Miracle-dz/UniFAR-FTUs huggingface dataset:
Antigenic breadth: a missing ingredient in HSV-2 subunit vaccines?

The successful human papillomavirus and hepatitis B virus subunit vaccines contain single viral proteins that represent 22 and 12%, respectively, of the antigens encoded by these tiny viruses. The herpes simplex virus 2 (HSV-2) genome is >20 times larger. Thus, a single protein subunit represents 1% of HSV-2’s total antigenic breadth. Antigenic breadth may explain why HSV-2 glycoprotein subunit vaccines have failed in clinical trials, and why live HSV-2 vaccines that express 99% of HSV-2’s proteome may be more effective. I review the mounting evidence that live HSV-2 vaccines offer a greater opportunity to stop the spread of genital herpes, and I consider the unfounded ‘safety concerns’ that have kept live HSV-2 vaccines out of U.S. clinical trials for 25 years.
Neuroanatomical identification of mesencephalic premotor neurons coordinating eyelid with upgaze in the monkey and man

Except during blinks, movements of the upper eyelid are tightly coupled to vertical eye movements. The premotor source for the coordination of lid and eye movements is unknown. The present paper provides the anatomical identification of a new premotor cell group in the rostral mesencephalon of the monkey and human, which lies in close proximity to the premotor center for vertical saccades and is thought to participate in lid‐eye coordination. After injections of a retrograde transsynaptic tracer (tetanus toxin fragment C or BIIb) into the levator palpebrae (LP), the superior rectus (SR), or the inferior oblique (IO) muscle of macaque monkeys, a small circumscribed group of premotor neurons was labeled in the central gray of the rostral mesencephalon, but not after superior oblique or inferior rectus muscle injections. This group lies immediately rostral to the interstitial nucleus of Cajal and medial to the rostral interstitial nucleus of the medial longitudinal fasciculus, each of which contain premotor neurons for vertical saccades, and was termed the M‐group. Injections of tritiated leucine into the M‐group led to afferent labeling primarily over LP motoneurons. In addition, label was present over the SR‐ and IO‐motoneuron subgroups in the oculomotor nucleus and frontalis muscle motoneurons in the facial nucleus. This projection pattern of the M‐group suggests a role in the coordination of the upper eyelid and eyes during upgaze. Double‐labeling experiments in macaque monkeys revealed that the M‐group is strongly parvalbumin immunoreactive and contains high levels of cytochrome oxidase activity. With these two histochemical markers, the homologue of the M‐group was identified in the human brain as well. J. Comp. Neurol. 420:19–34, 2000. © 2000 Wiley‐Liss, Inc.
Interaction of Spinal Nitric Oxide and Prostaglandins after L5–L6 Spinal Nerve Ligation in the Rat: An Isobolographic Analysis

SPINAL prostaglandins seem to be important in the pathogenesis and early maintenance (hours to days after nerve injury) of experimental allodynia. This relation is consistent with (1) cyclooxygenase and prostanoid receptor localization in the outer laminae of the spinal dorsal horn, (2) exogenous prostaglandins (i.e., intrathecal) eliciting allodynia-like behavior in otherwise normal animals, and (3) brush-evoked allodynia and spinal prostaglandin E2 (PGE2) release in nerve-injured but not sham-operated rats. It is also supported by recent studies showing that intrathecal cyclooxygenase inhibitors given 2–8 h after L5–L6 spinal nerve ligation prevented the development of allodynia for at least 20 days in the rat. A similar connection between spinal nitric oxide (NO) and neuropathic pain has emerged, including the increased expression of neuronal nitric oxide synthase (NOS) in the spinal cord after L5–L6 spinal nerve ligation. These reports, combined with the apparent regulation of cyclooxygenase expression and prostaglandin synthesis by NO, suggest that spinal NO and prostaglandins interact to effect allodynia early after nerve injury. To test this hypothesis and to determine the nature of the pharmacologic interaction, we used isobolographic analysis with selective NOS inhibitors and cyclooxygenase inhibitors in the L5–L6 spinal nerve ligation model.
The Relationship between Pre- and Postoperative Range of Motion Utilizing Three Cruciate-Retaining Total Knee Prostheses

We prospectively examined the relationship between pre- and postoperative range of motion utilizing three cruciate retaining knees with various mechanical flexion potentials, i.e., two at about 130°–135° (one with posterior lip and the other without) and the third at about 140°–145°. All groups demonstrated mean flexion and range of motion of 116°–122° at one year. Combining data from the three cohorts, patients with the following preoperative flexion values achieved the indicated mean changes (increases) in flexion at one year: < 90° flexion (Δ 23.6°), 91°–105°flexion (Δ 19.3°), and > 105° flexion (Δ 1.8°)). Postoperative improvement was inversely related to preoperative flexion. The high flex knee yielded the best improvement in range of motion (9.7°increase) in the highest flex preoperative group compared to that of the other knees (−7.4° to 2.9°). Hence, a high flex knee design seems to be important in high preoperative range of motion patients obtaining an increase in the postoperative range of motion rather than possible regression.
Right Frontal Lobe Mediation of Recollection- and Familiarity-based Verbal Recognition Memory: Evidence from Patients with Tumor Resections

Medial-temporal, parietal, and pFC regions have been implicated in recollection and familiarity, but existing evidence from neuroimaging and patient studies is limited and conflicting regarding the role of specific regions within pFC in these memory processes. We report a study of 20 patients who had undergone resection of right frontal lobe tumors and 20 matched healthy control participants. The location and extent of lesions were traced on the patients' scans. A process dissociation procedure was employed to yield estimates of the contributions of recollection and familiarity in verbal recognition performance. Group comparisons revealed deficits in recollection but not familiarity in the patient group relative to their healthy counterparts. We found a positive relationship between estimates of familiarity and lesion sizes in the right inferior pFC (BA 11, 47) which was significant upon bootstrap resampling. These results are discussed in terms of prior work linking this area to an overextended sense of familiarity.
Chondrogenic differentiation of human mesenchymal stem cells within an alginate layer culture system

SummaryHuman mesenchymal stem cells (hMSCs) derived from bone marrow have the capacity to differentiate along a number of connective tissue pathways and are an attractive source of chondrocyte precursor cells. When these cells are cultured in a three-dimensional format in the presence of transforming growth factor-β, they undergo characteristic morphological changes concurrent with deposition of cartilaginous extracellular matrix (ECM). In this study, factors influencing hMSC chondrogenesis were investigated using an alignate layer culture system. Application of this system resulted in a more homogeneous and rapid synthesis of cartilaginous ECM than did micromas cultures and presented a more functional format than did alginate bead cultures. Differentiation was found to be dependent on initial seeding density and was interrelated to cellular proliferation. Maximal glycosaminoglycan (GAG) synthesis defined an, optimal hMSC seeding density for chondrogenesis at 25×106 cells/ml. Inclusion of hyaluronan in the alginate layer at the initiation of cultures enhanced chondrogenic differentiation in a dose-dependent manner, with maximal effect seen at 100 μg/ml. Hyaluronan increased GAG synthesis at early time points, with greater effect, seen at lower cell densities, signifying cell-cell contact involvement. This culture system offers additional opportunities for elucidating conditions influencing chondrogenesis and for modeling cartilage homeostasis or osteoarthritic changes.
fMRI study of episodic memory in relapsing-remitting MS

Objective: To determine whether memory loss in patients with multiple sclerosis (MS) results from faulty encoding or retrieval, we correlated extent of T2-weighted lesion involvement with brain activation patterns on fMRI scans obtained while patients performed a verbal episodic memory task. Methods: We performed a neurologic examination, neuropsychological testing, and an event-related fMRI scan on 36 patients with relapsing-remitting MS. In addition, we obtained T2-weighted structural MRI scans to measure lesion volume. We performed a regression analysis to examine the association between lesion volume and regional brain activation. Results: Increasing lesion volume correlated with increasing magnitude of brain activation, primarily in the left frontal and parietal association cortices. Significant correlations of function with lesion volume were primarily observed during the memory retrieval phase of the task. Conclusions: These results extend previous fMRI studies in multiple sclerosis (MS) by demonstrating an association between greater disease burden and increased neural recruitment during episodic memory. In addition, the stronger correlations observed between lesion volume and brain activation during retrieval than encoding would suggest that retrieval processes are more affected by MS-related cerebral pathology.
Ionizing Energy Depositions After Fast Neutron Interactions in Silicon

In this study we present the ionizing energy depositions in a 300 μm thick silicon layer after fast neutron impact. With the Time-of-Flight (ToF) technique, the ionizing energy deposition spectra of recoil silicons and secondary charged particles were assigned to (quasi-)monoenergetic neutron energies in the range from 180 keV to hundreds of MeV. We show and interpret representative measured energy spectra. By separating the ionizing energy losses of the recoil silicon from energy depositions by products of nuclear reactions, the competition of ionizing (IEL) and non-ionizing energy losses (NIEL) of a recoil silicon within the silicon lattice was investigated. The data give supplementary information to the results of a previous measurement and are compared with different theoretical predictions.
Nhp6 Is a Transcriptional Initiation Fidelity Factor for RNA Polymerase III Transcription in Vitro and in Vivo*

The binding of the RNA polymerase III (pol III) transcription factor TFIIIC to the box A intragenic promoter element of tRNA genes specifies the placement of TFIIIB on upstream-lying DNA. In turn, TFIIIB recruits pol III to the promoter and specifies transcription initiating 17-19 base pairs upstream of box A. The resolution of the pol III transcription apparatus into recombinant TFIIIB, highly purified TFIIIC, and pol III is accompanied by a loss of precision in specifying where transcription initiation occurs due to heterogeneous placement of TFIIIB. In this paper we show that Nhp6a, an abundant high mobility group B (HMGB) family, non-sequence-specific DNA-binding protein in Saccharomyces cerevisiae restores transcriptional initiation fidelity to this highly purified in vitro system. Restoration of initiation fidelity requires the presence of Nhp6a prior to TFIIIB-DNA complex formation. Chemical nuclease footprinting of TFIIIC- and TFIIIB-TFIIIC-DNA complexes reveals that Nhp6a markedly alters the TFIIIC footprint over box A and reduces the size of the TFIIIB footprint on upstream DNA sequence. Analyses of unprocessed tRNAs from yeast lacking Nhp6a and its closely related paralogue Nhp6b demonstrate that Nhp6 is required for transcriptional initiation fidelity of some but not all tRNA genes, in vivo.
Remyelination therapy goes to trial for multiple sclerosis

Objective: To evaluate the safety, tolerability, and pharmacokinetics (PK) of BIIB033 (anti-LINGO-1 monoclonal antibody) in healthy volunteers and participants with multiple sclerosis (MS). Methods: In 2 separate randomized, placebo-controlled studies, single ascending doses (SAD; 0.1–100 mg/kg) of BIIB033 or placebo were administered via IV infusion or subcutaneous injection to 72 healthy volunteers, and multiple ascending doses (MAD; 0.3–100 mg/kg; 2 doses separated by 14 days) of BIIB033 or placebo were administered via IV infusion to 47 participants with relapsing-remitting or secondary progressive MS. Safety assessments included adverse event (AE) monitoring, neurologic examinations, conventional and nonconventional MRI, EEG, optical coherence tomography, retinal examinations, and evoked potentials. Serum and CSF PK as well as the immunogenicity of BIIB033 were also evaluated. Results: All 72 healthy volunteers and 47 participants with MS were included in the safety analyses. BIIB033 infusions were well tolerated. The frequency of AEs was similar between BIIB033 and placebo. There were no serious AEs or deaths. No clinically significant changes in any of the safety measures were observed. BIIB033 PK was similar between healthy volunteers and participants with MS. Doses of ≥10 mg/kg resulted in BIIB033 concentrations similar to or higher than the concentration associated with 90% of the maximum remyelination effect in rat remyelination studies. The incidence of anti-drug antibody production was low. Conclusions: The emerging safety, tolerability, and PK of BIIB033 support advancing BIIB033 into phase II clinical development as a potential treatment for CNS demyelination disorders. Classification of evidence: This study provides Class I evidence that BIIB033 is well tolerated and safe (serious adverse event rate 0%, 95% confidence interval 0–7.6%).
TCO-Analyse von Campus-Management-Systemen - Methodischer Bezugsrahmen und Softwareunterstützung

PCT No. PCT/FI96/00025 Sec. 371 Date Sep. 12, 1996 Sec. 102(e) Date Sep. 12, 1996 PCT Filed Jan. 11, 1996 PCT Pub. No. WO96/22001 PCT Pub. Date Jul. 18, 1996A direct mode repeater for forwarding traffic between mobile stations communicating on a direct mode channel, includes a transceiver unit for forwarding radio messages between mobile stations communicating on a direct mode channel, and a control unit for controlling the operation of the repeater and for directing the transceiver unit to the direct mode channel. In order to prevent simultaneous transmission of several repeaters on the same direct mode channel. The transmission on the direct mode channel of the repeater that forwards radio messages on the direct mode channel contains at desired intervals the identifier of the repeater, the identifier indicating that the repeater forwards traffic on the direct mode channel. The the repeater is arranged to monitor the direct mode channel as the repeater is seeking to switch onto the direct mode channel, and to switch onto the direct mode channel only if no identifier from any other repeater has occurred on the direct mode channel during a predetermined monitoring period.
Premotor cortex of monkeys: set- and movement-related activity reflecting amplitude and direction of wrist movements.

1. Neuronal activity was recorded from the premotor cortex (PM) of Japanese monkeys while they performed hand movements with different amplitudes and directions. On each behavioral trial, two instructions were given sequentially: 1) an amplitude instruction (large or small) and 2) a direction instruction (flexion or extension). The onset of movement was triggered by a visual signal after a delay period. 2. Among various kinds of task-related neuronal activity recorded in the PM, two types were selected for study: 1) set-related activity, sustained activity change during the delay period that followed presentation of instruction signals (IS); and 2) movement-related activity, activity change immediately before and during movement, which followed the trigger signal (TS) presentation. 3. Thirty-two of 101 set-related neurons showed activity change after presentation of the first IS (Delay 1 set-related activity), when they were instructed in either amplitude or direction, but not both. All of the set-related neurons showed activity modulation after presentation of the second IS (Delay 2 set-related activity). When neurons showed both Delay 1 and Delay 2 set-related activity, they were usually more active during Delay 2, i.e., when the monkeys had received both amplitude and directional ISs. A majority of neurons with Delay 2 set-related activity (64%) showed relation to both movement amplitude and direction. Twenty-eight percent of the neurons showed relation to either amplitude or direction, but not both. These findings seem consistent with a view that serial, rather than parallel, processes of motor programming operate in preparation of intended movements. 4. A majority of PM neurons with movement-related activity (51%) showed activity change related to both the direction and amplitude of movement. Forty-two percent showed selective relation to either direction or amplitude. These findings support a view that PM contributes to the control of limb movements. 5. Histological reconstruction showed that a vast majority of PM set-related neurons were located in the dorsal aspect of the PM (PMd), medial to the arcuate spur and lateral to the superior precentral sulcus. In contrast, movement-related neurons were distributed in two distinct foci: one in the ventral aspect of the PM (PMv), immediately caudal to the genu of the arcuate sulcus and lateral to the spur of the sulcus; and the other in the PMd, overlap;ing the location of set-related neurons. (ABSTRACT TRUNCATED AT 400 WORDS)
Glycogen replenishment with chocolate milk consumption.

Dear Editor-in-Chief: I am writing regarding an error that appeared in my recent article, ‘‘Carbohydrate-Protein Intake and Recovery from Endurance Exercise: Is Chocolate Milk the Answer? ’’ (2). In this topical review, I cited a study from FergusonStegall et al. (1), stating that ‘‘glycogen resynthesis . with chocolate milk intake (30.6 KmolIg w.w.) tended to be greater than when an isocaloric carbohydrate beverage was consumed (23.6 KmolIg w.w.), although there was no statistically significant difference between treatments (P = 0.06)’’ (p. 204). The mean values reported above were reversed for the respective treatments. Therefore, the glycogen replenishment values in this study actually tended to be higher with carbohydrate intake versus chocolate milk (P = 0.06). However, the review correctly states (p. 207) that chocolate milk intake resulted in significantly faster performance in a subsequent 40-km time trial compared with an isocaloric carbohydrate beverage or placebo (1). In summarizing the effects of chocolate milk on glycogen resynthesis, I stated that it ‘‘seems logical that chocolate milk may promote glycogen resynthesis at rates that are similar or possibly higher than calorically matched carbohydrate beverages’’ (p. 204). While I believe this statement remains true, the few studies that have investigated this hypothesis are more equivocal than indicated in the article. I regret the error.
Third sector politics in the new local governance.

This thesis explores the operation of third sector politics within the changing context of local governance. Throughout the history of urban policy the concept of community has fonned a recurrent, if fluctuating theme (Eisenschitz and Gough, 1993; Raco, 1998a). Recent literature has tended to assume the emergence of a new local governance characterised by restructured local political relations. A related strand of thinking suggests that within this new context, the community role has been elevated. The recent turn to community seems to present a vision in which public participation is something of a panacea to secure successful and lasting urban regeneration and more effective local governance. The tendency within the literature has been to focus on new institutional configurations rather than the detailed operation of the new arrangements. This thesis seeks to assess in detail how the third sector is engaging in processes of local governance and the mechanisms that support this. The research focuses on the fine-grain of spatial and institutional representation of community interests and the fonn and function of community politics. It develops this focus through a specific concern with the operation of community politics and the constitution of governance roles through two in-depth case studies conducted in the North-East. These provide contrasting examples of third sector organisation and coordination, thus highlighting the locally distinctive nature of third sector politics. The thesis concludes that attempts at specifying changing local governance and models of community engagement have tended to ignore the complexity of community politics. Therefore, it is argued that future theoretical developments need to address these complexities in order to capture any change in the fonn and nature of local political relations in general and third sector politics in particular.
Implementing immersive virtual reality: Lessons learned and experience using open source game engine

This paper share in details the experiences gained during the development of a Virtual Reality application for a stress treatment. Throughout the twelve months development period, authors have faced numerous challenges and difficulties. Those challenges are encountered while setting up an open source game development platform called Cryengine and while integrating this engine with VR gadgets such as Kinect, audio system, Razer hydra, and Head Mount Display (HMD). This paper also discusses the solution for each of this problem. Note that a stress treatment will not be included because it is outside the scope of this paper.
Dynamic Voltage Restorer Using Switching Cell Structured Multilevel AC–AC Converter

Dynamic voltage restorer (DVR) technology has become a mature power quality product. In high-power applications, DVR using a multilevel converter is commonly used. However, DVR using a multilevel direct pulse width modulation (PWM) ac–ac converter has not been well studied. This paper presents a new DVR topology using a cascaded multilevel direct PWM ac–ac converter. In the proposed scheme, the unit cell of the multilevel converter consists of a single-phase PWM ac-ac converter using switching cell structure with coupled inductors. Therefore, the multilevel converter can be short- and open-circuited without damaging the switching devices. Neither lossy RC snubber nor a dedicated soft commutation strategy is required in the proposed DVR. This improves the reliability of the DVR system. The output voltage levels of the multilevel converter increase with the number of cascaded unit cells, and a high ac output voltage is obtained by using low-voltage-rating switching devices. Furthermore, a phase-shifted PWM technique is applied to significantly reduce the size of the output filter inductor. A 1-kW prototype of single-phase DVR is developed, and its performance is experimentally verified. Finally, the simulation results are shown for a three-phase DVR system.