Judahite Refortification of the Lachish Frontier

Throughout the history of Judah a series of fortification systems was constructed to assist in the military protection of Judah. These systems changed over time in order to meet the military and political situations then present in the Levant. This thesis is a study of the changing patterns of fortification in southwest Judah throughout its existence. Prior to the time of Rehoboam, Israel and Judah were protected first by the mobile armies of Saul and David and later by four major centers which garrisoned the troops of Solomon. Additional Solomonic fortification was erected for internal usage in what became known as the Levitical Cities. After the division of the Israelite kingdom and the creation of an independent Judah the earlier systems were destroyed during an Egyptian raid. Rehoboam refortified Judah by constructing major defensive walls around the cities of Judah and by creating a military observation system throughout the hill country of Judah which allowed for rapid transmission of information and for quickly military deployment during a crisis. This system was altered during the reigns of Asa and Jehoshaphat when the observation points were populated and strongly fortified, becoming well defneded cities. Also the other major cities were strengthened. Lachish, having first been occupied as an observation point during the reign of Rehoboam, became the focal point in the system as well as Judah’s largest and strongest fortress outside of Jerusalem. For added defense of southern and western Judah, a subsidiary fortification line was constructed along the Lachish frontier. This subsidiary fortification line placed extended observation points along the wadi system of the northwest Negeb and Philistine Plain, and probably marked the limit of settled agrarian life at this time, the border of Judah. Through the end of the 8th century BCE, Judahite fortification kept utilizing the same plan. The Assyrian conquest of Judah ended the systematic fortification of Judah. A later 7th century BCE system, centered around Lachish and Azekah, was constructed, but it was oriented in a different manner and is not yet understood. The Babylonian conquest of Judah between 589 and 586 BCE ended the political entity of Judah and with it Judahite fortification

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Historical geography and its impact on the analysis and publication of excavated ceramics in the British and American traditions of Palestinian archaeology

For the past century the archaeological discipline of Palestine has concentrated its efforts in the collection of ever more precise stratigraphic data and in ever more refined ceramic chronological study in order to determine the most specific archaeological history possible for all sites examined. Such data have then been compared with textual evidence to prepare geographic studies of ancient Palestine. Throughout the history of the discipline its practitioners have attempted to go beyond history and examine the material culture of ancient Palestine, but almost all such efforts have ended in failure because of an anomaly in the paradigm which defines the discipline. Petrie and Bliss assumed a static site formation model which did not allow for the subsequent redeposition of materials from one layer to another. This movement in materials has been recognized for about fifty years, but its implication for the study of non-chronologically indicative materials has not been examined previously. In order to go beyond chronology and interpret non-chronological aspects of material culture from within the stratigraphic matrix it will be necessary to formulate a new site formation model to replace the Petrie-Bliss paradigm with a new dynamic paradigm

Historical geography and its impact on the analysis and publication of excavated ceramics in the British and American traditions of Palestinian archaeology

For the past century the archaeological discipline of Palestine has concentrated its efforts in the collection of ever more precise stratigraphic data and in ever more refined ceramic chronological study in order to determine the most specific archaeological history possible for all sites examined. Such data have then been compared with textual evidence to prepare geographic studies of ancient Palestine. Throughout the history of the discipline its practitioners have attempted to go beyond history and examine the material culture of ancient Palestine, but almost all such efforts have ended in failure because of an anomaly in the paradigm which defines the discipline. Petrie and Bliss assumed a static site formation model which did not allow for the subsequent redeposition of materials from one layer to another. This movement in materials has been recognized for about fifty years, but its implication for the study of non-chronologically indicative materials has not been examined previously. In order to go beyond chronology and interpret non-chronological aspects of material culture from within the stratigraphic matrix it will be necessary to formulate a new site formation model to replace the Petrie-Bliss paradigm with a new dynamic paradigm

Reinforcement magnitude and pausing on progressive-ratio schedules

Rats responded under progressive-ratio schedules for sweetened milk reinforcers; each session ended when responding ceased for 10 min. Experiment 1 varied the concentration of milk and the duration of postreinforcement timeouts. Postreinforcement pausing increased as a positively accelerated function of the size of the ratio, and the rate of increase was reduced as a function of concentration and by timeouts of 10 s or longer. Experiment 2 varied reinforcement magnitude within sessions (number of dipper operations per reinforcer) in conjunction with stimuli correlated with the upcoming magnitude. In the absence of discriminative stimuli, pausing was longer following a large reinforcer than following a small one. Pauses were reduced by a stimulus signaling a large upcoming reinforcer, particularly at the highest ratios, and the animals tended to quit responding when the past reinforcer was large and the stimulus signaled that the next one would be small. Results of both experiments revealed parallels between responding under progressive-ratio schedules and other schedules containing ratio contingencies. Relationships between pausing and magnitude suggest that ratio pausing is under the joint control of inhibitory properties of the past reinforcer and excitatory properties of stimuli correlated with the upcoming reinforcer, rather than under the exclusive control of either factor alone