Who, When, and Why – Investigating Cultural Footprints at Early Iron Age Tel Kinrot

Ancient Kinneret (Tel Kinrot [Hebrew]; Tell el-‘Orēme [Arabic]) is located on a steep limestone hill on the northwestern shores of the Sea of Galilee (map ref. 2508.7529 [NIG]; 35.56/32.87 [WGS84]). The site, whose settlement history began sometime during the Pottery-Neolithic or the early Chalcolithic period, is emerging as one of the major sites for the study of urban life in the Southern Levant during the Early Iron Age (c. 1130–950 BCE). Its size, accessibility by major trade routes, and strategic location between different spheres of cultural and political influence make Tel Kinrot an ideal place for studying the interaction of various cultures on urban sites, as well as to approach questions of ethnicity and regionalism during one of the most debated periods in the history of the ancient Southern Levant.

Ancient History as a Means of Transforming Colonial India in the Late-Eighteenth and Early-Nineteenth Centuries

This article focuses on the studies and discourses of mostly British scholars of the early colonial period belonging to two schools of thought. It shows how the studies of both schools – European orientalism and utilitarianism – were intricately connected to the political development of the emerging British paramountcy over the South Asian sub-continent, as both were looking for means of establishing and/or strengthening colonial rule. Nevertheless, the debate was not just a continuation of discussions in Europe. Whereas the ideas of the European Enlightenment had some influence, the transformation of the Mughal Empire and especially the idea of a decline of Muslim rule offered ample opportunities for understanding the early history of India either as some sort of “Golden Age,” as the orientalists and their indigenous supporters did, or as something static and degenerate, as the utilitarians did, and from which the population of sub-continent had to be saved by colonial rule and colonial values. Fearing the spread of the ideas of the French Revolution, the first group of British scholars sought to persuade the native elites of South Asia to take the lessons of their past for the future development of their homeland. Just as the classicists back in Europe, these scholars were convinced that large-scale explanations of the past could also teach political and moral lessons for the present although it was important to deal with the distant past in an empirical manner. The utilitarians on the other hand believed that India had to be saved from its own depravity through the English language and Western values, which amounted to nothing less than the modern transformation of the true Classical Age.

Town and Countryside in early modern Hungary The Case of Sopron, c. 1500-1800

The town of Sopron (Ödenburg) is situated near the western border of Hungary at the junction of major routes of commerce, no further than 70 km from Vienna. As early as in 1291 the town had become a chartered town or free royal town, which meant the most fully-fledged municipial autonomy in this period. The town was subordinated only to the king and could represent itself in parliament from 1445. The surrounding seigniorial towns and villages often lodged an appeal with the Town Court due to its wide legal autonomy. The inhabitants of seigniorial towns and the villagers could have been under the necessity of going to the town, and the legal proceedings they experienced in Sopron may have meant a model pattern for them. The seigniorial town (oppidum) is a settlement under the landlord's authority, with limited legal privileges, concentrated mostly on agricultural production and on the exchange of products of its immediate hinterland. Sopron as a county town was gradually becoming significant during the early modern period. The county (megye) was not only the unit of administration in Hungary, but that of the autonomy of nobility, too. The importance of Sopron as a county town attracted many noblemen dwelling in Sopron county to the town. The county was one of the most densely populated in the 15-18th c., at the beginning of the 18th c., for example, the density was 32 person/km2 and it rose more than 40 p/km2 by the end of the century. The population of Sopron was approximately 3500-3700 in the middle of the 15th c., and due to the decline during the later decades some 3000 persons lived in the town in the early 16th c. According to the first national census the population of Sopron was 12600 in 1784-87. These data place Sopron at the high level of Hungarian urban hierarchy in this period. This paper will explore two significant aspects of the relation between the town and its countryside: the problems of mutual economic dependence and the role of Sopron as a centre of culture.

An experimental geochemical characterization analysis of archaeological iron from the contact period of Newfoundland and Labrador

This research uses scanning electron microscopy-energy dispersive X-ray spectrometry (SEM-EDX) and inductively coupled plasma-mass spectrometry (ICP-MS) on cross-sections of iron artifacts sectioned from along shafts to determine the elemental constituents of a collection of Inuit and European artifacts from along the coast of Labrador. Hand-wrought iron nails from early historic period (16th – 18th centuries CE) Inuit sites in Labrador were originally manufactured by and acquired from early whalers and fishers of various European nationalities. The purpose of this research was to assess if the elements in different samples are sufficiently homogeneous to be viable for a provenience analysis to discern which Inuit nails were originally derived from which European groups; the Basque, English or French. The consistent relationships between the geochemical signatures of iron nails found in Inuit sites and historic nails derived from specific European groups could provide insights into the prevalence, activity and the nature of indigenous interactions of different European nationalities in the region over time. The results show that the methods applied to evaluate the geochemistry of the nails was not sufficient to detect meaningful patterns because the nails did not demonstrate the necessary degree of chemical uniformity among different samples in the same artifacts.

Early Modern Trading Networks in Europe. Cooperation and the case of Simon Ruiz.

In the early modern period, trade became a truly global phenomenon. The logistics, financial and organizational complexity associated with it increased in order to connect distant geographies and merchants from different backgrounds. How did these merchants prevent their partners from dishonesty in a time where formal institutions and legislation did not traverse these different worlds? This book studies the mechanisms and criteria of cooperation in early modern trading networks. It uses an interdisciplinary approach, through the case study of a Castilian long-distance merchant of the sixteenth century, Simon Ruiz, who traded within the limits of the Portuguese and Spanish overseas empires. Early Modern Trading Networks in Europe discusses the importance of reciprocity mechanisms, trust and reputation in the context of early modern business relations, using network analysis methodology, combining quantitative data with qualitative information. It considers how cooperation and prevention could simultaneously create a business relationship, and describes the mechanisms of control, policing and punishment used to avoid opportunism and deception among a group of business partners. Using bills of exchange and correspondence from Simon Ruiz’s private archive, it charts the evolution of this business network through time, debating which criteria should be included or excluded from business networks, as well as the emergence of standards. This book intends to put forward a new approach to early modern trade which focuses on individuals interacting in self-organized structures, rather than on states or empires. It shows how indirect reciprocity was much more frequent than direct reciprocity among early modern merchants and how informal norms, like ostracism or signaling, helped to prevent defection and deception in an effective way.

Nervo alógeno conservado em glicerol: estudo experimental em ratos

A utilização de aloenxerto de nervo conservado em glicerol é uma alternativa a auto-enxertia em casos de lesões de nervos periféricos com perda de substância que diminui a morbidade cirúrgica e provem material suficiente para a reparação neural. O objetivo deste trabalho foi comparar o grau de reparação nervosa, utilizando análises histológica e funcional, através da interposição de enxerto autógeno (grupo A), de tubo de veia conservada em glicerol (grupo B) e de interposição de nervo alógeno conservado em glicerol (grupo C) em defeitos de 5 mm no nervo fibular de ratos Wistar. A análise histológica foi feita após o sacrifício dos animais( 6 semanas) , usando o corante azul de toluidina a 1%. No grupo A (auto-enxerto) verificou-se reação tecidual perineural e escape de fibras axonais mielinizadas para fora dos limites do epineuro que foi maior se comparada ao verificado no Grupo B (Veia autógena + glicerol) e Grupo C (aloenxerto de nervo).A avaliação funcional foi feita através da análise dos padrões das pegadas das patas posteriores dos ratos ("Walking Track Analysis"), nos períodos: pré-operatório, pós-operatório imediato, na terceira e sexta semanas. Na recuperação funcional, não houve diferença estatisticamente significativa entre os três grupos em nenhum dos períodos avaliados.

Morfologia e desenvolvimento ultraestrutural do sistema renal de embriões bovinos com idade gestacional entre 10 e 50 dias

O presente estudo teve como objetivo descrever o desenvolvimento dos sistemas renais de bovinos durante o período embrionário compreendido entre 10 e 50 dias. Embriões bovinos coletados em frigorífico foram fotografados e medidos utilizando-se o método Crow-Rump (CR) para estimar a idade gestacional. Os embriões destinados à miscroscopia óptica foram fixados em solução de Bouin para a avaliação do desenvolvimento do sistema renal, assim como suas estruturas. Alguns embriões também foram fixados em Glutaraldeído 2,5% e destinados à microscopia eletrônica de transmissão para o estudo ultraestrutural das células do sistema renal. Embriões entre o 14° e o 15° dia de desenvolvimento (E14-15) não apresentaram pronefro, mas apresentaram mesonefro, assim como indícios morfológicos que indicam sua atividade funcional. O mesonefro apresentou, no interior de suas células tubulares, inúmeras mitocôndrias e interdigitações, indicando uma alta atividade de transporte iônico. O metanefro, ou rim definitivo, iniciou seu desenvolvimento em E23-24. Os achados emonstram que a involução do mesonefro acontece simultaneamente com a diferenciação metanefrogênica. Em E45-46, já iniciando a fase fetal, o metanefro possuiu unidades filtradoras (néfrons), com seus respectivos glomérulos, túbulos contorcidos proximais e distais e alça de Henle. Nessa fase, o rim ainda não apresenta lobação externa.

Errors in lamina growth of primary olfactory axons in the rat and mouse olfactory bulb

In the adult olfactory nerve pathway of rodents, each primary olfactory axon forms a terminal arbor in a single glomerulus in the olfactory bulb. During development, axons are believed to project directly to and terminate precisely within a glomerulus without any exuberant growth or mistargeting. To gain insight into mechanisms underlying this process, the trajectories of primary olfactory axons during glomerular formation were studied in the neonatal period. Histochemical staining of mouse olfactory bulb sections with the lectin Dolichos biflorus-agglutinin revealed that many olfactory axons overshoot the glomerular layer and course into the deeper laminae of the bulb in the early postnatal period. Single primary olfactory axons were anterogradely labelled either with the lipophilic carbocyanine dye, 1,1'-dioctodecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI), or with horseradish peroxidase (HRP) by localized microinjections into the nerve fiber layer of the rat olfactory bulb. Five distinct trajectories of primary olfactory axons were observed in DLI-labelled preparations at postnatal day 1.5 (P1.5). Axons either coursed directly to and terminated specifically within a glomerulus, branched before terminating in a glomerulus, bypassed glomeruli and entered the underlying external plexiform layer, passed through the glomerular layer with side branches into glomeruli, or branched into more than one glomerulus. HRP-labelled axon arbors from eight postnatal ages were reconstructed by camera lucida and were used to determine arbor length, arbor area, and arbor branch number. Whereas primary olfactory axons display errors in laminar targeting in the mammalian olfactory bulb, axon arbors typically achieve their adult morphology without exuberant growth. Many olfactory axons appear not to recognize appropriate cues to terminate within the glomerular layer during the early postnatal period. However, primary olfactory axons exhibit precise targeting in the glomerular layer after P5.5, indicating temporal differences in either the presence of guidance cues or the ability of axons to respond to these cues. (C) 1999 Wiley-Liss, Inc.

Development of P2 olfactory glomeruli in P2-internal ribosome entry site-tau-lacZ transgenic mice

Primary olfactory neurons project their axons to the olfactory bulb, where they terminate in discrete loci called glomeruli. All neurons expressing the same odorant receptor appear to terminate in a few glomeruli in each olfactory bulb. In the P2-IRES-tau-LacZ line of transgenic mice, LacZ is expressed in the perikarya and axons of primary olfactory neurons that express the P2 odorant receptor. In the present study, we examined the developmental appearance of P2 neurons, the topographical targeting of P2 axons, as well as the formation of P2 glomeruli in the olfactory bulb. P2 axons were first detected in the olfactory nerve fiber layer at embryonic day 14.5 (E14.5), and by E15.5 these axons terminated in a broad locus in the presumptive glomerular layer. During the next 5 embryonic days, the elongated cluster of axons developed into discrete glomerulus-like structures. In many cases, glomeruli appeared as pairs, which were initially connected by a fascicle of P2 axons. This connection was lost by postnatal day 7.5, and double glomeruli at the same locus were observed in 85% of adult animals. During the early postnatal period, there was considerable mistargeting of P2 axons. In some cases P2 axons entered inappropriate glomeruli or continued to grow past the glomerular layer into the deeper layers of the olfactory bulb. These aberrant axons were not observed in adult animals. These results indicate that olfactory axons exhibit errors while converging onto a specific glomerulus and suggest that guidance cues may be diffusely distributed at target sites in the olfactory bulb.

Role for postoperative cortisol response to desmopressin in predicting the risk for recurrent Cushing`s disease

In the early postoperative period of Cushing`s disease patients, desmopressin may stimulate ACTH secretion in the remnant corticotrophic tumour, but not in nontumour suppressed cells. Objective The aim of this study is to evaluate the serum cortisol responses to desmopressin after pituitary surgery, establishing an optimal cut-off for absolute increment (Delta) of serum cortisol (F) suitable to predict recurrence risk. Design Retrospective case record study. Patients Fifty-seven Cushing`s disease patients submitted to pituitary surgery and desmopressin stimulation in the early postoperative with a long-term follow-up (20-161 months) were studied. Methods and measurements Serum cortisol levels after desmopressin test (10 mu g IV) 15-30 days after adenomectomy were used to determine Delta F (absolute increment of F: F peak - F baseline). Sensitivity and specificity of Delta F were calculated and a ROC curve was performed to establish an optimal cut-off for Delta F to predict recurrence risk. Results Fifteen patients had immediate postoperative failure (basal F > 165 nmol/l; 6 mu g/dl) and one patient was lost during the follow-up. Forty-one patients achieved initial remission and were followed-up. Five of 11 patients who recurred had Delta F > 193 nmol/l (7 mu g/dl), but none of 30 patients who remained in prolonged remission showed Delta F > 193 nmol/l after postoperative desmopressin stimulation. Conclusions Persistence of cortisol response (Delta F > 193 nmol/l) to desmopressin in the early postoperative period can help to identify Cushing`s disease patients with initial remission who present risk for later recurrence.

Mucosal and systemic anti-GAG immunity induced by neonatal immunization with HIV LAMP/gag DNA vaccine in mice

Vaccines capable of inducing mucosal immunity in early postnatal life until adulthood, protecting early sexual initiation, should be considered as strategies to vaccination against HIV. The HIV-1 GAG protein as a chimera with the lysosome-associated membrane protein (LAMP/gag), encoded by a DNA vaccine, is targeted to the endosomal/lysosomal compartment that contains class II MHC molecules and has been shown to be immunogenic in adult mice. Assuming that one such strategy could help to overcome the immunological immaturity in the early postnatal period, we have evaluated the systemic and mucosal immunogenicity of LAMP/gag immunization in neonatal mice. Intranasal immunization with LAMP/gag vaccine induced higher levels of sIgA and IgG anti-GAG antibodies in intestinal washes than did the gag vaccine. The combination of ID injections and the IN protocol with the chimeric vaccine promoted the increase of Ab levels in sera. Both vaccines induced splenic IFN-gamma- secreting cells against GAG peptide pools, as well as in vivo cytotoxic T lymphocyte (CTL) function, and increased the percentage of CD8+ T cells to the immunodominant class I peptide in gut and spleen. However, only the chimeric vaccine was able to enhance Th1/Th2 cytokine secretion in response to class II GAG peptide and to enhance IL-4-secreting cells against GAG peptides and p24 protein stimuli. Long-lasting humoral and cellular responses were detected until adult age, following neonatal immunization with the chimeric vaccine. The LAMP/gag vaccination was able to induce potent GAG-specific T and B cell immune responses in early life which are essential to elicit sustained and long-lasting mucosal and systemic humoral response. (C) 2010 Elsevier GmbH. All rights reserved.

Immunization of neonatal mice with LAMP/p55 HIV gag DNA elicits robust immune responses that last to adulthood

Successful T cell priming in early postnatal life that can generate effective long-lasting responses until adulthood is critical in HIV vaccination strategies because it prevents early sexual initiation and breastfeeding transmission of HIV. A chimeric DNA vaccine encoding p55 HIV gag associated with lysosome-associated membrane protein 1 (LAMP-1; which drives the antigen to the MIIC compartment), has been used to enhance cellular and humoral antigen-specific responses in adult mice and macaques. Herein, we investigated LAMP-1/gag vaccine immunogenicity in the neonatal period in mice and its ability to generate long-lasting effects. Neonatal vaccination with chimeric LAMP/gag generated stronger Gag-specific immune responses, as measured by the breadth of the Gag peptide-specific IFN-gamma, proliferative responsiveness, cytokine production and antibody production, all of which revealed activation of CD4+ T cells as well as the generation of a more robust CTL response compared to gag vaccine alone. To induce long-lived T and B cell memory responses, it was necessary to immunize neonates with the chimeric IAMP/gag DNA vaccine. The LAMP/gag DNA vaccine strategy could be particularly useful for generating an anti-HIV immune response in the early postnatal period capable of inducing long-term immunological memory. (C) 2010 Elsevier Inc. All rights reserved.

Influence of the Fibroblast Growth Factor Receptor 4 Expression and the G388R Functional Polymorphism on Cushing`s Disease Outcome

Context: Abnormal FGFR4 expression has been detected in pituitary tumors, especially in larger and invasive adenomas. In addition, the FGFR4 functional polymorphism G388R has been associated with poor outcome in several human malignancies. Then, we hypothesized that FGFR4 expression and genotype could be markers of adverse outcome of Cushing`s disease after transsphenoidal surgery. Objectives: The objective was to investigate whether there is an association between the postoperative outcome of Cushing`s disease (remission/recurrence) and the FGFR4 G388R genotype or the FGFR4 expression in corticotrophinomas. Design and Patients: Clinical, hormonal, and pathological data of 76 patients who underwent the first transsphenoidal surgery were retrospectively reviewed. All patients were genotyped for G388R polymorphism. FGFR4 expression was assessed by real-time PCR in 18 corticotrophinomas. Main Outcome Measures: The outcome measures included the FGFR4 G388R genotype and FGFR4 expression in postoperative remission and recurrence of Cushing`s disease. Results: Homozygosis for FGFR4 glycine (Gly(388)) allele was associated with reduced disease-free survival, in the univariate analysis (hazard ratio of 6.91; 95% confidence interval of 1.14-11.26; P = 0.028). Male gender (P = 0.036), lack of pathology confirmation (P = 0.009), and cortisol levels more than 2 mu g/dl in the early postoperative period (P < 0.001) were also significant predictors of Cushing`s disease recurrence in the univariate analysis. FGFR4 overexpression was found in 44% of the corticotrophinomas, and it was associated with lower postoperative remission rate (P = 0.009). Conclusions: Our data suggest that homozygosis for FGFR4 Gly(388) allele and FGFR4 overexpression are associated with higher frequency of postoperative recurrence and persistence of Cushing`s disease, respectively. (J Clin Endocrinol Metab 95: E271-E279, 2010)

Corneal stroma PDGF blockade and myofibroblast development

Myofibroblast development and haze generation in the corneal stroma is mediated by cytokines, including transforming growth factor-beta (TGF-beta), and possibly other cytokines. This study examined the effects of stromal PDGF-beta blockade on the development of myofibroblasts in response to -9.0 diopter photorefractive keratectomy in the rabbit. Rabbits that had haze generating photorefractive keratectomy (PRK, for 9 diopters of myopia) in one eye were divided into three different groups: stromal application of plasmid pCMV.PDGFRB.23KDEL expressing a subunit of PDGF receptor b (domains 2-3, which bind PDGF-B), stromal application of empty plasmid pCMV, or stromal application of balanced salt solution (BSS). The plasmids (at a concentration 1000 ng/mu l) or BSS was applied to the exposed stroma immediately after surgery and every 24 h for 4-5 days until the epithelium healed. The group treated with pCMV.PDGFRB.23KDEL showed lower alpha SMA+ myofibroblast density in the anterior stroma compared to either control group (P <= 0.001). Although there was also lower corneal haze at the slit lamp at one month after surgery, the difference in haze after PDGF-B blockade was not statistically significant compared to either control group. Stromal PDGF-B blockade during the early postoperative period following PRK decreases stromal alpha SMA+ myofibroblast generation. PDGF is an important modulator of myofibroblast development in the cornea. (C) 2008 Elsevier Ltd. All rights reserved.

Incidence of ipsilateral postoperative deep venous thrombosis in the amputated lower extremity of patients with peripheral obstructive arterial disease

Objective: Patients undergoing amputation of the lower limb due to peripheral arterial disease (PAD) are at risk of developing deep venous thrombosis (DVT). Few studies in the research literature report the incidence of DVT during the early postoperative period or the risk factors for the development of DVT in the amputation stump. This prospective study evaluated the incidence of DVT during the first 35 postoperative days in patients who had undergone amputation of the lower extremity due to PAD and its relation to comorbidities and death. Methods: Between September 2004 and March 2006, 56 patients (29 men), with a mean age of 67.25 years, underwent 62 amputations, comprising 36 below knee amputations (BKA) and 26 above knee amputations (AKA). Echo-Doppler scanning was performed preoperatively and on postoperative days 7 and 31 (approximately). All patients received acetylsalicylic acid (100 mg daily) preoperatively and postoperatively, but none received prophylactic anticoagulation. Results: DVT occurred in 25.8% of extremities with amputations (10 ARA and 6 BKA). The cumulative incidence in the 35-day postoperative period was 28% (Kaplan-Meier). There was a significant difference (P = .04) in the incidence of DVT between AKA (37.5%) and BKA (21.2%). Age >= 70 years (48.9% vs 16.8%, P = .021) was also a risk factor for DVT in the univariate analysis. Of the 16 cases, 14 (87.5%) were diagnosed during outpatient care. The time to discharge after amputation was averaged 6.11 days in-hospital stay (range, 1-56 days). One symptomatic nonfatal pulmonary embolism occurred in a patient already diagnosed with DVT. There was no relation between other comorbidities and DVT. The multivariate analysis showed no association between risk factors and the occurrence of DVT in the amputated extremity. DVT ipsilateral to the amputation did not influence the mortality rate (9.7%). Conclusion: The incidence of DVT in the early postoperative period (<= 35 days) was elevated principally in patients aged >= 70 years and for AKA. Patients with PAD who have recently undergone major amputations should be considered at high risk for DVT, even after hospital discharge. Given the high rate of postoperative DVT observed in this study, we now recommend prophylactic anticoagulation for these patients, but further study is needed to determine the optimal duration and efficacy of this treatment. (J Vasc Surg 2008;48:1514-9.)