Washington — Enhancing first responders’ education and training on hazardous materials is the focus of more than $30 million in recent Pipeline and Hazardous Materials Safety Administration grant funding.

Washington — OSHA has scheduled a virtual public meeting for Nov. 16 in advance of the 43rd session of the United Nations Sub-Committee of Experts on the Globally Harmonized System of Classification and Labeling of Chemicals.

West Lafayette, IN – A common procedure used to repair water pipes can release hazardous chemicals into the air and should be re-evaluated for its risks to workers, the public and the environment, according to researchers from Purdue University.

Denver – On the heels of a recent Purdue University study suggesting that a popular method for repairing water pipes can release hazardous chemicals into the air, the National Environmental Health Association will host a one-hour webinar on Oct. 5 to discuss potential risks to workers and the public.

West Lafayette, IN — Researchers at Purdue University have outlined recommendations for enhancing the safety of a popular method for repairing water pipes that may release hazardous chemicals into the air, as part of a recent study on rehabilitating damaged drainage culverts.

A 49-year-old subcontracting pipefitter was hit in the chest and knocked backward by a pressurized 12-inch diameter vertical section of a polyvinyl chloride pipe during a hydrostatic pressure test of a fire suppression system.

Washington – Vehicles with a model year of 2007 or earlier may be at risk for brake pipe corrosion from exposure to road salt, according to a National Highway Traffic Safety Administration safety advisory.

Cincinnati — Workers replacing old water service lines may be exposed to lead piping or lead-contaminated soil – and could bring the metal home, a new NIOSH guidance document cautions.

The post NIHR launches pipeline of Mental Health Research Groups across England [ £27 million to support mental health research teams in nine regions ] was curated by information for practice.

Theologian and Pastor John Piper weighed in on a question from a listener struggling with guilt after having an abortion in an episode of his podcast "Ask Pastor John."

Crystal structure and topology of two new thiosulfates formed with mono- and diprotonated species of 1-methylpiperazine is reported.

In the title compound, C6H10N2O2, the piperazine-2,3-dione ring adopts a half-chair conformation. In the crystal, the mol­ecules are linked by weak C—H⋯O hydrogen bonds, forming (010) sheets.

Electron cryo-microscopy image-processing workflows are typically composed of elements that may, broadly speaking, be categorized as high-throughput workloads which transition to high-performance workloads as preprocessed data are aggregated. The high-throughput elements are of particular importance in the context of live processing, where an optimal response is highly coupled to the temporal profile of the data collection. In other words, each movie should be processed as quickly as possible at the earliest opportunity. The high level of disconnected parallelization in the high-throughput problem directly allows a completely scalable solution across a distributed computer system, with the only technical obstacle being an efficient and reliable implementation. The cloud computing frameworks primarily developed for the deployment of high-availability web applications provide an environment with a number of appealing features for such high-throughput processing tasks. Here, an implementation of an early-stage processing pipeline for electron cryotomography experiments using a service-based architecture deployed on a Kubernetes cluster is discussed in order to demonstrate the benefits of this approach and how it may be extended to scenarios of considerably increased complexity.

Data acquisition and processing for cryo-electron tomography can be a significant bottleneck for users. To simplify and streamline the cryo-ET workflow, Tomo Live, an on-the-fly solution that automates the alignment and reconstruction of tilt-series data, enabling real-time data-quality assessment, has been developed. Through the integration of Tomo Live into the data-acquisition workflow for cryo-ET, motion correction is performed directly after each of the acquired tilt angles. Immediately after the tilt-series acquisition has completed, an unattended tilt-series alignment and reconstruction into a 3D volume is performed. The results are displayed in real time in a dedicated remote web platform that runs on the microscope hardware. Through this web platform, users can review the acquired data (aligned stack and 3D volume) and several quality metrics that are obtained during the alignment and reconstruction process. These quality metrics can be used for fast feedback for subsequent acquisitions to save time. Parameters such as Alignment Accuracy, Deleted Tilts and Tilt Axis Correction Angle are visualized as graphs and can be used as filters to export only the best tomograms (raw data, reconstruction and intermediate data) for further processing. Here, the Tomo Live algorithms and workflow are described and representative results on several biological samples are presented. The Tomo Live workflow is accessible to both expert and non-expert users, making it a valuable tool for the continued advancement of structural biology, cell biology and histology.

Tri­chlorido­(4-methyl­piperidine)­gold(III), [AuCl3(C6H13N)], 1, crystallizes in Pbca with Z = 8. Tri­bromido­(4-methyl­piperidine)­gold(III), [AuBr3(C6H13N)], 2, crystallizes as two polymorphs, 2a in Pnma with Z = 4 (imposed mirror symmetry) and 2b, which is isotypic to 1. The Au—N bonds trans to Cl are somewhat shorter than those trans to Br, and the Au—Cl bonds trans to N are longer than those cis to N, whereas the Au—Br bonds trans to N are slightly shorter than the cis bonds. The methyl and AuX3 groups (X = halogen) occupy equatorial positions at the six-membered ring. The packing of all three structures involves chains of mol­ecules with offset stacking of the AuX3 moieties associated with short Au⋯X contacts; for 1 and 2b these are reinforced by N—H⋯X hydrogen bonds, whereas for 2a there are no classical hydrogen bonds and the chains are inter­connected by Br⋯Br contacts.

The two mol­ecules in the asymmetric unit of the title compound, C23H24N2O2S, have a structural overlap with an r.m.s. deviation of 0.82 Å. The piperidine rings adopt a distorted boat conformation. Intra- and inter­molecular C—H⋯O hydrogen bonds are responsible for the cohesion of the crystal packing. The inter­molecular inter­actions were qu­anti­fied and analysed using Hirshfeld surface analysis. The mol­ecular structure optimized by density functional theory (DFT) at the B3LYP/6–311++G(d,p)level is compared with the experimentally determined mol­ecular structure in the solid state.

In the title salt, C6H16N22+ ·H2P2O72−, the complete dication is generated by a crystallographic centre of symmetry with the methyl groups in equatorial orientations. The complete dianion is generated by a crystallographic twofold axis with the central O atom lying on the axis: the P—O—P bond angle is 135.50 (12)°. In the crystal, the di­hydrogen diphosphate anions are linked by O—H⋯O hydrogen bonds, generating (001) layers. The organic cations bond to the inorganic layers by way of N—H⋯O and C—H⋯O hydrogen bonds. A Hirshfeld surface analysis shows that the most important contributions for the crystal packing are from O⋯H/H⋯O (60.5%) and H⋯H (39.4%) contacts.

A systematic procedure is introduced for modeling charge-neutral non-polar surfaces of ionic minerals containing polyatomic anions. By integrating distance- and charge-based clustering to identify chemical species within the mineral bulk, our pipeline, PolyCleaver, renders a variety of theoretically viable surface terminations. As a demonstrative example, this approach was applied to forsterite (Mg2SiO4), unveiling a rich interface landscape based on interactions with formaldehyde, a relevant multifaceted molecule, and more particularly in prebiotic chemistry. This high-throughput method, going beyond techniques traditionally applied in the modeling of minerals, offers new insights into the potential catalytic properties of diverse surfaces, enabling a broader exploration of synthetic pathways in complex mineral systems.

In addressing the challenges faced by laboratories and universities with limited (or no) cryo-electron microscopy (cryo-EM) infrastructure, the ESRF, in collaboration with the Grenoble Institute for Structural Biology (IBS), has implemented the cryo-EM Solution-to-Structure (SOS) pipeline. This inclusive process, spanning grid preparation to high-resolution data collection, covers single-particle analysis and cryo-electron tomography (cryo-ET). Accessible through a rolling access route, proposals undergo scientific merit and technical feasibility evaluations. Stringent feasibility criteria demand robust evidence of sample homogeneity. Two distinct entry points are offered: users can either submit purified protein samples for comprehensive processing or initiate the pipeline with already vitrified cryo-EM grids. The SOS pipeline integrates negative stain imaging (exclusive to protein samples) as a first quality step, followed by cryo-EM grid preparation, grid screening and preliminary data collection for single-particle analysis, or only the first two steps for cryo-ET. In both cases, if the screening steps are successfully completed, high-resolution data collection will be carried out using a Titan Krios microscope equipped with a latest-generation direct electron counting detector coupled to an energy filter. The SOS pipeline thus emerges as a comprehensive and efficient solution, further democratizing access to cryo-EM research.

Presented and discussed here is the implementation of a software solution that provides prompt X-ray diffraction data analysis during fast dynamic compression experiments conducted within the dynamic diamond anvil cell technique. It includes efficient data collection, streaming of data and metadata to a high-performance cluster (HPC), fast azimuthal data integration on the cluster, and tools for controlling the data processing steps and visualizing the data using the DIOPTAS software package. This data processing pipeline is invaluable for a great number of studies. The potential of the pipeline is illustrated with two examples of data collected on ammonia–water mixtures and multiphase mineral assemblies under high pressure. The pipeline is designed to be generic in nature and could be readily adapted to provide rapid feedback for many other X-ray diffraction techniques, e.g. large-volume press studies, in situ stress/strain studies, phase transformation studies, chemical reactions studied with high-resolution diffraction etc.

Source: Streetwise Reports 11/08/2024

Vertex Pharmaceuticals Inc. (VRTX:NASDAQ) has reported a robust financial performance for the third quarter of 2024. The report has demonstrated the company's continued revenue growth and the strengthening of its innovative pipeline. For Q3 2024, Vertex's product revenue reached US$2.77 billion, a 12% increase from the previous year. This was primarily driven by strong demand for its TRIKAFTA®/KAFTRIO® therapies. Based on this momentum, Vertex raised its full-year product revenue guidance to a range of US$10.8 billion to US$10.9 billion, citing a solid trajectory in its cystic fibrosis (CF) portfolio and expected future launches.

In Q3, the company made notable advancements in its pipeline. Three programs have begun moving into Phase 3 clinical development: suzetrigine in diabetic peripheral neuropathy (DPN), povetacicept in IgA nephropathy (IgAN), and VX-880 in type 1 diabetes (T1D). Vertex is also preparing for the launch of two potential treatments in early 2025, with PDUFA dates set for January 2 for the vanzacaftor triple therapy for CF and January 30 for suzetrigine, the latter being a pain medication in a new therapeutic class aimed at reducing reliance on opioids.

GAAP and Non-GAAP net income both reached US$1.0 billion, largely driven by increased product revenue, which offset rising R&D and SG&A expense. This was s due to investments in global commercialization and late-stage clinical development. For Q3, Vertex's combined R&D and SG&A expenses were US$1.2 billion and US$1.1 billion, respectively, an increase from last year attributed to new global program advancements and upcoming launch support.

Vertex's cash position remained strong, with US$11.2 billion in cash, cash equivalents, and marketable securities as of September 30. The decline from US$13.7 billion at the end of 2023 primarily reflects the acquisition of Alpine Immune Sciences and share repurchases under the company's buyback program.

A Look At Biotechnology and Pharma

The U.S. Pharmaceuticals Report for 2024 by Nova One Advisor detailed the size and growth trajectory of the U.S. pharmaceutical market. Valued at US$602.19 billion in 2023, the sector is projected to exceed US$1 trillion by 2033. The report pointed to a "high healthcare expenditure provided by government bodies" as a primary growth driver, further bolstered by the aging population's demand for advanced treatments.

In an October 24 article, The Investing News Network reported on a dynamic landscape within the biotechnology sector. The report highlighted advancements in AI-powered drug discovery. Despite a cautious investment climate, interest remained strong in AI's potential to reshape healthcare, with venture capital investment reaching US$6.59 billion. At the HealthTech Ignite conference, Susie Roberts from Relay Therapeutics expressed confidence, noting, "We will definitely see AI design drugs in the next 10 years."

On November 4, Yahoo! Finance shared insights from MIT professors Andrew Lo and Dennis Whyte. They emphasized that biotechnology's rapid advancement over the past five decades offers valuable lessons for future innovation. In their research paper, Lo and Whyte proposed initiatives to accelerate biotechnology's growth, underscoring the importance of "reducing risk and uncertainty" to foster a robust investment ecosystem that supports groundbreaking discoveries.

Catalysts Driving Vertex Pharma

According to Vertex's November 2024 investor presentation, the company sees multiple growth catalysts over the next few years. Vertex aims to meet its goal of achieving "five launches in five years," focusing on expanding the treatable patient base in CF with vanzacaftor triple, addressing critical needs in sickle cell disease (SCD) and beta thalassemia (TDT) with CASGEVY, and launching suzetrigine for acute pain management.

Additionally, Vertex expects its expansive R&D pipeline to support long-term growth. This includes pivotal clinical trials for VX-880 in T1D, povetacicept in IgAN, and NaV1.8 pain inhibitors like suzetrigine, indicating a commitment to treating a range of chronic and life-threatening conditions with limited therapeutic options.

By driving advancements in CF therapies, diversifying its portfolio with novel pain treatments, and pursuing accelerated approvals for renal and blood-related disorders, Vertex is strategically positioning itself to sustain growth and achieve several near-term milestones.

What Are Experts Saying About Vertex?

In a November 5, 2024, H.C. Wainwright & Co. update, the analysts highlighted promising data from Vertex's recent Phase 2 trial for suzetrigine, which showed encouraging reductions in pain intensity. [OWNERSHIP_CHART-4085]

The analysts noted that suzetrigine's peripheral nervous system-specific mechanism could potentially address "a significant, unmet medical need worldwide" in non-opioid pain management. They set a price target of US$600.00, projecting Vertex's continued growth from its strong cystic fibrosis franchise and pipeline expansion.

From the November 7 Kingswood Capital Partners report, analysts noted Vertex Pharmaceuticals' "sustained execution" in advancing product development programs and achieving robust operating margins, enabling "continued, significant investments" in both its pipeline and commercial capabilities. The firm maintained a "Buy" rating with a 12-month target price of US$550.00, attributing this outlook to Vertex's deep cash resources and historical successes in clinical trials.

Ownership and Share Structure

According to Refinitiv, 95.44% of Vertex Pharmaceuticals is held by Institutions. The top among them are Capital World Investors at 10.37%, The Vanguard Group at 8.88%, BlackRock Institutional Trust with 5.49%, State Street Global Advisors (US) with 4.55%, and Fidelity Management and Research with 4.11%. Strategic Investors hold .12%. The rest is retail.

The company's market cap is US$129,395.59 million with 257.07 million free float shares. The 52 week range is US$341.90–$510.64.

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1) James Guttman wrote this article for Streetwise Reports LLC and provides services to Streetwise Reports as an employee.

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( Companies Mentioned: VRTX:NASDAQ, )

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