Engineered Two-Dimensional Transition Metal Dichalcogenides for Energy Conversion and Storage.

Designing efficient and cost-effective materials is pivotal to solving the key scientific and technological challenges at the interface of energy, environment, and sustainability for achieving NetZero. Two-dimensional transition metal dichalcogenides (2D TMDs) represent a unique class of materials that have catered to a myriad of energy conversion and storage (ECS) applications. Their uniqueness arises from their ultra-thin nature, high fractions of atoms residing on surfaces, rich chemical compositions featuring diverse metals and chalcogens, and remarkable tunability across multiple length scales. Specifically, the rich electronic/electrical, optical, and thermal properties of 2D TMDs have been widely exploited for electrochemical energy conversion (e.g., electrocatalytic water splitting), and storage (e.g., anodes in alkali ion batteries and supercapacitors), photocatalysis, photovoltaic devices, and thermoelectric applications. Furthermore, their properties and performances can be greatly boosted by judicious structural and chemical tuning through phase, size, composition, defect, dopant, topological, and heterostructure engineering. The challenge, however, is to design and control such engineering levers, optimally and specifically, to maximize performance outcomes for targeted applications. In this review we discuss, highlight, and provide insights on the significant advancements and ongoing research directions in the design and engineering approaches of 2D TMDs for improving their performance and potential in ECS applications.

Phase Stability of Hexagonal/Cubic Boron Nitride Nanocomposites.

Boron nitride (BN) is an exceptional material, and among its polymorphs, two-dimensional (2D) hexagonal and three-dimensional (3D) cubic BN (h-BN and c-BN) phases are most common. The phase stability regimes of these BN phases are still under debate, and phase transformations of h-BN/c-BN remain a topic of interest. Here, we investigate the phase stability of 2D/3D h-BN/c-BN nanocomposites and show that the coexistence of two phases can lead to strong nonlinear optical properties and low thermal conductivity at room temperature. Furthermore, spark-plasma sintering of the nanocomposite shows complete phase transformation to 2D h-BN with improved crystalline quality, where 3D c-BN possibly governs the nucleation and growth kinetics. Our demonstration might be insightful in phase engineering of BN polymorph-based nanocomposites with desirable properties for optoelectronics and thermal energy management applications.

Manganese(I)-Catalyzed Chemoselective Transfer Hydrogenation of the C=C Bond in Conjugated Ketones at Room Temperature.

Chemoselective transfer hydrogenation of C=C bond in α,ß-unsaturated ketones is demonstrated at room temperature employing a manganese(I) catalyst and half an equivalent of ammonia-borane (H3 N-BH3 ). A series of mixed-donor pincer-ligated Mn(II) complexes, (tBu2 PN3 NPyz )MnX2 [κP ,κN ,κN -(N-(di-tert-butylphosphaneyl)-6-(1H-pyrazol-1-yl)pyridin-2-amine)MnX2 ] {X=Cl (Mn2), X=Br (Mn3), X=I (Mn4)} were synthesized and characterized. Amongst the Mn(II) complexes, (Mn2, Mn3, Mn4) and Mn(I) complex, (tBu2 PN3 NPyz )Mn(CO)2 Br (Mn1) screened; the Mn1 acts as an efficient catalyst for the chemoselective C=C bond reduction in α,ß-unsaturated ketones. Various synthetically important functionalities like halides, methoxy, trifluoromethyl, benzyloxy, nitro, amine, and unconjugated alkene and alkyne groups, including heteroarenes, were compatible and provided saturated ketones in excellent yields (up to 97 %). A preliminary mechanistic study highlighted the crucial role of metal-ligand (M-L) cooperation through the dearomatization-aromatization process in catalyst Mn1 for the chemoselective C=C bond transfer hydrogenation.

Safety outcomes of pembrolizumab with platinum agent chemotherapy combined with 5-fluorouracil or taxane derivative in head and neck cancer.

INTRODUCTION: For patients with metastatic head and neck squamous cell cancer (HNSCC), the outcomes of pembrolizumab in combination with a platinum agent and taxane as first-line therapy remain unknown. The purpose of this study is to characterize the impact of substituting the 5-fluorouracil (5-FU) backbone for a taxane in this chemoimmunotherapy regimen on safety/tolerability and survival outcomes. METHODS: This was an IRB-approved, single-center, retrospective, active comparator, new-user design study in adult patients with HNSCC treated between January 2018 and September 2021. The primary objective was to assess safety and tolerability of pembrolizumab in combination with a platinum agent and taxane against an active comparator arm of pembrolizumab in combination with a platinum agent and 5-FU. Safety and tolerability were evaluated by assessing differences in overall toxicities, with further secondary analysis evaluating differences in hematologic toxicities and pre-defined non-hematologic toxicities. RESULTS: There was no statistical difference demonstrated with the primary endpoint between the cohorts. Reduced toxicity rates were found in the taxane arm for mucositis and creatinine levels. No grade 4 non-hematologic toxicities were reported. Patients receiving 5-FU were more likely to have dose reductions upfront, discontinue treatment due to intolerances and had significantly higher mucositis. CONCLUSIONS: This study helps to characterize the safety profile and activity of pembrolizumab in combination with a platinum agent and taxane derivative in HNSCC patients. Within our study, substitution of 5-FU with a taxane did not show an increased risk of toxicities, worsened survival, or decreased odds of achieving a response. Mucositis and elevated creatinine rates were significantly reduced within the taxane arm.

Facets of facet joint interventions.

Facet joint (FJ) disease is a common cause of axial low back pain with many minimally invasive image-guided treatment options. This article discusses fluoroscopic and CT-guided intraarticular FJ injections, medial branch (MB) radiofrequency ablation (RFA), and lumbar facet synovial cyst (LFSC) aspiration, rupture, or fenestration. Additionally, the article will highlight medial branch blocks (MBBs) utilized to diagnose facet-mediated pain and to predict outcomes to RFA.

Cas3/I-C mediated target DNA recognition and cleavage during CRISPR interference are independent of the composition and architecture of Cascade surveillance complex.

In type I CRISPR-Cas system, Cas3-a nuclease cum helicase-in cooperation with Cascade surveillance complex cleaves the target DNA. Unlike the Cascade/I-E, which is composed of five subunits, the Cascade/I-C is made of only three subunits lacking the CRISPR RNA processing enzyme Cas6, whose role is assumed by Cas5. How these differences in the composition and organization of Cascade subunits in type I-C influence the Cas3/I-C binding and its target cleavage mechanism is poorly understood. Here, we show that Cas3/I-C is intrinsically a single-strand specific promiscuous nuclease. Apart from the helicase domain, a constellation of highly conserved residues-which are unique to type I-C-located in the uncharacterized C-terminal domain appears to influence the nuclease activity. Recruited by Cascade/I-C, the HD nuclease of Cas3/I-C nicks the single-stranded region of the non-target strand and positions the helicase motor. Powered by ATP, the helicase motor reels in the target DNA, until it encounters the roadblock en route, which stimulates the HD nuclease. Remarkably, we show that Cas3/I-C supplants Cas3/I-E for CRISPR interference in type I-E in vivo, suggesting that the target cleavage mechanism is evolutionarily conserved between type I-C and type I-E despite the architectural difference exhibited by Cascade/I-C and Cascade/I-E.

Light-Assisted Rechargeable Lithium Batteries: Organic Molecules for Simultaneous Energy Harvesting and Storage.

Lithium batteries that could be charged on exposure to sunlight will bring exciting new energy storage technologies. Here, we report a photorechargeable lithium battery employing nature-derived organic molecules as a photoactive and lithium storage electrode material. By absorbing sunlight of a desired frequency, lithiated tetrakislawsone electrodes generate electron-hole pairs. The holes oxidize the lithiated tetrakislawsone to tetrakislawsone while the generated electrons flow from the tetrakislawsone cathode to the Li metal anode. During electrochemical operation, the observed rise in charging current, specific capacity, and Coulombic efficiency under light irradiation in contrast to the absence of light indicates that the quinone-based organic electrode is acting as both photoactive and lithium storage material. Careful selection of electrode materials with optimal bandgap to absorb the intended frequency of sunlight and functional groups to accept Li-ions reversibly is a key to the progress of solar rechargeable batteries.

Photo Rechargeable Li-Ion Batteries Using Nanorod Heterostructure Electrodes.

New ways of directly using solar energy to charge electrochemical energy storage devices such as batteries would lead to exciting developments in energy technologies. Here, a two-electrode photo rechargeable Li-ion battery is demonstrated using nanorod of type II semiconductor heterostructures with in-plane domains of crystalline MoS2 and amorphous MoOx . The staggered energy band alignment of MoS2 and MoOx limits the electron holes recombination and causes holes to be retained in the Li intercalated MoS2 electrode. The holes generated in the MoS2 pushes the intercalated Li-ions and hence charge the battery. Low band gap, high efficiency photo-conversion and efficient electron-hole separation help the battery to fully charge within a few hours using solar light. The proposed concept and materials can enable next generation stable photo-rechargeable battery electrodes, in contrast to the reported materials.

Recent advances in nanomaterials based biosensors for point of care (PoC) diagnosis of Covid-19 - A minireview.

Early diagnosis and ultrahigh sample throughput screening are the need of the hour to control the geological spread of the COVID-19 pandemic. Traditional laboratory tests such as enzyme-linked immunosorbent assay (ELISA), reverse transcription polymerase chain reaction (RT-PCR) and computed tomography are implemented for the detection of COVID-19. However, they are limited by the laborious sample collection and processing procedures, longer wait time for test results and skilled technicians to operate sophisticated facilities. In this context, the point of care (PoC) diagnostic platform has proven to be the prospective approach in addressing the abovementioned challenges. This review emphasizes the mechanism of viral infection spread detailing the host-virus interaction, pathophysiology, and the recent advances in the development of affordable PoC diagnostic platforms for rapid and accurate diagnosis of COVID-19. First, the well-established optical and electrochemical biosensors are discussed. Subsequently, the recent advances in the development of PoC biosensors, including lateral flow immunoassays and other emerging techniques, are highlighted. Finally, a focus on integrating nanotechnology with wearables and smartphones to develop smart nanobiosensors is outlined, which could promote COVID-19 diagnosis accessible to both individuals and the mass population at patient care.

The Effectiveness of Intraosseous Basivertebral Nerve Radiofrequency Neurotomy for the Treatment of Chronic Low Back Pain in Patients with Modic Changes: A Systematic Review.

OBJECTIVE: Determine the effectiveness of intraosseous basivertebral nerve radiofrequency neurotomy for the treatment of chronic low back pain with type 1 or 2 Modic changes. DESIGN: Systematic review. POPULATION: Persons aged ≥18 years with chronic low back pain with type 1 or 2 Modic changes. INTERVENTION: Intraosseous basivertebral nerve radiofrequency neurotomy. COMPARISON: Sham, placebo procedure, active standard care treatment, or none. OUTCOMES: The primary outcome of interest was the proportion of individuals with ≥50% pain reduction. Secondary outcomes included ≥10-point improvement in function as measured by Oswestry Disability Index as well as ≥2-point reduction in pain score on the Visual Analog Scale or Numeric Rating Scale, and decreased use of pain medication. METHODS: Three reviewers independently assessed publications before May 15, 2020, in MEDLINE and Embase and the quality of evidence was evaluated using the Grades of Recommendation, Assessment, Development, and Evaluation framework. RESULTS: Of the 725 publications screened, seven publications with 321 participants were ultimately included. The reported 3-month success rate for ≥50% pain reduction ranged from 45% to 63%. Rates of functional improvement (≥10-point Oswestry Disability Index improvement threshold) ranged from 75% to 93%. For comparison to sham treatment, the relative risk of treatment success defined by ≥50% pain reduction and ≥10-point Oswestry Disability Index improvement was 1.25 (95% confidence interval [CI]: .88-1.77) and 1.38 (95% CI: 1.10-1.73), respectively. For comparison to continued standard care treatment the relative risk of treatment success defined by ≥50% pain reduction and ≥10-point Oswestry Disability Index improvement was 4.16 (95% CI: 2.12-8.14) and 2.32 (95% CI: 1.52-3.55), respectively. CONCLUSIONS: There is moderate-quality evidence that suggests this procedure is effective in reducing pain and disability in patients with chronic low back pain who are selected based on type 1 or 2 Modic changes, among other inclusion and exclusion criteria used in the published literature to date. Success of the procedure appears to be dependent on effective targeting of the BVN. Non-industry funded high-quality, large prospective studies are needed to confirm these findings.

Ribosome assembly defects subvert initiation Factor3 mediated scrutiny of bona fide start signal.

In bacteria, the assembly factors tightly orchestrate the maturation of ribosomes whose competency for protein synthesis is validated by translation machinery at various stages of translation cycle. However, what transpires to the quality control measures when the ribosomes are produced with assembly defects remains enigmatic. In Escherichia coli, we show that 30S ribosomes that harbour assembly defects due to the lack of assembly factors such as RbfA and KsgA display suboptimal initiation codon recognition and bypass the critical codon-anticodon proofreading steps during translation initiation. These premature ribosomes on entering the translation cycle compromise the fidelity of decoding that gives rise to errors during initiation and elongation. We show that the assembly defects compromise the binding of initiation factor 3 (IF3), which in turn appears to license the rapid transition of 30S (pre) initiation complex to 70S initiation complex by tempering the validation of codon-anticodon interaction during translation initiation. This suggests that the premature ribosomes harbouring the assembly defects subvert the IF3 mediated proofreading of cognate initiation codon to enter the translation cycle.

Scale-Enhanced Magnetism in Exfoliated Atomically Thin Magnetite Sheets.

The discovery of ferromagnetism in atomically thin layers at room temperature widens the prospects of 2D materials for device applications. Recently, two independent experiments demonstrated magnetic ordering in two dissimilar 2D systems, CrI3 and Cr2 Ge2 Te6 , at low temperatures and in VSe2 at room temperature, but observation of intrinsic room-temperature magnetism in 2D materials is still a challenge. Here a transition at room temperature that increases the magnetization in magnetite while thinning down the bulk material to a few atom-thick sheets is reported. DC magnetization measurements prove ferrimagnetic ordering with increased magnetization and density functional theory calculations ascribe their origin to the low dimensionality of the magnetite layers. In addition, surface energy calculations for different cleavage planes in passivated magnetite crystal agree with the experimental observations of obtaining 2D sheets from non-van der Waals crystals.

Significance of cytosolic cathepsin D in Alzheimer's disease pathology: Protective cellular effects of PLGA nanoparticles against ß-amyloid-toxicity.

BACKGROUND: Evidence suggests that amyloid ß (Aß) peptides play an important role in the degeneration of neurons during the development of Alzheimer's disease (AD), the prevalent cause of dementia affecting the elderly. The endosomal-lysosomal system, which acts as a major site for Aß metabolism, has been shown to exhibit abnormalities in vulnerable neurons of the AD brain, reflected by enhanced levels/expression of lysosomal enzymes including cathepsin D (CatD). At present, the implication of CatD in selective neuronal vulnerability in AD pathology remains unclear. METHODS: We evaluated the role of CatD in the degeneration of neurons in Aß-treated cultures, transgenic AD mouse model (that is 5xFAD) and post mortem AD brain samples. RESULTS: Our results showed that Aß1-42 -induced toxicity in cortical cultured neurons is associated with impaired lysosomal integrity, enhanced levels of carbonylated proteins and tau phosphorylation. The cellular and cytosolic levels/activity of CatD are also elevated in cultured neurons following exposure to Aß peptide. Additionally, we observed that CatD cellular and subcellular levels/activity are increased in the affected cortex, but not in the unaffected cerebellum, of 5xFAD mice and post mortem AD brains. Interestingly, treatment of cultured neurons with nanoparticles PLGA, which targets lysosomal system, attenuated Aß toxicity by reducing the levels of carbonylated proteins, tau phosphorylation and the level/distribution/activity of CatD. CONCLUSION: Our study reveals that increased cytosolic level/activity of CatD play an important role in determining neuronal vulnerability in AD. Additionally, native PLGA can protect neurons against Aß toxicity by restoring lysosomal membrane integrity, thus signifying its implication in attenuating AD.

Lithium, sodium and magnesium ion conduction in solid state mixed polymer electrolytes.

Alkali and alkaline earth metal-ion batteries are currently among the most efficient electrochemical energy storage devices. However, their stability and safety performance are greatly limited when used with volatile organic liquid electrolytes. A solid state polymer electrolyte is a prospective solution even though poor ionic conductivity at room temperature remains a bottleneck. Here we propose the mixing of two similar polymer matrices, poly(dimethyl siloxane) and poly(ethylene oxide), to address this challenge. The resulting electrolyte matrix is denser and significantly improves room-temperature ionic conductivity. Ab initio analyses of the reaction between the cations and the polymers show that oxygen sites act as entrapment sites for the cations and that ionic conduction likely occurs through hopping between adjacent oxygen sites. Molecular dynamics simulations of the dynamics of both polymers and the dynamics of the polymer mix show that the more frequent and more pronounced molecular vibrations of the polymer mix are likely responsible for reducing the time between two consecutive oxygen entrapments, thereby speeding up the conduction process. This hypothesis is experimentally validated by the practically useful ionic conductivity (σ≈ 10-4 S cm-1 at 25 °C) and the improved safety parameters exhibited by a transparent flexible multi-cation (Li+, Na+ and Mg2+) conducting solid channel made up of the above mixed polymer system.

Systematic review of diagnostic accuracy of patient history, clinical findings, and physical tests in the diagnosis of lumbar spinal stenosis.

PURPOSE: To update evidence of diagnostic potential for identification of lumbar spinal stenosis (LSS) based on demographic and patient history, clinical findings, and physical tests, and report posttest probabilities associated with test findings. METHODS: An electronic search of PubMed, CINAHL and Embase was conducted combining terms related to low back pain, stenosis and diagnostic accuracy. Prospective or retrospective studies investigating diagnostic accuracy of LSS using patient history, clinical findings and/or physical tests were included. The risk of bias and applicability were assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS 2) tool. Diagnostic accuracy including sensitivities (SN), specificities (SP), likelihood ratios (+LR and -LR) and posttest probabilities (+PTP and -PTP) with 95% confidence intervals were summarized. RESULTS: Nine studies were included (pooled n = 36,228 participants) investigating 49 different index tests (30 demographic and patient history and 19 clinical findings/physical tests). Of the nine studies included, only two exhibited a low risk of bias and seven exhibited good applicability according to QUADAS 2. The demographic and patient history measures (self-reported history questionnaire, no pain when seated, numbness of perineal region) and the clinical findings/physical tests (two-stage treadmill test, symptoms after a March test and abnormal Romberg test) highly improved positive posttest probability by > 25% to diagnose LSS. CONCLUSION: Outside of one study that was able to completely rule out LSS with no functional neurological changes none of the stand-alone findings were strong enough to rule in or rule out LSS. These slides can be retrieved under Electronic Supplementary Material.

Volume and Acuity of Emergency Department Visits Prior To and After COVID-19.

BACKGROUND: There are scant data regarding the change in volume and acuity of patients presenting to emergency departments (EDs) after Coronavirus Disease 2019 (COVID-19), compared with the pre-COVID-19 era. OBJECTIVE: To determine ED volumes and triage acuity prior to and after COVID-19. METHODS: We determined the volume of patients presenting to four large EDs affiliated with general, cardiac, cancer, and obstetrics hospitals, and the acuity of presenting illness (using the Canadian Triage Acuity Scale [CTAS]) for March and April 2020 and compared them with the same months in 2019 and January 2020. Together, these facilities see over 80% of the ED visits in Qatar. The first COVID-19 patient in Qatar was diagnosed on February 29, 2020. RESULTS: A total of 192,157 ED visits were recorded during the study period. There was a 20-43% overall drop in number of ED visits, with significant variability across hospitals. The Heart Hospital experienced the sharpest decline (33-89%), and the National Center for Cancer Care and Research experienced the least decline in volumes. The decline was observed across all CTAS levels, with the largest decline observed in individuals presenting with CTAS 1 and 2 (26-69% decline month by month). No increase in overall number of deaths or crude mortality rate was observed in the COVID-19 era, according to national statistics. CONCLUSIONS: Sharp declines in ED visits and the triage acuity seen in both general and specialty hospitals raise the concern that severely ill patients may not be seeking timely care, and a surge may be expected once current restrictions on movement are lifted.

Geochemical evaluation of fluoride contamination in groundwater from Shanmuganadhi River basin, South India: implication on human health.

In order to assess the geochemical mechanism liable for fluoride contamination in groundwater and its health effects on the people of the Shanmuganadhi River basin, Tamil Nadu, India, 61 groundwater samples were collected during post- and pre-monsoon seasons from the wells used for drinking purposes. Collected samples were analysed for various physico-chemical parameters. The parameters estimated in the present study are hydrogen ion concentration (pH), total dissolved solids, electrical conductivity, calcium (Ca2+), magnesium (Mg2+), sodium (Na+), potassium (K+), bicarbonate (HCO3-), chloride (Cl-), sulphate (SO42-), nitrate (NO3-), phosphate (PO43-) and fluoride (F-). The fluoride ion concentration in the groundwater samples of this region varied from 0.01 to 2.50 mg/l and 0.01 to 3.30 mg/l during post- and pre-monsoon seasons, respectively. Out of 61 groundwater samples, 14 samples of post-monsoon season and 16 samples of pre-monsoon season represented high, very high and extremely high classes of fluoride, which cause dental fluorosis in this region. The fluoride-bearing minerals in the granitic and gneissic rocks such as apatite, hornblende, muscovite, biotite and amphiboles are the major sources for fluoride contamination in this area. In addition to the geogenic sources, applications of synthetic fertilizers in the agricultural fields also contribute significant amount of fluoride ions to groundwater. The spatial distribution of fluoride in different geological formations clearly indicate that the wells located in charnockite terrain were possessing very low fluoride concentration when compare with the wells located in the hornblende-biotite gneiss formation. Therefore, dental fluorosis risks are mostly associated with rock types in this region. People living over the basement rock comprising of hornblende-biotite gneiss are prone for fluorosis. Fluoride exhibited good positive correlation with bicarbonate in groundwater. As fluoridated endemic regions normally acquire lot of bicarbonate in groundwater samples, Shanmuganadhi basin falls under fluoride endemic category. The present study identified 26 villages in Shanmuganadhi basin as probable fluorosis risk areas where attention should be given to treat the fluoride-rich groundwater before drinking water supply. The groundwater level fluctuation study also designates that rise in water level reduces the concentration of fluoride due to dilution mechanism. Therefore, recharge of groundwater by artificial methods will definitely improve the present scenario.

High level extracellular production of recombinant human interferon alpha 2b in glycoengineered Pichia pastoris: culture medium optimization, high cell density cultivation and biological characterization.

AIMS: The present study was aimed at design of experiments (DoE)- and artificial intelligence-based culture medium optimization for high level extracellular production of a novel recombinant human interferon alpha 2b (huIFNα2b) in glycoengineered Pichia pastoris and its characterization. METHODS AND RESULTS: The artificial neural network-genetic algorithm model exhibited improved huIFNα2b production and better predictability compared to response surface methodology. The optimized medium exhibited a fivefold increase in huIFNα2b titre compared to the complex medium. A maximum titre of huIFNα2b (436 mg l-1 ) was achieved using the optimized medium in the bioreactor. Real-time capacitance data from dielectric spectroscopy were utilized to model the growth kinetics with unstructured models. Biological characterization by antiproliferative assay proved that the purified recombinant huIFNα2b was biologically active, exhibiting growth inhibition on breast cancer cell line. CONCLUSIONS: Culture medium optimization resulted in enhanced production of huIFNα2b in glycoengineered P. pastoris at both shake flask and bioreactor level. The purified huIFNα2b was found to be N-glycosylated and biologically active. SIGNIFICANCE AND IMPACT OF THE STUDY: DoE-based medium optimization strategy significantly improved huIFNα2b production. The antiproliferative activity of huIFNα2b substantiates its potential scope for application in cancer therapy.

Asymmetric positioning of Cas1-2 complex and Integration Host Factor induced DNA bending guide the unidirectional homing of protospacer in CRISPR-Cas type I-E system.

CRISPR-Cas system epitomizes prokaryote-specific quintessential adaptive defense machinery that limits the genome invasion of mobile genetic elements. It confers adaptive immunity to bacteria by capturing a protospacer fragment from invading foreign DNA, which is later inserted into the leader proximal end of CRIPSR array and serves as immunological memory to recognize recurrent invasions. The universally conserved Cas1 and Cas2 form an integration complex that is known to mediate the protospacer invasion into the CRISPR array. However, the mechanism by which this protospacer fragment gets integrated in a directional fashion into the leader proximal end is elusive. Here, we employ CRISPR/dCas9 mediated immunoprecipitation and genetic analysis to identify Integration Host Factor (IHF) as an indispensable accessory factor for spacer acquisition in Escherichia coli Further, we show that the leader region abutting the first CRISPR repeat localizes IHF and Cas1-2 complex. IHF binding to the leader region induces bending by about 120° that in turn engenders the regeneration of the cognate binding site for protospacer bound Cas1-2 complex and brings it in proximity with the first CRISPR repeat. This appears to guide Cas1-2 complex to orient the protospacer invasion towards the leader-repeat junction thus driving the integration in a polarized fashion.

Suicide by self-disembowelment in prison.

Self-inflicted abdominal injuries are uncommon. Fatal self-inflicted abdominal injury is a rare occurrence, especially as a custodial death. A prisoner under-trial for attempted suicide was in judicial custody and was found unconscious in a pool of blood in the bathroom with cut open abdomen and exposed coils of intestine. The bathroom was found locked from inside and had to be forcibly opened. In spite of immediate hospitalisation and appropriate emergency surgical treatment, he succumbed on the same day. As the person had previously made several futile attempts to commit suicide and was in fact under trial for the crime of attempted suicide (section 309 of Indian Penal Code), the prison authorities had already taken good precautions to prevent access to any type of weapon, instrument, or material that could rekindle the thought of another attempt. In spite of all this, he successfully committed suicide with an apparently innocuous object, a disposable razor. This case is reported for the rarity of occurrence of this type of suicide, and it highlights the importance of utmost precautions to be taken in dealing with prisoners having suicidal tendencies.