49 research outputs found

    دراسة التوازن الاستراتيجي في الشركة السورية للحبوب دراسة ميدانية على فرع اللاذقية

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    هدفت هذه الدراسة إلى تسليط الضوء على مفهوم التوازن الاستراتيجي وأبعاده، وأهميته في المنظمات، إذ أن المنظمات التي تحافظ على توازنها الاستراتيجي تضمن لنفسها الاستدامة والنمو المستمر لا سيما في ظروف بلد كسورية تسوده ظروف اقتصادية غير مستقرة. تم إجراء الدراسة في الشركة السورية للحبوب- فرع اللاذقية على عينة قصدية من المديرين في جميع المستويات والأقسام الإدارية حيث تم توزيع 60 استبانة استرد منها 53 استبانة صالحة للتحليل الاحصائي، للحصول من خلالها على إجابات عن الموضوع المدروس، تم اتباع المنهج الوصفي التحليلي واستخدام الإحصاء الاستدلالي من خلال البرنامج الاحصائي 23 SPSS للوصول إلى النتائج. توصلت الدراسة إلى أن الشركة تحقق التوازن الاستراتيجي إذ تقوم بتنفيذ استراتيجياتها وبممارسة عملياتها الاستراتيجية المطلوبة، إلا أن خطتها الاستراتيجية غير معلنة لجميع أفرادها. وقد أوصت الدراسة بضرورة نشر الخطة الاستراتيجية للشركة ووضعها في متناول موظفيها، والحرص على إيجاد تكامل ثقافي بين الشركات المندمجة يساعد على تحقيق التوازن الاستراتيجي للشركة. ضرورة تمكين العاملين وإشراكهم في العمل واتخاذ القرارات ما يساعد على تنفيذ تدفق العمليات الاستراتيجية بكل مرونة، ضرورة وجود خطط طوارئ لمواجهة حالة التغير البيئي المستمر من أجل تحقيق التوازن الاستراتيجي الديناميكي

    A practical guide to conversation research: how to study what people say to each other

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    Conversation—a verbal interaction between two or more people—is a complex, pervasive, and consequential human behavior. Conversations have been studied across many academic disciplines. However, advances in recording and analysis techniques over the last decade have allowed researchers to more directly and precisely examine conversations in natural contexts and at a larger scale than ever before, and these advances open new paths to understand humanity and the social world. Existing reviews of text analysis and conversation research have focused on text generated by a single author (e.g., product reviews, news articles, and public speeches) and thus leave open questions about the unique challenges presented by interactive conversation data (i.e., dialogue). In this article, we suggest approaches to overcome common challenges in the workflow of conversation science, including recording and transcribing conversations, structuring data (to merge turn-level and speaker-level data sets), extracting and aggregating linguistic features, estimating effects, and sharing data. This practical guide is meant to shed light on current best practices and empower more researchers to study conversations more directly—to expand the community of conversation scholars and contribute to a greater cumulative scientific understanding of the social world

    Deficient histone H3 propionylation by BRPF1-KAT6 complexes in neurodevelopmental disorders and cancer

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    Lysine acetyltransferase 6A (KAT6A) and its paralog KAT6B form stoichiometric complexes with bromodomain- and PHD finger-containing protein 1 (BRPF1) for acetylation of histone H3 at lysine 23 (H3K23). We report that these complexes also catalyze H3K23 propionylation in vitro and in vivo. Immunofluorescence microscopy and ATAC-See revealed the association of this modification with active chromatin. Brpf1 deletion obliterates the acylation in mouse embryos and fibroblasts. Moreover, we identify BRPF1 variants in 12 previously unidentified cases of syndromic intellectual disability and demonstrate that these cases and known BRPF1 variants impair H3K23 propionylation. Cardiac anomalies are present in a subset of the cases. H3K23 acylation is also impaired by cancer-derived somatic BRPF1 mutations. Valproate, vorinostat, propionate and butyrate promote H3K23 acylation. These results reveal the dual functionality of BRPF1-KAT6 complexes, shed light on mechanisms underlying related developmental disorders and various cancers, and suggest mutation-based therapy for medical conditions with deficient histone acylation

    Novel diagnostic DNA methylation episignatures expand and refine the epigenetic landscapes of Mendelian disorders

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    Overlapping clinical phenotypes and an expanding breadth and complexity of genomic associations are a growing challenge in the diagnosis and clinical management of Mendelian disorders. The functional consequences and clinical impacts of genomic variation may involve unique, disorder-specific, genomic DNA methylation episignatures. In this study, we describe 19 novel episignature disorders and compare the findings alongside 38 previously established episignatures for a total of 57 episignatures associated with 65 genetic syndromes. We demonstrate increasing resolution and specificity ranging from protein complex, gene, sub-gene, protein domain, and even single nucleotide-level Mendelian episignatures. We show the power of multiclass modeling to develop highly accurate and disease-specific diagnostic classifiers. This study significantly expands the number and spectrum of disorders with detectable DNA methylation episignatures, improves the clinical diagnostic capabilities through the resolution of unsolved cases and the reclassification of variants of unknown clinical significance, and provides further insight into the molecular etiology of Mendelian conditions

    Brief Optogenetic Inhibition of Dopamine Neurons Mimics Endogenous Negative Reward Prediction Errors

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    Correlative studies have strongly linked phasic changes in dopamine activity with reward prediction error signaling. But causal evidence that these brief changes in firing actually serve as error signals to drive associative learning is more tenuous. While there is direct evidence that brief increases can substitute for positive prediction errors, there is no comparable evidence that similarly brief pauses can substitute for negative prediction errors. Lacking such evidence, the effect of increases in firing could reflect novelty or salience, variables also correlated with dopamine activity. Here we provide such evidence, showing in a modified Pavlovian over-expectation task that brief pauses in the firing of dopamine neurons in rat ventral tegmental area at the time of reward are sufficient to mimic the effects of endogenous negative prediction errors. These results support the proposal that brief changes in the firing of dopamine neurons serve as full-fledged bidirectional prediction error signals

    Novel diagnostic DNA methylation episignatures expand and refine the epigenetic landscapes of Mendelian disorders.

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    Overlapping clinical phenotypes and an expanding breadth and complexity of genomic associations are a growing challenge in the diagnosis and clinical management of Mendelian disorders. The functional consequences and clinical impacts of genomic variation may involve unique, disorder-specific, genomic DNA methylation episignatures. In this study, we describe 19 novel episignature disorders and compare the findings alongside 38 previously established episignatures for a total of 57 episignatures associated with 65 genetic syndromes. We demonstrate increasing resolution and specificity ranging from protein complex, gene, sub-gene, protein domain, and even single nucleotide-level Mendelian episignatures. We show the power of multiclass modeling to develop highly accurate and disease-specific diagnostic classifiers. This study significantly expands the number and spectrum of disorders with detectable DNA methylation episignatures, improves the clinical diagnostic capabilities through the resolution of unsolved cases and the reclassification of variants of unknown clinical significance, and provides further insight into the molecular etiology of Mendelian conditions

    A self-initiated cue-reward learning procedure for neural recording in rodents

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    Background: Single-unit recording in Pavlovian conditioning tasks requires the use of within-subject designs as well as sampling a considerable number of trials per trial type and session, which increases the total trial count. Pavlovian conditioning, on the other hand, requires a long average intertrial interval (ITI) relative to cue duration for cue-specific learning to occur. These requirements combined can make the session duration unfeasibly long. New method: To circumvent this issue, we developed a self-initiated variant of the Pavlovian magazine-approach procedure in rodents. Unlike the standard procedure, where the animals passively receive the trials, the self-initiated procedure grants animals agency to self-administer and self-pace trials from a predetermined, pseudorandomized list. Critically, whereas in the standard procedure the typical ITI is in the order of minutes, our procedure uses a much shorter ITI (10 s). Results: Despite such a short ITI, discrimination learning in the self-initiated procedure is comparable to that observed in the standard procedure with a typical ITI, and superior to that observed in the standard procedure with an equally short ITI. Comparison with existing method(s): The self-initiated procedure permits delivering 100 trials in a ∼1-h session, almost doubling the number of trials safely attainable over that period with the standard procedure. Conclusions: The self-initiated procedure enhances the collection of neural correlates of cue-reward learning while producing good discrimination performance. Other advantages for neural recording studies include ensuring that at the start of each trial the animal is engaged, attentive and in the same location within the conditioning chamber
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