bluuebunny/crossref_metadata_2025 huggingface dataset:
Work-Life Balance as A Moderator Between Teaching Competence Standards and Teachers’ Performance in Public Primary Schools in Igembe North Sub-County, Meru County
Authors: Gitonga Harriet Karamana , Kibaara Tarsila , Gichohi Paul Maku
Published: October 2024

The evaluative systems by TSC expect teachers to deliver good performance in every aspect of the teaching competence standards. However, the performance of primary school teachers has continued to raise concerns from different stakeholders, raising a question of whether the teaching competence standards are sufficient in explaining the annual teacher's performance or whether there are other issues such as the work-life balance that have a bearing on the teacher's performance outcome. This study assessed the moderating effect of the work-life balance on the relationship between the teaching competence standards and the teachers' performance in public primary schools in the Igembe North sub-county in Meru County. The descriptive survey research design was adopted. A sample size of 202 teachers, 14 headteachers, and one Sub-County Education Officer participated in the study. A proportionate simple random sampling technique was used in selecting teachers and headteachers, while the Sub-County Education Officer was purposively selected. Data was collected using questionnaires and an interview guide whose validity and reliability was verified. The mean, standard deviation, correlation, and regression analysis were used in analyzing the quantitative data, while thematic analysis was used on qualitative data. Most teachers had multiple roles with competing interests; hence, balancing work, family, personal, and community responsibilities was a daunting task. The work-life balance was found statistically significant in moderating the relationship between the teaching competence standards and the teacher's performance in public primary schools. The study recommends strengthening supportive systems on all three teaching competence standards and embracing work-life balance practices by the TSC. The TSC and principals should ensure that teachers of public primary schools have moderated work-related responsibilities and develop a workplace policy on work-life balance. The findings have enormous implications on organizational culture, leadership, and human resources management practices in public primary schools.
Availability of Learning Resources and Management of KCSE Irregularities in Nairobi County, Kenya
Authors: Mugambi Samuel Kinoti , Kibaara Tarsilla , Gichohi Paul
Published: October 2024

Examinations play a critical role in the education sector in assessing learners' knowledge and skill mastery. Therefore, they must be credible and free of irregularities. However, over the years, Kenya has seen an increase in examination malpractice. This has compelled the Kenya National Examination Council to devise some solutions to these problems. Despite the strict measures in place, several cases of KCSE examination irregularities every year are usually reported. This demonstrates that none of the existing measures have been able to eliminate examination malpractices, particularly in secondary schools in Nairobi County. This study investigated the impact of learning resource availability on the management of KCSE examination irregularities in Nairobi County, Kenya. The study population included all 99 secondary schools in Nairobi County, of which 80 were chosen. The descriptive survey design was used. The principal, dean of students, student leaders, and the county director of education were the units of observation. Data was gathered using an interview guide and questionnaires. The instruments were pre-tested to ensure their content, construct validity, and reliability. Data were analyzed by computing descriptive and inferential statistics using SPSS. The study discovered a positive link between the availability and the management of KCSE irregularities. The study, therefore, concluded that adequate learning resources such as laboratory equipment, instructional or teaching aids, textbooks, revision books, a well-equipped school library, and spacious classrooms were very helpful in the management of examination irregularities. It recommended that sufficient funds be committed to developing school infrastructure, facilities, equipment, and learning resources and that the government, through the ministry of education, disburse adequate funds and material resources. The findings provide new insight on how to address examination irregularities.
Management of Information Literacy Programmes in Selected Technical Training Institution Libraries in Nairobi County, Kenya
Authors: Vennah Mogere Nyakerario , Gichugu Dr. Martin
Published: October 2024

Technical Training Institution Libraries are facing the challenge of managing information literacy programs. Also, there are limited information literacy programmes in Technical Institution Libraries. This study, therefore, sought to determine the management of information literacy programmes in selected Technical Training Institution Libraries in Nairobi County. The objectives were to establish the implementation strategies of information literacy programmes in selected technical institutional libraries; to establish how frequent information literacy programmes are reviewed in selected technical institutional libraries; to determine the perceptions of the implemented information literacy programmes amongst users in selected technical institutional libraries; to identify the major challenges associated with the implementation of information literacy programmes in selected technical institutional libraries. This study adopted a descriptive survey design. A total of 333 respondents comprising 5 librarians, 190 teaching staff, and 138 students from five selected Technical Training Institutions constituted the subjects for this study. The study established that Technical Institution Libraries were implementing various forms of strategies for information literacy; information literacy programmes are reviewed after every orientation process using a feedback form; important skills are acquired by the library patrons during information literacy training, and librarians were facing several challenges as they implemented information literacy programmes.
Direct and Indirect Salt Effects on Homotypic Phase Separation
Authors: MacAinsh Matthew , Dey Souvik , Zhou Huan-Xiang
Published: October 2024

The low-complexity domain of hnRNPA1 (A1-LCD) phase separates in a salt-dependent manner. Unlike many intrinsically disordered proteins (IDPs) whose phase separation is suppressed by increasing salt concentrations, the phase separation of A1-LCD is promoted by > 100 mM NaCl. To investigate the atypical salt effect on A1-LCD phase separation, we carried out all-atom molecular dynamics simulations of systems comprising multiple A1-LCD chains at NaCl concentrations from 50 to 1000 mM NaCl. The ions occupy first-shell as well as more distant sites around the IDP chains, with Arg sidechains and backbone carbonyls the favored partners of Cl
−
and Na
+
, respectively. They play two direct roles in driving A1-LCD condensation. The first is to neutralize the high net charge of the protein (+9) by an excess of bound Cl
−
over Na
+
; the second is to bridge between A1-LCD chains, thereby fortifying the intermolecular interaction networks in the dense phase. At high concentrations, NaCl also indirectly strengthens π-π, cation-π, and amino-π interactions, by drawing water away from the interaction partners. Therefore, at low salt, A1-LCD is prevented from phase separation by net charge repulsion; at intermediate concentrations, NaCl neutralizes enough of the net charge while also bridging IDP chains to drive phase separation. This drive becomes even stronger at high salt due to strengthened π-type interactions. Based on this understanding, four classes of salt dependence of IDP phase separation can be predicted from amino-acid composition.
Polysaccharide breakdown products drive degradation-dispersal cycles of foraging bacteria through changes in metabolism and motility
Authors: Stubbusch Astrid Katharina Maria , Keegstra Johannes M , Schwartzman Julia , Pontrelli Sammy , Clerc Estelle E , Charlton Samuel , Stocker Roman , Magnabosco Cara , Schubert Olga T , Ackermann Martin , D'Souza Glen G
Published: October 2024

Most of Earth’s biomass is composed of polysaccharides. During biomass decomposition, polysaccharides are degraded by heterotrophic bacteria as a nutrient and energy source and are thereby partly remineralized into CO2. As polysaccharides are heterogeneously distributed in nature, following the colonization and degradation of a polysaccharide hotspot the cells need to reach new polysaccharide hotspots. Even though many studies indicate that these degradation-dispersal cycles contribute to the carbon flow in marine systems, we know little about how cells alternate between polysaccharide degradation and motility, and which environmental factors trigger this behavioral switch. Here, we studied the growth of the marine bacterium Vibrio cyclitrophicus ZF270 on the abundant marine polysaccharide alginate, both in its soluble polymeric form as well as on its breakdown products. We used microfluidics coupled to time-lapse microscopy to analyze motility and growth of individual cells, and RNA sequencing to study associated changes in gene expression. We found that single cells grow at reduced rate on alginate until they form large groups that cooperatively break down the polymer. Exposing cell groups to digested alginate accelerates cell growth and changes the expression of genes involved in alginate degradation and catabolism, central metabolism, ribosomal biosynthesis, and transport. However, exposure to digested alginate also triggers cells to become motile and disperse from cell groups, proportionally increasing with the group size before the nutrient switch, and this is accompanied by high expression of genes involved in flagellar assembly, chemotaxis, and quorum sensing. The motile cells chemotax toward polymeric but not digested alginate, likely enabling them to find new polysaccharide hotspots. Overall, our findings reveal cellular mechanisms that might also underlie bacterial degradation-dispersal cycles, which influence the remineralization of biomass in marine environments.
Biochemical Changes and Germination Response of Indian Sandalwood (Santalum album L.) Seeds Subjected to Biopriming Techniques and Variable Post-priming Storage
Authors: Debta Harish , Kunhamu T.K. , Santhoshkumar A.V , Jamaludheen V. , Binu N.K. , Jisha K.C.
Published: October 2024

Understanding of the storage behaviour of endangered plant species such as Indian Sandalwood, Santalum album L. is important for successful conservation. We tested biopriming method with five biopriming agents (e.g. Effective microorganisms; Plant growth promoting rhizobacteria (PGPR-I and PGPR-II); Pseudomonas fluorescens and Piriformospora indica) with four uniform durations of treatments viz. 2, 4, 6 and 8 days. Hydropriming was also performed with similar condition for comparison of seed performance. The study examined the biochemical changes that occur in Sandalwood seeds during different post-priming storage periods (0, 30, 60, 90 days) to assess the efficacy of biopriming techniques on seed germination and health. Biopriming with Pseudomonas fluorescens for eight days recorded the highest germination percentage (70.67%) and the highest germination rate index (0.84). Longer durations of PGPR-I and Piriformospora indica treatment (6-8 days) lowered the imbibition period and mean germination time while increasing the germination rate. After a post-priming storage period of 30 days, only EM and Pseudomonas fluorescens treated seeds germinated while all other treatments failed to germinate. Absence of germination in any biopriming group at 60 and 90 days storage period indicated that the sandal seeds deteriorated over extended storage period. The reduction in seed viability of sandal seeds was consequent to the changes in the biochemical characteristics and action of enzymes (α and β amylases) involved in seed food reserve depletion and loss in membrane integrity.
Predictors of Individual Work Performance among Private Business Companies for an Enhanced Organizational Human Resource Plan
Authors: Soriano Melvin
Published: October 2024

This study aimed to examine the influence of organizational culture and multi-dimensional self-control as predictors of individual work performance among employees in private business companies. A descriptive-correlational research design was employed, involving 110 respondents from Santo Tomas, Davao del Norte, selected through stratified sampling. Data were collected using three standardized questionnaires, and statistical tools such as Mean, Pearson r, Standard Deviation, and Regression Analysis were applied. The results indicated that both organizational culture and multi-dimensional self-control had significant positive relationships with individual work performance. Specifically, organizational culture was rated with an overall mean of 4.32 (strongly agree), while multi-dimensional self-control scored 3.80 (agree), and individual work performance received an overall mean of 3.75 (agree). These findings suggest that fostering a strong organizational culture and enhancing employee self-control are key strategies for improving work performance, especially in culturally diverse environments. While Presidential Decree No. 442, Article 3, emphasizes the protection of workers' rights and labor laws, its relevance in this study lies in the broader context of promoting effective organizational practices. The study concludes that interventions to strengthen company culture and develop training programs focused on enhancing self-control may significantly boost employee performance. Future recommendations call for more specific and targeted approaches to implement these interventions within organizational frameworks.
Two Endogenous Endophthalmitis Cases Accompanying Nephrological Condition in Diabetic Patients
Authors: Moutei Hassan , Benaddou Sara , Bennis Ahmed , Chraibi Fouad , Abdellaoui Meriem , Benatiya Idriss
Published: October 2024

Aims: This report aims to highlight the importance of prompt diagnosis and intervention in cases of endogenous endophthalmitis, with particular focus on its nephrological etiology and associated systemic infections.
Presentation of Case: Two cases of endogenous endophthalmitis were observed in patients with nephrological complications. Case 1 involved a 50-year-old man with end-stage renal disease on hemodialysis, who presented with severe visual impairment in the right eye due to Staphylococcus aureus sepsis from a hemodialysis catheter infection. Despite aggressive treatment with intravitreal and systemic antibiotics, the patient’s visual prognosis was poor. Case 2 involved a 65-year-old woman with acute pyelonephritis and undiagnosed diabetes, presenting with unilateral visual loss and ocular inflammation. Systemic and intravitreal antibiotics, alongside corticosteroids, led to a favorable outcome with a final visual acuity of 7/10.
Discussion: Diabetic patients with nephrological conditions are particularly susceptible to endogenous endophthalmitis due to compromised immunity and increased risk of systemic infections. Both cases underscore the link between systemic infections, particularly in patients with renal or diabetic conditions, and endogenous endophthalmitis. Prompt recognition of ocular symptoms in patients with systemic infections is critical, as appropriate intervention can preserve visual function. The role of broad-spectrum antibiotics, intravitreal injections, and systemic infection control is emphasized.
Conclusion: These cases illustrate the importance of multidisciplinary intervention in managing endogenous endophthalmitis secondary to nephrological infections. While outcomes vary depending on disease severity and patient health, rapid diagnosis and treatment are vital to improving prognosis and preserving vision.
Cytochrome P450 (CYP1A2) Genetic Polymorphism as a Genetic Marker for Treatment Outcome in Early Breast Cancer Patients
Authors: Elaziz Lamiaa Mahmoud Abd , Gad Omnea Abd El-Fattah , Badawy Thoraya El-Sayed , El-Bendary Amal Said
Published: October 2024

Background: Cytochrome P450(CYP1A2) has a crucial role in drug metabolism, and some neurotoxins. Polymorphisms of Cytochrome P450(CYP1A2) have a role in cancer activity through affecting aromatic hydrocarbon metabolism. This work was aimed at studying CYP1A2 polymorphism as a genetic predictive marker of treatment out come in breast cancer (BC) female cases.
Methods: This case control research included 70 cases. Patients’ group (50 cases) were categorized into two groups: Group I A (n=20): failed BC cases for hormonal therapy during treatment period, group I B (n=30):  after 5 years of hormonal treatment which subdivided into two groups: [treatment failure (recurrence or metastasis) and patients with successful outcome] and group II (n=20): normal female subjects.
Results: The occurrence of treatment events was significant in patients carrying Polymorphism of Cytochrome P450(CYP1A2) (CYP1A2 rs762551) C/A. Also, relapse was earlier in patients with CYP1A2 carrying C allele and earlier among CC compared to C/A and wild allele. There was significantly higher in positive family history than in negative ones, with about 85.0% of positive family patients carrying C/A polymorphism and 77.8% in CC polymorphism. The incidence of BC events was studied using Kaplan-Meier scale to study event free survival in relation to CYP1A2 rs 762551 in postmenopausal BC patients treated with AI along five years treatment.
Conclusions: CYP1A2 genetic polymorphism is associated with early treatment events among female cases developing BC treated by aromatase inhibitors.
Differential requirement for ATG2A domains for localization to autophagic membranes and lipid droplets
Authors: Tamura Norito , Nishimura Taki , Sakamaki Yuriko , Koyama‐Honda Ikuko , Yamamoto Hayashi , Mizushima Noboru
Published: November 2017

ATG2 is one of the autophagy‐related (ATG) proteins essential for autophagosome formation and localizes to isolation membranes and lipid droplets in mammalian cells. Here, we investigated the requirement of regions in ATG2A for its organellar localization and function. The N‐terminal amino acids 1–198 and the C‐terminal amino acids 1830–1938 are required for the localization to isolation membranes and lipid droplets, respectively. The C‐terminal region is not required for the localization to isolation membranes and for autophagy. We also identified an amphipathic helix in ATG2A that is required for both its localization to organelles and autophagosome formation. These data suggest that the dual localization of ATG2A is regulated by different regions.
Mitochondrial helicase Irc3 translocates along double‐stranded DNA
Authors: Sedman Tiina , Garber Natalja , Gaidutšik Ilja , Sillamaa Sirelin , Paats Joosep , Piljukov Vlad J. , Sedman Juhan
Published: November 2017

Irc3 is a superfamily II helicase required for mitochondrial DNA stability in Saccharomyces cerevisiae. Irc3 remodels branched DNA structures, including substrates without extensive single‐stranded regions. Therefore, it is unlikely that Irc3 uses the conventional single‐stranded DNA translocase mechanism utilized by most helicases. Here, we demonstrate that Irc3 disrupts partially triple‐stranded DNA structures in an ATP‐dependent manner. Our kinetic experiments indicate that the rate of ATP hydrolysis by Irc3 is dependent on the length of the double‐stranded DNA cosubstrate. Furthermore, the previously uncharacterized C‐terminal region of Irc3 is essential for these two characteristic features and forms a high affinity complex with branched DNA. Together, our experiments demonstrate that Irc3 has double‐stranded DNA translocase activity.
Dabrafenib inhibits the growth of BRAF‐WT cancers through CDK16 and NEK9 inhibition
Authors: Phadke Manali , Remsing Rix Lily L. , Smalley Inna , Bryant Annamarie T. , Luo Yunting , Lawrence Harshani R. , Schaible Braydon J. , Chen Yian A. , Rix Uwe , Smalley Keiran S. M.
Published: November 2017

Although the BRAF inhibitors dabrafenib and vemurafenib have both proven successful against BRAF‐mutant melanoma, there seem to be differences in their mechanisms of action. Here, we show that dabrafenib is more effective at inhibiting the growth of NRAS‐mutant and KRAS‐mutant cancer cell lines than vemurafenib. Using mass spectrometry‐based chemical proteomics, we identified NEK9 and CDK16 as unique targets of dabrafenib. Both NEK9 and CDK16 were highly expressed in specimens of advanced melanoma, with high expression of both proteins correlating with a worse overall survival. A role for NEK9 in the growth of NRAS‐ and KRAS‐mutant cell lines was suggested by siRNA studies in which silencing was associated with decreased proliferation, cell cycle arrest associated with increased p21 expression, inhibition of phospho‐CHK1, decreased CDK4 expression, and the initiation of a senescence response. Inhibition of CDK4 but not CHK1 recapitulated the effects of NEK9 silencing, indicating this to be the likely mechanism of growth inhibition. We next turned our attention to CDK16 and found that its knockdown inhibited the phosphorylation of the Rb protein at S780 and increased expression of p27. Both of these effects were phenocopied in NRAS‐ and KRAS‐mutant cancer cells by dabrafenib, but not vemurafenib. Combined silencing of NEK9 and CDK16 was associated with enhanced inhibition of melanoma cell proliferation. In summary, we have identified dabrafenib as a potent inhibitor of NEK9 and CDK16, and our studies suggest that inhibition of these kinases may have activity against cancers that do not harbor BRAF mutations.
A Dynamical Explanation of the Topographically Bound Easterly Low‐Level Jet Surrounding Antarctica
Authors: Fulton Scott R. , Schubert Wayne H. , Chen Zhengqing , Ciesielski Paul E.
Published: November 2017

This study investigates the topographically bound easterly low‐level jet surrounding Antarctica. This jet is modeled as a balanced flow that satisfies the potential vorticity invertibility principle, based on local linear balance in spherical coordinates and expressed in isentropic coordinates. In this way, this easterly low‐level jet is shown to be the balanced flow associated with the topography of the Antarctic plateau, moderated by a shallow potential vorticity anomaly atop the plateau produced by radiative cooling. The dynamical connection of the jet with katabatic winds can be understood through the meridional circulation equation. Model results based on the simple theoretical arguments developed here are found to be consistent with high‐resolution reanalysis data from the European Centre for Medium‐Range Weather Forecasts for the 2008–2010 period.
Emerging Stress and Relative Resiliency of Giant Sequoia Groves Experiencing Multiyear Dry Periods in a Warming Climate
Authors: Su Yanjun , Bales Roger C. , Ma Qin , Nydick Koren , Ray Ram L. , Li Wenkai , Guo Qinghua
Published: November 2017

The relative greenness and wetness of Giant Sequoia (Sequoiadendron giganteum) groves and the surrounding Sierra Nevada, California forests were investigated using patterns in vegetation indices from Landsat imagery for the period 1985–2015. Vegetation greenness (normalized difference vegetation index) and thus forest biomass in groves increased by about 6% over that 30 year period, suggesting a 10% increase in evapotranspiration. No significant change in the surrounding nongrove forest was observed. In this period, local temperature measurements showed an increase of about 2.2°C. The wetness of groves (normalized difference wetness index) showed no overall long‐term trend but responded to changes in annual water‐year precipitation and temperature. The long‐term trends of grove greenness and wetness varied by elevation, with the lower rain‐snow transition elevation zone (1,700–2,100 m) marking a change from an increasing trend at lower elevations to a decreasing trend at higher elevations. The 2011–2015 drought brought an unprecedented drop in grove wetness, over 5 times the 1985–2010 standard deviation, and wetness in SEGI groves dropped 50% more than in nongrove areas. Overall, the wetness and greenness of SEGI groves showed a larger response to the warming climate and drought than nongrove areas. The influence of droughts on the wetness of SEGI groves reflected effects of both the multidecadal increase in forest biomass and the effects of warmer drought‐year temperatures on the evaporative demand of current grove vegetation, plus sufficient regolith water storage of rain and snowmelt to sustain that vegetation through seasonal and multiyear dry periods.
Interacting Effects of Leaf Water Potential and Biomass on Vegetation Optical Depth
Authors: Momen Mostafa , Wood Jeffrey D. , Novick Kimberly A. , Pangle Robert , Pockman William T. , McDowell Nate G. , Konings Alexandra G.
Published: November 2017

Remotely sensed microwave observations of vegetation optical depth (VOD) have been widely used for examining vegetation responses to climate. Nevertheless, the relative impacts of phenological changes in leaf biomass and water stress on VOD have not been explicitly disentangled. In particular, determining whether leaf water potential (ψL) affects VOD may allow these data sets as a constraint for plant hydraulic models. Here we test the sensitivity of VOD to variations in ψL and present a conceptual framework that relates VOD to ψL and total biomass including leaves, whose dynamics are measured through leaf area index, and woody components. We used measurements of ψL from three sites across the US—a mixed deciduous forests in Indiana and Missouri and a piñon‐juniper woodland in New Mexico—to validate the conceptual model. The temporal dynamics of X‐band VOD were similar to those of the VOD signal estimated from the new conceptual model with observed ψL (R2 = 0.6–0.8). At the global scale, accounting for a combination of biomass and estimated ψL (based on satellite surface soil moisture data) increased correlations with VOD by ~ 15% and 30% compared to biomass and water potential, respectively. In wetter regions with denser and taller canopy heights, VOD has a higher correlation with leaf area index than with water stress and vice versa in drier regions. Our results demonstrate that variations in both phenology and ψL must be considered to accurately interpret the dynamics of VOD observations for ecological applications.
Safety of Retroviral Vectors in Clinical Applications: Lessons from Retroviral Biology and Pathogenesis
Authors: Neil James C
Published: November 2017

The ability of retroviruses to integrate a precise copy of the viral genome into host cell DNA (deoxyribonucleic acid) has been harnessed in the development of retroviral vectors for stable delivery of foreign genes to target cells. Over several decades, these tools have been utilised in human medicine in diverse applications from cell lineage tracing by gene marking to correction of single‐gene disorders and therapy of cancer. The unanticipated occurrence of leukaemias due to vector insertional mutagenesis in trials of gene therapy led to an urgent search for safer vectors and delivery systems. The advent of T‐cell therapy for cancer has led to renewed interest in retroviral vectors as stable and efficient delivery vehicles and is supported by observations suggesting that mature T cells are relatively resistant to oncogenic transformation by retroviruses. However, this evidence is circumstantial and the long‐term risks are poorly understood. Retroviral vector safety is considered here from the perspective of the biology and pathogenesis of their parental viruses. It is suggested that robust cell suicide strategies to remove transduced cells are likely to be important if retroviral vectors are to be adopted widely for delivery of T‐cell therapy for cancer and other diseases.

Key Concepts

Retroviral vectors are useful tools for delivery of foreign genes to host cells
in vitro
and
in vivo
.

The term retroviral vector is generally used for a vector based on a gamma‐retrovirus such as murine leukaemia virus.

The term lentiviral vector is generally used for a vector based on human immunodeficiency virus type 1.

Retroviral vectors have been tested in many clinical applications including cell lineage tracing, gene therapy and cancer therapy.

Retroviruses can cause disease due to insertional mutagenesis or transduction of host cell genes.

Retroviral and lentiviral integration are nonrandom processes that favour active regions of the genome, increasing the risks of insertional mutagenesis.

Examples of retroviral transduction of host genes include a T‐cell receptor β‐chain gene, providing a parallel with cells engineered for use in T‐cell therapy of cancer.
CRISPR‐Cas9
: A New Tool for Gene Therapy
Authors: Sharma Saumya , Maiti Souvik , Chakraborty Debojyoti
Published: November 2017

Programmable RNA (ribonucleic acid)‐guided genome engineering using the recently developed clustered regularly interspaced short palindromic repeats (CRISPR)‐associated (CRISPR Cas) system has revolutionised the field of gene editing owing its adaptability and versatility in addressing a wide range of biological questions. It relies on harnessing critical components of the bacterial acquired immune system, namely the Cas9 protein and its associated guide ribonucleic acid (gRNA), to selectively target and edit a desired gene, thereby underscoring its potential as a promising gene therapy agent. Its application, however, encompasses several critical parameters, ranging from safe delivery of the agent to tackling issues of unintended off‐targeting in the genome. Similar to its predecessor molecular scissors, namely zinc finger nucleases (ZFNs) and transcription activator‐like nucleases (TALENs), CRISPR‐Cas9 has been studied extensively along these lines to facilitate its use in therapeutic interventions and has shown some early promise in taking benchtop discoveries to the clinic.

Key Concepts

CRISPR‐Cas9 is the most recent addition to the repertoire of ‘molecular scissors’ for genome editing.

The system relies on an RNA‐guided protein that can make desirable changes in the genome.

CRISPR‐Cas9 has shown a lot of promise for
in vivo
and
in vitro
editing, which can be translatable for disorders, particularly monogenic ones.

Components of the system have been used for correcting several disease‐relevant mutations in mice through zygotic, somatic or
ex vivo
gene‐editing strategies.

The success of CRISPR as a therapeutic tool depends on its inherent properties of efficiency and specificity.

Protein and sgRNA engineering combined with improved delivery strategies have led to the discovery of potent CRISPR‐based therapy products.

The first clinical trials using CRISPR are currently under process.
External Possession and Possessor Raising
Authors: Deal Amy Rose
Published: November 2017

External possession is a phenomenon where a nominal is syntactically encoded as a verbal dependent but semantically understood as the possessor of one of its co‐arguments. While the general pattern is cross‐linguistically very common, there is much variation in its precise syntax and semantics. In this chapter, I review the classic analyses of external possession as possessor raising and possessor binding. The evidence behind these analyses indicates that raising and binding are indeed each appropriate for certain subtypes of external possession, as is an analysis in terms of movement to thematic positions. I propose a typology that groups these analyses under the first of two major types of external possession. This first type presents significant parallels to the domain of raising and control, subsuming possessor raising, possessor binding, possessor control, and a variant of exceptional case marking (ECM). Examples are found in Nez Perce, German, Brazilian Portuguese, and English. A second major type of external possession involves subjects only and brings information structural effects. Examples are found in Malagasy, Chickasaw, Tz'utujil, and Japanese.
Ellipsis in Noun Phrases
Authors: Lobeck Anne , Sleeman Petra
Published: November 2017

In early analyses of nominal ellipsis in generative syntax, ellipsis was analyzed as null anaphora, where missing material is interpreted under identity with an antecedent in much the same way as a lexical pronoun. Ellipsis was analyzed either as the result of a deletion transformation, in which ellipsis results from deletion of a lexical pro‐form,one, or as a base‐generated empty category subject to rules of interpretation. Within the Principles and Parameters framework, nominal ellipsis was subsequently analyzed as involving proper government ofpro, an empty pronominal category, which has to be licensed and identified. This approach led to in‐depth, cross‐linguistic analyses of the properties of the determiner and quantifier systems to determine the feature specifications of different functional heads, and the role those features play in licensing and identification. This research also explored connections between ellipsis in DP and substantive adjective and partitive constructions, in particular partitives which involve cliticen(French) andne(Italian). In current research the same questions are still debated, but in more recent theoretical frameworks: the Minimalist Program, Distributed Morphology and Cartography. The questions concern PF‐deletion or late insertion, the role of functional projections such as Classifier Phrase and nP, and the role of focus.
Double Nominatives in Japanese
Authors: Tateishi Koichi
Published: November 2017

It is well known that nominative subjects can be doubled or multiplied in Japanese in ordinary clausal contexts. Various types of analysis have been proposed on the topic. However, many of them mix up notions involved in the issue of the Double Nominative Construction in Japanese. First of all, it has never been logically proven that it is nominative that is involved in the construction (and in “subjecthood” in Japanese in general). Second, nominatives, doubled or not, have “semantic” contents that English nominative subjects do not have. Third, if, in the Government‐and‐Binding/‐Minimalist spirit, the nominative is assigned/licensed by a functional category in Japanese, then we will be situated in a paradoxical state in which case (including nominative) can be multiplied but complementizers can not necessarily. Fourth, in Japanese, the mode of realization of case is different from that in languages like English, as a result of which various sorts of case particles are developed therein. Finally, we do not yet know the true relationship between Japanese case particles and Japanese “adverbial” particles such as
wa
(
top
) and
mo
‘also’. The conventional term “matrix clause phenomena” cannot explain everything on this. In a nutshell, to discuss and analyze the Double Nominative Construction in Japanese, we need to know what the subject is in Japanese, what case is, and whether case in some sense exists in Japanese at all. Various types of Double Nominative/Subject Constructions are compared and it will be pointed out that we at least need to keep in mind several levels of “subjecthood” when we come to discussions of Japanese subjects/nominatives.
Freezing Effects
Authors: Corver Norbert
Published: November 2017

The notion of freezing refers to the phenomenon whereby a constituent becomes an island for extraction when that constituent has undergone syntactic movement (displacement). In other words, the constituent is opaque (“frozen”) in its movement‐derived position. This chapter presents different types of movement‐derived syntactic configurations that display freezing effects and discusses various approaches that have been proposed in generative grammar in order to account for the frozen status of displaced constituents. The chapter further addresses the question as to whether a displaced constituent is an absolute barrier for extraction. That is, are there syntactic configurations from which extraction out of a displaced constituent is possible after all?
Verb‐Initial Word Orders, Primarily in Austronesian and Mayan Languages
Authors: Clemens Lauren Eby , Polinsky Maria
Published: November 2017

This chapter presents several approaches to the syntax of verb‐initial (V1) languages with a special emphasis on Mayan and Austronesian languages. Some V1 languages are strictly VSO, others are VOS, and a significant number combine both orders. This chapter focuses on data from VSO/VOS languages and the factors that underlie these alternations. A number of V1 languages can be more adequately characterized as predicate‐initial, with V1 representing just a subset of possible clause‐initial predicates. The chapter presents a number of structural properties that are or may be associated with V1 and discusses possible implicational relations between such properties and V1. While there are certain common characteristics observed across V1 languages, it is also clear that there are several distinct subtypes of V1. These subtypes call for different syntactic analyses; main approaches include the derivation of V1 via phrasal movement (VP‐raising) and via head‐movement (verb‐raising). Other syntactic approaches to the derivation of V1 include the parametrization of specifier direction within a single language, non‐configurational syntax, and subject lowering. In addition to these purely syntactic analyses, several recent approaches place the derivation of V1 outside syntax or at the syntax–PF interface. Careful, in‐depth analyses of individual languages are required to test the different approaches to V1; in quite a few cases such analyses are still lacking.
Control Phenomena
Authors: Potsdam Eric , Haddad Youssef A.
Published: November 2017

Control phenomena have been at the center of syntactic theorizing almost since the inception of generative grammar. To first approximation, control is an interpretive dependency between two arguments: a lexicalized noun phrase (the controller) and a null argument in a dependent clause (the controllee), as inSandyhopes [∅to succeed]. The primary concerns of syntactic theories have been accounting for various characteristics of the null controllee and the identification of its controller. This chapter surveys some of the phenomena that have driven our current understanding of these issues. Within the domain of obligatory control, some phenomena speak to the controller: the behavior of polyadic predicates, implicit control, variable control and control shift, and exceptional cases likepromise. Other phenomena speak to the controllee: exhaustive control, partial control, split control, and control in embedded questions. Assuming that non‐obligatory control is a kind of elsewhere case, the phenomena relevant to non‐obligatory control are those where obligatory control restrictions on controller choice fail to materialize: control into subjects, extraposed clauses, and some adjunct clauses. The chapter also discusses phenomena with a non‐canonical realization of the control relation: backward control and copy control. Within the context of these phenomena, the chapter surveys current generative approaches to the analysis of control: dominant PRO‐based approaches, the movement theory of control, and restructuring analyses. Relative strengths and weaknesses are highlighted.
Measure Phrases and Semi‐Lexical Nouns
Authors: Csirmaz Anikó , Stavrou Melita
Published: November 2017

Measure phrases (MPs, e.g., “two pounds”) appear in a wide variety of environments: nominal, adjectival, adpositional, and verbal structures. The goal of the chapter is to present an overview of the variety of constructions involving MPs as well as the different treatments that were proposed for these structures. Accordingly, the chapter reviews the internal structure of measure expressions as well as the function (predicate nominal, modifier or argument) and position of MPs inside the larger structures that contain them. The structures to be discussed include positive and differential MPs, which appear with adjectives as well as in compound, partitive, and pseudopartitive constructions with nominals. The chapter also addresses variation in the acceptability of MPs, both language‐internally and across languages, as well as the cross‐linguistically distinct realizations of structures that contain MPs. Other topics to be discussed are issues specific to spatial (“twenty miles”) and temporal measure expressions (“twenty minutes”) as well as classifier and container constructions.
Article Doubling
Authors: Lekakou Marika
Published: November 2017

This chapter deals with the doubling of the definite and indefinite article. After a brief introduction to the syntactic and semantic function of (in)definite articles and to the relevance of doubling for syntactic and semantic research, I review the main instantiations of each type of phenomenon. I deal with definite doubling as it is attested in North Germanic languages, in Modern Greek, and in Hebrew. Doubling occurs in these varieties predominantly when adjectival modification is involved; it is obligatory in Hebrew and in certain Northern Germanic languages, and optional in Greek, where it incurs semantic effects related to the restrictive interpretation of the adjective. In the case of Hebrew and Northern Germanic, the debate has revolved around the choice between head movement and phrasal movement within a determiner phrase (DP) analysis of nominals and around the status of the doubling elements; for Hebrew, the idea of a concord relation between the doubling elements has also been exploited. In the case of Greek, major points of controversy have been whether doubling involves an underlying predicative structure and a DP‐internal focus projection. Indefinite doubling is much less widespread cross‐linguistically. It is known to occur in some dialectal variants of Swedish and Norwegian, where it can be argued to involve a predication structure. A different instance of indefinite doubling occurs in Bavarian in the presence of quantificational elements. In this final case, doubling is argued to involve non‐identical elements. The suggestion is made that indefinite doubling as such does not exist at all.
Prolepsis
Authors: Salzmann Martin
Published: November 2017

The linguistic termprolepsisrefers to a construction where a structural complement of the matrix verb is semantically related to the predicate of an embedded clause. In an example likeI believe of John that he likes Mary, the proleptic constituentJohnis related to the position occupied by the coreferential pronounhe.. At first sight one may take the proleptic constituent to be an argument of the matrix verb with the pronoun establishing an anaphoric dependency, but things are more complex. First, the construction is possible with a very wide range of matrix verbs, casting doubt on the argumenthood of the object. Second, a coreferential element is obligatory, which argues against a mere aboutness relationship. There is conflicting evidence concerning the base position of the proleptic object. On the one hand, there is solid evidence from anaphor binding and superiority that the proleptic object occupies an A‐position in the matrix clause. On the other hand, the proleptic object reconstructs into the complement clause. This suggests that the proleptic object originates in the embedded clause, but an analysis involving movement from the complement clause fails for conceptual (Improper Movement, Freezing) and empirical (selective reconstruction effects) reasons. It is proposed that these paradoxical properties follow if the proleptic object is licensed by predication. The complement clause involves a base‐generated operator which turns it into an open sentence. The coreferential pronoun is the variable bound by the operator. The proleptic object, then, is the subject of the predication. The relationship between the proleptic object and the silent operator involves ellipsis, as does the relationship between the operator and the coreferential pronoun. Ellipsis derives the (selective) reconstruction effects, and predication explains the necessity of a coreferential element.
Pied‐Piping
Authors: Horvath Julia
Published: November 2017

“Pied‐piping” has been viewed throughout the evolution of generative grammar as involving the displacement of a constituent that is larger than, and properly contains, the element the particular movement operation is normally targeting (such as awh‐word contained within some larger phrase, e.g.,which (boy)/whoseinwhich boy's father/whose friends). Being an effect directly associated with movement operations, its status and accounts have undergone significant shifts in the course of the evolution of the theory of grammar. The chapter provides a comprehensive overview of pied‐piping phenomena and discusses proposed analyses along with the theoretical contexts in which they arose. It lays out the variety of pied‐piping effects and central generalizations observed in the literature of the past decades regarding what pretheoretically can be considered pied‐piping structures. Starting with Ross' Pied‐Piping Convention, the chapter critically assesses the status and treatments of (apparent) pied‐piping, from Ross’ stipulation of a split between what triggers movement and what size constituents end up moving, via the Government and Binding model's “feature percolation” mechanisms and “Move α,” to potential accommodation of pied‐piping effects within the Minimalist Program's restrictive framework, relying only on projection, not feature percolation crossing maximal projections, and on “Agree.” The chapter delineates the descriptive dimensions of pied‐piping primarily based onwh‐movement. It examines attested construction‐specific variation – namely,wh‐pied‐piping in restrictive and non‐restrictive relative clauses,wh‐questions, and free relatives – and explores structural properties of the phenomenon such as the phrase‐internal position of the pied‐piper, the category types of pied‐piped phrases, and non‐wh‐pied‐pipers. The related theoretical issues assessed include the locality/structural limitations on what can induce a pied‐piping effect, the “repair” nature of pied‐piping, the status of marked “massive” pied‐piping, and attested parametric variation. The chapter discusses feature percolation approaches and outlines two recent alternatives dispensing with the latter within a minimalist perspective.
Topic Prominence
Authors: Paul Waltraud , Whitman John
Published: November 2017

We assimilate the typological feature of topic prominence to established treatments of the left periphery. East Asian languages grouped together as topic‐prominent turn out to display important differences. In Japanese and Korean, the A‐domain extends higher than in Chinese, to include a fused FocusP/FiniteP projection. Descriptive properties sometimes associated with topic prominence include (1) obligatoriness of topics, (2) null topics, (3) overt spell‐out of the head of TopicP, (4)whin situ, (5) obligatory topicalization of generic DPs, (6) multiple topics, and (7) free ordering of argument and adjunct topics. However, all or most of these features can be found in non‐East Asian languages with an active left periphery, including full and residual V2 languages. The salient feature of the languages traditionally labeled topic‐prominent is that they do not fill the functional head of the Topic projection by movement; if at all, this head is filled by topic particles.