Gotowa bibliografia na temat „Inc Six Moon Hill”

In this work, a survey is carried out on six MPPT algorithms which include conventional and artificial intelligence based approaches. Maximum Power Point Tracking (MPPT) algorithms are used in PV systems to extract the maximum power in varying climatic conditions. The following most popular MPPT techniques are being reviewed and studied: Hill Climbing (HC), Perturb and Observe (P&O), Incremental Conductance (INC), Open-Circuit Voltage (OCV), Short Circuit Current (SCC), and Fuzzy Logic Control (FLC). The algorithms are evaluated, analyzed, and interpreted using a Matlab-Simulink environment to show the performance and limitations of each algorithm

Background: Shoulder instability is a common diagnosis among patients undergoing shoulder surgery. Purpose: To perform a descriptive analysis of patients undergoing surgery for shoulder instability through a large multicenter consortium. Study Design: Case series; Level of evidence, 4. Methods: All patients undergoing surgery for shoulder instability who were enrolled in the MOON Shoulder Instability Study were included. Baseline demographics included age, sex, body mass index, and race. Baseline patient-reported outcomes (PROs) included the American Shoulder and Elbow Surgeons (ASES) score, Shoulder Activity Score, Western Ontario Shoulder Instability Index (WOSI), 36-Item Health Survey (RAND-36), and Single Assessment Numeric Evaluation (SANE). The preoperative physician examination included active range of motion (ROM) and strength testing. Preoperative imaging assessments with plain radiography, magnetic resonance imaging (MRI), and computed tomography were also included and analyzed. Results: Twenty-six surgeons had enrolled 863 patients (709 male, 154 female) across 10 clinical sites. The mean age for the cohort was 24 years (range, 12-63 years). Male patients represented 82% of the cohort. The primary direction of instability was anterior for both male (74%) and female (73%) patients. Football (24%) and basketball (13%) were the most common sports in which the primary shoulder injury occurred. No clinically significant differences were found in preoperative ROM between the affected and unaffected sides for any measurement taken. Preoperative MRI scans were obtained in 798 patients (92%). An anterior labral tear was the most common injury found on preoperative MRI, seen in 66% of patients, followed by a Hill-Sachs lesion in 41%. Poor PRO scores were recorded preoperatively (mean: ASES, 72.4; WOSI, 43.3; SANE, 46.6). Conclusion: The MOON Shoulder Instability Study has enrolled the largest cohort of patients undergoing shoulder stabilization to date. Anterior instability is most common among shoulder instability patients, and most patients undergoing shoulder stabilization are in their early 20s or younger. The results of this study provide important epidemiological information for patients undergoing shoulder stabilization surgery.

To achieve large-missile guidance qualification, modification, and reliability tests and analysis, the Hill Air Force Base Survivability & Vulnerability Integration Center (SVIC) has installed a six-degree-of-freedom shock and vibration system. Designed and developed by Wyle Laboratories Inc., this system in driven in the frequency range of 5 to 2000 Hz by eight electrodynamics shakers, two in each horizontal axis and four in the vertical axis. The major design concern is the coupling of the shakers through a rigid table due to kinetic and dynamic effects and the behavior of the structure. This has made the control task very challenging. A method was developed that coordinates the drive signals to compensate for cross-coupling effects. Based upon tests to date, the system is an effective, reliable, and capable test platform. In this paper, we discuss the design objectives, provide a brief description of the hardware, and elaborate on the high-speed, digital control system driving the eight electrodynamics shakers. A brief description of the test results is provided.

The continuous administration of GnRH leads to the desensitization and down-regulation of GnRH receptors on pituitary gonadotropes (Parker and Schimmer 2001 in Goodman & Gilman's The Pharmacological Basis of Therapeutics, New York: McGraw-Hill, 1541–1562). In this study, we combined the use of a GnRH analogue with calcium/naloxone association (Sciorsci et al. 2000 Immunopharmacol. Immunotoxicol. 22, 575−626) to obtain a desensitizing effect on LH receptors in an attempt to regulate spermatogenesis in dogs. Eight post-pubertal mixed breed dogs were divided into two groups: (A) four subjects were pharmacologically treated with a 30 day administration of buserelin acetate (Suprefact Aventis Pharma, Italy) 0.3 mg/each s.c. TID, associated with 0.1-mL/kg/bw i.m. injection SID of calcium gluconate 20% (New ICC, Upjohn, Italy) in which 0.4 mg/mL of naloxone hydrochloride (Diosynth, The Netherlands) was dissolved; (B) four subjects received placebo (NaCl 0.9% s.c. TID for 30 days). At the end of the treatment, hemiorchidectomy was performed and 4 months later the second testis was removed. Clinical examination of the genital tract was done by ultrasound monitoring. Before and after pharmacological treatment and until total orchidectomy, semen was collected and evaluated for macroscopic and microscopic parameters. Plasma testosterone concentration was measured twice a week by RIA. Testicular specimens were fixed in formalin solution, embedded in paraffin wax and stained with hematoxylin–eosin. The presence of germ cells and the testicular tubule diameters were analyzed using a computer assisted image analyzer (MONO system, Italy). Data were analyzed by the ANOVA test. In the treated group, all dogs showed a reduction in testicular and prostatic diameters compared to the control group. Transient elevations in testosterone concentrations were observed in response to the early injections and reached baseline levels after 8–10 days. The testosterone decline resulted in lower ejaculate volume and, at the end of treatment, azoospermia was observed. At the end of treatment, testosterone values had progressively regained normal values over 2 months and, when measured immediately before total orchidectomy, sperm concentration and motility had returned to normal. At the histological observation, seminiferous tubules showed the block of spermatogenesis at the level of spermatocytes with a statistically significant cell reduction in spermatides and spermatozoa (P < 0.001) whereas the seminiferous tubular morphometry was normal. Total orchidectomy demonstrated that a normal histological testicular structure had been restored. In the control group, no modifications were observed. As observed in a previous study (Aiudi et al. 2005 Reprod. Fert. Dev. 17(2), 280–281), GnRH induced suppression of the reproductive function in male dogs. In this study, we demonstrated that GnRH analogue associated with calcium and naloxone induces the same effect in a shorter time and that this effect is reversible. These devices designed for the shutdown of gonadal steroidogenesis and spermatogenesis would be useful for treating sex hormone-dependent syndromes such as malignant and benign prostatic tumors.

California yellowtail (CYT), Seriola dorsalis, is a promising candidate for aquaculture due to its rapid growth and high-quality flesh, particularly in markets like Japan, Australia, China, and the United States. Soy protein has shown success as a replacement for marine protein sources in CYT diets, reducing fishmeal levels, though concerns about potential intestinal inflammation persist with the inclusion of solvent-extracted soybean meal. To address this, processing strategies like fractionation, enzymatic treatment, heat treatment, and microbial fermentation have been employed to mitigate the negative impacts of soybean meal on fish nutrition and immune systems. This study focuses on optimizing soybean meal inclusion levels by incorporating advanced soy variants into CYT diets. The eight-week feeding trial, conducted in a recirculation system, featured six diets with sequential inclusion levels (0, 50, 100%) of high protein low oligosaccharide soybean meal (Bright Day, Benson Hill, St Louis, MO) and enzyme-treated soybean meal (HP 300, Hamlet Protein Inc., Findlay, OH), replacing solvent-extracted soybean. The study compares these formulations against a soy-free animal protein-based diet. At the end of the trial, fish were sampled for growth performance, body proximate composition, intestinal morphology, and immune response from gut samples. Results showed consistent FCR (P = 0.775), weight gain (P = 0.242), and high survival rate (99.4 ± 0.5%) among dietary treatments (P>0.05). Histological evaluations revealed no gut inflammation and gene expression analysis demonstrated no significant variations in immune, physiological, and digestive markers apn (P = 0.687), mga (P = 0.397), gpx1 (P = 0.279), atpase (P = 0.590), il1β (P = 0.659). The study concludes that incorporating advanced soybean meal products, replacing up to 20% of fishmeal does not negatively affect CYT’s growth and intestinal health. This suggests that all three soy sources, contributing 35% of total protein (15.4 g 100 g-1 diet), can be included in practical diets without compromising CYT’s intestinal integrity or growth. These findings have positive implications for the commercial production of CYT and future research on the incorporation of plant-based proteins in aquaculture diets.

Objective: Information about full-digital protocols for bite registration with intraoral scanners on multiple implants in the edentulous jaw is scarce. The purpose of this comparative in vivo study was to investigate the reliability and time efficiency of a novel full-digital bite registration technique for the manufacture of full-arch maxillary fixed implant prostheses. Material and methods: In ten patients, a full-arch maxillary fixed implant prosthesis was manufactured on multi-unit abutment level through an analog prosthetic workflow. The bite registration was performed with use of a screw-retained polymethyl methacrylate (PMMA) verification jig with detachable wax rim. To articulate the definitive edentulous maxillary implant cast in centric relation at the appropriate occlusal vertical dimension (OVD) to the mandibular antagonist cast, a type II articulator (Artex, Amann Girrbach) was used. Three to six months later, a full-digital bite registration was performed with use of dual-function scan bodies and bilateral connected bite pillars. The bite pillars screwed into the scan bodies were used to adjust and articulate the edentulous maxillary implant arch to the mandibular antagonist arch at the defined OVD. Treatment time for analog and digital bite registration technique was measured in each patient. The reliability of the digital bite registration technique was evaluated by 3D comparison of two sets of stereo lithographic (STL) files obtained from each patient. The three-dimensional deviation was defined along the X-, Y- and Z-axes (Geomagic Control X, 3D Systems Inc., Rock Hill, SC, USA). Results: The treatment time for digital bite registration using dual-function scan bodies and bite pillars was significantly shorter than analog bite registration with verification jig and wax rim (60.30%, SD 5.72%). Minor differences between the two techniques were observed with a linear deviation range of 1115 µm (SD 668 µm) overall, 46.2 µm (SD 731.3 µm) along the X-axis, −200.3 µm (SD 744.3 µm) along the Y-axis and 67.1 µm (SD 752.2 µm) along the Z-axis. Bilateral balanced contacts were registered in all patients during full-digital bite registration. Conclusions: The novel digital bite registration technique with dual-function scan bodies and bite pillars allows for a full-digital workflow for full-arch implant supported restorations. The digital bite workflow was 60% faster, and the overall deviation was around 1 mm, which can be considered clinically acceptable.

Robert William Fogel and G. R. Elton. Which Road to the Past? Two Views of History. New Haven and London: Yale University Press, 1983. Pp. vii, 136. Cloth, $14.95. Review by Stephen Kneeshaw of The School of the Ozarks. Emmanuel LeRoy Ladurie. The Mind and Method of the Historian. Translated by Sian Reynolds and Ben Reynolds. Chicago: University of Chicago Press, 1981. Pp. v, 310. Paper, $9.95. Review by Richard Harvey of Ohio University. John E. O'Connor, ed. American History/ American Television: Interpreting the Video Past. New York: Frederick Ungar Publishing Company, 1983. Pp. 463. Cloth, $17.50; Paper, $8.95. Review by D' Ann Campbell of Indiana University. Foster Rhea Dulles & Melvyn Dubofsky. Labor in America: A History. Arlington Heights, Illinois: Harlan Davidson, Inc., 1984. 4th edition. Pp. ix, 425. Cloth, $25.95. Paper, $15.95. Review by Robert W. Dubay of Bainbridge Junior College. Karen Ordahl Kupperman. Roanoke: The Abandoned Colony. Totowa, New Jersey: Rowman & Allanheld, 1984. Pp. viii, 182. Cloth, $24.95; Paper, $12.50. Review by John T. Reilly of Mount Saint Mary College. Kevin O'Reilly. Critical Thinking in American History: Exploration to Constitution. South Hamilton, Massachusetts: Hamilton-Wenham Regional High School, 1983. Pp. 86. Paper, $2.95. Teacher's Guides: Pp. 180. Paper, $12.95; Kevin O'Reilly. Critical Thinking in American History: New Republic to Civil War. South Hamilton, Massachusetts: Hamilton-Wenham Regional High School, 1984. Pp. 106. Paper, $2.95. Teacher's Guide: Pp. 190. Paper, $12.95. Review by James F. Marran of New Trier Township High School, Winnetka, Illinois. Michael J. Cassity, ed. Chains of Fear: American Race Relations Since Reconstruction. Westport, Connecticut: Greenwood Press, 1984. Pp. xxxv, 253. Cloth, $35.00. Review by Ann W. Ellis of Kennesaw College. L. P. Morris. Eastern Europe Since 1945. London and Exeter, New Hampshire: Heinemann Educational Books, 1984. Pp. 211. Paper, $10.00. Review by Thomas T. Lewis, Mount Senario College. John Marks. Science and the Making of the Modern World. Portsmouth, New Hampshire: Heinemann Educational Books, Inc., 1983. Pp. xii, 507. Paper, $25.00. Review by Howard A. Barnes of Winston-Salem State University. Kenneth G. Alfers, Cecil Larry Pool, William F. Mugleston, eds. American's Second Century: Topical Readings, 1865-Present. Dubuque, Iowa: Kendall/ Hunt Publishing Co., 1984. Pp. viii, 381. Paper, $8.95. Review by Richard D. Schubart of Phillips Exeter Academy. Sam C. Sarkesian. America's Forgotten Wars: The Counterrevoltuionary Past and Lessons for the Future. Westport, Connecticut: Greenwood Press, 1984. Pp. xiv, 265. Cloth, $29.95. Review by Richard Selcer of Mountain View College. Edward Wagenknecht. Daughters of the Covenant: Portraits of Six Jewish Women. Amherst: University of Massachusetts, 1983. Pp. viii, 192. Cloth, $17.50. Review by Abraham D. Kriegel of Memphis State University. Morton Borden. Jews, Turks, and Infidels. Chapel Hill and London: University of North Carolina Press, 1984. Pp. x, 163. Cloth, $17.95. Review by Raymond J. Jirran of Thomas Nelson Community College. Richard Schlatter, ed. Recent Views on British History: Essays on Historical Writing Since 1966. New Brunswick: Rutgers University Press, 1984. Pp. xiii, 524. Cloth, $50.00. Review by Fred R. van Hartesveldt of Fort Valley State College. Simon Hornblower. The Greek World, 479-323 B.C. London and New York: Methuen, 1983. Pp. xi, 354. Cloth, $24.00; Paper, $11.95. Review by Dan Levinson of Thayer Academy, Braintree, Massachusetts. H. R. Kedward. Resistance in Vichy France. New York: Oxford University Press, 1978. Paper edition 1983. Pp. ix, 311. Paper, $13.95. Review by Sanford J. Gutman of the State University of New York at Cortland.

Abstract Improved anticoagulation control results in improved outcomes, with a decrease in the incidence of bleeding and thromboembolic events. The outcomes of oral anticoagulation therapy (OAT) are dependent on the model of care used to manage warfarin therapy, with better outcomes associated with the use of a specialised anticoagulation management service (AMS), computerized decision support and increased testing frequency (facilitated by patient self-testing (PST) of the international normalised ratio (INR)) (Ansell and Hughes 1996). This study uses a novel strategy to combine the advantages of these three approaches to warfarin management. A prospective, randomized controlled cross-over study was carried out at the anticoagulation clinic of Cork University Hospital, Ireland, to test the hypothesis that supervised PST using an internet based expert system could provide comparable anticoagulation control to that provided by traditional outpatient AMS management. This was a cross-over study; patients served in both AMS and supervised PST arms, with random assignment as to the order of management. Both arms were six months in duration. Patients on established long term OAT who had internet access were eligible for enrolment. During the supervised PST arm of the study, patients measured their INR at home using the CoaguChek XS® point of care meter, (Roche Diagnostics, UK) either twice weekly, weekly or every two weeks depending on their anticoagulation control. They entered this result along with other information relating to their warfarin therapy (e.g. signs or symptoms of thrombosis or hemorrhage, missed doses, concurrent illnesses, dietary or medication changes etc) onto the CoagCare® (Zycare Inc, Chapel Hill, NC) web page. Patients with a therapeutic INR and no other issues were automatically provided with algorithm-derived dosing and repeat testing instructions. Patients with non-therapeutic results, or symptoms suggestive of thromboembolic or hemorrhagic complications, were prioritized for caregiver review according to problem severity. During the AMS arm, patients were required to attend the clinic every four to six weeks, or more frequently, if clinically indicated. Dosage adjustments were performed by the anticoagulant clinic staff using the laboratory INR and the APEX® (iSOFT, UK) computer decision support software. The primary outcome variable to assess anticoagulation control was the difference in time in therapeutic range (TTR) during the AMS management and supervised PST management period. In addition, the number of INR measurements indicative of serious under- or over-anticoagulation and the number of serious hemorrhagic or thrombotic adverse events were also compared. One hundred and sixty two patients were enrolled over a nine-month period (July 2006–April 2007). The majority of study patients were male (61.4%) and the mean age of the study population was 59.6 +/−14.3 years. One hundred and thirty two (81.5%) patients completed both arms of the study. The mean TTR during the AMS arm was 60.2% +/−19.5%, which increased to 71.4% +/− 13.6% during the PST period (p<0.001). Eighty-seven patients (65.91%) achieved better anticoagulation control during the supervised PST period. Patients measured their INR almost four times more frequently while home-testing giving a mean frequency of INR testing of 4.5 days compared with 17.4 days for the AMS period. Extreme INR values (< 1.5 and > 5.0) occurred more frequently during the AMS arm of the study (6% vs 2.4%, p<0.001). There was no significant difference in the adverse event rate between the two study periods. Table 1. Table 1. Adverse events Model of care Hemorrhagic Thromboembolic AMS Gastric bleed (INR 2.5) TIA (INR 2.2) Supervised PST None DVT (INR 1.6) DVT (1.4) Daily time to manage 70 patients ranged from 10 to 45 minutes (mean 23.19+/−9.48 mins/day). This novel system of supervised PST using an internet based expert system improves the clinical effectiveness of OAT when compared with management by a specialized anticoagulant management service.

Wind speed is the principal climatic element that drives the Marmaton season in West African sub region. It drives the season by conveying huge amount of dust across the Northeastern Nigeria. The presence of dust in the atmosphere brought by the Northeast trade winds during the Harmattan season plays a vital role in absorbing and scattering solar radiation. The study examines the spatial and temporal variations of wind speed in Northeastern Nigeria during the Harmattan season with the sole aim of ascertaining its variability, patterns and trends from1984 to 2014. Descriptive and statistics such as mean, standard deviation, coefficient of variation, and time series analysis with ArcGIS 10.3 was used in examine the temporal and spatial variations of wind speed from 1984–2014 in six synoptic stations of Northeastern Nigeria. The findings show that wind speed varied both temporally and spatially in the last three decades. The pattern of variations in the six synoptic stations shows rising trends within the study years. It was also found that latitude playing a crucial role in determining the speed of the wind in the study area and as the speed of the wind increases with increasing latitude. Keywords: Wind speed, Harmattan, Season, Northeast, Variation and ITD. References Adaramola,M.S.andOyewola,O. M. (2011). Wind Speed Distribution and Characteristics in Nigeria. Asian Research Publishing Network (ARPN). Journal of Engineering and Applied Sciences.ISSN 1819-6608.www.arpnjournals.com Amadi, S. O., Udo, S. O. and Ewona, I. O. (2014). Trends in Monthly Mean Minimum and Maximum Temperature Data over Nigeria for the Period 1950-2012. International Research Journal of Pure and Applied Physics, 2(4), 1-27. Ayoade, J.O. (2004). Introduction to Climatology for the Tropics.2nd ed. Spectrum Books Limitted, Spectrum House Ring Road Ibadan, Nigeria. Balarabe, M., Abdallah, K., and Nawawi, M. (2015). Long- Term Trend and Seasonal Variability of Horizontal Visibility in Nigerian Troposphere.Journal of Atmosphere 6:1462-1486; doi:10.3390/atmos6101462. Dahuwa, D., Promise, K. U., Umar, W., Bello, I. and Mohammed, R. (2018). Analysis of Wind Speed And Frequency InAzare North eastern Part of Nigeria. IOSR Journal of Applied Physics (IOSR-JAP) e-ISSN: 2278-4861.Volume 10, Issue 1 Ver. I. PP 09-17 www.iosrjournals.org DOI: 10.9790/4861-1001010917 www.iosrjournals.org Danlami, D., Gwari, M., Suleiman, S., and Bara, A. (2018). Temporal and Spatial variations of Groung Surface visibility during Harmattan Season in North-Eastern Nigeria.Ceylon Journal Science, 47(4), 337 – 346. DOI: http://doi.org/10.4038/cjs.v47i4.7551. Danlami, D. (2017). Spatio-Temporal Variations of Harmattan Season in Northeastern Nigeria.M.Sc. Dissertation (Not published) Submitted to the Department of Geography, Bayero University, Kano, Nigeria. De Longueville, F., Hountondji, Y. C., Henry, S. and Ozer, P. (2010). What do we Know about the Effects of Desert Dust on Air Quality and Human Health in West Africa compared to other regions? Journal: Science of Total Environment Fagbenle, R.L., Fasade, A.O., Amuludun A.K. andLala,P.O.( 1980). Wind power potentials of Nigeria. 12th Biennial conference of the West African Science Association, University of Ife, Nigeria. Getis, A., Getis, J., Bjelland, M. and Fellmann, J.D. (2011).Introduction to Geography. 13thed. The McGraw-Hill Companies, Inc., 1221 Avenue of the Americas, NY10020. Karabulut, M., Demirci, A. and Kora, F. (2012). Analysis of spatially distributed annual, seasonal and monthly temperatures in Istanbul from 1975 to 2006.World Applied Sciences Journal, 12(10), 1662-1675 Ojosu, J.O. and Salawu, R.I. (1990).An evaluation of wind energy potential as a power generation source in Nigeria.Solar & Wind Technology.ELSEVIER.Volume 7, Issue 6, 1990, Pages 663-673 Schwanghart, W. and Schutt, B. (2007). Meteorological causes of Harmattan dust in West Africa. Journal of Science Direct Geomorphology. Shuman, M. (2007) Evaluation of five GIS basedInterpolation techniques for estimating the Radonconcentration for unmeasured zip codes in thestate of Ohio, Master of Science Degree in Civil Engineering, University of Toledo, 28-29 Pp. Waewsak, J., Chancham, C., Landry, M. and Gagnon, Y (2011).An Analysis of Wind Speed Distribution at Thasala, Nakhon Si Thammarat, Thailand.Journal of Sustainable Energy & Environment 2 pp 51-55 Willmott, C., Robeson, S. and Philpot, W. (1985). Small- scale climate maps: A sensitivity analysisof some common assumptions associated withgrid-point interpolation and contouring. American Cartographer 12(1):5-16. Copyright (c) 2019 Geosfera Indonesia Journal and Department of Geography Education, University of Jember This work is licensed under a Creative Commons Attribution-Share A like 4.0 International License

Chimeric Antigen Receptor T cells (CART) have led to unprecedented clinical responses in relapsed or refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL), non-Hodgkin lymphomas (NHL), and multiple myeloma. However, despite these exciting results, most patients treated with CART therapy either do not respond or eventually relapse. Moreover, CART therapy has not yet been proven effective in several hematological malignancies, such as T cell lymphoma and leukemia (T-NHL/T-ALL) and acute myeloid leukemia (AML). Thus, there is a need to enhance currently available CART products and also to develop next-generation CART therapies to successfully treat additional neoplasms like T-NHL /T-ALL and AML. To this goal, we studied the cysteine-rich scavenger receptor CD5, an attractive target for CART immunotherapy because of its dual role in malignant cells and normal T cells. In malignant cells, CD5 is expressed by ~90% of TCL cells, by ~15-20% of AML cells, and also by most cases of chronic lymphocytic leukemia and mantle cell lymphoma (MCL). Of note, promising results using a CD28-based anti-CD5 CART against T-NHL and T-ALL were reported at this meeting in 2019 (LaQuisa C. Hill #199). In T cells, CD5 is highly expressed and inhibits T cell receptor (TCR)-mediated activation through several mediators including SHP-1, CBL, CBL-B, and GRB2. Therefore, we hypothesized that the genetic deletion of CD5 in engineered T cells could potentially enhance their effector functions. First, we designed and screened six 4-1BB-costimulated anti-CD5 lentiviral CAR constructs designed to have high, medium, and low affinity for CD5. We then selected the lead CAR5 construct (high affinity, heavy to light light chain orientation) based on its superior anti-tumor function in vivo in NOD-SCID IL2Rgnull (NSG) mice engrafted with T-cell leukemia (Jurkat). Then, to further improve CART5 activity, we optimized a CD5 short-guide RNA and deleted CD5 in CART5 cells using CRISPR-Cas9. CD5 gene deletion was reproducibly efficient (95-100% by flow cytometry and TIDE) during manufacturing (6 donors). Interestingly, the growth rate of wild type (WT) CART5 was comparable to CD5 KO CART5 and the expression of CD5 in WT CART5 was reduced. However, at the end of manufacturing, CD5 KO CART5 had increased central memory T cells (33.0% vs. 18.4%) and reduced expression of activation/exhaustion markers (PD-1 4.4% vs. 14.8%, LAG3 13.1% vs. 55.9%) compared to WT CART5, potentially indicating that CD5 KO reduces CART5-CART5 fratricide during manufacturing. We then compared wild type (WT) CART5 to CD5 KO CART5 in vitro using several T-NHL/T-ALL, MCL, and AML models, including primary samples (Sezary cells, primary MCL cells, and CD5+ AML cells). Both WT and CD5 KO CART5 were highly effective in killing CD5+ malignant cells, but CD5 KO CART5 showed enhanced proliferation upon activation. In two xenograft models of T-cell leukemia (primary T-ALL and Jurkat), CD5 KO CART5 showed dramatically increased tumor control compared to WT (Fig.1A, median overall survival for WT= 62 days vs. CD5 KO=not reached, p = 0.006, Mantel-Cox). This enhanced anti-tumor effect was associated with increased expansion of CD5 KO CART5 in the peripheral blood (PB) compared to WT CART5. To test the hypothesis that deletion of CD5 could increase the anti-tumor effect of CART targeting antigens other than CD5, we knocked out CD5 in anti-CD19 CART cells and tested their function in a CD19+ B-ALL xenograft model (NALM6). Remarkably, CD5 KO CART19 displayed significantly enhanced anti-leukemia activity and PB expansion compared to WT (Fig.1B,C, p&lt;0.05, p = 0.001, Mantel-Cox). Finally, we aimed to define the mechanisms by which CD5 KO enhances CART anti-tumor efficacy. We analyzed the phosphorylation of multiple targets in T cells after 15 minutes of CAR stimulation. Remarkably, CD5 KO CART5 cells had higher (&gt;2fold) phosphorylation of several signaling proteins, including key regulators of T cell activation, migration, and survival compared to WT CART5 (Fig. 1D). To confirm that the CD5 pathway was indeed the mediator of this effect, we knocked out SHP-1 in CART19 cells using CRISPR/Cas9 and observed increased leukemia killing. In conclusion, we demonstrate that CRISPR-Cas9 KO of CD5 enhances the anti-tumor activity of CAR T cells by enhancement of CAR-mediated activation and proliferation. These findings support the development of CD5 KO CART products in early-phase clinical trials. Disclosures Schuster: Novartis, Genentech, Inc./ F. Hoffmann-La Roche: Research Funding; AlloGene, AstraZeneca, BeiGene, Genentech, Inc./ F. Hoffmann-La Roche, Juno/Celgene, Loxo Oncology, Nordic Nanovector, Novartis, Tessa Therapeutics: Consultancy, Honoraria. Barta:Atara: Honoraria; Monsanto: Consultancy; Seattle Genetics: Honoraria, Research Funding; Janssen: Honoraria; Pfizer: Honoraria. June:Tmunity Therapeutics: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding; Ziopharm Oncology: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; Novartis: Patents & Royalties, Research Funding; Bluesphere Bio: Membership on an entity's Board of Directors or advisory committees; Cabaletta Bio: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; Carisma Therapeutics: Membership on an entity's Board of Directors or advisory committees; Cellares: Membership on an entity's Board of Directors or advisory committees; Celldex: Consultancy, Membership on an entity's Board of Directors or advisory committees; DeCART Therapeutics: Membership on an entity's Board of Directors or advisory committees; Immune Design: Membership on an entity's Board of Directors or advisory committees; Kiadis Pharma: Current equity holder in private company. Ruella:Abclon, BMS, NanoString: Consultancy; UPenn/Novartis: Patents & Royalties; Abclon: Consultancy, Research Funding.

This chapter details the growing frustration of political exiles and opposition groups in the Philippines. In 1978, the KBL party had won control of the new legislature, and Imelda Marcos had been appointed to the cabinet. At the end of 1979, Marcos would call for nationwide elections for governors and mayors. His KBL candidates were expected to sweep the field (which they ultimately did). During a meeting of the Movement for a Free Philippines in San Francisco in September 1979, the members were in a combative mood. Was there no stopping the man? Where was the light at the end of this long, dark tunnel, which was already six years in the making? They had received reports that the moderate opposition in the Philippines was likewise frustrated and angry, and even—surprisingly—calling for violence. These were not the radical leftists who had always endorsed aggressive means and followed their convictions by joining the militant National Democratic Front and its military arm, the New People's Army, in the hills. The moderate voices who were now advocating for a shift in tactics reasoned that peaceful means had gotten them nowhere, and that the dictatorship was as entrenched as ever. It was time to take up arms.

I remember how one day Cavor suddenly opened six of our shutters and blinded me so that i cried aloud at him. The whole area was moon, a stupendous scimitar of white dawn with its edge hacked out by notches of darkness, the crescent shore of an ebbing tide of darkness, out of which peaks and pinnacles came climbing into the blaze of the sun. I take it the reader has seen pictures or photographs of the moon,^* so that I need not describe the broader features of that landscape, those spacious ringlike ranges vaster than any terrestrial mountains, their summits shining in the day, their shadows harsh and deep, the grey disordered plains, the ridges, hills, and craterlets, all passing at last from a blazing illumination into a common mystery of black. Athwart this world we were flying scarcely a hundred miles above its crests and pinnacles. And now we could see, what no eye on earth will ever see, that under the blaze of the day the harsh outlines of the rocks and ravines of the plains and crater floor grew grey and indistinct under a thickening haze, that the white of their lit surfaces broke into lumps and patches, and broke again and shrank and vanished, and that here and there strange tints of brown and olive grew and spread.