dorsal raphe nucleus, Edinger‐Westphal nucleus, and the locus coeruleus. To our surprise, the expression of NPW precursor was not detected. Our study greatly expands the preliminary in situ data previously reported. With this map of the NPB/NPW system in the rat brain, a better understanding of the functional implications of the system in various behavioral paradigms is now possible. J. Comp. Neurol. 497:367–383, 2006. © 2006 Wiley‐Liss, Inc.