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تعد كفاءة الاستثمار احد اهم مواضيع الادارة المالية، لأنها تمكن الشركات من حسناستغلال الموارد وصولاً الى تعظيم قيمتها، وان استخدام نظرية الليمون للتعرف على اسبابانحراف الشركات عن مستوى الكفاءة في الاستثمار عبر النقص به او الافراط به قد اضافة بعدااخر لعرض الموضوع والبحث في تلك الاسباب بما يتوافق مع حافات المعرفة المالية مما قد يمكنالشركات من تلافيها، وقد تم تطبيق ذلك على عينة تمثل ب ) 15 ( شركة صناعية سعودية مدرجةفي سوق الاوراق المالية، منطلقا من هدف رئيس مفاده تفسير كفاءة الاستثمار وفق مدخل نظريةالليمون، مستخدما البيانات الطولية وفق انموذج الانحدار المتعدد الذي يأخذ حجم الاستثمار الفعليبعده متغيراً معتمداً ومحددات كفاءة الاستثمار بعدها متغيرات تفسيرية يتم من خلالها تقدير حجمالاستثمار المقدر، فاذا ما كان حجم الاستثمار الفعلي اكبر من الاستثمار المقدر فان هذا مؤشر علىالافراط في الاستثمار، اما اذا كان حجم الاستثمار المقدر اكبر من نظيره الفعلي فان هذا مؤشرعلى النقص في الاستثمار، مما يعني الاعتماد على بواقي انموذج الانحدار لتقدير مستوى الكفاءةفي الاستثمار فالبواقي الايجابية تدل على الافراط في الاستثمار، اما البواقي السلبية فتدل علىالنقص في الاستثمار، وقد توصل البحث الى تباين الشركات الصناعية السعودية من حيث الافراطفي الاستثمار والنقص به، وان الاول ناتج عن عدم تماثل المعلومات الذي يدفع المستثمرين الىتسعير اسهم الشركات ذات النوعية المنخفضة والتي تسعى الى اصدارها لتمويل استثماراتها بسعرمضخم والثاني ناتج عن عدم تماثل المعلومات الذي يدفع المستثمرين الى تسعير اسهم الشركاتذات النوعية العالية التي تسعى الى اصدارها لتمويل استثماراتها بسعر مخفض، مما يتوجب علىالشركات الافصاح عن معلوماتها بكل شفافية وبوقتها المناسب قبل ان تفقد اهميتها وان تتصفبالتمثيل الامين لواقع ادائها.

Al-TiC nanocomposites are prepared by powder metallurgy technique. The effect of milling time and TiC percent on the mechanical properties and microstructure are studied. Nano TiC powders with 5, 10, and 20 wt. % is added to the Al matrix. The mixed powders are mechanically milled by a 35:1 ball to powder ratio and 110 rpm for 6, 12, 24, and 48 hr. milling time (MT). Mixed powders are compacted by a uniaxial press under 600 Mpa and sintered at 600 °C for 1 hr. in a vacuum furnace. According to Archimedes’ principle, the density was estimated, which indicated it is decreasing for 6 hr. milling time, followed by an increase for 12 and 24 hrs., then another decreasing for 48 hrs. The addition of nano TiC increases the density values gradually by increasing its percent. Both the phase composition and microstructure of both composite powders and sintered samples are examined using XRD & FE-SEM, respectively. XRD results indicated forming the aluminum carbide (Al4C3) phase that is formed during the sintering process. The microstructure shows the homogeneous distribution of TiC on the Al matrix and the reduction of Al particle size by increasing both milling time and TiC percent. Hardness, compression strength, and wear resistance are improved by increasing TiC content and MT up to 24 hours. Al-20 wt. % TiC composite with 24 hr. milling time exhibited the highest hardness (196.5667 HV) and the lowest wear rate (0.001 g/min).

Cu-(TiC/Al2O3) nanocomposite was synthesized successfully using the powder metallurgy route. The constituents are first ball-milled and then sintered using the spark plasma sintering technique. The tribological and physical properties are investigated. The homogeneity and of ceramics distribution were also evaluated using SEM and XRD. Results showed that TiC and Al2O3 nanoparticles were homogeneously distributed all over the Cu matrix. Copper reinforced with 3 wt.% Al2O3 and hybrid (3 wt. % TiC and Al2O3) had the lowest relative density (95 %). The hybrid (3 wt. % TiC and Al2O3) sample had a higher wear rate value (1.7 * 10-3) at 25 N load, while the sample reinforced with 3 wt.% TiC had the lowest value (0.5 * 10-3) at 25 N load. Cu-Al2O3 exhibited a higher hardness value (149 HV). The highest electrical and thermal conductivities are recorded for the Cu -TiC that were (20.76 MS/m) and (149.03 W/m. k) respectively.

Aim: This study aimed to compare the fatigue behavior of resin composite and dental amalgam restorative materials used below the occlusal rest of removable partial denture (RPD). Subjects and methods: Thirty extracted first maxillary molars were prepared with standard class II cavities and divided to three groups (n=10 per group). Group I and group II were filled with composite (Charisma Smart and Flitek Z250) respectively and group III was filled with amalgam (Dispersalloy). After 24 hours, 30 standard saucer shaped rest seats were prepared. The samples were stored in distilled water for 14 days prior to testing. Fatigue resistance test was evaluated by the step-test method on a computer controlled materials testing machine. One way ANOVA followed by pair-wise Tukey’s post-hoc tests was used to determine the significance between groups. Results: The difference between groups was statistically non-significant as indicated by the one way ANOVA followed by pair-wise Tukey’s post-hoc multiple comparison tests (p=8910>0.05). Conclusion: There was insignificant difference in the fatigue fracture resistances between the tested groups.

224 Background: Common drivers in advanced prostate cancer (PC) involve fusions of the 3’ DNA binding domain-containing region of an Erythroblast Transformation Specific (ETS) transcription factor gene with a 5’ region of another gene, often one that is androgen-regulated. Previous work indicates that PCs harboring TMPRSS2:ERG fusions are more dependent on androgen signaling, and men with such tumors may, therefore, be more responsive to the effects of androgen deprivation therapy than men lacking this fusion. In this study, we examined the frequency of fusions involving ETS-family genes, including TMPRSS2:ERG, and determined how often such fusions would be missed if detection relied solely on DNA sequencing. Methods: To identify fusions and compare DNA-only versus DNA plus RNA sequencing, we utilized the Oncomap ExTra genomic profiling assay. This assay performs whole-exome, whole-transcriptome DNA and RNA sequencing of tumor and matched normal samples to identify somatic alterations in tumors. Single-nucleotide variants, indels, copy number alterations, alternative transcripts, and gene fusions are all detected. We specifically searched for fusions involving ETS transcription factor genes ERG and ETV1- 7. Results: A total of 512 PC patient samples assayed between April 2018 and July 2022 were included in the analysis; 226 ETS fusions were present in 223 (43.6%) patients; 3 patients carried two fusions. There were 196 ERG fusions including 185 (36.1%) patients having the familiar TMPRSS2: ERG fusion and 8 (1.6%) patients with a SLC45A3: ERG fusion, which is known to be associated with particularly poor prognosis. ETV1, 4, and 5 fusions were found in 29 (5.7%) patients and involved 12 different 5’ partner genes, the most common of which were SLC45A3 (6 fusions) and CANT1 (4 fusions). The two partner genes were on the same chromosome in 192 fusions, with 190 requiring a single deletion to create the fusion and 2 requiring a single inversion. For the 34 fusions involving genes on different chromosomes, a single translocation would be sufficient to produce the fusion gene in 23 cases; in 11 cases more than one structural rearrangement would be required. A total of 66 (29.6%) fusions were not detected in the DNA sequencing data, including 40 (21.6%) TMPRSS2: ERG fusions. In addition, 16 fusions were detected only in the DNA data, as RNA could not be sequenced, including 13 TMPRSS2: ERG fusions. Conclusions: In addition to TMPRSS2: ERG, the Oncomap ExTra assay identified several low frequency ETS fusions, all of which could be used to assist patients and physicians to select appropriate treatments. The identification of ETS fusions appears to be limited when using only DNA sequencing. Oncomap ExTra RNA analysis identified 66 additional fusions, representing almost 30% of those present, not identified by whole-exome DNA sequencing, suggesting RNA plus DNA assays detect fusions more reliably than DNA-only assays.

806 Background: BRAF V600E mutations can lead to activation of the MEK/ERK pathway. The combination of dabrafenib plus trametinib was recently FDA-approved for use in these BRAF V600E altered unresectable or metastatic cancers. BRAF non-V600 alterations also increase phosphorylation of MEK and ERK and are potential candidates for MEK/ERK inhibitors. Here we examine the frequency of BRAF mutations and their genomic background across GI cancers. Methods: The Oncomap ExTra genomic profiling assay utilizes tumor-normal, whole-exome, whole-transcriptome DNA and RNA sequencing to identify somatic alterations in tumors. The assay detects single-nucleotide substitutions, indels, copy number alterations, alternative transcripts, and gene fusions. Tumor mutational burden (TMB) and microsatellite instability (MSI) are also assessed. The frequency of BRAF and other gene alterations were identified across all GI cancers. Reported BRAF alterations were limited to those linked to an FDA approved therapy, clinical trial eligibility, and those deemed significant from review of the literature. Results: A total of 1927 patients with GI cancers were assayed between April 2018 to July 2022. The BRAF gene was mutated in 85 (4.4%) patients, which included 53 (2.8%) that were V600E and 32 (1.5%) that were non-V600, representing 37.6% of BRAF mutations. Colorectal and small bowel cancers had the highest frequencies of BRAF mutations at 7.6% and 7.1% respectively, and the frequency was lower in other GI cancers (0-2.3%). In addition to BRAF V600E, other mutations occurred across the kinase domain, including D594 (0.6%), K601E (0.3%), G466 (0.3%) and G469 (0.2%). BRAF fusions were found in 1 CRC and 2 pancreatic cancer cases. BRAF mutational status (altered versus not) was significantly associated with mutations in several other genes. In addition, BRAF status was significantly associated with TMB-high and MSI-high. Conclusions: Analysis of whole-exome and whole transcriptome sequencing data found actionable BRAF mutations in 4.4% of GI cancer patients, 37.6% of whom had BRAF mutations not at V600. Several biomarkers were significantly associated with BRAF alterations. Assays that are limited to DNA sequencing, or to targeted gene panels, may not detect mutations and fusions that could aid in therapy selection and prognosis. [Table: see text]

A convenient route to the synthesis of pyrazolo[3,4-b]pyridin-3-ones via condensation of 3- amino-1-phenylpyrazolin-5-one with 4-hydroxy-6-methylpyran-2-one. The isomeric pyrazolo[3,4-b]pyridin-3-ones obtained are functionalized in position 4 or 6 by aliphatic and aromatic amines, on the other hand position 1 of another derivative pyrazolopyridinic was functionalized by a synthetic grouping. The serotoninergic activity of the various compounds obtained was also examined and discussed., Moroccan Journal of Heterocyclic Chemistry, Vol 20, No 4 (2021)

Background: Immune-oncology (I-O) drugs show promise across multiple tumor types, and several biomarkers (BM) predict responsiveness to I-O therapy. In this descriptive study of clinical lab experience (2018-2021), we investigated the prevalence of genomic BMs associated with sensitivity and resistance to I-O drugs across solid tumors. Methods: The GEM ExTra® assay was used to exome-sequence 2,359 paired samples at 180X and 400X coverage for germline and tumor DNA respectively. Reportable alterations were single base substitutions, indels, copy number alterations, fusions, alternate transcripts, as well as tumor mutational burden (TMB) and microsatellite instability (MSI) status. For I-O sensitive BMs we recorded MSI-High status, TMB-High (> 10 mut/Mb) status, and mutations in POLE/POLD1, MLH1, MSH2/3/6, PMS1/2, PD-L1/-L2, CTLA4, CD28, ARID2, and PBRM1. For I-O resistance BMs, IDO1 amplification and mutations in B2M, JAK1/2, IDO1, KRAS and STK11 were tallied. Results: I-O sensitive BMs varied from 0% to 58% (results in Table 1 for selected tumor types). Overall, TMB-High was in 6% of samples and MSI-High in 3%; all MSI-High were also TMB-High. In the 46% of renal cell carcinoma samples with I-O-sensitive BMs, PBRM1 mutation was common (94%). In 3 TMB-High endometrial samples, POLE/POLD1 was mutated, indicative of an ultra-mutated phenotype. Of note, 35% of colorectal cancer and 8% of melanoma samples with I-O sensitive mutations also had loss-of-function mutations in JAK1/2 and B2M, suggestive of I-O resistance. In non-small cell lung cancer, co-mutation of STK11 and KRAS, suggesting inferior response to I-O therapy, was present in 4% of samples with I-O BMs. IDO1 amplification was present in less than 1% of entire cohort. Conclusions: Our study found I-O sensitive BMs in common and in rare aggressive cancers. The GEM ExTra assay can stratify cancer patients for likely responsiveness to immunotherapy. Table 1. Immune-oncology sensitive biomarkers observed across select tumors Solid tumor type % of samples with signature All (n = 2,360) 13% Melanoma (n = 50) 54% Other skin cancers (n = 13) 62% Renal cell carcinoma (n = 200) 46% Urothelial (n = 86) 22% Endometrial (n = 88) 20% Gastro-intestinal (n = 360) 12% Sarcoma (n = 90) 11% Prostate (n = 151) 6% Lung (n = 100) 4% Breast (n = 297) 2% Central nervous system (n = 60) 0% Citation Format: Pawan Noel, David W. Hall, Sameer S. Udhane, Min Wang, Fadel S. Alyaqoub, Szabolcs Szelinger, Audrey A. Ozols, Janine R. LoBello, Frederick L. Baehner, Gargi D. Basu. Comprehensive genomic profiling to identify biomarkers predictive of response to immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1263.

3124 Background: Deleterious events in DNA damage response (DDR) are hallmarks of cancer associated with sensitivity to PARP inhibitors (PARPi) and immune checkpoint inhibitors (CPI). This study investigated DDR pathway alterations across solid tumors. Methods: Samples were sequenced with the Oncomap ExTra assay using tumor-normal paired whole-exome DNA sequencing to detect single base substitutions, indels, and copy number alterations that were clinically actionable, defined as associated with FDA approved drugs or clinical trial enrollment. Here, we report the frequency of MSI-high and TMB-high (>10 mutations/Mb), and clinically-actionable alterations for the following 49 DDR genes: ARID1A, ATM, ATR, ATRX, BAP1, BARD1, BLM, BRCA1/2, BRIP1, CDK12, CHEK1/2, EPCAM, ERCC1/2/3/4/5, FANCA/C/D2/E/F/G/I/L/M, MLH1, MRE11A, MSH2/6, MUTYH, NBN, PALB2, PMS2, PPP2R2A, PTEN, RAD21/50/51/51B/51C/51D/52/54L, XRCC1/2/3. Results: Of the 6055 patient samples profiled, 1633 (27.0%) had clinically actionable alterations in DDR genes; DDR alterations varied from 0-64.3% across tumor types. For the 5657 samples with TMB/MSI data, 429 (7.6%) had high TMB and 193 (3.4%) were MSI-high; MSI-high samples were usually TMB-high (n = 180; 93.2%). The percent of cancers that were TMB-high or MSI-high varied from 0-64.8% and 0-20.8% respectively. Actionable BRCA1/2 gene alterations were present in 319 patients (5.3%, range 0-15.3%). Three cancers (biliary, brain and liver) had BRCA1/2 alterations in less than 2% of patients but across the 49 DDR genes alterations were present in more than 20% of patients, representing a greater than 10-fold difference. Across solid tumors, this analysis identifies a group of 1314 patients (21.7%) who harbor a DDR gene alteration other than BRCA1/2. Conclusions: Defective DNA repair as detected by deleterious alterations in DDR genes along with TMB/MSI status has the potential to guide clinicians to FDA-approved therapy or clinical trial enrollment in a large percentage of patients across solid tumor types.[Table: see text]

1096 Background: The use of targeted therapies identified using genetic and genomic approaches is now routine in breast cancer (BC). In this clinical lab experience study the frequency of actionable somatic alterations in DNA repair pathway genes associated with the use of PARP inhibitors (PARPi) is described. Methods: BC samples were sequenced with the Oncomap ExTra assay, which uses whole-exome DNA sequencing with germline subtraction to detect somatic single base substitutions, indels, and copy number alterations, and RNA sequencing to detect gene fusions. Clinically actionable alterations were defined as associated with FDA approved drugs or clinical trial enrollment. Here, the focus is on 49 repair genes associated with PARPi response: ARID1A, ATM, ATR, ATRX, BAP1, BARD1, BLM, BRCA1/2, BRIP1, CDK12, CHEK1/2, EPCAM, ERCC1/2/3/4/5, FANCA/C/D2/E/F/G/I/L/M, MLH1, MRE11A, MSH2/6, MUTYH, NBN, PALB2, PMS2, PPP2R2A, PTEN, RAD21/50/51/51B/51C/51D/52/54L, XRCC1/2/3. Results: Of 1103 BCs, 246 (22.3%) had mutations in repair genes; 69 (6.3%) were in BRCA1/2. Repair gene mutations were less common in HER2+ cancers (n=27, 14.3%) compared to HR+ HER2- (n=156, 23.9%) or TN cancers (n=49, 26.1%) (p+ cancers (p- germline BRCA1/2 mutated BC patients. Recent evidence suggests somatic BRCA1/2 mutations predict PARPi benefit (Tung, NM. J Clin Oncol 2020). In addition to BRCA1/2 alterations, our study also highlights the importance of alterations in other DNA repair genes associated with response to PARPi. Trials are ongoing to determine if these genes predict for PARPi benefit.[Table: see text]

This paper aimed to clarify the role that the Balanced Scorecard (BSC) as a performance measurement tool in the company of Algeria Post. The BSC is a strategic performance management system, has been proven suitable for the public sector as the financial aspect is not their only concern. The BSC is « A multidimensional performance measurement system that should serve as decision support for managers. It includes indicators of progress and delay as well as internal and external indicators. It organizes the measures in a coherent system around four balanced perspectives: financial perspective, customer perspective, internal process, learning, and growth ». (Kaplan. S & Norton, 2004, P186). This study focused to improve the company of Algeria Post overall performance, the management control systems established should be re-evaluated and its tools should be improved to ensure reactivity in the decision-making and the measuring of the company performance. Our work consists of proposing a new approach to the performance management system for the model of the BSC as a performance measurement tool in the company of Algeria Post. The purpose of this article is to answer the main question of the study: should the company rely on the balanced scorecard as a performance measurement tool to achieve its strategic goals? First able, we counted on the stages of scientific research by gathering information about the company of Algeria Post, after that to conduct our study, we opted for a qualitative approach, using documentary research, interviews, and observation as tools for data collection. In the course of our designing of the proposed model of the BSC for the company. During our design of the proposed model of the balanced scorecard for the company we decided to follow a specific methodology to obtain the desired results taking into account the governmental nature of the organization of the company’s. We deemed it necessary to apply a public sector BSC model, using a top-down principle from (Kaplan and Norton, 2014) combined with the implementation procedures described in the theoretical side by (Alain Fernandez, 2013). It is noted that through the performance indicators of the customer perspective that the company realized some respectful objectives, but most of them are short lived ones, simultaneously, the internal processes perspective was the most performing by focusing on improving the quality of electronic services and the commercial network as a whole.

Specific variants of endoplasmic reticulum-associated aminopeptidase 1 (ERAP1) identified by genome-wide association study modify the risk for developing ankylosing spondylitis. We previously confirmed that disease-associated ERAP1 variants have altered enzymatic abilities that can impact upon the production of pro-inflammatory cytokines from cells expressing the same ERAP1 variants. To determine if these ERAP1 variants also impacted immune responses in vivo, we generated two strains of transgenic mice expressing human ERAP1 genes containing non-synonymous single-nucleotide polymorphisms associated with an increased (ERAP1-High) or decreased (ERAP1-Low) risk for developing autoimmune disease. After vaccination with foreign antigens, ERAP1-High mice generated unique populations of antigen-specific T-cell clones. The expression of ERAP1-High also reduced MHC-I expression on the surface of multiple cell types, demonstrating a global impact on the MHC-I peptidome. ERAP1 variants also affected the innate immune system, because NK cells from murine ERAP1 (mERAP1) knockout mice and ERAP1-High/mERAP1−/− mice had decreased surface expression of the activating receptor NKG2D on their NK and T cells, and NK cells derived from mERAP1−/− mice or ERAP1-Low mice demonstrated more active NK cell killing than NK cells derived from wild-type or ERAP1-High mice. Finally, these studies were conducted in female mice, as all male ERAP1-High mice died in utero or shortly after birth, making ERAP1-High one of the only dominant lethal autosomal genes known in mammals. Together, these results present the first direct evidence that human disease-associated ERAP1 variants can greatly alter survival, as well as antigen presentation, T-cell repertoire and NK cell responses in vivo.