Digital Commons Network^™

Chemotherapy In Synergy With Innate Immune Agonists Enhances T Cell Priming For Checkpoint Inhibitor Treatment In Pancreatic Cancer, Nan Niu, Keyu Li, Junke Wang, Vanessa Funes, Birginia Espinoza, Pan Li, Jianxin Wang, Melissa Lyman, Mengni He, Brian Herbst, Michael Wichroski, Ruslan Novosiadly, Sami Shoucair, Yiping Mou, Lei Zheng

Faculty, Staff and Student Publications

Background: The combination of conventional chemotherapy and immune checkpoint inhibitors (ICIs) has been unsuccessful for pancreatic ductal adenocarcinoma (PDAC). Administration of maximum tolerated dose of chemotherapy drugs may have immunosuppressive effects.

Methods: We thus tested, by using the preclinical model of PDACs including the genetically engineered mouse KPC spontaneous pancreatic tumor model and the pancreatic KPC tumor orthotopic implant model, the combinations of synthetic innate immune agonists including STING and NLRP3 agonist, respectively, and ICIs with or without chemotherapy.

Results: We found that innate agonists potentiate the role of chemotherapy in inducing effector T cells and subsequently to prime the …

Immuno-Bioinformatics Study Of Secondary Metabolites From Watercress Nasturtium Officinale As Immunostimulant In Whiteleg Shrimp Litopenaeus Vannamei By Targeting Peroxinectin And Scavenger Receptor Class B, Qurrota A’Yunin, Muhaimin Rifa’I, Maftuch Maftuch, Yoga Dwi Jatmiko, Muhammad Hermawan Widyananda, Triyanto Triyanto, Muhammad Tegar Handrianto

Karbala International Journal of Modern Science

The viral disease affects the whiteleg shrimp (Litopenaeus vannamei) and causes losses. Immunostimulants are recognized as a more environmentally friendly approach to disease management and antimicrobial properties of aquatic organisms. Watercress (Nasturtium officinale) is an aquatic plant species that contains antioxidant properties that can protect the organism from disease and boost the immune system. Shrimp rely heavily on innate immunity to combat infectious agents due to their absence of adaptive immunity. Peroxinectin and scavenger receptor class B (SRB) play essential roles in the shrimp defense system. This research employs a bioinformatic to assess the immunostimulatory potential …

Development And Characterization Of Cd44-Targeted X-Aptamers With Enhanced Binding Affinity For Cancer Therapeutics, Hongyu Wang, Weiguo He, Miguel-Angel Elizondo-Riojas, Xiaobo Zhou, Tae Jin Lee, David G Gorenstein

Faculty, Staff and Student Publications

CD44, a pivotal cell surface molecule, plays a crucial role in many cellular functions, including cell-cell interactions, adhesion, and migration. It serves as a receptor for hyaluronic acid and is involved in lymphocyte activation, recirculation, homing, and hematopoiesis. Moreover, CD44 is a commonly used cancer stem cell marker associated with tumor progression and metastasis. The development of CD44 aptamers that specifically target CD44 can be utilized to target CD44-positive cells, including cancer stem cells, and for drug delivery. Building on the primary sequences of our previously selected thioaptamers (TAs) and observed variations, we developed a bead-based X-aptamer (XA) library by …

Genome-Wide Profiling Of Trna Modifications By Induro-Trnaseq Reveals Coordinated Changes, Yuko Nakano, Howard Gamper, Henri Mcguigan, Sunita Maharjan, Jiatong Li, Zhiyi Sun, Erbay Yigit, Sebastian Grünberg, Keerthana Krishnan, Nan-Sheng Li, Joseph Piccirilli, Ralph Kleiner, Nicole Nichols, Brian Gregory, Ya-Ming Hou

Department of Biochemistry and Molecular Biology Faculty Papers

While all native tRNAs undergo extensive post-transcriptional modifications as a mechanism to regulate gene expression, mapping these modifications remains challenging. The critical barrier is the difficulty of readthrough of modifications by reverse transcriptases (RTs). Here we use Induro-a new group-II intron-encoded RT-to map and quantify genome-wide tRNA modifications in Induro-tRNAseq. We show that Induro progressively increases readthrough over time by selectively overcoming RT stops without altering the misincorporation frequency. In a parallel analysis of Induro vs. a related RT, we provide comparative datasets to facilitate the prediction of each modification. We assess tRNA modifications across five human cell lines and …

Influence Of High Eimeria Tenella Immunization Dosages On Total Oocyst Output And Specific Antibodies Recognition Response In Hybrid Pullets (Gallus Gallus)-A Pilot Study, Marco A. Juarez-Estrada, Guillermo Tellez-Isaias, Victor M. Petrone-Garcia, Amanda Gayosso-Vazquez, Xochitl Hernandez-Velasco, Rogelio A. Alonso-Morales

Political Science Faculty Publications and Presentations

Background: Two high primary-immunization doses of a wild-type E. tenella strain were assessed in healthy pullets (5K versus 10K sporulated oocysts/bird) to understand the effects of coccidia infection. Methods: Acquired immunity was evaluated following primary immunization and two booster doses with the homologous strain. Total oocyst shedding, clinical signs, and viability of every bird/group after each immunization/booster were recorded. Indirect ELISA measured the time course of humoral responses from each immunization group against sporozoite and second-generation merozoite of E. tenella. Antigen pattern recognition on these two asexual zoite stages of E. tenella was analyzed using Western blotting with antibodies from …

Sigma1 Inhibitor Suppression Of Adaptive Immune Resistance Mechanisms Mediated By Cancer Cell Derived Extracellular Vesicles, Paola A. Castagnino, Derick A. Haas, Luca Musante, Nathalia A. Tancler, Bach V. Tran, Rhonda Kean, Alexandra R. Steck, Luis A. Martinez, Elahe A. Mostaghel, D. Craig Hooper, Felix J. Kim

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Adaptive immune resistance in cancer describes the various mechanisms by which tumors adapt to evade anti-tumor immune responses. IFN-γ induction of programmed death-ligand 1 (PD-L1) was the first defined and validated adaptive immune resistance mechanism. The endoplasmic reticulum (ER) is central to adaptive immune resistance as immune modulatory secreted and integral membrane proteins are dependent on ER. Sigma1 is a unique ligand-regulated integral membrane scaffolding protein enriched in the ER of cancer cells. PD-L1 is an integral membrane glycoprotein that is translated into the ER and processed through the cellular secretory pathway. At the cell surface, PD-L1 is an immune …

The Economics And Productivity Of Us Cow-Calf Production, Richard Nehring, Hannah Shear, Kelvin L. Leibold, Andrew Swanson

Journal of Applied Farm Economics

We explore US beef cow-calf production in 2018 and estimate net returns, returns to scale, and technical efficiency associated with backgrounding versus nonbackgrounding by size and production system. We determine the relative profitability of cow-calf operations by type, region, and size. Results, using both stochastic production frontier analysis and data envelopment analysis, indicate that larger operations tend to be more scale and technically efficient than smaller operations. While larger operations may be more scale and technically efficient and have lower variable costs per cow, off-farm income helps smaller operations become competitive. The availability of detailed cost of production information in …

Review Of New Treatment Options For Toxoplasmosis, Kiley Roman

D.U.Quark

Toxoplasmosis is an infectious disease caused by the parasite, Toxoplasma Gondii. The parasite is often carried in cats and contaminated food and water. Toxoplasmosis is not serious most of the time but can be harmful to immunocompromised people, pregnant women, and their fetuses or babies. Treatments are commonly given to the immunocompromised. However, there are problems with the current treatments, in which they only treat active parasites and cannot remove the cysts created by disease progression. Due to the treatments’ inability to remove cysts, an infected person may not fully recover from the infection. This review evaluated the new …

Relative Chronology Of The Proto-Historic Remains At Naḥal Saflul 71 In The Gal‘Ed Hills (Hebrew, Pp. 1*–20*; English Summary, Pp. 221–223), Nimrod Getzov

'Atiqot

Two areas were excavated (A, B) at the site, and a report on Meir’s Excavation C (1976–1982) is included as well. Six round, rock-hewn pits were exposed in Area A, all of which probably belong to one system. In Area B, three natural steps were found on bedrock, as well as part of a pressing installation(?) for wine or oil production. Areas A and B were covered with gray soil that contained stones, potsherds, flint items and animal bones. The site also yielded limestone and basalt vessels, pottery spindle weights, bone points and archaeozoological remains. The pottery at the site …

Excavations At Tel Lod: Remains From The Pottery Neolithic A, Chalcolithic, Early Bronze Age I, Middle Bronze Age I And Byzantine Periods (Pp. 141–218), Edwin C.M. Van Den Brink, Liora Kolska Horwitz, Robert Kool, Nili Liphschitz, Henk K. Mienis, Vladimir Zbenovich

'Atiqot

The salvage excavations at the ancient tell of Lod revealed six strata (I–VI). Stratum I consisted of much-disturbed topsoil. The partial remains of three buildings were uncovered in Stratum II, dated to the Byzantine period. Stratum III consisted of sand deposits with a high concentration of MB I potsherds. Stratum IV represented the main phase of human occupation at the site, containing the remains of two superimposed settlements (Strata IVa, IVb), dating from the later phases of EB I. Stratum IVa revealed segments of three sundried mud-brick walls, lacking stone foundations; a large storage jar was found sunk into a …

Tell Qasile (North): Remains Of A Pre-Ghassulian Structure On Fichmann Street, Tel Aviv (Pp. 131–139), Ronit Lupu, Ayelet Dayan Israel Antiquities Authority

'Atiqot

The excavation revealed remains of walls, living surfaces, pottery sherds, flint artifacts, stone vessels and animal bones that can be attributed mainly to Pre-Ghassulian entities dating within the first half of the fifth millennium BCE. The small assemblage of finds from the site suggests a chrono-cultural attribution within the transitional period between the late Wadi Rabah and the beginning of the Ghassulian Chalcolithic cultures. The faunal assemblage comprises mainly sheep/goat remains, as well as a single hippopotamus(?) bone. The site represents an important milestone in the research of late prehistory in the Tel Aviv area, attesting to the presence of …

Abu Ghosh, Jasmine Street: A Pre-Ghassulian Site In The Judean Hills (Pp. 85–130), Ianir Milevski, Ofer Marder, Henk K. Mienis, Liora Kolska Horwitz

'Atiqot

The excavations at Abu Ghosh revealed two phases dated to the Pre-Ghassulian period, between the end of the sixth millennium and the mid-fifth millenium BCE. Three archaeological-sedimentary layers were identified at the site: Layer I—topsoil, Layer II—possibly EB I, and Layer III—Pre-Ghassulian. The architecture of Layer III consisted of rectilinear units, with apparent passages and entrances between them, whose walls were built on stone foundations. Most of the pottery shows affinities with the Qatifian-Besorian horizons typical of southern sites. The lithic assemblages are characterized by sickle blades, bifacials and perforators. The groundstone tools and stone bowls are characteristic of repertories …

Beisamun: An Early Pottery Neolithic Site In The Hula Basin (Pp. 1–61), Hamoudi Khalaily, Tali Kuperman, Nimrod Marom, Ianir Milevski, Dmitry Yegorov

'Atiqot

The excavation was conducted along the western fringes of the site of Beisamun. Three areas were opened (Areas A–C), revealing four layers. Layer I, the upper layer, is a dark brown clayey soil, which contained few archaeological finds. Layer II is a gray-brown clayey soil, rich in organic material and ash—most of the artifacts and architectural remains, dating to the Pottery Neolithic, were found in this layer. Layer III (in Area C) was rich in architectural remains dating to the Pre-Pottery Neolithic period. The lowest layer (Layer III in Areas A and B; Layer IV in Area C) is of …

Neolithic Flint Workshops At Giv‘At Rabi (East) In Lower Galilee (Pp. 63–83), Omry Barzilai, Ianir Milevski Israel Antiquities Authority

'Atiqot

This article presents the flint assemblages from the Neolithic workshops exposed at Giv‘at Rabi (East), which produced bidirectional blades, unidirectional blades and bifacial tools. The Neolithic blades were produced from wide cores with relatively few preparations. The bifacial tools included unfinished and finished cortical axes and adzes. These techno-typological characteristics suggest that the workshops at Giv‘at Rabi (East) should be dated to the Final Pre-Pottery Neolithic (PPNB) and the Early Pottery Neolithic (PN) periods. The discovery of the Neolithic workshops at Giv‘at Rabi (East) contributes to our understanding of the organization of the lithic industries in the region of Lower …

Excavations At The Dar El-Gharbiya Neighborhood Of Kafr Yasif: A Crusader Estate In The Territory Of ‘Akko (With A Contribution By Yael Gorin-Rosen)(Pp. 233–261), Danny Syon, Edna J. Stern

'Atiqot

Six excavation squares and three test trenches were opened. In Square A, a building was unearthed, probably first constructed in the Byzantine period and reused, probably as a stable, in the Crusader period (twelfth century); the last phase of the building (also a stable?) dates to the Mamluk period (fourteenth–fifteenth centuries). The earliest architectural stratum in Squares B and D dates to the late Byzantine or Early Islamic period, followed by an architectural phase from the Crusader period (the twelfth century); the last phase, including a water system, dates to the Mamluk period. Square C contained a large quantity of …

Middle Bronze Age Iia And Later Settlement Remains Near Yehud On The Coastal Plain (Pp. 131–174), Edwin C.M. Van Den Brink, Oren Shmueli, Eli Yannai, Liora Kolska Horwitz, Eyal Vadaei

'Atiqot

Three areas (A–C) were excavated and six archaeological strata were identified. Area A yielded sparse remains of the late Byzantine (Stratum I), Persian (Stratum II) and transitional Iron Age II/Persian (Stratum III) periods. Area B yielded the poorly preserved remains of a pottery kiln of the vertical or up-draft type, dated by pottery to the late Byzantine period. Area C yielded three strata (VI–VIII) with sparse remains dating from MB IIA. The pottery included local wares and imports from Cyprus, analogous to the finds from the Palace III phase at Afeq, between the end of MB IIA and the beginning …

Rescue Excavations At The Early Bronze Age Site Of Qiryat Ata––Area S (With A Contribution By Hamoudi Khalaily) (Pp. 63–98), Amir Golani

'Atiqot

The excavations in Area S, within the Early Bronze Age site of Qiryat Ata, revealed four settlement phases, all of which are associated with EB II (General Site Stratum I). Phase 4 consists of several beaten-earth surfaces and a few architectural remains. Two adjacent and nearly complete structures (Structures 1 and 2) were exposed in Phase 3; they appear to have been part of a much larger building complex. In Phase 2, a large architectural unit was unearthed (compound? insula?), comprising several buildings of irregular plan around an open courtyard; the nature of this compound may indicate a public function. …

Animal-Based Economy And Local Ecology: The Early Bronze Age Ii Fauna From Qiryat Ata––Area S (Pp. 99–109), Edward F. Maher

'Atiqot

The species exploited at Qiryat Ata are dominated by domestic animals, the most common being sheep and goats. Very few wild animals are present in the assemblage, comprising less than 6% of the identifiable remains, including fallow deer, wild pig and sea turtle.

Faunal Remains From The Early Bronze Age Site Of Qiryat Ata—Area N (Pp. 45–57), Nuha Agha

'Atiqot

The assemblage consists of animal remains recovered from clear stratigraphic EB IB (N = 64) and EB II (N = 66) contexts. The identified remains were of livestock—sheep, goats, cattle and pigs—and a few wild animals, such as mountain gazelle and fallow deer. The age of the cattle remains in the EB II phase attests that most animals reached maturity; hence, their value was in secondary products, such as milk and/or labor, rather than their meat. In both periods, hunting of wild animals played only a marginal role in the economy of the site. These finds revealed that the transition …

Rescue Excavations At The Early Bronze Age Site Of Qiryat Ata––Area N (Pp. 11–44), Amir Golani

'Atiqot

The excavations in Area N revealed building remains attributed to four phases, dating to EB IB (General Strata III–II) and EB II (General Stratum I). In Phase 4, structures with rounded outer corners were uncovered, characteristic of EB IB and early EB II in the southern Levant. During Phases 3–1, dated to EB II, smaller and more compact spaces were created, pointing to ongoing renovations in the buildings. These complex architectural remains may represent evidence of social organization at a time when the site was apparently a fully urbanized settlement. The ceramic finds fit in well with the pottery corpus …

Three Canaanite Design Scarabs, One Egyptian Obsidian Scarab And One Syrian Cylinder Seal From A Burial Cave Near Ras ‘Ali, In Naḥal Zippori (Pp. 1–11), Baruch Brandl

'Atiqot

Four scarabs and a cylinder seal were unearthed in a burial cave near Ras ‘Ali, in Naḥal Zippori. Three of the scarabs are made of glazed steatite and one, of obsidian; the seal is made of serpentine. The three glazed steatite scarabs are locally made Canaanite products, while the obsidian scarab seems to have been imported from Egypt. The cylinder seal is a Syrian product that was imported from the Syrian coast, most probably from Ugarit. All the glyptic finds are typical of MB IIC in Canaan (sixteenth century BCE).

Crusader, Ayyubid And Mamluk-Period Remains From Tiberias (Pp. 183–208), Edna J. Stern

'Atiqot

The excavation exposed five primary phases of occupation, dating from the Roman to the Ottoman periods. In Phase 5, accumulations containing Roman- to Fatimid-period pottery were found. In Phase 4, a building was erected, a small part of which was excavated; twelfth-century pottery was found, as well as some residual sherds dating to the Umayyad, Abbasid and Fatimid periods. Phase 3 continued the use of the Phase 4 building, with the addition of walls and the raising of floors; finds on the floor included pottery vessels, glass vessels and a stone mortar, all dating to the thirteenth century. Phase 2 …

The Fatimid, Crusader And Mamluk–Early Ottoman Ceramic Finds From The ‘Akko Marina: Some Insights Into Medieval Maritime Activity (Pp. 139–168), Edna J. Stern

'Atiqot

Ceramic sherds, dating from the Fatimid, Crusader and Mamluk–early Ottoman periods (eleventh to c. sixteenth centuries CE), were found while deepening the ‘Akko Marina. Of the Fatimid period, only a cooking bowl and a glazed bowl are represented. The pottery dating to the Crusader period consists of different types of glazed bowls, cooking ware, amphorae, a lid and oil lamps. The few sherds from the Mamluk–early Ottoman period belong to glazed vessels. The pottery retrieved from the ‘Akko Marina might have originated in trade, served as ballast, or may have arrived with pilgrims, merchants or other individuals who came to …

The Burial Ground At Ḥorbat Za‘Aq (Pp. 1–23), Irit Yezerski

'Atiqot

Thirty-two rock-cut burial tombs were documented in the burial ground excavated at Ḥorbat Za‘aq, in the southern Judean Shephelah. The majority of the tombs date to Iron Age IIB–III; one tomb (Tomb 13) dates to MB IIB–C; another (Tomb 48), to the Roman or Byzantine period; and two tombs (Tombs 22 and 23) were reused in the Early Roman period. These tombs probably belonged to families who lived in villages or farms in the vicinity of the burial ground. The Iron Age IIB–III rock-cut tombs at H. Za‘aq were hewn according to local architectural traditions; however, they share certain features …

The Finds From The Ḥorbat Za‘Aq Burial Ground (Pp. 25–70), Irit Yezerski, Pirhiya Nahshoni

'Atiqot

The bulk of the finds from the Ḥorbat Za‘aq burial ground comprise Iron Age pottery, with MB IIB–C artifacts originating in a single tomb (Tomb 13) and Roman finds from a number of others. The MB IIB–C ceramic assemblage is domestic in nature, comprising bowls, storage jars and juglets. The Iron Age IIB–III grave goods include pottery, metal artifacts and beads that are comparable to assemblages from Judahite settlements and burial sites. The finds consist mainly of small vessels, such as lamps, bowls, jugs and juglets. This Iron IIB–III pottery assemblage is typical of the second quarter of the eighth …

An Early Islamic Settlement And A Possible Open-Air Mosque At Eilat (With A Contribution By Tamar Schick) (Pp. 129–165), Yehudah Rapuano

'Atiqot

Salvage excavations were carried out in the southernmost sector of an Early Islamic settlement within the industrial zone of Eilat. Three separate, rectilinear building units were uncovered, situated in close proximity to one another, each comprising rooms and courtyards. This Early Islamic village was part of a wider phenomenon of settlements that flourished on the desert periphery, in the shadow of the ancient port city of Ayla. After its abandonment, in the later part of the eighth century, the site was briefly reused, evidently in the ninth century; this use is marked by pits, some of which contained burials.

A Site From The Roman And Byzantine Periods At Khirbat El-Burj (With Contributions By Robert Kool And Moshe Sade) (Hebrew, Pp. 1*–30*; English Summary, Pp. 167–169), Ilan Peretz, Pirhiya Nahshoni

'Atiqot

The site is located at the foot of the Hebron Hills, one kilometer south of Tell Beit Mirsim. Two areas were excavated (Areas A and B). In Area A, a row of three rooms, possibly associated with a Roman bathhouse, was exposed. The artifacts recovered from the fills and the floors included tubuli, ceramic tiles and segments of mosaic panels, as well as fragments of pottery and glass vessels, and three coins. These finds date mostly to the Late Roman and early Byzantine periods (end of third–fifth centuries CE). In Area B, the remains of a plastered installation, partly built …

Two Roman–Byzantine Subsurface Features At Ḥorbat Qastra (Castra), At The Foot Of Mount Carmel (Pp. 71–127), Edwin C.M. Van Den Brink, Orit Rutgaizer, Yael Gorin-Rosen, Liora K. Horwitz, Nili Liphschitz, Henk K. Mienis

'Atiqot

Two subterranean features were uncovered at Ḥorbat Qastra, situated on the southern outskirts of Haifa: Cave 1070, probably a reservoir, including two adjoining chambers (possibly a ritual bath, miqveh); and Cave 1071, consisting of two chambers, probably intended for dwelling. The caves yielded many restorable glass vessels, as well as pottery, dating from the fourth to seventh/eight centuries CE. The glass finds are characterized by their homogeneous fabric, workmanship and forms, indicating the existence of a local production center. Charred pieces of wood and a few carbonized seeds were found in Cave 1071, belonging to five species that still grow …

Early Bronze Age Fauna From Qiryat Ata—Area O (Pp. 61–70), Liora Kolska Horwitz

'Atiqot

Extensive salvage excavations at the site of Qiryat Ata exposed faunal remains dating to the three phases identified at the site: Phase 3, Early Bronze Age IB; Phase 2, Late Early Bronze Age IB; and Phase 1, Early Bronze Age II. The most common species in the Phase 3 assemblage is pig, followed by sheep/goat and cattle. For Phase 2, remains of cattle are the most numerous, followed by pig, with only scarce remains of sheep/goat. The largest proportion of identified bones from Area O was recovered from Phase 1: cattle predominate, with smaller numbers of pig and sheep/goat remains, …

Rescue Excavations At The Early Bronze Age Site Of Qiryat Ata—Area O (With Contributions By Raphael Greenberg, Hamoudi Khalaily And Henk K. Mienis) (Pp. 27–60), Amir Golani

'Atiqot

The excavation at Qiryat Ata, Area O, was undertaken in the southern, peripheral zone of the site. Three primary settlement episodes were revealed: Phases 3 and 2 date to EB IB and consist of two buildings and associated surfaces, while Phase 1 dates to EB II and mainly consists of a large fortification wall. These three phases correlate with the three main occupation strata (III–I) that have been identified at the site. The finds in Area O include two large and homogenous pottery assemblages, dating to EB IB and EB II; four cylinder-seal impressions; flints, representing a relatively ‘clean’ EB …