Solution to the Fokker-Planck equation for slowly driven Brownian motion: Emergent geometry and a formula for the corresponding thermodynamic metric.

Considerable progress has recently been made with geometrical approaches to understanding and controlling small out-of-equilibrium systems, but a mathematically rigorous foundation for these methods has been lacking. Towards this end, we develop a perturbative solution to the Fokker-Planck equation for one-dimensional driven Brownian motion in the overdamped limit enabled by the spectral properties of the corresponding single-particle Schrödinger operator. The perturbation theory is in powers of the inverse characteristic timescale of variation of the fastest varying control parameter, measured in units of the system timescale, which is set by the smallest eigenvalue of the corresponding Schrödinger operator.

Critical Point-Finding Methods Reveal Gradient-Flat Regions of Deep Network Losses.

Despite the fact that the loss functions of deep neural networks are highly nonconvex, gradient-based optimization algorithms converge to approximately the same performance from many random initial points. One thread of work has focused on explaining this phenomenon by numerically characterizing the local curvature near critical points of the loss function, where the gradients are near zero. Such studies have reported that neural network losses enjoy a no-bad-local-minima property, in disagreement with more recent theoretical results.

Pure Cerebellar Ataxia with Homozygous Mutations in the PNPLA6 Gene.

Autosomal-recessive cerebellar ataxias (ARCA) are clinically and genetically heterogeneous conditions primarily affecting the cerebellum. Mutations in the PNPLA6 gene have been identified as the cause of hereditary spastic paraplegia and complex forms of ataxia associated with retinal and endocrine manifestations in a field where the genotype-phenotype correlations are rapidly expanding. We identified two cousins from a consanguineous family belonging to a large Zoroastrian (Parsi) family residing in Mumbai, India, who presented with pure cerebellar ataxia without chorioretinal dystrophy or hypogonadotropic hypogonadism.

Docking studies on novel alkaloid tryptanthrin and its analogues against enoyl-acyl carrier protein reductase (InhA) of Mycobacterium tuberculosis.

Isoniazid resistance is a serious threat in the battle against the treatment of multi-drug resistant tuberculosis (MDR-TB) and extremely drug-resistant tuberculosis (XDR-TB). Isoniazid is an inhibitor of enoyl-acyl carrier protein reductase (InhA) of Mycobacterium tuberculosis, which is an important and functional enzyme of the type II fatty acid synthesis system and important therapeutic target. Natural alkaloid tryptanthrin and its analogues have shown anti-tubercular activity against MDR-TB, but their cellular target is unknown.

Selective, circuit-wide sparing of floccular connections in hereditary olivopontine cerebellar atrophy with slow saccades.

We present a systems-oriented histopathologic analysis of the ocular motor control circuits in the cerebellum and brainstem from a patient with a hereditary form of olivopontine cerebellar atrophy of the Wadia type, which has a characteristic ocular motor presentation of slow saccades but relative preservation of smooth pursuit and gaze-holding. This differential pattern of clinical involvement is associated with a lobule-specific pattern of cerebellar degeneration. We asked whether these patterns of sparing and degeneration were consistent throughout the associated deep cerebellar and brainstem structures.

The neuroanatomical basis of slow saccades in spinocerebellar ataxia type 2 (Wadia-subtype).

In a case of spinocerebellar ataxia type 2, Wadia-subtype (SCA2), with slow horizontal saccades, we used parvalbumin immunohistochemistry to identify the omnipause (OPNs) excitatory (EBNs), and inhibitory burst neurons (IBNs) of the saccade generator. Nissl sections was used to measure neuronal diameters, and synaptophysin staining to estimate of synaptic density on the cell somata. Morphometric and synaptic density measurements of the abducens motoneurons were identical in SCA2 and the control.

Late-onset episodic ataxia type 2 due to an in-frame insertion in CACNA1A.

Episodic ataxia type 2 (EA2) is caused by calcium channel (CACNA1A) mutations and typically begins before age 20 years. The molecular basis of late-onset EA2 is unclear. The authors describe a case of late-onset EA2 associated with the first multiple-base pair insertion in CACNA1A.

Search for pi(0)-->nu(mu)nu(mu) decays in the LSND detector.

We observe a net beam excess of 8.7+/-6.3(stat)+/-2.

A proposal to declare neurocysticercosis an international reportable disease.

Neurocysticercosis is an infection of the nervous system caused by Taenia solium. It is the most important human parasitic neurological disease and a common cause of epilepsy in Africa, Asia, and Latin America, representing enormous costs for anticonvulsants, medical resources and lost production. Neurocysticercosis is a human-to-human infection, acquired by the faecal-enteric route from carriers of intestinal T.

Posttraumatic akinetic-rigid syndrome resembling Parkinson's disease: a report on three patients.

We describe three patients who developed a rapidly evolving posttraumatic akinetic-rigid syndrome (ARS), the clinical manifestations of which were similar to Parkinson's disease, including response to levodopa. Despite initial imaging studies showing traumatic damage to the substantia nigra, the ARS appeared after a delay of 1-5 months after the injury. We stress the importance of magnetic resonance imaging to illustrate nigral damage in all patients in whom head trauma precedes an ARS.

A common disease haplotype segregating in spinocerebellar ataxia 2 (SCA2) pedigrees of diverse ethnic origin.

The identification of a CAG trinucleotide repeat expansion, located within the coding sequence of the ataxin-2 gene, as the mutation underlying spinocerebellar ataxia 2 (SCA2) has facilitated direct investigation of pedigrees previously excluded from linkage analysis due to insufficient size or pedigree structure. We have previously described the identification of the ancestral disease haplotype segregating in the Cuban founder population used to assign the disease locus to chromosome 12q23-24.1.

Acute renal failure with neurological involvement in adults associated with measles virus isolation.

Background: Three people with clinical manifestations of acute renal failure with neurological involvement of unknown cause were admitted to a hospital in Mumbai, India. We describe clinical presentations and investigations of the cause.

Methods: We analysed case reports and laboratory findings for the patients (age 37-43 years, two men, one woman) that were provided by the clinicians in charge.

A clinicogenetic analysis of six Indian spinocerebellar ataxia (SCA2) pedigrees. The significance of slow saccades in diagnosis.

Clinical revaluation and genetic analysis of six Indian pedigrees, segregating autosomal dominant cerebellar ataxia, slow saccades and peripheral neuropathy, has been undertaken, and expansion at the spinocerebellar ataxia 2 (SCA2) locus was confirmed in 14 affected family members. These families became available from 31 phenotypically similar families seen over the years. In common with other neurodegenerative disorders resulting from expansion of a CAG trinucleotide repeat motif, an inverse correlation between repeat size and age at onset and severity is observed, although the size range (36-45 repeat units) for the expanded alleles is comparatively limited.

Proposal of diagnostic criteria for human cysticercosis and neurocysticercosis.

Taenia solium cysticercosis is a major public health problem in several areas of the world. While the disease has a recognized etiologic agent, its definitive histological diagnosis is not possible in most cases because this parasite tends to lodge in cerebral tissues where routine biopsy is not feasible. Therefore, the diagnosis of human cysticercosis (and neurocysticercosis) should rest on the proper interpretation of the patients' symptoms together with data provided by radiological studies and immunologic tests for the detection of anticysticercal antibodies.

Autosomal recessive hereditary sensory neuropathy with spastic paraplegia.

Five patients are described with a progressive sensory neuropathy in association with a spastic paraplegia and a mutilating lower limb acropathy. Disease onset was in childhood. Two pairs of siblings were both the offspring of normal consanguinous parents, suggesting autosomal recessive inheritance.

IgM deposits at nodes of Ranvier in a patient with amyotrophic lateral sclerosis, anti-GM1 antibodies, and multifocal motor conduction block.

We studied a patient with amyotrophic lateral sclerosis, multifocal motor conduction block, and IgM anti-GM1 antibodies. A sural nerve biopsy demonstrated deposits of IgM at nodes of Ranvier by direct immunofluorescence. The deposits were granular and located in the nodal gap between adjacent myelin internodes, and in some instances, they extended along the surface of the paranodal myelin sheath.

Multiple sclerosis is prevalent in the Zoroastrians (Parsis) of India.

Using Schumacher's classification, we determined the prevalence rate of clinically definite multiple sclerosis (MS) in the distinct but tiny Zoroastrian (largely Parsi) community in the adjacent cities of Bombay (latitude, 18.55 degrees) and Poona (Pune). On prevalence day, 16 clinically definite cases of MS were counted, 14 in Bombay and 2 in Poona, from a total Zoroastrian population of 50,053 and 3,399, respectively.

Disseminated cysticercosis. New observations, including CT scan findings and experience with treatment by praziquantel.

Although the symptom complex of disseminated cysticercosis has been well recognized for over half a century, it is not clearly included in recent disease classifications. Three such patients are described whose main features were uncontrolled seizures, progressive dementia, behaviour disorder, muscular pseudohypertrophy, and a relative paucity of localizing neurological signs or signs of raised intracranial pressure. Radiographic calcification in muscles was not seen.